Heparin‐induced Thrombocytopenia: Effect of Heparin Platelet Antibody on Platelets

Chong, Beng H.; Grace, C. S.; Rozenberg, M. C.

doi:10.1111/j.1365-2141.1981.tb07261.x

Cited by 136 publications

(65 citation statements)

References 24 publications

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“…The HIT antibody screening was carried out by two laboratory tests: the assessment of EIA and by a functional assay the HIPAG test (modified by us) which comprises the assessment of PAT described by Chong in 1981 and 1993 [24,25]. The results of EIA were expressed quantitatively in graded OD ranges, taking into account that the strength of a positive EIA test result correlates strongly with the presence of plateletactivating antibodies and that approximately 5-15% of HIT-positive samples yield a weak positive result, that is OD of 0.900-1.100 in the EIA [28].…”

Section: Resultsmentioning

confidence: 99%

“…The detection of HIT antibodies was carried out with EIA followed by the detection of their reactivity using the HIPAG test with the application of a two-point definition for a positive assay according to Chong [24,25], and by adding a third point, namely 2.5 U/mL of heparin (HIPAG) to increase the sensitivity of the test. This concentration possibly correlates with one of the lower concentrations of heparin used during CPB [35].…”

Section: Discussionmentioning

confidence: 99%

“…HIT was also assessed by a functional test for the detection of HIT-reactive antibodies. The test was carried out through monitoring donor's platelet activation by antibodies to PF4-heparin in patient's plasma and stimulated by heparin according to the method described by Chong [24,25] but modified slightly by us adding a third point (heparin, 2.5 IU/mL) instead of two (HIPAG) to increase the sensitivity of the test. The assessment was carried out on a standard platelet aggregometer.…”

Section: Methodsmentioning

confidence: 99%

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Perioperative use of iloprost in cardiac surgery patients diagnosed with heparin‐induced thrombocytopenia‐reactive antibodies or with true HIT (HIT‐reactive antibodies plus thrombocytopenia): An 11‐year experience

et al. 2015

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*Thrombocytopenia and thromboembolism(s) may develop in heparin immune-mediated thrombocytopenia (HIT) patients after reexposure to heparin. At the Onassis Cardiac Surgery Center, 530 out of 17,000 patients requiring heart surgery over an 11-year period underwent preoperative HIT assessment by ELISA and a threepoint heparin-induced platelet aggregation assay (HIPAG). The screening identified 110 patients with HITreactive antibodies, out of which 46 were also thrombocytopenic (true HIT). Cardiac surgery was performed in HIT-positive patients under heparin anticoagulation and iloprost infusion. A control group of 118 HITnegative patients received heparin but no iloprost during surgery. For the first 20 patients, the dose of iloprost diminishing the HIPAG test to 5% was determined prior to surgery by in vitro titration using the patients' own plasma and donor platelets. In parallel, the iloprost "target dose" was also established for each patient intraoperatively, but before heparin administration. Iloprost was infused initially at 3 ng/kg/mL and further adjusted intraoperatively, until ex vivo aggregation reached 5%. As a close correlation was observed between the "target dose" identified before surgery and that established intraoperatively, the remaining 90 patients were administered iloprost starting at the presurgery identified "target dose." This process significantly reduced the number of intraoperative HIPAG reassessments needed to determine the iloprost target dose, and reduced surgical time, while maintaining similar primary clinical outcomes to controls. Therefore, infusion of iloprost throughout surgery, under continuous titration, allows cardiac surgery to be undertaken safely using heparin, while avoiding life-threatening iloprost-induced hypotension in patients diagnosed with HIT-reactive antibodies or true HIT.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Perioperative use of iloprost in cardiac surgery patients diagnosed with heparin‐induced thrombocytopenia‐reactive antibodies or with true HIT (HIT‐reactive antibodies plus thrombocytopenia): An 11‐year experience

et al. 2015

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“…HIT antibodies cause platelets to release ADP [7], and ADP enhances FcgIIa receptor-dependent platelet activation by IgG antibodies such as certain platelet-activating monoclonal antibodies [8]. Polga´r et al [9] found that pretreatment of platelets with the ADP receptor antagonist AR-C66096 blocked FcgIIa receptor-dependent platelet activation by HIT antibodies.…”

Section: Introductionmentioning

confidence: 99%

Immune heparin-induced thrombocytopenia can occur in patients receiving clopidogrel and aspirin

Selleng¹,

Selleng²,

Raschke³

et al. 2005

Am. J. Hematol.

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Platelet adenosine diphosphate (ADP) receptors may play a role in potentiating platelet activation induced by IgG from patients with immune heparin-induced thrombocytopenia (HIT), as shown by previous studies using the ADP receptor antagonists AR-C66096 and ticlopidine. Consistent with these observations, we found that platelet activation by HIT sera is also significantly reduced in patients receiving clopidogrel, an ADP receptor antagonist prodrug now in wide clinical use. Despite these in vitro and ex vivo findings, we observed two patients develop acute HIT while receiving both clopidogrel and aspirin: both patients' sera tested strongly positive in a heparin-dependent washed platelet activation assay (100% serotonin release) and PF4/heparin-enzyme-immunoassay (2.594 and 2.190 absorbance units). Both patients also developed HIT-associated clinical sequelae (acute systemic reaction postintravenous heparin bolus; thrombotic stroke) in association with their episode of HIT. We conclude that combined therapy with aspirin and clopidogrel does not necessarily protect against clinical HIT, at least in patients with HIT antibodies that have strong platelet-activating characteristics. Am.

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“…A common feature of these reports was evidence of platelet activation induced by patient serum, plasma, or purified immunoglobulin. [11][12][13][14][15][16][17] HIT: an immune disorder or a consumptive coagulopathy?Doubts persisted regarding the immune basis of HIT. After all, Rhodes and colleagues had also noted that when their patients were deliberately rechallenged with heparin several months after their episode of HIT, thrombocytopenia failed to recur.…”

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confidence: 99%

Heparin-induced thrombocytopenia: a historical perspective

Kelton

Warkentin

2008

Blood

169

113

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Heparin was discovered 90 years ago, 1 and within 2 decades it was being widely used as an anticoagulant. 2 The numerous advantages of heparin lend to its broad use including its immediate onset of action, relatively short half-life (ϳ60 minutes), simple laboratory monitoring (aPTT), ability to be reversed (using protamine), and low cost. Despite a long experience of using heparin, the counterintuitive notion that an anticoagulant could be intensely prothrombotic took almost 4 decades to become recognized.Our understanding of heparin-induced thrombocytopenia (HIT) has increased considerably and to a large measure exemplifies the best of translational research. Sometimes, basic studies investigating the pathophysiology of HIT lead to clinical insights. In other instances, clinical observations prompted basic studies. Together, these basic and applied investigations have dramatically enhanced our understanding of the pathogenesis and treatment of HIT. Heparin-induced arterial embolismOn June 1, 1957, at the Fifth Scientific Meeting of the International Society of Angiology in New York, Rodger E. Weismann, an Assistant Professor of Clinical Surgery at the Dartmouth Medical School, and his Resident in Surgery, Dr Richard W. Tobin, described 10 patients who developed arterial embolism during systemic heparin therapy. 3 The first reported embolic event was a femoral artery embolic occlusion, which occurred in a 62-year-old woman who was receiving heparin because of a deep-vein thrombosis (DVT). Three days after successful femoral embolectomy, and while continuing to receive heparin, she developed sudden occlusion of the distal aorta requiring distal aortic and bilateral iliac embolectomies. 3 Multiple thromboemboli were observed in 9 of the 10 patients reported. Six patients died as a result of the thromboembolism, and 2 survivors underwent above-knee amputation. 3 The clots were described as "pale, soft, salmon-colored" and were composed mostly of fibrin, platelets, and leukocytes. The arterial emboli began on average 10 days after commencing heparin treatment.An additional 11 patients were described 5 years later by Roberts and colleagues. 4 These vascular surgeons noted the paradox of "unexplained arterial embolization [occurring] for the first time while being treated with heparin for some condition that could not of itself reasonably be expected to cause arterial emboli. All patients had been receiving heparin for 10 days or more when the initial embolus occurred." Thus, both groups 3,4 noted the temporal hallmark of HIT, a delay of approximately 1 week from initiation of heparin to onset of its thrombotic manifestations. Heparin-induced thrombocytopeniaRoutine platelet count measurements were not routinely performed until the 1970s. This may explain why thrombocytopenia was not reported in the first 24 patients with heparin-induced arterial emboli. [3][4][5][6] In 1969, the term "heparin-induced thrombocytopenia" was used by Natelson 7 to describe a 78-year-old man with pulmonary embolism who developed severe t...

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Heparin‐induced Thrombocytopenia: Effect of Heparin Platelet Antibody on Platelets

Cited by 136 publications

References 24 publications

Perioperative use of iloprost in cardiac surgery patients diagnosed with heparin‐induced thrombocytopenia‐reactive antibodies or with true HIT (HIT‐reactive antibodies plus thrombocytopenia): An 11‐year experience

Perioperative use of iloprost in cardiac surgery patients diagnosed with heparin‐induced thrombocytopenia‐reactive antibodies or with true HIT (HIT‐reactive antibodies plus thrombocytopenia): An 11‐year experience

Immune heparin-induced thrombocytopenia can occur in patients receiving clopidogrel and aspirin

Heparin-induced thrombocytopenia: a historical perspective

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