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 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, leading to hemorrhage. DIC is always triggered by another (often serious) condition, including severe sepsis Sepsis Organ dysfunction resulting from a dysregulated systemic host response to infection separates sepsis from uncomplicated infection. The etiology is mainly bacterial and pneumonia is the most common known source. Patients commonly present with fever, tachycardia, tachypnea, hypotension, and/or altered mentation. Sepsis and Septic Shock, trauma, malignancy, or obstetric complications. Acute DIC often presents dramatically, with rapid onset of spontaneous bleeding from multiple locations throughout the body simultaneously. A chronic form of DIC also exists, typically in patients with late-stage malignancies. Management involves stabilizing the patient, replacing consumed 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 and coagulation factors, and treating the triggering condition.

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Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

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Overview

Definition

Disseminated intravascular coagulation (DIC) is a condition characterized by systemic bodywide activation of the coagulation cascade that results in both:

  • Widespread microvascular thrombi contributing to multiple organ dysfunction
  • 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 leading to hemorrhage

Epidemiology

  • Incidence rates:
    • 1% of all hospitalized patients in tertiary care centers
    • 30%–50% of septic patients
    • Approximately 40% of severe trauma patients
    • 20% of pregnant patients with HELLP syndrome
    • 66% of pregnant patients with amniotic fluid embolism
  • Gender bias Bias Epidemiological studies are designed to evaluate a hypothesized relationship between an exposure and an outcome; however, the existence and/or magnitude of these relationships may be erroneously affected by the design and execution of the study itself or by conscious or unconscious errors perpetrated by the investigators or the subjects. These systematic errors are called biases. Types of Biases: none, equal incidence between sexes
  • Age bias Bias Epidemiological studies are designed to evaluate a hypothesized relationship between an exposure and an outcome; however, the existence and/or magnitude of these relationships may be erroneously affected by the design and execution of the study itself or by conscious or unconscious errors perpetrated by the investigators or the subjects. These systematic errors are called biases. Types of Biases: none, may develop at any age
  • Ethnic bias Bias Epidemiological studies are designed to evaluate a hypothesized relationship between an exposure and an outcome; however, the existence and/or magnitude of these relationships may be erroneously affected by the design and execution of the study itself or by conscious or unconscious errors perpetrated by the investigators or the subjects. These systematic errors are called biases. Types of Biases: none, occurs in all races
  • Prognosis: 
    • Depends on the severity of the coagulopathy and the underlying condition that led to the disease
    • Generally poor if untreated

Classification

Acute DIC:

  • Sudden overwhelming activation of systemic coagulation and subsequent fibrinolysis
  • Occurs in the setting of an acute process:
    • Trauma
    • Sepsis
    • Pregnancy Pregnancy Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-HCG test (typically a qualitative urine test) and pelvic ultrasound. Pregnancy: Diagnosis, Maternal Physiology, and Routine Care complications
  • Frequently results in significant hemorrhage and end-organ damage

Chronic DIC:

  • Insidious presentation due to continuous exposure to systemic procoagulants
  • Typically occurs in late-stage malignancies
  • More likely to result in thrombotic (rather than hemorrhagic) complications

Etiology

Disseminated intravascular coagulation is always a complication of other conditions:

Table: Etiologies of disseminated intravascular coagulation
Infection
  • Bacterial:
    • Sepsis (both gram-positive and gram-negative species)
    • Escherichia coli Escherichia coli The gram-negative bacterium Escherichia coli is a key component of the human gut microbiota. Most strains of E. coli are avirulent, but occasionally they escape the GI tract, infecting the urinary tract and other sites. Less common strains of E. coli are able to cause disease within the GI tract, most commonly presenting as abdominal pain and diarrhea. Escherichia coli
    • Neisseria Neisseria Neisseria is a genus of bacteria commonly present on mucosal surfaces. Several species exist, but only 2 are pathogenic to humans: N. gonorrhoeae and N. meningitidis. Neisseria species are non-motile, gram-negative diplococci most commonly isolated on modified Thayer-Martin (MTM) agar. Neisseria meningitidis
  • Viral:
    • HIV
    • Cytomegalovirus Cytomegalovirus CMV is a ubiquitous double-stranded DNA virus belonging to the Herpesviridae family. CMV infections can be transmitted in bodily fluids, such as blood, saliva, urine, semen, and breast milk. The initial infection is usually asymptomatic in the immunocompetent host, or it can present with symptoms of mononucleosis. Cytomegalovirus
    • Varicella
    • Hepatitis
  • Parasitic: 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. Malaria
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
  • Pancreatitis
  • Fulminant 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 failure
Malignancy
  • Acute promyelocytic leukemia
  • Metastatic adenocarcinomas, especially:
    • Pancreas Pancreas The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. This organ has both exocrine and endocrine tissue. Pancreas
    • Stomach
    • Ovary
    • Prostate Prostate The prostate is a gland in the male reproductive system. The gland surrounds the bladder neck and a portion of the urethra. The prostate is an exocrine gland that produces a weakly acidic secretion, which accounts for roughly 20% of the seminal fluid. Prostate and other Male Reproductive Glands
Obstetric causes
  • Amniotic fluid embolism
  • Placental abruption
  • Postpartum hemorrhage Postpartum hemorrhage Postpartum hemorrhage is one of the most common and deadly obstetric complications. Since 2017, postpartum hemorrhage has been defined as blood loss greater than 1,000 mL for both cesarean and vaginal deliveries, or excessive blood loss with signs of hemodynamic instability. Postpartum Hemorrhage
  • Preeclampsia/eclampsia/HELLP syndrome
  • Retained stillbirth
  • Septic abortion
  • Acute fatty 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 of pregnancy
Trauma
  • Burns Burns A burn is a type of injury to the skin and deeper tissues caused by exposure to heat, electricity, chemicals, friction, or radiation. Burns are classified according to their depth as superficial (1st-degree), partial-thickness (2nd-degree), full-thickness (3rd-degree), and 4th-degree burns. Burns
  • Frostbite Frostbite Injuries due to cold weather are common among children and athletes who are involved in sports played in cold conditions. Frostbite is a direct freezing injury to the peripheral tissues and occurs when the skin temperature drops below 0°C (32°F). Common sites of frostbite include the nose, ears, fingers, and toes. Frostbite
  • Head injuries
  • Snake bites
Hematologic and vascular causes
  • Hemolytic transfusion reaction (e.g., ABO incompatibility)
  • Large hemangiomas (Kasabach–Merritt syndrome)
  • Abdominal aortic aneurysm Aneurysm An aneurysm is a bulging, weakened area of a blood vessel that causes an abnormal widening of its diameter > 1.5 times the size of the native vessel. Aneurysms occur more often in arteries than in veins and are at risk of dissection and rupture, which can be life-threatening. Extremity and Visceral Aneurysms/dissection (chronically exposed subendothelium)

Pathophysiology

In DIC, coagulation and subsequent fibrinolysis are activated systemically, which is abnormal and leads to microthrombi throughout the vasculature. These microthrombi consume large amounts 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 and coagulation factors, leading to a severe coagulopathy and clinical bleeding.

Normal activation of coagulation

  • Platelets bind exposed von Willebrand factor (VWF) on injured endothelial cells:
    • Adherent 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 activate and express glycoprotein (Gp) IIb/IIIa receptors.
    • GpIIb/IIIa receptors bind fibrinogen.
    • Fibrinogen can bind one platelet on each side → platelet aggregation/formation of the platelet plug
    • Activated 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 secrete substances that augment further platelet aggregation and the coagulation cascade.
  • Tissue factor (TF) binds circulating factor VII and activates the extrinsic pathway (initial activation of the coagulation cascade):
    • Membrane-bound glycoprotein expressed on injured endothelial cells
    • Restricts activation of the cascade primarily to local sites of injury
  • The initial thrombin produced activates factor XI in the intrinsic pathway.
    • The intrinsic pathway significantly amplifies the local response.
    • Coagulation factors form multicomponent enzyme complexes, which are also bound to membrane surfaces.
    • Keeps coagulation localized
  • Thrombin converts fibrinogen to fibrin, forming a stable clot.
  • Plasmin Plasmin A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (b) and heavy (a), with a molecular weight of 75, 000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. Hemostasis is produced to break down fibrin.
  • Fibrin degradation products (FDPs):
    • Have anticoagulant properties
    • Are cleared by 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

Activation of systemic coagulation (abnormal)

  • Abnormal systemic activation of the coagulation cascade may occur owing to:
    • An overwhelming systemic inflammatory response (e.g., severe sepsis Sepsis Organ dysfunction resulting from a dysregulated systemic host response to infection separates sepsis from uncomplicated infection. The etiology is mainly bacterial and pneumonia is the most common known source. Patients commonly present with fever, tachycardia, tachypnea, hypotension, and/or altered mentation. Sepsis and Septic Shock)
    • Sudden exposure of the blood to procoagulants, including:
      • TF
      • Thromboplastin
      • VWF
    • Examples of procoagulant exposure:
      • Sepsis: Bacterial endotoxins can trigger release of circulating TF.
      • Malignancy: Some cancers can produce circulating TF.
      • Trauma: Significant vascular endothelial damage results in ↑ amounts of TF.
      • Obstetric: The placenta Placenta The placenta consists of a fetal side and a maternal side, and it provides a vascular communication between the mother and the fetus. This communication allows the mother to provide nutrients to the fetus and allows for removal of waste products from fetal blood. Placenta, Umbilical Cord, and Amniotic Cavity can release a proteolytic enzyme capable of activating factor X.
  • Effects of systemic coagulation:
    • With systemic activation of the coagulation cascade, thrombi are formed throughout the vasculature.
    • Thrombi can affect both small and large vessels.
    • Extensive, systemwide coagulation consumes large amounts 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 and coagulation factors.
  • Fibrinolysis:
    • Activated in conjunction with coagulation cascade
    • Plasmin Plasmin A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (b) and heavy (a), with a molecular weight of 75, 000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. Hemostasis cleaves fibrin polymers and produces FDPs.
    • ↑ Levels of FDPs interfere with new fibrin clot formation and platelet aggregation → impaired hemostasis Hemostasis Hemostasis refers to the innate, stepwise body processes that occur following vessel injury, resulting in clot formation and cessation of bleeding. Hemostasis occurs in 2 phases, namely, primary and secondary. Primary hemostasis involves forming a plug that stops the bleeding temporarily. Secondary hemostasis involves the activation of the coagulation cascade. Hemostasis
  • End-organ damage occurs by:
    • Widespread microthrombi formation
    • Hemorrhage
    • Ischemic effects from hemorrhagic hypovolemia
  • Organ dysfunction can include:
    • Change in mental status
    • Acute kidney injury Acute Kidney Injury 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
    • Respiratory dysfunction
    • Hepatic dysfunction
    • Cardiac tamponade Cardiac tamponade Pericardial effusion is the accumulation of excess fluid in the pericardial space around the heart. The pericardium does not easily expand; thus, rapid fluid accumulation leads to increased pressure around the heart. The increase in pressure restricts cardiac filling, resulting in decreased cardiac output and cardiac tamponade. Pericardial Effusion and Cardiac Tamponade
    • Hemothorax Hemothorax A hemothorax is a collection of blood in the pleural cavity. Hemothorax most commonly occurs due to damage to the intercostal arteries or from a lung laceration following chest trauma. Hemothorax can also occur as a complication of disease, or hemothorax may be spontaneous or iatrogenic. Hemothorax
    • Intracerebral hemorrhage Intracerebral Hemorrhage Intracerebral hemorrhage (ICH) refers to a spontaneous or traumatic bleed into the brain parenchyma and is the 2nd-most common cause of cerebrovascular accidents (CVAs), commonly known as stroke, after ischemic CVAs. Intracerebral Hemorrhage
    • Gangrene and loss of digits

Acute versus chronic disseminated intravascular coagulation

Acute DIC is decompensated DIC:

  • Rapid systemic activation of coagulation 
  • Leads to rapid 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 and coagulation factors 
  • Consumption significantly outpaces production.
  • ↑ Number of thrombi → ↑ fibrinolysis → ↑ FDPs → pathologically prevents new clots and platelet aggregation
  • End result: severe clinical bleeding/hemorrhage plus thrombotic end-organ damage

Chronic DIC is compensated DIC:

  • Typically occurs in patients with:
    • Advanced malignancy 
    • Large aneurysms
  • Develops when blood is continuously (or intermittently) exposed to smaller amounts of procoagulants
  • Compensation mechanisms:
    • New production 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 and coagulation factors
    • Liver is able to clear FDPs.
  • Compensation mechanisms are able to balance the ongoing consumption of products and production of FDPs.
  • Thrombotic complications are more common than bleeding.

Clinical Presentation

Acute disseminated intravascular coagulation

Acute DIC typically presents rapidly and dramatically, with acute and severe bleeding from multiple sites simultaneously throughout the body. Other manifestations are related to thrombotic end-organ dysfunction.

Table: Clinical manifestations of acute disseminated intravascular coagulation
Vital signs
  • Hypovolemic shock Shock Shock is a life-threatening condition associated with impaired circulation that results in tissue hypoxia. The different types of shock are based on the underlying cause: distributive (↑ cardiac output (CO), ↓ systemic vascular resistance (SVR)), cardiogenic (↓ CO, ↑ SVR), hypovolemic (↓ CO, ↑ SVR), obstructive (↓ CO), and mixed. Types of Shock
  • Hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension
  • Tachycardia
Skin
  • Petechiae
  • Ecchymosis
  • Bleeding from IV and drain sites
  • Surgical site bleeding
  • Purpura fulminans (life threatening):
    • Extensive tissue thrombosis
    • Skin necrosis
    • Retiform purpura
    • Associated with protein C deficiency
  • Gangrene
Mucosal
  • Gingival bleeding
  • Epistaxis
Renal
  • Hematuria
  • Oliguria
  • Azotemia
Pulmonary
  • Hemoptysis Hemoptysis Hemoptysis is defined as the expectoration of blood originating in the lower respiratory tract. Hemoptysis is a consequence of another disease process and can be classified as either life threatening or non-life threatening. Hemoptysis can result in significant morbidity and mortality due to both drowning (reduced gas exchange as the lungs fill with blood) and hemorrhagic shock. Hemoptysis
  • Hemothorax Hemothorax A hemothorax is a collection of blood in the pleural cavity. Hemothorax most commonly occurs due to damage to the intercostal arteries or from a lung laceration following chest trauma. Hemothorax can also occur as a complication of disease, or hemothorax may be spontaneous or iatrogenic. Hemothorax
  • ARDS ARDS Acute respiratory distress syndrome is characterized by the sudden onset of hypoxemia and bilateral pulmonary edema without cardiac failure. Sepsis is the most common cause of ARDS. The underlying mechanism and histologic correlate is diffuse alveolar damage (DAD). Acute Respiratory Distress Syndrome
GI
  • Hematochezia
  • Hematemesis
Neurologic
  • Altered mental status
  • Hemorrhagic stroke
  • Ischemic stroke Ischemic Stroke An ischemic stroke (also known as cerebrovascular accident) is an acute neurologic injury that occurs as a result of brain ischemia; this condition may be due to cerebral blood vessel occlusion by thrombosis or embolism, or rarely due to systemic hypoperfusion. Ischemic Stroke
  • Focal neurologic deficits
  • Headache
  • Seizure
Skin manifestation of dic - purpura

Skin manifestation of DIC:
Note the petechiae and purpura.

Image: “ Purpura” by George Henry Fox. License: Public Domain

Chronic disseminated intravascular coagulation

  • Frequently asymptomatic
  • Thrombotic sequelae are more common than bleeding complications.
  • Manifestations can include:
    • Venous thromboembolism
    • Petechiae and ecchymosis
    • Bleeding from IV lines, catheters, and mucosal surfaces

Diagnosis

The diagnosis is made on the basis of clinical history and laboratory findings, though no single test is diagnostic for DIC. Laboratory tests also aid in management.

Laboratory tests

In DIC, coagulation 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 are rapidly consumed in the formation of systemwide microthrombi. Lab findings in DIC include:

  • CBC:
    • Mild-to-moderate thrombocytopenia Thrombocytopenia Thrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000-450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. Thrombocytopenia ( 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 are consumed)
    • 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 (due to hemorrhage and hemolysis)
  • Peripheral blood smear:
    • Microangiopathic hemolytic anemia Hemolytic Anemia Hemolytic anemia (HA) is the term given to a large group of anemias that are caused by the premature destruction/hemolysis of circulating red blood cells (RBCs). Hemolysis can occur within (intravascular hemolysis) or outside the blood vessels (extravascular hemolysis). Hemolytic Anemia
    • Schistocytes: fragmented, jagged RBCs
  • PT: 
    • ↑ (prolonged) in DIC
    • Interpretation: Factors in the extrinsic and/or common pathways have been consumed.
  • aPTT: 
    • ↑ (prolonged) in DIC
    • Interpretation: Factors in the intrinsic and/or common pathways have been consumed.
  • Fibrinogen:
    • Usually ↓ owing to consumption
    • May be normal despite significant consumption if fibrinogen was originally ↑, which occurs in patients with:
      • Sepsis
      • Malignancy
      • Other inflammatory conditions
  • D-dimer: 
    • ↑↑ in DIC
    • An FDP, which indicates recent or ongoing thrombosis
    • Interpretation: A negative test for D-dimer essentially rules out DIC.
  • Findings in chronic DIC:
    • Thrombocytopenia (mild)
    • ↓ or normal PT and aPTT
    • ↑ D-dimer
Schistocytes as diagnostic of dic

Peripheral blood smear showing schistocytes, which are indicative of intravascular hemolysis

Image: “Disseminated carcinomatosis with DIC” by Ed Uthman, MD. License: Public Domain

Imaging

No specific imaging study confirms the diagnosis of DIC. Specific imaging methods may be indicated to assist in:

  • The diagnosis of the underlying etiology (e.g., abdominal imaging for suspected malignancy)
  • Evaluation of end-organ damage (e.g., head CT in patients with evidence of stroke)

Management

The most important principles in management are to treat the underlying cause and stabilize the patient.

Acute disseminated intravascular coagulation

  • Emergency care: airway, breathing, circulation:
    • Ensure that the airway is secure and support ventilation.
    • Hemodynamic support:
      • Volume resuscitation with IV fluids IV fluids Intravenous fluids are one of the most common interventions administered in medicine to approximate physiologic bodily fluids. Intravenous fluids are divided into 2 categories: crystalloid and colloid solutions. Intravenous fluids have a wide variety of indications, including intravascular volume expansion, electrolyte manipulation, and maintenance fluids. Intravenous Fluids
      • Vasopressors
      • Blood transfusion
  • Product replacement: coagulation 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 (see Blood component replacement below)
  • Treat the underlying cause: treatment may include:
    • Antimicrobial agents
    • Delivery of fetus in obstetric cases

Blood component replacement

  • Platelets:
    • 1 pool of 5–6 units should ↑ platelet counts by approximately 30,000/µL 
    • Indications:
      • Active bleeding
      • Platelets < 50,000/µL with need for urgent surgery
      • Platelets < 10,000/µL
  • Fresh frozen plasma (FFP)
    • 1 unit = 200–300 mL
    • Contains all soluble plasma proteins and clotting factors 
    • Indications: 
      • Serious bleeding and ↑ PT or aPTT 
      • Serious bleeding and ↓ fibrinogen
  • Cryoprecipitate
    • 1 unit = 10–20 mL 
    • Contains:
      • Fibrinogen
      • Factors VIII and XIII
      • VWF
    • Indication: fibrinogen < 100 mg/dL
    • Used to help boost fibrinogen without significant extra volume

Chronic disseminated intravascular coagulation

  • Anticoagulation with heparins (for deep vein thrombosis Deep vein thrombosis Deep vein thrombosis (DVT) usually occurs in the deep veins of the lower extremities. The affected veins include the femoral, popliteal, iliofemoral, and pelvic veins. Proximal DVT is more likely to cause a pulmonary embolism (PE) and is generally considered more serious. Deep Vein Thrombosis ( DVT DVT Deep vein thrombosis (DVT) usually occurs in the deep veins of the lower extremities. The affected veins include the femoral, popliteal, iliofemoral, and pelvic veins. Proximal DVT is more likely to cause a pulmonary embolism (PE) and is generally considered more serious. Deep Vein Thrombosis) prophylaxis)
  • Treat the underlying cause (usually malignancy)

Differential Diagnosis

  • 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: 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 is the primary site of synthesis for a majority of the clotting factors. In addition to impaired synthesis of clotting factors, cirrhosis also may independently result in thrombocytopenia Thrombocytopenia Thrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000-450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. Thrombocytopenia owing to splenic 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 and decreased thrombopoietin production. Platelets themselves may also be dysfunctional. Like DIC, cirrhosis can lead to both bleeding and thrombosis. A history of 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 injury and abnormal liver function tests Liver function tests Liver function tests, also known as hepatic function panels, are one of the most commonly performed screening blood tests. Such tests are also used to detect, evaluate, and monitor acute and chronic liver diseases. Liver Function Tests can help distinguish cirrhosis from DIC. Of note, fulminant 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 failure may actually trigger DIC, as well.
  • 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): a bleeding disorder marked by a pentad of microangiopathic hemolytic anemia Hemolytic Anemia Hemolytic anemia (HA) is the term given to a large group of anemias that are caused by the premature destruction/hemolysis of circulating red blood cells (RBCs). Hemolysis can occur within (intravascular hemolysis) or outside the blood vessels (extravascular hemolysis). Hemolytic Anemia, thrombocytopenia Thrombocytopenia Thrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000-450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. Thrombocytopenia, renal failure, neurologic symptoms, and fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever: 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 occurs because of a congenital or acquired deficiency of ADAMTS13, which is a metalloproteinase that cleaves VWF. Deficiencies of ADAMTS13 result in large VWF multimers that increase platelet aggregation, leading to microvascular thrombosis and 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. Unlike DIC, in TTP, the PT and PTT are usually normal (or only mildly elevated) and fibrinogen is normal or even increased.
  • Immune thrombocytopenia Thrombocytopenia Thrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000-450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. Thrombocytopenia ( 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): an autoimmune disorder characterized by anti-GpIIb/IIIa autoantibodies that lead to the 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: Immune thrombocytopenia Thrombocytopenia Thrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000-450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. Thrombocytopenia often occurs after GI or respiratory viral infections, though it can also be drug-induced. Clinically, it may present with prolonged bleeding, petechiae, easy bruising, and/or purpura. Unlike DIC, in 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, there is no coagulation defect, so the PT and PTT are normal. 

References

  1. Marcel, M. (2020). Disseminated intravascular coagulation (DIC). Retrieved March 21, 2021, from https://emedicine.medscape.com/article/199627-overview
  2. Leng, L. (2021). Disseminated intravascular coagulation (DIC) in adults: Evaluation and management. Retrieved March 21, 2021, from https://www.uptodate.com/contents/disseminated-intravascular-coagulation-dic-in-adults-evaluation-and-management
  3. Longo, D., Fauci, A., Kasper, D., Hauser, S., Jameson, J., Loscalzo, J. (2012). Harrison’s Manual of Medicine, 18th ed. McGraw-Hill Professional, pages 2188–2191.

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