How does heparin work?

Heparin is a highly sulfated, natural glycosaminoglycan. Commercial preparations are derived from porcine intestine or bovine lung. Its anticoagulant affect is mediated through antithrombin

III, which has a native ability to inhibit thrombin, activated Factor X (Xa), and activated Factor IX (IXa). Once heparin binds to antithrombin III, this inhibition is increased up to 1000 times. Anticoagulation is almost instantaneous.

Before starting therapy with heparin, what baseline tests should you obtain?

Hematocrit, platelet count, activated partial thromboplastin time (aPTT), and prothrombin time (PTâ”with INR). The aPTT serves as a baseline value to gauge the therapeutic dose of heparin; the PT/INR is the baseline for anticipated warfarin therapy. The hematocrit and platelet count provide pretreatment values if complications arise.

How do you achieve and monitor the therapeutic level of heparin?

Heparin therapy is very empirical, and there are many patterns for initiating and monitoring it. Most clinicians give an intravenous bolus of 5000 U (or 80 U/kg), then start a continuous infusion of 1000 U/hr (or 18 U/kg/hr). The aPTT is checked at 4â”6 hours. If it is not within the goal of 1.5-2.5 times baseline, the rate is adjusted up or down (100-200 U/hr). Minimally prolonged aPTT may require a re-bolus of 5000 U. If the aPTT is markedly prolonged, the infusion is held for 1 hour and then a reduced rate resumed. The aPTT is rechecked at 4â”6 hours.

The body-weight dosing schedule reaches the therapeutic threshold (aPTT 1.5 times control) in more cases (90 % vs. 77%) than the standard dosing schedule. In life-threatening situations, achieving a therapeutic level promptly is very important. With interpatient variability, the clinician must be alert and not assume that the dose selected is correct without laboratory confirmation. Once an adequate rate is achieved, the aPTT should be checked each day.

Brill-Edwards et al. have pointed out a considerable variation among aPTT reagents. A therapeutic range using protamine titrated heparin levels of 0.2-0.4 U/ml would be more accurate than relying on prolongation of aPTT vs control.

Subcutaneous heparin, used prophylactically is started at 5000 U every 8-12 hours. It is not monitored because therapeutic goals are achieved at levels that may not prolong the aPTT.

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