Clinical Picture of Heparin-Induced Thrombocytopenia

To assess the safety and efficacy of low-molecular-weight heparins (LMWHs) for thromboprophylaxis and treatment of venous thromboembolism (VTE) in pregnancy, a systematic review of studies to the end of 2003 was undertaken. Data on VTE recurrence and side effects were extracted and cumulative incidences of VTE and adverse effects calculated. Of 81 reports identified, 64 reporting 2777 pregnancies were included. In 15 studies (174 patients) the indication for LMWH was treatment of acute VTE, and in 61 studies (2603 pregnancies) it was thromboprophylaxis or adverse pregnancy outcome. There were no maternal deaths. VTE and arterial thrombosis (associated with anti-phospholipid syndrome) were reported in 0.86% (95% confidence interval [CI], 0.55%-1.28%) and 0.50% (95% CI, 0.28%-0.84%) of pregnancies, respectively. Significant bleeding, generally associated with primary obstetric causes, occurred in 1.98% (95% CI, 1.50%-2.57%), allergic skin reactions in 1.80% (95% CI, 1.34%-2.37%), heparin-induced thrombocytopenia in 0%, thrombocytopenia (unrelated to LMWH) in 0.11% (95% CI, 0.02%-0.32%), and osteoporotic fracture in 0.04% (95% CI, < 0.01%-0.20%) of pregnancies. Overall, live births were reported in 94.7% of pregnancies, including 85.4% in those receiving LMWH for recurrent pregnancy loss. LMWH is both safe and effective to prevent or treat VTE in pregnancy.

Heparin-induced thrombocytopenia is a relatively common antibody-mediated drug reaction. We studied the temporal relation between previous or current heparin therapy and the onset of heparin-induced thrombocytopenia. We examined the time between the start of heparin therapy and the onset of thrombocytopenia in 243 patients with serologically confirmed heparin-induced thrombocytopenia. We also investigated the persistence of circulating heparin-dependent antibodies by performing a platelet serotonin-release assay and an assay for antibodies against platelet factor 4. The outcome in seven patients who had previously had an episode of heparin-induced thrombocytopenia and were later treated again with heparin was also examined. A fall in the platelet count beginning four or more days after the start of heparin therapy occurred in 170 of the 243 patients (70 percent); in these patients, a history of previous heparin treatment did not influence the timing of the onset of thrombocytopenia. In the remaining 73 patients (30 percent), the onset of thrombocytopenia was rapid (median time of onset, 10.5 hours after the start of heparin administration); all these patients had been treated with heparin within the previous 100 days. During recovery from thrombocytopenia, heparin-dependent antibodies in the serum fell to undetectable levels at a median of 50 to 85 days, depending on the assay performed. In the seven patients who were given heparin again after the disappearance of heparin-dependent antibodies, a new episode of heparin-induced thrombocytopenia did not occur. Heparin-induced thrombocytopenia can begin rapidly in patients who have received heparin within the previous 100 days. Heparin-dependent antibodies do not invariably reappear with subsequent heparin use.

To determine the sites of thromboses (venous versus arterial circulation) that complicate the clinical course of immunemediated heparin-induced thrombocytopenia, and to determine the 30-day risk for thrombosis in patients who are initially recognized with isolated heparin-induced thrombocytopenia. We analyzed objectively documented thrombotic events that complicated the clinical course of 127 patients with serologically confirmed heparin-induced thrombocytopenia identified in one medical community over a 14-year period. We classified heparin-induced thrombocytopenia patients into two groups: patients recognized with heparin-induced thrombocytopenia only after a new thrombosis had occurred, and patients initially recognized with isolated heparin-induced thrombocytopenia. We determined the subsequent 30-day risk for thrombosis for the cohort of patients initially recognized with isolated thrombocytopenia. Heparin-induced thrombocytopenia was associated with the development of new venous thrombotic events and arterial thrombotic events in 78 and 18 patients, respectively (ratio venous/arterial thrombosis = 4:1). Pulmonary embolism was the most common life-threatening thrombotic event, occurring in 25% of all patients. Approximately half of all heparin-induced thrombocytopenia patients were recognized only after they had a complicating thrombotic event. Of the remaining 62-patient cohort initially recognized with isolated thrombocytopenia, the subsequent 30-day risk of thrombosis was 52.8%. The risk of thrombosis did not differ whether the heparin had been discontinued alone or whether warfarin had been substituted for the heparin. Venous thrombosis complicates heparin-induced thrombocytopenia more frequently than does arterial thrombosis. The high risk of thrombosis in patients initially recognized with isolated thrombocytopenia suggests that conventional management approaches require reappraisal.