Unfractionated

Unfractionated, in medical contexts, most often refers to unfractionated heparin (UFH), a complex mixture of heparin polysaccharide chains with a broad range of molecular weights. It contrasts with fractionated products such as low molecular weight heparins (LMWH) and synthetic agents like fondaparinux, which are produced by depolymerizing or refining the original heparin.

Mechanism and components: UFH enhances the activity of antithrombin III, leading to inhibition of thrombin (factor IIa) and factor Xa, with a relatively broad effect due to its long chains. This results in diminished formation of fibrin clots. The variable chain lengths mean that UFH has a less predictable anticoagulant response than LMWH.

Administration and pharmacokinetics: UFH is not orally active and is given by intravenous infusion or subcutaneous injection. Intravenous administration yields rapid anticoagulation, while subcutaneous dosing is often used for prophylaxis. The dose-response relationship is variable because UFH binds to plasma proteins and cells, necessitating laboratory monitoring in many settings. The half-life is dose- and patient-dependent and can be prolonged in renal or hepatic impairment.

Monitoring and reversal: Anticoagulation is commonly monitored with the activated partial thromboplastin time (aPTT) to guide dosing when given by IV infusion. Protamine sulfate can reversibly neutralize UFH, with the degree of reversal depending on the total heparin dose.

Safety and uses: Bleeding is the main risk; there is also a risk of heparin-induced thrombocytopenia (HIT), which is more common with UFH than with LMWH. UFH remains favored in certain clinical scenarios requiring rapid, controllable anticoagulation or full reversal, such as during certain cardiovascular procedures or when rapid dose adjustments are needed.

Production and context: UFH is derived from animal sources and represents a heterogeneous mixture, whereas LMWH products are processed to consist of shorter, more uniform chains.