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Delayed-Onset Heparin-Induced Thrombocytopenia and Cerebral Thrombosis after a Single Administration of Unfractionated Heparin
N Engl J Med 2003; 348:1067-1069March 13, 2003
- Article
To the Editor:
Delayed-onset heparin-induced thrombocytopenia, a newly described syndrome of immune-mediated thrombocytopenia that begins several days after heparin therapy has been discontinued,1,2 is caused by IgG antibodies that are reactive against platelet factor 4–heparin complexes that activate platelets even in the absence of pharmacologic heparin.1 The minimal amount of heparin required to initiate this syndrome is unknown.
We describe a 44-year-old woman who received a single injection of unfractionated heparin (5000 units) before undergoing Roux-en-Y gastric bypass for obesity. Previous exposure to heparin was unlikely, since she did not have a history of thrombosis or hospitalizations (other than two hospitalizations for childbirth, which were without complications). The preoperative platelet count was 163,000 per cubic millimeter (Figure 1Figure 1
Delayed-Onset Heparin-Induced Thrombocytopenia (HIT) after Exposure to a Single Dose of Heparin.). Because of hematemesis and postoperative dilutional thrombocytopenia, no further heparin was given. No blood transfusions or heparin flushes were administered. The patient was discharged on the fourth postoperative day.Seven days after surgery, scintillations developed in the left lower visual field, with a persistent occipital headache, followed two days later by mild left-sided hemiparesis and hemisensory loss; a computed tomographic (CT) scan of the head was normal. The platelet count was 23,000 per cubic millimeter eight days after surgery. Left hemiplegia developed, and the left hemisensory deficit worsened. Repeated CT scans showed infarction in the right superior–parietal region (on day 11), with subsequent hemorrhagic conversion (on day 22). Cerebral venous thrombosis was suspected, on the basis of the prominent headache, the subacute progression of the disorder, and the ultimate hemorrhagic infarction (not confirmed by angiography).
Severe thrombocytopenia (nadir platelet count, 7000 per cubic millimeter) and disseminated intravascular coagulation were present, with no apparent cause other than heparin-induced thrombocytopenia. The nadir plasma fibrinogen level was 133 mg per deciliter (normal range, 200 to 425), with an elevated international normalized ratio (1.6; normal range, 1.0 to 1.2), and increased fibrin-degradation products. No anticoagulants were administered because of the severe thrombocytopenia. Venous thromboembolism also occurred (on day 23). The platelet count gradually rose to 152,000 per cubic millimeter (on day 60). An enzyme immunoassay (Asserachrom, Diagnostica Stago) that detects antibodies against platelet factor 4–heparin complexes was strongly positive (3.57 absorbance units; normal value, less than 0.50).
This case indicates that a single exposure to 5000 units of heparin can cause the onset of immune heparin-induced thrombocytopenia and disseminated intravascular coagulation about one week later. Disseminated intravascular coagulation may be more common in cases of heparin-induced thrombocytopenia with a delayed onset than in typical cases, perhaps because heparin is not present to inhibit antibody-induced hypercoagulability.1 Cerebral venous thrombosis has been described as a complication of heparin-induced thrombocytopenia.3,4 This patient's course suggests that anticoagulation therapy should be considered for progressive cerebrovascular thrombosis complicating immune heparin-induced thrombocytopenia, even when severe thrombocytopenia is present.5
5 ReferencesTheodore E. Warkentin, M.D.
McMaster University, Hamilton, ON L8L 2X2, CanadaRichard A. Bernstein, M.D., Ph.D.
Northwestern University, Chicago, IL 60611-30781
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