Incidence of Heparin-Induced Thrombocytopenia in Patients With Newly Implanted Mechanical Circulatory Support Devices

2021 ◽  
pp. 106002802110387
Author(s):  
Long To ◽  
Dana Attar ◽  
Brittany Lines ◽  
Melissa McCarty ◽  
Hassan Nemeh ◽  
...  
Keyword(s):  
Negative Predictive Value ◽  
Predictive Value ◽  
Mechanical Circulatory Support ◽  
Serotonin Release ◽  
Circulatory Support ◽  
Anticoagulation Management ◽  
Heparin Induced Thrombocytopenia ◽  
Mechanical Circulatory Support Devices ◽  
High Negative Predictive Value ◽  
Release Assay

Background: Heparin exposure and device-related thrombocytopenia complicate the diagnosis of heparin-induced thrombocytopenia (HIT) in patients receiving mechanical circulatory support (MCS). To improve anticoagulation management for patients with newly implanted MCS devices, incidence of confirmed HIT needs to be further characterized. Objectives: The purpose of this study is to describe the incidence of HIT and clinical utility of the 4Ts score in patients with newly implanted MCS devices. Methods: This is a retrospective analysis of MCS patients receiving unfractionated heparin from 2014 to 2017. The primary end point was incidence of laboratory-confirmed HIT. Strong positive, likely positive, low probability, and negative HIT categories were established based on heparin-induced platelet antibody (HIPA) and serotonin release assay (SRA). Secondary end points include characterization of platelet trends, argatroban use, incidence of HIT among each of the MCS devices, and utility of 4Ts score. Results: A total of 342 patient encounters met inclusion criteria, of which 68 HIPA tests and 25 SRAs were ordered. The incidence of HIT was 0.88% (3/342) and 4.4% (3/68) in patients with suspected HIT. Of the 68 HIPA tests, 3 (4.4%) were considered strong positive and 3 of the 25 SRAs were positive. Median 4Ts score was 4 [2.5-4] and optical density 0.19 [0.11-0.54]. The positive predictive value for the 4Ts score was 0.15 (CI = 0.03-0.46) and negative predictive value, 0.93 (CI = 0.82-0.98). Conclusion and Relevance: HIT occurs infrequently with newly implanted MCS devices. The 4Ts score appears to have a high negative predictive value for ruling out HIT.

scholarly journals Performance of the New Automated Latex Immunoturbidometric Assay in the Diagnosis of Heparin Induced Thrombocytopenia: A Single Institution Experience

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4689-4689
Author(s):  
Sriman Swarup ◽  
Somedeb Ball ◽  
Nimesh Adhikari ◽  
Anita Sultan ◽  
Khatrina Swarup ◽  
...  
Keyword(s):  
Positive Predictive Value ◽  
Negative Predictive Value ◽  
Sensitivity And Specificity ◽  
Predictive Value ◽  
Serotonin Release ◽  
Small Sample ◽  
Second Phase ◽  
Heparin Induced Thrombocytopenia ◽  
Study Population ◽  
Release Assay

Introduction: Heparin induced thrombocytopenia (HIT) is a severe prothrombotic condition, usually triggered by exposure to heparin products. It is characterized by platelet activation induced by the formation of antibodies to the platelet factor 4 (PF4)/ heparin polyanion complexes. Diagnostic algorithm includes clinical scoring (4T score) alongside serological test for detection of these antibodies (HIT-Ab), while serotonin release assay (SRA) remains the gold- standard for confirmation. The automated latex immunoturbidometric assay (LIA) has recently been FDA approved as a screening tool for HIT and is a potential alternative to the conventional particle immunofiltration assay (PIFA) for time-sensitive detection of HIT-Ab to guide treatment considerations. We recently introduced LIA in our institution. In this study, we present our experience with LIA in comparison to PIFA in the diagnosis of HIT. Methods: We retrospectively reviewed the charts of all the patients on whom a PIFA was ordered between March 2017 and March 2018 in our hospital. We collected information on the results of the PIFA and SRA (if available). We replaced PIFA with LIA for HIT screening. Then, we introduced a structured protocol for diagnosis of HIT in our institution by incorporating 4T scoring alongside LIA order in the electronic medical record (EMR), in December 2018. We reviewed the EMR of all the patients on whom HIT-Ab test (LIA) was ordered between January and June of 2019, and collected similar information as before. All the data were compiled in a single master excel sheet for calculation of performance characteristics (sensitivity, specificity, positive and negative predictive values) for both PIFA and LIA. A patient was considered to have the diagnosis of HIT if the result of SRA was available and positive. Results: In the first phase, a total of 31 orders for SRA was noted against 170 PIFA orders. Five patients had a positive SRA, of whom two were PIFA negative. Half the patients with a negative SRA result were positive for PIFA. Hence, the sensitivity and specificity of PIFA test for our study population were noted to be 60% and 50%, respectively. PIFA had a positive predictive value (PPV) of mere 18.75% for the diagnosis of HIT, whereas the negative predictive value (NPV) was found to be 86.66%. Introduction of structured protocol for HIT diagnosis substantially reduced the number of inappropriate SRA orders in the second phase. On review of data for six months with the new HIT-Ab test LIA, SRA was ordered in only eight patients, to go with 69 orders for the LIA. The result of LIA was positive in all three patients with a positive SRA, whereas it was false positive in four instances. Only one patient was negative for both LIA and SRA during this period. LIA was found to be 100% sensitive and 20% specific for the diagnosis of HIT in our sample. PPV and NPV for LIA were 42.85% and 100%, respectively. Conclusion: The sensitivity and specificity of LIA were found to be 100% and 20%, respectively, in our study population, which is different from the earlier report (Warkentin et al. 2017). The small sample size is a limitation of our study. Higher PPV and NPV for LIA, with its quick turnaround time, make it a useful alternative for the time-sensitive determination of post-test probability for HIT in patients. [HIT- Ab- Heparin Induced Thrombocytopenia Antibody, PIFA- Particle Immunofiltration Assay, LIA- Latex Immunoturbidometric Assay, SRA- Serotonin Release Assay, +ve- Positive, -ve - Negative, PPV- Positive Predictive Value, NPV- Negative Predictive Value] Disclosures No relevant conflicts of interest to declare.

Low Risk 4T Score Can Rule out Heparin-Induced Thrombocytopenia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1328-1328
Author(s):  
Prapti A. Patel ◽  
Catherine Burke ◽  
Karen Matevosyan ◽  
Eugene P. Frenkel ◽  
Ravindra Sarode ◽  
...  
Keyword(s):  
Negative Predictive Value ◽  
Predictive Value ◽  
Thrombin Inhibitors ◽  
Bleeding Complications ◽  
High Dose ◽  
Heparin Induced Thrombocytopenia ◽  
Dose Heparin ◽  
High Negative Predictive Value ◽  
4T Score ◽  
Rule Out

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.

Correlation Of Heparin Confirmatory Test (HCT) With Optical Density (OD) and Serotonin Release Assay (SRA) In The Diagnosis Of Heparin Induced Thrombocytopenia (HIT)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4754-4754 ◽  
Author(s):  
Ravneet Thind ◽  
Danielle Heidemann ◽  
Sundara Raman ◽  
Philip Kuriakose
Keyword(s):  
Optical Density ◽  
Predictive Value ◽  
Serotonin Release ◽  
Thrombin Inhibitors ◽  
Confirmatory Test ◽  
Functional Assay ◽  
Heparin Induced Thrombocytopenia ◽  
Laboratory Confirmation ◽  
Confirmation Test ◽  
Release Assay

Introduction Heparin-induced thrombocytopenia (HIT) is a potentially fatal, thrombotic complication of heparin therapy mediated by antibodies to complexes between platelet factor 4 (PF4) and heparin. Accurate and rapid diagnosis with prompt commencement of therapy are imperative as delays in treatment are associated with an increasing risk of thrombosis, amputation, or death. On the flip side, initiation of therapy with direct thrombin inhibitors without laboratory confirmation carries a significant risk of bleeding. Two types of laboratory tests are available for detection of these antibodies: a widely available immunoassay (ELISA), which is very sensitive to the presence of anti-heparin/PF4 antibodies, but is less specific to the clinical syndrome of HIT because of detection of non-pathological antibodies. The Serotonin Release Assay (SRA) is a functional assay that is now considered the gold standard for confirmatory diagnosis of HIT due to its high specificity. However, the downside of SRA is the cost involved, limited availability and a turnaround time of 5-7 days. As such, a heparin confirmatory test (HCT) with excess heparin has been in use since mid 2011 on positive ELISA samples in our laboratory to improve test specificity. This test is more cost and time efficient, with a turnover time of no more than 48 hours. As noted in prior studies, inhibition of a positive ELISA result by 50% or more in the presence of excess heparin is considered confirmatory of heparin-dependent antibodies. Likewise a negative confirmatory test is defined as a decrease of 50% or less in antibody binding in the presence of heparin. Aim a) Correlation of Heparin Confirmatory test (HCT) with strength of HIT ELISA, vis-à-vis optical density (OD) of 0.4 - 0.99 and OD of >/= 1.0. b) Correlation of HCT results with SRA, to see if the latter can be replaced by the heparin confirmatory test. Patients and Methods A retrospective chart review of adult patients hospitalized at our institution with suspected HIT from July 2011 until January 2013 was done. There were 101 such patients. All patients who had a positive HIT ELISA, then had HCT as per our standard lab practice, with an SRA test done for diagnosis/confirmation of HIT, as per standard clinical practice. Historically, the major strength of SRA assay is its specificity. The optical density on HIT ELISA and SRA results were then compared with the Heparin Confirmatory test to establish clinical significance. Results Of the 101 patients tested for HIT ELISA, 49 were positive. HCT and SRA were performed on all 49 samples, 1 out of which was reported as indeterminate. Hence 48 samples were used for primary analysis, comparing HCT to the OD as well as the SRA results. Out of 48 patients, 6 had positive SRA with Heparin inhibition of >50% (sensitivity 6/6 = 100%). Remaining 42 patients had negative SRA, 7 out of which had Heparin inhibition of <50% (specificity 7/42 = 16.6%). All 7 patients with a negative HCT had a negative SRA, making the negative predictive value of the HCT 100%; however positive predictive value was only 14.6% (6/41). There was no correlation between the OD and Heparin Confirmation test. Conclusions Although there is data suggesting that there might be some value to the Heparin Confirmation test, we were unable to show a significant correlation between HCT and OD or between HCT and SRA. The prospect of having a cost effective and rapid assay for laboratory confirmation of HIT will always be a relevant need. We feel that a larger, prospective study should be conducted to definitively assess the relationship between HCT and SRA. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Frequency of Anti-PF4/Heparin Antibodies in Patients Treated with Extra-Corporeal Membrane Oxygenation and Detection By Sensitized Serotonin Release Assay of Pathogenic Heparin-Induced Thrombocytopenia Antibodies

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1143-1143
Author(s):  
Caroline Vayne ◽  
Marc-Antoine May ◽  
Thierry Bourguignon ◽  
Eric Lemoine ◽  
Eve-Anne Guéry ◽  
...  
Keyword(s):  
Serotonin Release ◽  
Circulatory Support ◽  
Plasma Samples ◽  
Extra Corporeal Membrane Oxygenation ◽  
Platelet Factor ◽  
Detection Range ◽  
Heparin Induced Thrombocytopenia ◽  
Membrane Oxygenation ◽  
Release Assay ◽  
The Impact

Abstract Introduction: Extra-Corporeal Membrane Oxygenation (ECMO) provides circulatory support in case of severe cardiac failure and is associated, as cardiopulmonary bypass, with strong activation of platelets, which likely leads to the release in patient blood of large amounts of platelet factor 4 (PF4). Therefore, systematic use of unfractionated heparin (UFH) for maintaining patency of circuits and to prevent thrombosis, exposes patients to heparin-induced thrombocytopenia (HIT). However, the risk of HIT in this particular clinical setting remains poorly documented. Objectives: In this monocentric study, the frequency of development of antibodies to PF4 modified by heparin (anti-PF4/H Abs) was prospectively evaluated in patients who had underwent ECMO, and the impact of these Abs on platelet count (PC) and clinical course was assessed. Patients and Methods: From February 2014 to January 2018, we enrolled in the University Hospital of Tours all consecutive adult patients with ECMO and treated with UFH for at least 5 days. Plasma samples were collected daily, and PF4-specific Abs were systematically detected using HAT45® (GTI), an ELISA assaying IgG, IgA and IgM isotypes, and another kit specific for IgG to modified PF4 (HAT45G®; GTI). Serotonin release assay (SRA) was also performed to detect platelet-activating Abs (and therefore potentially pathogenic) in plasma samples containing significant levels of anti-PF4/H IgG. Noticeably, SRA was also done after adding 10 μg/ml of PF4 in the reaction mixture (PF4-SRA), since we recently showed this modification might improve the detection of pathogenic HIT antibodies (Vayne et al, Brit J Haematol, 179(5):811-819, 2017). Demographics, PC, and clinical events were collected in all patients until the end of ECMO. Results: Fifty-seven patients with a median age of 57 years (range: 24-76) and who were mainly men (sex ratio W/M: 0.3) were enrolled. ECMO was performed due to medical issues (dilated cardiomyopathy, myocardial infarction, acute myocarditis) in 70 % of cases and in surgical settings in the others. Significant titres of anti-PF4/H IgG/A/M Abs were detected before ECMO in 6 of 57 patients (10.5%), with anti-PF4/H IgG present in only 3 cases (5%). After ECMO was initiated, 28 patients (49%) developed IgG/A/M anti-PF4/H Abs, with anti-PF4/H IgG present in 17 of them (30%). Half of these patients were immunized within 5 days after ECMO initiation and 95% of them within 10 days, with a median delay of 8 days before Abs detection (range: 4-26 days). Only 3 patients (5%) exhibited pathogenic anti-PF4/H IgG with positive SRA and the level of platelet release was always stronger when the test was performed with exogenous PF4 (SRA-PF4). Moreover, in one patient, pathogenic HIT Abs were detected earlier by PF4-SRA, i.e. 2 days before conventional SRA was positive. An abnormal PC pattern was evidenced in 2 of the 3 patients with positive SRA, with a dramatic PC fall after day 5 (of 49% and 31.5 % between days 9-10 and 5-6 respectively). The diagnosis of HIT was confirmed in these 2 cases, which also had suggestive clinical manifestations (arterial thrombosis and cutaneous necrosis). In the third patient, HIT was not suspected, because of low PC before ECMO with persistent thrombocytopenia post-operatively and early death on day 9. In the patients with negative SRA, the development of anti-PF4/H IgG did not appear to impact the biological and clinical evolution, with similar rates of thrombosis and death than in non-immunized patients. Therefore, patients with non-pathogenic anti-PF4/H IgG displayed the same PC pattern than non-immunized patients, with decreasing PC from ECMO initiation until day 5, followed by a slow PC recovery. Conclusion: The development of anti-PF4/H Abs is frequent during ECMO but these antibodies are rarely pathogenic, and not associated with a less favourable prognosis. PC evolution analysis during ECMO appears reliable for suspecting HIT, and a dramatic PC fall or a non-recovery of PC after day 5 should prompt to look for platelet-activating anti-PF4/H Abs. Therefore, IgG specific immunoassays should always be combined with platelet activation tests to improve the specificity of HIT diagnosis in this particular clinical condition. Interestingly, the addition of exogenous PF4 when performing SRA could allow an earlier detection of HIT pathogenic antibodies in patients undergoing ECMO. Disclosures No relevant conflicts of interest to declare.

Prospective Evaluation of 4T’s Score and Rapid Particle Gel Immuno-Assay Specific to H/PF4 Complexes To Exclude Heparin-Induced Thrombocytopenia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1244-1244
Author(s):  
Claire Pouplard ◽  
Marc Fouassier ◽  
Catherine Ternisien ◽  
Pierre Gueret ◽  
Marc Trossaert ◽  
...  
Keyword(s):  
Predictive Value ◽  
Medical Records ◽  
Scoring System ◽  
Serotonin Release ◽  
Igg Antibodies ◽  
Heparin Induced Thrombocytopenia ◽  
Biological Assays ◽  
Release Assay ◽  
Immuno Assay ◽  
Positive Results

Abstract Heparin-induced thrombocytopenia (HIT) is a severe complication of heparin treatment because of the risk of venous and arterial thromboses. HIT is often difficult to diagnose in practice since most patients have several potential causes of thrombocytopenia. A scoring system named 4T’s and based on four criteria (i.e. Thrombocytopenia, Timing of platelet count fall, Thrombosis or other sequelae, oTher cause of thrombocytopenia) has recently been proposed to estimate the probability of HIT before laboratory testing (T Warkentin, BJH 2003), and a particle gel immunoassay (H/PF4-PaGIA, Diamed, Switzerland) has also been developed to provide a rapid detection of HIT antibodies in less than one hour after blood sampling. The aim of this study was to compare the performance of both methods to exclude HIT in emergency conditions. One hundred twenty consecutive patients suspected of having HIT were included in 4 different centers over 9 months. Medical records were independently analyzed by two physicians, and the probability of HIT was evaluated using the 4T’s score blind to the results of the PaGIA. In addition to PaGIA performed on the day of suspicion, serotonin release assay (previously identified as higly specific for HIT) and PVS/PF4 ELISA (GTI, Brookfiled, WI) were also performed, and HIT was confirmed when both assays were positive. The risk of HIT was evaluated by the 4T’s score as low (LR), intermediate (IR) and high (HR) in 35% (n = 42), 63% (n = 73) and 4% (n = 5) of patients, respectively (Table). Since SRA (that detects pathogenic HIT IgG antibodies) was negative in all LR patients, the negative predictive value (NPV) of the 4T’s score, which allowed the diagnosis of HIT to be eliminated in 35% of cases, was 100%. PaGIA was negative in 99 cases, including 16 patients for whom PVS/PF4 ELISA was positive (median 0.519, range 0.410 – 2.4). The diagnosis of HIT was excluded in all of these patients by the clinical evolution and since SRA was consistently negative. The NPV of PaGIA was thus 100% and this test was able to eliminate HIT in 82% of patients. The diagnosis of HIT was confirmed in 12 patients (SRA positive), including 5 evaluated as HR and 7 as IR by the 4T’s score, and PaGIA was positive in all these cases (sensitivity 100%). However, the positive predictive value (PPV) of PaGIA was lower (51%) since positive results were also obtained in 9 cases for whom the diagnosis of HIT was eliminated. In conclusion, the 4T’s scoring system appears to be a reliable first step to evaluate the likelihood of HIT, and to avoid unecessary biological assays in patients evaluated as LR. In addition, PaGIA can be applied to eliminate HIT with a high NPV, and could be particularly useful in patients classified as IR by the 4T’s score. Finally, platelet activation tests such as SRA are always mandatory to confirm HIT in every patient having developed antibodies specific to polyanion-modified PF4. PaGIA PVS/PF4 ELISA SRA 4T’s score n −/+ −/+ −/+ Low Risk (LR) 42 37/5 33/9 42/0 Intermediate Risk (IR) 73 62/11 52/21 66/7 High Risk (HR) 5 0/5 0/5 0/5 Total 120 99/21 85/35 108/12

FDG-PET in Hodgkin lymphoma

2008 ◽  
Vol 47 (06) ◽  
pp. 235-238 ◽  
Author(s):  
M. Dietlein ◽  
C. Mauz-Körholz ◽  
A. Engert ◽  
P. Borchmann ◽  
O. Sabri ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Negative Predictive Value ◽  
Predictive Value ◽  
Fdg Pet ◽  
Study Groups ◽  
Therapy Control ◽  
German Study ◽  
High Negative Predictive Value ◽  
Consolidation Radiotherapy

SummaryThe high negative predictive value of FDG-PET in therapy control of Hodgkin lymphoma is proven by the data acquired up to now. Thus, the analysis of the HD15 trial has shown that consolidation radiotherapy might be omitted in PET negative patients after effective chemotherapy. Further response adapted therapy guided by PET seems to be a promising approach in reducing the toxicity for patients undergoing chemotherapy. The criteria used for the PET interpretation have been standardized by the German study groups for Hodgkin lymphoma patients and will be reevaluated in the current studies.

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