Heparin & Low Molecular Weight Heparins

Heparin and low molecular weight heparins bind to antithrombin II, which potentiates the inactivation of factor Xa.  Decreased factor Xa levels reduces activation of the clotting cascade.  Heparin also potentiates the inhibition of thrombin.  Heparin & LMWHs are used to treat venous thrombosis/thromboembolism, prophylaxis for DVT, acute MI, and to treat clot formation during pregnancy. Bleeding can be a side effect. Heparin induced thrombocytopenia (HIT) is associated primarily with heparin use and is a result of an immune response.  HIT paradoxically causes venous and/or arterial thromboembolism.

Class Drugs

• Heparin

• LMWH:

Enoxaparin

• Dalteparin

• Tinzaparin

Class Mechanism of Action

• Heparin & LMWH:

Binds to antithrombin III, which potentiates inactivation of factor Xa

• Decreased factor Xa levels reduces coagulation

• Heparin:

In addition, heparin potentiates inhibition of thrombin

• Decreased thrombin levels reduces coagulation

Sites of action of the coagulation cascade of heparin and low molecular weight heparin

Class Applications

Treatment of DVT/PE

• Prevents fibrin formation

DVT prophylaxis in post-operative surgery

Treatment of acute MI

Class Adverse Effects

Bleeding, can be life threatening

• Reversal agent for Heparin Only is protamine sulfate

Contraindications: Recent neurologic or ophthalmologic surgeryHeparin Induced Thrombocytopenia (HIT)

• Poorly understood immune response

• Primarily develops with use of heparin, but LMWH can also cause HIT

• Induces thrombin generation resulting in paradoxical venous or arterial thromboembolism

Hypersensitivity

• Urticaria, chills, fever, anaphylactic shock

• Heparin is derived from porcine sources

• Primarily develops after use of heparin, but previous development of hypersensitivity reaction to heparin makes LMWH contraindicated

Drug Table

Drug Name	Application	Comments	Image
Heparin		Pharmacokinetics ; Variable response to dosing due to unpredictable binding to neutralizing proteins; Requires monitoring of Factor Xa levels to determine activity; Given IV or subcutaneously; Short half-life (1.5-2 hrs), allows heparin to be "turned-off"; Reversal agent protamine sulfate also available	"Hemp" "Pear"
Enoxaparin		Pharmacokinetics ; No monitoring needed unless renal insufficiency is present; Given subcutaneously; Longer half-life (3-12 hrs); Reversal agent protamine sulfate also available but less effective than with heparin	"An Ox" "Pear"
Dalteparin		Pharmacokinetics ; No monitoring needed unless renal insufficiency is present; Given subcutaneously; Longer half-life (3-12 hrs); Reversal agent protamine sulfate also available but less effective than with heparin	"Delta" "Pear"
Tinzaparin		Pharmacokinetics ; No monitoring needed unless renal insufficiency is present; Given subcutaneously; Longer half-life (3-12 hrs); Reversal agent protamine sulfate also available but less effective than with heparin	"Tin Can" "Pear"