A Road Paved with Good Intentions: A Platelet Count-Based Alert to Facilitate Diagnosis of Heparin-Induced Thrombocytopenia

Abstract Background: Heparin-induced thrombocytopenia (HIT) is a rare disorder with potential to cause significant morbidity and mortality. Early identification and initiation of non-heparin anticoagulation can prevent devastating thrombotic events. However, over-testing is common and can lead to result misinterpretation, unnecessary heparin avoidance, and increased cost. When there is concern for HIT, guidelines from the American Society of Hematology recommend calculation of the 4Ts score to determine the need for laboratory testing. The Choosing Wisely® initiative recommends against laboratory testing in patients with a low probability score of ≤3. In patients with an intermediate or high probability score (≥4), screening with enzyme-linked immunosorbent assay (ELISA) is performed first. If positive, the diagnosis of HIT is confirmed with a functional assay, commonly the serotonin release assay (SRA). Methods: In an effort to increase recognition of HIT, providers at a large academic medical center received a non-interruptive alert in the electronic medical record (EMR) on all patients in whom the platelet count declined by ≥50% starting in Aug 2017. We performed a retrospective evaluation of 1) the number of alerts and 2) all ELISA results obtained with or without an alert, over a 90-day period (Dec 2019 to March 2020). A 4Ts score was calculated by chart review by the first author in real-time as the alert was sent (blinded to ELISA and SRA results). Among those patients with multiple alerts or test orders, the first instance was used for analysis. Demographic and clinical characteristics were reported using frequencies and percentages, means (standard deviation, SD), and medians (interquartile range, IQR). Patients with alerts and ELISA testing ordered were compared with 2 groups: 1) patients with alerts but no ELISA ordered; 2) patients with no alerts but ELISA ordered. Comparisons were performed using chi squared tests, Fisher's exact tests, t-tests and Wilcoxon rank-sum tests as appropriate. Results: In the 90-day observation period, 302 alerts were fired in 270 patients (Figure 1). Thirty alerts (28 patients, 10%) were generated for patients admitted for organ donation or post-stem cell transplantation, for whom platelet count decline was expected. Excluding these patients, there were 272 alerts in 242 patients (approximately 3 alerts per day in a 1,157-bed hospital). Of patients with alerts, 22 (8%) had a platelet count inaccuracy (i.e. platelets clump or another reason) and 18 (7%) did not receive heparin prior to platelet decline, for a cumulative total of 40 (15%) inappropriate alerts. In patients with an alert, the ELISA was ordered more frequently for those with a lower platelet nadir (77x10 9/L vs. 115x10 9/L, p<0.0001) or in those with a thrombotic event (11 patients (17%) vs. 6 patients (4%), p=0.0021) (Table 1). Those without an ELISA ordered were more likely to have a low 4Ts score (23 patients (36%) vs. 81 patients (58%), p<0.0001). In addition to 71 patients with an alert, an ELISA was also ordered for 67 patients without an alert (n=138) (Figure 1). Close to half of ELISA-tested patients had a low 4Ts score (n=51, 46%) (Figure 2). In patients with an alert and ELISA not ordered, 18 (27%) had an intermediate or high 4Ts score. Seven patients were diagnosed with HIT based on a positive SRA, 6 with an alert and 1 without. The alert demonstrated a sensitivity of 86% (95% CI, 59.8-100%) and specificity of 50% (95% CI, 41.8-58.9%) with a positive predictive value of 0.0845 (95% CI, 0.0198-0.1492) and negative predictive value of 0.9851 (95% CI, 0.9560-1.0000). Conclusion: An EMR alert based on platelet count decline had multiple shortcomings including frequent inappropriate firings and a lack of guidance on appropriate indications for testing. This evaluation of institutional testing practices indicates frequent use and misinterpretation of ELISA discordant with evidence-based guidelines. Although prompt diagnosis of HIT is important, alternative strategies for identification of at-risk patients and communication of recommended actions to providers should be considered. Because the 4Ts score includes variables difficult to automate in the EMR, our institution is exploring electronic consultation and real-time expert provider access to overcome these limitations. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Failure of Fondaparinux in Autoimmune Heparin-Induced Thrombocytopenia

TH Open ◽

10.1055/s-0040-1713175 ◽

2020 ◽

Vol 04 (04) ◽

pp. e305-e308

Author(s):

Michelangelo Sartori ◽

Benilde Cosmi

Keyword(s):

Platelet Count ◽

Thrombotic Event ◽

Enzyme Linked Immunosorbent Assay ◽

Base Line ◽

Heparin Induced Thrombocytopenia ◽

Vein Thrombosis ◽

Life Threatening ◽

History Of ◽

Thrombotic Complications ◽

Few Data

AbstractHeparin-induced thrombocytopenia (HIT) is an immune adverse reaction to heparin that is associated with life-threatening thrombotic complications. More rarely, HIT may begin after stopping of heparin or after flushes of heparin (autoimmune HIT). Fondaparinux has been proposed as a candidate treatment for HIT, but there are few data on its use in autoimmune HIT. An 86-year-old man with a history of diabetes mellitus, arterial hypertension, and hypercholesterolemia was admitted to our hospital for carotid endarterectomy. During surgery, only one heparin dose of 5,000 U was used. Platelet count started to decrease on the 11th day after surgery. Since the patient was not receiving heparin treatment/prophylaxis, HIT was not suspected. On day 19, platelet count was 61 × 103/μL, and the patient was investigated for a diagnosis of HIT. Immunoglobulin (Ig)-G-specific enzyme-linked immunosorbent assay (ELISA) was positive and HIT was confirmed by a platelet aggregation test; fondaparinux 5 mg once a day was started. During fondaparinux treatment, platelet count did not increase and a lower leg deep vein thrombosis occurred. Fondaparinux was stopped and rivaroxaban 15 mg twice a day was started. Platelet count returned to base line after 10 days from fondaparinux withdrawal. There was no thrombotic event or bleeding complication during rivaroxaban treatment. Anecdotal evidence suggests risk of failure of fondaparinux treatment for autoimmune HIT and supports the use of rivaroxaban for treatment of HIT, justifying larger studies.

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Utility and Pitfalls of Stepwise Laboratory Testing for Heparin Induced Thrombocytopenia: Retrospective Review from an Academic Medical Center

Blood ◽

10.1182/blood-2019-125824 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2371-2371 ◽

Cited By ~ 1

Author(s):

Joshua Kra ◽

Helen Horng

Keyword(s):

Laboratory Testing ◽

Laboratory Tests ◽

Medical Center ◽

Academic Medical Center ◽

Clinical Suspicion ◽

Functional Assay ◽

Heparin Induced Thrombocytopenia ◽

Academic Medical ◽

Elisa Testing ◽

4T Score

Introduction: Heparin induced thrombocytopenia (HIT) occurs in up to 5% of adults exposed to heparin due to formation of heparin-dependent antibodies to the heparin/platelet factor 4 (PF4) complex. Patients develop thrombocytopenia and are at risk for severe thrombotic complications. Mortality rates can be as high as 20%, but are often much lower with prompt recognition, cessation of heparin, and treatment with alternative anticoagulants. However, these alternative medications are often both labor-intensive drips and expensive, highlighting the need for quick decision making in such challenging cases. The classic workup of HIT involves assessing clinical suspicion (often using the "4T score" on a scale of 0-8), followed by lab testing for detection of the heparin-dependent antibody and then a functional assay to confirm pathogenicity of the antibody. Our institution uses an in-house rapid Particle ImmunoFiltration Assay (PIFA), which is a same-day test and reported as "positive" or "negative." Other testing available includes send-out tests for Enzyme-Linked Immunoassay (ELISA) to IgG, A, and M of the PF4 antibody as well as the C-14 Serotonin Release Assay (SRA) functional assay. The goal of this retrospective review is to analyze the utility of an algorithmic approach to laboratory testing in aiding the rapidity of diagnosis of HIT without missing possible critical cases. Methods: This was a single institutional study at a large urban academic medical center. We reviewed inpatient charts from 2015-2018 of patients who had any lab testing for HIT. As per institutional guidelines, first-line testing is recommended by using the in-house same-day testing PIFA. If positive, a sample is automatically reflexed and sent-out for PF4 ELISA testing and SRA. Furthermore, clinicians are able to directly order ELISA and SRA testing at their medical discretion. Our analysis looked at those patients with at least two different "HIT-related" laboratory tests to best analyze the concordance and discordance rates of the above testing to assess for sensitivity, specificity, and overall accuracy of using a stepwise testing approach. We used a cutoff value of >0.4 optical density (OD) for ELISA testing, and >20% release at low-dose heparin concentration for SRA testing. Results: There were 118 patients who had at least two different HIT-related laboratory tests sent. 91 patients had both PIFA and ELISA testing, with 37/79 (47%) positive concordance rate and 6/12 (50%) negative concordance rate, for a sensitivity of 86% and specificity of 13%. 3 patients with positive PIFA also had positive SRA, and there were 2 patients with negative PIFA with positive SRA testing (see attached Table). When comparing ELISA testing to SRA, 4/41 (10%) had concordant positive testing, while no patient with a negative ELISA test had a positive SRA (28 concordant negative cases). Overall, of 94 SRA tests run, 5 were positive, of which 2/5 had negative PIFA and 0/4 had negative ELISA testing. Conclusions: While PIFA testing had a high sensitivity compared to ELISA, the overall accuracy compared to ELISA was low, while ELISA testing was 100% sensitive in this analysis. Furthermore, there was still a risk of missing cases of HIT using PIFA testing alone. In both cases of positive SRA with a negative PIFA, patients had a high 4T score of >6, consistent with a high clinical suspicion for HIT. We conclude that PIFA testing is not equivalent to ELISA testing, and that use of a laboratory "algorithm only" approach would be inappropriate in the diagnosis of HIT. Our results highlight the importance of using both clinical scoring systems and appropriate lab testing together in the workup and diagnosis of HIT. Disclosures No relevant conflicts of interest to declare.

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Clinical Significance of the Serotonin Release Assay and Platelet Count Monitoring After Cardiac Surgery

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029617734308 ◽

2017 ◽

Vol 24 (6) ◽

pp. 944-949 ◽

Cited By ~ 1

Author(s):

Shinya Motohashi ◽

Takefumi Matsuo ◽

Hidenori Inoue ◽

Makoto Kaneko ◽

Shunya Shindo

Keyword(s):

Cardiac Surgery ◽

Platelet Count ◽

Clinical Course ◽

Serotonin Release ◽

Enzyme Linked Immunosorbent Assay ◽

Heparin Induced Thrombocytopenia ◽

Release Assay ◽

Immunological Assays ◽

Platelet Count Monitoring ◽

The Relationship

Heparin-induced thrombocytopenia (HIT) is one of the serious complications in patients who undergo cardiac surgery. However, there remains a major problem in diagnosing HIT because the current immunological assays for detection of HIT antibody have limitations. Furthermore, the clinical course of thrombocytopenia in this surgery makes it increasingly difficult to diagnose HIT. We investigated the relationship between platelet count and HIT antibody in 59 patients who underwent cardiac surgery using cardiopulmonary bypass (CPB). The number of postoperative HIT antibody-positive patients evaluated using enzyme-linked immunosorbent assay kit (polyanion IgG/IgA/IgM complex antibodies/antiplatelet factor 4 enhanced) was 37 (62.7%). In contrast, platelet activation by HIT antibody was evaluated using the serotonin release assay (SRA). More than 20% and 50% release of serotonin was obtained from 12 patients (20.3%) and 8 patients (13.6%), respectively. The levels of d-dimer were significantly different on postoperative day 14 between SRA-positive and SRA-negative groups; however, postoperative thrombus complication was not detected using sonography in the patients with positive serotonin release at all. After being decreased by the operation, their platelet count recovered within 2 weeks in both groups equally. In our study, although the patients were positive in the platelet activating HIT antibody assay, they remained free from thrombosis and their platelet count recovered after early postoperative platelet decrease. Therefore, in addition to the SRA, monitoring of platelet count might be still considered an indispensable factor to facilitate the prediction of HIT thrombosis prior to manifestation in the patients undergoing cardiac surgery using CPB.

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Serologic Results in >1000 Patients With Suspected Heparin-Induced Thrombocytopenia

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029607304721 ◽

2007 ◽

Vol 14 (4) ◽

pp. 410-414 ◽

Cited By ~ 8

Author(s):

Suresh G. Shelat ◽

Anne Tomaski ◽

Eleanor S. Pollak

Keyword(s):

Laboratory Diagnosis ◽

Serotonin Release ◽

Enzyme Linked Immunosorbent Assay ◽

Functional Assay ◽

Platelet Factor ◽

Heparin Induced Thrombocytopenia ◽

Life Threatening ◽

Release Assay ◽

Pathogenic Antibodies

Heparin-induced thrombocytopenia (HIT) can lead to life-threatening and limb-threatening thrombosis. HIT is thought to be initiated by the interaction of pathogenic antibodies toward a complex platelet factor 4 (PF4) and heparin (PF4:H), which can activate platelets and predispose to thrombosis. As such, the laboratory diagnosis of HIT includes antigenic and functional assays to detect antibodies directed at PF4:H complexes. We performed a retrospective analysis of 1017 consecutive samples tested by serotonin-release assay and by enzyme-linked immunosorbent assay (ELISA). Most samples showed no serologic evidence of HIT, whereas 4% to 5% of samples demonstrated both antigenic and functional serological evidence for HIT. Approximately 12% to 18% of samples showed immunologic evidence of anti-PF4:H antibodies but without functional evidence of serotonin release in vitro. Interestingly, a small minority of samples (0.7%) caused serotonin release but were negative in the ELISA. The results are presented using cutoff values established at our hospital and for the ELISA manufacturer. This study provides a pretest probability of the serologic results from an antigenic assay (ELISA) and a functional assay (serotonin-release assay) in patients clinically suspected of having HIT.

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The Incidence of Thrombosis in Patients with Isolated Heparin Induced Thrombocytopenia.

Blood ◽

10.1182/blood.v108.11.1049.1049 ◽

2006 ◽

Vol 108 (11) ◽

pp. 1049-1049 ◽

Cited By ~ 1

Author(s):

Rachel P. Rosovsky ◽

Omar I. Abdel-Wahad ◽

Elizabeth M. Van Cott ◽

David J. Kuter

Keyword(s):

Platelet Count ◽

Mortality Rate ◽

Massachusetts General Hospital ◽

Thrombotic Event ◽

Radiographic Examination ◽

Platelet Factor ◽

Heparin Induced Thrombocytopenia ◽

Total Incidence ◽

Objective Evidence ◽

Heparin Exposure

Abstract Introduction: Heparin-induced thrombocytopenia type-II (HIT) is a serious prothrombotic disorder caused by heparin exposure. The incidence of thrombosis in patients with isolated HIT, defined as HIT without clinically evident thrombosis at the time of diagnosis, is not well established. Aim: The purpose of this prospective study was to determine the total incidence of thrombotic events after diagnosis of isolated HIT from radiographic evidence of asymptomatic deep venous thrombosis (DVT) plus radiographic confirmation of symptomatic thrombosis. Patients and Methods: We evaluated all patients with a positive enzyme-linked immunoassay (ELISA) for heparin-platelet factor 4 (PF4) antibody (Ab) daily at Massachusetts General Hospital from 10/10/05 to 5/13/06. Inpatients with (1) a positive PF4 Ab test, (2) thrombocytopenia, as defined by a ≥50% drop from baseline platelet count and/or a fall in platelet count to <150×109/L, in association with heparin exposure, (3) no signs or symptoms of thrombosis at time of the positive Ab test, and (4) no other definitive etiology of thrombocytopenia were considered to have isolated HIT and included for study. Patients with a prior diagnosis of HIT, DVT, pulmonary embolism, or peripheral arterial thrombosis were excluded. Within 72 hours of diagnosis and of initiation of a non-heparin anticoagulant, all included patients underwent radiographic examination for asymptomatic DVT in the lower extremities (LE). Objective evidence of thrombotic events other than LE DVT after the diagnosis was also recorded. Daily platelet count, type and timing of all anticoagulants, use of blood products, and PF4 Ab titer were collected to determine if there was an association between these factors and development of thrombosis. Mortality rate during hospitalization was also recorded. Results: Of the 158 patients with a positive heparin-PF4 Ab, 64 patients met criteria for study, 14 of which were lost to follow-up. Among the 50 remaining eligible patients, the total incidence of thrombosis was 20% (12% were found to have an asymptomatic thrombotic event and 8% developed a symptomatic thrombotic event). Development of thrombosis was independently associated with platelet transfusion (p=0.005) and with the degree of platelet count nadir as expressed by platelet count (p=0.038) or by percent decrease from baseline (p=0.031). There was no association between the PF4 Ab titer or the type and timing of non-heparin anticoagulant and development of thrombosis. The overall mortality rate in patients diagnosed with isolated HIT during hospitalization was 22%. Conclusion: The total incidence of thrombotic events in isolated HIT was 20%, with greater than half of the events being asymptomatic thromboses found only by radiographic examination. This high incidence of asymptomatic LE DVT suggests that routine investigation for LE DVT should be performed in this patient population and that patients with isolated HIT should be treated with a non-heparin anticoagulant. Our findings also confirm the current recommendation to avoid platelet transfusions in patients with isolated HIT as we found an increased rate of thrombosis associated with this practice.

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

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029617721013 ◽

2017 ◽

Vol 24 (5) ◽

pp. 749-754 ◽

Cited By ~ 1

Author(s):

Gang Zheng ◽

Michael B. Streiff ◽

Clifford M. Takemoto ◽

Jennifer Bynum ◽

Elise Gelwan ◽

...

Keyword(s):

Diagnostic Accuracy ◽

Predictive Value ◽

Clinical Utility ◽

Predictive Accuracy ◽

High Sensitivity ◽

Neutralization Assay ◽

Serotonin Release ◽

Enzyme Linked Immunosorbent Assay ◽

Heparin Induced Thrombocytopenia ◽

Heparin Neutralization

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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Comparison of an IgG-Specific Enzyme-Linked Immunosorbent Assay Cutoff of 0.4 Versus 0.8 and 1.0 Optical Density Units for Heparin-Induced Thrombocytopenia

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029615606532 ◽

2016 ◽

Vol 23 (3) ◽

pp. 282-286 ◽

Cited By ~ 5

Author(s):

Brianne M. Ritchie ◽

Jean M. Connors ◽

Katelyn W. Sylvester

Keyword(s):

Optical Density ◽

Immunosorbent Assay ◽

Predictive Value ◽

Retrospective Chart Review ◽

Serotonin Release ◽

Enzyme Linked Immunosorbent Assay ◽

Platelet Factor ◽

Heparin Induced Thrombocytopenia ◽

Institutional Review ◽

Sensitivity Specificity

Background: Previous studies have demonstrated optimized diagnostic accuracy in utilizing higher antiheparin–platelet factor 4 (PF4) enzyme-linked immunosorbent assay (ELISA) optical density (OD) thresholds for diagnosing heparin-induced thrombocytopenia (HIT). We describe the incidence of positive serotonin release assay (SRA) results, as well as performance characteristics, for antiheparin–PF4 ELISA thresholds ≥0.4, ≥0.8, and ≥1.0 OD units in the diagnosis of HIT at our institution. Methods: Following institutional review board approval, we conducted a single-center retrospective chart review on adult inpatients with a differential diagnosis of HIT evaluated by both antiheparin–PF4 ELISA and SRA from 2012 to 2014. The major endpoints were to assess incidence of positive SRA results, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy at antiheparin–PF4 ELISA values ≥0.4 OD units when compared to values ≥0.8 and ≥1.0 OD units. Clinical characteristics, including demographics, laboratory values, clinical and safety outcomes, length of stay, and mortality, were collected. Results: A total of 140 patients with 140 antiheparin–PF4 ELISA and SRA values were evaluated, of which 23 patients were SRA positive (16.4%) and 117 patients were SRA negative (83.6%). We identified a sensitivity of 91.3% versus 82.6% and 73.9%, specificity of 61.5% versus 87.2% and 91.5%, PPV of 31.8% versus 55.9% and 63.0%, NPV of 97.3% versus 96.2% and 94.7%, and accuracy of 66.4% versus 86.4% and 88.6% at antiheparin–PF4 ELISA thresholds ≥0.4, ≥0.8, and ≥1.0 OD units, respectively. Conclusion: Our study suggests an increased antiheparin–PF4 ELISA threshold of 0.8 or 1.0 OD units enhances specificity, PPV, and accuracy while maintaining NPV with decreased sensitivity.

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Correlation Of Heparin Confirmatory Test (HCT) With Optical Density (OD) and Serotonin Release Assay (SRA) In The Diagnosis Of Heparin Induced Thrombocytopenia (HIT)

Blood ◽

10.1182/blood.v122.21.4754.4754 ◽

2013 ◽

Vol 122 (21) ◽

pp. 4754-4754 ◽

Cited By ~ 1

Author(s):

Ravneet Thind ◽

Danielle Heidemann ◽

Sundara Raman ◽

Philip Kuriakose

Keyword(s):

Optical Density ◽

Predictive Value ◽

Serotonin Release ◽

Thrombin Inhibitors ◽

Confirmatory Test ◽

Functional Assay ◽

Heparin Induced Thrombocytopenia ◽

Laboratory Confirmation ◽

Confirmation Test ◽

Release Assay

Introduction Heparin-induced thrombocytopenia (HIT) is a potentially fatal, thrombotic complication of heparin therapy mediated by antibodies to complexes between platelet factor 4 (PF4) and heparin. Accurate and rapid diagnosis with prompt commencement of therapy are imperative as delays in treatment are associated with an increasing risk of thrombosis, amputation, or death. On the flip side, initiation of therapy with direct thrombin inhibitors without laboratory confirmation carries a significant risk of bleeding. Two types of laboratory tests are available for detection of these antibodies: a widely available immunoassay (ELISA), which is very sensitive to the presence of anti-heparin/PF4 antibodies, but is less specific to the clinical syndrome of HIT because of detection of non-pathological antibodies. The Serotonin Release Assay (SRA) is a functional assay that is now considered the gold standard for confirmatory diagnosis of HIT due to its high specificity. However, the downside of SRA is the cost involved, limited availability and a turnaround time of 5-7 days. As such, a heparin confirmatory test (HCT) with excess heparin has been in use since mid 2011 on positive ELISA samples in our laboratory to improve test specificity. This test is more cost and time efficient, with a turnover time of no more than 48 hours. As noted in prior studies, inhibition of a positive ELISA result by 50% or more in the presence of excess heparin is considered confirmatory of heparin-dependent antibodies. Likewise a negative confirmatory test is defined as a decrease of 50% or less in antibody binding in the presence of heparin. Aim a) Correlation of Heparin Confirmatory test (HCT) with strength of HIT ELISA, vis-à-vis optical density (OD) of 0.4 - 0.99 and OD of >/= 1.0. b) Correlation of HCT results with SRA, to see if the latter can be replaced by the heparin confirmatory test. Patients and Methods A retrospective chart review of adult patients hospitalized at our institution with suspected HIT from July 2011 until January 2013 was done. There were 101 such patients. All patients who had a positive HIT ELISA, then had HCT as per our standard lab practice, with an SRA test done for diagnosis/confirmation of HIT, as per standard clinical practice. Historically, the major strength of SRA assay is its specificity. The optical density on HIT ELISA and SRA results were then compared with the Heparin Confirmatory test to establish clinical significance. Results Of the 101 patients tested for HIT ELISA, 49 were positive. HCT and SRA were performed on all 49 samples, 1 out of which was reported as indeterminate. Hence 48 samples were used for primary analysis, comparing HCT to the OD as well as the SRA results. Out of 48 patients, 6 had positive SRA with Heparin inhibition of >50% (sensitivity 6/6 = 100%). Remaining 42 patients had negative SRA, 7 out of which had Heparin inhibition of <50% (specificity 7/42 = 16.6%). All 7 patients with a negative HCT had a negative SRA, making the negative predictive value of the HCT 100%; however positive predictive value was only 14.6% (6/41). There was no correlation between the OD and Heparin Confirmation test. Conclusions Although there is data suggesting that there might be some value to the Heparin Confirmation test, we were unable to show a significant correlation between HCT and OD or between HCT and SRA. The prospect of having a cost effective and rapid assay for laboratory confirmation of HIT will always be a relevant need. We feel that a larger, prospective study should be conducted to definitively assess the relationship between HCT and SRA. Disclosures: No relevant conflicts of interest to declare.

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Proficiency Testing Results for Heparin-Induced Thrombocytopenia in North America

Seminars in Thrombosis and Hemostasis ◽

10.1055/s-0034-1365842 ◽

2014 ◽

Vol 40 (02) ◽

pp. 254-260 ◽

Cited By ~ 12

Author(s):

Kristi Smock ◽

Marlies Ledford-Kraemer ◽

Piet Meijer ◽

Peihong Hsu ◽

Elizabeth Van Cott

Keyword(s):

North America ◽

Proficiency Testing ◽

Immunosorbent Assay ◽

Laboratory Testing ◽

Positive Sample ◽

Enzyme Linked Immunosorbent Assay ◽

Heparin Induced Thrombocytopenia ◽

Coefficients Of Variation ◽

Agglutination Method

Between 2010 and 2012, North American Specialized Coagulation Laboratory Association (NASCOLA) distributed five proficiency testing challenges to evaluate laboratory testing for heparin-induced thrombocytopenia (HIT). Results (n = 355) were submitted from 43 unique laboratories for 10 samples (3 positive, 2 weak positive, and 5 negative). The vast majority of results were from commercial enzyme-linked immunosorbent assay (ELISA) methods, predominantly polyvalent assays. Laboratories performed well in the classification of clear negative and positive samples. All results (100%) submitted for the five negative samples (n = 173) and 97% of immunological results submitted for the three positive samples (n = 105) were correctly classified (the incorrect responses were two borderline classifications and, from a gel-agglutination method, one negative classification). There was more difficulty in the classification of the two weak positive samples (n = 70). In one survey, 61% of results from the weak positive sample were classified as positive, while 21% were called negative, 16% were called borderline, and 2% were called inconclusive. In a second survey, 16% of results from the weak positive sample were called positive, while 56% were called negative, and 28% were called borderline. Significant interlaboratory variation was observed for ELISA results, with coefficients of variation of about 20 to 30%. We conclude that there is variability in HIT laboratory testing and that identification of weak positive samples can be challenging.

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Have You Been HIT?

Angiology ◽

10.1177/0003319711405509 ◽

2011 ◽

Vol 62 (8) ◽

pp. 641-644 ◽

Cited By ~ 1

Author(s):

Jane Cross ◽

Mary Weisters ◽

Robina Aslam ◽

David Keeling ◽

Ashok Handa

Keyword(s):

Platelet Count ◽

Rare Complication ◽

Major Complication ◽

Clinical Suspicion ◽

Enzyme Linked Immunosorbent Assay ◽

Significant Morbidity ◽

Vascular Surgeon ◽

Heparin Induced Thrombocytopenia ◽

Heparin Administration ◽

Alternative Anticoagulation

This review is specifically designed to aid the vascular surgeon in the management of heparin-induced thrombocytopenia (HIT). Heparin-induced thrombocytopenia is a rare complication of heparin administration, which poses significant morbidity and mortality. Its onset is usually 5 to 10 days after the heparin administration and should be suspected if platelet counts drop by at least 50%. Confirmation is given by the presence of HIT antibodies on an enzyme-linked immunosorbent assay (ELISA) or in functional platelet activation assays. The major complication is thrombosis and surprisingly bleeding is rare. Heparin must be stopped immediately if there is a clinical suspicion of HIT and alternative anticoagulation must be started. Anticoagulation is required for at least 2 to 3 months to prevent recurrence of thrombosis. Oral anticoagulation with warfarin should not be initiated until the platelet count has been recovered and there should be an overlap of at least 5 days between starting warfarin and stopping the alternative anticoagulant.

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