Bleeding Disorders II

Question 1

What are the different tests employed to check for coagulation disorders?

Answer 1

• PT — tests function of common and extrinsic pathway (factors I, II, V, VII, and X). Defect leads to increased ŽPT.
• INR (international normalized ratio) — calculated from PT. 1 = normal, > 1 = prolonged. Most common test used to follow patients on warfarin.
• PTT—tests function of common and intrinsic pathway (all factors except VII and XIII). Defect leads to increased PTT.

Question 2

Explain hemophilia.

Answer 2

Hemophilia is defined as intrinsic pathway coagulation defect.

• A: deficiency of factor VIII ; X-linked recessive.
• B: deficiency of factor IXŽ; X-linked recessive.
• C: deficiency of factor XIŽ; autosomal recessive.
• PTT is increased
• Platelet count and bleeding time is normal in all hemophilia
• Macrohemorrhage in hemophilia—hemarthroses (bleeding into joints, such as knee), easy bruising, bleeding after trauma or surgery (eg, dental procedures).
• Treatment: desmopressin + factor VIII concentrate (A); factor IX concentrate (B); factor XI concentrate (C).

Question 3

What are the different types of Hemophilia A?

Answer 3

• Severe (50%), moderate (10%) and mild (40%)
• In severe there is spontaneous bleeding, mainly due to the development of FVIII inhibitor.
• Moderate and mild only result from factor VIII deficiency, there is prolong bleeding only after trauma or surgery.
• Hence blood transfusion will help mild and moderate hemophilia A but not severe.
• Treatment for severe hemophilia A consists of recombinant FVIII and recombinant FVIIa

Question 4

Explain FXIII deficiency.

Answer 4

Factor XIII Deficiency

• Rare autosomal recessive bleeding disorder
• Causes defective fibrin cross-linking and an unstable fibrin clot
• Manifested by bleeding and delayed wound healing
• Normal PT, normal PTT, normal bleeding time
• Abnormal urea solubility test (blood clot dissolves in urea, a denaturing agent)

Question 5

Explain Von Willebrand Disease.

Answer 5

• Intrinsic pathway coagulation defect: decreased vWF leads to increased ŽPTT (vWF acts to carry/protect factor VIII).
• Defect in platelet plug formation: decreased vWF leads to Ždefect in platelet-to-vWF adhesion.
• Autosomal dominant.
• Petechiae are observed.
• Mild but most common inherited bleeding disorder.
• Platelet count is normal, bleeding time is increased, PT is normal, PTT is increased.
• No platelet aggregation with ristocetin cofactor assay.

Question 6

How is vWF treated?

Answer 6

Von Willebrand Disease -Treatment

• Humate P (VWF concentrate)
• Cryoprecipitate -good source of VWF
• Desmopressin (anti-diuretic hormone) -stimulates endothelial cells to release remaining VWF stores

Question 7

Explain acquired factor VIII inhibitor disease.

Answer 7

Acquired Factor VIII Inhibitor Pathogenesis

• Idiopathic (elderly)
• Secondary (autoimmune disease: SLE, rheumatoid arthritis, postpartum, hemophilia A)
• specificity against factor VIII
• Clinical features - mild to severe bleeding, spontaneous resolution or chronic
• PTT is increased, PT is normal
• Treatment is immunosuppressive drugs, recombinant FVIIa

Question 8

Explain DIC.

Answer 8

Defined as anacquired hemorrhagic and/or thrombotic disorder caused by excessive release of tissue factor into the blood, leading to over activation of the coagulation system and secondary fibrinolysis. Pathogenesis

• release of tissue factor into the blood
• risk factors: bacterial sepsis, massive trauma, acute promyelocytic leukemia, carcinoma, placental abruption, retained dead fetus
• excess thrombin and plasmin generation
• clotting factor and platelet consumption Clinical features
• bleeding (venipuncture sites, etc.)
• thrombosis (arterial and venous; brain, heart, lung, kidney, adrenal gland, spleen, liver, etc.)
• syndromes (Waterhouse-Friderichsen, Kasabach-Merritt) Pathologic features
• hyaline microthrombi of microvessels
• platelet and fibrin rich thrombi
• thrombocytopenia
• prolonged PT and/or PTT
• decreased fibrinogen
• elevated D-dimer
• microangiopathic hemolysis (schistocytes on blood smear

Question 9

What are some of the other acquired coagulation disorders?

Question 10

What are some of the acquired fibrinolytic protein deficiency disorders?