Hematology 1

Question 1

What is the most common cause of anemia worldwide?

Answer 1

Iron deficiency anemia is the most common cause of anemia worldwide.

Question 2

What is the difference between heme and non-heme iron?

Answer 2

Heme iron is ferrous (Fe2+) and is found in meat, which is better absorbed. Non-heme iron is ferric (Fe3+) and is found in vegetables and cereals; it is reduced to Fe2+ by the brush border ferrireductase enzyme.

Question 3

How is iron transported and stored in the body?

Answer 3

Iron is transported in plasma bound to transferrin. It is stored as ferritin and hemosiderin in hepatocytes, skeletal muscle, and macrophages.

Question 4

What are the causes of iron deficiency anemia?

Answer 4

Blood loss (most common cause), increased demand (growth, pregnancy), poor intake, and decreased absorption (e.g., gastrectomy, small bowel disease like celiac or tropical sprue).

Question 5

What are the signs and symptoms of iron deficiency anemia?

Answer 5

Fatigue, pallor, shortness of breath (SOB), tachycardia, brittle hair and nails, atrophic glossitis, and angular stomatitis.

Question 6

What investigations are done for iron deficiency anemia?

Answer 6

CBC shows decreased hemoglobin (Hb), microcytic (low MCV), hypochromic (low MCH), decreased reticulocytes, increased RDW, and reactive thrombocytosis. Blood film shows small hypochromic RBCs, anisocytosis (variations in size), and poikilocytosis (variations in shape). Iron studies show decreased iron, decreased ferritin, decreased transferrin saturation, increased TIBC, and increased transferrin receptor.

Question 7

How is iron deficiency anemia treated?

Answer 7

Treat the underlying cause. Oral iron supplements (e.g., ferrous sulfate/gluconate) for 3 to 6 months before evaluating the response. IV iron is used if oral iron is not tolerated or if rapid iron replenishment is needed before surgery.

Question 8

What is sideroblastic anemia?

Answer 8

Sideroblastic anemia is caused by abnormal RBC iron metabolism, leading to refractory anemia. It can be hereditary or acquired (e.g., due to myelodysplasia, alcohol, lead toxicity, drugs like isoniazid, chloramphenicol, or Vitamin B6 deficiency).

Question 9

What are the blood film and bone marrow findings in sideroblastic anemia?

Answer 9

Blood film shows hypochromic cells. Bone marrow shows ringed sideroblasts (erythroblasts with iron deposits in mitochondria, detectable with Prussian blue stain).

Question 10

How is sideroblastic anemia treated?

Answer 10

Remove the causative agent. Some patients may respond to pyridoxine (Vitamin B6).

Question 11

What is thalassemia?

Answer 11

Thalassemia is a genetic disorder that affects hemoglobin production. It is discussed under ‘Hemolytic anemia.’

Question 12

What is megaloblastic anemia?

Answer 12

Megaloblastic anemia is caused by Vitamin B12 or folate deficiency, which leads to defective DNA synthesis, resulting in megaloblasts in the bone marrow and hypersegmented neutrophils in the blood. There may also be thrombocytopenia.

Question 13

What is Vitamin B12, and how is it absorbed?

Answer 13

Vitamin B12 is found in meat and dairy products.

In the stomach, Vitamin B12 is released from animal protein by acid and pepsin and binds to the
R-binder (transcobalamin) from saliva.

In the duodenum, pancreatic enzymes release Vitamin B12 from the R-binder, and it binds to the Intrinsic Factor (IF), which is produced by gastric parietal cells.

The Vitamin B12-IF complex is absorbed in the terminal ileum, where Vitamin B12 is transported by Transcobalamin II and stored in the liver.

Question 14

What are the causes of Vitamin B12 deficiency?

Answer 14

Poor diet (e.g., vegan diet), malabsorption (e.g., celiac, tropical sprue, ileal resection, gastrectomy, tapeworm), and pernicious anemia.

Question 15

What is pernicious anemia, and how does it cause Vitamin B12 deficiency?

Answer 15

Pernicious anemia is an autoimmune disease where autoantibodies target parietal cells and/or intrinsic factor (IF), leading to a loss of IF production and subsequent Vitamin B12 malabsorption. It is associated with atrophic gastritis and is more common in the elderly, particularly women. There is an increased risk of gastric carcinoma, and it may be linked to other autoimmune diseases (e.g., thyroid disease, Addison’s disease, vitiligo).

Question 16

What neurological features are associated with Vitamin B12 deficiency?

Answer 16

The most characteristic lesion is Subacute Combined Degeneration of the spinal cord (SCDC), while the most common feature is peripheral polyneuropathy (e.g., absent reflexes). SCDC affects the posterior and lateral columns of the spinal cord, leading to UMNL signs such as weakness, ataxia, hyperreflexia, and spastic paraplegia. There may be a loss of vibration and proprioception. Other symptoms include dementia, optic atrophy, and visual disturbances.

Question 17

What is folate, and how is it absorbed?

Answer 17

Folate is found in green vegetables and offal (e.g., liver, kidney) and is absorbed in the duodenum.

Question 18

What are the causes of folate deficiency?

Answer 18

Poor intake (most common cause), excess utilization (e.g., pregnancy, ICU), malabsorption (e.g., celiac, tropical sprue), and drugs (e.g., methotrexate, phenytoin, trimethoprim, sulfasalazine).

Question 19

How do Vitamin B12 and folate deficiencies differ neurologically?

Answer 19

Folate deficiency does not cause neurological symptoms, while Vitamin B12 deficiency leads to neurological damage such as peripheral neuropathy and subacute combined degeneration of the spinal cord (SCDC).

Question 20

What investigations are done for megaloblastic anemia?

Answer 20

CBC shows decreased hemoglobin (Hb), decreased reticulocytes, and macrocytic (high MCV) anemia.

Blood film shows hypersegmented neutrophils.

Bone marrow (not always necessary) shows hypercellularity with megaloblastic changes.

Vitamin B12 studies: Serum Vitamin B12 levels <50 ng/L (normal >160 ng/L).
Red cell folate may be decreased, as Vitamin B12 is needed for folate conversion.
If pernicious anemia is suspected, anti-parietal cell antibodies and anti-IF antibodies may be present. Homocysteine and methylmalonic acid (MMA) levels are elevated in Vitamin B12 deficiency.

Question 21

What treatment is used for megaloblastic anemia?

Answer 21

Vitamin B12 is treated with IM hydroxocobalamin or oral B12 (2 mg/day).
Folate is treated by addressing the underlying cause and giving oral folic acid (5 mg/day for 4 months).
A complication of replacing Vitamin B12 and folate is hypokalemia due to rapid cell production.
Folate replacement in B12 deficiency can mask hematological symptoms, but neurological symptoms may worsen.

Question 22

What are the causes of macrocytic anemia with normoblastic bone marrow?

Answer 22

Physiological conditions such as pregnancy and newborns. Alcohol excess. Liver disease. Myelodysplastic syndromes (MDS), sideroblastic anemia, aplastic anemia. Medications like hydroxyurea and azathioprine. Cold agglutinin disease. Hemolysis. Increased reticulocyte count (e.g., due to hemorrhage or hemolysis).

Question 23

What is anemia of chronic disease?

Answer 23

Anemia of chronic disease is typically normocytic normochromic or microcytic anemia, resulting from decreased iron release from the bone marrow, reduced erythropoietin response, and increased hepcidin levels. It often occurs due to chronic inflammatory diseases (e.g., Crohn’s disease, rheumatoid arthritis), chronic infections (e.g., tuberculosis), malignancy, or chronic kidney disease.

Question 24

What laboratory findings are associated with anemia of chronic disease?

Answer 24

Elevated hepcidin, decreased serum iron, decreased TIBC (total iron binding capacity), and normal or increased ferritin.

Question 25

How is anemia of chronic disease treated?

Answer 25

The underlying cause must be treated. Recombinant erythropoietin may be used if the anemia is due to chronic kidney disease.

Question 26

What is aplastic anemia?

Answer 26

Aplastic anemia is characterized by pancytopenia and hypocellularity of the bone marrow, with decreased numbers of pluripotent stem cells, and an immune reaction affecting the remaining stem cells, impairing their ability to repopulate the bone marrow.

Question 27

What are the causes of aplastic anemia?

Answer 27

Hereditary causes like Fanconi’s anemia, which is an autosomal recessive DNA repair defect associated with congenital malformations and an increased risk of AML, SCC, and tumors in the liver, brain, or kidneys. Idiopathic cases (67% of cases). Drugs: chemotherapy (dose-related), and idiosyncratic reactions to drugs like chloramphenicol, phenytoin, NSAIDs, and carbamazepine. Exposure to chemicals like benzene and insecticides, or radiation. Infections such as EBV, HIV, TB, hepatitis, and parvovirus B19. Paroxysmal nocturnal hemoglobinuria, systemic lupus erythematosus (SLE), and deficiencies in Vitamin B12 and folate.

Question 28

What are the symptoms of aplastic anemia?

Answer 28

Symptoms of anemia. Increased susceptibility to infections, particularly mouth infections. Bleeding symptoms such as bruising, bleeding gums, and epistaxis.

Question 29

What diagnostic tests are performed for aplastic anemia?

Answer 29

Pancytopenia with decreased or absent reticulocytes. Bone marrow biopsy shows hypocellularity with increased fat spaces (BM trephine biopsy is essential, with dry aspiration).

Question 30

How is aplastic anemia treated?

Answer 30

The course of aplastic anemia can be variable (spontaneous remission or persistent, progressively severe cases). Poor prognosis is associated with neutrophils < 0.5 x 10^9, platelets < 20 x 10^9, or reticulocytes < 40 x 10^9. For patients under 40 years, bone marrow transplantation (BMT) from an HLA-identical donor is the definitive treatment. For those over 40 years, immunosuppressive treatment (e.g., antilymphocyte globulin and cyclosporine) is the recommended approach.

Question 31

What are hemolytic anemias?

Answer 31

Hemolytic anemias are characterized by increased destruction of red blood cells (RBCs), leading to a decreased lifespan of RBCs. This causes an increase in reticulocytes (immature RBCs) as a compensatory response. Common findings include elevated LDH (lactate dehydrogenase), increased indirect bilirubin, decreased haptoglobin, jaundice, and pigmented gallstones.

Question 32

How are hemolytic anemias classified?

Answer 32

Hemolytic anemias are classified as inherited vs acquired and extravascular vs intravascular hemolysis.

Question 33

What are the causes of inherited hemolytic anemias?

Answer 33

Red cell membrane defects (e.g., hereditary spherocytosis). Hemoglobin abnormalities (e.g., thalassemia, sickle cell disease). Metabolic defects such as enzyme deficiencies (e.g., G6PD deficiency, pyruvate kinase deficiency).

Question 34

What are the causes of acquired hemolytic anemias?

Answer 34

Immune causes (e.g., autoimmune hemolytic anemia, alloimmune hemolytic anemia, drug-induced hemolysis). Non-immune causes such as paroxysmal nocturnal hemoglobinuria (PNH), microangiopathic hemolytic anemia (MAHA), malaria, and hemolysis secondary to systemic diseases (e.g., chronic liver disease).

Question 35

What is extravascular hemolysis?

Answer 35

Extravascular hemolysis occurs when RBCs are removed by macrophages in the reticuloendothelial system (primarily the spleen), which is associated with splenomegaly.

Question 36

What is intravascular hemolysis?

Answer 36

Intravascular hemolysis occurs when RBCs are rapidly destroyed within the blood vessels, leading to hemoglobinemia (free hemoglobin in circulation). This hemoglobin binds to haptoglobin, which becomes saturated and is cleared by the liver. Hemoglobin can also be oxidized into methemoglobin and ferriheme, which binds to albumin and is detected in plasma (positive Schumm’s test).

Question 37

What are the causes of extravascular hemolysis?

Answer 37

Hemoglobinopathies (e.g., sickle cell anemia, thalassemia). Hereditary spherocytosis. Warm autoimmune hemolytic anemia (IgG). Hemolytic disease of the newborn.

Question 38

What are the causes of intravascular hemolysis?

Answer 38

G6PD deficiency (often with some extravascular component if Heinz bodies are present). Red cell fragmentation due to MAHA (e.g., TTP, HUS, DIC, HELLP syndrome) or heart valve abnormalities. Mismatched transfusion. Paroxysmal nocturnal hemoglobinuria (PNH). Cold autoimmune hemolytic anemia (IgM). Malaria.

Question 39

What is hereditary spherocytosis?

Answer 39

Hereditary spherocytosis is a defect in the RBC membrane caused by a deficiency in spectrin, which increases the permeability to sodium. This makes RBCs more rigid and less deformable, leading to premature destruction in the spleen.

Question 40

What are the symptoms of hereditary spherocytosis?

Answer 40

Symptoms can range from asymptomatic to severe hemolysis with anemia, jaundice, and splenomegaly. Some patients may experience aplastic crises (particularly after infection with parvovirus), hemolytic crises, or megaloblastic crises due to hyperactivity of the bone marrow. Chronic cases can lead to pigmented gallstones.

Question 41

What are the symptoms of hereditary spherocytosis?

Answer 41

Symptoms can range from asymptomatic to severe hemolysis with anemia, jaundice, and splenomegaly. Some patients may experience aplastic crises, hemolytic crises, or megaloblastic crises due to hyperactivity of the bone marrow. Chronic cases can lead to pigmented gallstones.

Question 42

What investigations are done for hereditary spherocytosis?

Answer 42

CBC shows anemia and reticulocytosis. Blood film shows spherocytes. Signs of hemolysis include increased serum bilirubin and urinary urobilinogen.

Question 43

How is hereditary spherocytosis treated?

Answer 43

Chronic folic acid supplementation and splenectomy (usually after childhood to minimize the risk of overwhelming infections).

Question 44

What is hereditary elliptocytosis?

Answer 44

Hereditary elliptocytosis is a condition where RBCs are elliptical in shape. It is milder clinically and typically does not require splenectomy.

Question 45

What are hemoglobin abnormalities, and how are they inherited?

Answer 45

Hemoglobin abnormalities are typically inherited in an autosomal recessive manner. If both parents are carriers, there is a 25% chance their offspring will be affected, a 50% chance they will be carriers, and a 25% chance they will be normal.

Question 46

What is thalassemia?

Answer 46

Thalassemia is a genetic disorder characterized by a decreased synthesis of one or more globin chains, leading to a reduced amount of normal hemoglobin. This results in the formation of insoluble hemotetramers, causing cell damage and RBC hemolysis.

Question 47

What are the different types of thalassemia?

Answer 47

Alpha-thalassemia: Caused by a reduced synthesis of alpha chains. Beta-thalassemia: Caused by a reduced synthesis of beta chains.

Question 48

How are alpha-thalassemia and beta-thalassemia genetically different?

Answer 48

Alpha-thalassemia: Caused by defects in chromosome 16. Beta-thalassemia: Caused by defects in chromosome 11.

Question 49

What are the different forms of alpha-thalassemia?

Answer 49

Alpha-thalassemia trait and minor: If 1 locus is affected, the person is asymptomatic. If 2 loci are affected, the person has mild microcytic anemia but remains asymptomatic. HbH disease: If 3 loci are affected, this causes severe microcytic hypochromic anemia. Hb Bart’s: Complete absence of alpha chains, leading to a fatal condition at birth.

Question 50

What are the different forms of beta-thalassemia?

Answer 50

Beta-thalassemia minor: Asymptomatic or mild microcytic anemia. Beta-thalassemia intermedia: Moderate anemia, does not typically require transfusions. Beta-thalassemia major: Severe anemia, presents in the first year of life.

Question 51

How is beta-thalassemia major treated?

Answer 51

Blood transfusion, long-term folic acid supplementation, splenectomy for severe splenomegaly, and iron chelation therapy if serum ferritin exceeds 1000 µg/L.

Question 52

What is sickle cell anemia, and how does it develop?

Answer 52

Sickle cell anemia is caused by a mutation in the beta-globin gene, leading to the formation of rigid, sickle-shaped RBCs when deoxygenated.

Question 53

What factors precipitate sickling in sickle cell anemia?

Answer 53

Factors that shift the oxygen dissociation curve to the right, such as hypoxia, dehydration, infection, acidosis, or cold weather.

Question 54

What are the clinical features of sickle cell anemia?

Answer 54

Symptoms usually begin after 6 months of age. Features include hemolytic anemia, vaso-occlusive crisis, avascular necrosis, autosplenectomy, acute chest syndrome, and priapism.

Question 55

What are some complications of sickle cell anemia?

Answer 55

Splenic sequestration crisis, aplastic crisis, increased susceptibility to infections, and sickle cell nephropathy.

Question 56

What investigations are performed for sickle cell anemia?

Answer 56

Decreased Hb and normal MCV, sickled RBCs on blood film, Hb electrophoresis shows 80-90% HbSS and absence of HbA.

Question 57

How is sickle cell anemia managed?

Answer 57

Chronic folic acid supplementation, hydroxyurea, antibiotics for fever, pain management, vaccinations, and exchange transfusion in specific cases.

Question 58

What is sickle cell trait?

Answer 58

Sickle cell trait occurs when an individual has 60% HbA and 40% HbS. It is asymptomatic except in extreme circumstances.

Question 59

What is G6PD deficiency?

Answer 59

G6PD deficiency is an X-linked recessive condition that affects men primarily, leading to hemolysis when exposed to certain triggers.

Question 60

What are common triggers for hemolysis in G6PD deficiency?

Answer 60

Infection, acidosis, fava beans, and certain drugs.

Question 61

What are the clinical features of G6PD deficiency?

Answer 61

Most patients are asymptomatic. Hemolysis can lead to dark urine, jaundice, and episodic intravascular hemolysis.

Question 62

How is G6PD deficiency diagnosed?

Answer 62

Blood film shows bite cells, Heinz bodies, and decreased pyruvate kinase enzyme activity.

Question 63

How is G6PD deficiency treated?

Answer 63

Avoid precipitants and ensure good hydration. Transfusion may be required if necessary.

Question 64

What is pyruvate kinase deficiency?

Answer 64

Pyruvate kinase deficiency is an autosomal recessive condition leading to ATP deficiency in RBCs, causing hemolysis.

Question 65

What are the clinical features of pyruvate kinase deficiency?

Answer 65

Typically presents in newborns with jaundice and hemolysis, along with splenomegaly, pallor, fatigue, and weakness.

Question 66

How is pyruvate kinase deficiency diagnosed?

Answer 66

Diagnosis is made by measuring decreased pyruvate kinase enzyme activity and identifying a mutation in the PKLR gene.

Question 67

How is pyruvate kinase deficiency treated?

Answer 67

Treatment includes phototherapy and/or exchange transfusions for hemolysis. Splenectomy may be required for severe cases.

Question 68

What is warm autoimmune hemolytic anemia?

Answer 68

It is the most common type of autoimmune hemolytic anemia caused by IgG autoantibodies reacting with self-RBCs at body temperature.

Question 69

What are the causes of warm autoimmune hemolytic anemia?

Answer 69

Primary or secondary to chronic lymphocytic leukemia, lymphoma, systemic lupus erythematosus, or certain drugs.

Question 70

What investigations are performed in warm autoimmune hemolytic anemia?

Answer 70

Blood film shows spherocytes. Direct Coombs’ test detects IgG antibodies on the surface of RBCs.

Question 71

How is warm autoimmune hemolytic anemia treated?

Answer 71

First-line treatment is glucocorticoids. Recurrent episodes may respond to splenectomy or other immunosuppressive therapies.

Question 72

What is cold agglutinin disease?

Answer 72

Cold agglutinin disease is a condition where IgM autoantibodies react with self-RBCs at low temperatures, leading to hemolysis.

Question 73

What is cold agglutinin disease?

Answer 73

Cold agglutinin disease is a condition where IgM autoantibodies react with self-RBCs at low temperatures (4°C to 23°C), leading to complement activation and intravascular hemolysis.

Question 74

What are the causes of cold agglutinin disease?

Answer 74

It can be primary (especially in the elderly) or secondary to infections such as Mycoplasma pneumoniae, Epstein-Barr virus (EBV), or cytomegalovirus (CMV). It can also be secondary to lymphoid or plasma cell malignancies, including B-cell lymphomas, CLL, or Waldenström’s macroglobulinemia.

Question 75

What are the clinical features of cold agglutinin disease?

Answer 75

Symptoms can include cold-induced signs such as acrocyanosis, livedo reticularis, Raynaud’s phenomenon, and numbness or mottling of the extremities. Hemolysis can range from mild to severe.

Question 76

What investigations are performed in cold agglutinin disease?

Answer 76

Direct Coombs’ test is positive for complement. Cold agglutinin titer is the most accurate test. Blood film shows red cell agglutination at room temperature.

Question 77

How is cold agglutinin disease treated?

Answer 77

Treatment includes addressing the underlying condition (if secondary), keeping the patient warm, and using warm blankets or a blood warmer during transfusions. Steroids and splenectomy are not beneficial. Rituximab can be used, along with plasmapheresis or cyclophosphamide or cyclosporine as additional options.

Question 78

What is paroxysmal nocturnal hemoglobinuria (PNH)?

Answer 78

PNH is an acquired intravascular hemolytic anemia caused by a clonal stem cell defect with a mutation in the PIGA gene, leading to a deficiency of complement regulatory proteins (CD55 and CD59), increasing RBC sensitivity to complement, especially in an acidic environment, causing hemolysis and thrombosis.

Question 79

What are the clinical features of PNH?

Answer 79

Hemolysis results in episodic dark urine. Cytopenias may be present, such as pancytopenia or iron deficiency anemia. Thrombosis is a common and dangerous complication, often occurring in unusual locations.

Question 80

What investigations are performed in PNH?

Answer 80

Hemolysis is indicated by elevated LDH, low haptoglobin, and high unconjugated bilirubin. Urine may show hemoglobinuria. The direct Coombs’ test is negative. The most accurate test is decreased levels of CD55 and CD59 on RBCs.

Question 81

What are the complications of PNH?

Answer 81

Thrombosis is the most common cause of death in PNH patients. Infections are the second most common cause of death. Iron deficiency anemia (IDA) and acute leukemia (AML) may also occur.

Question 82

How is PNH treated?

Answer 82

The best initial therapy for hemolysis is prednisone. Eculizumab, a monoclonal antibody targeting C5 to inhibit complement activation, is beneficial for both hemolysis and thrombosis. Prior to starting eculizumab, the patient must be vaccinated against meningococcal infections. Iron and folic acid replacement are important. Blood transfusions may be required as needed. Allogeneic bone marrow transplant is the only cure.