Anemia: Overview

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 may occur from blood loss, decreased RBC production such as in iron deficiency, or increased RBC destruction such as in hemolysis. Management is aimed at improving Hb levels and treating the underlying conditions.

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Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

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Overview

Definition

Anemia is a quantitative deficiency of Hb, the oxygen-carrying component of RBCs. Anemia is noted when Hb levels are approximately:

  • < 13.5 g/dL in adult males
  • < 12 g/dL in adult females 
  • < 11 g/dL in children

Normal levels can vary depending on the laboratory reference range.

Epidemiology

  • Found in patients of all ages, from infants to elderly
  • More common in women than in men
  • Prevalence:
    •  > 20% of individuals who are > 85 years of age
    • Mild iron deficiency anemia Iron Deficiency Anemia Iron deficiency anemia is the most common type of anemia worldwide. This form of anemia is caused by insufficient iron due to a decreased supply, an increased loss, or an increased demand. Iron deficiency anemia is seen across all ages, sexes, and socioeconomic strata; however, children, women of childbearing age, and patients from lower socioeconomic strata are at higher risk. Iron Deficiency Anemia is common in women of reproductive age.
  • Hemoglobinopathies are more common in certain ethnicities:
    • Sickle cell disease Sickle cell disease Sickle cell disease (SCD) is a group of genetic disorders in which an abnormal Hb molecule (HbS) transforms RBCs into sickle-shaped cells, resulting in chronic anemia, vasoocclusive episodes, pain, and organ damage. Sickle Cell Disease: Black or African descent
    • Hereditary spherocytosis Hereditary Spherocytosis Hereditary spherocytosis (HS) is the most common type of hereditary hemolytic anemia. The condition is caused by a cytoskeletal protein deficiency in the RBC membrane. This results in loss of membrane stability and deformability of the RBC, giving the cell its spherical shape (spherocyte). Hereditary Spherocytosis: European descent
    • Thalassemia Thalassemia Thalassemia is a hereditary cause of microcytic hypochromic anemia and results from a deficiency in either the α or β globin chains, resulting in hemoglobinopathy. The presentation of thalassemia depends on the number of defective chains present and can range from being asymptomatic to rendering the more severely affected patients to be transfusion dependent. Thalassemia: Mediterranean and Southeast Asian descent

Anatomy and physiology review

  • RBCs are produced in the bone marrow Bone marrow Bone marrow, the primary site of hematopoiesis, is found in the cavities of cancellous bones and the medullary canals of long bones. There are 2 types: red marrow (hematopoietic with abundant blood cells) and yellow marrow (predominantly filled with adipocytes). Composition of Bone Marrow.
  • Pluripotent hematopoietic stem cells → common myeloid stem cell → proerythroblast → erythrocyte
  • RBC production is stimulated by erythropoietin Erythropoietin Glycoprotein hormone, secreted chiefly by the kidney in the adult and the liver in the fetus, that acts on erythroid stem cells of the bone marrow to stimulate proliferation and differentiation. Erythrocytes, which is made in the 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.
  • RBCs are cleared through 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: Senescent, rigid, or abnormal RBCs unable to squeeze through the narrow splenic slits are retained and cleared.

Etiology

Anemia can be caused by:

  • Blood loss
  • Decreased RBC production
  • Increased RBC destruction

Classification of anemia according to etiology

Table: Classification of anemia according to etiology
Etiology Categories Types of anemia
Blood loss Acute
  • Trauma
  • Surgery
  • 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
  • Severe epistaxis
Chronic
  • GI bleeding (upper or lower):
    • Peptic ulcer disease Peptic ulcer disease Peptic ulcer disease (PUD) refers to the full-thickness ulcerations of duodenal or gastric mucosa. The ulcerations form when exposure to acid and digestive enzymes overcomes mucosal defense mechanisms. The most common etiologies include Helicobacter pylori (H. pylori) infection and prolonged use of non-steroidal anti-inflammatory drugs (NSAIDs). Peptic Ulcer Disease
    • Diverticular disease Diverticular disease Diverticula are protrusions of the bowel wall occurring most commonly in the colon. The condition of having diverticula (called diverticulosis) is mostly asymptomatic. These diverticula can become symptomatic, however, when associated with diseases. Diverticulitis is the inflammation of diverticula, often presenting with lower abdominal pain and changes in bowel habits. Diverticular Disease
    • Cancer
  • Heavy menstrual bleeding
Decreased RBC production Abnormal proliferation or differentiation of stem cells
  • 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
  • Pure red cell aplasia
  • Anemia of renal failure (due to ↓ erythropoietin Erythropoietin Glycoprotein hormone, secreted chiefly by the kidney in the adult and the liver in the fetus, that acts on erythroid stem cells of the bone marrow to stimulate proliferation and differentiation. Erythrocytes)
Defective DNA DNA The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival. DNA Types and Structure synthesis in erythroblasts
  • Vitamin B12 deficiency
  • 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 deficiency
Defective Hb synthesis
  • Defective heme synthesis:
    • Iron deficiency anemia
    • Lead poisoning
  • Defective globin chains:
    • Hemoglobinopathies, including sickle cell anemia
    • Thalassemias
Unknown or multiple mechanisms
  • Sideroblastic anemia Sideroblastic anemia Sideroblastic anemias are a heterogeneous group of bone marrow disorders characterized by abnormal iron accumulation in the mitochondria of erythroid precursors. The accumulated iron appears as granules in a ringlike distribution around the nucleus, giving rise to the characteristic morphological feature of a ring sideroblast. Sideroblastic Anemia
  • Anemia of chronic infections
Increased RBC destruction Abnormal Hb
  • Sickle cell anemia
  • Thalassemias
Enzyme deficiencies
  • Glucose-6-phosphate dehydrogenase (G6PD)
  • Glutathione synthetase
  • Pyruvate kinase
  • Hexokinase
Membrane disorders
  • Spherocytosis
  • Elliptocytosis
  • Paroxysmal nocturnal hemoglobinuria Paroxysmal Nocturnal Hemoglobinuria Paroxysmal nocturnal hemoglobinuria (PNH) is a rare but serious acquired hemolytic anemia with periodic exacerbations. This anemia is caused by nonmalignant clonal expansion of ≥ 1 hematopoietic stem cells that have acquired a somatic mutation of the phosphatidylinositol N-acetylglucosaminyltransferase subunit A (PIG-A) gene. Paroxysmal Nocturnal Hemoglobinuria (PNH)
Immune-mediated
  • Autoimmune disease:
    • Idiopathic (primary)
    • 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
    • Malignant neoplasms
  • Drug-associated:
    • Antibiotics
    • NSAIDs
    • Anticancer agents
  • Transfusion reactions Transfusion reactions Transfusion-related complications occur during or after a blood product is given. These complications can be classified as immunologic, non-immunologic and acute, and delayed. Non-immunologic reactions are caused by the transmission of disease in blood products, and immunologic reactions are antigen-antibody-mediated. Transfusion Reactions
Mechanical trauma to RBCs
  • 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)
  • 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
  • Cardiac trauma
Infections
  • 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
  • Hookworm

Classification

Anemia is most commonly classified into the subtype microcytic, normocytic, or macrocytic based on the size of the RBCs. MCV reflects the size of the RBCs and is reported on a CBC.

Anemia overview chart

Classification of anemia based on the MCV

Image by Lecturio.

Microcytic anemia

Microcytic anemia is characterized by small RBCs with a low MCV. These features are usually due to a decreased Hb content within the RBCs. Causes include:

  • Iron deficiency anemia: 
    • The most common cause of anemia
    • Causes include:
      • Chronic GI blood loss
      • Chronic heavy menstrual bleeding
      • Malabsorption Malabsorption Malabsorption involves many disorders in which there is an inability of the gut to absorb nutrients from dietary intake, potentially including water and/or electrolytes. A closely related term, maldigestion is the inability to break down large molecules of food into their smaller constituents. Malabsorption and maldigestion can affect macronutrients (fats, proteins, and carbohydrates), micronutrients (vitamins and minerals), or both. Malabsorption and Maldigestion of iron in chronic GI disease (e.g., Crohn’s or celiac disease Celiac disease Celiac disease (also known as celiac sprue or gluten enteropathy) is an autoimmune reaction to gliadin, which is a component of gluten. Celiac disease is closely associated with HLA-DQ2 and HLA-DQ8. The immune response is localized to the proximal small intestine and causes the characteristic histologic findings of villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis. Celiac Disease)
      • Insufficient dietary iron
      • 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
  • Thalassemia Thalassemia Thalassemia is a hereditary cause of microcytic hypochromic anemia and results from a deficiency in either the α or β globin chains, resulting in hemoglobinopathy. The presentation of thalassemia depends on the number of defective chains present and can range from being asymptomatic to rendering the more severely affected patients to be transfusion dependent. Thalassemia
  • Anemia of chronic disease (later stages)
  • Lead poisoning
  • Sideroblastic anemia Sideroblastic anemia Sideroblastic anemias are a heterogeneous group of bone marrow disorders characterized by abnormal iron accumulation in the mitochondria of erythroid precursors. The accumulated iron appears as granules in a ringlike distribution around the nucleus, giving rise to the characteristic morphological feature of a ring sideroblast. Sideroblastic Anemia

Mnemonic:

To remember the causes of microcytic anemia use the mnemonic TAILS:

  • Thalassemia
  • Anemia of chronic disease
  • Iron deficiency anemia
  • Lead poisoning
  • Sideroblastic anemia

Normocytic anemia

Normocytic anemias have a normal MCV. Often, the reticulocyte count is used to help narrow the differential diagnosis. (Reticulocytes are “new” blood cells in circulation, and their level reflects the rate of new RBC production.) Causes of normocytic anemia include:

Hemolytic anemias:

  • Will have a corrected reticulocyte count > 3%: indicates normally functioning bone marrow Bone marrow Bone marrow, the primary site of hematopoiesis, is found in the cavities of cancellous bones and the medullary canals of long bones. There are 2 types: red marrow (hematopoietic with abundant blood cells) and yellow marrow (predominantly filled with adipocytes). Composition of Bone Marrow
  • Caused by intrinsic RBC defects:
    • Sickle cell disease Sickle cell disease Sickle cell disease (SCD) is a group of genetic disorders in which an abnormal Hb molecule (HbS) transforms RBCs into sickle-shaped cells, resulting in chronic anemia, vasoocclusive episodes, pain, and organ damage. Sickle Cell Disease
    • G6PD deficiency G6PD Deficiency Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a type of intravascular hemolytic anemia. The condition is inherited in an X-linked recessive manner. Patients have episodic hemolysis due to an oxidative stressor that causes damage to red blood cells, which lack sufficient NADPH to protect them from oxidative injury. Glucose-6-phosphate Dehydrogenase (G6PD) Deficiency
    • PNH
    • Hereditary spherocytosis Hereditary Spherocytosis Hereditary spherocytosis (HS) is the most common type of hereditary hemolytic anemia. The condition is caused by a cytoskeletal protein deficiency in the RBC membrane. This results in loss of membrane stability and deformability of the RBC, giving the cell its spherical shape (spherocyte). Hereditary Spherocytosis
  • Causes due to extrinsic defects:
    • Autoimmune hemolytic anemias (e.g., systemic lupus erythematosus)
    • 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 (e.g., TTP, hemolytic uremic syndrome (HUS), 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)
    • Macroangiopathic 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 (e.g., with prosthetic heart valves or aortic stenosis Aortic stenosis Aortic stenosis (AS), or the narrowing of the aortic valve aperture, is the most common valvular heart disease. Aortic stenosis gradually progresses to heart failure, producing exertional dyspnea, angina, and/or syncope. A crescendo-decrescendo systolic murmur is audible in the right upper sternal border. Aortic Stenosis)
    • Infections (e.g., malaria)

Nonhemolytic anemias: 

  • Will have corrected reticulocyte count < 3%: indicates that the bone marrow Bone marrow Bone marrow, the primary site of hematopoiesis, is found in the cavities of cancellous bones and the medullary canals of long bones. There are 2 types: red marrow (hematopoietic with abundant blood cells) and yellow marrow (predominantly filled with adipocytes). Composition of Bone Marrow is not responding to the stressor, leading to underproduction of RBCs
  • Causes:
    • Anemia of chronic disease (earlier stages), usually CKD CKD Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease
    • Anemia of congestive heart failure Congestive heart failure Congestive heart failure refers to the inability of the heart to supply the body with normal cardiac output to meet metabolic needs. Echocardiography can confirm the diagnosis and give information about the ejection fraction. Congestive Heart Failure ( CHF CHF Congestive heart failure refers to the inability of the heart to supply the body with normal cardiac output to meet metabolic needs. Echocardiography can confirm the diagnosis and give information about the ejection fraction. Congestive Heart Failure)
    • Anemia due to endocrine deficiency (e.g., hypothyroidism Hypothyroidism Hypothyroidism is a condition characterized by a deficiency of thyroid hormones. Iodine deficiency is the most common cause worldwide, but Hashimoto's disease (autoimmune thyroiditis) is the leading cause in non-iodine-deficient regions. Hypothyroidism or adrenal insufficiency Adrenal Insufficiency Adrenal insufficiency (AI) is the inadequate production of adrenocortical hormones: glucocorticoids, mineralocorticoids, and adrenal androgens. Primary AI, also called Addison’s disease, is caused by autoimmune disease, infections, and malignancy, among others. Adrenal insufficiency can also occur because of decreased production of adrenocorticotropic hormone (ACTH) from disease in the pituitary gland (secondary) or hypothalamic disorders and prolonged glucocorticoid therapy (tertiary). Adrenal Insufficiency and Addison’s Disease)
    • Diabetes mellitus Diabetes mellitus Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus
    • Obesity
    • Malignancy
    • Aplastic anemias
    • Blood loss < 1 week ago ( bone marrow Bone marrow Bone marrow, the primary site of hematopoiesis, is found in the cavities of cancellous bones and the medullary canals of long bones. There are 2 types: red marrow (hematopoietic with abundant blood cells) and yellow marrow (predominantly filled with adipocytes). Composition of Bone Marrow working properly, but has not yet had enough time to catch up with blood loss)

Macrocytic anemia

Macrocytic anemias have an elevated MCV, or large RCBs. Causes include: 

  • Megaloblastic anemias (the problem is within the bone marrow Bone marrow Bone marrow, the primary site of hematopoiesis, is found in the cavities of cancellous bones and the medullary canals of long bones. There are 2 types: red marrow (hematopoietic with abundant blood cells) and yellow marrow (predominantly filled with adipocytes). Composition of Bone Marrow):
    • Deficiencies of vitamins needed for proper DNA DNA The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival. DNA Types and Structure synthesis (due to either insufficient dietary intake or malabsorption):
      • Vitamin B12 deficiency 
      • 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 deficiency
    • Rare causes:
      • Diamond-Blackfan anemia: a congenital erythroid aplasia that usually presents in infancy; WBCs 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 usually normal
      • Orotic aciduria Orotic aciduria Orotic aciduria is an extremely rare genetic disorder that can result in crystalluria, megaloblastic anemia, developmental delay, and failure to thrive. The disorder is caused by an enzyme deficiency in the pyrimidine synthesis pathway resulting in the accumulation of orotic acid. Orotic Aciduria: autosomal recessive Autosomal recessive Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal recessive diseases are only expressed when 2 copies of the recessive allele are inherited. Autosomal Recessive and Autosomal Dominant Inheritancedisease presenting with physical and intellectual delays in infancy, resulting from defects in the metabolism of orotic acid 
  • Nonmegaloblastic anemias (the problem is outside the bone marrow Bone marrow Bone marrow, the primary site of hematopoiesis, is found in the cavities of cancellous bones and the medullary canals of long bones. There are 2 types: red marrow (hematopoietic with abundant blood cells) and yellow marrow (predominantly filled with adipocytes). Composition of Bone Marrow); can be due to:
    • Liver disease
    • Alcohol use disorder Alcohol use disorder Alcohol is one of the most commonly used addictive substances in the world. Alcohol use disorder (AUD) is defined as pathologic consumption of alcohol leading to impaired daily functioning. Acute alcohol intoxication presents with impairment in speech and motor functions and can be managed in most cases with supportive care. Alcohol Use Disorder
    • Reticulocytosis
    • Drugs (many)

Other ways to classify anemia

  • Acute or chronic 
  • Inherited or acquired defects
  • Primary or secondary

Clinical Presentation

History

Important details when considering a diagnosis of anemia:

  • History of eating disorder
  • History of gastric or intestinal surgery
  • Family history of hematologic diseases
  • Medications that cause or worsen bleeding
  • Medications that may cause 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
  • Travel history
  • Special diet that may lead to a vitamin deficiency (e.g., vegan)
  • Amount of alcohol use

Symptoms and physical exam findings

Symptoms develop based on the rate and severity of Hb decrease from baseline. Anemia is also often asymptomatic and found on laboratory studies only.

Table: Clinical presentation of anemia
Body region/organ system Symptoms Possible physical exam findings
General
  • Fatigue
  • Generalized weakness
  • Loss of appetite
  • Cold hands or feet
  • Restless legs
  • Pica Pica Pica is an eating disorder characterized by a desire or recurrent compulsion to eat substances that are nonnutritive and not food. These compulsions and ingested substances are inappropriate for age or culture. Pica (eating nonfood substances like ice or clay)
  • Pallor
  • 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
Integumentary
  • Itching
  • Dry 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. Structure and Function of the Skin
  • Easy bruising
  • Pallor
  • Jaundice Jaundice Jaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice
  • Purpura
  • Nails with koilonychia (“spoon nails”)
Cardiorespiratory
  • Chest pain Chest Pain Chest pain is one of the most common and challenging complaints that may present in an inpatient and outpatient setting. The differential diagnosis of chest pain is large and includes cardiac, gastrointestinal, pulmonary, musculoskeletal, and psychiatric etiologies. Chest Pain
  • Palpitations
  • Dyspnea
  • Tachycardia
  • Tachypnea
  • Orthostatic 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
  • Signs of CHF CHF Congestive heart failure refers to the inability of the heart to supply the body with normal cardiac output to meet metabolic needs. Echocardiography can confirm the diagnosis and give information about the ejection fraction. Congestive Heart Failure:
    • ↑ Jugular venous pressure
    • S3
    • Respiratory crackles
    • Ankle edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
Head, eyes, ears, nose Nose The nose is the human body's primary organ of smell and functions as part of the upper respiratory system. The nose may be best known for inhaling oxygen and exhaling carbon dioxide, but it also contributes to other important functions, such as tasting. The anatomy of the nose can be divided into the external nose and the nasal cavity. Anatomy of the Nose, and throat (HEENT) Epistaxis
  • Pale conjunctiva
  • Atrophic glossitis
Neurologic
  • Headaches
  • Light-headedness
  • Paresthesias Paresthesias Subjective cutaneous sensations (e.g., cold, warmth, tingling, pressure, etc.) that are experienced spontaneously in the absence of stimulation. Respiratory Alkalosis
  • Decreased sensation
  • Abnormal reflexes
GI/abdomen
  • Hematochezia/rectal bleeding
  • Melena
  • Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea
  • Hematemesis
  • Hepatomegaly
  • 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
  • Hemorrhoids Hemorrhoids Hemorrhoids are normal vascular cushions in the anal canal composed of dilated vascular tissue, smooth muscle, and connective tissue. They do not cause issues unless they are enlarged, inflamed, thrombosed, or prolapsed. Patients often present with rectal bleeding of bright red blood, or they may have pain, perianal pruritus, or a palpable mass. Hemorrhoids
  • Rectal mass
Genitourinary
  • Hematuria
  • Heavy or frequent menstrual bleeding
  • Enlarged uterus Uterus The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The uterus has a thick wall made of smooth muscle (the myometrium) and an inner mucosal layer (the endometrium). The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Posterior Abdominal Wall

Diagnosis

The diagnostic process typically starts by assessing the CBC, MCV, and reticulocyte count, which are best evaluated simultaneously to start narrowing the differential diagnosis. Additional studies may be obtained on the basis of the patient’s clinical presentation.

Serologic studies

  • CBC findings: 
    • Decreased Hb (component of RBCs)
    • Decreased Hct (ratio of the volume of RBCs to the volume of blood, expressed as a percentage)
    • MCV: helps narrow the differential diagnosis
    • Pancytopenia: usually seen in megaloblastic anemia Megaloblastic anemia Megaloblastic anemia is a subset of macrocytic anemias that arises because of impaired nucleic acid synthesis in erythroid precursors. This impairment leads to ineffective RBC production and intramedullary hemolysis that is characterized by large cells with arrested nuclear maturation. The most common causes are vitamin B12 and folic acid deficiencies. Megaloblastic Anemia 
    • Factors that elevate Hb and may mask underlying anemia:
      • Smoking
      • Hemoconcentration due to hypovolemia
      • High altitude
  • Reticulocyte evaluation:
    • Reticulocyte count: 
      • Reticulocytes are immature RBCs in circulation
      • Can be expressed as a percentage of all RBCs or as an absolute number
    • ↑ Reticulocyte count indicates:
      • Hemolysis
      • Recovery from bleeding
      • Removal of a bone marrow Bone marrow Bone marrow, the primary site of hematopoiesis, is found in the cavities of cancellous bones and the medullary canals of long bones. There are 2 types: red marrow (hematopoietic with abundant blood cells) and yellow marrow (predominantly filled with adipocytes). Composition of Bone Marrow insult (e.g., drug)
      • Repletion of deficient nutrients
    • Corrected reticulocyte counts: 
      • Reveals adequate versus inadequate bone marrow Bone marrow Bone marrow, the primary site of hematopoiesis, is found in the cavities of cancellous bones and the medullary canals of long bones. There are 2 types: red marrow (hematopoietic with abundant blood cells) and yellow marrow (predominantly filled with adipocytes). Composition of Bone Marrow response
      • Calculation: Reticulocyte count × (patient’s Hct/reference Hct)
  • Iron studies: 
    • Includes: 
      • Serum iron
      • Transferrin and transferrin saturation
      • Ferritin
      • Total binding iron capacity
    • ↓ Level of total body iron → iron deficiency anemia Iron Deficiency Anemia Iron deficiency anemia is the most common type of anemia worldwide. This form of anemia is caused by insufficient iron due to a decreased supply, an increased loss, or an increased demand. Iron deficiency anemia is seen across all ages, sexes, and socioeconomic strata; however, children, women of childbearing age, and patients from lower socioeconomic strata are at higher risk. Iron Deficiency Anemia
  • Laboratory tests when 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 is suspected:
    • Haptoglobin: ↓ with hemolysis 
    • Lactate dehydrogenase: ↑ with hemolysis
    • Indirect bilirubin: ↑ with hemolysis 
    • Direct Coombs test: detects 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 attached to RBCs, such as in erythroblastosis fetalis (due to Rh incompatibility)
    • Indirect Coombs test: detects 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 against foreign RBCs, which are present in autoimmune hemolytic anemia Autoimmune Hemolytic Anemia Autoimmune hemolytic anemia (AIHA) is a rare type of hemolytic anemia characterized by antibody production against self RBCs, leading to destruction of these cells in the spleen and other reticuloendothelial tissues. The disease is generally categorized as warm or cold, depending on the thermal reactivity of the autoantibodies. Autoimmune Hemolytic Anemia 
  • Other serologic tests:
    • CMP: to evaluate renal and hepatic function
    • Thyroid-stimulating hormone (TSH)
    • Vitamin B12 level
    • 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 level

Peripheral blood smear

A peripheral blood smear can be helpfuling in establishing the underlying cause of an anemia.

Table: Abnormal RBC findings in a peripheral blood smear
Abnormality Description Associated pathology
Sickle cells Sickle-shaped cells
  • Sickle cell anemia
Howell-Jolly bodies Peripherally located purple bodies representing nuclear remnants of RBCs
  • Sickle cell anemia
  • Asplenia Asplenia Asplenia is the absence of splenic tissue or function and can stem from several factors ranging from congenital to iatrogenic. There is a distinction between anatomic asplenia, which is due to the surgical removal of the spleen, and functional asplenia, which is due to a condition that leads to splenic atrophy, infarct, congestion, or infiltrative disease. Asplenia
Bite cells (degmacytes) RBCs with loss of semicircular portions G6PD
Heinz bodies Red-pink inclusions within RBCs representing aggregates of abnormal Hb
  • G6PD
  • Thalassemias
Spherocytes Dense, small spherical cells with no central pallor
  • Hereditary spherocytosis Hereditary Spherocytosis Hereditary spherocytosis (HS) is the most common type of hereditary hemolytic anemia. The condition is caused by a cytoskeletal protein deficiency in the RBC membrane. This results in loss of membrane stability and deformability of the RBC, giving the cell its spherical shape (spherocyte). Hereditary Spherocytosis
  • Autoimmune 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 Irregularly shaped RBC fragments Due to mechanical damage:
  • 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
  • Macroangiopathic 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
Normoblasts Nucleated RBCs Severe hemolysis
Target cells (codocytes) Bull’s-eye appearance (central area of hemoglobinization)
  • Hemoglobinopathies :
    • Thalassemia Thalassemia Thalassemia is a hereditary cause of microcytic hypochromic anemia and results from a deficiency in either the α or β globin chains, resulting in hemoglobinopathy. The presentation of thalassemia depends on the number of defective chains present and can range from being asymptomatic to rendering the more severely affected patients to be transfusion dependent. Thalassemia
    • HbC disease
  • Liver disease
  • Asplenia Asplenia Asplenia is the absence of splenic tissue or function and can stem from several factors ranging from congenital to iatrogenic. There is a distinction between anatomic asplenia, which is due to the surgical removal of the spleen, and functional asplenia, which is due to a condition that leads to splenic atrophy, infarct, congestion, or infiltrative disease. Asplenia
Basophilic stippling Purple-blue dots within RBCs representing ribosomal precipitates
  • Sideroblastic anemia Sideroblastic anemia Sideroblastic anemias are a heterogeneous group of bone marrow disorders characterized by abnormal iron accumulation in the mitochondria of erythroid precursors. The accumulated iron appears as granules in a ringlike distribution around the nucleus, giving rise to the characteristic morphological feature of a ring sideroblast. Sideroblastic Anemia
  • Lead poisoning
  • Thalassemias
Dacrocytes (teardrop cells) Teardrop-shaped RBCs Due to bone marrow Bone marrow Bone marrow, the primary site of hematopoiesis, is found in the cavities of cancellous bones and the medullary canals of long bones. There are 2 types: red marrow (hematopoietic with abundant blood cells) and yellow marrow (predominantly filled with adipocytes). Composition of Bone Marrow infiltration:
  • Myelofibrosis
  • Myelodysplastic syndrome
Macroovalocytes Large, oval-shaped erythrocytes Erythrocytes 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 Megaloblastic anemia

Additional tests based on clinical presentation

  • Copper level for deficiency 
  • Hb electrophoresis
  • Serum protein electrophoresis
  • EGD and colonoscopy: to assess for occult source of GI bleeding, especially > 50 years of age
  • 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. Structure of Bones marrow biopsy:
    • Important to consider if other cell lines abnormal 
      • Leukopenia
      • 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
    • Abnormal findings
      • Ringed sideroblasts: sideroblastic anemia or lead poisoning 
      • Hypocellular bone marrow Bone marrow Bone marrow, the primary site of hematopoiesis, is found in the cavities of cancellous bones and the medullary canals of long bones. There are 2 types: red marrow (hematopoietic with abundant blood cells) and yellow marrow (predominantly filled with adipocytes). Composition of Bone Marrow (dry bone marrow Bone marrow Bone marrow, the primary site of hematopoiesis, is found in the cavities of cancellous bones and the medullary canals of long bones. There are 2 types: red marrow (hematopoietic with abundant blood cells) and yellow marrow (predominantly filled with adipocytes). Composition of Bone Marrow tap): aplastic anemia
      • > 20% blasts: leukemia 

Management

Restore blood counts

  • Allow the body to replenish its own RBCs:
    • Supplementation of missing nutrients
    • Stop pathologic bleeding.
    • Treat underlying disease.
  • Transfusion of RBCs to maintain Hb
    • > 7 g/dL in a majority of patients
    • > 8 g/dL in patients with cardiovascular disease

Educate the patient regarding lifestyle

If lifestyle factors are thought to be contributing to the anemia, education can be provided regarding:

  • Alcohol use
  • Smoking
  • Adequate dietary intake and supplementation

Treat the underlying cause

  • Oral nutrient replacement for nutrient deficiencies:
    • Iron
    • Vitamin B12
    • 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
  • Address malabsorption issues (e.g., celiac sprue).
  • Treat source of bleeding if pathologic, for example:
    • Malignancy:
      • Endometrial cancer Endometrial Cancer Endometrial carcinoma (EC) is the most common gynecologic malignancy in the developed world, and it has several histologic types. Endometrioid carcinoma (known as type 1 EC) typically develops from atypical endometrial hyperplasia, is hormonally responsive, and carries a favorable prognosis. Endometrial Hyperplasia and Endometrial Cancer
      • Colon, gastric, or other GI malignancy
    • Peptic ulcer disease Peptic ulcer disease Peptic ulcer disease (PUD) refers to the full-thickness ulcerations of duodenal or gastric mucosa. The ulcerations form when exposure to acid and digestive enzymes overcomes mucosal defense mechanisms. The most common etiologies include Helicobacter pylori (H. pylori) infection and prolonged use of non-steroidal anti-inflammatory drugs (NSAIDs). Peptic Ulcer Disease
    • Inflammatory bowel disease (e.g., ulcerative colitis Ulcerative colitis Ulcerative colitis (UC) is an idiopathic inflammatory condition that involves the mucosal surface of the colon. It is a type of inflammatory bowel disease (IBD), along with Crohn's disease (CD). The rectum is always involved, and inflammation may extend proximally through the colon. Ulcerative Colitis)
    • Severe diverticular disease 
  • Treat underlying chronic diseases, as possible (e.g., consider erythropoietin Erythropoietin Glycoprotein hormone, secreted chiefly by the kidney in the adult and the liver in the fetus, that acts on erythroid stem cells of the bone marrow to stimulate proliferation and differentiation. Erythrocytes injection for CKD CKD Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease).
  • Treat endocrinopathies, if present (e.g., levothyroxine for hypothyroidism Hypothyroidism Hypothyroidism is a condition characterized by a deficiency of thyroid hormones. Iodine deficiency is the most common cause worldwide, but Hashimoto's disease (autoimmune thyroiditis) is the leading cause in non-iodine-deficient regions. Hypothyroidism).
  • Evaluate benefits and risks of long-term medications that may worsen anemia.

Comparison of Common Types of Anemia

Nonhemolytic anemias

  • Iron deficiency anemia: most common type of anemia worldwide. Iron deficiency anemia is due to a decreased supply of iron, an increased loss of iron (e.g., through unrecognized GI bleeding), or an increased demand for iron (e.g., pregnancy). Treatment is with supplementation and/or managing the underlying contributing disease.
  • Thalassemia Thalassemia Thalassemia is a hereditary cause of microcytic hypochromic anemia and results from a deficiency in either the α or β globin chains, resulting in hemoglobinopathy. The presentation of thalassemia depends on the number of defective chains present and can range from being asymptomatic to rendering the more severely affected patients to be transfusion dependent. Thalassemia: hereditary cause of microcytic, hypochromic anemia. Thalassemia Thalassemia Thalassemia is a hereditary cause of microcytic hypochromic anemia and results from a deficiency in either the α or β globin chains, resulting in hemoglobinopathy. The presentation of thalassemia depends on the number of defective chains present and can range from being asymptomatic to rendering the more severely affected patients to be transfusion dependent. Thalassemia is a deficiency in either the alpha (⍺) or beta (𝛽) globin chains resulting in both ineffective erythropoiesis Erythropoiesis Erythropoiesis starts with hematopoietic stem cells, which develop into lineage-committed progenitors and differentiate into mature RBCs. The process occurs in stages, and extrusion of the nuclei and organelles occurs prior to maturation. Thus, mature RBCs lack nuclei and have a biconcave shape. Erythrocytes and hemolysis. Clinical presentations range from asymptomatic carriers to severe anemia with shortened life expectancy.
  • Megaloblastic anemia: subset of macrocytic anemia that arises because of impaired nucleic acid synthesis in erythroid precursors: This impaired synthesis leads to ineffective RBC production and intramedullary hemolysis. The most common causes are vitamin B12 and folic acid deficiencies, which can be due to low dietary intake, underlying malabsorptive conditions, and medications. Clinical presentation includes anemia, GI symptoms, and neurologic manifestations.
  • Sickle cell anemia (sickle cell disease ( SCD SCD Sickle cell disease (SCD) is a group of genetic disorders in which an abnormal Hb molecule (HbS) transforms RBCs into sickle-shaped cells, resulting in chronic anemia, vasoocclusive episodes, pain, and organ damage. Sickle Cell Disease)): inherited autosomal recessive Autosomal recessive Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal recessive diseases are only expressed when 2 copies of the recessive allele are inherited. Autosomal Recessive and Autosomal Dominant InheritanceHb due to a single point mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations in the beta-globin gene. The abnormal Hb polymerizes when it becomes deoxygenated, leading to sickle-shaped deformation of the RBCs. These sickled RBCs are hemolyzed easily and cause microvascular obstruction with associated organ ischemia, severe pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain crises, and systemic complications. Sickle cells can usually be seen on a peripheral blood smear.
  • Sideroblastic anemia Sideroblastic anemia Sideroblastic anemias are a heterogeneous group of bone marrow disorders characterized by abnormal iron accumulation in the mitochondria of erythroid precursors. The accumulated iron appears as granules in a ringlike distribution around the nucleus, giving rise to the characteristic morphological feature of a ring sideroblast. Sideroblastic Anemia: This heterogeneous group of bone marrow Bone marrow Bone marrow, the primary site of hematopoiesis, is found in the cavities of cancellous bones and the medullary canals of long bones. There are 2 types: red marrow (hematopoietic with abundant blood cells) and yellow marrow (predominantly filled with adipocytes). Composition of Bone Marrow disorders is characterized by abnormal iron accumulation in the mitochondria of erythroid precursors. The accumulated iron appears as granules in a ring-like distribution around the nucleus (ring sideroblasts). Sideroblastic anemias may be due to inherited defects in heme synthesis or can be acquired through alcoholism, lead poisoning, medications, and vitamin deficiencies. Serum iron levels are typically elevated. 

Hemolytic anemias

Hemolytic anemias are result of the destruction or premature clearance of RBCs. Specifically, they can be due to either damage caused by a narrowed vascular lumen (intravascular hemolysis) or increased splenic clearance (extravascular hemolysis). Splenic clearance can result from intrinsic abnormalities of the RBCs (e.g., abnormal membranes, enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body's constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes, or Hb) or extrinsic antibody coating by the immune system (e.g., ABO incompatibility). 

Examples of hemolytic anemias include:

  • Hereditary spherocytosis Hereditary Spherocytosis Hereditary spherocytosis (HS) is the most common type of hereditary hemolytic anemia. The condition is caused by a cytoskeletal protein deficiency in the RBC membrane. This results in loss of membrane stability and deformability of the RBC, giving the cell its spherical shape (spherocyte). Hereditary Spherocytosis (HS): caused by a cytoskeletal protein deficiency in the RBC membrane. This deficiency results in loss of membrane stability and deformability of the RBC, causing its spherical shape (spherocyte). These cells are predisposed to splenic degradation, leading to extravascular hemolysis. Physical findings include jaundice and splenomegaly, while laboratory tests are consistent with 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. The definitive treatment for HS is splenectomy.
  • G6PD deficiency G6PD Deficiency Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a type of intravascular hemolytic anemia. The condition is inherited in an X-linked recessive manner. Patients have episodic hemolysis due to an oxidative stressor that causes damage to red blood cells, which lack sufficient NADPH to protect them from oxidative injury. Glucose-6-phosphate Dehydrogenase (G6PD) Deficiency: This X-linked recessive intravascular 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 is due to an inherited abnormality in the RBC enzyme G6PD, which generates nicotinamide adenosine dinucleotide phosphate ( NADPH NADPH Nicotinamide adenine dinucleotide phosphate. A coenzyme composed of ribosylnicotinamide 5'-phosphate (nmn) coupled by pyrophosphate linkage to the 5'-phosphate adenosine 2. Pentose Phosphate Pathway), protecting RBCs from oxidative injury. Patients have episodic hemolysis when cells encounter oxidative stressors.
  • 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): rare life-threatening condition characterized by pancytopenia and hypocellularity of the bone marrow Bone marrow Bone marrow, the primary site of hematopoiesis, is found in the cavities of cancellous bones and the medullary canals of long bones. There are 2 types: red marrow (hematopoietic with abundant blood cells) and yellow marrow (predominantly filled with adipocytes). Composition of Bone Marrow, in the absence of any abnormal cells, reflecting damage to the hematopoietic stem cells (HSCs). 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 can be acquired or inherited. Multiple causes are known, including autoimmune damage to HSCs, medications, chemicals, whole-body radiation, viral infections, immune diseases, pregnancy, Fanconi 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.
  • Autoimmune 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: rare type of 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 characterized by the production of autoantibodies directed against RBCs, leading to the destruction of these 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. Autoimmune 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 is categorized as “warm” or “cold,” depending on the thermal reactivity of the autoantibodies. The etiology is diverse and includes infections, autoimmune diseases, lymphoproliferative disorders, and drugs.
  • Paroxysmal nocturnal hemoglobinuria Paroxysmal Nocturnal Hemoglobinuria Paroxysmal nocturnal hemoglobinuria (PNH) is a rare but serious acquired hemolytic anemia with periodic exacerbations. This anemia is caused by nonmalignant clonal expansion of ≥ 1 hematopoietic stem cells that have acquired a somatic mutation of the phosphatidylinositol N-acetylglucosaminyltransferase subunit A (PIG-A) gene. Paroxysmal Nocturnal Hemoglobinuria (PNH): rare and serious acquired chronic 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 (HA) with periodic exacerbations. PNH often follows a diagnosis of bone marrow Bone marrow Bone marrow, the primary site of hematopoiesis, is found in the cavities of cancellous bones and the medullary canals of long bones. There are 2 types: red marrow (hematopoietic with abundant blood cells) and yellow marrow (predominantly filled with adipocytes). Composition of Bone Marrow failure/aplastic anemia, but it can also arise de novo. The underlying defect is a somatic mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations in a multipotent hematopoietic stem cell of the X-linked PIGA gene, followed by clonal expansion of the mutated stem cells. These abnormal RBCs undergo mostly intravascular hemolysis and may form a part of a unique clinical triad that also includes pancytopenia and venous thrombosis.

References

  1. Auerbach, M. (2021). Causes and diagnosis of iron deficiency anemia in adults. UpToDate. Retrieved April 21, 2021, from https://www.uptodate.com/contents/causes-and-diagnosis-of-iron-deficiency-and-iron-deficiency-anemia-in-adults
  2. Means, R.T. (2021). Diagnostic approach to anemia in adults. UpToDate. Retrieved April 21, 2021, from https://www.uptodate.com/contents/diagnostic-approach-to-anemia-in-adults
  3. Despotovic, J.M. (2021). Overview of hemolytic anemias in children. UpToDate. Retrieved April 21, 2021, from https://www.uptodate.com/contents/overview-of-hemolytic-anemias-in-children
  4. Camaschella, C., Weiss, G. (2020). Anemia of chronic disease/anemia of inflammation. UpToDate. Retrieved April 21, 2021, from https://www.uptodate.com/contents/anemia-of-chronic-disease-anemia-of-inflammation
  5. Brodsky, R.A. (2021). Diagnosis of hemolytic anemia in adults. UpToDate. Retrieved April 21, 2021, from https://www.uptodate.com/contents/diagnosis-of-hemolytic-anemia-in-adults
  6. Turner, J., Parsi, M. (2021). Anemia. StatPearls. Retrieved April 28, 2021, from https://www.statpearls.com/articlelibrary/viewarticle/17527/ 
  7. Aster, J.C. (2005). Red blood cell and bleeding disorders. In Kumar, V., Abbas, A.K., Fausto, N. (Eds). Robbins and Cotran Pathologic Basis of Disease, 7th ed., pp. 622–649.

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