OnlineMedEd: Hematology Oncology - "Thrombophilia"

Question 1

What do proteins C and S do?

Answer 1

• Protein S activates protein C

* Protein C deactivates factor Va

Question 2

Explain the pathway of factors I, II, III, V, and X.

Answer 2

1) Factor Xa (activated by the extrinsic –VIIa –and intrinsic –IXa – pathways) activates factor II using Va as a cofactor.
2) Factor IIa converts I to Ia (better known as fibrinogen and fibrin).
3) Factor Ia makes clots.
4) Factor IIIa (antithrombin) deactivates IIa and Xa.
5) Factor Va is deactivated by proteins S and C.

Question 3

Review the pathophysiology of factor V Leiden.

Answer 3

Factor Va is mutated so that it doesn’t respond to protein C. Thus, it remains activated and continues to allow Xa to activate II, leading to excess clotting.

Question 4

What mutation leads to prothrombin mutation?

Answer 4

Prothrombin 20210A

This leads to IIa that does not deactivate as easily.

Question 5

________________ are rarer but more potent thrombophilias than prothrombin and factor V Leiden mutations.

Answer 5

Protein C, protein S, and antithrombin deficiencies

Question 6

Explain the relative risk of thromboembolism from factor V Leiden, surgery, and cancer.

Answer 6

• Surgery or trauma: 10x RR
• Cancer: 20x RR
• Factor V Leiden: 1.5x

Question 7

Describe the classic pattern of clotting seen in antiphospholipid antibody syndrome.

Answer 7

Arterial and venous clots

Question 8

Why is APS a special diagnosis in the realm of thrombophilias?

Answer 8

With all of the thrombophilias, you wait until the person has a second unprovoked clot to treat with warfarin/LMWH. With APS, you treat after the first one if it is diagnosed (which you would suspect in a person with SLE who has clots).

Question 9

How is APS diagnosed?

Answer 9

Russell viper venome test