4T Score Research Articles

HEPARIN-INDUCED THROMBOCYTOPENIA IN MEDICAL ICU: HITTING BACK AT OVER-TESTING

SESSION TITLE: Tuesday Electronic Posters 3 SESSION TYPE: Original Inv Poster Discussion PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM PURPOSE: Heparin Induced Thrombocytopenia (HIT) is a complication of heparin exposure with thrombocytopenia and thrombotic risk. HIT is more common in surgical patients and has a low incidence in medical intensive care unit (MICU) populations. Initial testing for HIT includes antiplatelet factor 4 antibody (PF4 Ab) testing, which has poor specificity. Diagnosis is confirmed days later via the highly specific C-serotonin release assay (SRA). Utilization of a pretest clinical scoring system, the 4T score, can stratify risk and minimize testing in those with low pretest probability. The 4T score categorizes by low, intermediate or high probability of HIT. Scores of METHODS: We performed a retrospective study from a single tertiary academic hospital analyzing PF4 Ab testing for patients from 01/2017 to 12/2017 in our MICU. Chart review was performed for 4T score documentation, SRA results, argatroban exposure, transfusions, and bleeding events. We independently calculated 4T scores with comparison to documented scores. RESULTS: 66 patients had PF4 Ab testing. Retrospectively calculated 4T scores showed 36/66 (54.5%) low probability and 30/66 (45%) intermediate or high probability. Only 20/66 (30.3%) had a documented 4T score. When comparing documented and retrospective 4T scores, 16/20 (80%) had the same probability score. Of those with documented 4T scores, the retrospective 4T scores showed 6/20 (30%) low probability and 14/20 (70%) intermediate or high probability. Of those without documented 4T scores, retrospective scores showed 30/46 (65%) low probability and 16/46 (35%) intermediate or high probability. 13 study patients were started on empiric argatroban. Of these, 6 had a documented 4T score, 4 required transfusion and 1 had a major adverse bleed. 11/66 PF4 Ab tests were positive and 0 had a positive SRA. CONCLUSIONS: Consistent with its rare incidence, we found no occurrences of HIT in our non-surgical study population. An apparent low utilization of the 4T score was found in our study, with only 30.3% of patients tested having a documented score. Of the tested patients without a documented 4T score, 65% had a score of <4 per retrospective calculation. Only 30% of patients with a documented 4T score had a score of <4 which suggests a reduction in over-testing of those with the lowest risk of HIT. Actual reduction of testing secondary to the use of 4T score is difficult to quantify because patients categorized as low risk who did not undergo PF4 AB testing were not captured in the study population. CLINICAL IMPLICATIONS: This study provides a foundation for the promotion of 4T score incorporation and review of its changes in testing patterns and outcomes. DISCLOSURES: No relevant relationships by Cheryl Augenstein, source=Web Response Advisory Committee Member relationship with Roche Diagnostics Please note: $1001 - $5000 Added 03/19/2019 by Robert Christenson, source=Web Response, value=Research Contracts Research Contracts relationship with Siemens Healthineers Please note: $1001 - $5000 Added 03/19/2019 by Robert Christenson, source=Web Response, value=Consulting fee Research Contracts relationship with Becton Dickinson Please note: $1001 - $5000 Added 03/19/2019 by Robert Christenson, source=Web Response, value=Consulting fee Research Contract relationship with Quidel Please note: $1001 - $5000 Added 03/19/2019 by Robert Christenson, source=Web Response, value=Consulting fee Research Contracts relationship with PixCell Corporation Please note: $1001 - $5000 Added 03/19/2019 by Robert Christenson, source=Web Response, value=Consulting fee No relevant relationships by alison grazioli, source=Web Response No relevant relationships by Daniel Herr, source=Web Response No relevant relationships by Mary Richert, source=Web Response

A structured algorithm for judicious use of antibody test in diagnosis of heparin-induced thrombocytopenia (HIT).

314 Background: HIT diagnosis combines 4T scoring &amp; HIT antibodies (HIT-Ab) testing, with confirmatory serotonin release assay (SRA). Latex immunoturbidometric assay (LIA) shows promise in quick &amp; accurate HIT diagnosis, compared to particle immunofiltration assay (PIFA). We designed a HIT workflow &amp; replaced PIFA with LIA at our hospital, to improve 4T usage rates &amp; HIT diagnosis accuracy in a cost-efficient manner. Methods: In phase I, patients (pts) charts with HIT-Ab (PIFA) ordered between Mar2017-Mar2018 were retrospectively reviewed. Three investigators independently calculated 4T &amp; reviewed PIFA/SRA results, with any alternative anticoagulation (AC) used. In phase II, a new workflow on electronic health record incorporating 4T algorithm with HIT-Ab test order was implemented. Our lab replaced PIFA with LIA. In phase II, charts for pts with LIA results from Jan-Mar 2019 were reviewed. Results: In phase I, 170 pts had PIFA results &amp; 5 such pts (0.02%) had 4T score documented in chart. Per investigators, 113 (66.4%) pts had 4T scores. PIFA showed 60% sensitivity &amp; 50% specificity compared to SRA. 19 pts received AC (4 pts had low 4T with negative PIFA). In phase II, 40 pts with LIA tested, 4T scoring by ordering physicians improved to 100%. Per investigators, 42.5% pts had low 4T scores. Clinicians documented high 4T in 11 pts; investigators confirmed high 4T in 2 pts. AC was used in 5 pts (4 with intermediate-high 4T per investigators) Conclusions: Our study showed that incorporation of 4T scoring in HIT algorithm significantly reduced unnecessary ordering of HIT-Ab, with 100% compliance in 4T reporting. Use of AC was consistent with the level of probability by 4T. Further clinician education can help in reduction of up scoring of 4T noted in our results. [Table: see text]

A case of unfractionated heparin-induced thrombocytopenia during the treatment of a gastric stromal tumor

Intensive care unit (ICU) patients are usually at high risk of platelet activation because of a combination of conditions, such as infections, septicemia, and shock. Patients with heparin-induced thrombocytopenia (HIT) have antibodies that recognize platelet factors (PF4) when HIT is in a complex with heparin. HIT is often considered during the differential diagnosis. In this case, the patient suffered from a gastric stromal tumor and liver metastasis and received unfractioned heparin (UFH) to flush the intravascular catheter and anticoagulation in vitro to soak the pipe filter. The PF4-heparin antibody was positive (OD =1.205), and the concentration level was 19.957 U/mL (>18 U/mL) as revealed by semi-quantitative interpretations. According to the clinical information and the 4T scoring system, the 4T score was 5. The patient suffered from HIT after using UFH. Our results suggest that platelet counts of ICU patients should be monitored after the administration of heparin. The patient’s prognosis is good as a result of the early detection of HIT.

Prospective evaluation of heparin-induced thrombocytopenia expert probability and 4T scores in Chinese patients with suspected heparin-induced thrombocytopenia.

Diagnosis of heparin-induced thrombocytopenia (HIT) is challenging. This study aimed to compare the diagnostic performance of HIT expert probability (HEP) and 4T scores, and to evaluate the inter-observer reliability for the 4T score in a clinical setting. This prospective study included HIT-suspected patients between 2016 and 2018. Three hematologists assessed the HEP and 4T scores. Correlations between scores and anti-platelet factor 4 (anti-PF4)/heparin antibodies were evaluated. Receiver operating characteristic curves and area under the curve (AUC) were used to assess the predictive accuracy of these two scoring models. The intraclass correlation coefficient (ICC) was used to assess the inter-observer agreement of 4T scores between residents and hematologists. Of the 89 subjects included, 22 (24.7%) were positive for anti-PF4/heparin antibody. The correlations between antibody titer and either HEP or 4T scores were similar (r = 0.392, P < 0.01 for the HEP score; r = 0.444, P < 0.01 for the 4T score). No significant difference in the diagnostic performance was displayed between these two scores (AUC for the HEP score: 0.778 vs. AUC for the 4T score: 0.741, P = 0.357). Only 72 4T scores were collected from the residents, with a surprisingly low percentage of observers (43.1%) presenting the four individual item scores which made up their 4T score. The AUC of 4T score assessed by residents and hematologists was 0.657 (95% confidence interval [CI]: 536-0.765) and 0.780 (95% CI: 0.667-0.869, P < 0.05), respectively. The ICC of 4T score between residents and hematologists was 0.49 (95% CI: 0.29-0.65, P < 0.01), demonstrating a fair inter-observer agreement. The HEP score does not display a better performance for predicting HIT than the 4T score. With the unsatisfactory completion rate, the inter-observer agreement of 4T score in a tertiary hospital is fair, underscoring the necessity for continuing education for physicians.

PB2257 USE OF ARGATROBAN AS AN ANTICOAGULANT TREATMENT ALTERNATIVE IN CRITICAL PATIENTS WITH HEPARIN‐INDUCED THROMBOCYTOPENIA. EXPERIENCE IN A THIRD LEVEL HOSPITAL.

Background:Heparin is a widely used drug. The most frequent complication derived from its use is the haemorrhage. However, an uncommon but potentially serious adverse effect is heparin‐induced thrombocytopenia (HIT). The goal of treatment of HIT is to reduce platelet activation and thrombin formation to decrease the risk of thrombosis. Argatroban is the drug of choice in HIT patients as an alternative anticoagulant treatment in critically ill patients with high risk of haemorrhage, postoperative cardiac events or renal failure, since it allows close control of anticoagulation.Aims:To analyze the clinical, laboratory and therapeutic characteristics of patients treated with Argatroban by HIT in our hospitalMethods:Retrospective analysis or patients treated with Argatroban for diagnosed HIT during the last year.Results:Four patients have required treatment with Argatroban for HIT since they required maintenance of anticoagulation due to mitral prosthesis, unstable angina, DVT in the right lower extremity and acute ischemia in the left lower extremity. Median age 68 years (43‐79). All of them were diagnosed with HIT according to the 4T score during their admission to the Intensive Care Unit. PF4/Heparin antibody testing was positive in the four patients.The median number of days from the start of Heparin treatment (2 with unfractioned and 2 with low molecular weight) to the onset of thrombocytopenia was 6 days (1‐8). Median platelets at diagnosis were 73x109/L (49‐82). Median number of days from the start of Argatroban to platelet recovery was 6 days (3‐12). Median number of days of treatment with Argatroban was 9.5 days (2‐18). Argatroban dose was adjusted to maintain aPTT at 1.5‐3.0 times baseline. 3 patients presented thrombotic events, 2 directly related to HIT (1 ischemic stroke and 1 acute ischemia of right upper extremity) and 1 with worsening of reperfusion of the limb. 2 patients required amputation of the limb. No adverse events associated with Argatroban, including haemorrhage, were observed.Summary/Conclusion:HIT is a potentially catastrophic complication of heparin treatment which requires urgent detection and treatment with a non‐heparin anticoagulant such as Argatroban should be initiated. Even in critically ill patients, Argatroban anticoagulation improves clinical outcomes in patients who have HIT, without increasing bleeding risk.

Evaluation of heparin induced thrombocytopenia using probability scores in a mechanical circulatory support population.

Patients on mechanical circulatory support (MCS) devices carry a high risk for thrombocytopenia and due to the routine use of heparin, heparin induced thrombocytopenia (HIT) is frequently suspected. HIT Expert Panel (HEP) and 4T scoring tools have been validated in the general medicine population to assess the probability of HIT diagnosis, however, these tests have not been validated for use in patients requiring MCS support. The objective of this study was to assess the association of 4T and HEP scores to available assess HIT diagnostic tests in patients requiring MCS. We conducted a retrospective review of patients requiring MCS who had heparin PF4 antibody optical density and/or serotonin release assay results reported. A 4T and HEP score at the time of heparin antibody ordering was calculated. Utilizing previously described ranges for HIT diagnostic tests, patients were categorized into two HIT probability categories: probable and not probable. Descriptive statistics were used for the 4T and HEP scores in both HIT probability categories and t-test and receiver operating characteristic (ROC) analysis were used to determine the association and agreement between each scoring tool and HIT probability. Eighty-five patients were identified who had HIT diagnostic tests ordered while on MCS; 7 patients were classified as HIT probable and 78 patients were classified as HIT not probable. Based on ROC analysis, 4T score and HEP score had an AUC of 0.88 (± 0.06) and 0.96 (± 0.02), respectively demonstrating high predictability of HIT. Utilizing sensitivity and specificity analysis through ROC curves, a cut off score of 3 for 4T score and 1 for HEP score was established. Based on our analysis, both 4T and HEP scores have high predictability of HIT in the mechanical circulatory support population.

Limited impact of clinician education on reducing inappropriate PF4 testing for heparin-induced thrombocytopenia.

A high frequency of PF4-ELISA testing in patients suspected to have heparin-induced thrombocytopenia (HIT) despite low 4T scores has been observed in multiple medical centers. Education of clinicians has been suggested to reduce inappropriate testing. We determined trends of PF4-ELISA testing in our institution after the introduction of a HIT education program for clinicians. A HIT Program was developed that included ongoing education, individual feedback, and continuous clinical audit of PF4-ELISA utilization. To assess the impact of education on PF4-ELISA testing trends, we conducted a prospective cohort review of all adult patients who had a PF4-ELISA ordered over a 3month period (the last quarter of the academic year). 72 PF4-ELISA tests were ordered during the study period. Prospectively calculated 4T scores by investigators revealed 60 low-risk (83.3%), 9 intermediate-risk (12.5%), and 3 high-risk (4.16%). We observed divergent 4T scores with the ordering clinician calculating a higher 4T score compared to the Hematology Quality Improvement (QI) team. The majority of PF4-ELISA testing was ordered by the intensive care units (ICUs) (n = 32, 44.44%). Our study revealed that the frequency of calculation of 4T scores remains poor with the majority inappropriately performed in the ICU setting, with ordering clinicians calculating higher 4T scores than the Hematology QI team. This suggests that clinician education alone is insufficient. Introducing mandatory 4T score calculation prior to PF4-ELISA testing may not be helpful as ordering clinicians can bypass the restriction through inaccurate 4T score calculation.

Characterization of hospitalized cardiovascular patients with suspected heparin-induced thrombocytopenia.

Little is known about heparin-induced thrombocytopenia (HIT), a pro-thrombotic, potentially life-threatening immune-mediated reaction to heparin exposure, in conservative and interventional cardiovascular medicine. The 4T score, validated for prediction of HIT in surgical patients before, is also suitable for assessing HIT probability in cardiovascular patients with unclear thrombocytopenia. A total of 403 consecutive patients from our Department of Cardiology, Angiology and Pneumology in whom a HIT screening test was performed between 2009 and 2016 were identified. All 72 patients with a positive screening test were subjected to a functional confirmation test (heparin-induced platelet activation test, HIPA), resulting in 23 patients with serologically confirmed HIT (positive screening test, positive HIPA) and 49 patients with nonconfirmed HIT (positive screening test, negative HIPA). The 4TScore had a sensitivity of 82.6% and a specificity of 28.6% in our patients, suggesting that it might not sufficiently predict the clinical probability of HIT in cardiovascular patients. In both confirmed and nonconfirmed HIT, intrahospital mortality was high without a significant difference (30% in confirmed HIT vs 43% in nonconfirmed HIT). Bacteremia was more often found in patients with nonconfirmed HIT, suggesting infection as a frequent differential diagnosis of thrombocytopenia in these patients (49% vs 17%, P = 0.0185). HIT screening should be initiated in cardiovascular patients with unclear thrombocytopenia despite a low 4Tscore in order to distinguish patients requiring alternative anticoagulants from those with other causes such as infections. Further research is needed to specify the risk profile for HIT in cardiovascular patients.

Limited Impact of Clinician Education on Reducing Inappropriate PF4 Testing for Heparin-Induced Thrombocytopenia

IntroductionStudies have shown that medical centers are faced with a major challenge in making an accurate diagnosis of heparin -induced thrombocytopenia (HIT). Some centers have decreased overdiagnosis with the implementation of anticoagulation stewardship programs, collaboration between pharmacy and hospital laboratory, and mandating clinicians to calculate the 4T score prior to testing. A high frequency of PF4-ELISA testing in patients with low 4T scores has been observed in multiple medical centers, including our institution. Education of ordering clinicians has been suggested to reduce inappropriate testing.In this study, we determined current trends of PF4-ELISA testing in our institution after the introduction of a HIT program that included ongoing education, feedback, and continuous clinical audit of PF4-ELISA utilization.MethodsA HIT Program was developed over a 6-year period. This program consisted of: i) providing department-wide lectures to residents, fellows, and attendings on HIT testing and management including 4T score calculation; ii) providing individual feedback from the Anticoagulation and Bleeding Management service to the ordering clinician when a false positive PF4-ELISA test was ordered inappropriately; iii) providing interactive lectures based on real life case scenarios to internal medicine residents on calculating 4T scores.To assess the impact of the education provided on PF4-ELISA testing trends, we conducted a prospective cohort review of all adult patients (age≥18) who had a PF4-ELISA ordered over a 3-month period (the last quarter of the academic year, March - June 2018) at our academic medical center (an 800-bed hospital). The Hematology Quality Improvement (QI) fellow and attending received a list of all PF4-ELISA tests ordered from the laboratory technician daily. All PF4-ELISA tests requested prior to 12pm are resulted on the same day in the afternoon. 4T scores were independently assessed prior to the results being available to avoid bias. Testing trends, 4T scores, ordering services, and documentation of 4T scores by ordering clinicians were assessed.Results72 PF4-ELISA tests were ordered during the study period. Prospectively calculated 4T scores by investigators revealed 60 low-risk (83.3%), 9 intermediate-risk (12.5%), and 3 high-risk (4.16%). 1 patient had a positive serotonin-release assay (SRA); optical density (O.D.) of the PF4-ELISA was 2.499 and 4T score revealed intermediate risk. The 4T score was documented by the ordering team in only 7 cases; 5 of these revealed discordant calculation between the ordering clinician and the Hematology QI team. All documented 4T scores were by Internal Medicine services. In all discordant cases, ordering clinicians' scores were higher than scores calculated by the Hematology QI team. The majority of PF4-ELISA testing was ordered by the intensive care units (ICUs) (n=32, 44.44%), followed by medical (n=20, 27.77%) and surgical teams (n=20, 27.77%)ConclusionOur study revealed that calculation of 4T scores remains poor and is not universally applied, suggesting that clinician education alone is insufficient. We also observed divergent 4T scores with the ordering clinician calculating a higher 4T score compared to the Hematology QI team. As such, introducing mandatory 4T score calculation prior to PF4-ELISA testing may not be helpful as ordering clinicians can bypass the restriction through inaccurate 4T score calculation.The majority of PF4-ELISA testing was performed in the ICU setting. This is concerning as studies have shown that thrombocytopenia is a common laboratory finding in up to 50% of ICU patients. This seems to suggest the difficulties that ordering clinicians have in distinguishing the multiple causes of thrombocytopenia in ICU patients.Further study is required to assess if initiating an automatic non-malignant hematology consult for each PF4 testing would be an effective addition to our continued attempts to decrease inappropriate testing for HIT. DisclosuresNo relevant conflicts of interest to declare.

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

BackgroundThe 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.MethodWe 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.ResultsA 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.ConclusionThe 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. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Enforcing the 4T: Including a Hard Stop 4T Calculator into the Electronic Medical Record for Heparin Induced Thrombocytopenia

Background: Among many causes of thrombocytopenia acquired during hospitalization, heparin-induced thrombocytopenia (HIT), an immune complex-mediated thrombogenic state with high morbidity and mortality, is one of the most feared etiologies. The clinical ‘4T’ score is an established method to assess risk for HIT and guide immediate management(Lo, Juhl et al. 2006). However, the 4T score is not consistently used by clinicians, leading to potential over-testing and suboptimal management of suspected HIT. Our objective in this Quality Improvement (QI) project was to implement a mandatory 4T calculator (4TC) into the electronic medical record (EMR) to improve the positive predictive value of HIT antibody (HITA) testing, decrease the incidence of testing of low-risk patients, and to improve clinical management of suspected HIT.Methods: We developed a 4TC that assisted clinicians by integrating EMR-derived data on heparin exposure and the five most recent platelet counts with a link to an online calculator as well as clinical suggestions (Figure). As a part of this QI project, clinicians were required to enter the calculated 4T score before ordering a polyspecific HITA assay, which serves as the screening test for HIT in our institution. We reviewed laboratory records for all HITA tests performed over a six-month period, including 3 months before and after the implementation of a “hard stop” for HITA order in the EMR. We extracted data on the ordering hospital service team, 4T score documented in notes (if any), as well as quality of care indicators including rates of clinically recommended heparin cessation and initiation of alternative anticoagulation in the subgroup of patients with intermediate or high 4T score at the time of HITA order. In this QI project, we refrained from any statistical testing and summarized pre-specified outcome measures: incidence of HITA testing, positive predictive value of the HITA assay, and quality of care indicators.Results: We identified 99 (53 prior to the 4TC and 46 post) cases of HITA orders in the study period, among which there were 4 cases of confirmed HIT (either with positive IgG or positive serotonin-release assay [SRA]). Three HIT cases occurred after the 4TC was implemented. After the implementation of the 4TC, the positive predictive value for the HITA assay increased from 9% to 21%. The rate of clinically appropriate heparin order discontinuation increased from 72% to 88%, as did the initiation of alternative anticoagulation from 14% to 27%.HITA assay was most commonly ordered by the internal medicine service (35% of tests), non-cardiac intensive care service (30%), coronary care and cardiothoracic surgery services (21%), neurology (5%), and general surgery/other services (9%). Implementation of the 4TC did not significantly change this distribution, but the overall incidence of HITA orders decreased from 4.0 to 3.4 per 1000 admissions. We observed a high frequency of confirmatory SRA testing requested (18%), which is the reflex confirmatory test performed at our institution, even in cases of negative polyspecific HITA or HIT IgG.Conclusions: Addition of a 4T score calculator into the EMR which provides immediate feedback on patient's prior heparin exposure and recent platelet counts allows clinicians to consistently use the 4T score when considering HIT. Importantly, it also helps to educate non-hematologists on the proper management of HIT. Improved predictive value of the HITA assay suggests that our 4TC led to ordering HITA in a more appropriate patient population. We also demonstrated improved quality of care for suspected HIT, with increased rates of heparin cessation and initiation of alternative anticoagulation in patients with intermediate or high pre-test probability. Identifying clinical teams that order a disproportionate number of HITA assays will help us to direct education to improve clinical management. This QI project has led to other areas of improvement, particularly with regard to rational ordering of the SRA. At only three months of review since implementation of the 4TC, we have noted an improvement in the management of suspected HIT and a slight reduction in the incidence of testing. With continued review, we hope to demonstrate further improvement, as practitioners continue to use the 4TC and rely on clinical rationale rather than reflexive laboratory testing when evaluating thrombocytopenia in the hospital. [Display omitted] DisclosuresOlszewski:TG Therapeutics: Research Funding; Spectrum Pharmaceuticals: Consultancy, Research Funding; Genentech: Research Funding. Reagan:Alexion: Honoraria; Takeda Oncology: Research Funding; Pfizer: Research Funding.

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

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. DisclosuresNo relevant conflicts of interest to declare.

Utilizing the Predictive Value of the 4T Scoring System to Reduce Unnecessary HIT Panel Costs in the Community Hospital Setting

AbstractStudy Objective-Heparin Induced Thrombocytopenia (HIT) is a life-threatening immunological response to heparin. The objectives for this study were to determine if the 4T scoring system was being utilized as a tool for predicting HIT, and to look at the costs associated with HIT panels.Methods-This was a retrospective chart review of patients greater than 18 years of age who had HIT panels performed between January 2013 and June 2014 in a community hospital. Any duplicate HIT panels sent during the same admission period were excluded. Study investigators were trained in two 30-minute intervals in the area of data collection and retrospective calculation of 4T score.Results- Of the 154 patients studied, 73 (47.4%) were male, and 81 (52.6%)were female. All patients had a 4T score calculated by study investigators during data analysis, and 1.29% (n=2) had a 4T score calculated before a HIT panel was sent by the team taking care of the patient. 62.3% (n=96) of patients had a low 4T score and 37. 7%( n=58) had an intermediate to high 4T score. Hematology was consulted on 57.7% (n=89) and anticoagulant administration was stopped on 74 % (n=114), while in 26 % ( 40/ 154) heparin was continued despite sending HIT. 25.4%(29/114) were started on alternate anti- coagulants after stopping heparin . Throughout the course of the study, 20 patients died, with only 1 of these patients being HIT positive.If 100 unnecessary HIT panels were performed in a year, the hospital would be charged more than $20,000 by the diagnostic lab. Additional costs include the halting of Heparin administration and starting an alternate anticoagulant such as Argatroban. 24 hour administration of Argatroban costed $1,000 for continuous infusion. HIT panels have a turnaround time of 4-5 days, resulting in the additional charge of $5,000 just for Argatroban administration. A lengthened stay in the hospital due to HIT panel turnaround time is also a source of increased costs. Combined, the ordering of a HIT panel, alternate anticoagulant administration, and bed charges could amount to $40,000 over the course of four days. This time and money could be put to better use treating the underlying disease of the patient, instead of focusing on the testing for HIT.Conclusion-Management of HIT in community hospital was sub-optimal. Lack of utilization of the 4T scoring system led to unnecessary ordering of HIT panels. This increased duration of hospital stay, elevated the cost of treatment, and resulted in the holding of prophylactic anticoagulants. DisclosuresNo relevant conflicts of interest to declare.

Are We Doing Too Many HIT Tests III?

BackgroundIn USA in 2007, it was estimated that approximately one third of hospitalized patients, approximately 12 million patients per year receive heparin. Heparin induced thrombocytopenia (HIT) is one of the serious complications of Heparin resulting from immune mediated antibody.4Ts score is the imperative tool to help differentiate HIT from other causes of thrombocytopenia. The 4Ts score decreases not only risk of bleeding by avoiding anticoagulant but also cost of health care by testing only patients with intermediate to high pretest probability.Our study suggests 4Ts scores calculators are to be introduced as a part of order set for HIT tests.ObjectiveThis retrospective study is Part III of our prior studies “ Are We Doing Too Many HIT tests”, to decrease false positive HIT patients by improving use and awareness about high negative predictive value of 4T score among physicians. This study was carried out to determine outcomes of our previous study of this series in order to assess the reduction of unnecessary ELISA test orders to diagnose HIT in a single urban community hospital in Chicago. MethodA retrospective chart review of medical records of the patients (n=181) who underwent H-PF4-ELISA for HIT screening from January 1st, 2016 to December 31st 2017 was conducted.Data was collected from patient's charts which included the requesting department (i.e. ICU, ED, Medical and surgical floors). Also, date of admission, date of onset of platelet drop, degree of thrombocytopenia, incidence of DVT, PE, arterial thrombosis and bleeding and alternative reasons of platelet count drop other than HIT were collected. For each patient a for calculation of Pretest probability by the 4T score was conducted.We stratified these patients based on 4Ts score (0-3) for low probability, (4-5) intermediate probability and (6-8) high probability risk for HIT.We reviewed all charts for which both ELISA and SRA were ordered. Pharmacy department and Hematology labs were contacted to calculate costs of ELISA, SRA and anticoagulation.ResultsOur results showed that 114 (62.98%) of 181 ELISA tests ordered had low pretest probability for HIT. None of these records were found to be true positive by SRA. However, 24(20%) of low probability category were found positive by ELISA and received anticoagulation and thus were exposed to higher risk of bleeding and additional health care costs.There were 57 (31.49%) out of 181 records had intermediate probability. 16 patients with intermediate probability were ELISA test positive. However, 3 (5.26%) of intermediate probability patients were found to be true positive by SRA.While only 6 (3.31%) out of 181 patients records had high probability for HIT and 3 patients (50%) of high probability were found to be true positive by SRA.However, 11 patients from low probability category and 5 patients from intermediate probability category did not have SRA results in their medical record.DiscussionIn our previous study, 74.3% of patients tested for HIT during Jan.2013 to Dec. 2014were found to have low probability compared to 62.98% of our current study.Interestingly, patients with intermediate probability have increased to 31.49% from 18% from our previous study. This is a desired decreased.Cost for ELISA test for HIT ranges $200 to $300 per test and cost of SRA is roughly $50 to $60. Cost of one day of Argatroban treatment is roughly $670 which brings the total cost per patient roughly $1000 per day for all those patients who are tested positive by ELISA.34,200 USD were spent on ELISA test for 114 patients with low probability 4T score who were found true negative.Furthermore, 20 patients with false positive ELISA from low probability 4T category were exposed to 40,200 USD worth of Argatroban during three days while SRA results were awaited.As per our study, educational interventions in our hospital have made remarkable improvement in decreasing the number of ELISA test in patients with low pretest probability from 74.3% to 62.98%Lastly, more than 74,000 USD per 114 patients (with low probability score) could be reduced by introducing “4T score calculation Alert” as a part of order set for HIT in EMR software.We conclude that incorporating prescreening for HIT with 4T score calculation as a part of order set for ELISA could decrease not only the risk of bleeding but also avoidable additional health care cost. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Confirmation of the Utility of the 4T Scoring System for HIT

Background: Heparin-induced thrombocytopenia (HIT) is a complication of heparin-based anticoagulation (AC) resulting in thrombocytopenia and thrombosis. Laboratory testing can often be avoided as the 4T score (4TS) has a negative predictive value (NPV) of 0.998 for low risk patients. Despite this scoring system, which has been validated since 2006, physicians continue to send inappropriate studies despite a low probability of HIT. We sought to evaluate our academic institution's compliance, perform a cost analysis and determine if appropriate AC was initiated. By analyzing our data, we sought to educate our staff and implement measures to improve cost efficiency and quality of care.Methods: We performed a retrospective chart review of patients admitted to Hahnemann University Hospital (HUH) between November 1, 2016 and April 30, 2017 who had HIT antibodies (HITAb) and serotonin release assay (SRA) studies. These laboratory tests were performed at Quest Diagnostics. This data was compiled from the EMR at HUH. According to the 4TS, patients were assigned a score of 0-8: 0-3 for low, 4-5 for intermediate, 6-8 for high probability respectively. Laboratory results of HITAb and SRA were then compared to the calculated 4TS. We then investigated whether appropriate AC was initiated. Data on the cost associated with the inappropriate management of suspected HIT was compiled.Results: 72 patients had HITAb sent during the interval studied. Table 1 shows the 4TS and results of HITAb and SRA testing. Table 2 lists the AC used based on the 4TS.The NPV of not having HIT in the low probability group was 100%. The positive predictive value (PPV) of having HIT in the high probability group was 100%. At our institution, HITAb with reflex SRA costs $503. Expenditure due to inappropriate testing was estimated to be around $23,000 dollars over the study's time course. Inappropriately switching to argatroban cost up to $1,000 per day or fondaparinux $500 per day of overspending on anticoagulation per patient.Discussion: We found the majority of HITAb and SRA testing was unnecessary based on the 4TS. Our data showed a low 4TS had a very high NPV confirming the scoring system's utility. HIT testing was often overutilized as part of a general workup for thrombocytopenic patients who were often septic, on marrow suppressive medications and had multiple comorbidities such as hepatitis and HIV infections which confounded their clinical picture. Furthermore, this scoring system had a very high PPV in the high probability group. This study confirmed that HIT laboratory studies rarely change patient management in these scenarios. With the turnaround time of laboratory studies taking up to 4 days, there is a significant increase to the cost of patient care when solely relying on HITAb and SRA due to the use of expensive anticoagulants. In contrast, it remains unknown if HITAb and SRA could be useful in patients with an intermediate 4TS as our data is limited with no SRA results for patients with intermediate scores and a positive HITAb.To prevent unnecessary testing in the future and to improve the management of HIT, we propose to implement the following at our institution: 1. create a hard stop in our EMR which would prevent studies from being sent off inappropriately; 2. add a 4TS to the calculator section of the EMR and encourage collaboration with the hematology department if additional questions remain after calculating a 4TS; 4. start resident based educational sessions on the importance of calculating a 4TS and its significance prior to sending laboratory studies. In conclusion, the 4TS remains a useful tool to prevent unnecessary diagnostic testing and use of expensive therapeutic anticoagulants in patients with suspected HIT. DisclosuresNo relevant conflicts of interest to declare.

Hypofibrinogenemia in Patient with Extended Exposure to Argatroban Therapy

A 42 year old female with past medical history of asthma and recent admission for Alprazolam overdose presented to our hospital with dyspnea and generalized weakness.. She was noted by paramedics to be hypoxic, hypotensive and bradycardic, and she was intubated in the field prior to arrival.. Medication prior to admission, Albuterol HFA. Patient had no known drug allergies. On presentation to the emergency department, patient appeared critically ill, hypotensive to 74/50 , hypoxic with oxygen saturation of 60%, heart rate of 137 BPM, respiratory rate 15/min, temp 99 F, and unresponsive to verbal stimuli. Endotrachial tube placement was confirmed using laryngoscope. Whilein ED, patient went into Pulseless Electrical activity state and CPR was started immediately. She was given one round of Epinephrine with return of spontaneous circulation after 3 minutes.Bedside transthoracic echo suggestive of right heart strain, patient was given Tenecteplase given high risk of Pulmonary embolism. She was then transferred to the Intensive care unit and was started on pressure support.. Initial Chest CT angiogram showed no signs of pulmonary embolism. Pertinent laboratory values at admission were, serum Creatinine 1.28 mg/dl , WBC 14 K/mcl, HGB 12/4 g/dl, Platelet count 186 K/mcl, PT 12.4 sec, INR 1.1, APTT 29.9 sec, Arterial blood gas with PH 7.039, PCO2 70.9 mmhg, PO2 35.9 mmhg, HCO3 18.2 mmol/l and Lactate 11.0 mmol/l. Hepatic function panel showing Albumin 3.7 gm/dl, Total protein 7.2 gm/dl, Total Bilirubin 0.6 mg/dl, Direct Bilirubin 0.1 ml/dl, ALK Phos 95 U/L, ALT 58 U/L, AST 73 U/L.Patient respiratory status improved and was extubated on day 2, she was transferred to step down unit. Patient initially was on DVT prophylaxis dose of LMWH 5000 unit at bed time. However on day 5 laboratory values were notable for a drop in Platelets to 37 K/mcl, suspicion that patient developed HIT as 4T score of 6 ( high probability of of HIT 64%) which was confirmed with positive Serotonin releasing essay. On day 6 post admission, patient reported right calf pain, venous duplex studyof the lower extremity was performed showing lack of compressibility in right proximal, middle and distal superficial femoral veins consistent deep venous thrombosis . A lung perfusion scan was done showing high probability of pulmonary thromboembolic process. Administration of Argatroban was initiated at 2 mcg/kg/min IV titrated to goal of APTT 1.5-3x of baseline up 100 sec. Subsequent daily labs showing continuous drop in Fibrinogen levels(persistent <35 mg/dl, Normal 233-394) with appropriate increase in APTT values ( therapeutic goal of 45-90) and normal PT, INR values.Subsequently, patient was receiving fresh frozen plasma twice daily. After careful review of the case with hematology consult, the drop in Fibrinogen levels was noted to be corresponding with he 12 days of Argatroban administration, so decision was made to stop Argatroban and switch to fondaparinaux. Fibrinogen values returned to normal within 1 day of discontinuation of Argatroban therapy (bridging to W arfarin), raising the concern for Argatroban induced hypofibrinogenemia. DisclosuresNo relevant conflicts of interest to declare.

Evaluation of STic Expert® HIT Kit and Its Comparison with ID-PaGIA™ Test in Suspected Heparin-Induced Thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction caused by heparin. HIT occurs due to IgG antibodies directed against heparin-bound platelet factor 4 (PF4). The aim of this study was to evaluate the STic® Expert HIT for detection of anti-PF4/heparin antibodies in comparison with ID-PaGIA™ kit. The results were further confirmed by Heparin-induced platelet aggregation test (HIPA). A total of 17 patients with a suspected diagnosis of HIT were enrolled. The 4T scoring of each case was performed. Testing for HIT was carried out by ID-PaGIA™, STic® Expert HIT, and HIPA. Testing by STic® Expert HIT test demonstrated positivity in three cases while testing by ID-PaGIA™ test kit revealed four positive cases. Two of these cases were confirmed as HIT by HIPA. The study suggests that STic® Expert HIT an equally effective test, in combination with the 4T scoring system for detecting/excluding the diagnosis of HIT. A large number of cases are needed for validation.

Incidence of heparin-induced thrombocytopenia in lower-extremity free flap reconstruction correlates with the overall surgical population

Lower-extremity free flap reconstruction is a growing trend in the management of lower extremity wounds. Heparin-induced thrombocytopenia (HIT) is a significant risk to free flap reconstruction. The purpose of this study was to investigate the incidence of HIT in patients receiving lower-extremity free flap surgery. We conducted a retrospective, single center, IRB approved cohort study in which we reviewed all patients who received lower-extremity free flap surgeries between 2011 and 2016. The 4T and HIT Expert Probability (HEP) scores were calculated to assess the likelihood of HIT. One hundred patient charts revealed three patients with HIT. One patient was excluded due to a prior diagnosis of HIT. HIT incidence in patients receiving lower-extremity free flaps was between 1% and 3%, which is consistent with the national average. 4T scores indicated that two of three HIT-positive patients had a high probability of HIT (approximately 64%), and one of three HIT-positive patients had an intermediate probability (approximately 14%). HEP scoring indicated that all the three (100%) patients had HIT. These data suggest that the incidence of HIT in patients receiving lower-extremity free flaps correlates with the incidence of HIT nationally. The use of available scoring methods and other algorithms, combined with patient history helps to assess the immediate perioperative risks of HIT in the absence of rapid immunologic confirmatory tests. This knowledge can allow for successful free flap salvage or for performance of free flaps in patients with a history of HIT.

A novel diagnostic algorithm for heparin-induced thrombocytopenia.

While diagnostic algorithm using PF4-heparin enzyme-linked immunosorbent assay (ELISA) optical density (OD), and heparin neutralization assay (HNA), or 4T score have been proposed to replace serotonin-release assay (SRA) for heparin-induced thrombocytopenia (HIT), their performance against SRA is unclear. In this study, we proposed and validated the performance of a new algorithm combining PF4-heparin ELISA optical density (OD), HNA and 4T score against SRA for HIT diagnosis. Heparin neutralization assays were performed on specimens submitted for HIT testing with positive PF4-heparin ELISA from December 2015 to September 2017, which were separated into a "training" and a "validation" data set. 4T scores were calculated for ELISA positive cases. A total of 123 consecutive unique patient samples had positive PF4-heparin ELISA with also HNA data, SRA data, and 4T scores available. Compared to SRA, a "laboratory criteria" (ELISA OD≥1.4 and HNA≥70%) had a sensitivity of 88% (14/16) and specificity of 91% (42/46), and a "combined criteria" (4T score=8, or 4T score=6 or 7 and ELISA OD≥1.0, or 4T score=4 or 5 and ELISA OD≥2.0) had a sensitivity of 75% (12/16) and specificity of 98% (45/46) in the training data set. Laboratory and combined criteria had 90% (56/62) concordance rate. Importantly, for these concordant cases, the diagnostic specificity is 100% (46/46). Based on the data, a novel diagnostic algorithm combining these 2 criteria was proposed and validated prospectively. A novel algorithm has high diagnostic accuracy and potentially could eliminate the need for SRA testing in at least 90% patients with suspected HIT.

HIT or miss? A comprehensive contemporary investigation of laboratory tests for heparin induced thrombocytopenia

Heparin induced thrombocytopenia (HIT) is a rare but potentially fatal complication of heparin therapy, which in a proportion of patients causes platelet activation and thrombosis. Initial clinical assessment of the likelihood of HIT is facilitated by laboratory testing to confirm or exclude HIT. This prospective investigation was performed over an 18-month period, and has involved testing of over 300 test samples from over 100 consecutive patients. Clinical assessment by 4T score was supplemented by laboratory tests that comprised both immunological [lateral flow ('STiC'), chemiluminescence (AcuStar; HIT-IgG(PF4-H)), ELISA (Asserachrom HPIA IgG)] and functional assays [SRA, platelet aggregation using whole blood ('Multiplate') and platelet rich plasma ('LTA')]. We observed both false positive and false negative test findings with most assays. Overall, the whole blood aggregation method provided a reasonable alternative to SRA for identifying functional HIT. STiC, AcuStar and ELISA procedures were fairly comparable in terms of screening for HIT, although STiC and AcuStar both yielded false negatives, albeit also resulting in fewer false positives than ELISA. The 4T score had less utility in our patient cohort than we were expecting, although there was an association with the likelihood of HIT. Nevertheless, we accept that our observations are based on limited test numbers. In conclusion, no single approach (clinical or laboratory) was associated with optimal sensitivity or specificity of HIT exclusion or identification, and thus, a combination of clinical evaluation and laboratory testing will best ensure the accuracy of diagnosis.