Unfractionated HeparinEdit

Unfractionated heparin (UFH) is a traditional, widely used anticoagulant that has served as a workhorse in hospital medicine for decades. It is administered intravenously or subcutaneously and acts quickly to dampen the blood’s tendency to clot. UFH remains a foundational option in settings ranging from surgical prophylaxis to treatment of acute thromboembolism and certain cardiovascular emergencies, even as newer anticoagulants have entered clinical practice. Its long history and well-characterized profile give clinicians a familiar tool, even as its use sits amid ongoing debates about risk, monitoring, and cost in modern healthcare systems.

Mechanism of action UFH is a heterogenous mixture of sulfated polysaccharide chains that exerts its anticoagulant effect primarily by potentiating the activity of endogenous antithrombin antithrombin; this accelerates the inactivation of multiple clotting factors. The result is inhibition of thrombin (Factor IIa) and, to a lesser extent, Factor Xa, with a variable effect on other serine proteases in the coagulation cascade. The degree of inhibition and the spectrum of factors affected depend on the particular UFH preparation and the chain length of individual molecules. For a broader view of the coagulation system, see blood coagulation; for the key enzymatic players, see thrombin and Factor Xa.

Pharmacology and pharmacokinetics UFH is typically given by continuous IV infusion for therapeutic anticoagulation or by intermittent subcutaneous injections for prophylaxis. Its pharmacokinetics are complex and dose-dependent, with variable bioavailability and a distribution phase that reflects binding to plasma proteins, endothelial surfaces, and reticuloendothelial tissue. Unlike some synthetic anticoagulants, UFH does not have a single predictable half-life, which is why clinicians rely on laboratory tests to guide dosing during treatment. Monitoring commonly uses the activated partial thromboplastin time activated partial thrombocytin time or, in some settings, anti-Xa activity anti-Xa to gauge the anticoagulant effect. When rapid and titratable anticoagulation is required, IV infusion allows closer control than subcutaneous routes.

Medical uses - Prophylaxis of venous thromboembolism in surgical and high-risk medical patients, particularly when extended immobility is anticipated. The goal is to reduce postoperative DVT deep vein thrombosis without excessively increasing bleeding risk. - Treatment of acute venous thromboembolism, including DVT and pulmonary embolism pulmonary embolism, often in combination with other therapies or as a bridge to longer-term anticoagulation (for example, to transition to a vitamin K antagonist like warfarin or to a direct oral anticoagulant). - Anticoagulation in certain cardiovascular settings, including acute coronary syndromes and during percutaneous interventions, where rapid, controllable anticoagulation is advantageous. - Bridge therapy around procedures or when transitioning between anticoagulants, balancing immediate protection against thrombosis with the need to limit bleeding.

Dosing and administration - Prophylaxis: UFH is commonly given as a fixed dose by subcutaneous injection (for example, several thousand units two to three times daily, depending on protocol and patient factors) to deter clot formation in immobilized patients. - Treatment: In active thrombosis, a weight-based IV bolus followed by a continuous infusion is used to rapidly achieve therapeutic anticoagulation, with frequent laboratory monitoring guiding dose adjustments. - Practical note: The dose and monitoring strategy vary by institution, patient risk factors, renal function, and concurrent medications. Clinicians frequently adjust based on aPTT or anti-Xa results and clinical status.

Adverse effects and safety considerations - Bleeding: The most common and clinically significant risk is bleeding. The likelihood and severity depend on dose, duration, concurrent procedures, and comorbidities. - Heparin-induced thrombocytopenia (HIT): A prothrombotic immune-mediated reaction can occur with UFH exposure, sometimes despite a low platelet count. When HIT is suspected or confirmed, heparin must be stopped and alternative anticoagulation considered. See heparin-induced thrombocytopenia for more detail. - Osteoporosis: Long-term, high-dose UFH use has been associated with bone loss and osteoporosis, particularly in prolonged inpatient regimens. - Other effects: Injection site reactions, hypersensitivity, hyperkalemia, and elevated liver enzymes can occur in some patients.

Monitoring and reversal - Monitoring: Ongoing assessment of bleeding risk and laboratory tests (aPTT and/or anti-Xa) guides dosing during treatment. Anti-Xa measurements reflect the actual anticoagulant effect independent of patient-specific variables that influence aPTT. - Reversal: If bleeding occurs or surgery is required, UFH can be rapidly reversed with protamine sulfate, which neutralizes the anticoagulant activity of heparin to a large extent. - Special populations: In pregnancy, UFH is preferred over some other anticoagulants because it does not cross the placenta, but it still requires careful monitoring due to bleeding risk and other potential complications.

Contraindications and interactions - Absolute contraindications include active major bleeding, severe bleeding risk, or known hypersensitivity to heparin products. - Drug interactions: Concomitant antiplatelet therapy, nonsteroidal anti-inflammatory drugs, or other anticoagulants can increase bleeding risk, necessitating careful balancing of therapeutic goals.

Manufacture and sources - UFH is derived from animal tissues, historically from porcine intestinal mucosa and, to a lesser extent, bovine sources. The heterogeneity of UFH preparations reflects their complex mixture of polysaccharide chains, which underpins both its therapeutic versatility and its monitoring challenges.

History and context - UFH was developed in the mid-20th century and became a cornerstone of anticoagulation in both medical and surgical settings. Its long history provides a rich record of clinical experience, including lessons about monitoring, reversal, and patient selection that continue to inform current practice, even as newer anticoagulants have broadened the therapeutic landscape.

See also - anticoagulant - heparin-induced thrombocytopenia - low molecular weight heparin - protamine sulfate - activated partial thromboplastin time - anti-Xa activity - thrombin - Factor Xa - antithrombin - deep vein thrombosis - pulmonary embolism - warfarin