The following points should be considered in all patients receiving heparin: Platelet counts should be performed frequently; thrombocytopenia appearing in a time frame consistent with an immune response to heparin should be considered suspicious for HIT; and any new thrombus occurring in a patient receiving heparin therapy should raise suspicion of HIT. Patients who develop HIT are treated by discontinuance of heparin and administration of the direct thrombin inhibitor argatroban.
Heparin is contraindicated in patients with HIT, hypersensitivity to the drug, active bleeding, hemophilia, significant thrombocytopenia, purpura, severe hypertension, intracranial hemorrhage, infective endocarditis, active tuberculosis, ulcerative lesions of the gastrointestinal tract, threatened abortion, visceral carcinoma, or advanced hepatic or renal disease. Heparin should be avoided in patients who have recently had surgery of the brain, spinal cord, or eye; and in patients who are undergoing lumbar puncture or regional anesthetic block. Despite the apparent lack of placental transfer, heparin should be used in pregnant women only when clearly indicated.
The indications for the use of heparin are described in the section on clinical pharmacology. A plasma concentration of heparin of 0.2–0.4 unit/mL (by protamine titration) or 0.3–0.7 unit/mL (anti-Xa units) is considered to be the therapeutic range for treatment of venous thromboembolic disease. This concentration generally corresponds to a PTT of 1.5–2.5 times baseline. However, the use of the PTT for heparin monitoring is problematic. There is no standardization scheme for the PTT as there is for the prothrombin time (PT) and its international normalized ratio (INR) in warfarin monitoring. The PTT in seconds for a given heparin concentration varies between different reagent/ instrument systems. Thus, if the PTT is used for monitoring, the laboratory should determine the clotting time that corresponds to the therapeutic range by protamine titration or anti-Xa activity, as listed above.
In addition, some patients have a prolonged baseline PTT due to factor deficiency or inhibitors (which could increase bleeding risk) or lupus anticoagulant (which is not associated with bleeding risk but may be associated with thrombosis risk). Using the PTT to assess heparin effect in such patients is problematic. An alternative is to use anti-Xa activity to assess heparin concentration, a test now widely available on automated coagulation instruments. This approach measures heparin concentration; however, it does not provide the global assessment of intrinsic pathway integrity of the PTT.
The following strategy is recommended: prior to initiating anticoagulant therapy of any type, the integrity of the patient’s hemostatic system should be assessed by a careful history of prior bleeding events, as well as baseline PT and PTT. If there is a prolonged clotting time, the cause of this (deficiency or inhibitor) should be determined prior to initiating therapy, and treatment goals stratified to a risk-benefit assessment. In high-risk patients measuring both the PTT and anti-Xa activity may be useful. When intermittent heparin administration is used, the aPTT or anti-Xa activity should be measured 6 hours after the administered dose to maintain prolongation of the aPTT to 2–2.5 times that of the control value. However, LMW heparin therapy is the preferred option in this case, as no monitoring is required in most patients.