Overdiagnosis Of Heparin-induced Thrombocytopenia Research Articles

Clinical decision support to reduce unnecessary diagnostic testing for heparin-induced thrombocytopaenia.

Appropriate evaluation of heparin-induced thrombocytopaenia (HIT) is imperative because of the potentially life-threatening complications. However, overtesting and overdiagnosis of HIT are common. Our goal was to evaluate the impact of clinical decision support (CDS) based on the HIT computerized-risk (HIT-CR) score, designed to reduce unnecessary diagnostic testing. This retrospective observational study evaluated CDS that presented a platelet count versus time graph and 4Ts score calculator to clinicians who initiated a HIT immunoassay order in patients with predicted low risk (HIT-CR score 0-2). The primary outcome was the proportion of immunoassay orders initiated but cancelled after firing of the CDS advisory. Chart reviews were conducted to assess anticoagulation usage, 4Ts scores and the proportion of patients who had HIT. In a 20-week period, 319 CDS advisories were presented to users who initiated potentially unnecessary HIT diagnostic testing. The diagnostic test order was discontinued in 80 (25%) patients. Heparin products were continued in 139 (44%) patients, and alternative anticoagulation was not given to 264 (83%). The negative predictive value of the advisory was 98.8% (95% CI: 97.2-99.5). HIT-CR score-based CDS can reduce unnecessary diagnostic testing for HIT in patients with a low pretest probability of HIT.

Heparin-Induced Thrombocytopenia in Critically Ill Patients

Many critically ill patients receive heparin, either before intensive care unit (ICU) admission (e.g., postcardiac surgery), for prophylaxis/treatment of thrombosis, for hemodialysis/filtration, or even incidentally (e.g., flushing of intravascular catheters), and are therefore at risk for developing immune heparin-induced thrombocytopenia (HIT), a prothrombotic drug reaction caused by platelet-activating antiplatelet factor 4 (PF4)/heparin antibodies. However, HIT explains at most 1 in 100 thrombocytopenic ICU patients (HIT frequency 0.3-0.5% vs. 30-50% background frequency of ICU-associated thrombocytopenia), and most patients who form anti-PF4/heparin antibodies do not develop HIT; hence, HIT overdiagnosis often occurs. This review discusses HIT-related issues relevant to ICU patients, including how to (1) distinguish HIT both clinically and serologically from non-HIT-related thrombocytopenia; (2) recognize HIT-mimicking disorders, such as the acute disseminated intravascular coagulation (DIC)/liver necrosis-limb necrosis syndrome; (3) prevent HIT in the ICU through use of low-molecular-weight heparin; and (4) treat HIT, including awareness of "PTT confounding" when anticoagulating patients with DIC.

Heparin Induced Thrombocytopenia in Pediatric Patients: Utility of Laboratory Testing

Abstract 1171▪▪This icon denotes a clinically relevant abstract Background:Heparin-induced thrombocytopenia (HIT) is characterized by the development of platelet-activating antibodies in response to heparin exposure, resulting in thrombocytopenia and a paradoxical risk for thrombotic complications. The diagnosis of HIT rests on clinical findings with supporting laboratory evaluation. The major features of HIT (thrombocytopenia and thrombosis after heparin exposure) are often seen in critically-ill children, but this is usually due to causes other than HIT. Clinical scoring systems (such as the 4T scoring system) to assess the pre-test probability of HIT are used widely in adults, but have yet to be fully validated in children. However, without prompt diagnosis and discontinuation of heparin, HIT can result in life and limb threatening thrombosis; on the other hand, overdiagnosis of HIT can lead to unnecessary exposure to alternative anticoagulants. Tests for HIT antibodies include ELISA immunoassays (EIA) for anti-PF4/heparin antibodies, which are widely available. The ELISA has high sensitivity but poor specificity with a high false positive rate. Functional tests, such as the 14C serotonin release assay (SRA), have high sensitivity and specificity, but are not routinely performed at most hospitals. In adults, higher antibody titers by ELISA are associated with SRA positivity and clinical manifestations of HIT. While the predictive value of these laboratory tests have been studied extensively for the diagnosis of HIT in adults, relatively little is known about their performance in the evaluation of pediatric patients. The aim of this study is to assess the utility of the ELISA and SRA tests, and clinical scoring systems to diagnosis HIT pediatric patients. Methods/Results: We identified 194 patients < 22 years of age who were referred for HIT testing between March 2001 and February 2010 at Johns Hopkins Hospital. 263 samples were evaluated by ELISA and/or SRA. ELISA was performed on 221 samples. Using the adult cut off value of 0.4 OD, 197 were negative, and 25 were positive (11%). SRA was performed on 39 samples and 3 were positive (8%). We found that positive SRA assays were found only in patients with ELISA OD values > 1.0. Two out of these three patients with SRA positivity had clinical HIT as diagnosed by treating physicians. The 4T Score (Warkentin, Br J Haem, 2003) and the HIT Expert Probability (Cuker, J Thromb Haemost, 2010) are pre-test scoring models that stratifies patients to high, intermediate, and low probability of HIT but have not been evaluated in pediatrics. A retrospective evaluation of utility of these scoring systems is currently underway. Conclusion: The utility of HIT antibody testing has not been formally evaluated in children. Only a subset of patients with positive ELISA tests will show SRA positivity. Higher titers of anti-PF4/heparin antibodies are associated with SRA positivity in pediatric patients, similar to adults. Further studies to validate predictive scoring systems in pediatic patients for the diagnosis of HIT is warranted. Disclosures:Streiff:BristolMyers Squibb: Research Funding; sanofi-aventis: Consultancy; Daiichi-Sankyo: Consultancy; Eisai:; sanofi-aventis: Honoraria.

Overdiagnosis of Heparin-Induced Thrombocytopenia in Surgical ICU Patients

Heparin use in surgical patients places them at increased risk for developing heparin-induced thrombocytopenia (HIT). The false positive rate of HIT using the current standard criteria is unknown in surgical ICU patients, who often have confounding factors that cause thrombocytopenia. Surgical ICU patients, admitted over a 2-year period with a positive screening test for HIT (platelet factor [PF] 4 ≥ 0.4 optical density [OD]), were reviewed retrospectively at a single institution. Correlation of the Warkentin 4-T score and commercial heparin PF4 ELISA with serotonin releasing assay (SRA) was performed. Logistic regression was used to determine independent risk factors associated with the development of HIT. PF4 tests were requested in 643 patients based on a clinical suspicion of HIT. Of these, 104 patients had a PF4 result, an SRA value (%), and a 4-T score available. Twenty patients (19%) had true positive HIT, defined as a positive PF4 and positive SRA (SRA ≥ 20%). Eighty-four patients (81%) were false positive, defined as a positive PF4 and negative SRA. Five of 58 patients with Warkentin score of 0 to 3, and 6 of 14 patients with Warkentin score of 6 to 8 were HIT positive by SRA. In surgical ICU patients, clinical suspicion for HIT necessitates PF4 and SRA analysis. Testing for HIT or treatment with a direct thrombin inhibitor should not depend on the Warkentin 4-T score alone. Although a PF4 ≥ 0.4 OD is considered a positive screening test for HIT, a PF4 ≥ 2.0 OD is preferable in surgical ICU patients.

Heparin-induced thrombocytopenia (HIT) in 2011: An epidemic of overdiagnosis

Heparin-induced thrombocytopenia (HIT) in 2011: An epidemic of overdiagnosis

Heparin-Induced Thrombocytopenia in the Intensive Care Unit

Heparin-induced thrombocytopenia (HIT) occurs following an immune reaction to the administration of heparin, which results in increased platelet activation and thrombocytopenia, and lead to arterial and venous thrombosis in untreated cases. It may be considered as an idiosyncratic, drug-induced reaction in which heparin injections result in the formation of complexes with platelet factor 4 (PF4), triggering an antibody-mediated reaction in certain individuals. Low platelet count in this instance is secondary to platelet aggregation and can lead to thrombotic complications by vascular occlusion and other mechanisms. Early recognition of this complication is essential to prevent life- and limb-threatening thrombosis. Therefore, it is important that intensive care physicians who administer heparin in different forms are aware of this potential adverse event and follow a regular plan in monitoring the platelet count while the patient is on heparin. In a patient whose platelet count falls while on heparin, when no other diagnostic possibilities can easily explain it, immediate withdrawal of any form of heparin and commencement of an alternative anticoagulant is necessary until the diagnosis of HIT is confirmed or excluded. At the same time, it is important that over-diagnosis of HIT is not made to avoid unwanted bleeding complications from the alternative anticoagulants. This review outlines the pathophysiology, diagnosis and management of HIT with a focus on the intensive care setting.

Heparin Induced Thrombocytopenia; A Diagnostic Dilemma.

Abstract 4468 IntroductionThe diagnosis of HIT can be challenging. Short of the serotonin release assay, which can be difficult to get in a timely manner, the 4T method developed by Lo et al., in conjunction with the HIT elisa assay (EIA), is the best established criteria for the rapid diagnosis of Heparin Induced Thrombocytopenia (HIT). We sought to determine how often the 4Ts were being applied at a large academic institution. In addition, we sought to understand the outcome of patients started on direct thrombin inhibitors (DTIs) who did not meet the 4T/EIA criteria for HIT. MethodsA retrospective case series identified patients placed on DTI for HIT treatment from 10/2006 to 5/2008. The 4T pretest probability was then applied retrospectively. HIT EIA Ab testing, optical densities, duration of DTI treatment, and bleeding incidence were recorded. Liberal and modified conservative criteria from Lo et al.'s study were used to define patients with HIT. Overdiagnosis of HIT was then recorded based on the above criteria. Results76 patients were included for analysis. The average age was 61.4 years. Based on the 4T pretest probability, 30 patients were classified as low risk, 37 intermediate risk, and 9 high risk for HIT. The average HIT OD for low, intermediate, and high pretest probability was 0.49, 1.17, and 2.05.76% and 36% of patients treated with DTIs for HIT met the liberal and modified conservative HIT definitions, respectively. 18 patients (24%) did not meet liberal HIT criteria but remained on DTI treatment for 1 to 60 days. Cost of DTI overuse in this subset was $84,960. Cost of DTI use in patients who did not meet modified conservative criteria was $462,246. All 16 patients who developed bleeding complications fulfilled a liberal diagnosis of HIT while only 6 of these patients fulfilled the modified conservative definition of HIT. Conclusions1) The 4T method for diagnosing HIT is not being applied to a large percentage of patients in a tertiary academic center. 2) There is an overdiagnosis of HIT regardless of definition criteria with 24% of patients treated for HIT not meeting the liberal definition while 64% of patients did not meet the modified conservative definition. This overdiagnosis has both a significant monetary and morbidity cost. Disclosures:No relevant conflicts of interest to declare.

Incidence and clinical significance of anti‐PF4/heparin antibodies of the IgG, IgM, and IgA class in 755 consecutive patient samples referred for diagnostic testing for heparin‐induced thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is usually caused by anti-platelet factor 4 (PF4)/heparin antibodies, leading to intravascular platelet activation. These antibodies can be detected by PF4/polyanion antigen assays or platelet activation assays. While antigen assays are very sensitive and recognize immunoglobulin (Ig)G, IgA, and IgM antibodies, the role of IgM and IgA HIT-antibodies is debated. Platelet activation assays recognize IgG and are more specific for clinical HIT. We analyzed sera from 755 consecutive patients referred for diagnostic testing for HIT using a PF4/heparin enzyme-linked immunosorbent assay (ELISA) for IgG, IgA, and IgM and by the heparin-induced platelet activation (HIPA) test. Clinical information was provided by the treating physicians. A total of 108 of 755 (14.3%) patients tested positive, 105 (13.9%) in the PF4/heparin IgG/A/M ELISA [28 (26.7%) only for IgM/A]; 53 (7.0%) sera were positive in the HIPA, of those 50 tested also positive in the ELISA. In 77 patients sufficient clinical information was provided. Available clinical information for 17 of the 28 patients who had only IgM and/or IgA detected showed plausible alternative (non-HIT) explanations in four of seven who had thromboembolic complications and in nine of 10 who had isolated HIT. Detection of IgG, IgM and IgA class antibodies by PF4/heparin ELISA yields a positive test result about twice as often as does a platelet activation assay, with only a minority of the additional patients detected likely having HIT. Thus, there is a potential for considerable over-diagnosis of HIT by laboratories that utilize only an ELISA for diagnostic testing.