HIT Expert Probability Score Research Articles

Comparison of Interobserver Agreement between the 4T and the HIT Expert Probability (HEP) Scores: We Agreed Not to Agree

Background: Diagnosis of heparin induced thrombocytopenia (HIT) is challenging. The 4T score is the principal scoring system for HIT. The HIT Expert Probability (HEP) score, based on expert opinion, was proposed in 2010. Both scores have a very high sensitivity, being capable of ruling out HIT in low-risk individuals. However inter-observer agreement (IOA) of HEP score in comparison to the 4T score remains uncertain. Aim: This study aimed to compare IOA between the 4T and the HEP score among hospitalized patients. Specific objectives: Comparison of IOA between the 4T and the HEP score in the 1-whole cohort 2-non-ICU 3- ICU Identify which item of the score have the lowest IOA (magnitude of thrombocytopenia, timing of thrombocytopenia, existence of other causes of thrombocytopenia, presence of thrombosis) Methods: Patients: This is a retrospective study at a single tertiary hospital. All inpatients 16 years or older who have been tested for HIT between June 2019 to end of June 2021 were included. Patients were excluded if the reason for sending HIT was a repeat test. Data were collected retrospectively by manual chart review. Assessment of HEP score and 4Ts score: Two hematologists rated the HEP score and 4Ts score independently for every patient. The score's calculation was blinded between observers and, they were blinded to the HIT Eliza result. Low 4Ts score is defined as score less than 4 and for HEP score if less than 3. HIT test was done using Stago Asserachrom HPIA-IgGAM ELISA with level of < 0.4 considered negative. Statistical analysis: Continuous variables are reported as mean ± standard deviation (SD) or median (interquartile range; IQR), as appropriate. Categorical variables are reported as frequency and percentage. The Kappa coefficient (к) with 95 % confidence interval (CI) was used to assess the IOA of 4T score and HEP score, it was calculated for the individual risk categories - low vs high score in: 1-the whole patients 2-ICU 3- non-ICU We also calculated the IOA for each item of the score, magnitude of thrombocytopenia, timing of thrombocytopenia, existence of other causes of thrombocytopenia, presence of thrombosis (as total score). A P-value less than 0.05 was considered significant. Statistical analyses were performed using SAS version 9.4 (SAS institute, CARY, NC, USA). The study was approved by the local ethical board. Informed consent was waived. Results: After exclusion of the repeat test (13), 302 patients were included in this study. Median age 66 years old. Most common reason for request was thrombocytopenia 288 (95%). HIT ELISA ≥ 0.4 in 34 (11%). Inter-observer agreement: All patients: We found similar IOA between the 4T score and the HEP score к (95 % CI) of 4T score was .14(-0.13-0.41, P < 0.01), compared 0.17(-0.16-0.5, P < 0.01) in the HEP score. Non-ICU patients: The IOA was similar between the 4T score and the HEP score, к of 4T score was 0.24(0.11-0.38, P < 0.01) compared 0.17(0.03-0.31 P < 0.01) in the HEP score. ICU patients: The IOA of 4Tscore was lower than HEP score к of 4T score was -020(-0.20.16, P = 0.83) compared 0.16(-0.037-0.37, P = 0.86) in the HEP score. Among the four individual items of 4T score, “existence of other causes of thrombocytopenia” achieved the lowest к with 0.03 and 0.1 in 4Tscore and HEP score respectively. Conclusion: In this retrospective study, we found a lower interobserver agreement of the 4T score compared to the HEP score in ICU patients. The poor IOA of the 4T score in ICU patients is attributed to worse agreement in (existence of other causes of thrombocytopenia item). Ascertaining the cause of thrombocytopenia in ICU patients is challenging and the 4T score seems to depend on physician gestalt rather than objective points. Our data suggests that the HEP score is the preferred score in in patients with critical illness.

Identification of Heparin-Induced Thrombocytopenia in Surgical Critically Ill Patients by Using the HIT Expert Probability Score: An Observational Pilot Study.

Background: Heparin-induced thrombocytopenia (HIT) remains a challenging diagnosis especially in surgical intensive care unit (SICU) patients. The aim of the study was to evaluate for the first time the diagnostic accuracy of the HIT Expert Probability (HEP) score in the early identification of HIT in SICU patients. Methods: The HEP and 4Ts scores were calculated in all patients with suspected HIT during their stay in our SICU. The diagnosis of HIT was finally confirmed (HIT+ group) or excluded (HIT− group) by an independent committee blinded to the HEP and 4Ts score values. The primary outcome was the sensitivity and specificity of a HEP score ≥ 5 for the diagnosis of HIT. The secondary outcome was the area under the ROC curve (AUC) of the HEP and 4Ts scores in the diagnosis of HIT. Results: Respectively 6 and 113 patients were included in the HIT+ and HIT− groups. A HEP score value ≥ 5 had a sensitivity (95% confidence interval (95% CI)) of 1.00 (0.55–1.00), and a specificity (95% CI) of 0.92 (0.86–0.96). The AUC (95% CI) was significantly higher for the HEP score versus for the 4Ts score (0.967 (0.922–1.000) versus 0.707 (0.449–0.965); p = 0.035). Conclusions: A HEP score value < 5 could be helpful to rule out HIT in SICU patients.

The Predictive Value of the 4Ts and HEP Score at Recommended Cutoffs in Patients With Mechanical Circulatory Support Devices

Despite the increasing utilization of mechanical circulatory support (MCS) devices, the 4Ts and heparin-induced thrombocytopenia (HIT) Expert Probability (HEP) scores have not been validated in patients with suspected HIT requiring MCS. A retrospective cohort study. At a tertiary university hospital. Adults with suspected HIT requiring any MCS. A diagnostic investigation of HIT. Of the 299 patients included, there were 374 diagnostic investigations of HIT, of which 32 (8.6%) were HIT-probable (heparin PF4 immunoassay optical density ≥1 or positive serotonin release assay). The 4Ts score ≥4 demonstrated a pretest sensitivity of 0.56 (95% confidence interval [CI]: 0.39-0.72) and specificity of 0.8 (95% CI: 0.75-0.83). The HEP score ≥3 demonstrated a pretest sensitivity of 0.31 (95% CI: 0.18-0.49) and specificity of 0.83 (95% CI: 0.79-0.87). The area under the receiver operating characteristic curve for the 4Ts and HEP scores were 0.68 (95% CI: 0.63-0.73) and 0.63 (95% CI: 0.59-0.68), respectively, and were not statistically different (p=0.21). In patients with an intra-aortic balloon pump, neither the 4Ts nor HEP score had discriminatory ability to differentiate probable HIT. The HEP score had no discriminatory ability in patients with concomitant MCS devices. The 4Ts and HEP scores have a modest predictive performance for probable HIT in patients requiring MCS devices. A low 4Ts or HEP score does not reliably rule out HIT in patients requiring MCS, and clinical suspicion for HIT should be investigated, utilizing laboratory tests in this population.

Accuracy of a modified 4Ts score in predicting heparin-induced thrombocytopenia in critically ill patients: A pilot study.

Thrombocytopenia is common among critically ill patients and heparin-induced thrombocytopenia (HIT) is often on the differential. Professional guidelines recommend calculating a pre-test probability score before performing HIT testing. The 4Ts score is widely utilized but accuracy has been questioned in critically ill patients. The HIT Expert Probability (HEP) score is available, but complexity limits use. Our objective was to compare a modified intensive care unit (ICU)-4Ts score to available scoring tools. This was a single-center retrospective pilot study. Adult ICU patients that were tested for HIT and had a documented 4Ts score were included. A blinded investigator retrospectively calculated the HEP and ICU-4Ts score. Receiver operating characteristics (ROC) area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were compared. In 194 included patients, ROC AUC was significantly higher for the ICU-4Ts compared to the 4Ts score (0.80 versus 0.66, respectively; p=0.044). The ICU-4Ts score had the highest specificity, PPV, and NPV. The sensitivity was similar between the HEP and ICU-4Ts score. The ICU-4Ts score better predicted the diagnosis of HIT compared to the 4Ts score. Prospective validation studies are needed to confirm these results.

Heparin-Induced Thrombocytopenia: Are We Ordering Too Much

Introduction:Heparin induced thrombocytopenia (HIT) is a well described cause of IgG antibody mediated platelet consumption.Over-testing for HIT is highly prevalent in the hospital setting. Physicians' fear of missing the diagnosis might contribute to these findings, despite the high negative predictive value of the 4T probability score and the HIT Expert Probability (HEP) score. Also, the initiation of HIT treatment pending confirmatory testing, results in a subsequent increase of costs and exposure of patients to the unnecessary risks of anticoagulation. The aim of our study is to identify clinical and laboratory factors that might affect the decision of testing for HIT in the setting of low or intermediate pretest probability and to prove that this entity is over-investigated and over-treated in the in-hospital environment.Methods:We conducted a cross-sectional retrospective observational study at Hofstra University Northwell Health Staten Island Hospital. Inclusion criteria were patients 18 years and older who had undergone anti-PF4-heparin antibody testing on an inpatient basis, from January 2013 till August 2015. Patients were excluded only if the test was done as outpatient. Statistical analysis was conducted using independent-sample t- test, Chi-square test or Fisher's exact test. All statistical tests were 2-sided and conducted at the 0.05 level of significance. Data was analyzed using the SAS® System Version 9.3 (SAS Institute Inc., Cary, NC).Results:Data was collected on 89 patients who underwent anti-PF4-heparin antibody testing. 84 patients (94%) underwent HIT testing with a low 4T score, as compared to 5 patients (6%) with a high 4T score. There was no significant difference in the proportion of testing with respect to gender, age, the service under which the patient was admitted (medicine vs. surgery), presence of a hematology consult, a history of cardiac surgery, type of heparin used and an elevated Charleson score. 80% (n=74) of patients had another cause for thrombocytopenia and had the HIT panel ordered despite a low/intermediate 4T score (Table 1).In our study, 5 patients tested positive for HIT. 3 of the patients had high 4T and HEP score pretest probability, while 2 of the patients had intermediate 4 T score and high HEP score pretest probability. All 60 patients with a low 4 T score tested negative for HIT (Table 2).After ordering HIT serology, heparin was discontinued in 82 patients. 17 patients with low/intermediate 4T score were started on anticoagulation, 2 of them had new bleeding event. 6 patient with high 4T score were started on anticoagulation, and 1 of them had a bleeding event (Table 3).Conclusion:HIT poses a significant diagnostic challenge. It is an uncommon cause of thrombocytopenia that carries significant morbidity and mortality. Our study showed that HIT testing using ELISA immunoassays is being ordered excessively in the setting of low to intermediate pretest probability leading to unwarranted treatments at significant costs and carrying an important burden on the healthcare system. However, a high number of comorbidities did not seem to lower the threshold for ordering HIT panel. It is very challenging to conduct randomized trials on less common diseases in the clinical setting to improve test ordering practices. The HEP score might be an important adjunct to clinical decision making in the future but this requires more studies being conducted. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

A Comparison of Scoring Systems for Predicting HIT in CABG Patients

Heparin induced thrombocytopenia is seen in patients with exposure to unfractionated heparin or low molecular weight heparin products. Surgical patients are at the highest risk for heparin induced thrombocytopenia (HIT) and patients undergoing coronary artery bypass graft (CABG) surgery have the second highest risk for developing heparin antibodies leading to HIT. Eight percent of heparin treated patients develop antibodies and 1-5% develop HIT; of these, 30-50% develop thrombosis along with the thrombocytopenia with a 20-30% morbidity and mortality rate. There are three different scoring systems typically used to determine the probability of HIT. These include the 4T score (most commonly used), HIT Expert Probability (HEP) score, and the Lillo-Le Louet (LLL) model scoring system (used exclusively for post-CABG patients). To date there have been limited studies done to compare the various scoring systems specifically in post CABG patients. The purpose of this study was to determine which scoring system was best at predicting the probability of HIT in a CABG patient. This is a single institution retrospective chart review of all patients between 2017-2019 who underwent CABG surgery. A total of 165 patients were studied and the patients who had HIT workup done were selected for further evaluation. Patient charts were reviewed to document initial platelet counts and post-CABG surgery platelet counts. Platelet counts were followed and documented for up to post-op day #15, if available. Review also included identification of new cases of arterial or venous thrombosis. For each patient that had HIT work-up, the HIT probability score was calculated by three different methods (4T score, HEP score, and LLL score). Sensitivity and specificity of the scoring systems was calculated. ANOVA test was used to determine if there was a difference between the three scoring systems and paired T-test was used to assess between the scoring systems. A total of 37 patients were studied and paired-T tests were used to compare between the scoring systems. There were a total of 6 patients with confirmed HIT based on a positive serotonin release assay (SRA) and 31 patients who had a negative work-up for HIT. The PPV of 4T, HEP, LLL was 0.545, 0.545, 0.667 respectively. Specificity was highest for LLL model: 0.912 and 0.861 for both HEP and 4T. ANOVA test determined in patients with a definitive HIT diagnosis that there was no difference among the 3 tests (p value=0.47792); however there was a difference between the scoring systems when the patients tested negative for HIT (p value= 0.00001). Furthermore, when individually comparing LLL to either 4T or HEP there was a significant difference in both true HIT and non-HIT patients p-value &amp;lt;0.03. These findings suggest that LLL is a better predictor of HIT in patients with CABG and it is especially superior in ruling out HIT in comparison to 4T and HEP. This further goes to support using LLL over 4T score in patients with CABG to help improve predictability of HIT. LLL is a simple calculation similar to 4T score and hence we should utilize it more often in our CABG patients. Disclosures No relevant conflicts of interest to declare.

Heparin-Induced Thrombocytopenia in a Pediatric Population: Implications for Clinical Probability Scores and Testing

To determine the applicability of the 4Ts score and the Heparin-Induced Thrombocytopenia (HIT) Expert Probability (HEP) score in children with suspected HIT and to estimate the number of children potentially at risk of HIT. We retrospectively estimated 4Ts and HEP scores in a cohort of 50 children referred for laboratory screening with enzyme immunoassay. In addition, minor modifications were introduced to the 4Ts score (modified 4Ts score) to adapt it for use in the pediatric setting. All patients with positive enzyme immunoassays were tested with serotonin release assay. We also extracted the number of patients started on heparins in a similar period of time. The median age at the time of testing was 4years (25th-75th percentile, 8.7months to 13.5years); 78% of patients had low and 22% had intermediate risk pretest probability scores using the original 4Ts score; 86% had low risk and 14% had intermediate risk scores using the modified 4Ts score; 54% of children had a HEP score of ≥2. Six patients (12%) had a positive (≥0.40 optical density units) enzyme immunoassay, but none had a positive serotonin release assay. Based on anticoagulation dose, there were 1-2 new daily potentially high-risk exposures to heparinoids at our institution. The modified 4Ts and original 4Ts scores may be more adequate than the HEP score to determineHIT pretest probability in children. Despite the number of patients potentially at risk, HIT is rare in pediatrics.

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.

Predictive value of scoring tools in determining heparin-induced thrombocytopenia in patients on extracorporeal membrane oxygenation.

There are currently no scoring tools validated for use in predicting heparin-induced thrombocytopenia in patients receiving extracorporeal membrane oxygenation. This study aims to determine the predictive value of the Warkentin 4T score, Lilo-Le Louet score, and the heparin-induced thrombocytopenia expert probability score in detecting heparin-induced thrombocytopenia in patients on extracorporeal membrane oxygenation. This was a single center, retrospective, observational cohort study of patients at Rush University Medical Center. Heparin-induced thrombocytopenia-positive patients were defined as those with an optical density greater than or equal to 0.4, consistent with a positive anti-platelet 4 heparin antibody. Out of 39 patients on extracorporeal membrane oxygenation with suspected heparin-induced thrombocytopenia, six (15.4%) were found to be anti-platelet 4-positive. A heparin-induced thrombocytopenia diagnosis was confirmed by serotonin-release assay in two patients (5.1%). The 4T, heparin-induced thrombocytopenia expert probability, and Lilo-Le Louet scoring tools all demonstrated a low positive predictive value (21.4%, 16.7%, and 6.7%, respectively), with the 4T and heparin-induced thrombocytopenia expert probability scores demonstrating the highest specificity (66.7% and 84.8%, respectively) and lowest sensitivity (50% and 16.7%, respectively). The Lilo-Le Louet score had high sensitivity (100%) and low specificity (12.5%) in post-cardiopulmonary bypass patients. Based on the findings of this study, all three scoring tools have limited utility for predicting heparin-induced thrombocytopenia in patients on extracorporeal membrane oxygenation.

DIAGNOSTIC ACCURACY OF 4TS SCORE COMPARED TO HEPARIN-INDUCED THROMBOCYTOPENIA EXPERT PROBABILITY SCORE FOR IDENTIFYING HEPARIN-INDUCED THROMBOCYTOPENIA IN A MEDICAL ICU

SESSION TITLE: Tuesday Abstract Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM PURPOSE: Heparin-induced thrombocytopenia (HIT) is challenging to diagnose in critically ill patients due to a higher incidence of acute thrombocytopenia. Underdiagnosis of HIT is potentially fatal, but overdiagnosis leads to unnecessary exposure to non-heparin anticoagulation. The 4Ts score was developed to aid in diagnosis but has limitations in the intensive care unit (ICU). The HIT expert probability (HEP) score is an alternative scoring system shown to have increased diagnostic accuracy in ICU patients in a subgroup analysis. We aim to validate these findings in a purely medical ICU. METHODS: 4Ts and HEP scores were retrospectively calculated for 91 patients with suspected HIT seen in an academic, tertiary care center medical ICU between January 2017 and April 2018. All patients had serotonin release assays (SRA) ordered. SRA positivity was used as the gold standard for HIT diagnosis. Scorers were blinded to both SRA and calculated results of the alternate scoring system. 4Ts scores equal to or greater than four and HEP scores equal to or greater than three represented positive scores. Sensitivity, specificity and likelihood ratios were calculated. McNemar’s test was used to evaluate differences in score results, sensitives and specificities. For significant differences, 95% confidence intervals were calculated using the Wald method. All statistical analyses used a significance level of 0.05. RESULTS: Three of our 91 patients had positive SRAs. The 4Ts score had a sensitivity of 0.67 (0.09-0.99), specificity of 0.45 (0.35-0.56) and a positive likelihood ratio (LR+) of 1.22 (0.54-2.78). The HEP score had a sensitivity of 1.00 (0.29-1.00), specificity of 0.69 (0.59-0.79) and a LR+ of 3.26 (2.83-4.46). Receiver operative characteristic (ROC) curve could not be created due to the low number of positive HIT cases. CONCLUSIONS: The accuracy measures of the HEP score were superior to the 4Ts score among medical ICU patients. The study was limited by single center status, small sample size of true positive HIT, retrospective design and having less experienced physicians conducting scoring, which has been suggested to favor HEP scoring in a previous study. Future studies continuing to look at this population are needed. CLINICAL IMPLICATIONS: The HEP score may have better diagnostic accuracy for HIT than the 4Ts score in the medical ICU population. DISCLOSURES: No relevant relationships by Thomas Iden, source=Web Response No relevant relationships by Audrey Jernigan, source=Web Response No relevant relationships by Markos Kashiouris, source=Web Response No relevant relationships by Victoria Okhomina, source=Web Response No relevant relationships by Xian Qiao, source=Web Response No relevant relationships by Kathleen Waybill, source=Web Response

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.

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.

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

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

External validation of the HIT Expert Probability (HEP) score.

The diagnosis of heparin-induced thrombocytopenia (HIT) can be challenging. The HIT Expert Probability (HEP) Score has recently been proposed to aid in the diagnosis of HIT. We sought to externally and prospectively validate the HEP score. We prospectively assessed pre-test probability of HIT for 51 consecutive patients referred to our Consultative Service for evaluation of possible HIT between August 1, 2012 and February 1, 2013. Two Vascular Medicine fellows independently applied the 4T and HEP scores for each patient. Two independent HIT expert adjudicators rendered a diagnosis of HIT likely or unlikely. The median (interquartile range) of 4T and HEP scores were 4.5 (3.0, 6.0) and 5 (3.0, 8.5), respectively. There were no significant differences between area under receiver-operating characteristic curves of 4T and HEP scores against the gold standard, confirmed HIT [defined as positive serotonin release assay and positive anti-PF4/heparin ELISA] (0.74 vs 0.73, p = 0.97). HEP score ≥ 2 was 100 % sensitive and 16 % specific for determining the presence of confirmed HIT while a 4T score > 3 was 93 % sensitive and 35 % specific. In conclusion, the HEP and 4T scores are excellent screening pre-test probability models for HIT, however, in this prospective validation study, test characteristics for the diagnosis of HIT based on confirmatory laboratory testing and expert opinion are similar. Given the complexity of the HEP scoring model compared to that of the 4T score, further validation of the HEP score is warranted prior to widespread clinical acceptance.

Interrater agreement for two systems used to determine the probability of heparin-induced thrombocytopenia.

The interrater reliability of the 4T's method and the HIT expert probability (HEP) score for clinical evaluation of suspected heparin-induced thrombocytopenia (HIT) was investigated. Patients hospitalized over a three-year period who were tested for HIT via anti-platelet factor 4 (anti-PF4) antigen assay were identified using laboratory data; 127 patient cases met the study inclusion criteria. Nine clinical pharmacists with expertise in HIT management evaluated the 127 cases using two pretest scoring systems: the 4T's score and the HEP score. Each case was independently evaluated using both 4T's and HEP scores. The primary endpoint was interrater agreement of overall 4T's and HEP scores and individual item scores. Raw agreement of values assigned by the two raters for each of the four items comprising the 4T's score ranged from 0.54 to 0.86, with agreement of 0.63 for final patient categorizations. Raw agreement of rater weightings of the eight HEP scoring items ranged from 0.34 to 1.0; for dichotomization of patients at the suggested screening cutoff value (>2.0), agreement was 0.65. Kappa coefficients were 0.15-0.45 for 4T's item scores and 0.17-0.70 for HEP score item scores. With both scoring systems, low rater agreement mainly related to determination of the timing of thrombocytopenia and possible other causes of the disorder. In a retrospective study, inter-rater agreement in scoring of HIT probability via the 4T's and HEP scoring systems was relatively low. The HEP score did not increase interrater reliability or correlation with anti-PF4 antibodies compared with the 4T's score.

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

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

The HIT Expert Probability (HEP) Score: a novel pre-test probability model for heparin-induced thrombocytopenia based on broad expert opinion.

The diagnosis of heparin-induced thrombocytopenia (HIT) is challenging. Over-diagnosis and over-treatment are common. To develop a pre-test clinical scoring model for HIT based on broad expert opinion that may be useful in guiding clinical decisions regarding therapy. A pre-test model, the HIT Expert Probability (HEP) Score, was constructed based on the opinions of 26 HIT experts. Fifty patients referred to a reference laboratory for HIT testing comprised the validation cohort. Two hematology trainees scored each patient using the HEP Score and a previously published clinical scoring system (4 T's). A panel of three independent experts adjudicated the 50 patients and rendered a diagnosis of HIT likely or unlikely. All subjects underwent HIT laboratory testing with a polyspecific HIT ELISA and serotonin release assay (SRA). The HEP Score exhibited significantly greater interobserver agreement [intraclass correlation coefficient: 0.88 (95% CI 0.80-0.93) vs. 0.71 (0.54-0.83)], correlation with the results of HIT laboratory testing and concordance with the diagnosis of the expert panel (area under receiver-operating curve: 0.91 vs. 0.74, P = 0.017) than the 4 T's. The model was 100% sensitive and 60% specific for determining the presence of HIT as defined by the expert panel and would have allowed for a 41% reduction in the number of patients receiving a direct thrombin inhibitor (DTI). The HEP Score is the first pre-test clinical scoring model for HIT based on broad expert opinion, exhibited favorable operating characteristics and may permit clinicians to confidently reduce use of alternative anticoagulants. Prospective multicenter validation is warranted.