bleeding disorders

Question 1

Bernard Soulier disease

Answer 1

• GP1b (vWF receptor) mutation
• abnormal adhesion/agglutination
• prolonged bleeding time
• thrombocytopenia with LARGE platelets

Question 2

Glanzmann’s thrombasthenia

Answer 2

• GPIIb/IIIa (fibrinogen receptor) mutation
• abnormal aggregation and PFA-100
• prolonged bleeding time

Question 3

aspirin

Answer 3

IRREVERSIBLY inhibits COX

-reduced thromboxane A2 synthesis/release

Question 4

NSAIDs

Answer 4

REVERSIBLY inhibit COX

-reduced thromboxane A2 synthesis/release

Question 5

Thrombotic thrombocytopenia purpura (TTP)

Answer 5

• thrombocytopenia, acquired
• microangiopathic anemia
• ADAMTS13 destruction
• large uncleaved monomers of vWF –> thrombi
• normal PT/PTT
• Tx: plasma exchange

Question 6

Hemolytic uremic syndrome (HUS)

Answer 6

• thrombocytopenia, acquired
• microangiopathic anemia
• normal PT/PTT
• NO destruction of ADAMTS13
• E. coli damages endothelial cells –> microthrombi
• children
• diarrhea, E. coli

Question 7

disseminated intravascular coagulation (DIC)

Answer 7

• pathologic activation of coagulation
• widespread microthrombi –> ischemia
• consumption of platelets and factors results in bleeding
• SECONDARY to sickness (obstetric, sepsis, malignancy, venom)
• skin necrosis

increased PTT/PT
decreased fibrinogen
decreased platelet count
increased d dimer

Tx: transfusion/replacement of factors

Question 8

von Willebrand disease (vWD)

Answer 8

• variable vWF levels
• mucocutaneous bleeding, easy bruising
• AD or acquired
• normal or increased PT/PTT
• increased bleeding time
• decreased FVIII activity
• abnormal PFA-100

Question 9

acquired vWD

Answer 9

Autoantibodies:
-SLE, malignancy, myeloma, MGUS, infections

Hypothyroidism
-decreased synthesis of vWF

Cardiac (destruction of vWF)
-aortic stenosis, congenital heart disease, mitral valve prolapse

Drugs

Question 10

hemophilia A

Answer 10

• X linked recessive (males affected)
• FVIII deficiency
• normal PT
• prolonged PTT
• factor assay

Question 11

hemophilia B

Answer 11

• X linked recessive (males affected)
• FIX deficiency
• normal PT
• prolonged PTT
• factor assay

Question 12

hemophilia C

Answer 12

• factory XI deficiency
• variable bleeding phenotype
• Ashkenazi Jews
• Tx: fresh frozen plasma

Question 13

antiphospholipid antibody syndrome

Answer 13

• immune mediated disorder
• venous or arterial thrombosis, recurrent fetal loss
• thrombocytopenia
• livido reticularis
• increased PTT (falsely bc binds phospholipid, prothrombin in assays)
• mixing studies: inhibitor