Heparin

Unfractionated heparin is the anticoagulant you can shut off in an hour — and the one whose worst complication makes patients clot instead of bleed.

Unfractionated heparin (UFH) is an indirect anticoagulant: it binds antithrombin III (AT-III) and accelerates AT-III's inactivation of thrombin (factor IIa) and factor Xa roughly 1,000-fold. Without adequate AT-III, heparin cannot work. UFH prevents a clot from propagating — it does NOT dissolve an existing clot (that is thrombolysis, e.g. alteplase). Therapeutic UFH is given as a weight-based continuous IV infusion on a programmable pump (a high-alert medication), titrated to an aPTT of 1.5–2.5 times the control value, commonly about 46–70 seconds. The aPTT is drawn 6 hours after initiation and 6 hours after any rate change, because that is when steady state is reached. Low-dose subcutaneous UFH (5,000 units every 8–12 hours) is used for prophylaxis, and dilute heparin flushes maintain line patency. UFH's short half-life (~60–90 minutes IV) and complete reversibility with protamine sulfate (1 mg per 100 units of heparin) make it the choice whenever rapid on-off control is needed: cardiac bypass, an unstable patient who may go to surgery, or significant renal impairment, where LMWH accumulates. The most dangerous adverse effect is heparin-induced thrombocytopenia (HIT), a type II immune reaction in which antibodies against the heparin–platelet factor 4 complex activate platelets. It appears 5–10 days into exposure, drops the platelet count by 50% or more from baseline, and causes paradoxical thrombosis rather than bleeding. The nursing response is to stop ALL heparin — infusion, flushes, and heparin-coated lines — notify the provider, and anticipate a non-heparin anticoagulant such as argatroban or bivalirudin. Never transfuse platelets in HIT; they fuel the thrombosis. Baseline and serial platelet counts every 2–3 days are standard during heparin therapy.

Key Distinctions

Match the drug to its lab: aPTT monitors UFH, PT/INR monitors warfarin, and anti-Xa is the level used for LMWH — swapping these is a classic exam trap. Match the drug to its antidote: protamine sulfate reverses heparin, vitamin K reverses warfarin. Do not confuse anticoagulation with thrombolysis: heparin prevents clot extension, alteplase breaks clot down. And do not read HIT as a bleeding problem — the platelet count falls, but the patient clots, so the danger is a new DVT, PE, or limb ischemia, not hemorrhage. UFH differs from LMWH in every practical way: IV titratable versus fixed-dose subcutaneous, aPTT-monitored versus not routinely monitored, fully reversible versus partially reversible.

Clinical Pearl

Heparin is the bodyguard, not the assassin — it stops the clot from recruiting reinforcements while the body dissolves it. Monitor with aPTT (1.5–2.5× control), reverse with protamine, and remember the cruel twist of HIT: the platelets fall but the patient CLOTS.

Low-Molecular-Weight Heparin / Enoxaparin

Low-molecular-weight heparins (LMWHs) — enoxaparin is the prototype — are short heparin fragments that bind antithrombin III but, because the chains are too short to bridge to thrombin, inactivate factor Xa almost exclusively with little activity against thrombin (factor IIa). That selectivity is why the aPTT barely moves and is NOT used to monitor LMWH. Absorption after subcutaneous injection is near-complete and predictable, so LMWH is given in fixed or weight-based doses without routine laboratory monitoring: enoxaparin 40 mg subcutaneously daily for prophylaxis, or 1 mg/kg every 12 hours for treatment. When a level is genuinely needed — significant renal impairment, pregnancy, obesity, or very low body weight — an anti-Xa level is drawn, not an aPTT. Because LMWH is cleared renally it accumulates when creatinine clearance falls below 30 mL/min, and the dose must be reduced. Administration technique is heavily tested and counterintuitive: the prefilled syringe contains an air bubble that must NOT be expelled, because it clears the last of the dose into the tissue; inject into the abdomen at least 2 inches from the umbilicus, at a 90-degree angle into a pinched skinfold, without aspirating and without massaging afterward, alternating sides with each dose. Enoxaparin carries an FDA boxed warning for spinal or epidural hematoma in patients receiving neuraxial anesthesia or undergoing spinal puncture — new back pain, leg numbness or weakness, or bowel or bladder dysfunction is an emergency, not a routine complaint. Protamine sulfate only partially reverses LMWH (roughly 60% of anti-Xa activity). HIT is less common than with UFH but still occurs, and a history of HIT contraindicates LMWH because the antibodies cross-react. LMWH does not cross the placenta, making it the anticoagulant of choice in pregnancy, where warfarin is teratogenic.

Key Distinctions

The single most-missed point: do NOT expel the air bubble from an enoxaparin prefilled syringe — the opposite of every other subcutaneous injection you have been taught. Match the drug to its lab: LMWH is not aPTT-monitored (that is UFH); if a level is needed it is an anti-Xa, and INR belongs to warfarin. Protamine fully reverses UFH but only partially reverses LMWH, so LMWH is the wrong choice when anticoagulation may need to be undone quickly or when renal function is poor. Lower HIT risk is not zero risk, and a prior HIT diagnosis rules LMWH out entirely. Finally, the boxed warning is about neuraxial procedures, not about bleeding in general — the assessment it demands is neurologic (back pain, leg weakness), not just a look at the injection site.

Clinical Pearl

Enoxaparin is heparin with the guesswork removed: fixed dose, no aPTT, and the patient can give it at home. Two things still bite — leave the air bubble IN the syringe, and treat new back pain or leg weakness after an epidural as a spinal hematoma until proven otherwise.