Prevalence, isotype, and functionality of antiheparin–platelet factor 4 antibodies in patients treated with heparin and clinically suspected for heparin-induced thrombocytopenia

Untch, Brian R.; Ahmad, Sarfraz; Jeske, Walter; Messmore, Harry L.; Hoppensteadt, Debra; Walenga, Jeanine M.; Lietz, Helen; Fareed, Jawed

doi:10.1016/s0049-3848(02)00004-x

Cited by 45 publications

(39 citation statements)

References 19 publications

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“…1) and had negative serotonin release and platelet aggregation tests [17]. In one of the three studies, none of 50 subjects had a positive PF4/PVS ELISA or serotonin release assay, although in-house assays detected IgG antibody in two subjects and IgM antibody in 33 subjects [25].…”

Section: Antibody Prevalence and Characterization Of Positive Resultsmentioning

confidence: 94%

“…One article in our literature set reported that in 50 healthy subjects who were seronegative by both PF4/PVS ELISA and serotonin release assay, in-house, Ig class-specific immunoassays detected IgG PF4/heparin antibodies in two subjects and IgM antibodies in 33 [25]. The authors speculated that this reflected a possible humoral response in the donors to the PF4/heparin complex, prior to exogenous heparin exposure.…”

Section: Discussionmentioning

confidence: 99%

“…In three of these seven articles, the described assay ultimately served as basis of a commercial assay [12,13,19]. The literature set comprised the remaining 11 articles [10,16,17,[20][21][22][23][24][25][26][27], each of which reported the prevalence of PF4/heparin antibodies in healthy subjects, as assessed by a commercial immunoassay according to manufacturer's directions (Table 1). …”

Section: Literature Data Setmentioning

confidence: 99%

“…In the literature set (Table 1), the PF4/heparin ELISA was used in nine studies [10,16,17,[20][21][22][23][24]26], the PF4/PVS ELISA in three studies [17,24,25], and the PF4/heparin PGIA in three studies [17,24,27]. No study used the PIFA.…”

Section: Literature Data Setmentioning

confidence: 99%

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Platelet factor 4/heparin antibody (IgG/M/A) in healthy subjects: a literature analysis of commercial immunoassay results

Arepally

Hursting

2008

J Thromb Thrombolysis

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Purpose-We determined the seroprevalence of platelet factor 4 (PF4)/heparin antibodies in healthy subjects.Methods-A literature search identified studies in which healthy subjects were evaluated using commercial immunoassays for PF4/heparin antibody (IgG/M/A). Proportions of test-positive subjects were calculated, by assay.Results-Across 11 eligible studies, 860 healthy subjects were tested using the Stago enzymelinked immunosorbent assay (ELISA) (nine studies), GTI ELISA (three studies), and/or DiaMed particle gel immunoassay (PGIA) (three studies). Seropositivity occurred in 17 of 790 (2.2%, 95% CI, 1.1-3.2%) subjects by Stago ELISA, one of 100 (1.0%, 95% CI, 0-3.0%) subjects by GTI ELISA, and three of 70 (4.3%, 95% CI, 0-9.0%) subjects by PGIA (P > 0.20). Of seven seropositive subjects tested further, none had platelet-activating antibodies.Conclusion-Commercial immunoassays detect PF4/heparin antibody in 1.0-4.3% of healthy subjects. Because this "background" prevalence overlaps seropositivity rates in heparin-treated patients in various clinical settings, normality cut-offs may require refinement.

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Section: Antibody Prevalence and Characterization Of Positive Resultsmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Literature Data Setmentioning

confidence: 99%

Section: Literature Data Setmentioning

confidence: 99%

See 2 more Smart Citations

Platelet factor 4/heparin antibody (IgG/M/A) in healthy subjects: a literature analysis of commercial immunoassay results

Arepally

Hursting

2008

J Thromb Thrombolysis

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“…In a study published in 2002, the authors specifically looked at isotype breakdown of HIT antibodies in patients with suspected HIT compared with normal healthy controls. Their data was surprising in that 66% of normal human subjects (subjects not suspected of HIT with no history of heparin exposure, thrombocytopenia or thrombosis, and negative SRAs) had detectable IgM by GTI's EIA [41]. This finding remains to be confirmed, as few studies look at the incidence of HIT antibodies in normal healthy subjects, and even fewer look specifically at isotype breakdown.…”

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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Purpura and Microvascular Occlusion

Cox¹,

Piette²

2004

Rook's Textbook of Dermatology

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Prevalence, isotype, and functionality of antiheparin–platelet factor 4 antibodies in patients treated with heparin and clinically suspected for heparin-induced thrombocytopenia

Cited by 45 publications

References 19 publications

Platelet factor 4/heparin antibody (IgG/M/A) in healthy subjects: a literature analysis of commercial immunoassay results

Platelet factor 4/heparin antibody (IgG/M/A) in healthy subjects: a literature analysis of commercial immunoassay results

Heparin‐induced thrombocytopenia: Current status and diagnostic challenges

Purpura and Microvascular Occlusion

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