Heparin | Notion

Heparin

There are two main types of heparin - unfractionated, 'standard' heparin or low molecular weight heparin (LMWH). Heparins generally act by activating antithrombin III. Unfractionated heparin forms a complex which inhibits thrombin, factors Xa, IXa, XIa and XIIa. LMWH however only increases the action of antithrombin III on factor Xa

Adverse effects of heparins include:

bleeding
thrombocytopenia - see below
osteoporosis and an increased risk of fractures
hyperkalaemia - this is thought to be caused by inhibition of aldosterone secretion

The table below shows the differences between standard heparin and LMWH:

	Standard heparin	Low molecular weight heparin (LMWH)
Administration	Intravenous	Subcutaneous
Duration of action	Short	Long
Mechanism of action	Activates antithrombin III. Forms a complex that inhibits thrombin, factors Xa, IXa, Xia and XIIa	Activates antithrombin III. Forms a complex that inhibits factor Xa
Side-effects	BleedingHeparin-induced thrombocytopaenia (HIT)Osteoporosis	BleedingLower risk of HIT and osteoporosis with LMWH
Monitoring	Activated partial thromboplastin time (APTT)	Anti-Factor Xa (although routine monitoring is not required)
Notes	Useful in situations where there is a high risk of bleeding as anticoagulation can be terminated rapidly. Also useful in renal failure	Now standard in the management of venous thromboembolism treatment and prophylaxis and acute coronary syndromes

Both unfractionated heparin and LMWH can bind to antithrombin to increase its activity against Factor Xa. Only unfractionated heparin is able to bind to both antithrombin and thrombin to allow antithrombin to inactivate thrombin. (it has longer sequence that can hold together)

LMWHs (eg, enoxaparin, dalteparin) act predominantly on factor Xa.

Feature	Unfractionated Heparin (UFH)	Low Molecular Weight Heparin (LMWH)
Administration	IV infusion or SC	SC injection
Monitoring	APTT (Target 1.5–2.5x control)	Usually none (Anti-Xa in special cases)
Half-life	Short (1–2 hours)	Long (4–6 hours)
Renal Impairment	Safe (Hepatic clearance)	Accumulates (Renal clearance)
Reversibility	Fully reversible with Protamine	Only partially reversible
HIT Risk	Higher	Lower

Fondaparinux acts only on factor Xa.

In the presence of pregnancy, renal failure, or obesity, laboratory monitoring is recommended for proper dosing. Anti-Xa levels should be measured four hours after subcutaneous injection; dosing should be titrated to achieve a level of 0.6 to 1.0 international units/mL if administered twice daily, or 1.0 to 2.0 international units/mL if administered once daily.

Low-molecular-weight heparin (Clexane) has proven more effective than unfractionated heparin for thromboprophylaxis following orthopedic surgery/ joint procedures such as total knee replacement.

However, unfractionated heparin is used for prevention of DVT in immobile patients or in hospitalized patients with renal failure.

Record the patient’s weight (in kg) accurately on the inpatient drug chart and in the medical records.

The treatment dose should be calculated based on the patients’ actual body weight (kg) except during pregnancy when the patient’s early weight should be used I.e. weight in the first trimester.