Thrombotic Disorders II

Question 1

Explain prothrombin gene mutation disease.

Answer 1

Mutation in 3′ untranslated region leading to increased stability of prothrombin mRNA, leads to increased Žproduction of prothrombinŽ, causes increased plasma levels and venous clots.High prevalence in Caucasians.Diagnosis is made by checking for mutation via PCR.

Question 2

Explain Protein C and Protein S deficiency disease.

Answer 2

• Decreased ability to inactivate factors Va and VIIIa.
• Leads to increased risk of thrombotic skin necrosis with hemorrhage after administration of warfarin. If this occurs, think protein C deficiency.
• Patients have a high risk of DVT
• Those who are homozygous for the mutation can express this as neonates that have skin thrombosis and necrosis at birth, disease called Neonatal Purpura Fulminans
• There are decreased levels of Protein C (or Protein S)in the plasma so mutation analysis is not required, other causes of protein C or S deficiency can be warfarin, liver disease, vitamin K deficiency and DIC

Question 3

Explain Anti thrombin III deficiency.

Answer 3

• Inherited deficiency of antithrombin: has no direct effect on the PT, PTT, or thrombin time but diminishes the increase in PTT following heparin administration.
• Can also be acquired: renal failure/nephrotic syndromeŽ, leads to antithrombin loss in urine, as a result there is a decrease inŽinhibition of factors IIa and Xa.
• Hallmark of this disease is that there is resistance to heparin therapy, PTT doesn’t increase when heparin is administered.
• There is decreased plasma levels of anti thrombin III, could be due to other factors such as liver disease, nephrotic syndrome, DIC

Question 4

Explain antiphospholipid syndrome.

Answer 4

• APSis an acquired disease characterized by the acquisition of one or more thrombosis-promoting autoantibodies called antiphospholipid antibodies.
• Can be primary or secondary due to lupus Primary antigen isβ2 glycoprotein.
  Diagnose based on clinical criteria including history of thrombosis (arterial or venous)or spontaneous abortion along with laboratory findings of
• Lupus anticoagulant
• Anticardiolipin
• Anti-β2 glycoprotein antibodies.
• Treatment issystemic anticoagulation and immunosuppression. Anticardiolipin antibodies and lupus anticoagulant can cause false-positive VDRL/RPR (syphilis test)and prolonged PTT. Viral infections can give a false positive, must give a positive test on 2 occasions 12 weeks apart.

Question 5

Explain lupus induced APS.

Answer 5

• Causes a prolonged PTT with a noncorrected 1:1 mixed study Must perform two tests to confirm the diagnosis:
• dilute Russell Viper venom time
• hexagonal phase phospholipid neutralization test
• Lupus anticoagulant is diagnosed if either test is positive
• Must show positive test on 2 occasions, 12 weeks apart, to exclude transient lupus anticoagulant due to infection

Question 6

Explain HIT.

Answer 6

Heparin Induced ThrombocytopeniaDefinition: A drug induced thrombotic disorder caused by antibodies directed against the heparin-platelet factor 4 complex

Question 7

HIT clinical features.

Question 8

HIT diagonsis and treatment.