Heparin‐induced thrombocytopenia: a prospective study on the incidence, platelet‐activating capacity and clinical significance of antiplatelet factor 4/heparin antibodies of the IgG, IgM, and IgA classes

Greinacher, Andreas; Juhl, David; Strobel, Ulrike; Wessel, Antje; Lübenow, Norbert; Selleng, Kathleen; Eichler, Petra; Warkentin, Theodore E.

doi:10.1111/j.1538-7836.2007.02617.x

Cited by 216 publications

(220 citation statements)

References 35 publications

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“…These patients had a very low probability of HIT since clinical HIT is strongly associated with positive reactivity in the SRA [30]. In previous studies, up to 50% of EIA-positive samples were negative in the SRA [9,14,30]. In this study, 53.7% (169/315) of EIA-positive samples were SRA-negative in 2008 but the frequency of results showed an increasing trend during the 6 years of the study (Table I).…”

Section: Discussionmentioning

confidence: 41%

“…Platelet-rich plasma was prepared by differential centrifugation of whole blood collected into acid-citrate dextrose. Platelets were radiolabeled with 14 C-serotonin and then washed in calcium/albumin-free Tyrodes. Washed platelets were resuspended in albumin-free Tyrodes (75 lL/well; 450,000/ mL) and incubated with heat-inactivated patient serum or control serum (20 mL/ well).…”

Section: Methodsmentioning

confidence: 99%

“…Immunoassays such as the anti-platelet factor 4 (PF4)/heparin enzyme-immunoassay (EIA) are commonly used as a screening test for HIT because they have a high sensitivity (>99%) and are readily available. However, EIAs detect antibodies that might not be clinically significant and they cannot discriminate between pathogenic and nonpathogenic anti-PF4/heparin antibodies [2,7,14]. The reliance on immunoassays as the sole diagnostic test for HIT has increased even though they result in a high rate of false-positive results and over-calling the diagnosis of HIT [15].…”

Section: Introductionmentioning

confidence: 99%

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Pitfalls in the diagnosis of heparin‐Induced thrombocytopenia: A 6‐year experience from a reference laboratory

et al. 2015

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Heparin-induced thrombocytopenia (HIT) is caused by platelet-activating antibodies against complexes of platelet factor 4 (PF4) and heparin. The diagnosis of HIT is contingent on accurate and timely laboratory testing. Recently, alternative anticoagulants for the treatment of HIT have been introduced along with algorithms for better HIT diagnosis. However, the increased reliance on immunoassays for the diagnosis of HIT may have harmful consequences due to the high rate of false positive results. To compare trends and implications of current HIT testing approaches, we analyzed results over a six-year period from the McMaster University Platelet Immunology Reference Laboratory. From 2008 to 2013, 8,546 samples were investigated for HIT using both an in-house IgG-specific anti-PF4/heparin enzyme immunoassay (EIA) and the serotoninrelease assay (SRA). Of 8,546 samples tested, 13.4% were true-positives (positive in both assays); 65.6% were true-negatives (negative in both assays); 20.9% were presumed false positive for HIT (EIA-positive/SRAnegative); and 0.2% were EIA-negative/SRA-positive. The frequency of EIA-positive/SRA-negative results increased over time (from 12.9% in 2008 to 22.9% in 2013). We found that the number of SRA-negative samples was reduced from referring centers that used an immunoassay as an initial screen; however, 41% of those samples tested negative in the immunoassay and in the SRA at the reference laboratory. The suspicion of HIT continues at a high rate and the agreement between the EIA and SRA test results remains problematic.

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Section: Discussionmentioning

confidence: 41%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Pitfalls in the diagnosis of heparin‐Induced thrombocytopenia: A 6‐year experience from a reference laboratory

et al. 2015

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“…Antibodies (immunoglobulin G) are produced to the complex of platelet factor 4, a protein on the surface of activated platelets, and heparin and result in thrombocytopenia with extreme platelet activation 61,62 and resultant hypercoagulability. The diagnosis of HIT is made from a combination of clinical signs and laboratory confirmation of heparin-dependent platelet-activating antibodies or their inference from a positive test for platelet factor 4/heparin-reactive antibodies.…”

Section: Heparin-induced Thrombocytopeniamentioning

confidence: 99%

Prevention and Treatment of Thrombosis in Pediatric and Congenital Heart Disease

Giglia¹,

Massicotte²,

Tweddell³

et al. 2013

Circulation

268

244

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“…Its sensitivity is very high, upwards of 95%, so persistently negative tests argue strongly against the diagnosis of HIT. The specificity, however, is quite a bit lower (74-86% or higher, depending in part on the assay manufacturer), accounting for the high rate of false positives [18,24,25]. Interestingly, the rate of false positive results (defined as positive serology in the absence of thrombocytopenia and other clinical criteria for the diagnosis of HIT) varies depending on the patient population.…”

Section: Laboratory Detection Of Hit Antibodiesmentioning

confidence: 97%

Heparin‐induced thrombocytopenia: Current status and diagnostic challenges

Otis

Zehnder

2010

American J Hematol

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Heparin‐induced thrombocytopenia (HIT) is a fairly common and potentially catastrophic complication of heparin therapy. Diagnosing HIT remains a challenge, as the patients at risk often have other reasons for thrombocytopenia and/or thrombosis. HIT is considered a clinicopathologic disorder whose diagnosis is generally made on the basis of both clinical criteria and the presence of “HIT antibodies” in the patient's serum or plasma. There are two basic laboratory approaches to detect HIT antibodies. The immunoassays detect antibodies based on their binding properties, whereas the functional assays detect antibodies based on their platelet‐activating properties. Prompt and accurate diagnosis of HIT is imperative, as overdiagnosis exposes patients to alternative anticoagulants and their associated bleeding risks, whereas under‐ or delayed diagnosis leaves patients vulnerable to the thromboembolic sequelae of HIT, which can be life threatening. A critical interpretation of laboratory results by the clinician is an essential component of diagnosing HIT. This requires a keen understanding of the current concepts in the pathophysiologic mechanisms of the disease, and the application of these concepts when interpreting the results of both the functional and immunoassays. Equally important is an awareness of the strengths and weaknesses, as well as the current lack of standardization and proficiency testing, of these assays. Am. J. Hematol., 2010. © 2010 Wiley‐Liss, Inc.

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Heparin‐induced thrombocytopenia: a prospective study on the incidence, platelet‐activating capacity and clinical significance of antiplatelet factor 4/heparin antibodies of the IgG, IgM, and IgA classes

Cited by 216 publications

References 35 publications

Pitfalls in the diagnosis of heparin‐Induced thrombocytopenia: A 6‐year experience from a reference laboratory

Pitfalls in the diagnosis of heparin‐Induced thrombocytopenia: A 6‐year experience from a reference laboratory

Prevention and Treatment of Thrombosis in Pediatric and Congenital Heart Disease

Heparin‐induced thrombocytopenia: Current status and diagnostic challenges

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