Achieve Mastery of Medical Concepts

Study for medical school and boards with Lecturio

Thrombocytopenia

Thrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology is usually 150,000–450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration Splenic sequestration Severe Congenital Neutropenia of platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship are often asymptomatic until platelet counts Platelet counts The number of platelets per unit volume in a sample of venous blood. Coagulation Studies are < 50,000/µL. Clinical manifestations of thrombocytopenia include easy bruising Easy bruising Chédiak-Higashi Syndrome or bleeding, petechiae Petechiae Primary Skin Lesions, purpura, and when severe, spontaneous mucosal and/or internal bleeding. Diagnosis is made with a CBC and blood smear Blood smear Myeloperoxidase Deficiency; additional testing may be required to determine the underlying etiology if it is not evident from the clinical scenario. Management involves treating the underlying etiology and platelet transfusions.

Last updated: 7 May, 2021

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Overview

Definition

Thrombocytopenia is a deficiency of platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology, typically defined as < 150,000 platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology per microliter of whole blood.

Epidemiology

  • Platelet counts Platelet counts The number of platelets per unit volume in a sample of venous blood. Coagulation Studies are naturally slightly higher in:
    • Females
    • Younger persons 
    • Non-Hispanic Black persons (as compared with White persons)
  • Most common cause: immune-mediated thrombocytopenia 
  • Second most common cause: infection-induced thrombocytopenia
  • Epidemiologic statistics are related to the underlying etiology.

Classification

Thrombocytopenia can be classified as mild, moderate, or severe on the basis of platelet counts Platelet counts The number of platelets per unit volume in a sample of venous blood. Coagulation Studies:

  • Mild: 100,000–150,000/μL 
  • Moderate: 50,000–99,000/μL
  • Severe: < 50,000/μL

Etiology

Thrombocytopenia can be caused by decreased production, increased destruction, or sequestration of platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology.

Causes of thrombocytopenia

Table: Causes of thrombocytopenia
Mechanism Examples
Decreased production Failure of bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow:
  • Chemotherapy Chemotherapy Osteosarcoma
  • Radiotherapy
  • Aplastic anemia Aplastic Anemia Aplastic anemia (AA) is a rare, life-threatening condition characterized by pancytopenia and hypocellularity of the bone marrow (in the absence of any abnormal cells) reflecting damage to hematopoietic stem cells. Aplastic anemia can be acquired or inherited, however, most cases of AA are acquired and caused by autoimmune damage to hematopoietic stem cells. Aplastic Anemia
  • Myelodysplasia Myelodysplasia Non-Hodgkin Lymphomas
  • Malignant infiltration of the bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow
Decreased thrombopoietin Thrombopoietin A humoral factor that stimulates the production of thrombocytes (blood platelets). Thrombopoietin stimulates the proliferation of bone marrow megakaryocytes and their release of blood platelets. The process is called thrombopoiesis. Platelets: Histology:
  • Liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy disease
Nutritional:
  • Vitamin B12 deficiency
  • Folate deficiency Folate deficiency A nutritional condition produced by a deficiency of folic acid in the diet. Many plant and animal tissues contain folic acid, abundant in green leafy vegetables, yeast, liver, and mushrooms but destroyed by long-term cooking. Alcohol interferes with its intermediate metabolism and absorption. Folic acid deficiency may develop in long-term anticonvulsant therapy or with use of oral contraceptives. This deficiency causes anemia, macrocytic anemia, and megaloblastic anemia. It is indistinguishable from vitamin B12 deficiency in peripheral blood and bone marrow findings, but the neurologic lesions seen in B12 deficiency do not occur. Megaloblastic Anemia
Congenital Congenital Chorioretinitis:
  • Wiskott–Aldrich syndrome
  • Fanconi anemia Fanconi anemia Congenital disorder affecting all bone marrow elements, resulting in anemia; leukopenia; and thrombopenia, and associated with cardiac, renal, and limb malformations as well as dermal pigmentary changes. Spontaneous chromosome breakage is a feature of this disease along with predisposition to leukemia. There are at least 7 complementation groups in Fanconi anemia: fanca, fancb, fancc, fancd1, fancd2, fance, fancf, fancg, and fancl. Aplastic Anemia (inherited pancytopenia Pancytopenia Deficiency of all three cell elements of the blood, erythrocytes, leukocytes and platelets. Aplastic Anemia)
  • Congenital Congenital Chorioretinitis amegakaryocytic thrombocytopenia
Increased destruction Immune-mediated:
  • Immune thrombocytopenic purpura Immune thrombocytopenic purpura Immune thrombocytopenic purpura (ITP), formerly known as idiopathic thrombocytopenic purpura, is a condition that develops secondary to immune-mediated destruction of platelets, resulting in thrombocytopenia (platelet count < 100,000/mm³). Immune thrombocytopenic purpura can be either primary or secondary due to drugs or underlying disease. Immune Thrombocytopenic Purpura ( ITP ITP Immune thrombocytopenic purpura (ITP), formerly known as idiopathic thrombocytopenic purpura, is a condition that develops secondary to immune-mediated destruction of platelets, resulting in thrombocytopenia (platelet count < 100,000/mm³). Immune thrombocytopenic purpura can be either primary or secondary due to drugs or underlying disease. Immune Thrombocytopenic Purpura)
  • Systemic lupus erythematosus Systemic lupus erythematosus Systemic lupus erythematosus (SLE) is a chronic autoimmune, inflammatory condition that causes immune-complex deposition in organs, resulting in systemic manifestations. Women, particularly those of African American descent, are more commonly affected. Systemic Lupus Erythematosus ( SLE SLE Systemic lupus erythematosus (SLE) is a chronic autoimmune, inflammatory condition that causes immune-complex deposition in organs, resulting in systemic manifestations. Women, particularly those of African American descent, are more commonly affected. Systemic Lupus Erythematosus)
  • Drug-induced, most commonly:
    • HIT
    • Quinine Quinine An alkaloid derived from the bark of the cinchona tree. It is used as an antimalarial drug, and is the active ingredient in extracts of the cinchona that have been used for that purpose since before 1633. Quinine is also a mild antipyretic and analgesic and has been used in common cold preparations for that purpose. It was used commonly and as a bitter and flavoring agent, and is still useful for the treatment of babesiosis. Quinine is also useful in some muscular disorders, especially nocturnal leg cramps and myotonia congenita, because of its direct effects on muscle membrane and sodium channels. The mechanisms of its antimalarial effects are not well understood. Antimalarial Drugs
    • Sulfonamides Sulfonamides A group of compounds that contain the structure so2nh2. Sulfonamides and Trimethoprim
Consumption in thrombi
  • Thrombotic thrombocytopenic purpura Thrombotic thrombocytopenic purpura Thrombotic thrombocytopenic purpura (TTP) is a life-threatening condition due to either a congenital or an acquired deficiency of ADAMTS-13, a metalloproteinase that cleaves multimers of von Willebrand factor (VWF). The large multimers then aggregate excessive platelets resulting in microvascular thrombosis and an increase in consumption of platelets. Thrombotic Thrombocytopenic Purpura ( TTP TTP Thrombotic thrombocytopenic purpura (TTP) is a life-threatening condition due to either a congenital or an acquired deficiency of adamts-13, a metalloproteinase that cleaves multimers of von Willebrand factor (vWF). The large multimers then aggregate excessive platelets resulting in microvascular thrombosis and an increase in consumption of platelets. Thrombotic Thrombocytopenic Purpura)
  • Hemolytic uremic syndrome Hemolytic uremic syndrome A syndrome that is associated with microvascular diseases of the kidney, such as renal cortical necrosis. It is characterized by hemolytic anemia; thrombocytopenia; and acute renal failure. Hypocoagulable Conditions ( HUS HUS Hemolytic uremic syndrome (HUS) is a clinical phenomenon most commonly seen in children that consists of a classic triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Hemolytic uremic syndrome is a major cause of acute kidney injury in children and is most commonly associated with a prodrome of diarrheal illness caused by shiga-like toxin-producing bacteria. Hemolytic Uremic Syndrome)
  • Disseminated intravascular coagulation Disseminated intravascular coagulation Disseminated intravascular coagulation (DIC) is a condition characterized by systemic bodywide activation of the coagulation cascade. This cascade results in both widespread microvascular thrombi contributing to multiple organ dysfunction and consumption of clotting factors and platelets, leading to hemorrhage. Disseminated Intravascular Coagulation ( DIC DIC Disseminated intravascular coagulation (DIC) is a condition characterized by systemic bodywide activation of the coagulation cascade. This cascade results in both widespread microvascular thrombi contributing to multiple organ dysfunction and consumption of clotting factors and platelets, leading to hemorrhage. Disseminated Intravascular Coagulation)
Sequestration in the spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen: Anatomy
  • Portal hypertension Portal hypertension Portal hypertension is increased pressure in the portal venous system. This increased pressure can lead to splanchnic vasodilation, collateral blood flow through portosystemic anastomoses, and increased hydrostatic pressure. There are a number of etiologies, including cirrhosis, right-sided congestive heart failure, schistosomiasis, portal vein thrombosis, hepatitis, and Budd-Chiari syndrome. Portal Hypertension (e.g., cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis)
  • Splenomegaly Splenomegaly Splenomegaly is pathologic enlargement of the spleen that is attributable to numerous causes, including infections, hemoglobinopathies, infiltrative processes, and outflow obstruction of the portal vein. Splenomegaly
  • Mononucleosis Mononucleosis Infectious mononucleosis (IM), also known as “the kissing disease,” is a highly contagious viral infection caused by the Epstein-Barr virus. Its common name is derived from its main method of transmission: the spread of infected saliva via kissing. Clinical manifestations of IM include fever, tonsillar pharyngitis, and lymphadenopathy. Mononucleosis
Mixed or unclear mechanisms Infection-induced thrombocytopenia:
  • Viral infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease:
    • HIV HIV Anti-HIV Drugs
    • EBV EBV Epstein-barr virus (EBV) is a linear, double-stranded DNA virus belonging to the herpesviridae family. This highly prevalent virus is mostly transmitted through contact with oropharyngeal secretions from an infected individual. The virus can infect epithelial cells and B lymphocytes, where it can undergo lytic replication or latency. Epstein-Barr Virus
    • CMV
    • Rubella Rubella An acute infectious disease caused by the rubella virus. The virus enters the respiratory tract via airborne droplet and spreads to the lymphatic system. Rubella Virus
    • Varicella
    • Mumps Mumps Mumps is caused by a single-stranded, linear, negative-sense RNA virus of the family Paramyxoviridae. Mumps is typically a disease of childhood, which manifests initially with fever, muscle pain, headache, poor appetite, and a general feeling of malaise, and is classically followed by parotitis. Mumps Virus/Mumps
    • Parvovirus
    • Hepatitis C Hepatitis C Hepatitis C is an infection of the liver caused by the hepatitis C virus (HCV). The infection can be transmitted through infectious blood or body fluids and may be transmitted during childbirth or through IV drug use or sexual intercourse. Hepatitis C virus can cause both acute and chronic hepatitis, ranging from a mild to a serious, lifelong illness including liver cirrhosis and hepatocellular carcinoma (HCC). Hepatitis C Virus
  • Bacterial infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease:
    • Sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock
    • Gram-negative bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology
    • Helicobacter Helicobacter Helicobacter pylori is a gram-negative bacterium that causes gastric infection. It is the most well known and clinically significant species of Helicobacter. Transmission is believed to occur by ingestion of contaminated food or water; therefore, a higher prevalence of infection is seen in areas with poor sanitation. Helicobacter pylori
    • Tick-borne infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease
  • Parasites: malaria Malaria Malaria is an infectious parasitic disease affecting humans and other animals. Most commonly transmitted via the bite of a female Anopheles mosquito infected with microorganisms of the Plasmodium genus. Patients present with fever, chills, myalgia, headache, and diaphoresis. Plasmodium/Malaria
Obstetric causes of thrombocytopenia:
Dilution
  • Massive fluid resuscitation Resuscitation The restoration to life or consciousness of one apparently dead. . Neonatal Respiratory Distress Syndrome
  • Massive transfusions of RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology without proportionate transfusion of platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology
Pseudothrombocytopenia (a falsely low platelet count due to clumping)
  • Ethylene-diamine-tetraacetic acid (EDTA) in blood collection tubes
  • Incompletely mixed or inadequately anticoagulated samples

Drugs definitively associated with isolated thrombocytopenia

  • Abciximab
  • Acetaminophen Acetaminophen Acetaminophen is an over-the-counter nonopioid analgesic and antipyretic medication and the most commonly used analgesic worldwide. Despite the widespread use of acetaminophen, its mechanism of action is not entirely understood. Acetaminophen
  • Acyclovir Acyclovir A guanosine analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes. Herpes Zoster (Shingles)
  • Aminosalicylic acid
  • Amiodarone Amiodarone An antianginal and class III antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting potassium channels and voltage-gated sodium channels. There is a resulting decrease in heart rate and in vascular resistance. Pulmonary Fibrosis
  • Amphotericin B Amphotericin B Macrolide antifungal antibiotic produced by streptomyces nodosus obtained from soil of the orinoco river region of venezuela. Polyenes
  • Ampicillin Ampicillin Semi-synthetic derivative of penicillin that functions as an orally active broad-spectrum antibiotic. Penicillins
  • Carbamazepine Carbamazepine A dibenzazepine that acts as a sodium channel blocker. It is used as an anticonvulsant for the treatment of grand mal and psychomotor or focal seizures. It may also be used in the management of bipolar disorder, and has analgesic properties. First-Generation Anticonvulsant Drugs
  • Chlorpropamide
  • Danazol Danazol A synthetic steroid with antigonadotropic and anti-estrogenic activities that acts as an anterior pituitary suppressant by inhibiting the pituitary output of gonadotropins. It possesses some androgenic properties. Danazol has been used in the treatment of endometriosis and some benign breast disorders. Antiestrogens
  • Diclofenac Diclofenac A non-steroidal anti-inflammatory agent (nsaid) with antipyretic and analgesic actions. It is primarily available as the sodium salt. Nonsteroidal Antiinflammatory Drugs (NSAIDs)
  • Digoxin Digoxin A cardiotonic glycoside obtained mainly from digitalis lanata; it consists of three sugars and the aglycone digoxigenin. Digoxin has positive inotropic and negative chronotropic activity. It is used to control ventricular rate in atrial fibrillation and in the management of congestive heart failure with atrial fibrillation. Its use in congestive heart failure and sinus rhythm is less certain. The margin between toxic and therapeutic doses is small. Cardiac Glycosides
  • Eptifibatide Eptifibatide Cyclic peptide that acts as a platelet glycoprotein iib-iiia antagonist, reversibly inhibiting the binding of fibrinogen; von Willebrand factor; and other adhesive molecules to the gpiib-iiia receptors of platelets. It is used in the management of unstable angina and in patients undergoing coronary angioplasty and stenting procedures. Antiplatelet Drugs
  • Hydrochlorothiazide Hydrochlorothiazide A thiazide diuretic often considered the prototypical member of this class. It reduces the reabsorption of electrolytes from the renal tubules. This results in increased excretion of water and electrolytes, including sodium, potassium, chloride, and magnesium. It is used in the treatment of several disorders including edema, hypertension, diabetes insipidus, and hypoparathyroidism. Thiazide Diuretics
  • Ibuprofen Ibuprofen A nonsteroidal anti-inflammatory agent with analgesic properties used in the treatment of rheumatism and arthritis. Nonsteroidal Antiinflammatory Drugs (NSAIDs)
  • Levamisole
  • Octreotide Octreotide A potent, long-acting synthetic somatostatin octapeptide analog that inhibits secretion of growth hormone and is used to treat hormone-secreting tumors; diabetes mellitus; hypotension, orthostatic; hyperinsulinism; hypergastrinemia; and small bowel fistula. Antidiarrheal Drugs
  • Phenytoin Phenytoin An anticonvulsant that is used to treat a wide variety of seizures. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs. First-Generation Anticonvulsant Drugs
  • Quinine Quinine An alkaloid derived from the bark of the cinchona tree. It is used as an antimalarial drug, and is the active ingredient in extracts of the cinchona that have been used for that purpose since before 1633. Quinine is also a mild antipyretic and analgesic and has been used in common cold preparations for that purpose. It was used commonly and as a bitter and flavoring agent, and is still useful for the treatment of babesiosis. Quinine is also useful in some muscular disorders, especially nocturnal leg cramps and myotonia congenita, because of its direct effects on muscle membrane and sodium channels. The mechanisms of its antimalarial effects are not well understood. Antimalarial Drugs
  • Rifampin Rifampin A semisynthetic antibiotic produced from streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits dna-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. Epiglottitis
  • Tamoxifen Tamoxifen One of the selective estrogen receptor modulators with tissue-specific activities. Tamoxifen acts as an anti-estrogen (inhibiting agent) in the mammary tissue, but as an estrogen (stimulating agent) in cholesterol metabolism, bone density, and cell proliferation in the endometrium. Antiestrogens
  • Tirofiban Tirofiban Tyrosine analog and platelet glycoprotein gpiib-iiia complex antagonist that inhibits platelet aggregation and is used in the treatment of acute coronary syndrome. Antiplatelet Drugs
  • Trimethoprim Trimethoprim The sulfonamides are a class of antimicrobial drugs inhibiting folic acid synthesize in pathogens. The prototypical drug in the class is sulfamethoxazole. Although not technically sulfonamides, trimethoprim, dapsone, and pyrimethamine are also important antimicrobial agents inhibiting folic acid synthesis. The agents are often combined with sulfonamides, resulting in a synergistic effect. Sulfonamides and Trimethoprim sulfamethoxazole Sulfamethoxazole A bacteriostatic antibacterial agent that interferes with folic acid synthesis in susceptible bacteria. Its broad spectrum of activity has been limited by the development of resistance. Sulfonamides and Trimethoprim
  • Vancomycin Vancomycin Antibacterial obtained from streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. Glycopeptides

Review of Normal Physiology

Platelet production

Under normal physiologic conditions, platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology are produced from the fragmentation Fragmentation Chronic Apophyseal Injury of megakaryocytes in the bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow.

  • Upon release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology from the bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow:
    •  ⅔ of platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology will circulate in the blood for 8–10 days.
    • Remaining ⅓ are sequestered in the spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen: Anatomy.
    • Senescent platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology are removed by phagocytic cells in the spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen: Anatomy ( monocytes Monocytes Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. Innate Immunity: Phagocytes and Antigen Presentation, macrophages Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells. Innate Immunity: Phagocytes and Antigen Presentation).
    • No platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology are stored in the bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow.
  • Decreased platelet counts Platelet counts The number of platelets per unit volume in a sample of venous blood. Coagulation Studies stimulate megakaryocytes to release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology.
  • Thrombopoietin Thrombopoietin A humoral factor that stimulates the production of thrombocytes (blood platelets). Thrombopoietin stimulates the proliferation of bone marrow megakaryocytes and their release of blood platelets. The process is called thrombopoiesis. Platelets: Histology (TPO):
    • Regulates platelet levels
    • Stimulates multipotent hematopoietic stem cells Hematopoietic stem cells Progenitor cells from which all blood cells derived. They are found primarily in the bone marrow and also in small numbers in the peripheral blood. Bone Marrow: Composition and Hematopoiesis
    • Produced in the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy and kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy
    • Binds megakaryocytes:
      • Prevents apoptosis Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, I.e., DNA fragmentation. It is genetically-programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Ischemic Cell Damage
      • Stimulates their number, size, ploidy, and maturation
    • Binds platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology: lowers their threshold Threshold Minimum voltage necessary to generate an action potential (an all-or-none response) Skeletal Muscle Contraction for activation
  • Cytokines Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Adaptive Immune Response:
    • Stimulates megakaryocytes and platelet production independently of TPO
    • Platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology ↑ during acute infection or inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation.
    • Exact mechanism unknown but thought to include IL-6 and IL-11.

Platelet function

Platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology are the principle cells involved in formation of the initial platelet plug Platelet plug Hemostasis (i.e., primary hemostasis Primary hemostasis Hemostasis).

  • Disrupted endothelial surface exposes von Willebrand factor von Willebrand factor A high-molecular-weight plasma protein, produced by endothelial cells and megakaryocytes, that is part of the factor VIII/von Willebrand factor complex. The von Willebrand factor has receptors for collagen, platelets, and ristocetin activity as well as the immunologically distinct antigenic determinants. It functions in adhesion of platelets to collagen and hemostatic plug formation. The prolonged bleeding time in von Willebrand diseases is due to the deficiency of this factor. Hemostasis (VWF) to the passing blood. 
  • Platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology bind BIND Hyperbilirubinemia of the Newborn to the VWF via their glycoprotein (Gp) Ib receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors and are activated. 
  • Platelet activation Platelet activation A series of progressive, overlapping events, triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. Hemostasis triggers Triggers Hereditary Angioedema (C1 Esterase Inhibitor Deficiency) them to secrete ADP, which stimulates the expression of the GpIIb/IIIa receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors on the platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology
  • GpIIb/IIIa receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors bind BIND Hyperbilirubinemia of the Newborn to fibrinogen Fibrinogen Plasma glycoprotein clotted by thrombin, composed of a dimer of three non-identical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides a and b, the proteolytic action of other enzymes yields different fibrinogen degradation products. Hemostasis, which is able to bind BIND Hyperbilirubinemia of the Newborn a platelet on each end, causing platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology to aggregate. 
  • As more platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology are bound to one another, the platelet plug Platelet plug Hemostasis is generated. 
  • As the coagulation cascade Coagulation cascade The coagulation cascade is a series of reactions that ultimately generates a strong, cross-linked fibrin clot. Hemostasis is activated, thrombin Thrombin An enzyme formed from prothrombin that converts fibrinogen to fibrin. Hemostasis converts the weaker fibrinogen Fibrinogen Plasma glycoprotein clotted by thrombin, composed of a dimer of three non-identical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides a and b, the proteolytic action of other enzymes yields different fibrinogen degradation products. Hemostasis into the stronger fibrin Fibrin A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. Rapidly Progressive Glomerulonephritis, creating a much more stable clot.
Formation of the temporary hemostatic plug

Formation of the temporary hemostatic plug:
The disrupted endothelial surface exposes VWF to the passing blood. Platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology bind BIND Hyperbilirubinemia of the Newborn to the VWF via their GpIb receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors and are activated. Platelet activation Platelet activation A series of progressive, overlapping events, triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. Hemostasis triggers Triggers Hereditary Angioedema (C1 Esterase Inhibitor Deficiency) them to secrete ADP, which stimulates the expression of the GpIIb/IIIa receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors on the platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology. The GpIIb/IIIa receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors bind BIND Hyperbilirubinemia of the Newborn to fibrinogen Fibrinogen Plasma glycoprotein clotted by thrombin, composed of a dimer of three non-identical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides a and b, the proteolytic action of other enzymes yields different fibrinogen degradation products. Hemostasis, which is able to bind BIND Hyperbilirubinemia of the Newborn a platelet on each end, causing platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology to aggregate. As more platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology are bound to one another, the platelet plug Platelet plug Hemostasis is generated. As the coagulation cascade Coagulation cascade The coagulation cascade is a series of reactions that ultimately generates a strong, cross-linked fibrin clot. Hemostasis is activated, thrombin Thrombin An enzyme formed from prothrombin that converts fibrinogen to fibrin. Hemostasis converts the weaker fibrinogen Fibrinogen Plasma glycoprotein clotted by thrombin, composed of a dimer of three non-identical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides a and b, the proteolytic action of other enzymes yields different fibrinogen degradation products. Hemostasis into the stronger fibrin Fibrin A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. Rapidly Progressive Glomerulonephritis, creating a much more stable clot.

Image by Lecturio.

Pathophysiology

Pathophysiology of platelet deficiency

In thrombocytopenia, a platelet deficiency results in:

  • Decreased ability to produce the platelet plug Platelet plug Hemostasis after a vessel wall injury
  • Requirement for the coagulation cascade Coagulation cascade The coagulation cascade is a series of reactions that ultimately generates a strong, cross-linked fibrin clot. Hemostasis to form a clot
  • End results:

Drug-induced thrombocytopenia

Drug-induced thrombocytopenia may be due to direct toxic effects on the bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow (e.g., chemotherapy Chemotherapy Osteosarcoma) or to drug-dependent antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions. Drug-dependent antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions:

  • React with specific platelet surface antigens
  • Result in thrombocytopenia only when the drug is present
  • More common with quinine Quinine An alkaloid derived from the bark of the cinchona tree. It is used as an antimalarial drug, and is the active ingredient in extracts of the cinchona that have been used for that purpose since before 1633. Quinine is also a mild antipyretic and analgesic and has been used in common cold preparations for that purpose. It was used commonly and as a bitter and flavoring agent, and is still useful for the treatment of babesiosis. Quinine is also useful in some muscular disorders, especially nocturnal leg cramps and myotonia congenita, because of its direct effects on muscle membrane and sodium channels. The mechanisms of its antimalarial effects are not well understood. Antimalarial Drugs and sulfonamides Sulfonamides A group of compounds that contain the structure so2nh2. Sulfonamides and Trimethoprim
  • Thrombocytopenia typically occurs after an initial exposure Exposure ABCDE Assessment.
  • Typically resolves 7–10 days after discontinuation of the drug

Heparin-induced thrombocytopenia

Unlike most drug-induced thrombocytopenias, HIT is associated with a markedly increased risk of thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus rather than bleeding.

  • Antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions form against the complex of platelet factor 4 + heparin
  • These antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions activate platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology and endothelial cells → thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus
  • More common with unfractionated heparin Unfractionated heparin A highly acidic mucopolysaccharide formed of equal parts of sulfated d-glucosamine and d-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc. , of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. Anticoagulants ( UFH UFH A highly acidic mucopolysaccharide formed of equal parts of sulfated d-glucosamine and d-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc. , of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. Anticoagulants) than with low-molecular-weight heparin (LMWH)
  • Begins within 5–10 days after heparin exposure Exposure ABCDE Assessment

HIV HIV Anti-HIV Drugs-associated thrombocytopenia

  • Early in an HIV HIV Anti-HIV Drugs infection: antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions against HIV HIV Anti-HIV Drugs Gp120 Gp120 External envelope protein of the human immunodeficiency virus which is encoded by the HIV env gene. It has a molecular weight of 120 kda and contains numerous glycosylation sites. Gp120 binds to cells expressing CD4 cell-surface antigens, most notably t4-lymphocytes and monocytes/macrophages. Gp120 has been shown to interfere with the normal function of CD4 and is at least partly responsible for the cytopathic effect of HIV. HIV Infection and AIDS antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination can cross-react with GpIIb/IIIa antigens on platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology ( molecular mimicry Molecular Mimicry The structure of one molecule that imitates or simulates the structure of a different molecule. Rheumatic Fever) → ↑ destruction
  • Later in HIV HIV Anti-HIV Drugs infection: ↓ production (often associated with pancytopenia Pancytopenia Deficiency of all three cell elements of the blood, erythrocytes, leukocytes and platelets. Aplastic Anemia)

Clinical Presentation

  • Bleeding symptoms:
    • Petechiae Petechiae Primary Skin Lesions: pinpoint hemorrhages (< 2 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma)
    • Purpura: coalesced petechiae Petechiae Primary Skin Lesions 
    • Ecchymoses (bruises): bleeding into the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions
    • Clinical bleeding:
  • Expected bleeding based on platelet count:
    • > 50,000/μL: often asymptomatic
    • 20,000–50,000/μL: excessive bleeding with trauma
    • < 20,000/μL: ↑ risk of spontaneous bleeding (e.g., mucosal, intracrainal, GI, genitourinary)
    • < 5000/μL: hematologic emergency
  • Other potential exam findings: helpful in determining the underlying etiology
    • Hepatomegaly → liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy disease
    • Splenomegaly Splenomegaly Splenomegaly is pathologic enlargement of the spleen that is attributable to numerous causes, including infections, hemoglobinopathies, infiltrative processes, and outflow obstruction of the portal vein. Splenomegaly liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy disease, infectious Infectious Febrile Infant disease
    • Lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy → recent infection, HIV HIV Anti-HIV Drugs, malignancy Malignancy Hemothorax, autoimmune/inflammatory conditions
  • Heparin-induced thrombocytopenia (HIT):

Diagnosis

The diagnosis of thrombocytopenia itself is made with laboratory evaluations. Clues to the underlying etiology can be obtained from the history and exam, and additional lab testing can further aid in diagnosis.

Routine testing

The following tests should be ordered for all patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with thrombocytopenia:

  • CBC: 
    • Evaluate platelet count: establishes the diagnosis of thrombocytopenia
    • Determine if there are other cytopenias Cytopenias IPEX Syndrome: presence suggests a bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow issue
  • Peripheral blood smear Peripheral Blood Smear Anemia: Overview and Types
    • Microscopic evaluation of the number and appearance of blood cells, including platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology
    • Excludes pseudothrombocytopenias (falsely low platelet counts Platelet counts The number of platelets per unit volume in a sample of venous blood. Coagulation Studies)
    • Schistocytes Schistocytes Hemolytic Uremic Syndrome: suggest a microangiopathic process (e.g., DIC DIC Disseminated intravascular coagulation (DIC) is a condition characterized by systemic bodywide activation of the coagulation cascade. This cascade results in both widespread microvascular thrombi contributing to multiple organ dysfunction and consumption of clotting factors and platelets, leading to hemorrhage. Disseminated Intravascular Coagulation, TTP TTP Thrombotic thrombocytopenic purpura (TTP) is a life-threatening condition due to either a congenital or an acquired deficiency of adamts-13, a metalloproteinase that cleaves multimers of von Willebrand factor (vWF). The large multimers then aggregate excessive platelets resulting in microvascular thrombosis and an increase in consumption of platelets. Thrombotic Thrombocytopenic Purpura, HUS HUS Hemolytic uremic syndrome (HUS) is a clinical phenomenon most commonly seen in children that consists of a classic triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Hemolytic uremic syndrome is a major cause of acute kidney injury in children and is most commonly associated with a prodrome of diarrheal illness caused by shiga-like toxin-producing bacteria. Hemolytic Uremic Syndrome)
    • Teardrop cells Teardrop Cells Primary Myelofibrosis and nucleated RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology: suggest an infiltrative process in the bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow
    • Immature or dysplastic WBCs: suggest leukemia or myelodysplasia Myelodysplasia Non-Hodgkin Lymphomas
    • Multilobed/hypersegmented neutrophils Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. Innate Immunity: Phagocytes and Antigen Presentation: suggest deficiency of vitamin B12 or folate Folate Folate and vitamin B12 are 2 of the most clinically important water-soluble vitamins. Deficiencies can present with megaloblastic anemia, GI symptoms, neuropsychiatric symptoms, and adverse pregnancy complications, including neural tube defects. Folate and Vitamin B12
  • HIV HIV Anti-HIV Drugs test
  • Hepatitis C Hepatitis C Hepatitis C is an infection of the liver caused by the hepatitis C virus (HCV). The infection can be transmitted through infectious blood or body fluids and may be transmitted during childbirth or through IV drug use or sexual intercourse. Hepatitis C virus can cause both acute and chronic hepatitis, ranging from a mild to a serious, lifelong illness including liver cirrhosis and hepatocellular carcinoma (HCC). Hepatitis C Virus

Additional testing

The following tests should be ordered only as clinically indicated to help identify the underlying etiology.

  • Coagulation studies Coagulation studies Coagulation studies are a group of hematologic laboratory studies that reflect the function of blood vessels, platelets, and coagulation factors, which all interact with one another to achieve hemostasis. Coagulation studies are usually ordered to evaluate patients with bleeding or hypercoagulation disorders. Coagulation Studies
    • Evaluate the function of the coagulation cascade Coagulation cascade The coagulation cascade is a series of reactions that ultimately generates a strong, cross-linked fibrin clot. Hemostasis
    • Key tests: PT, PTT
  • Bleeding time Bleeding time Duration of blood flow after skin puncture. This test is used as a measure of capillary and platelet function. Hemostasis
    • Measures the time for bleeding to stop after a lancet incision
    • An indirect measure of platelet function
  • CMP: 
    • Evaluates metabolic health and organ function 
    • Liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy function tests: suggests liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy disease
    • ↑ Creatinine and BUN: suggests renal disease
  • Bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow aspiration and/or biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma:
    • Normal or ↑ megakaryocytes:  thrombocytopenia is due to ↑ destruction (e.g., ITP ITP Immune thrombocytopenic purpura (ITP), formerly known as idiopathic thrombocytopenic purpura, is a condition that develops secondary to immune-mediated destruction of platelets, resulting in thrombocytopenia (platelet count < 100,000/mm³). Immune thrombocytopenic purpura can be either primary or secondary due to drugs or underlying disease. Immune Thrombocytopenic Purpura or drug-induced)
    • ↓ Megakaryocytes + ↓ cellularity overall: ↓ production (e.g., aplastic anemia Aplastic Anemia Aplastic anemia (AA) is a rare, life-threatening condition characterized by pancytopenia and hypocellularity of the bone marrow (in the absence of any abnormal cells) reflecting damage to hematopoietic stem cells. Aplastic anemia can be acquired or inherited, however, most cases of AA are acquired and caused by autoimmune damage to hematopoietic stem cells. Aplastic Anemia)
    • ↓ Megakaryocytes with otherwise normal cellularity: most commonly seen in SLE SLE Systemic lupus erythematosus (SLE) is a chronic autoimmune, inflammatory condition that causes immune-complex deposition in organs, resulting in systemic manifestations. Women, particularly those of African American descent, are more commonly affected. Systemic Lupus Erythematosus
    • Dysplasia Dysplasia Cellular Adaptation: myelodysplastic disorder
  • Platelet factor 4 antibody assays (HIT antibody)
  • ANA
  • Vitamin B12 and folate Folate Folate and vitamin B12 are 2 of the most clinically important water-soluble vitamins. Deficiencies can present with megaloblastic anemia, GI symptoms, neuropsychiatric symptoms, and adverse pregnancy complications, including neural tube defects. Folate and Vitamin B12 levels
  • Blood cultures Cultures Klebsiella
Hypocellular bone marrow showing only little hematopoiesis

Hypocellular bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow in a patient with aplastic anemia Aplastic Anemia Aplastic anemia (AA) is a rare, life-threatening condition characterized by pancytopenia and hypocellularity of the bone marrow (in the absence of any abnormal cells) reflecting damage to hematopoietic stem cells. Aplastic anemia can be acquired or inherited, however, most cases of AA are acquired and caused by autoimmune damage to hematopoietic stem cells. Aplastic Anemia

Image: “Hypocellular bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow showing only little hematopoiesis Hematopoiesis The development and formation of various types of blood cells. Hematopoiesis can take place in the bone marrow (medullary) or outside the bone marrow (extramedullary hematopoiesis). Bone Marrow: Composition and Hematopoiesis” by Department of Obstetrics of Gynaecology, Erasmus University Medical Center, PO Box 2040, 3000 CA CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts) Rotterdam, The Netherlands. License: CC BY 2.0

Management

Management of thrombocytopenia depends mainly on addressing the underlying cause, monitoring platelet counts Platelet counts The number of platelets per unit volume in a sample of venous blood. Coagulation Studies, and preventing/controlling any bleeding complications.

  • Routine monitoring of the platelet count for stable patients Stable Patients Blunt Chest Trauma
  • Consider activity restrictions (generally for severe thrombocytopenia only).
  • Treatment of the underlying cause:
    • Discontinue medications known to induce immune-mediated platelet destruction.
    • Discontinue cytotoxic Cytotoxic Parvovirus B19 medications.
    • Antibiotics to treat bacterial infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease/ sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock
    • Antiretrovirals to manage HIV HIV Anti-HIV Drugs
    • Administration of glucocorticoids Glucocorticoids Glucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs. Glucocorticoids and/or IV immunoglobulin Iv Immunoglobulin Dermatomyositis ( IVIG IVIG Dermatomyositis) is indicated for symptomatic ITP ITP Immune thrombocytopenic purpura (ITP), formerly known as idiopathic thrombocytopenic purpura, is a condition that develops secondary to immune-mediated destruction of platelets, resulting in thrombocytopenia (platelet count < 100,000/mm³). Immune thrombocytopenic purpura can be either primary or secondary due to drugs or underlying disease. Immune Thrombocytopenic Purpura.
    • Treatment of neoplastic, autoimmune, or inflammatory diseases
  • Platelet transfusions:
    • Indications:
      • Life-threatening bleeding: intracranial hemorrhage Intracranial hemorrhage Subarachnoid hemorrhage (SAH) is a type of cerebrovascular accident (stroke) resulting from intracranial hemorrhage into the subarachnoid space between the arachnoid and the pia mater layers of the meninges surrounding the brain. Most sahs originate from a saccular aneurysm in the circle of willis but may also occur as a result of trauma, uncontrolled hypertension, vasculitis, anticoagulant use, or stimulant use. Subarachnoid Hemorrhage or massive GI bleed
      • Prophylactic prevention of bleeding if platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology < 10,000/μL (afebrile) or < 20,000/μL (febrile) 
      • Prophylactic treatment in severe thrombocytopenia prior to invasive procedures
    • Goal platelet counts Platelet counts The number of platelets per unit volume in a sample of venous blood. Coagulation Studies for prophylactic transfusions depend on the procedure to be performed; examples include:
      • Neurosurgery Neurosurgery Neurosurgery is a specialized field focused on the surgical management of pathologies of the brain, spine, spinal cord, and peripheral nerves. General neurosurgery includes cases of trauma and emergencies. There are a number of specialized neurosurgical practices, including oncologic neurosurgery, spinal neurosurgery, and pediatric neurosurgery. Neurosurgery: 100,000/μL
      • Most other major surgery: 50,000/μL
      • Central line placement: 20,000/μL
  • Consider splenectomy Splenectomy Surgical procedure involving either partial or entire removal of the spleen. Rupture of the Spleen for sequestration.

Clinical Relevance

  • Immune thrombocytopenic purpura Immune thrombocytopenic purpura Immune thrombocytopenic purpura (ITP), formerly known as idiopathic thrombocytopenic purpura, is a condition that develops secondary to immune-mediated destruction of platelets, resulting in thrombocytopenia (platelet count < 100,000/mm³). Immune thrombocytopenic purpura can be either primary or secondary due to drugs or underlying disease. Immune Thrombocytopenic Purpura ( ITP ITP Immune thrombocytopenic purpura (ITP), formerly known as idiopathic thrombocytopenic purpura, is a condition that develops secondary to immune-mediated destruction of platelets, resulting in thrombocytopenia (platelet count < 100,000/mm³). Immune thrombocytopenic purpura can be either primary or secondary due to drugs or underlying disease. Immune Thrombocytopenic Purpura): condition that develops secondary to immune-mediated destruction of platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology: IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions target the platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology, which are then cleared by the spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen: Anatomy. Immune thrombocytopenic purpura Immune thrombocytopenic purpura Immune thrombocytopenic purpura (ITP), formerly known as idiopathic thrombocytopenic purpura, is a condition that develops secondary to immune-mediated destruction of platelets, resulting in thrombocytopenia (platelet count < 100,000/mm³). Immune thrombocytopenic purpura can be either primary or secondary due to drugs or underlying disease. Immune Thrombocytopenic Purpura may be primary or secondary and is usually a diagnosis of exclusion. Severity of thrombocytopenia in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with ITP ITP Immune thrombocytopenic purpura (ITP), formerly known as idiopathic thrombocytopenic purpura, is a condition that develops secondary to immune-mediated destruction of platelets, resulting in thrombocytopenia (platelet count < 100,000/mm³). Immune thrombocytopenic purpura can be either primary or secondary due to drugs or underlying disease. Immune Thrombocytopenic Purpura is variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables. Treatment includes platelet transfusion, steroids Steroids A group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. Benign Liver Tumors, IVIG IVIG Dermatomyositis, and sometimes splenectomy Splenectomy Surgical procedure involving either partial or entire removal of the spleen. Rupture of the Spleen.
  • Thrombotic thrombocytopenic purpura Thrombotic thrombocytopenic purpura Thrombotic thrombocytopenic purpura (TTP) is a life-threatening condition due to either a congenital or an acquired deficiency of ADAMTS-13, a metalloproteinase that cleaves multimers of von Willebrand factor (VWF). The large multimers then aggregate excessive platelets resulting in microvascular thrombosis and an increase in consumption of platelets. Thrombotic Thrombocytopenic Purpura ( TTP TTP Thrombotic thrombocytopenic purpura (TTP) is a life-threatening condition due to either a congenital or an acquired deficiency of adamts-13, a metalloproteinase that cleaves multimers of von Willebrand factor (vWF). The large multimers then aggregate excessive platelets resulting in microvascular thrombosis and an increase in consumption of platelets. Thrombotic Thrombocytopenic Purpura): life-threatening condition due to either a congenital Congenital Chorioretinitis or an acquired deficiency of ADAMTS-13, a metalloproteinase that cleaves multimers of VWF: These large multimers then aggregate excessive platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology, resulting in microvascular thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus and an increase in consumption of platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology. Clinical presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor can consist of thrombocytopenia, hemolytic anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types, hematuria Hematuria Presence of blood in the urine. Renal Cell Carcinoma, GI symptoms, neurologic symptoms, and renal involvement.
  • Disseminated intravascular coagulation Disseminated intravascular coagulation Disseminated intravascular coagulation (DIC) is a condition characterized by systemic bodywide activation of the coagulation cascade. This cascade results in both widespread microvascular thrombi contributing to multiple organ dysfunction and consumption of clotting factors and platelets, leading to hemorrhage. Disseminated Intravascular Coagulation ( DIC DIC Disseminated intravascular coagulation (DIC) is a condition characterized by systemic bodywide activation of the coagulation cascade. This cascade results in both widespread microvascular thrombi contributing to multiple organ dysfunction and consumption of clotting factors and platelets, leading to hemorrhage. Disseminated Intravascular Coagulation): a condition characterized by systemic body-wide activation of the coagulation cascade Coagulation cascade The coagulation cascade is a series of reactions that ultimately generates a strong, cross-linked fibrin clot. Hemostasis. This activation results in both widespread microvascular thrombi contributing to multiple organ dysfunction and consumption of clotting factors and platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology, leading to hemorrhage. DIC DIC Disseminated intravascular coagulation (DIC) is a condition characterized by systemic bodywide activation of the coagulation cascade. This cascade results in both widespread microvascular thrombi contributing to multiple organ dysfunction and consumption of clotting factors and platelets, leading to hemorrhage. Disseminated Intravascular Coagulation is always triggered by another (often serious) condition, including severe sepsis Severe Sepsis Sepsis in Children, trauma, malignancy Malignancy Hemothorax, or obstetric complications.
  • Hemolytic uremic syndrome Hemolytic uremic syndrome A syndrome that is associated with microvascular diseases of the kidney, such as renal cortical necrosis. It is characterized by hemolytic anemia; thrombocytopenia; and acute renal failure. Hypocoagulable Conditions ( HUS HUS Hemolytic uremic syndrome (HUS) is a clinical phenomenon most commonly seen in children that consists of a classic triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Hemolytic uremic syndrome is a major cause of acute kidney injury in children and is most commonly associated with a prodrome of diarrheal illness caused by shiga-like toxin-producing bacteria. Hemolytic Uremic Syndrome): clinical phenomenon most commonly seen in children: Hemolytic uremic syndrome Hemolytic uremic syndrome A syndrome that is associated with microvascular diseases of the kidney, such as renal cortical necrosis. It is characterized by hemolytic anemia; thrombocytopenia; and acute renal failure. Hypocoagulable Conditions consists of the classic triad of microangiopathic hemolytic anemia Microangiopathic Hemolytic Anemia Hemolytic Uremic Syndrome, thrombocytopenia, and AKI AKI Acute kidney injury refers to sudden and often reversible loss of renal function, which develops over days or weeks. Azotemia refers to elevated levels of nitrogen-containing substances in the blood that accompany AKI, which include BUN and creatinine. Acute Kidney Injury and is most commonly associated with a prodrome Prodrome Symptoms that appear 24–48 hours prior to migraine onset. Migraine Headache of diarrheal illness caused by Shiga-like toxin Shiga-Like Toxin Hemolytic Uremic Syndrome–producing bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology.
  • Aplastic anemia Aplastic Anemia Aplastic anemia (AA) is a rare, life-threatening condition characterized by pancytopenia and hypocellularity of the bone marrow (in the absence of any abnormal cells) reflecting damage to hematopoietic stem cells. Aplastic anemia can be acquired or inherited, however, most cases of AA are acquired and caused by autoimmune damage to hematopoietic stem cells. Aplastic Anemia ( AA AA Amyloidosis): rare life-threatening condition characterized by pancytopenia Pancytopenia Deficiency of all three cell elements of the blood, erythrocytes, leukocytes and platelets. Aplastic Anemia and hypocellularity of the bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow: Aplastic anemia Aplastic Anemia Aplastic anemia (AA) is a rare, life-threatening condition characterized by pancytopenia and hypocellularity of the bone marrow (in the absence of any abnormal cells) reflecting damage to hematopoietic stem cells. Aplastic anemia can be acquired or inherited, however, most cases of AA are acquired and caused by autoimmune damage to hematopoietic stem cells. Aplastic Anemia is due to damaged hematopoietic stem cells Hematopoietic stem cells Progenitor cells from which all blood cells derived. They are found primarily in the bone marrow and also in small numbers in the peripheral blood. Bone Marrow: Composition and Hematopoiesis (HSCs). It can be acquired or inherited. Most cases are acquired and caused by autoimmune damage to HSCs. Other causes include medications and chemicals, high doses of whole-body radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma, viral infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease, immune diseases, pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care, Fanconi anemia Fanconi anemia Congenital disorder affecting all bone marrow elements, resulting in anemia; leukopenia; and thrombopenia, and associated with cardiac, renal, and limb malformations as well as dermal pigmentary changes. Spontaneous chromosome breakage is a feature of this disease along with predisposition to leukemia. There are at least 7 complementation groups in Fanconi anemia: fanca, fancb, fancc, fancd1, fancd2, fance, fancf, fancg, and fancl. Aplastic Anemia, and Down syndrome Down syndrome Down syndrome, or trisomy 21, is the most common chromosomal aberration and the most frequent genetic cause of developmental delay. Both boys and girls are affected and have characteristic craniofacial and musculoskeletal features, as well as multiple medical anomalies involving the cardiac, gastrointestinal, ocular, and auditory systems. Down syndrome (Trisomy 21).

References

  1. Gauer, R. (2012). Thrombocytopenia. American Family Physician 85(6):612–622.
  2. Arnold, D. (2021). Diagnostic approach to the adult with unexplained thrombocytopenia. Retrieved April 10, 2021, from https://www.uptodate.com/contents/diagnostic-approach-to-the-adult-with-unexplained-thrombocytopenia
  3. Tuan, S. (2021). Clinical and laboratory aspects of platelet transfusion therapy. Retrieved April 10, 2021, fromhttps://www.uptodate.com/contents/clinical-and-laboratory-aspects-of-platelet-transfusion-therapy
  4. Longo, D., Fauci, A., Kasper, D., Hauser, S., Jameson, J., Loscalzo, J. (2012). Harrison’s Manual of Medicine, 18th ed. McGraw-Hill Professional, pp. 673–675.
  5. Konkle, B. A. (2008). Disorders of platelets and vessel wall. In Fauci, A. S., Braunwald, E., Kasper, D. L., et al. (Eds.), Harrison’s Internal Medicine, 17th ed., McGraw-Hill, pp. 718–723.
  6. Kuter, D. J. (2021) Megakaryocyte biology and the production of platelets. In Tirnauer, J.S. (Ed.), UpToDate. Retrieved April 14, 2021, from https://www.uptodate.com/contents/megakaryocyte-biology-and-the-production-of-platelets 

USMLE™ is a joint program of the Federation of State Medical Boards (FSMB®) and National Board of Medical Examiners (NBME®). MCAT is a registered trademark of the Association of American Medical Colleges (AAMC). NCLEX®, NCLEX-RN®, and NCLEX-PN® are registered trademarks of the National Council of State Boards of Nursing, Inc (NCSBN®). None of the trademark holders are endorsed by nor affiliated with Lecturio.

Study on the Go

Lecturio Medical complements your studies with evidence-based learning strategies, video lectures, quiz questions, and more – all combined in one easy-to-use resource.

Learn even more with Lecturio:

Complement your med school studies with Lecturio’s all-in-one study companion, delivered with evidence-based learning strategies.

User Reviews

¡Hola!

Esta página está disponible en Español.

🍪 Lecturio is using cookies to improve your user experience. By continuing use of our service you agree upon our Data Privacy Statement.

Details