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

Effectiveness of a new immuno-assay for the diagnosis of heparin-induced thrombocytopenia and improved specificity when detecting IgG antibodies

2010 ◽  
Vol 103 (01) ◽  
pp. 145-150 ◽  
Author(s):  
Claire Pouplard ◽  
Dorothée Leroux ◽  
Sandra Regina ◽  
Jérôme Rollin ◽  
Yves Gruel
Keyword(s):  
Antiphospholipid Antibodies ◽  
Serotonin Release ◽  
Platelet Lysate ◽  
Igg Antibodies ◽  
Heparin Induced Thrombocytopenia ◽  
Biological Assays ◽  
Clinical Criteria ◽  
Microtiter Plates ◽  
Release Assay ◽  
Immuno Assay

SummaryThe diagnosis of heparin-induced thrombocytopenia (HIT) is based on clinical criteria and biological assays. Most immunoassays detect antibodies (either IgG alone or additionally IgA and IgM) against PF4 immobilised in wells of microtiter plates with stoichiometric concentrations of polyanion (heparin or polyvinylsulfonate). We studied whether diagnostic sensitivity and/or specificity for HIT could be improved using a novel assay in which unfractionated heparin is immobilised alone to the microwells, with PF4 (and, potentially, other heparin-dependent antigen proteins) provided by adding platelet lysate during the procedure. Samples from 101 patients with suspected HIT and from 101 controls (including 50 with antiphospholipid antibodies) were tested. The global assay (Zymutest HIA IgG/A/M®, Hyphen BioMed) was positive for 39 of 40 patients with definite HIT (positive PF4-specific ELISA and positive serotonin release assay). It was positive in only two of the 101 control patients studied and also in 14 of the 61 patients with suspected HIT for whom the disease was excluded (specificity (sp): 77%). On the other hand, Zymutest HIA IgG®, an IgG-specific assay, was positive in only six patients without HIT (Sp: 90%). Heparin-dependent IgG antibodies were present at higher levels in patients with definite HIT than in those for whom the diagnosis of HIT was ruled out. A single ELISA that detects IgG antibodies is more effective for the diagnosis of HIT in clinical practice. These results also support the hypothesis that heparin-dependent antibodies of IgG class have a major role in the pathogenesis of HIT.

A New Enzyme Immuno-Assay That Only Detects IgG Antibodies to Heparin-PF4 Complexes (Zymutest HIA IgG®) Improves the Specificity of the Diagnosis of HIT without Loss of Sensitivity.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2096-2096
Author(s):  
Claire Pouplard ◽  
Sandra Regina ◽  
Jean Baptiste Valentin ◽  
Yves Gruel
Keyword(s):  
Platelet Activation ◽  
High Specificity ◽  
Serotonin Release ◽  
Igg Antibodies ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia ◽  
Release Assay ◽  
Immuno Assay ◽  
Enzyme Immuno Assay ◽  
Test Probability

Abstract Heparin-induced thrombocytopenia (HIT) is associated in most patients with the development of antibodies to heparin-modified platelet factor 4 (PF4). Commercial immuno-assays frequently detect these antibodies after cardiac surgery but only few patients develop clinical HIT. Therefore, platelet activation tests such as serotonin release assay (SRA) are necessary to ensure the diagnosis of HIT with high specificity. Another approach to increase diagnosis specificity could be to detect IgG antibodies which are of major clinical relevance since they are the only class able to directly activate platelets in the presence of heparin. Therefore, we evaluated the performances of a new commercial immuno-assay specific to IgG for the diagnosis of HIT Abs (Zymutest HIA IgG®, Hyphen Biomed, Neuville sur Oise, France). Samples from 101 patients with suspected HIT were analysed. 40 cases had developed significant levels of Abs to PF4 measured with PVS/PF4 ELISA (HAT45®,GTI, Brookfiled, WI, USA) and the diagnosis of HIT had been confirmed since SRA was positive. Every sample was then tested with a global assay named Zymutest HIA G/A/M® as followed: each diluted plasma (200 μl) was incubated for 1 hour with 50 μl of platelet lysate providing PF4 into wells previously coated with unfractionated heparin. After washings and incubation (1 hour) with anti IgG/A/M-HRP immunoconjugate, the enzyme activity was developed and absorbance was read at 450nm. In case of positive result (A450 ≥ 0.5), the isotype distribution was analysed with a specific and standardized assay using monospecific anti-IgG-, anti-IgA- and anti IgM-HRP conjugates (Zymutest HIA-IgG® or -IgA® or -IgM®). A450 values ≥ 0.5 were also considered as positive. GTI assay that detected IgG/A/M Abs to PVS/PF4 complexes in the 40 patients with HIT (Ss 100%) was also positive in 30 of the 61 cases with no HIT (Sp 50.8%). Comparatively, Zymutest HIA® global assay was positive in 39 of the 40 patients with HIT (Ss 97.5%) and in 14 of 61 cases without HIT (Sp 77%). On the other hand, significant levels of heparin-dependent IgG antibodies were also measured in these 39 HIT patients using Zymutest HIA IgG® assay (mean A450: 1.81; range A450: 0.5 – 2.76), and only in 6 patients without HIT (Sp: 90%). However, IgG levels measured in patients without HIT were significantly lower (mean A450: 0.60; range A450: 0.08 – 2.20) than in those with HIT (p < 0.0001). In addition, IgA or IgM heparin-dependent antibodies were only present, i.e. without IgG, in samples from patients for whom the diagnosis of HIT had been ruled out (n = 3). In conclusion, this study supports that the detection of significant levels of IgG heparin-dependent antibodies improves the diagnosis specificity in patients with a suspicion of HIT without loss of sensitivity. Nonetheless, whether IgG-specific immunoassays could avoid to perform platelet activation tests in patients with a strong pre-test probability of HIT warrant further study.

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.

Hematology Consultation along with the 4 T’s Clinical Scoring System Improves the Evaluation and Management of Heparin Induced Thrombocytopenia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3031-3031
Author(s):  
Nathan M. Shumway ◽  
Brendan M. Weiss ◽  
Lloyd H. Ketchum ◽  
Thomas J. Reid
Keyword(s):  
Scoring System ◽  
Serotonin Release ◽  
Pretest Probability ◽  
Hospital Death ◽  
Heparin Induced Thrombocytopenia ◽  
Clinical Probability ◽  
Clinical Scoring ◽  
Release Assay ◽  
Antibody Levels ◽  
Test Probability

Abstract Background. Heparin-induced thrombocytopenia (HIT) is a clinicopathologic diagnosis requiring thrombocytopenia, a thrombotic or other heparin-related toxicity and demonstration of heparin-PF4 antibodies. A recently described clinical scoring system to determine the pre-test probability of HIT, the 4 T’s, appears promising in evaluation of suspected HIT when based on serotonin release assay (ASH 2003, #1963). We sought to evaluate this scoring system in conjunction with the heparin-PF4 ELISA, which is more widely available. Furthermore, we sought to determine if optical density (OD), as a correlate of heparin-PF4 antibody levels, may have clinical significance. Methods. A retrospective review of all heparin-PF4 antibody tests (GTI, Waukesha, WI) at our institution over 3 years was performed. The clinical probability of HIT was calculated using the 4 T’s model through an extensive review of computerized medical records. The clinical probability was compared to the OD of the ELISA for heparin-PF4. Results. There were 134 heparin-PF4 tests performed, sufficient clinical data was available for 104 patients. The distribution of low probability (LP), moderate probability (MP) and high probability (HP) was 41%, 43% and 15%, respectively. Overall, 14% received LMWH, 82% received unfractionated heparin, and 5% received no documented heparin. The indications for anticoagulation were prophylaxis in 49% and treatment in 46%. In-hospital death occurred in 25% of patients. Hematology consultation was obtained in 54% of cases. In patients who received a hematology consultation and had a high clinical probability of HIT, 78% were started on an alternate anticoagulant (p=0.002). In patients who did not receive a hematology consultation and who had a high clinical probability, only 29% received alternate anticoagulation (p=0.099). The OD of the ELISA for heparin-PF4 antibodies was 0.146 (0.066–0.552), 0.239 (0.087–2.883) and 0.396 (0.135–3.689), for LP, MP and HP groups, respectively. This was statistically significant between LP and MP and between LP and HP, (p <0.0005), but not statistically significant between MP and HP (p=0.060). Conclusions. There is a trend toward higher heparin-PF4 antibodies as measured by OD as clinical probability of HIT increases; larger prospective studies are needed to confirm these findings. The use of alternate anticoagulation more closely reflects clinical scores when hematology consultation is obtained. Likelihood of alternate anticoagulation based on pretest probability (4T’s) without hematology consultation (−) alt. anticoagulation (+) alt. anticoagulation Total Low 20 (95%) 1 (5%) 21 (100%) Moderate 16 (76%) 5 (24%) 21 (100%) High 5 (71%) 2 (29%) 7 (100%) Likelihood of alternate anticoagulation based on pretest probability (4T’s) with hematology consultation (−) alt. anticoagulation (+) alt. anticoagulation Total Low 18 (82%) 4 (18%) 22 (100%) Moderate 12 (50%) 12 (50%) 24 (100%) 2 (22%) 7 (78%) 9 (100%)

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.

Incidence of Thrombosis in Serotonin Release Assay Negative Patients and Correlation with Pretest Heparin-Induced Thrombocytopenia Scoring System.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1816-1816 ◽  
Author(s):  
Christopher Hueser ◽  
Anjali J Patel ◽  
John N Allan
Keyword(s):  
Platelet Count ◽  
Scoring System ◽  
Thrombotic Event ◽  
Study Groups ◽  
Serotonin Release ◽  
Single Institution ◽  
Heparin Induced Thrombocytopenia ◽  
Significant Difference ◽  
Release Assay ◽  
4T Score

Abstract Introduction: Heparin-induced thrombocytopenia (HIT) is an immune mediated, adverse effect related to both unfractionated heparin (UFH) and low-molecular weight heparin (LMWH). HIT may result in significant morbidity and mortality. The serotonin release assay (SRA) is utilized in conjunction with clinical information to diagnosis HIT. Employment of the pretest clinical scoring system, known as the “4Ts”, classifies patients as having a low, intermediate or high probability for developing HIT. Previous investigators have reported clinically diagnosed HIT in patients with a negative SRA. However, there is no systematic study evaluating such a group of patients. We determined the frequency of thromboses in SRA negative patients and determined the correlation between the 4T score in patients with and without thromboses. Methods: We report a descriptive, single institution, retrospective study of 181 consecutive samples over the course of one year sent to the Coagulation Laboratory of St. Louis University for the work up of suspected HIT. A total of 142 patients were eligible. Patients with SRA negative samples were evaluated for evidence of thrombosis. Diagnosis of a thrombotic event was made by computed tomography (CT), venous Doppler ultrasonography (US), and ventilation-perfusion scanning (V/Q). Defined patient study groups were: all evalulable patients (PALL), patients with thromboses (TPOS) and patients without thromboses (TNEG). Analyses, between each patient group, the 4T score, mean platelet count prior to heparin therapy, and mean platelet nadirs were performed. Results: The overall incidence of proven thromboses in evaluable SRA negative patients was 14.8% (n=21). Of the 21 thromboses, 17(81.0%) were deep venous thromboses (DVT), 3(14.3%) were DVT and pulmonary embolus (PE), and 1(0.7%) was an isolated PE. A significant difference in 4T score was observed between TPOS vs PALL (p&lt;0.0001) and TPOS vs TNEG (p&lt;0.0001) groups. There was no difference between the patient groups PALL vs TNEG (p=0.985). No statistically significant difference between the study groups was seen for either initial platelet averages (TPOS vs PALL [p=0.8923], TPOS vs TNEG [p=0.2091], PALL vs TNEG [p=0.2550]) or nadirs (TPOS vs PALL [p=0.4664], TPOS vs TNEG [p=0.3763], PALL vs TNEG [p=0.7860]). Total Evaluable Patients (PALL) Patients without Thrombosis (TNEG) Patients with Thrombosis (TPOS) * Missing data was included in calculations for patients without thrombosis n 142 (100%) 110 (77.46)/121(85.2%)* 21(14.8%) Avg. 4T Score 3.23 (±1.81) 2.79 (±1.61)* 5.50 (±0.83) Avg. Initial Platelet Count (1X10 9 /L) 198.98 (±97.19) 194.16 (±99.39)* 223.90 (±79.31) Avg. Platelet Nadir (1X10 9 /L) 75.02 (±48.57) 73.41 (±46.47)* 82.86 (±59.42) Avg. Platelet Drop (1X10 9 /L) 123.96 (62.30%) 94.77 (48.81%)* 141.04 (62.99%) NO Data* 11 11(7.75%)* NA Conclusions: A higher incidence of thrombotic events in SRA negative patients was seen compared to historical data. A strong positive and negative correlation exists between high and low 4T scores, respectively, and the probability of thromboses from HIT. Prospective data are needed to address the incidence of thrombosis for patients in whom the pretest probability of HIT is high and in whom the SRA is negative. Studies evaluating the utility of serial SRA testing in such patients may lead to earlier identification of those at high risk for thromboses. Limitations of this study were the retrospective design, single institution, and the lack of serial SRA testing.

scholarly journals Clinical Significance of the Serotonin Release Assay and Platelet Count Monitoring After Cardiac Surgery

2017 ◽  
Vol 24 (6) ◽  
pp. 944-949 ◽  
Author(s):  
Shinya Motohashi ◽  
Takefumi Matsuo ◽  
Hidenori Inoue ◽  
Makoto Kaneko ◽  
Shunya Shindo
Keyword(s):  
Cardiac Surgery ◽  
Platelet Count ◽  
Clinical Course ◽  
Serotonin Release ◽  
Enzyme Linked Immunosorbent Assay ◽  
Heparin Induced Thrombocytopenia ◽  
Release Assay ◽  
Immunological Assays ◽  
Platelet Count Monitoring ◽  
The Relationship

Heparin-induced thrombocytopenia (HIT) is one of the serious complications in patients who undergo cardiac surgery. However, there remains a major problem in diagnosing HIT because the current immunological assays for detection of HIT antibody have limitations. Furthermore, the clinical course of thrombocytopenia in this surgery makes it increasingly difficult to diagnose HIT. We investigated the relationship between platelet count and HIT antibody in 59 patients who underwent cardiac surgery using cardiopulmonary bypass (CPB). The number of postoperative HIT antibody-positive patients evaluated using enzyme-linked immunosorbent assay kit (polyanion IgG/IgA/IgM complex antibodies/antiplatelet factor 4 enhanced) was 37 (62.7%). In contrast, platelet activation by HIT antibody was evaluated using the serotonin release assay (SRA). More than 20% and 50% release of serotonin was obtained from 12 patients (20.3%) and 8 patients (13.6%), respectively. The levels of d-dimer were significantly different on postoperative day 14 between SRA-positive and SRA-negative groups; however, postoperative thrombus complication was not detected using sonography in the patients with positive serotonin release at all. After being decreased by the operation, their platelet count recovered within 2 weeks in both groups equally. In our study, although the patients were positive in the platelet activating HIT antibody assay, they remained free from thrombosis and their platelet count recovered after early postoperative platelet decrease. Therefore, in addition to the SRA, monitoring of platelet count might be still considered an indispensable factor to facilitate the prediction of HIT thrombosis prior to manifestation in the patients undergoing cardiac surgery using CPB.

Pathophysiology of Heparin-Induced Thrombocytopenia

2000 ◽  
Vol 124 (11) ◽  
pp. 1657-1666 ◽  
Author(s):  
Fabrizio Fabris ◽  
Sarfraz Ahmad ◽  
Giuseppe Cella ◽  
Walter P. Jeske ◽  
Jeanine M. Walenga ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Serotonin Release ◽  
Platelet Factor 4 ◽  
Thrombin Inhibitors ◽  
Platelet Factor ◽  
Cellular Activation ◽  
Heparin Induced Thrombocytopenia ◽  
New Information ◽  
Study Selection ◽  
Release Assay

Abstract Objective.—This review of heparin-induced thrombocytopenia (HIT), the most frequent and dangerous side effect of heparin exposure, covers the epidemiology, pathophysiology, clinical presentation, diagnosis, and treatment of this disease syndrome. Data Sources and Study Selection.—Current consensus of opinion is given based on literature reports, as well as new information where available. A comprehensive analysis of the reasons for discrepancies in incidence numbers is given. The currently known mechanism is that HIT is mediated by an antibody to the complex of heparin–platelet factor 4, which binds to the Fc receptor on platelets. New evidence suggests a functional heterogeneity in the anti-heparin-platelet factor 4 antibodies generated to heparin, and a “superactive” heparin-platelet factor 4 antibody that does not require the presence of heparin to promote platelet activation or aggregation has been identified. Up-regulation of cell adhesion molecules and inflammatory markers, as well as preactivation of platelets/endothelial cells/leukocytes, are also considered to be related to the pathophysiology of HIT. Issues related to the specificity of currently available and new laboratory assays that support a clinical diagnosis are addressed in relation to the serotonin-release assay. Past experience with various anticoagulant treatments is reviewed with a focus on the recent successes of thrombin inhibitors and platelet GPIIb/IIIa inhibitors to combat the platelet activation and severe thrombotic episodes associated with HIT. Conclusions.—The pathophysiology of HIT is multifactorial. However, the primary factor in the mediation of the cellular activation is due to the generation of an antibody to the heparin-platelet factor 4 complex. This review is written as a reference for HIT research.

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

Perfusion ◽  
2019 ◽  
Vol 35 (5) ◽  
pp. 378-383 ◽  
Author(s):  
Jaclyn Sullivan ◽  
Erica Bak ◽  
Mary Jane Sullivan ◽  
Payal K. Gurnani
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Predictive Value ◽  
Medical Center ◽  
High Sensitivity ◽  
Serotonin Release ◽  
Heparin Induced Thrombocytopenia ◽  
Membrane Oxygenation ◽  
Observational Cohort ◽  
Post Cardiopulmonary Bypass ◽  
Scoring Tools

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.

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