A Single Institution's Adherence to Heparin-Induced Thrombocytopenia and Thrombosis Testing Guidelines

Abstract Introduction: What was once an under-recognized clinical entity, heparin induced thrombocytopenia and thrombosis (HITT) has become a well-recognized and frequently tested disease. HITT is a serious and potentially fatal antibody mediated drug reaction to platelet factor 4 and early identification and treatment is essential. The 4T score is well-validated to guide appropriate testing of HITT where a low-probability score of 0-3 equates to a 99.8% negative predictive value for HITT2,3. In an effort to promote cost-conscious care and efficient use of healthcare resources, the American Society of Hematology (ASH) recommends against testing for HITT if the 4T score is 3 or less4. HITT laboratory testing at our institution is not restricted based on 4T score. We hypothesize that many providers are not following cost-conscious guidelines regarding HITT testing at our institution. Methods: We performed a single-institution retrospective analysis of patients who had a heparin-induced platelet antibody assay with reflexive serotonin release assay ordered between July 1, 2016 to July 1, 2017 at the University of Virginia Medical Center (UVA). We primarily assessed how our institution's ordering of heparin-induced platelet antibody for HITT compared to ASH's Choosing Wisely recommendation of forgoing laboratory testing on patients with a 4T score of 0-3 by retrospectively calculating 4T scores on all patients who had laboratory testing4. Patients were also assessed for episodes of bleeding and clotting and were scored on severity via the CTCAE and ISTH grading systems. Data on anticoagulant used after HITT testing was collected. We also checked to see if the blood specimen for assay was collected 2 hours after last heparin product as recommended by lab. Patients were excluded if they were not inpatient when their heparin-induced platelet antibody assay was drawn or if they were transferred or discharged immediately after assay was collected. Ultimately, of the initial 196 patients who had heparin-induced platelet antibody assay collected during this time frame, 184 patients were included for analysis. Results: Of the 184 patients who had a heparin-induced platelet antibody assay sent and were included in analysis, 55.4% of the patients (n=102) had a low pre-test probability of HITT with a 4T score of less than or equal to 3. Of the patients who had HITT testing sent, only 44% (n=81) received treatment with a non-heparin anticoagulant. Of the 102 patients who had a low pre-test probability of HITT with a 4T score of ≤3, 37.3% (n=38) were placed on an alternative anticoagulant. Of this low pre-test probability of HITT cohort, 7.8% (n=8) experienced bleeding as a complication. Interestingly, 15.5% (n=29) of all patients who had HITT testing continued to receive heparin products while awaiting results. Additionally, 19.3% (n=36) of samples were drawn within 2 hours of receiving heparin products. Conclusion: The guidelines for HITT testing and treatment have been well-validated and widely disseminated. Despite providers' familiarity with this clinical entity, the results depict that ordering practices at our institution do not follow guidelines in cost-conscious ordering nor in standard of treatment. Applying ASH's Choosing Wisely recommendation of not ordering laboratory testing on patients with a 4T low-probability score of 0-3, we see that 55.6% of the HITT assays ordered in this time period were inappropriate and at a cost of $455 to the institution per assay resulted in $46,865 of unnecessary health care costs to our institution in one year's time. This does not include the cost of alternative anticoagulation. Heparin costs just $0.04 per mL while argatroban costs $3.81 per mL and bivalirudin $12 per mL resulting in a 100 to 300 fold cost increase respectively. Standard work regarding HITT assay collection and treatment does not exist at our institution. Of concern, 15.5% of patients continued to receive heparin products after HITT testing was sent. The results of this study prompted implementation of a quality improvement project to decrease inappropriate HITT testing and standardize treatment of suspected HITT via an electronic medical record order set that uses the 4T score to suggest appropriate ordering of assays. We plan to collect data on changes in our ordering practices after this intervention. Disclosures No relevant conflicts of interest to declare.

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External Validation Of The HIT Expert Probability (HEP) Score, a Novel Pre-Test Probability Model For Heparin-Induced Thrombocytopenia Based On Broad Expert Opinion

Blood ◽

10.1182/blood.v122.21.1699.1699 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1699-1699

Author(s):

Lee Joseph ◽

Marcelo P.V. Gomes ◽

Firas Al Solaiman ◽

Julie St John ◽

Asuka Ozaki ◽

...

Keyword(s):

Expert Opinion ◽

Laboratory Testing ◽

Expert Panel ◽

Vascular Medicine ◽

Heparin Induced Thrombocytopenia ◽

Scoring Model ◽

Clinical Scoring ◽

Consultative Service ◽

Test Probability ◽

4T Score

Abstract Introduction The diagnosis of heparin-induced thrombocytopenia (HIT) is challenging due to the overlap of its clinical features with other entities, variable specificity of ELISA-based tests, poor availability of functional tests such as the serotonin release assay (SRA) and suboptimal positive predictive values of pre-test probability clinical scoring models, such as the 4T and Lillo-Le Louėt models. Improved diagnostic tools are desirable to guide early therapeutic decisions in patients with suspected HIT and to reduce inappropriate use of alternative anticoagulants. The HIT Expert Probability (HEP) Score, a pre-test probability clinical scoring model for HIT based on broad expert opinion, has recently been proposed to improve the diagnosis of HIT compared to the 4T score. We sought to externally and prospectively validate the HEP score. Methods Pre-test probability of HIT was prospectively assessed for 51 consecutive patients referred to the Cleveland Clinic Vascular Medicine Consultative Service for evaluation of possible HIT between August 1, 2012 and February 1, 2013. Electronic medical records were reviewed to obtain clinical, biochemical (including IgG specific HIT ELISA and SRA tests) and imaging data, and two Vascular Medicine fellows independently applied the 4T and HEP scores for each patient. Two independent HIT expert adjudicators rendered a diagnosis of HIT likely or unlikely. Both scorers and adjudicators were blinded to the Results of HIT laboratory testing, consultative service inputs and scores generated by other raters. Results The median 4T and HEP scores were 4.5 [range 3.0, 6.0] and 5 [range 3.0, 8.5], respectively. Interobserver agreement was lower for the HEP Score compared to 4T score, intraclass correlation coefficient: 0.50 (95% CI 0.16–0.85) vs. 0.69 (0.54–0.86). There were no significant differences between area under receiver-operating characteristics curves of 4T and HEP score against HIT ELISA testing (0.62 vs. 0.58, P = 0.62), SRA (0.74 vs. 0.73, P = 0.97), expert panel diagnosis (0.71 vs. 0.79, P = 0.20), concordant HIT ELISA and SRA (0.76 vs. 0.72, P = 0.65), and positive SRA or positive HIT ELSA with HIT likely expert panel diagnosis (0.73 vs. 0.75, P = 0.80). The HEP score model was 100% sensitive and 17% specific for determining the presence of HIT as defined by positive SRA or positive HIT ELISA with HIT likely expert panel diagnosis compared to 4T score (sensitivity, 94%; specificity 38%) (Figure 1, Table 1). Conclusion The HEP and 4T scores are excellent screening pre-test probability models for HIT, however, in this prospective validation study, test characteristics for the diagnosis of HIT based on confirmatory laboratory testing and expert opinion are similar. Given the complexity of the HEP scoring model compared to that of the 4T model, further validation of the HEP score is warranted prior to widespread acceptance. Disclosures: Kim: Philips US: Consultancy; GE: Research Funding.

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Testing for Heparin Induced Thrombocytopenia: Comparison of Practice at an Academic Center with Choosing Wisely Guidelines

Blood ◽

10.1182/blood.v126.23.3469.3469 ◽

2015 ◽

Vol 126 (23) ◽

pp. 3469-3469

Author(s):

DiMaria C Erica ◽

Alex Trussler ◽

Dyba Janique ◽

David Lee ◽

Michael J. Rauh ◽

...

Keyword(s):

Research Funding ◽

Clinical Characteristics ◽

Low Risk ◽

Choosing Wisely ◽

Observer Variability ◽

Heparin Induced Thrombocytopenia ◽

Inter Observer Variability ◽

Test Probability ◽

4T Score ◽

Heparin Exposure

Abstract Background: The American Society of Hematology Choosing Wisely Guidelines 2014 recommend against testing for treatment of Heparin Induced Thrombocytopenia (HIT) in individuals at low risk, defined by a 4T score ≤ 3. Diagnosis of HIT relies on a combination of clinical characteristics and laboratory testing. The 4T score is a pretest probability score that defines clinical characteristics of HIT with reported negative predictive value of 99.8%. A new scoring model, the HIT Expert Probability (HEP) score, was introduced in 2010 and postulated to reduce inter-observer variability. The primary objective of this study was to examine compliance with guidelines at our institution; a 456 bed university hospital. Secondary objectives were to compare the performance of the 4T and HEP score in regards to inter-observer variability and the predictive value of low risk scores. Methods: Local practice is initial testing with anti-PF4 antibody enzyme immunoassay (EIA), and subsequent reflex serotonin release assay (SRA) if the EIA is positive or indeterminate. Consecutive patients with requests for HIT testing were identified from laboratory records. With Research Ethics Board approval, retrospective chart review was conducted by 3 reviewers who independently applied 4T and HEP scores; discrepancies were resolved by consensus. Adverse events including thrombosis, skin necrosis, heparin infusion reactions, bleeding (classified as major by ISTH criteria) and mortality were recorded. Inter-observer variability was assessed using the intraclass correlation (ICC). Results: Between 2013 January 1 and 2015 Feb 21, 76 patients were referred for EIA testing. Excluded from this analysis were 7 patients with prior history of HIT or with testing requested from an outside institution. Of the remaining 69, median age was 67 years (range 24-90), 36 (56%) were male, 49 (71%) admitted with a medical diagnosis and 20 (29%) under a surgical service. Hematology service was consulted at some point during admission in 25 (36%). Pretest probability was documented in 16 (23%). A greater percentage of patients with documented pre-test probability had a hematology consult 11 (69%) than patients without 5 (31%). Also, 36 (86%) patients without a documented pre-test probability were considered low risk by the 4T score. Table 1.Scoring systemPre-test probabilityTotalN=69 (%)EIA positiveSRA positive*4TLow (≤3)42 (61)9 (13)1* (1)Intermediate (4-5)25 (36)10 (14)4 (6)High (6-8)2 (3)2 (3)1 (1)HEPLow (≤2)35 (51)7 (10)1* (1)Intermediate (2-5)20 (29)17 (25)1 (1)High (≥6)14 (20)7 (10)4 (6)*If SRA inconclusive, result confirmed with anti-PF4 IgG**Admitted with ischemic leg requiring catheter directed thrombolysis. Rapid onset thrombocytopenia within 24 hours of heparin exposure. Prior heparin exposure 150 days prior. Heparin stopped. No alternative anti-coagulation. No sequelae of HIT. The ICC for the pre-test probabilityscores was0.796(95% CI 0.714- 0.860) for 4T and 0.742 (95% CI- 0.645-0.821) for HEP score. By risk category, ICC for 4T score was 0.667 (95% CI 0.553 - 0.765) and HEP score was 0.702 (95% CI 0.553 - 0.765). HIT testing was performed in patients classified as low risk; 42 (61%) according to 4T and 35 (45%) according to HEP score. Among the 42 classified as low risk by 4T score, heparin was held in 26 (55) % pending results of testing and alternative anticoagulation commenced in 14 (33%) (fondaparinux 13, argatroban 1), at prophylactic dose in 12 and at therapeutic dose in 1 without a separate indication for anticoagulation. One low risk patient suffered major bleeding and 2 had thrombotic events. Overall, bleeding occurred in 10 (14%), major in 6 (9%), and thrombotic events occurred in 9 (13%). One patient presenting with septic shock, who developed thrombocytopenia with 4T score of 4, received argatroban and died on the same day from intracranial hemorrhage. All cause mortality during admission was 23 (33%). Conclusion: Compliance with Choosing Wisely Guidelines at our institution is low, and potentially associated with unnecessary financial expenditure and patient harm due to over-testing and over-treatment. We did not observe benefit of the more complex HEP score over the 4T score. Efforts are underway to increase awareness and align practice with recommendations. Disclosures James: Biogen Idec: Honoraria; Bayer: Honoraria, Research Funding; Octapharma: Honoraria, Research Funding; Baxter: Honoraria; CSL Behring: Honoraria, Research Funding.

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

Blood ◽

10.1182/blood-2021-145891 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 756-756

Author(s):

Jori E. May ◽

Kimberly D. Martin ◽

Laura J. Taylor ◽

Eric L. Wallace ◽

Marisa B. Marques

Keyword(s):

Platelet Count ◽

Real Time ◽

Predictive Value ◽

Laboratory Testing ◽

Thrombotic Event ◽

Enzyme Linked Immunosorbent Assay ◽

Functional Assay ◽

Heparin Induced Thrombocytopenia ◽

Probability Score ◽

Elisa Testing

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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A Restructured Approach to Diagnosis of Heparin Induced Thrombocytopenia in a Large Tertiary Hospital

Blood ◽

10.1182/blood-2018-99-114265 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 3525-3525

Author(s):

Sriman Swarup ◽

Somedeb Ball ◽

Nimesh Adhikari ◽

Courtney Alice Welch ◽

Jaden Fackrell ◽

...

Keyword(s):

Screening Test ◽

Laboratory Testing ◽

Conflicts Of Interest ◽

False Negative ◽

Serotonin Release ◽

Efficient Manner ◽

Improvement Project ◽

Heparin Induced Thrombocytopenia ◽

Cost Efficacy ◽

4T Score

Abstract Background The standard practice for diagnosis of heparin-induced thrombocytopenia (HIT) involves a combination of 4T score and laboratory tests, such as enzyme immunoassay for detection of antibodies. We noted a lack of widespread use of 4T score in our practice setting. We also found that our laboratory utilized Particle Immunofiltration Assay (PIFA) for HIT screening, which has been shown to have questionable diagnostic utility in HIT diagnosis (Warkentin et al., 2007). The study aims to improve the rate of 4T score usage in conjunction with an improved laboratory diagnostic test for patients with suspected HIT in a cost-efficient manner. Method We initiated a quality improvement project involving the review of all patients with laboratory orders for PIFA testing between March 2017 to March 2018, explicitly assessing for documented 4T scores before the ordering of PIFA. Three of the investigators also calculated 4T scores for these patients at the time of laboratory testing and noted the results of the serotonin release assay (SRA), if ordered. We further collected data on any alternative anti-coagulation used in such patients for a cost-efficacy analysis later. Results A total of 170 PIFA tests were ordered during the period of investigation. Only five (0.02%) of these patients had a documented 4T score at the time of testing. One hundred thirteen patients (66.4%) had a low 4T score per investigator-calculation. Forty-seven patients (27.6%) were noted to have intermediate 4T scores. Lastly, ten patients (0.05%) were observed to have high 4T scores. A total of 32 SRAs were ordered; five of which were positive (four with an intermediate 4T score and one with high 4T score). PIFA was false-negative in two confirmed cases of positive SRA and false-positive in 13 instances of negative SRA. Thus, in this study, the sensitivity of PIFA was noted to be 60%, and specificity was observed to be 50%. Nineteen patients also received alternative parenteral anti-coagulation (fondaparinux or argatroban); seven of these were with low, eight with intermediate, and four with high 4T scores. Conclusion The study highlights the need for improving 4T score usage rates in our hospital as well as a need for switching to an alternative HIT screening test to promote patient safety and cost efficacy. Hence, we have begun the integration of 4T score with laboratory testing into the electronic medical record, alongside a shift in our HIT screening test from PIFA to the recently FDA-approved automated latex immunoturbidimetric assay. We will be continuing analysis of patients with suspected HIT for another six months to assess the effects of the above interventions. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

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Testing for Heparin Induced Thrombocytopenia in Hospitalized Patients: In Line with Evidence?

Blood ◽

10.1182/blood-2021-153637 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 1957-1957

Author(s):

Udhayvir Singh Grewal ◽

Shiva Jashwanth Gaddam ◽

Sahith Reddy Thotamgari ◽

Tyiesha Brown ◽

Kavitha Beedupalli ◽

...

Keyword(s):

Conflicts Of Interest ◽

Heparin Therapy ◽

Hospitalized Patients ◽

Antibody Testing ◽

Drug Induced ◽

Platelet Factor ◽

Heparin Induced Thrombocytopenia ◽

Clinical Probability ◽

Test Probability ◽

4T Score

Abstract Background: Heparin-induced thrombocytopenia (HIT) is an immune complication of heparin therapy caused by antibodies to complexes of platelet factor 4 (PF4) and heparin. Both clinical probability and laboratory testing are needed for establishing a diagnosis of HIT. The 4Ts clinical scoring system, due to a very high negative predictive value when low, offers a robust means to exclude a diagnosis of HIT. However, these strategies are under-employed in clinical practice and limited evidence indicates a high prevalence of over-testing for HIT. Methods: This retrospective analysis was conducted to identify patients who underwent heparin/PF4 antibody testing over a period of 12 months. The testing was performed using an ELISA-based IgG anti-heparin/PF4 antibody assay and an optical density (OD) of 0.4 was used as a cut-off for a positive value. Electronic medical records were reviewed for 4T score documentation, anti-PF4 results, SRA testing and 4T scores were retrospectively calculated for all the patients. SAS v9.4 (Cary, NC) was used for statistical analysis. Results: A total of 105 patients who underwent anti-PF4 antibody testing were included for analysis. Majority of the patients in our cohort were admitted in an intensive care unit setting (75/105,71.4%). On chart review, only 17 patients (16.2%) were noted to have documentation of 4T score. Based on the retrospectively calculated 4T scores, 60 patients (57.1%) had low pre-test probability, 41 (39%) had intermediate pre-test probability and 4 (3.8%) patients were noted to have high pre-test probability. Anti-PF4/heparin antibodies were positive in 9 patients, of which 5 (55.5%) patients did not undergo concomitant SRA testing. Out of 9, 4 (44.4%) had weakly positive (0.4-1.0 OD units), 2 (21.1%) had strongly positive (1.0-2.0 OD units) and 2 (21.1%) patients had very strongly positive (>2 OD units) anti-PF4 antibody titers. Out of 105 patients, SRA was tested in 11 patients (10.5%) and was noted to be positive in 1 (0.95%). Overall, 2 patients were diagnosed and treated for HIT, out of which the diagnosis was not confirmed with SRA in 1 patient (due to high pre-test probability and very strong anti-PF4 titers). In the remaining patients, sepsis (48, 46.6%) and drug-induced thrombocytopenia (29, 28.2%) emerged as the most common possible causes of thrombocytopenia. Conclusion: Among hospitalized patients, over-testing for HIT is common. Practices to promote 4T score documentation and evidence-based anti-PF4 testing may help prevent unnecessary costs associated with serological testing and costly alternate anticoagulants. To improve overall outcomes, clinicians should also attempt to identify and treat other more likely causes of thrombocytopenia, especially in patients with low pre-test probability for HIT. Disclosures No relevant conflicts of interest to declare.

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Pre-test probability for SARS-Cov-2-related Infection Score: the PARIS score

10.1101/2020.04.28.20081687 ◽

2020 ◽

Cited By ~ 1

Keyword(s):

Cell Count ◽

White Blood Cell Count ◽

White Blood Cell ◽

High Probability ◽

Validation Cohort ◽

Rt Pcr ◽

Blood Cell Count ◽

Probability Score ◽

Low Probability ◽

Test Probability

AbstractBackgroundDiagnostic tests for SARS-CoV-2 infection (mostly RT-PCR and Computed Tomography) are not widely available in numerous countries, expensive and with imperfect performanceMethodsThis multicenter retrospective study aimed to determine a pre-test probability score for SARS-CoV-2 infection based on clinical and biological variables. Patients were recruited from emergency and infectious disease departments and were divided into a training and a validation cohort. Demographic characteristics, clinical symptoms, and results of blood tests (complete white blood cell count, serum electrolytes and CRP) were collected. The pre-test probability score was derived from univariate analyses between patients and controls, followed by multivariate binary logistic analysis to determine the independent variables associated with SARS-CoV-2 infection. Points were assigned to each variable to create the PARIS score. ROC curve analysis determined the area under the curve (AUC).FindingsOne hundred subjects with clinical suspicion of SARS-CoV-2 infection were included in the training cohort, and 300 other consecutive individuals were included in the validation cohort. Low lymphocyte (<1·3 G/L), eosinophil (<0·06G/L), basophil (<0·04G/L) and neutrophil counts (<5G/L) were associated with a high probability of SARS-CoV-2 infection. No clinical variable was statistically significant. The score had a good performance in the validation cohort (AUC=0.889 (CI: [0.846–0.932]; STD=0.022) with a sensitivity and Positive Predictive Value of high-probability score of 80·3% and 92·3% respectively. Furthermore, a low-probability score excluded SARS-CoV-2 infection with a Negative Predictive Value of 99.5%.InterpretationThe PARIS score based on complete white blood cell count has a good performance to categorize the pre-test probability of SARS-CoV-2 infection. It could help clinicians avoid diagnostic tests in patients with a low-probability score and conversely keep on testing individuals with high-probability score but negative RT-PCR or CT. It could prove helpful in countries with a low-availability of PCR and/or CT during the current period of pandemic.FundingNonePutting research into contextEvidence before this studyIn numerous countries, large population testing is impossible due to the limited availability and costs of RT-PCR kits and CT-scan. Furthermore, false-negativity of PCR or CT as well as COVID-19 pneumonia mimickers on CT may lead to inaccurate diagnoses. Pre-test probability combining clinical and biological features has proven to be a particularly useful tool, already used in clinical practice for management of patients with a suspicion of pulmonary embolism.Added value of this studyThis retrospective study including 400 patients with clinical suspicion of SARS-CoV-2 infection was composed of a training and a validation cohort. The pre-test probability score (PARIS score) determines 3 levels of probability of SARS-CoV2 infection based on white blood cell count (lymphocyte, eosinophil, basophil and neutrophil cell count).Implications of the available evidenceThis pre-test probability may help to adapt SARS-CoV-2 infection diagnostic tests. The high negative predictive value (99·5%) of the low probability category may help avoid further tests, especially during a pandemic with overwhelmed resources. A high probability score combined with typical CT features can be considered sufficient for diagnosis confirmation.

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Utility of Optical Density Values from Heparin-Platelet Factor 4 Antibody Testing and Probability Scoring Models To Diagnose Patients with Heparin Induced Thrombocytopenia.

Blood ◽

10.1182/blood.v108.11.1475.1475 ◽

2006 ◽

Vol 108 (11) ◽

pp. 1475-1475

Author(s):

Kim A. Janatpour ◽

Robert C. Gosselin ◽

William E. Dager ◽

Andrew Lee ◽

John T. Owings ◽

...

Keyword(s):

High Risk ◽

Optical Density ◽

Predictive Value ◽

Platelet Factor 4 ◽

Platelet Factor ◽

Predictive Values ◽

Heparin Induced Thrombocytopenia ◽

Sensitivity Specificity ◽

Test Probability ◽

4T Score

Abstract Background: Heparin induced thrombocytopenia (HIT) is a potentially life threatening complication of heparin administration caused by antibodies directed to the heparin-platelet factor 4 (PF4) complex and characterized by thrombocytopenia with a seemingly paradoxical high risk of thrombosis. Diagnosis is challenging, and is based on both clinical suspicion and laboratory detection of heparin-PF4 antibodies. The Warkentin 4 T’s “pre-test” probability and Chong’s “post-test” probability models have been developed to aid the diagnosis of HIT. Enzyme-linked immunoabosorbant assay (ELISA) laboratory measurement of heparin-PF4 antibodies is commonly used but has a low positive predictive value for thrombosis. Recent reports suggest that using an ELISA optical density (OD) value of ≥ 1 may improve the predictive value for thrombosis. Methods: We performed a retrospective analysis of 105 patients with suspected HIT who were treated with a direct thrombin inhibitor and evaluated the anti-heparin-PF4 ELISA OD values and Warkentin 4 T’s scores for sensitivity, specificity, and positive and negative predictive values (PPV and NPV, respectively) using the Chong’s score to define HITBoth the manufacturer’s OD threshold of 0.4 and ≥ 1 were evaluated. Table 1. Comparison of sensitivity, specificity, and predictive values for 4 T’s and OD levels, alone and in combination Sensitivity (%) Specificity (%) NPV (%) PPV (%) For calculations, Chong’s categories of definite/probable and unlikely were used to define presence or absence of HIT. 4T’s score (high and low) 81 100 80 100 OD level 0.4 69 75 65 78 OD level ≥1 38 85 52 77 4T’s + OD 0.4 94 100 94 100 4T’s +OD ≥1 69 85 81 75 Results: The sensitivity, specificity and predictive value of ELISA alone were inferior to the 4 T’s clinical scorings system. The sensitivity and negative predictive values of the 4T’s score were improved by considering positive or negative ELISA test results. Conclusions: Consistent with previous reports, the PPV of a high probability 4T score alone was 100%. Thus, ELISA results might not change clinical decisions in this situation. Alternative anticoagulation might be inappropriately withheld in 20% of patients if a low probability 4T score alone were to be used for decision-making. The addition of ELISA data using an OD level of 0.4 increased the NPV to a threshold that might be considered clinically acceptable (94%) to withhold therapy. Addition of an OD level of ≥ 1 did not improve the PV of the 4 T’s. However, in contrast to other studies that found better predictive value to using this higher OD threshold, our study group was limited to people considered high risk for HIT. Validation of this strategy in a prospective trial with clinical endpoints should be considered.

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Are We Doing Too Many HIT Tests? II

Blood ◽

10.1182/blood.v126.23.2310.2310 ◽

2015 ◽

Vol 126 (23) ◽

pp. 2310-2310

Author(s):

Ramez Heshmat Awad ◽

Seshan Subramanian ◽

Carlos f. Garcia

Keyword(s):

False Positive ◽

Arterial Thrombosis ◽

High Probability ◽

Elisa Test ◽

Confirmatory Test ◽

Severe Thrombocytopenia ◽

Observation Unit ◽

Probability Score ◽

Low Probability ◽

4T Score

Abstract Back Ground: Heparin Induced Thrombocytopenia is a complex immune disorder related to exposure to heparin that results in arterial and venous thrombosis and moderate to severe thrombocytopenia. Incidence is 0.8-1% in hospitalized patients exposed to heparin. However there is a problem with over testing for HIT syndrome that it is not only financially burdensome but that treating false positive patients with anticoagulation can increase their risk for bleeding. Objective: To determine the actual incidence of Type II-HIT compared to the frequency and necessity of testing in a single urban, teaching, community hospital in Chicago. Methods: A retrospective review of lab records for patients who were tested for HIT syndrome by H-PF4 -ELISA through 2 years Jan 2013-Dec 2014. Then each patient's chart was reviewed. Patients were categorized according to requesting department (i.e. ICU, ED, Medical and surgical floors) then screened for date of admission, date of onset of platelet drop, degree of platelet drop, incidence of DVT, PE, arterial thrombosis and bleeding and finally for possible reasons of platelet count drop other than HIT for calculation of Pretest probability by the 4T score. According to the 4T criteria patients were categorized as low (score 0-3), intermediate (score 4, 5) and high probability (score 6-8). All charts with positive ELISA were reviewed for SRA (Serotonin Release Assay) results. Also contacted lab and pharmacy for cost of HIT testing, confirmatory test with SRA and the cost of Argatroban to be able to determine the economic burden of over testing for HIT syndrome. Results: an average of about 20,000 admissions per year. Over the year 2013, 110 patients were screened for HIT. Over the year 2014, 87 patients were tested for HIT. Of total of 197 tests ordered over the 2 years period 19 Patients did not have enough data in the charts for determination of 4T score and were so excluded. Of the remaining 178, 85(45%) were sent from ICU, 61(32.6%) from Medical floors, 28(15%) from CCU, 9(4.8%) from Surgical floors, 1(0.5%) from Rehab unit, 1(0.5%) from ED and 1(0.5%) from Observation Unit. 17(9.5%) Patients had proven DVT, PE or arterial thrombosis. 2(1%) Patients had evidence of bleeding. According to 4T score139 (74.3%) of 178 were low, 34(18%) intermediate and 5(2.6%) were high probability. ELISA test was positive for only 34(19%) patients of the 178 of which only 3(1.6%) were proven true positive by SRA, 12(6%) had no SRA result in their chart and 19(10.6%) had negative SRA results. ELISA was positive in 22 cases with Low Probability score, 9 Intermediate probability and 3 high probability. Of the 22 low probability ELISA positive cases only 1 (4%) was SRA positive, 15(68%) were SRA negative and 6(27%) did not have SRA in the chart. ELISA test costs 233$, SRA test costs 50$ and one day of Argatroban costs average of 663.44$.Thus the calculated cost of testing for low probability patients reached 32,387 $ for ELISA and 800$ for SRA. Cost of treating false positive patients with Argatroban for an average of 3 days until SRA results are available is 43,758$. Conclusion: From this study we concluded that in our facility we continue to do too many HIT studies without appropriate prescreening with added cost of testing and treatment for low probability patients of almost 77,000$ over the period of two years. In planning to avoid unnecessary testing and treatment for false positive patients we plan to build a 4T score calculator into our Electronic Medical Record System that is started once a HIT test is ordered to improve the screening process. We will also continue work with the Internal Medicine residency program and medical staff to improve teaching on HIT syndrome and other conditions with similar presentations. Table 1. Number of Tests per Department Department Number of tests sent ICU 86(45%) CCU 28(15%) Medical Floors 61(32.6%) Surgical Floors 9(4.8%) Rehab Unit 1(0.5%) ED 1(0.5%) Observation Unit 1(0.5%) Total 187 Table 2. Tests Categorized into Low, Intermediate and High Probability according to 4T score Low Probability Intermediate Probability High Probability 139(74.3%) 34(18%) 5(2.6%) Table 3. SRA Results for ELISA positive patients per Each Probability Category Low Probability Intermediate Probability High Probability 22(64.7%) 9(26.4%) 3(8%) SRA Positive SRA Negative SRA Unavailable SRA Positive SRA Negative SRA Unavailable SRA Positive SRA Negative SRA Unavailable 1(4%) 15(68%) 6(27%) 2(22%) 4(44%) 3(33%) 0 1(33%) 2(66.6%) Disclosures No relevant conflicts of interest to declare.

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Evaluation of the Pre-Test Scoring System (4Ts) for the Evaluation and Management of Heparin Induced Thrombocytopenia

Blood ◽

10.1182/blood.v116.21.2551.2551 ◽

2010 ◽

Vol 116 (21) ◽

pp. 2551-2551

Author(s):

Rodina Vatanparast ◽

Prasad Pillai ◽

Gregory Crane ◽

Steven Minter ◽

Kristine Ward ◽

...

Keyword(s):

Retrospective Study ◽

Scoring System ◽

High Probability ◽

Conflicts Of Interest ◽

Direct Thrombin Inhibitor ◽

Thrombin Inhibitor ◽

Heparin Induced Thrombocytopenia ◽

Low Probability ◽

Turn Around Time ◽

4T Score

Abstract Abstract 2551 The initial diagnosis of Heparin Induced Thrombocytopenia (HIT) is made on clinical grounds, because the assays with the highest sensitivity (Heparin-PF4 Ab ELISA) and specificity (Serotonin Release Assay) may not be readily available and may have a slow turn-around time. The clinical utility of the pretest scoring system, the 4Ts, was developed and validated by Lo, GK et al in the Journal of Thrombosis and Haemostasis in 2006. The pretest scoring system looks at the degree of thrombocytopenia, timing of platelet fall, thrombosis or other sequelae, and the possibility of other etiologies for thrombocytopenia. Based on the 4T score, patients can be divided into high, intermediate, and low probability of having HIT. The American Society of Hematology developed a clinical practice guideline in 2009 incorporating the 4T scoring system in the evaluation and management of patients with suspected HIT. It is recommended that patients with intermediate to high probability for HIT start direct thrombin inhibitor (DTI) therapy without delay. We conducted a retrospective study on 100 consecutive patients who were tested for the HIT assay during their hospitalization at Hahnemann University Hospital in 2009. In the 100 patients analyzed, the distribution of the 4T score of low, intermediate, and high pretest probability were seen in 73, 23 and 4 patients, respectively. A positive HIT ELISA (optical density > 1.0) was detected in 0/73 (0%) of the low probability group, 5/23 (22%) of the intermediate probability group and 2/4 (50%) of the high probability group. The average turn-around time for the HIT ELISA was 4 to 5 days. Fourteen (19%) out of the 73 patients with a low pre-test probability for HIT were treated with a direct thrombin inhibitor (DTI). Ten out of the 14 (71%) patients in the low probability group treated with a DTI had a major complication of bleeding requiring blood transfusion support. Overall, twenty five patients received a DTI. Argatroban was the DTI used in 24 of 25 patients. Fourteen patients started on argatroban had a contraindication for the use of lepirudin. In this retrospective study, a low 4T score correlated 100% with a negative HIT antibody assay. The 4T score also predicted the patients likely to test positive for HIT into the intermediate to high probability group. There was significant patient morbidity in the group with low probability when treated with a direct thrombin inhibitor. Based on previous data and this retrospective study, empiric direct thrombin inhibitor therapy should not be initiated in patients with low probability of having HIT. Moreover, many of these patients were started on the more expensive direct thrombin inhibitor, argatroban. For our institution, if no contraindication exists, we recommend lepirudin for the treatment of HIT because it is easier to monitor and less costly. Furthermore, we recommend incorporating the 4T scoring system into institutional core measures when assessing a patient with suspected HIT, selecting only patients with intermediate to high probability for further therapeutic intervention, which may translate into reduced morbidity and lower health care costs. Disclosures: No relevant conflicts of interest to declare.

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Efficiency of Diagnosing HIT at a Large Academic Medical Center

Blood ◽

10.1182/blood.v126.23.2059.2059 ◽

2015 ◽

Vol 126 (23) ◽

pp. 2059-2059

Author(s):

Marcia N Paddock ◽

Bryce Clark ◽

Maria Teresa De Sancho

Keyword(s):

Laboratory Testing ◽

Conflicts Of Interest ◽

Academic Medical Center ◽

Tertiary Care ◽

Screening Tools ◽

High Morbidity ◽

Reference Laboratory ◽

Heparin Administration ◽

Low Probability ◽

4T Score

Abstract Background: Thrombocytopenia during heparin administration is common in hospitalized patients, leading to frequent testing for heparin-induced thrombocytopenia (HIT). The 4T score, which is based on degree and timing of thrombocytopenia, and whether there are other explanations for thrombocytopenia or the presence of thrombosis, is a commonly used tool to assess the clinical probability of HIT prior to performing laboratory testing. Published guidelines recommend further testing with an anti-PF4/heparin enzyme immunoassay (EIA) and confirmation with the serotonin-release assay (SRA) when the pretest probability of HIT is intermediate or high. The diagnosis of HIT confers high morbidity and mortality; therefore it is crucial to establish a definitive diagnosis in patients with suspected HIT. However, empiric treatment with alternative non-heparin anticoagulants increases the cost of hospitalization and may cause unnecessary risks in patients with a false positive EIA. The purpose of our study was to evaluate the utilization of EIA and SRA at a large tertiary care center and to assess the agreement between the 4T score, the EIA, and the SRA. Methods: We retrospectively reviewed all EIAs performed in our special hematology laboratory and SRAs sent to a reference laboratory at our institution in patients with suspected HIT between July 2012 and June 2014. First we evaluated the 4T score in all patients in whom laboratory testing was requested and subsequently assessed the correlation between the 4T score and the EIA and SRA results. A 4T score of 6 to 8 was high and a 4T score of 4 to 5 was intermediate. A strong positive EIA was defined as an EIA with an optical density (OD) of ≥ 1.00 and a weak/indeterminate EIA had an OD of 0.40-0.99. Results: A total of 583 unique PF4 EIAs were requested during the study period (Figure 1). Of these, 472 (81%) and 77 (13%) were performed in patients with intermediate/ high probability and with low-probability of HIT, respectively and in 34 patients (6%) the EIA was requested without documentation of the 4T score. Of the 472 patients with an intermediate or high 4T score, 36 (8%) had an EIA with an OD ≥ 1.0. Of these 36 patients, 27 (75%) had SRA performed and were positive in 14 patients (52%). Twenty-three (5%) of the 472 patients had a weakly positive EIA and in 18 (78%) of them the SRA was sent and were all negative. Five of the 472 patients (1%) had a positive SRA in the setting of an intermediate or high 4T score and a negative or indeterminate/weakly positive EIA. The SRA was sent in 24 patients with low probability 4T score (0-3) and in 9 patients with no documented 4T score. Two of these 33 (6%) patients had a positive SRA. Overall, the incidence of HIT based on a 4T score of 4 to 8, a positive EIA and positive SRA was found in 16 (3.4%) of the 472 patients; 2 of these 16 patients (12.5%) had a indeterminate/weakly positive EIA. Of the 216 SRAs sent, 21 were positive (9.7%). Patients with a lower pre-test probability based on a low or intermediate 4T score and negative/weakly positive EIA accounted for 33% of HIT cases observed. Patients with an intermediate/high 4T and strong or weakly positive EIA accounted for the remaining 67%. Conclusions: The incidence of definitive HIT in our study was low. There was a poor correlation between the 4T score and SRA positivity and between the EIA and SRA results. The combination of an intermediate/high 4T score and a strong EIA confirmed the diagnosis of HIT in only half of the patients. These findings underscore the need for improved screening tools for HIT. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

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