Heparin (Unfractionated Heparin)

Indications

Acute Coronary Syndrome (ACS) (see Coronary Artery Disease, [[Coronary Artery Disease]])
Atrial Fibrillation (AF) (see Atrial Fibrillation, [[Atrial Fibrillation]])

Venous Thromboembolism
- Deep Venous Thrombosis (DVT) Prophylaxis (see Deep Venous Thrombosis, [[Deep Venous Thrombosis]])
- Deep Venous Thrombosis (DVT) Treatment (see Deep Venous Thrombosis, [[Deep Venous Thrombosis]])
- Acute Pulmonary Embolism (PE) (see Acute Pulmonary Embolism, [[Acute Pulmonary Embolism]])

Heparin-Induced Thrombocytopenia (HIT) (see Heparin-Induced Thrombocytopenia, [[Heparin-Induced Thrombocytopenia]])

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)

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

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

Recommendations (Chest Antithrombotic Therapy and Prevention of Thrombosis 2012 Guidelines) [MEDLINE]
- Discontinue Heparin Drip 4-6 hrs Prior to Surgery/Procedure (Grade 2C Recommendation)

Epidemiology: rare
Clinical
- 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]])
Treatment: withdrawal of heparin