Anticoagulation

Work in Progress Updated Feb 6, 2026

Heparin

Most reports of ADR are delayed drug reactions, which occur in up to 7.5% of patients.

Rare reports of immediate drug allergy.

Reactions to Protamine - the main reversal agent for heparin-mediated anticoagulation has occurred

  • Protamine is a highly cationic peptide, originally derived from salman spermatozoa

Unfractionated heparin (UFH) and low molecular weight heparin (LMWH) have strong negative charge.

UFH

  • Sulfated carbohydrates from glycosaminoglycan family first purified from pig intestines

  • Naturally occuring inhibitors of antithrombin III, leading to anti-thrombin III-mediated inactivation of thrombin

  • Contain molecular weights 14-18 kDa

LMWH

  • Modified by fractionation or ?depolymerization to provide a purified product

~60% < 8 kDa

  • Purification leads to decreased “biological unpredictability” that is seen with UFH

Cross-reactivity

  • Wide range of cross-reactivity of UFH, heparinoids, LMWHs in DHR; however, fondaprinux and danaporid generally well-tolerated.
  • When an alternative anticoagulant is needed, a chemically unrelated product such as bivalirudin, argatroban, a direct oral anticoagulant, or fondaparinux may be substituted [105]. (From UpToDate)

Heparin is not cross-reactive with structurally distinct anticoagulants such as hirudins or factor Xa inhibitors.

HIT

IgG platelet factor 4, > 90% sensitivity

Serotonin release assay criteria standard, longer turn around time, specialized equipment, limited availability

Skin Testing

Heparin, LMWH

Management

Heparin desensitization

Heparin challenge 5000 units SC (DVT prophylaxis dose)

Enoxaparin 40 mg SQ (DVT prophylaxis dose)

Alternatives

Direct thrombin inhibitors

Bivalrudin

Argatroban

Fondaparinux - does not cross react with UFH, LMWH, heparinoids

Hirudins = natural peptides derived from medical leeches salivary gland (e.g. lepirudin)

Bivalrudin = synthetic; peptide sequence is an analog of hirudin