Unfractionated heparin versus low molecular weight heparin

What it is

Unfractionated heparin (UFH), low molecular weight heparin (LMWH) and fondaparinux are indirect parenteral anticoagulants that all work through antithrombin.

UFH activates anti-thrombin III, which forms a complex inhibiting clotting factors IIa and Xa as well as IX, XI and XII. LMWH - enoxaparin, tinzaparin - activates anti-thrombin III as well, and the two sources differ over what its complex inhibits: one writes the LMWH mechanism as a complex inhibiting clotting factor Xa, while the pharmacokinetic table sets Factor Inhibition for enoxaparin (LMWH) at IIa and Xa, beside IIa, Xa, IXa, XIa and XIIa for UFH. Fondaparinux is a synthetic derivative of LMWH and inhibits Xa only.

The molecular weight in kDa (mean) is 15,000 for UFH, 4000-5000 for enoxaparin and 1728 for fondaparinux. The anti-Xa:anti-IIa ratio is 1:1 for UFH and 2:1 to 4:1 for LMWH.

How it is treated

UFH is given intravenously and LMWH subcutaneously. Bioavailability after subcutaneous administration is 30% for UFH, 90% for enoxaparin and 100% for fondaparinux.

Half-life is short for UFH, about 1 hour (0.5-1.5, varies with dose), longer for LMWH at 3-6 hours (varies with CrCL) and 17-21 hours for fondaparinux. UFH is cleared rapidly by a saturable nonrenal route with first-order renal kinetics; LMWH and fondaparinux have renal clearance.

Monitoring: aPTT, anti-Xa or ACT for UFH; anti-Xa for LMWH, though routine monitoring is not needed. Anti-Xa activity may be checked in special situations - severe renal impairment, pregnancy, extreme body weight, high bleeding or thrombotic risk, prolonged therapy
Renal failure: UFH is useful; LMWH should be used with caution or avoided if GFR <30 because of increased risk of bleeding
Reversal: UFH is rapidly and fully reversible by protamine sulphate, which is useful where rapid reversal is required; LMWH is only partially reversible by protamine; fondaparinux is not reversible