Binds to Antithrombin (aka Antithrombin III or Heparin Cofactor I): heparin binding result in a conformational change in antithrombin, converting antithrombin from slow to rapid inactivator of thrombin, factor Xa, and to a lesser extent factor XIIa, factor XIa, and factor IXa
Inactivation of thrombin (but not factor Xa) requires the formation of a complex in which heparin binds to both antithrombin and a binding site on thrombin: this requires pentasaccharide-containing chains of at least 18 saccharide units long (which are present on unfractionated heparin, less commonly in low molecular weight heparins, and not at all in fondaparinux)
Consequently, low molecular weight heparins and fondaparinux have less antithrombin activity than unfractionated heparin
Heparin also directly binds to platelets
At high concentrations, heparin binds to heparin cofactor II
Placental Crossing: heparin does not cross the placenta (making it safer to use in pregnancy than coumadin)
Administration
SQ
DVT Prophylaxis: 5000 U BID-q8hrs
Full-Dose Anticoagulation: xxx
IV
Full-Dose Anticoagulation: xxx bolus, then xxx drip
Monitor PTT to Achieve Adequate Anticoagulation: aim for PTT equal to 1.5-2x control PTT (or 1.5-2x upper limit of normal PTT for the specific laboratory): generally, target PTT is 60-80
Relationship to Heparin Blood Level: this target PTT corresponds to a heparin blood level of at least 0.2 U/mL (as assessed by protamine titration assay)
PTT Monitoring: check PTT 4-6 hrs after initiation of heparin drip and/or a change in heparin drip rate
Utility of PTT Monitoring in Setting of Elevated Baseline PTT: in presence of baseline elevated PTT, monitoring the PTT for heparin dosing is unreliable -> the following options may be considered:
Option #1: If PTT is elevated due to unclear etiology, use unfractionated heparin -> monitor with anti-factor Xa assay or specific heparin assay
Option #2: If PTT is elevated due to lupus anticoagulant, use unfractionated heparin -> laboratory can use an alternate PTT assay which is not affected by the presence of the lupus anticoagulant
Option #3: Use low molecular weight heparin
If therapeutic effect is uncertain (due to conditions such as renal failure, obesity, or pregnancy), low molecular weight-specific anti-factor Xa assays are available for monitoring
Note: anti-factor Xa levels are different for low molecular weight heparins than they are for unfractionated heparin
Effect on Anticoagulation Tests
PT/INR: no effect
Heparin is an indirect thrombin inhibitor and should theoretically prolong the INR: however, most INR assay reagents contain heparin-binders which block the effect of heparin (or similar agents) at concentrations <1 unit/mL -> therefore, at heparin concentration of >1 unit/mL, the INR may be prolonged
PTT: prolonged
Anti-Factor Xa: prolonged
Management of Heparin Infusion Therapy Prior to Surgery/Procedures
Recommendations (Chest Antithrombotic Therapy and Prevention of Thrombosis 2012 Guidelines) [MEDLINE]
May appear similar to the lesions of coumadin skin necrosis
Occurrence at heparin injection sites should raise the suspicion of heparin-induced thrombocytopenia (HIT) (see Heparin-Induced Thrombocytopenia, [[Heparin-Induced Thrombocytopenia]])
