Heparin

Heparin, more specifically unfractionated heparin (UFH) to distinguish them from low-molecular-weight heparin (LMWH) is an anticoagulant. It's administered by intravenous or subcutaneous injection. Nowadays LMWH have replaced many use cases of UFH, as it's as efficacious and more predictable anticoagulant effect.

Heparin isn’t actually a single molecule but a family of large and sulphated glycosaminoglycans that all act on antithrombin III. Heparin is actually present endogenously in the body inside the granules of mast cells. To acquire heparin the pharmaceutical industry extracts them from beef lung or pig intestine. However, because heparin isn’t a single molecule can the biological activity of it differ depending on where it is extracted from. Because of this the dose of heparin is not given in units of mass but rather in units of activity. The molecular weight of heparin is between 5 and 35 kDa, depending on where it was extracted from.

Protamine sulphate is the antidote of heparin.

Indications

Heparin is preferred over coumarins like warfarin in cases where it is necessary that the anticoagulant effect begins immediately. It’s used to prevent/treat deep vein thrombosis, pulmonary embolism, and acute coronary syndrome.

Heparin is administered IV or s.c.

Mechanism of action

Heparin increases the effect of antithrombin III and therefore has strong anticoagulant activity.

Pharmacokinetics

It acts immediately when given IV but has a 60-minute delay when given subcutaneously. Because of its large molecular size heparin would not be absorbed through the GI tract.

Heparin is eliminated by the liver and by phagocytosis by macrophages. It’s safe to use in pregnancy.

Monitoring

Like for warfarin, patients receiving heparins may measure its effect frequently to ensure that they’re not overtreated or undertreated.

Heparin effect can be measured either by anti-factor Xa activity (preferred) or activated partial thromboplastin time (aPTT). One should aim for the anti-factor Xa activity to be 0.3 - 0.7 or the aPTT to be 1.5 – 2.5 times that of a control subject.

Side effects

Heparin may paradoxically cause thrombosis. It’s an uncommon but serious side effect called heparin-induced thrombocytopaenia (HIT). It occurs if IgG and IgM antibodies are produced against heparin and platelet factor 4. The immune complexes that form activate platelets and cause thrombosis. Opsonized platelets are phagocytosed, causing thrombocytopaenia.

HIT is treated by taking the patient off heparins and giving another anticoagulant instead, most commonly either danaparoid or argatroban. Platelet transfusion may be necessary. Warfarin can not be used due to it’s slow onset of action.

Antidote

The antidote of heparin is a drug called protamine sulphate, which can be used if there is excessive bleeding. It binds to and inactivates heparin.