Heparin-induced Thrombocytopenia Antibody Test Research Articles

When HIT Testing Hurts- the Financial and Clinical Repercussions of Heparin Induced Thrombocytopenia Testing: A Single Center Analysis

Introduction: Thrombocytopenia is a common inpatient hematologic concern. Most often, thrombocytopenia is a multifactorial phenomenon, without one clear cause. Heparin Induced Thrombocytopenia (HIT) is a rare but serious hematologic consequence of exposure to heparin. In many hospitalized patients, heparin is routinely used as venous thromboembolism (VTE) prophylaxis or for therapeutic anticoagulation. The incidence of HIT is approximately 0.5-1.0% in patients exposed to unfractionated heparin (UFH). Though rare, there seems to be over-testing of HIT antibody in the inpatient setting. As such, there is potential for high cost with low yield and false positives that alter patient management, resulting in prolonged hospital stays and further complications in patient care. Methods: This was a retrospective, observational study reviewing the indications, results, and patient characteristics of cases in which HIT testing was ordered. Indications for testing and influence of results on management were determined based on clinical documentation. The tests of interest included HIT antibody testing and Seratonin Release Assay (SRA). We analyzed how many times a HIT antibody was positive with a negative result in the SRA. We also determined whether there was an increased length of stay in patients who had HIT testing ordered. The study population included patients who were admitted to University of Florida Shands Medical Center, an academic institution in Jacksonville, FL in 2022. All patients were >18 years of age. Results: 190 patients were identified, for whom 190 HIT antibody tests were ordered and 75 SRAs. All patients who had a SRA performed had exposure to low dose heparin or therapeutic high dose heparin. Out of 190 patients, HIT testing was positive in 30 patients (15.8%). SRA testing was performed on 75 patients despite only 30 positive HIT tests. The true positives were 10 patients who had positive SRA confirmatory testing out of 190 patients with suspected HIT. Based on the results of confirmatory testing, the false positive fraction of HIT testing was 66%. When analyzing the 190 patients who underwent HIT testing, the average length of stay was 14 days. On average, a hospital stay in the US is 5.5 days and evaluation of HIT results in 8.5 additional days of hospital admission at our institution. The prolonged length of stay for HIT testing is likely impacted by awaiting SRA results along with other factors. Conclusion: This analysis examines the relative over-testing for HIT at a single institution. Compared with the known incidence of positive HIT tests, there is a significant number of positive HIT antibody tests at our hospital. The data further reveals a high probability of a false positive HIT antibody test results in the hospitalized patient, possibly due to immune reactivity. Of 190 patients suspected with HIT, only 10 patients had a positive confirmatory SRA, indicating that only 5% of suspected patients truly had HIT. This demonstrates that 95% of the time HIT assays ordered did not provide clinically useful information. From the time work up was initiated to the time of discharge, the average stay length was 14 days in a patient suspected with HIT. Cost burden of HIT testing was evaluated. Each HIT panel is $153.83 and each confirmatory SRA test is approximately $250, at a commercial laboratory. Taken together, the total average cost per patient with suspected HIT is $413.83 in diagnostic testing. Prolonged hospital stay contributes to approximately $25,000 increase in hospital stay per patient being evaluated for HIT. This does not include the cost of further work up or interventions. Changing to an alternate anticoagulant such as Argatroban increased costs by nearly $1,500 per case and this number increased further when adding the daily coagulation panel required while on this drug. In other studies, this cost has been estimated to add $90,000 to the hospital stay. Prolonged hospital stays are also associated with unintended incidents such as GI bleeding leading to blood transfusions, invasive testing (such as endoscopy/colonoscopy) and increased morbidity to the patient. We will use this information to implement a tool in our Electronic Medical Record (EMR) that will require answering the 4T score in order to establish high pre-test probability, prior to ordering HIT antibody testing at the University of Florida in Jacksonville.

Cost-Effectiveness and Return on Investment Analysis of an In-house HemosIL Heparin-Induced Thrombocytopenia Antibody Assay at a Mid-Sized Institution.

Laboratories face the challenge of providing quality patient care while managing costs and turnaround times (TATs). To this end, we brought the heparin-induced thrombocytopenia (HIT) antibody test in-house with the goal of reducing costs and the time to diagnosis. To determine the cost-effectiveness and return on investment of our in-house HIT antibody test by comparing it to send-out assays with TATs of 2, 3, or 4 days. We performed a retrospective chart review of all patients with a HIT antibody assay and analysis of laboratory financial records. Analysis included the percentage of patients receiving alternative treatment, cost of treatment, startup costs of bringing the test in-house, and average TAT of the in-house test. We found significant reductions in the cost of treatment for patients and the overall cost to the health care system. The in-house assay became cost-effective at between 8 and 20 tests, with a return on investment of up to 298%. Bringing the HIT antibody assay in-house becomes cost-effective at a very low test volume with excellent return on investment. This novel analysis can provide a framework for other laboratory medicine professionals to analyze the benefits of bringing this and other assays in-house.

Importance of gradual induction in oral anticoagulation therapy in a patient with heparin-induced thrombocytopenia with a left ventricular assist device: a case report

BackgroundWe encountered a case of a patient with heparin-induced thrombocytopenia (HIT) who developed multiple thromboses following implantable left ventricular assist device (iLVAD) implantation. We herein report this case along with a literature-based discussion on the timing of warfarin initiation for such patients.Case presentationA 15-year-old boy was rushed to our hospital due to cardiogenic shock associated with multiple organ dysfunction. A detailed examination, including cardiac catheterization and right heart biopsy, provided a diagnosis of dilated cardiomyopathy, for which an iLVAD placement as a bridge to cardiac transplantation was scheduled after the transplant workup. Three days before the surgery, the patient’s platelet count decreased drastically from 110,000 to 40,000/µL, suggesting HIT, and his blood sample was sent to a specialized laboratory outside our hospital. The HIT antibody test came back positive during the iLVAD implantation using heparin. Thus, we chose argatroban over heparin for postoperative anticoagulation therapy, which was initiated 6 h after the surgery. The day after surgery, the patient was successfully weaned off mechanical ventilation and extubated. Oral anticoagulation therapy with warfarin was also initiated; however, on postoperative day 2, contrast-enhanced computed tomography revealed multiple thrombi in the left iliac artery, right iliac vein, and right jugular vein. We suspected hypercoagulation associated with the initiation of warfarin, prompting us to suspend warfarin and continue anticoagulation therapy with argatroban alone. On postoperative day 8, the patient’s platelet count increased to 130,000/µL despite not reaching the normal range and showed two consecutive increases; therefore, we resumed oral warfarin, concerning the efficacy of argatroban as an anticoagulant for iLVAD. Thromboembolism did not recur; the patient was discharged 50 days after the operation and is currently awaiting heart transplantation.ConclusionsWe encountered a case of HIT type II in which multiple thromboses occurred following iLVAD implantation. If HIT antibodies are detected, it is crucial to initiate argatroban monotherapy and wait to start oral anticoagulation therapy with warfarin until platelet count has improved.

Diagnosis and Management of Heparin Induced Thrombocytopenia — Are We Choosing Wisely?

Introduction :Thrombocytopenia is a common problem in hospitalized patients. One of the rare but fatal causes of thrombocytopenia is Heparin Induced Thrombocytopenia (HIT), a complex immune disorder in which heparin leads to the production of IgG antibodies, targeting platelet factor 4 (PF4). Not diagnosing HIT when it is present or mistakenly diagnosing HIT when it is absent, both carry significant risks (eg, life-threatening thrombosis or life-threatening bleeding, respectively). Various institutional reviews have reported that clinicians tend to have a high suspicion and low threshold to order laboratory workup for HIT though the incidence of HIT is noted to be only 5%. The American Society of Hematology Choosing Wisely Guidelines 2014 recommend against testing for HIT in individuals at low risk, defined by a 4T score ≤ 3.The primary objective of our study was to examine compliance with guidelines at our institution. Secondary objectives were to assess correlation between 4T's score, HIT antibody and Serotonin Release Assay (SRA) in diagnosis of HIT, impact of Hematology consult on following appropriate guidelines.Methods:Patients with requests for HIT antibody testing between 1/1/2015 - 12/31/2016 were identified from laboratory records. A retrospective chart review was conducted on 92 patients who met criteria. Data collected included admitting department, clinical probability based on 4T's score, result of HIT antibody including optical density (OD), result of SRA, placement of Hematology consult, initiation of novel anticoagulant (NOAC). Using the algorithm below (Fig 1) , compliance with guidelines was analyzed. Data were tabulated by means of simple frequencies for single items, or in 2- or 3-way combinations.Results:Of the 92 charts reviewed, 38 (41.3%) patients had a low clinical probability based on 4T's score and yet had HIT antibody test ordered (table 1). Of these, heparin was stopped in 21 (55.3%) patients and NOAC was initiated in 10 (26.3%) patients (table 2) which is not recommended as per existing guidelines. Interestingly, of the 38 patients with low probability, 19 (50.0%) had OD between 0.4 - 1.99 with 1 positive SRA. Among 43 (46.7%) patients with intermediate clinical probability, 29 (47.5%) patients were HIT positive. Of these, 18 patients with OD < 2 and 21 patients with OD between 0.4 - 1.99 had SRA ordered which is not in compliance with guidelines, however 6 of these patients had positive SRA. 11 (12%) of the 92 patients had high clinical probability, and of these, in patients with OD> 2, SRA was positive 100% of the times; where as in patients with OD between 0.4 - 1.99 SRA was positive only in 45.5% patients. Hematology oncology service was consulted for 44 (47.8%) patients with positive HIT of which 7 had high probability, 22 had intermediate probability and 15 had low clinical probability; heparin was stopped and NOAC was initiated in 5(71%), 12 (54%), and 8 (53%) patients in each of these groups respectively which once again is not in compliance with existing guidelines. Majority of patients were admitted to ICU, however only 3.8% of ICU patients who had HIT antibody ordered had confirmed diagnosis of HIT.Conclusion:Compliance with Choosing Wisely Guidelines and recommended diagnostic algorithm for HIT at our institution is low, and potentially associated with significant harm to the patient due to overtesting and overtreatment. Hematology Oncology consult did not necessarily improve compliance with guidelines, although decision about NOAC were made prior to consult in most cases. However, while there was concern for overdiagnosis and wasteful resources, our study also noted that there were few patients with low clinical probability and intermediate clinical probability with OD between 0.4-1.99 with positive SRA. Limitations of our study is the small sample size and single institution based data. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Research on clinical characteristics and prognostic analysis of heparin-induced thrombocytopenia after surgery for acute type a aortic dissection

PurposeThe present study aimed to explore the clinical characteristics of heparin-induced thrombocytopenia (HIT) after surgery for acute type A aortic dissection and perform a relevant prognostic analysis.MethodsAfter continuous observation and analysis of 204 patients who underwent acute type A aortic dissection, we found that blood platelets decreased significantly after surgery and that these patients can be suspected to suffer HIT based on relevant 4Ts scores. For these suspected HIT patients, a latex particle-enhanced immunoturbidimetric assay was conducted to detect heparin-induced antibodies. Perioperative clinical data of patients in HIT and non-HIT groups were recorded as were blood platelet counts, HIT antibody test results, 4Ts scores, thromboembolic complications, clinical prognosis and outcomes.ResultsIn the present study, 38 suspected HIT patients, 16 HIT patients and 188 non-HIT patients were selected in the clinical setting. Among them, HIT patients were found to have prolonged cardiopulmonary bypass time (223 min on average vs. 164 min) and delayed aortic cross-clamp time (128 min on average vs. 107 min), and these differences between HIT patients and non-HIT patients were significant (P < 0.05). Additionally, the HIT group required longer operation time and higher dose of heparin, but showing no statistical differences (P > 0.05). The transfusions of blood platelets in the HIT group and non-HIT group were 18.7 ± 5.0u and 15.6 ± 7.34 u, respectively. In the HIT group, the mechanic ventilation time and the length of ICU stay were longer comparing the non-HIT group(P < 0.05), though no significant differences in total length of stay or In-hospital mortality were observed (P > 0.05). The incidence of continuous renal replacement therapy in HIT group was higher than the non-HIT group (P < 0.05). Additionally,there were no significant differences in 24-h postoperative drainage or reoperation for bleeding in both group(P > 0.05). However, the HIT antibody titer in the HIT group was significantly higher than that in the Suspected HIT group (2.7 ± 0.8 U/mL vs. 0.3 ± 0.2 U/mL) (P < 0.05). Among patients diagnosed with HIT, the incidence of thromboembolism reached 31.5%.For example, two HIT patients newly developed thromboembolism in both lower extremities,and three patients experienced cerebral infarction.ConclusionsAfter surgery for acute type A aortic dissection, HIT patients developed postoperative complications, the duration of ventilatory support and length of ICU stay were extended, and the incidence of thromboembolism increased. HIT antibody detection and risk classification should be implemented for high-risk patients showing early clinical characteristics.

Prediction of Heparin Induced Thrombocytopenia (HIT) Using a Combination of 4Ts Score and Screening Immune Assays

Clinical assessment (4Ts) followed by testing for Heparin/platelet factor 4 (HPF4) antibody in intermediate and high risk patients is the standard algorithm of pretest for Heparin induced thrombocytopenia (HIT), and the diagnosis is confirmed by serotonin releasing assay (SRA) in those who have positive antibodies. We conducted a retrospective analysis in a cohort of patients treated in a community hospital who had HIT antibody test by either ELISA or a rapid Particle Immunofiltration Assay (PIFA), regardless of their 4Ts scores. Among 224 patients, 17 had HIT. The PPV for those with a 4 T score ≥4 was 10.4%, which misdianosed 3 patients with HIT who tested positive for antibodies. Combining 4 T score ≥4 AND positive HIT antibody showed a PPV of 20.3% and a sensitivity of 70.6%, misdiagnosing 5 HIT patients. Using 4Ts ≥4 OR positive HIT antibody showed 100% sensitivity and 100% negative predictive value (NPV). The ELISA test had 100% sensitivity and 100% NPV, while the PIFA test missed 2 HIT patients, with sensitivity of 60% and NPV of 96.7%. Our results suggest that SRA testing should be conducted if a patient presents with a 4 T score ≥4 OR a positive HIT antibody, and antibody tests should be conducted for every patient suspected of HIT.

Is Heparin Induced Thrombocytopenia Expert Probability (HEP) Scoring System Superior to 4T'S Scoring in the Diagnosis of Heparin Induced Thrombocytopenia? a Prospective Observational Study from a Tertiary Care Cardiac Centre in India

Heparin-induced thrombocytopenia (HIT) is a drug-induced thrombocytopenia that results in thrombotic complications rather than bleeding.In many countries like India, the availability of functional assay for diagnosing HIT is unavailable. But with the utility of scoring systems the probability of HIT can be assessed and can guide the intervention required. Presently there are two well characterised and easily calculated scoring systems, which are the commonly used 4T scoring system and newly designed HEP score, to overcome some of the limitations of 4T`s scoring system. The 4Ts score has a negative predictive value (NPV) approaching 100%, but is limited by modest positive predictive value (PPV) and significant inter-observer variability.In this study we are comparing the two scoring systems and their relevance in the Indian scenario in patients undergoing cardiac intervention, receiving heparin. METHODS: - We recruited 100 patients with suspected HIT, for whom antibody testing was orderedat our centre (Narayana Health City, Bangalore, India) between November 2017 and May 2018. - Data were collected at baseline diagnosis in the form of clinical and laboratory data. 4T`s score and the HEP score was calculated based on the above details before the availability of antibody test. - HIT antibody testing was done using ID-PaGIA Heparin/pF4 Antibody Test Kit with control. In this 10 millilitre of serum is pippeted into the upper chamber of the appropriate microtube. Incubate the ID card at room temperature for 5mins at room temperature (18-25oc). Later centrifuge the ID-card for 10mins in the ID-centrifuge then read and records the results. - Patients were followed up daily till the discharge and complete blood picture including WBC count, development of any adverse effects including renal failure, sepsis, intra-arterial device insertion, bleeding was noted. - Area under the curve (AUC) for the receiver operating curve (ROC) of HEP and 4T scores was calculated and p value was obtained based on these curves. RESULTS: - 37 patients were HIT antibody positive out of 100 patients with suspected HIT from a patient population of 26430, who received heparin. The overall incidence of HIT in our institute is 0.14% (37/26430). - Out of the 100 suspected patients 37 were proven to have HIT by using ID-PaGIA Heparin/PF4 rapid gel agglutination assay. In this series, 91% patients had undergone cardiothoracic surgery forming the majority. Two-thirds of the study population was in the age group (41-70years). Males (61%) are more in the study than females (39%).The percentage of HIT positivity was more in females (43.5) than males (32.7%). - In 87 patients who received UFH, who presented with thrombocytopenia during their perioperative period, 30 were proven to have HIT (34.4%).We also observed during that the total leucocyte count at the nadir of platelet was higher in thr HIT positive group. However, it was not statistically significant (p-0.283) - Out of 100 patients with suspected HIT 49% expired. Of the 37 cases proven to have HIT 20 patients expired (54%). There was no statistically significant association between the occurrence of HIT and mortality ( p-value =0.438). - In this study, the areas under the curve for predicting HIT by 4T score was more than HEP score (0.754 and 0.66) with P value-0.093. As the HEP score was not superior to 4T score we have evaluated 2 subgroup analysis. - Among 36 subjects with the intra-arterial device (included in HEP score), 12 were positive for HIT (33.3%). Area under the Curve for the 4T score (0.698) was higher than that for HEP score (0.599) although the difference was not statistically significant(p-0.3906) - In this study, the incidence of renal replacement therapy (not included in HEP score)was 43%. In this patient population, 46% (n=20) are HIT positive. Among subjects on RRT, 4T score (814) had higher Area under the curve compared to HEP score (0.607) in the diagnosis of HIT positivity and the difference was statistically significant (p value 0.035). CONCLUSION The newly diagnosed HEP scoring system, which includes additional causes of thrombocytopenia was not superior to the 4T's score in this study. The inclusion of intra-arterial device in the HEP score did not make a difference in prediction of HIT. Conversely the 4T score was superior to HEP score in the evaluation of the subset of patients on renal replacement therapy, a significant cause of thrombocytopenia, which was not included in the scoring system. Disclosures No relevant conflicts of interest to declare.

Diagnostic Performance of Heparin-Platelet Factor 4 Antibodies in the Identification of Heparin-Induced Thrombocytopenia in Cancer Population

Introduction: Cancer patients appear to have a higher risk of heparin induced thrombocytopenia (HIT) related complications than non-cancer patients; yet data on the performance of conventional diagnostic tools for HIT in cancer is limited. Our aim was to determine among cancer patients with a 4T score ≥ 4, the performance of the conventional cut-off for HIT antibody testing (IgG anti PF4) to discriminate between serotonin release assay (SRA) positive and negative cases. Methods: Retrospective and prospective analysis of cases (2002-2019) was performed of the electronic medical records of adult cancer patients at MD Anderson Cancer Center with suspected HIT. Cases were included in the analysis if the 4T score was ≥ 4 and investigated with IgG anti-PF4 optical density (HIT OD) and SRA. Logistic regression model and the receiver operating characteristic curves were conducted to identify the sensitivity and specificity of different cut-off points for the HIT OD to discriminate HIT cases based on the SRA status. Results: Among 50 cases, 18 were SRA positive. Median HIT OD was 1.03. At a cut-off point of 0.4, the HIT OD performed with a sensitivity of 0.89 and a specificity of 0.50 to discriminate the cases of SRA positive HIT. When the cut-off HIT OD was 1.0, the sensitivity was 0.78 with a specificity of 0.66. Conclusions: Our findings suggest that in cancer patients the performance of IgG anti-PF4 is similar to that of non-cancer patients for the identification of HIT cases. Disclosures Oo: Janssen and Janssen: Other: Research: site co-investigator ; Medical Education Speakers Network: Honoraria.

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.

Quality improvement and safety curriculum for hematology/oncology fellows at Columbia University.

247 Background: It is imperative to provide Hem/Onc fellows with experiential training in quality improvement (QI) and patient safety methodology. Our objective was to design a curriculum that would provide experience in designing, implementing, and analyzing a QI/safety project with the ultimate aim of engagement in QI/safety efforts throughout their careers. Methods: The curriculum focused on experiential learning and was led by a faculty member with QI/safety methodology training who provided didactics and supervisory support of the projects. Fellows worked in groups (3-5 fellows) to implement a project. Plan-Do-Study-Act (PDSA) methodology was introduced early in the academic year and workshops continued over a one-year time period. At the year end, projects were presented at an institution-wide symposium. Two cohorts (2015-2016, 2017-2018) have completed the curriculum. Results: Program efficacy was measured in several ways. The QIKAT-R tool was administered prior to the curriculum in August 2015 (n = 12) and at completion June 2016 (n = 14). At baseline, the mean score was 3.97 (out of 9) which improved to 7.57 at completion. Comfort level with QI also increased by 42.9%. Annual ACGME survey questions pertaining to an institutional culture of patient safety increased from 88% (2015) to 100% (2016 and 2018) and participation in QI increased from 53% (2015) to 95% (2106) to 100% (2018). Further, fellows (n = 33) successfully completed nine projects which included: improvement of fertility preservation, improvement in the adequacy of bone marrow aspirates performed by fellows, increasing genetic counseling referrals in select patients with colorectal cancer, improvement in smoking cessation counseling, increasing timely chemotherapy order entry, and reduction of unnecessary heparin induced thrombocytopenia antibody testing. The curriculum is currently being adapted to other fellowship programs at Columbia. Conclusions: Our curriculum is an effective method to teach fellows at Columbia University Medical Center a skill set necessary to conduct successful QI/safety projects. PDSA methodology of small cycles of change can be used life-long to continuously assess and improve care quality and safety.

Heparin-Induced Thrombocytopenia Complicating Thrombotic Thrombocytopenic Purpura

Since the introduction of therapeutic plasma exchange for the management of thrombotic thrombocytopenic purpura, the prognosis of this disease improved signifi cantly. Some patients suffer from refractory disease and adjunctive therapy needs to be considered. In addition, alternative explanations for thrombocytopenia may bepresent. In this report we discuss a patient who presented with typical fi ndings of thrombotic thrombocytopenic purpura and responded initially to therapeutic plasma exchange and steroids. Shortlyafterwards, his platelet count deteriorated and he was found to have acute pulmonary embolism. Prior to the pulmonary embolism, the patient had received venous thromboembolism prophylaxis in the form of low molecular weight heparin and had a history of previous exposure to unfractionated heparin. Testing for heparin-induced thrombocytopenia antibodies was positive and the patient was started on an alternative anticoagulant. Despite these early interventions the patient did not survive. It is essential that physicians be aware of such possible associations to request appropriate investigations and start appropriate management, accordingly.

Heparin-Induced Thrombocytopenia Antibody Testing and Its Cost Effectiveness: Taking a Financial HIT

Introduction Heparin induced Thrombocytopenia (HIT) is a life threatening condition that can lead to significant morbidity and mortality in hospitalized patients. Thrombocytopenia in the setting of unfractionated heparin (UFH) exposure is a common occurrence in hospitalized patients and its diagnosis and management is associated with increased costs to the healthcare system. There is a 5-10X decreased risk of HIT with low molecular weight heparin (LMWH)(Martel N, et al. Blood. 2005;106 (8):2710-2715) while the incidence with fondaparinux is much more rare (Warkentin TE et al; Blood 2005, 106: 3791-3796). We conducted a single center, retrospective study to assess the correlation of HIT antibody (Ab) testing to '4T' score and the associated financial burden in our institution. Method Data collection Using retrospective chart review, we identified 78 hospitalized patients between 11/11/15 and 6/7/16 from various departments that underwent HIT Ab testing. The '4T' score was calculated as per Table 1. Data including admission service, type and duration of anticoagulation (AC) prior to and after HIT testing, HIT Ab and Serotonin release assay (SRA) positivity, type and duration of non-heparin AC and days of hospitalization were collected. HIT Ab was measured using platelet factor 4 complexed polyvinyl sulfonate (PVS) coated to the wells of a microtiter plate (Labcorp Burlington Test 150075). Patients with positive HIT (Optic Density&gt;0.4) were reflexed to confirmatory SRA (LabCorp Burlington Test 150018). Cost Analysis Pharmacy acquisition cost of non-heparin AC (argatroban /fondaparinux) used as empiric treatment during the HIT testing period was recorded. Pharmacy acquisition cost was also used to predict cost of prophylactic LMWH and fondaparinux for the same duration. Daily dose of continuous UFH was standardized to a 70Kg patient/day. The cost of testing for HIT incurred by the facility was obtained. Statistical analysis was done using ANOVA on VassarStats.net online computation. Results Seventy eight patients had HIT Ab evaluated (Table 2). 26.9% (n=21) had a positive HIT Ab test, and 2.5% had a positive SRA test (n=2). Of the 78 cases analyzed, 48 were categorized as low risk, 24 as intermediate, and 8 as high using the 4T score. HIT Ab testing was positive in 23.9% of low risk, 29% of intermediate risk and 37.5% of high risk patients. SRA was positive in only 2.5% of cases; 1 in the low risk and 1 in the high risk group (n=2) (Table 2). Breakdown of AC during hospital stay showed that 52% (n=41) had UFH on admission, 70% (n=29) of which was for DVT prophylaxis; however 56% (n=23) of these did not have heparin exposure within 100 days of admission. 18% (n=14) were placed on SCDs, 6 of which had no known heparin exposure within 100 days of admission. 23% (n=18) were exposed to prophylactic LMWH, 2.5% (n=2) to therapeutic LMWH, 1.2% (n=1) to dabigatran, apixaban and fondaparinux each (Table 3). Cost Analysis The total average cost per patient with suspected HIT requiring laboratory evaluation was $431.15 (n=78). If a patient required full dose non-heparin anticoagulation, the average cost increased to $1274.98 per patient (n=20) and average duration of anticoagulation was 4 days. Average length of hospitalization for patients suspected of HIT was 18.7 days. Using enoxaparin as an anticoagulation during this period would have cost on average $68.46 per patient, while the use of fondaparinux would cost $179.01. Conclusion Evaluation for HIT and empiric management poses a significant burden of expense on our strained healthcare system. The 4T score has been useful in predicting HIT positivity in other studies (Lo GK, J Thromb Haemost. 2006 Apr;4(4):759-65). In this study conducted in a real-world clinical setting however, we found the 4T score was not universally applied to calculate pretest probability. A suspicion of HIT cost on average $431 per patient per hospitalization. A positive HIT Ab lead to an expense of $955. Confirmed HIT by SRA, resulted in an expense of $1557 per patient per hospitalization. Of note, length of stay and patient discomfort was not included in the analysis. Improved education regarding pretest probability using 4T score is warranted, however using LMWH or non-heparin alternative as DVT prophylaxis may be the most cost-effective approach in today's cost-conscious, high-value healthcare system. Disclosures No relevant conflicts of interest to declare.

A high-value cost conscious approach to minimize heparin induced thrombocytopenia antibody (HITAb) testing using the 4T score.

Heparin Induced Thrombocytopenia (HIT) is a serious complication from administration of heparin products. The 4T score is a validated pre-test probability tool to screen for HIT in hospitalized patients. As the negative predictive value (NPV) is very high further testing for HIT in patients with a low score can be avoided. Our objective was to determine trends at our hospital with respect to utilization of HIT antibody (HITAb) testing and evaluate economic burden from unnecessary HIT testing. A retrospective cohort review was performed on patients age18 and above admitted to a tertiary care center from February 2013 to December 2014 who underwent HITAb testing. Surgical ICU patients were excluded.Patients were stratified into low, intermediate, and high risk for HIT based on the 4T model.Statistical analysis was performed using Chi square and regression models. Of 150 patients that underwent HITAb testing,134 met inclusion criteria.73 were male (54.47%) and mean agewas 55.50±17.27years.81 patients had a low 4T score 0-3. Analysis of testing trends showed 60.44% of patients were tested for HITAb despite being low riskusing the 4T model.Only three patients with low 4T score were positive on confirmatory SRA testing (NPV 96.29% CI 95=89.56-99.23%).Expenditure due to inappropriate testing and treatmentwas estimated at $103,348.13. The majority of HITAb testing was foundunnecessary based on the investigator calculated 4T score. We propose implementation ofan electronic medical record (EMR) based calculator in order to reduce unneeded testsand reduce use of costlier alternative anticoagulants.

The Appropriateness of Heparin Antibody Testing. A Single Institution Retrospective Analysis

Background: Heparin-induced thrombocytopenia (HIT) is a drug-induced, immune-mediated prothrombotic disorder associated with thrombocytopenia and venous and/or arterial thrombosis.Up to 5% of patients exposed to heparin for at least one week develop HIT, and approximately 50% of them will have thrombosis. Diagnosis of HIT is suspected from the clinical picture based on the ''4 T's'' (Thrombocytopenia, Timing, Thrombosis, no other cause of platelet fall) or the HIT Expert Probability (HEP) scoring system. However, often these "4 T's" are ignored and testing is inappropriately ordered in low risk patients. This could lead to possible morbidity and increase length of hospital stay. We opted to look back at the appropriateness of testing done within our academic center.Methods/ Design:All hospitalized patients with thrombocytopenia who underwent HIT antibody testing (HIT ELISA) during February 2013 were screened using our internal electronic medical record.Patients were subdivided to low, intermediate or high pretest probability group according to the 4Ts scoring system.Appropriateness of testing was determined according ASH 2013 Clinical Practice Guideline on the Evaluation and Management of Adults with Suspected Heparin-Induced Thrombocytopenia (HIT). HIT Ab test is recommended to be tested when there is intermittent to high probability of HIT (4T's score above or equal to 4).The percentage of appropriate/inappropriate testing was calculated.The results were then subdivided by ordering physician group.Results:120 HIT ab tests were performed during February 2013 in our institution. Only 13 patients tested had a positive HIT Ab. Internal medicine ordered the majority of these tests. Of the 120 patients tested, 7 patients had high risk and another 50 had intermediate risk as per 4T's scoring. 61 patients were low risk and should not have been tested. (Table 1)Table 1HIT antibody test ordered per Service and probability of HIT.Service ordering testLow probability of HITIntermediate/high probability of HITTOTALInternal Medicine282856Cardiothoracic Surgery131124Hematology Oncology7512Cardiology314Surgery145Emergency medicine011Infectious disease404Pulmonary011Critical care167Nephrology123Ob Gyn101Family Medicine202TOTAL6159120Conclusions:HIT testing has been overused within our institution. Low platelets, without other signs or symptoms of typical HIT were used as a trigger for testing the antibody. This has potential to cause harm due to increased bleeding risk, increased length of hospital stay, and the potential to utilize extended anticoagulation when not necessary. Better education on the appropriateness of the test can limit the potential harm of its use. DisclosuresNo relevant conflicts of interest to declare.

Assessing The Clinical And Economic Impact Of An Automated, On-Demand Immunoassay For The Diagnosis Of Heparin Induced Thrombocytopenia

To understand and quantify the clinical and economic impact of an automated, on-demand diagnostic test versus current diagnostic tests, for heparin-induced thrombocytopenia (HIT). A mixed methods study combining a literature review with primary research. The literature review searched multiple databases to identify data on test performance, clinical and economic data. Semi-structured interviews (n=4) provided insight into current practice and challenges faced, validated by a larger survey (n=90). Two flow diagrams modelling a hypothetical cohort of 1000 patients were used to calculate the clinical and cost impact of automated, on-demand testing. The automated, on-demand test had comparable or lower sensitivity, and a higher specificity than other available tests. Clinical data and survey findings indicate that the specificity of the most widely used antibody tests (ELISA) is suboptimal. The survey revealed that half of patients are speculatively switched off of heparin and onto replacement therapy based on clinical assessment alone, rather than based on clinical assessment and diagnostic test results as per guideline recommendations. Speculative treatment is driven by test turnaround time of >24 hours for >50% of respondents. The cost model indicated that the cost of replacement therapy whilst awaiting tests results of >24 hours’ turnaround time was between $7215 and $31268. Automated, on-demand antibody testing and switching patients off heparin based on test results reduced this cost to between $2737 and $13092. Automated, on-demand HIT antibody testing could enable physicians to use timely diagnostic test results with better specificity than current tests to make treatment decisions. This could potentially enable earlier treatment of HIT to reduce complications such as extended hospitalisation and death, thus improving clinical outcomes and reducing costs. Also, earlier informed treatment decisions could yield pathway cost reductions through reducing the use of replacement therapies in non-confirmed and false positive cases.

The transfusion‐related acute lung injury controversy: lessons from heparin‐induced thrombocytopenia

The transfusion‐related acute lung injury controversy: lessons from heparin‐induced thrombocytopenia

A Rapid Heparin Antibody Detection Assay Performs Better Than 4T’s Score in Predicting HIT Diagnosis: A Single Community Medical Center Retrospective Analysis

Introduction: The diagnosis of heparin induced thrombocytopenia (HIT) and thrombosis (HITT) is challenging due to poor availability of the gold standard serotonin releasing assay (SRA) and suboptimal positive predictive value from clinical scoring models such as 4T score. A common algorithm used for diagnosing HIT is: 4T’s pretest probability score estimation in cases suspected of HIT; followed by HIT antibody test in the intermediate to high risk groups; followed by confirmation with SRA test in HIT antibody positive patients. Since 2011, a Particle Immune-Filtration Assay (PIFA) Heparin/Platelet Factor 4 Rapid Assay (HPF4-RA) (Akers Bioscience, Inc, Thorofare, NJ) became available in our medical center and test results were available on the same day. We observed that HPF4-RA test was being routinely ordered along with SRA test at the same time. We performed this retrospective analysis to evaluate and compare the predictive performance for SRA positive HIT diagnosis using 4T score or HPF4-RA. We applied a regression analysis model, to calculate area under receiver operating characteristics (ROC) curve.Methods: A list of all consecutive patients who had HIT antibody test and/or SRA test performed between January 2010 and June 2013 was obtained, which consisted of 402 patients. Patients with duplication of tests were deleted from analysis. 283 patients had results reported for both HPF4-RA (positive in n=42, negative in n=241) and SRA tests (positive in n=16 and negative in n=267); and these results were used for calculation of HPF4-RA prediction model. Two patients had HPF4-RA negative result but SRA positive test result. 4T’s scores were calculated for 125 patients, consisting of all HPF4-RA positive patients (n=42), and patients randomly selected from the total HPF4-RA negative pool (n=83). Electronic medical records were reviewed for temporal trend of platelet counts, diagnosis, medication use, Doppler tests and competing causes of thrombocytopenia. Persons calculating the 4T’s score were blinded to the laboratory test results.Results: Stratification of the patients with 4T’s score analysis (n=125) revealed that the distribution of SRA positive patients (n=16) was 31.3% (n=5) in low risk, 31.3% (n=5) in intermediate risk, and 37.5% (n=6) in high risk groups; while the distribution of SRA negative patients (n=109) was 45.9% (n=50) in low risk, 43.1% (n=47) in intermediate risk and 11.0% (n=12) in high risk groups. The area under receiver operating characteristics (ROC) curve for 4T score as a continuous variable to predict SRA positive HIT was 0.659 (95% CI 0.516 - 0.802; p = 0.041), and the area under ROC curve for HPF4-RA to predict SRA positive HIT was 0.818 ( 95% CI 0.712 - 0.924; p = 0.00) (Figure 1). HPF4-RA test also showed better overall prediction parameters for HIT as shown in Table 1. A combination of HIT HPF4-RA positive result and a 4T score ≥ 4 did not increase the area under ROC curve for prediction of SRA positive HIT.Abstract 1457. Table1:Predictive performance of 4T’s score and HPF4-RA for HIT (defined by positive SRA)Sensitivity (95% CI) Specificity (95% CI) PPV (95% CI) NPV (95% CI) Number of patients (%)4T’s score ≤ 3 (Low Risk)0.31 (0.11 – 0.59)0.72 (0.64 - 0.79)0.11 (0.03 - 0.23)0.91 (0.84 - 0.95)56 (44.8)4T’s score ≥ 4 (Intermediate and High Risk)0.69 (0.41-0.89) 0.39 (0.29 - 0.48) 0.14 (0.72 - 0.24) 0.89 (0.77 - 0.96) 69 (55.2) 4T’s score ≥ 6 (High Risk)0.37 (0.15-0.65) 0.82 (0.74 - 0.89) 0.24 (0.09 - 0.45) 0.90 (0.82 - 0.95) 17 (13.6) HPF4-RA Test0.88 (0.62-0.98) 0.86 (0.81- 0.90) 0.26 (0.16 - 0.41) 0.99 (0.96 - 0.99) 283 PPV: Positive Predictive Value. NPV: Negative Predictive Value [Display omitted] Conclusions: Both 4T’s score and HPF4-RA testing predict SRA positive HIT more than chance; however HPF4-RA testing predicts SRA positive HIT better than 4T’s scores with higher sensitivity, specificity and NPV. This result challenges the pretesting algorithm for selecting patients for confirmatory SRA testing to diagnose HIT. Instead of using 4T’s score as a screening tool for selecting patients for HPF4 antibody testing; rapid HPF4 antibody assays when available, should be considered as upfront screening tool and positive results considered for confirmatory SRA testing for diagnosis of HIT. Further studies are warranted to confirm this data. DisclosuresNo relevant conflicts of interest to declare.

Retrospective Analysis of Heparin-Induced Thrombocytopenia Management at a Large Tertiary Hospital

Background: Heparin-induced thrombocytopenia (HIT) is a disease that is difficult to quickly and accurately diagnose. The 4T score calculation is often used to determine the probability of HIT in order to guide further work-up and therapeutics. Our study aims to assess current practices regarding the diagnosis and management of HIT, particularly in reference to the appropriateness and cost of work-up and initiation of heparin alternatives based on the 4T score. Methods: A retrospective chart review was carried out on patients at Scripps Mercy San Diego for whom work-up had been pursued with HIT antibody test and/or serotonin release assay between May 2011 and May 2012. For each of these patients a 4T score assessing the probability of HIT was carried out based on available chart information. Results : Of the 218 work-ups reviewed, 74% had a low pre-test probability of HIT and 53% occurred in the medical intensive care unit (ICU). Only five of the 218 work-ups and one of the 116 ICU patient work-ups resulted in a diagnosis of HIT. The cost of using heparin alternatives in patients without a final diagnosis of HIT was approximately $100,750 and the cost of pursuing serologic work-up in patients with a low 4T score was $33,360. Average optical density (OD) scores among patients with a low and intermediate 4T score did not reach the threshold value for positivity with values of 0.257 and 0.334, respectively. Patients in the high 4T score group had average OD values of 1.68, which is 5 above the threshold for a positive result and the probability of HIT being present did not reach 50% until the OD was above 1.40. Conclusions: This study demonstrates the significant costs associated with HIT diagnosis and management at a large hospital. Implementing a clinical decision support system to mitigate inappropriate ordering of serologic studies and initiation of heparin alternatives may be cost-saving. Further prospective studies will need to be undertaken to test this hypothesis. J Hematol. 2014;3(2):27-33 doi: http://dx.doi.org/10.14740/jh157w

Relationship between the 4Ts scoring system and the antiplatelet factor 4/heparin antibodies test in critically ill patients.

Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction and potentially progresses to fatal thrombosis. The 4Ts scoring system has been reported as a clinical pretest for HIT. However, its usefulness in critically ill patients has not yet been thoroughly examined. Thus, we evaluated the clinical usefulness of the 4Ts score in the diagnosis of HIT in critically ill patients. One hundred and four critically ill patients who were admitted to our intensive care unit and who underwent the antiplatelet factor 4/heparin complex antibodies (PF4/heparin Ab) test with suspected HIT were enrolled in the study. The primary endpoint variable was the 4Ts score. The secondary endpoint variables were laboratory data, length of stay, and mortality, compared between thePF4/heparin Ab positive and negative groups. There was no significant difference in the 4Ts scores between the PF4/heparin Ab positive and negative groups. The positive predictive value (HIT patients/4T high score patients) was 15.4% (2/13), the negative predictive value (non-HIT patients/4T low score patients) was 87.5% (42/48), and the false-negative rate for the 4Ts score (4T low score patients/HIT patients) was as high as 54.5% (6/11). The PF4/heparin Ab positive patients had longer stay in intensive care compared to the PF4/heparin Ab negative patients (P = 0.035). The present study showed the discrepancy between the 4Ts score and PF4/heparin Ab. When HIT is suspected in critically ill patients, an immediate HIT antibody test and initiation of therapeutic management of HIT are required regardless of the 4Ts score.

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Introduction: Heparin Induced Thrombocytopenia (HIT) in critically ill patients remains associated with increased morbidity and mortality. Yet, the burden of this disease in the intensive care unit (ICU) remains poorly understood. We sought to clarify the incidence of HIT in ICU patients. Hypothesis: HIT occurs infrequently in non-cardiac surgery ICU patients. Methods: We performed a prospective observational study in consecutive ICU patients who underwent HIT antibody testing (August 2009 – March 2012). The decision to pursue HIT diagnostically was left to the primary team. The enzyme immunoassay served as the initial screening test for HIT and by convention an optical density > 0.4 defined a positive test. The final diagnosis of HIT was confirmed by a serotonin release assay (SRA) which was performed in a central lab in all subjects. The incidence of HIT represented our primary endpoint. We then compared rates of HIT in various patient populations. Results: The cohort consisted of 218 subjects (mean age: 62.5 +/- 17.1; male gender: 56.0%). An SRA was positive and the diagnosis of HIT confirmed in 3.2% of patients tested. Physicians were more likely to order HIT in the surgical (SICU) compared to the medical service (67.5% vs 32.5%). HIT was diagnosed in 1.1% of the medical ICU patients tested vs 4.7% of the surgical ICU patients (p=0.17). Among the surgical population diagnosed with HIT, 83.3% had undergone cardiovascular surgery prior to the development of HIT. Coronary artery bypass grafting (CABG) was the most common cardiovascular surgery that predisposed to HIT (49.6%). In all non-cardiac surgery ICU patients, HIT occurred in 0.00%. Conclusions: HIT remains rare in the ICU, particularly in the general medical-surgical ICU patient population. The highest burden of this disease in the ICU is associated with those who undergo cardiovascular surgery. More importantly, patients who undergo CABG have higher risk than other general surgical ICU patients. Given the low prevalence of HIT in the non-cardiac ICU patient population, testing for HIT should only be pursued if the pre-test probability for HIT is high.