Heparin &Fondaparinux

Question 1

Mechanism of action?

Answer 1

Thrombin &factor Xa are key components in the final common coagulation pathway that leads to the formation of a fibrin clot. By inhibiting their function, heparin &fondaparinux prevent the formation &propagation of blood clots. Unfractionated heparin activated antithrombin that, in turn, inactivates both thrombin &Xa. Low molecular weight heparin (dalteparine &enoxaparine) preferentially inhibits Xa. LMWH have more predictable effects &, unlike UFH, do not usually require laboratory monitoring, making them preferred in current use.
Fondaparinux is a synthetic compound similar to heparin, it inhibits Xa only. Of similar efficacity to LMWH, fondaparinux is the trt of choice in ACS.

Question 2

Difference between heparin &fondaprinux?

Answer 2

heparin inhibits both thrombin &Xa, while fondaparinux only inhibits Xa.

Question 3

Difference between UFH, LMWH &fondaparinux?

Answer 3

• UFH inhibits both thrombin &Xa, LMWH preferentially inhibit factor Xa, fondaparinux only inhibits Xa without touching on thrombin.
• Risk of bleeding as an AE is lower with fondaparinux than with LMWH or UFH.
• Risk of heparin-induced thrombocytopenia is less likey with LMWH &fondaparinux than with UFH.
• In cases where the anticoagulation effect needs to be elevated, protamine can be administered but is effective for UFH, less so for LMWH &ineffective with fondaparinux.

Question 4

Indications?

Answer 4

• LMWH is first choice agent for pharmacological prophylaxis of VTE for hospital inpatients, it is the initial treatment for DVT &PE.
• In ACS, LMWH &fondaparinux are part of first-line therpay for revascularisation &preventing progression of intra-coronary thrombosis.

VTE venous thromboembolism, DVT deep vein thrombosis, PE pulmonary embolism, ACS acute coronary syndrome.

Question 5

Important AE ?

Answer 5

Injection site reactions, bleeding (lower with fonadparinux), heparin-induced thrombocytopenia (lower with LMWH &fondaparinux).

Question 6

Clinical tip

Answer 6

LMWH are used when initiating warfarin since the latter has a long onset delay.

Question 7

How are they taken ?

Answer 7

SC injection (UFH sometimes via IV infusion)
LMWH &fondaparinux's doses are dependent on the weight.

Question 8

Interest of associating LMWH (specifically) with Warfarin in new diagnosis of VTE ?

Answer 8

because Warfarin inhibits the natural anticoagulant activity of the proteins C&S, &it does this before inhibiting the other coagulation factors. Using LMWH assures anticoagulant cover during this intial ‘pro-coagulant period’, it is stopped when INR is in therapeutic ranges.