13 - Red blood cells and bleeding disorders

Question 1

Enumerate (3): most common causes of G6PD deficiency, in descending order:

Answer 1

1. infections 2. drugs 3. food

Question 2

Most common known cause of aplastic anemia:

Answer 2

drugs

Question 3

Most common cause of myelophthisic anemia:

Answer 3

metastatic cancer

Question 4

Most common inherited bleeding disorder:

Answer 4

von Willebrand disease

Question 5

Most common hereditary syndrome associated with life-threatening bleeding

Answer 5

hemophilia

Question 6

Characterized by defective red cell membrane proteins spectrin and ankyrin; on PBS, red cells are spherical which lack central pallor, and they show increased osmotic fragility when placed in hypotonic salt solutions; anemia with characteristically increased MCHC.

Answer 6

Hereditary spherocytosis (Intrinsic; extravascular)

Question 7

X-linked disorder in which red cells are unusually susceptible to damage cause by oxidants. (Drugs that produce oxidants include antimalarials, sulfonamides, nitrofurantoin, phenacetin, and vitamin K derivatives); Heinz bodies (derived from hemoglobin) seen on PBS of splenectomized patients; Bite cells seen on PBS of patients with intact spleen function.

Answer 7

Glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency) (Intrinsic; extravascular and intravascular)

Question 8

This results from substitution of valine for glutamic acid at the 6th position of the b-chain, producing HbS; bizarre, elongated, spindled or boat-shaped cells on PBS (evident on low oxygen tension states); clinically, prominent cheekbones and changes in skull resembling a crew-cut skull x-ray, due to bone marrow expansion; also with painful vaso-occlusive crisis; spleen may be enlarged, but in chronic cases may be small and fibrosed (autosplenectomy), rendering them susceptible to infections with encapsulated bacteria; treatment is Hydroxyurea that increases HbF.

Answer 8

Sickle cell anemia (Intrinsic; extravascular)

Question 9

Microcytic, hypochromic anemias characterized by deficiency of either a- or b-globin chains (memory device: the name is what it lacks).

Answer 9

Thalassemia (Intrinsic; extravascular)

Question 10

Condition caused by deletion of 1 a- globin gene.

Answer 10

Silent carrier

Question 11

Condition caused by deletion of 2 a- globin genes; symptomatic at birth because of deficiency in HbF.

Answer 11

a-Thalassemia

Question 12

Disease caused by deletion of 3 a-genes.

Answer 12

Hemoglobin H disease

Question 13

Condition caused by deletion of all four a-globin genes.

Answer 13

Hydrops fetalis

Question 14

In b-Thalassemia, an individual who inherits one abnormal allele (out of 2) has this asymptomatic to mildly symptomatic condition; Red cells with a central, dark-red puddle due to collection of hemoglobin (target cells) on PBS.

Answer 14

b-Thalassemia minor

Question 15

Individuals with b-Thalassemia who inherit two abnormal alleles, with severe anemia requiring regular blood transfusions; usually symptomatic at around six months of age because HbF synthesis ceases at this time; marked hypochromia, poikilocytosis (variation in cell size) and anisocytosis (variation in cell shape) with normoblasts (signifying erythropoietic drive).

Answer 15

b-Thalassemia major (Cooley anemia)

Question 16

A mutation in the gene pigA causes this disease; there is deficiency of PIG (phosphatidylinositol glycan) that anchors CD55 and CD59 to the red cell surface; without such, red cells become susceptible to complement-mediated lysis.

Answer 16

Paroxysmal nocturnal hemoglobinuria (Intrinsic; intravascular)

Question 17

Anemia caused by low-affinity IgM which bind to red cell membranes only at temp <30 degC, commonly experienced by distal parts of the body; associated with Mycoplasma pneumoniae, and EBV infections.

Answer 17

Cold antibody immune-hemolytic anemia (Extrinsic; intravascular)

Question 18

Hemolysis caused by IgG or IgA antibodies that are active at 37 deg C, which results in opsonization of red cells by the autoantibodies.

Answer 18

Warm antibody immune-hemolytic anemia (Extrinsic; intravascular)

Question 19

Anemia observed in a variety of pathologic states, in which small vessels become particularly obstructed (e.g. DIC, malignant HTN, SLE, etc.); schistocytes, Burr cells, helmet cells, triangle cells are seen in this condition.

Answer 19

Microangiopathic hemolytic anemia (Extrinsic; intravascular)

Question 20

Most common cause of anemia in both developing and developed countries; microcytic, hypochromic with low ferritin, low serum iron levels low transferrin saturation, and increased TIBC.

Answer 20

Iron deficiency anemia

Question 21

Most common cause of anemia in hospitalized patients; anemia characterized by high levels of hepcidin, responsible for blocking the transfer of iron to erythroid precursors, hence causing anemia; normocytic, normochromic but can be microcytic, hypochromic; increased ferritin, low serum iron levels, low transferrin saturation, and decreased TIBC.

Answer 21

Anemia of chronic disease

Question 22

Anemia characterized by hypercellular marrow as a result of increased number of megaloblasts, which are large cells that have delicate, finely reticulated nuclear chromatin and abundant basophilic cytoplasm; can be caused by Folate (without neurologic symptoms) or Cobalamin (with neurologic symptoms) deficiency; PBS findings include: hypersegmented neutrophils, large, egg-shaped macro-ovalocytes.

Answer 22

Megaloblastic anemia

Question 23

Bone marrow is markedly hypocellular, with >90% of the intertrabecular space being occupied by fat; normocytic, normochromic; most commonly caused by chemicals (Benzene) and drugs (Chloramphenicol).

Answer 23

Aplastic anemia

Question 24

Selective suppression of marrow erythroid precursors; can be autoimmune or infectious (Parvovirus) in etiology; presents with normocytic, normochromic anemia with virtuallyt absent eryhtroblasts in bone marrow, and normal granulo- and thrombopoietic elements; paraneoplastic syndrome of thymoma.

Answer 24

Pure red cell aplasia (PRCA)

Question 25

Anemia caused by replacement of the bone marrow by in infiltrative processes such as metastatic carcinoma and granulomatous disease; leads to the appearance of early erythroid and granulocytic precursors (leukoerythroblastosis) and teardrop-shaped red cells (dacrocytes) in the peripheral blood.

Answer 25

Myelophthisic anemia

Question 26

Denotes an increase in red cells per unit volume of peripheral blood, usually in association with an increase in hemoglobin concentration; maybe relative (hemoconcentration) or absolute; absolute may be primary (polycythemia vera) or secondary (increased erythropoietin, lung disease, high altitude, endurance athletes or erythropoietin-secreting tumors).

Answer 26

Polycythemia

Question 27

Caused by a systemic activation of coagulation pathways, leading to formation of thrombi throughout the microcirculation, and subsequent bleeding due to consumption of coagulation factors; laboratory findings include: thrombocytopenia, increased bleeding time and prolonged PT and PTT.

Answer 27

Disseminated intravascular coagulation (DIC)

Question 28

Caused by antiplatelet antibodies directed against glycoproteins IIb-IIIa, Ib-IX (usually IgG); laboratory findings include: decreased platelet count, prolonged bleeding time, and normal PT and PTT.

Answer 28

Immune thrombocytopenia/Immune thrombocytopenic purpura (ITP)

Question 29

Form of ITP usually affecting adults and females more than males; associated with SLE, HIV, B-cell neoplasms (CLL); glucocorticoids are indicated; other tretament modalities include, splenectomy, rituximab (anti CD20) in B-cell neoplasms, and TPO-mimetic (Romiplostim).

Answer 29

Chronic ITP

Question 30

Form of ITP usually affecting children; common antecedent viral illness; glucocorticoids are indicated only when severe; usually self-limited.

Answer 30

Acute ITP

Question 31

Thrombocytopenia with thrombosis, in a patient taking anticogulants raises suspicion of the this disorder.

Answer 31

Heparin-induced thrombocytopenia (HIT)

Question 32

Most common hematologic manifestation of HIV infection.

Answer 32

Thrombocytopenia

Question 33

Associated with pentad of fever, thrombocytopenia, microangiopathic hemolytic anemia, transient neurologic deficits and renal failure; primary defect is deficiency of ADAMTS13, a vWF metalloproteinase; laboratory findings include: decreased platelet count, prolonged bleeding time, and normal PT and PTT.

Answer 33

Thrombotic thrombocytopenic purpura (TTP)

Question 34

Associated with childhood onset microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure; no neurologic symptoms; often with a history of bloody diarrhea (E. coli O157:H7 infection); with normal ADAMTS13 activity; laboratory findings include: decreased platelet count, prolonged bleeding time, and normal PT and PTT.

Answer 34

Hemolytic Uremic Syndrome (HUS)

Question 35

Decreased gp Ib leads to defective platelet adhesion; laboratory findings include: decreased platelet count, prolonged bleeding time, and normal PT and PTT.

Answer 35

Bernard-Soulier syndrome

Question 36

Decreased gp IIb-IIIa leads to defective platelet aggregation, laboratory findings include: normal platelet count, prolonged bleeding time, and normal PT and PTT.

Answer 36

Glanzmann thrombasthenia

Question 37

Most common inherited bleeding disorder; most common presenting symptoms of this condition are spontaneous bleeding from mucous membranes, excessive bleeding from wounds, or menorrhagia; bleeding tendency often goes unnoticed until some hemostatic stress, such as surgery, reveals its presence; laboratory findings include normal platelet count, prolonged bleeding time, and normal PT and prolonged PTT.

Answer 37

Von Willebrand disease (vWD)

Question 38

• Patient with this disease has a tendency toward easy bruising and massive hemorrhage after trauma or operative procedures, and recurrent bleeding into the joints; laboratory findings include normal platelet count, bleeding time, PT and prolonged PTT.
• Enumerate the two types and the corresponding deficient factors

Answer 38

Hemophilia

• Hemophilia A - Factor VIII deficiency;
• Hemophilia B (Christmas disease) - Factor IX deficiency

Question 39

Vitamin K dependent coagulation and fibrinolytic factors, and laboratory picture of Vitamin K deficiency.

Answer 39

• Factors II, VII, IX, and X; Protein C and S;
• normal platelet count and bleeding time; prolonged PT and PTT

Question 40

Transfusion reaction to watch out for in patients with IgA deficiency.

Answer 40

Allergic reactions

Question 41

IgM-mediated destruction of donor red cells.

Answer 41

Acute hemolytic transfusion reaction (AHTR)

Question 42

IgG-mediated destruction of donor red cells in a previously-sensitized individual.

Answer 42

Delayed hemolytic transfusion reaction (DHTR)

Question 43

ARDS-like complication in patients who underwent transfusion; due to activation of PMNs in lung vasculature.

Answer 43

Transfusion related acute lung injury (TRALI)