dalteparin

**Class/Mechanism:** LMWH (about 5 kDa average), made by controlled nitrous acid depolymerization of porcine intestinal heparin. It binds antithrombin III (ATIII) and causes a conformational change that accelerates inactivation of factor Xa. The chains are too short to bridge ATIII and thrombin (IIa), so anti-Xa activity far exceeds anti-IIa activity. UFH has a 1:1 anti-Xa:anti-IIa ratio, and dalteparin's ratio is about 2.7:1. Aggregate effect: decreased thrombin generation and decreased fibrin formation.

**Pharmacokinetics:** - Given subcutaneously. Bioavailability is about 90%, and half-life is about 3–5 hr. - Dose-response is predictable, so there is no routine aPTT monitoring. If monitoring is needed, use an anti-Xa level (pregnancy, obesity, renal impairment). aPTT is not a reliable measure. - Cleared mostly by the kidneys, so it accumulates in renal failure (CrCl <30 mL/min). Use UFH or a dose-adjusted regimen instead. UFH is cleared by the reticuloendothelial system and by the kidney.

**Indications:** - DVT prophylaxis in medical patients with restricted mobility, abdominal surgery, and hip replacement surgery. - Treatment of acute DVT/PE as a bridge to warfarin. - Unstable angina/NSTEMI (ACS) to prevent ischemic complications. - Extended treatment of symptomatic cancer-associated VTE. This is a classic board point: LMWH is preferred over warfarin in malignancy, though DOACs are increasingly used. - Pediatric VTE (FDA-approved).

**Adverse effects:** - Bleeding is the main risk. - Heparin-induced thrombocytopenia (HIT) is less common than with UFH, but cross-reactivity exists. Stop it if HIT is suspected. - Osteoporosis with long-term use (less than with UFH). - Hyperkalemia (suppresses aldosterone). - **Epidural/spinal hematoma** with neuraxial anesthesia or lumbar puncture (boxed warning). Delay neuraxial procedures by ≥12 hr after a prophylactic dose and ≥24 hr after a treatment dose.

**Reversal:** Protamine sulfate partially reverses it, neutralizing anti-IIa activity but only about 60% of anti-Xa activity. Andexanet alfa is not formally indicated for LMWH.

**Comparison with UFH and other agents:** - LMWH vs UFH: LMWH has better bioavailability, a longer half-life, less HIT, no routine monitoring, and renal clearance. UFH is preferred in renal failure, when rapid reversibility is needed (surgery, unstable patients), and in pregnancy-adjacent settings that need titration. Both LMWH and UFH are safe in pregnancy because they don't cross the placenta. Warfarin is teratogenic. - Other LMWHs: enoxaparin (most commonly tested, with the highest anti-Xa:anti-IIa ratio of about 3.8:1) and tinzaparin. - Fondaparinux is a synthetic pentasaccharide with pure anti-Xa activity. It is renally cleared and has virtually no HIT risk. - Contraindications: active major bleeding, history of HIT, and hypersensitivity to pork products (porcine-derived).

**Pearls:** - The drug name suffix "-parin" signals heparin derivatives. - Heparin-induced thrombocytopenia (type II) presents 5–10 days after exposure with a ≥50% platelet drop and paradoxical thrombosis (anti-PF4/heparin IgG antibodies). Treat by stopping heparin and giving a direct thrombin inhibitor (argatroban, bivalirudin) or fondaparinux. - Monitoring: UFH is monitored by aPTT, warfarin by PT/INR, and LMWH by anti-Xa (only if needed).