Clinical Pathology: Hematology & Coagulation

• Unfractionated heparin (UFH) is a glycosaminoglycan consisting of repeating sulfated disaccharides with chains from 3 to 30 kDa in size.

• Heparin binds to antithrombin and accelerates its activity 1000-fold, leading to the inactivation of coagulation factors IIa, Xa, IXa, and XIa.

• UFH is the most common injectable anticoagulant and is used for the treatment of acute coronary syndromes, venous thromboembolism (VTE), and atrial fibrillation. It is also used as the anticoagulant in cardiac bypass and extracorporeal membrane oxygenation circuits.

• UFH is monitored by following the activated partial thromboplastin time (aPTT). The sensitivity of the aPTT to heparin concentration varies from lot to lot of aPTT reagent. Therefore, the therapeutic range should be established with each new lot of aPTT reagent.

• The Brill-Edwards method of establishing the UFH therapeutic range requires samples from patients currently on UFH therapy, but not on warfarin (the prothrombin time [PT] should be in the reference range). UFH anti-Xa activity and the aPTT are measured on each sample. A linear regression is performed; the aPTT corresponding to 0.3 to 0.7 U/mL anti-Xa activity is read from the regression line. The aPTT range is set as the therapeutic range. If heparin-protamine titration is used, then 0.2 to 0.4 U/mL heparin would be used to determine the therapeutic range.

• UFH is usually administered as a bolus dose and then a constant infusion. The half-life of heparin is 1 to 2 hours. Therefore, heparin therapy is usually monitored by measuring the aPTT every 6 hours while it is adjusted.

• Adverse reactions to heparin include heparin-induced thrombocytopenia, osteopenia, and hyperkalemia.

• Heparin is reversed by administered protamine; fresh frozen plasma (FFP) is not used to reverse heparin.