Tuesday, February 17, 2015

Study group discussion: Heparin, warfarin and the anti-fibrinolytics

Name the drugs which inhibit fibrinolysis.
TACA! Tranexaemic acid, amino caproic acid.

Describe the mechanism of action of heparin.
Binds to anti thrombin 3, blocks factor 10.

Which coagulation factors does warfarin affect?
Vitamin K dependent ones: 10, 9, 7, 2, protein C.

Why there is a lag of 2 - 3 days for warfarin to act?

Warfarin inhibits the formation of newly developed coagulation factors. It does nothing to reduce the concentration of already present coagulation factors in blood. Prothrombin has a half life of 60 hours. Hence the delay.

How do you monitor dosage of heparin and of warfarin?
Warfarin is by INR. Heparin by aPTT.
INR: International normalized ratio

How is INR measured?
Patient's PT / standard PT
PT meaning the prothrombin time

Antidote of heparin and warfarin?
Protamine sulfate for heparin. Vitamin K1 for warfarin.

In which genetic thrombophilia, giving heparin is useless?
Anti thrombin deficiency.

Causes of acquired AT3 deficiency? 
Occurs in anti phospholipid antibody syndrome and in ascites and nephrotic syndrome.

What is the treatment for AT3 deficiency, if you can't give heparin?
You will give AT3 substitute in case of AT3 deficiency :P
You can also give lepirudin, argatroban.

If a person develops severe necrosis of the skin after he recieves warfarin, what is he suffering from?
Hint: It's a disease related to the coagulation pathway. It's a zymogen which stops clot formation when coagulation pathway begins.

Protein C deficiency is the answer. 

Well, you see, the vitamin K dependent clotting factors have different half lives. Protein C is one of them and it has the shortest half life. So warfarin depletes all the protein C in the patient.. Which causes a transient hypercoagulable state. This causes thrombosis is the blood vessels of the skin. Hence, the skin necrosis.

So how to prevent this from happening?
Warfarin-induced skin necrosis:
Stop warfarin and give vitamin K.
Give heparin in therapeutic doses.
For protein C-deficient patients, give protein C to normalise protein C activity (as protein C concentrate or as fresh frozen plasma).

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