Modified 4T score for heparin-induced thrombocytopenia diagnosis in VA-ECMO patients

2020 ◽  
Vol 46 (7) ◽  
pp. 1481-1483 ◽  
Author(s):  
Amélie Renou ◽  
◽  
Arthur Neuschwander ◽  
Antoine Kimmoun ◽  
Daniel Brodie ◽  
...  
2016 ◽  
Vol 146 (suppl_1) ◽  
Author(s):  
Myra Wong ◽  
Thein Oo ◽  
Wei Qiao ◽  
Naveen Garg ◽  
Cristhiam Rojas Hernandez

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1328-1328
Author(s):  
Prapti A. Patel ◽  
Catherine Burke ◽  
Karen Matevosyan ◽  
Eugene P. Frenkel ◽  
Ravindra Sarode ◽  
...  

Abstract Abstract 1328 Poster Board I-350 Background Heparin-induced thrombocytopenia (HIT) is a clinicopathologic diagnosis based on pretest clinical assessment aided by the 4T score and confirmed by laboratory testing for the presence of anti-heparin-platelet factor 4 antibody (HIT Ab). Prompt and accurate diagnosis of HIT is paramount due to an extraordinarily high risk of thrombosis, and the inherent risk of bleeding and high cost of direct thrombin inhibitors (DTI). The polyspecific enzyme linked immunosorbent assay (poly-ELISA) for the HIT Ab is the most commonly available test that detects IgG, IgM and IgA HIT Ab. The IgG-specific ELISA detects only IgG HIT Ab, the antibody that is known to cause HIT. The use of a second step ELISA with high-dose heparin in the reagent improves the specificity by demonstrating heparin-dependence of the antibody detected. The 4T score was developed to predict the probability of HIT. This score takes into account the severity of thrombocytopenia, timing of platelet fall with relation to heparin use, presence of new thrombosis, and other causes of thrombocytopenia. The high negative predictive value of the 4T score has been validated in multiple studies (Bryant et al, BJH 2008). However, the polyspecific ELISA was used in most of these studies, increasing the possibility of false positive tests. Study We have collected a database of patients being tested for HIT at our institution, where the IgG-specific ELISA along with high-dose heparin inhibition is being used to detect the HIT Ab. We performed a retrospective review of the last 165 ELISAs performed and the clinical circumstances of the testing. We hypothesize that the high negative predictive value of the 4T score combined with the more specific IgG-specific ELISA could be used to rule out HIT and avoid the cost of testing and empiric use of DTI. Results 4T scores of 165 patients were analyzed and compared to the results of the HIT Ab. The distribution of optical density units of the ELISA according to 4T score is shown in Figure 1. Of the 165 patients, 107 patients (64%) had a 4T score of 0-3. Of those 107 patients, 2 patients had OD>0.4; both had no significant inhibition with the addition of high-dose heparin (Table 1). Thus none of the 107 patients had a positive IgG-specific ELISA for HIT Ab. Thus having a low 4T score has a sensitivity of 100% for IgG-specific ELISA for HIT Ab, specificity of 71%. This translates to a positive predictive value of 26%, and a negative predictive value of 100% (Table 2). Conclusion Based on our data, we conclude that patients with low 4T scores (0-3) are highly unlikely to have HIT. Therefore, we propose that patients with a low 4T score do not need the laboratory workup or empiric treatment for HIT. Since the majority of patients suspected to have HIT have low 4T scores, reserving testing and empiric therapy for patients with intermediate and high 4T scores can lead to significant cost savings, and avoidance of potentially devastating bleeding complications with DTI therapy. Disclosures No relevant conflicts of interest to declare.


2017 ◽  
Vol 44 (2) ◽  
pp. 261-266 ◽  
Author(s):  
Myra Wong ◽  
Thein Hlaing Oo ◽  
Wei Qiao ◽  
Naveen Garg ◽  
Cristhiam M. Rojas-Hernandez

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3525-3525
Author(s):  
Sriman Swarup ◽  
Somedeb Ball ◽  
Nimesh Adhikari ◽  
Courtney Alice Welch ◽  
Jaden Fackrell ◽  
...  

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


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1957-1957
Author(s):  
Udhayvir Singh Grewal ◽  
Shiva Jashwanth Gaddam ◽  
Sahith Reddy Thotamgari ◽  
Tyiesha Brown ◽  
Kavitha Beedupalli ◽  
...  

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


Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1073-1073
Author(s):  
Amarnadh Polisetty ◽  
Nataraj KS ◽  
Hamza Yusuf Dalal ◽  
Shilpa Prabhu ◽  
Devi Prasad Shetty ◽  
...  

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.


Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4896-4896
Author(s):  
Thein H. Oo ◽  
Cristhiam Mauricio Rojas Hernandez

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.


2021 ◽  
Vol 5 (4) ◽  
Author(s):  
Slavik L ◽  
◽  
Ulehlova J ◽  
Hrochova M ◽  
Hlusi A ◽  
...  

Background: Heparin-Induced Thrombocytopenia (HIT) represents a serious complication of heparin treatment. IgG antibodies binding Platelet Factor 4 (PF4) and heparin trigger the clinical manifestations of HIT. A 4T score is used to stratify the selection of patients suitable for examination. However, the selection of suitable patients remains at the discretion of the clinician, who is confronted with determining the cause of thrombocytopenia. The inclusion of the evaluation of the Immature platelet fraction result seems to be a suitable complement to the stratification of patients because we do not climb elevated IPF values when consuming platelets due to their immunization. Materials and Methods: In a group of 432 thrombocytopenic samples IPF was detected and analyzed in 45 patients with suspected HIT, a 4T score was determined; IPF and HIT functional tests were examined. IPF was determined by oxazine fluorescent dyeing structures of nucleic acid-containing platelets and fluorescence detection on a Sysmex XN 1000 analyser. To determine HIT, impedance aggregometry using the Multiplate® analyser (MEA) as heparin-induced aggregation techniques. The MEA method uses sensitization of donor platelets with patient plasma in the presence of heparin at a concentration of 0.5IU/mL. Results: From the results of the test, it is evident that 10 patients from our group of 45 examined showed positivity of HIT, which is a significant number due to the proven occurrence of HIT in patients treated with LMWH and showing thrombocytopenia. If we evaluate these 10 patients in terms of IPF value, it is evident that 6 of them have an increased value of IPF >10%, which is a 33% positive predictive value and 4 have IPF >30%, when the positive predictive value is even 100%. Conclusions: Diagnosis of HIT remains a complicated clinical laboratory issue. However, new diagnostic options provide considerable potential for solving this problem. The implementation of IPF assays helps us in the diagnosis of HIT on two levels. On the one hand, it provides us with information on platelet consumption in hospitalized patients and thus draws our attention to HIT as one of the options for congestive thrombocytopenia, unless, of course, disseminated intravascular coagulation or thrombotic microangiopathy. Secondly, its implementation will increase the predictive value of the 4T score in patients at medium risk, which is, however, the vast majority indicated for HIT examination.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 12-13
Author(s):  
Marwah W Farooqui ◽  
Samrin Samad ◽  
Brittany Blum ◽  
Yatri Desai ◽  
Sivangi Patel ◽  
...  

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 <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.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1475-1475
Author(s):  
Kim A. Janatpour ◽  
Robert C. Gosselin ◽  
William E. Dager ◽  
Andrew Lee ◽  
John T. Owings ◽  
...  

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


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