Blood Diseases

Question 1

Cause: Mutations in chromosome 9 or 12, 70% of patients with arterio-venous malformations have this disorder
Presentation: cutaneous telangiectasia, epistaxis (nose bleeds), visceral involvement, GI involvement

Answer 1

Hereditary Hemorrhagic Talangiectasia (HHT-1 or HHT-2)

Question 2

Cause: Autosomal dominant, most common hereditary bleeding disorder (7 subtypes)
Presentation: Excessive bleeding from mucosal membranes (Nose, gums, vagina), petechiae
Diagnostics: Prolonged PTT, unaffected PT

Answer 2

von Willebrand Disease

Question 3

Cause: Anti-factor VIII antibodies
Presentation: Serious or life-threatening bleeding, muscle and GI/GU bleeds are common, pregnancy/post-partum, autoimmune disease, or malignancy in older males

Answer 3

Acquired Hemophilia

Question 4

Cause: Mutation of thrombin binding site
Presentation: coagulation disorder, patients cannot be anti-coagulated with heparin or small molecule heparin mimics

Answer 4

Antithrombin III Deficiency

Question 5

Cause: Rare autosomal recessive disorder
Presentation: Recurrent purpura fulminans in infancy, DIC, and VTE (severe), incident and recurrent VTE (mild)

Answer 5

Protein C Deficiency

Question 6

Presentation: Recurrent VTE and fetal loss (moderate), DIC and recurrent purpura fulminans in infancy (severe)

Answer 6

Protein S Deficiency

Question 7

Cause: Mutation resulting in increased circulating levels of prothrombin
Presentation: Increases risk for VTE 2-3x, occurs in related populations at high risk for Factor V Leiden mutation

Answer 7

Prothrombin G2010A

Question 8

Cause: Autosomal dominant mutation (missense substitution) in the factor V gene, resulting in a factor V protein that resistant to activated protein C
Presentation: Increased risk for VTE

Answer 8

Factor V Leiden

Question 9

Cause: Deficiency of ADAMTS13 (commonly caused by auto-antibodies)
Presentation: Thrombotic microangiopathy, related to signs and symptoms of renal and CNS microthrombi, confusion, fever, renal failure, fatal without treatment
Diagnostics: Normal PT and PTT

Answer 9

Thrombotic Thrombocytopenia Purpura (TTP)

Question 10

Cause: Auto-antibodies that bind B2-GPI in the presence of anionic phospholipid
Presentation: Venous thromboembolism or pregnancy morbidity
Diagnostics: Lab results of anti-cardiolipin. anti-B2GPI, lupus anticoagulant activity

Answer 10

Antiphospholipid Syndrome (APLS)

Question 11

Cause: Occurs in < 1% of APLS patients
Presentation: Thrombotic occlusions occurring in three or more organs/tissues, “thrombotic storm”, mortality approaches 50% even with optimal treatment

Answer 11

Catastrophic Antiphospholipid Syndrome (CAPS)

Question 12

Cause: Malabsorption/dietary lack, chronic blood loss, inflammation/chronic disease
Presentation: microcytic, hypochromic cells, pica, koilonychia (spoon nails), cheilosis/glossitis/alopecia, fatigue (brain fog), possible thrombocytosis

Answer 12

Iron Deficiency Anemia

Question 13

Cause: dietary deficiency, increased requirement (pregnancy), defective absorption, metabolic disorders
Presentation: megaloblastic anemia, hyper-segmented neutrophils, “lemon-yellow” skin, atrophic glossitis (sore/smooth tongue)

Answer 13

Folate Deficiency

Question 14

Cause: Decreased intake, increased requirement, defective absorption
Presentation: megaloblastic anemia, peripheral neuropathy, dorsal and lateral tract symptoms, dementia

Answer 14

Vitamin B-12 Deficiency

Question 15

Cause: Immune or viral (Parvovirus B19) attack on erythrocyte progenitors, auto-immune in association with driving malignancy
Presentation: anemia, aplastic crisis in patients with prior anemia, severely low reticulocyte count

Answer 15

Pure Red Cell Aplasia (Aplastic Crisis)

Question 16

Cause: Immune or viral (CMV/EBV) attack on progenitor cells, direct toxic damage, inherited marrow defect
Presentation: anemia, increased fat storage in bone marrow, short stature, musculoskeletal abnormalities, dysplastic nails, skin changes

Answer 16

Aplastic Anemia

Question 17

Cause: autosomal dominant (or recessive) hemolytic anemia disorder (most common in Northern European people but can affect any ethnic group), AD: B-spectrin unable to bind to ankyrin, AR: a-spectrin unable to bind to ankyrin, leads to inability of cytoskeleton to bind to cell membrane, spherocytes become trapped in spleen

Presentation: well-compensated hemolysis with periodic exacerbations (fatigue, jaundice, splenomegaly), normocytic/normochromic
Diagnosis: Osmotic fragility test, Band 3 Erythrocyte Membrane Assay

Answer 17

Hereditary Spherocytosis (HS)

Question 18

Cause: defect in a-spectrin, b-spectrin and band 4.1 genes causing horizontal defect
Presentation: homozygotes have chronic hemolysis, worse with stress

Answer 18

Hereditary Elliptocytosis

Question 19

Cause: acquired genetic defect in PIGA gene in hematopoietic cell leading to loss of anchor proteins, lack of CD55/CD59 results in RBC destruction by complement
Presentation: hemolysis and atypical thrombosis due to inflammation, aplastic anemia, fatigue, chest pain, headaches, impotence

Answer 19

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Question 20

Cause: X-linked disorder, most common enzyme disorder, enzyme unable to reduce in settings of oxidative stress
Presentation: hemolysis associated with certain drugs, lab findings of poikilocytes, blister cells, bite cells, spherocytes, Heinz Bodies

Answer 20

G6PD Deficiency

Question 21

Cause: autosomal recessive
Presentation: RBCs become rigid due to decreased ATP, mild to severe hemolytic anemia, jaundice, gallstones

Answer 21

Pyruvate Kinase Deficiency

Question 22

Cause: IgG antibodies directed non-specifically at Rh complex, RBCs coated in IgG and complement and destroyed by macrophages
Presentation: Pallor, fatigue, splenomegaly, elevated LDH, Coombs test positive, microspherocytes

Answer 22

Warm Antibody Auto-Immune Hemolytic Anemia (AIHA)

Question 23

Cause: IgM antibodies after infection bind RBCs and activate complement, intravascular and extravascular hemolysis
Presentation: Usually self-limited hemolytic anemia

Answer 23

Cold Auto-Immune Hemolytic Anemia (AIHA)

Question 24

Cause: IgG directed at the P blood group antigens after viral infection or syphilis, caused by Donath-Landsteiner antibody
Presentation: Dark urine

Answer 24

Paroxysmal Cold Hemoglobinuria (Rare type of Cold AIHA)

Question 25

Cause: immune complexes, hapten formation, autoantibody induction, nonspecific adsorption of Igs
Presentation: Hemolytic anemia

Answer 25

Drug-Induced Immunohemolytic Anemia

Question 26

Cause: Sickle Cell Disease (main cause of death for HbSS patients)
Presentation: Pulmonary vaso-occlusive crisis, chest pain, progressive pulmonary infiltrates, progressive/refactory arterial hypoxemia

Answer 26

Acute Chest Syndrome

Question 27

Cause: obstruction of splenic veins
Presentation: hypotension, tachycardia, massive splenomegaly, pancytopenia, risk of sepsis, organ damage results in “autosplenectomy”

Answer 27

Splenic Sequestration Crisis

Question 28

Cause: venous occlusion of corpora cavernosa
Presentation: Intermittent or persistent painful erections

Answer 28

Priapism

Question 29

Cause: “Loop-deletion” of alpha globin genetics (prevalent in Asia and Africa)
Presentation: mild to severe anemia, target cells, microcytosis, MI < 12

Answer 29

Alpha Thalassemia

Question 30

Cause: Homozygous mutations in Beta globin genes (B0/B0, B+/B0)
Presentation: Severe anemia, microcytosis, reticulocytosis, frontal bossing/splayed teeth, hepatosplenomegaly

Answer 30

Beta Thalassemia

Question 31

Cause: Sporadic > AD > AR
Presentation: Recurrent infections, ANC < 200/ul

Answer 31

Severe Congenital Neutropenia

Question 32

Cause: AD > Sporadic
Presentation: recurrent infections AND mouth sores, ANC 200-500 /ul, 14-21 day cycle

Answer 32

Cyclic Neutropenia

Question 33

Cause: Analgesics, anti-thyroid drugs, antibiotics, antipsychotics, Phenothiazines
Presentation: Decreased ANC

Answer 33

Drug-Induced Neutropenia

Question 34

Cause: RA, SLE, Sjogrens syndrome
Presentation: decreased ANC

Answer 34

Autoimmune neutropenia

Question 35

Cause: FAS mediated apoptosis
Presentation: neutropenia, anemia, thrombocytopenia

Answer 35

LGL leukemia

Question 36

Cause: Autosomal recessive abnormal expression or activity of GP-Ib complex
Presentation: Platelet type bleeding, mild thrombocytopenia, giant platelets

Answer 36

Bernard-Soulier Syndrome

Question 37

Cause: AR GPIIb or GP IIIa defect
Presentation: platelet defect disorder

Answer 37

Glamzmann Thrombasthenia

Question 38

Cause: Auto-antibodies against GP IIb/IIIa, low levels of TPO
Presentation: peripheral thrombocytopenia, normal or increased megakaryocytes in bone marrow, absence of splenomegaly, children <20K platelets, bleeding in adults <50K

Answer 38

Idiopathic Thrombocytopenic Purpura (ITP)

Question 39

Cause: drugs, connective tissue diseases, lymphoproliferative disease, infections (CMV, HIV, EBV, Hep B/C, V. Zoster, H. Pylori), HIT/HITT
Presentation: Decreased platelet count

Answer 39

Secondary Autoimmune Thrombocytopenia

Question 40

Cause: Shiga toxin in children
Presentation: Renal failure, diarhea

Answer 40

Hemolytic Uremic Syndrome (HUS)

Question 41

Cause: Sepsis, malignancy, amniotic fluid embolism, snake bites
Presentation: Thrombocytopenia, intravascular consumption of platelets, thrombosis, bleeding

Answer 41

Disseminated Intravascular Coagulation (DIC)

Question 42

Cause: Known genetic defect, disregulation in NK, CD8, and T-cell function
Presentation: Fever, splenomegaly, cytopenia, hypertriglyceridemia, hyperfibrinogenemia, decreased or absent NK activity

Answer 42

Hemophagocytic Lymphohistiocytosis (HLH)

Question 43

Mutations in regulators of complement activation and inhibition leading to unchecked activated complement pathway

Answer 43

Atypical Hemolytic Uremic Syndrome (aHUS)