Five hematologic tests and treatments to question

Hicks, Lisa K.; Bering, Harriet; Carson, Kenneth R.; Haynes, Adam E.; Kleinerman, Judith; Kukreti, Vishal; Ma, Alice; Mueller, Brigitta U.; O’Brien, Sarah H.; Panepinto, Julie A.; Pasquini, Marcelo C.; Rajasekhar, Anita; Sarode, Ravindra; Wood, William A.

doi:10.1182/blood-2014-09-599399

Cited by 53 publications

(54 citation statements)

References 37 publications

(24 reference statements)

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“…Overdiagnosis and underdiagnosis of HIT have important medical and economic consequences. [24][25][26][27] Unfortunately, "gold standard" functional assays such as the SRA are not available in a timely manner in many medical centers. Therefore, an alternative assay that is rapidly and easily performed would be of significant utility.…”

Section: Discussionmentioning

confidence: 99%

The Clinical Utility of the Heparin Neutralization Assay in the Diagnosis of Heparin-Induced Thrombocytopenia

Zheng

Streiff

Takemoto

et al. 2017

Clin Appl Thromb Hemost

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Heparin-induced thrombocytopenia (HIT) remains diagnostically challenging. Immunoassays including PF4/heparin enzyme-linked immunosorbent assay (ELISA) have high sensitivity but low specificity. Whether the heparin neutralization assay (HNA) improves the diagnostic accuracy of the PF4/heparin ELISA for HIT is uncertain. In this study, to assess its clinical utility and evaluate whether it improves the diagnostic accuracy for HIT, we implemented HNA in conjunction with PF4/heparin ELISA over a 1-year period. A total of 1194 patient samples were submitted to the laboratory for testing from December 2015 to November 2016. Heparin neutralization assay alone is a poor predictor for HIT, but it has high negative predictive value (NPV): Cases with %inhibition <70% are always negative for serotonin release assay. It improves the diagnostic positive predictive value (PPV) of ELISA without compromising sensitivity: ELISA optical density (OD) !1.4 alone has a sensitivity of 88% (14/16) and a PPV of 61% (14/23); with HNA %inhibition !70%, the sensitivity remains 88% (14/16) and PPV is 82% (14/17). 4Ts score correlates with ELISA OD and predicts HIT; the predictive accuracy of 4Ts score is further improved by HNA. Interestingly, HNA %inhibition of <70% correlates with low 4Ts scores. Based on its high NPV, HNA has the potential to facilitate more timely and accurate HIT diagnosis.

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Section: Discussionmentioning

confidence: 99%

The Clinical Utility of the Heparin Neutralization Assay in the Diagnosis of Heparin-Induced Thrombocytopenia

Zheng

Streiff

Takemoto

et al. 2017

Clin Appl Thromb Hemost

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“…These include: (1) increase in the number of commercially available immunoassays for HIT testing with variable performance characteristics, (2) testing algorithms that rely on screening with immunoassays, (3) increase of HIT testing in low-risk patients, and (4) over-reliance on EIA results (especially strong EIApositive results) without confirmatory SRA testing. In its 2014 "Choosing Wisely" initiative, the American Society of Hematology recommended the limited use of testing in suspected HIT patients with low pretest probability of HIT [31] because of the high rate of false-positive HIT test results when using immunoassays.…”

Section: Discussionmentioning

confidence: 99%

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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“…Our study suggests a note of caution regarding application of the Choose Wisely recommendation 19 that advises against HIT testing in patients with a low pretest probability of HIT. We found that patients with a low 4Ts score had a frequency of HIT of 1.9%, but that frequency rose to 15% if the PF4/H-PaGIA result was positive.…”

Section: Discussionmentioning

confidence: 99%

Combination of 4Ts score and PF4/H-PaGIA for diagnosis and management of heparin-induced thrombocytopenia: prospective cohort study

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Lee

et al. 2015

Blood

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Key Points• A negative PaGIA test in a patient with low/intermediate 4Ts score excludes HIT with a high level of confidence.• A low 4Ts score was insufficient to exclude HIT in some cases because the posttest probability of HIT with a positive PaGIA was moderate.Rapid exclusion of heparin-induced thrombocytopenia (HIT) is needed to determine which patients can continue to receive heparin. In this prospective management study, 526 participants had a 4Ts score, rapid particle gel immunoassay (platelet factor 4/heparin [PF4/H]-PaGIA), and serotonin-release assay (SRA) performed. While awaiting SRA results, participants with a low 4Ts score (irrespective of PF4/H-PaGIA result) or intermediate 4Ts score plus a negative PF4/H-PaGIA result received prophylactic doses of danaparoid or fondaparinux; all others received therapeutic doses of nonheparin anticoagulants. The primary outcome was the frequency of management failures defined as HIT-positive participants with a low 4Ts score (irrespective of PF4/H-PaGIA result) or intermediate 4Ts score plus negative PF4/H-PaGIA result. Six participants (1.1%; 95% confidence interval [CI], 0.2-2.1%) were management failures. A negative PF4/H-PaGIA result reduced the pretest probability of HIT from 1.9% to 0% (95% CI, 0-1.3%), 6.7% to 0% (95% CI, 0-2.7%), and 36.6% to 0% (95% CI, 0-14.3%) in the low, intermediate, and high score groups, respectively. A positive PF4/H-PaGIA result increased the probability of HIT in the low score group to 15.4% (95% CI, 5.9-30.5). Thus, a low or intermediate 4Ts score plus negative PaGIA result excluded HIT, whereas any other combination of results justified the use of alternative anticoagulants until HIT could be excluded. This trial was registered at www.clinicaltrials.gov as #NCT00489437. (Blood. 2015;126(5):597-603)

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Five hematologic tests and treatments to question

Cited by 53 publications

References 37 publications

The Clinical Utility of the Heparin Neutralization Assay in the Diagnosis of Heparin-Induced Thrombocytopenia

The Clinical Utility of the Heparin Neutralization Assay in the Diagnosis of Heparin-Induced Thrombocytopenia

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

Combination of 4Ts score and PF4/H-PaGIA for diagnosis and management of heparin-induced thrombocytopenia: prospective cohort study

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