IgG classification of anti-PF4/heparin antibodies to identify patients with heparin-induced thrombocytopenia during mechanical circulatory support.
ABSTRACT Commercial immunoassays frequently detect anti-PF4/heparin antibodies during mechanical circulatory support (MCS), but only a small minority of patients develops heparin-induced thrombocytopenia (HIT). Whereas platelet functional tests can distinguish between platelet-activating and non-platelet-activating antibodies, commercial PF4-dependent immunoassays do not. Between 2003 and 2004, 113 patients were placed on MCS. Blood samples were obtained on postimplant day 5-7 for analyses by antibody assays and the functional heparin-induced platelet activation (HIPA) assay. Three distinct groups of patient sera were identified: platelet-activating anti-PF4/heparin antibodies (n = 10), non-platelet-activating anti-PF4/heparin antibodies (n = 53), and anti-PF4/heparin antibody negative (n = 50). Patients with platelet-activating antibodies had the highest risk for thromboembolic events (P < 0.005), whereas those with non-platelet-activating antibodies did not differ from antibody negative patients (P = 0.369). The enzyme-immunoassay and column agglutination assays, which cover all immunoglobulin classes, demonstrated adequate sensitivity and negative predictive value; yet, both lacked specificity with respect to the platelet-activating antibodies. If all antibody positive patients were further classified by an IgG-specific anti-PF4/heparin enzyme-immuno assay, specificity for platelet-activating antibodies increased. Whereas IgG-specific optical density (OD) values below 1.0 were likely for non-platelet-activating anti-PF4/heparin antibodies, higher values were progressively predictive for pathogenic platelet activation. The probability of the development of clinical HIT also increased steeply. In conclusion, platelet-activating anti-PF4/heparin antibodies are relatively common (about 9%) in patients on MCS and are associated with significantly higher thrombotic event rates. Low IgG-specific OD values (< 1.0) in the enzyme-immunoassay indicate low likelihood for the presence of platelet-activating antibodies. These results justify further validation so that anticoagulation during MCS becomes safer and adequate.
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ABSTRACT: Patients receiving mechanical circulatory support are at risk for the development of heparin-induced thrombocytopenia due to the prolonged postoperative use of heparin. We evaluated their antibody status and outcome. Between 2003 and 2004, 115 patients received mechanical circulatory support for more than 5 days. Blood samples from postoperative day 7 were retrospectively analyzed for anti-platelet factor 4/heparin antibodies and heparin-induced platelet activation. Overall, 12 (10.6%) patients had heparin-induced thrombocytopenia as defined by in vitro platelet activation, 28 (24.8%) had nonactivating antibodies, and 73 (64.6%) were classified as negative for antibodies. Patients positive for heparin-induced thrombocytopenia had the highest levels of anti-platelet factor 4/heparin immunoglobulin G antibodies. Freedom from thromboembolism was 33%, 33%, and 16% at 1, 3, and 6 months for positive patients, 77%, 68%, and 55% for negative patients (P < .001), and 70%, 53%, and 53% for patients with nonactivating antibodies (P = .068), respectively. The relative risk for thromboembolism in antibody positive patients peaked in the first month of support (odds ratio 7.46, P = .002). Independent risk factors for thromboembolic events included higher anti-platelet factor 4/heparin antibody titers, female gender, and higher fibrinogen levels. Heparin-induced thrombocytopenia was more prevalent in patients receiving mechanical circulatory support than in other cardiac patients. Frequent antibody screening is recommended due to the increased risk of thromboembolism. Heparin alternatives should be subjected to clinical trials in these high-risk patients.The Journal of thoracic and cardiovascular surgery 06/2006; 131(6):1373-81.e4. · 3.41 Impact Factor
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ABSTRACT: Heparin-associated thrombocytopenia (HAT) is a severe complication of heparin therapy. Its diagnosis is difficult. Conventional assays employ platelet aggregometry (PAA) and/or 14C-serotonin release (SRA) which are either insensitive (PAA) or require radioactive tracers (SRA). We here describe a newly developed sensitive and rapid assay based on visual evaluation of heparin-induced platelet activation (HIPA) in microtiter wells. Using sera of 34 patients with clinically suspected HAT we found the HIPA assay to be as sensitive as the SRA and superior to PAA. The HIPA assay allows investigation of crossreactivity with different types of heparins, low molecular weight (LMW) heparins and heparinoids. Three patients who required further parenteral anticoagulation and in whom the HIPA assay was negative before treatment with the LMW heparinoid Org 10172, were treated with this new heparinoid without adverse reactions. We conclude that the HIPA assay may be a useful tool for differential diagnosis and therapy in patients with HAT.Thrombosis and Haemostasis 01/1992; 66(6):734-6. · 6.09 Impact Factor
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ABSTRACT: Thromboembolism is a major complication in patients with ventricular assist devices (VAD). Anticoagulation with heparin, coumarin, and anti-platelet agents, particularly the development of biocompatible surfaces such as inner pseudo-endothelial layers or a coating with heparin, are intended to reduce these complications. However, the administration of heparin can lead to heparin induced thrombocytopenia type II (HIT II). Predominantly heparin/platelet factor 4 (HPF4) antibodies are responsible for the development of HIT II. The goal of the present investigation was to assess the prevalence of these antibodies in patients with heparin coated and noncoated VADs. Fifty-five patients were enrolled in the investigation. A heparin coated system was implanted in 30 patients, and a noncoated system was implanted in 25 patients. Antibodies were evaluated before, on days 7 and 14, and 3 months after implantation. Testing was performed with the Heparin/Platelet factor 4 enzyme-linked immunosorbent assay (ELISA) (Stago, France). In 40 of the 55 patients, the formation of HPF4 antibodies was observed (73%). In 35 of these patients (88%), HPF4 antibodies were present before surgery. There were no differences between the groups. In 11 patients (equal from both groups), the antibodies disappeared after termination of systemic heparinization. We conclude that in a rather high percentage of patients with VADs HPF4 antibodies are found. This finding may be explained by the repetitive and prolonged exposure of these patients to heparin. Immobilized heparin, as presently used in the carmeda coating, seems not to influence the formation and persistence of HPF4 antibodies. Further studies will have to prove whether HPF4 antibodies contribute to thromboembolic complications in these patients.ASAIO Journal 04/2000; 46(3):319-22. · 1.49 Impact Factor