High Levels IPF as Possible Predictor Heparin-Induced Thrombocytopenia

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.

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Utility of Optical Density Values from Heparin-Platelet Factor 4 Antibody Testing and Probability Scoring Models To Diagnose Patients with Heparin Induced Thrombocytopenia.

Blood ◽

10.1182/blood.v108.11.1475.1475 ◽

2006 ◽

Vol 108 (11) ◽

pp. 1475-1475

Author(s):

Kim A. Janatpour ◽

Robert C. Gosselin ◽

William E. Dager ◽

Andrew Lee ◽

John T. Owings ◽

...

Keyword(s):

High Risk ◽

Optical Density ◽

Predictive Value ◽

Platelet Factor 4 ◽

Platelet Factor ◽

Predictive Values ◽

Heparin Induced Thrombocytopenia ◽

Sensitivity Specificity ◽

Test Probability ◽

4T Score

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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Enforcing the 4T: Including a Hard Stop 4T Calculator into the Electronic Medical Record for Heparin Induced Thrombocytopenia

Blood ◽

10.1182/blood-2018-99-110375 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2442-2442

Author(s):

Thomas A Ollila ◽

Adam Zayac ◽

Adam J Olszewski ◽

Ross W Hilliard ◽

David Riley ◽

...

Keyword(s):

Quality Of Care ◽

Positive Predictive Value ◽

Predictive Value ◽

Clinical Management ◽

Research Funding ◽

Heparin Induced Thrombocytopenia ◽

Alternative Anticoagulation ◽

4T Score ◽

Heparin Exposure

Abstract Background: Among many causes of thrombocytopenia acquired during hospitalization, heparin-induced thrombocytopenia (HIT), an immune complex-mediated thrombogenic state with high morbidity and mortality, is one of the most feared etiologies. The clinical '4T' score is an established method to assess risk for HIT and guide immediate management(Lo, Juhl et al. 2006). However, the 4T score is not consistently used by clinicians, leading to potential over-testing and suboptimal management of suspected HIT. Our objective in this Quality Improvement (QI) project was to implement a mandatory 4T calculator (4TC) into the electronic medical record (EMR) to improve the positive predictive value of HIT antibody (HITA) testing, decrease the incidence of testing of low-risk patients, and to improve clinical management of suspected HIT. Methods: We developed a 4TC that assisted clinicians by integrating EMR-derived data on heparin exposure and the five most recent platelet counts with a link to an online calculator as well as clinical suggestions (Figure). As a part of this QI project, clinicians were required to enter the calculated 4T score before ordering a polyspecific HITA assay, which serves as the screening test for HIT in our institution. We reviewed laboratory records for all HITA tests performed over a six-month period, including 3 months before and after the implementation of a "hard stop" for HITA order in the EMR. We extracted data on the ordering hospital service team, 4T score documented in notes (if any), as well as quality of care indicators including rates of clinically recommended heparin cessation and initiation of alternative anticoagulation in the subgroup of patients with intermediate or high 4T score at the time of HITA order. In this QI project, we refrained from any statistical testing and summarized pre-specified outcome measures: incidence of HITA testing, positive predictive value of the HITA assay, and quality of care indicators. Results: We identified 99 (53 prior to the 4TC and 46 post) cases of HITA orders in the study period, among which there were 4 cases of confirmed HIT (either with positive IgG or positive serotonin-release assay [SRA]). Three HIT cases occurred after the 4TC was implemented. After the implementation of the 4TC, the positive predictive value for the HITA assay increased from 9% to 21%. The rate of clinically appropriate heparin order discontinuation increased from 72% to 88%, as did the initiation of alternative anticoagulation from 14% to 27%. HITA assay was most commonly ordered by the internal medicine service (35% of tests), non-cardiac intensive care service (30%), coronary care and cardiothoracic surgery services (21%), neurology (5%), and general surgery/other services (9%). Implementation of the 4TC did not significantly change this distribution, but the overall incidence of HITA orders decreased from 4.0 to 3.4 per 1000 admissions. We observed a high frequency of confirmatory SRA testing requested (18%), which is the reflex confirmatory test performed at our institution, even in cases of negative polyspecific HITA or HIT IgG. Conclusions: Addition of a 4T score calculator into the EMR which provides immediate feedback on patient's prior heparin exposure and recent platelet counts allows clinicians to consistently use the 4T score when considering HIT. Importantly, it also helps to educate non-hematologists on the proper management of HIT. Improved predictive value of the HITA assay suggests that our 4TC led to ordering HITA in a more appropriate patient population. We also demonstrated improved quality of care for suspected HIT, with increased rates of heparin cessation and initiation of alternative anticoagulation in patients with intermediate or high pre-test probability. Identifying clinical teams that order a disproportionate number of HITA assays will help us to direct education to improve clinical management. This QI project has led to other areas of improvement, particularly with regard to rational ordering of the SRA. At only three months of review since implementation of the 4TC, we have noted an improvement in the management of suspected HIT and a slight reduction in the incidence of testing. With continued review, we hope to demonstrate further improvement, as practitioners continue to use the 4TC and rely on clinical rationale rather than reflexive laboratory testing when evaluating thrombocytopenia in the hospital. Disclosures Olszewski: TG Therapeutics: Research Funding; Spectrum Pharmaceuticals: Consultancy, Research Funding; Genentech: Research Funding. Reagan:Alexion: Honoraria; Takeda Oncology: Research Funding; Pfizer: Research Funding.

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Comparison of Two Different ELISA Methods for Heparin-Induced Thrombocytopenia (HIT) Screening on an Automated ELISA Platform

Blood ◽

10.1182/blood-2019-125293 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4935-4935

Author(s):

Tatsiana Mardovina ◽

John G Chromczak ◽

Paul W Riley

Keyword(s):

Predictive Value ◽

False Negative ◽

High Sensitivity ◽

Clinical Findings ◽

Serotonin Release ◽

Laboratory Evaluation ◽

Platelet Factor ◽

Heparin Induced Thrombocytopenia ◽

Negative Results ◽

4T Score

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is an adverse complication of unfractionated and low molecular weight heparin caused by antibodies recognizing platelet factor 4-heparin (PF4/hep) complexes leading to platelet activation. The diagnosis of HIT is based on the combination of the clinical picture, using the 4T score along with screening and confirmatory methods to detect platelet activating anti‐PF4/H antibodies. OBJECTIVES: Performance was evaluated for two enzyme linked immunosorbent assays (ELISAs), 1) Asserachrom HPIA , Diagnostica Stago Inc., Parsippany, NJ, USA and 2) LIFECODES PF4 Enhanced, Immucor, Inc., Norcross, GA, USA for screening-based detection of PF4/hep antibodies. METHODS: ELISA assays were run per manufacturer recommendations and adapted for automation on a Dynex DS2 automated ELISA platform. Performance characteristics of the two immunoassays were assessed, including sensitivity, specificity, concordance with serotonin release assay (SRA), positive predictive value (PPV) and negative predictive value (NPV). 21 samples were used in the study. Results: Both assays, Asserachrom HPIA and LIFECODES PF4 Enhanced demonstrated 100% sensitivity and NPV, confirming both assays' reliability to detect and rule out HIT (see table). The diagnostic specificity was significantly higher for Asserachrom HPIA vs. LIFECODES PF4 Enhanced (77.8% vs 31.6%). Asserachrom HPIA showed fewer false positive results, with PPV of 42.9% for Asserachrom HPIA vs. 13.3% for LIFECODES PF4 Enhanced. No false negative results were found for either assay. Asserachrom HPIA demonstrated 81.0% concordance with SRA, vs. 38.1% for LIFECODES PF4 Enhanced. CONCLUSIONS: HIT is a life-threatening disorder, with diagnosis depending on clinical findings using the 4T score along with laboratory evaluation. Combining the 4T score with PF4/hep antibody screening increases the accuracy of excluding HIT. Our observations indicate Asserachrom HPIA provides results with high sensitivity and specificity, minimizing false positivess, allowing use of alternative anticoagulants more selectively in at risk patients, to potentially improve patient management while minimizing costs. Disclosures Mardovina: Diagnostica Stago, Inc.: Employment. Chromczak:Diagnostica Stago, Inc.: Employment. Riley:Diagnostica Stago, Inc.: Employment.

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PRT-060318, a novel Syk inhibitor, prevents heparin-induced thrombocytopenia and thrombosis in a transgenic mouse model

Blood ◽

10.1182/blood-2010-03-274969 ◽

2011 ◽

Vol 117 (7) ◽

pp. 2241-2246 ◽

Cited By ~ 80

Author(s):

Michael P. Reilly ◽

Uma Sinha ◽

Pierrette André ◽

Scott M. Taylor ◽

Yvonne Pak ◽

...

Keyword(s):

Mouse Model ◽

Transgenic Mouse ◽

Immune Complex ◽

Transgenic Mouse Model ◽

Control Group ◽

Platelet Factor ◽

Heparin Induced Thrombocytopenia ◽

Syk Inhibitor ◽

Induced Aggregation

AbstractHeparin-induced thrombocytopenia (HIT) is a major cause of morbidity and mortality resulting from the associated thrombosis. Extensive studies using our transgenic mouse model of HIT have shown that antibodies reactive with heparin-platelet factor 4 complexes lead to FcγRIIA-mediated platelet activation in vitro as well as thrombocytopenia and thrombosis in vivo. We tested PRT-060318 (PRT318), a novel selective inhibitor of the tyrosine kinase Syk, as an approach to HIT treatment. PRT318 completely inhibited HIT immune complex-induced aggregation of both human and transgenic HIT mouse platelets. Transgenic HIT model mice were treated with KKO, a mouse monoclonal HIT-like antibody, and heparin. The experimental group received orally dosed PRT318, whereas the control group received vehicle. Nadir platelet counts of PRT318-treated mice were significantly higher than those of control mice. When examined with a novel thrombosis visualization technique, mice treated with PRT318 had significantly reduced thrombosis. The Syk inhibitor PRT318 thus prevented both HIT immune complex-induced thrombocytopenia and thrombosis in vivo, demonstrating its activity in HIT.

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Comparison of an IgG-Specific Enzyme-Linked Immunosorbent Assay Cutoff of 0.4 Versus 0.8 and 1.0 Optical Density Units for Heparin-Induced Thrombocytopenia

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029615606532 ◽

2016 ◽

Vol 23 (3) ◽

pp. 282-286 ◽

Cited By ~ 5

Author(s):

Brianne M. Ritchie ◽

Jean M. Connors ◽

Katelyn W. Sylvester

Keyword(s):

Optical Density ◽

Immunosorbent Assay ◽

Predictive Value ◽

Retrospective Chart Review ◽

Serotonin Release ◽

Enzyme Linked Immunosorbent Assay ◽

Platelet Factor ◽

Heparin Induced Thrombocytopenia ◽

Institutional Review ◽

Sensitivity Specificity

Background: Previous studies have demonstrated optimized diagnostic accuracy in utilizing higher antiheparin–platelet factor 4 (PF4) enzyme-linked immunosorbent assay (ELISA) optical density (OD) thresholds for diagnosing heparin-induced thrombocytopenia (HIT). We describe the incidence of positive serotonin release assay (SRA) results, as well as performance characteristics, for antiheparin–PF4 ELISA thresholds ≥0.4, ≥0.8, and ≥1.0 OD units in the diagnosis of HIT at our institution. Methods: Following institutional review board approval, we conducted a single-center retrospective chart review on adult inpatients with a differential diagnosis of HIT evaluated by both antiheparin–PF4 ELISA and SRA from 2012 to 2014. The major endpoints were to assess incidence of positive SRA results, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy at antiheparin–PF4 ELISA values ≥0.4 OD units when compared to values ≥0.8 and ≥1.0 OD units. Clinical characteristics, including demographics, laboratory values, clinical and safety outcomes, length of stay, and mortality, were collected. Results: A total of 140 patients with 140 antiheparin–PF4 ELISA and SRA values were evaluated, of which 23 patients were SRA positive (16.4%) and 117 patients were SRA negative (83.6%). We identified a sensitivity of 91.3% versus 82.6% and 73.9%, specificity of 61.5% versus 87.2% and 91.5%, PPV of 31.8% versus 55.9% and 63.0%, NPV of 97.3% versus 96.2% and 94.7%, and accuracy of 66.4% versus 86.4% and 88.6% at antiheparin–PF4 ELISA thresholds ≥0.4, ≥0.8, and ≥1.0 OD units, respectively. Conclusion: Our study suggests an increased antiheparin–PF4 ELISA threshold of 0.8 or 1.0 OD units enhances specificity, PPV, and accuracy while maintaining NPV with decreased sensitivity.

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

Blood ◽

10.1182/blood-2019-127312 ◽

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.

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A Novel PF4-Heparin Microbead Assay and Plasma Protein Biomarker Profiling for Improved Diagnosis of Heparin Induced Thrombocytopenia.

Blood ◽

10.1182/blood.v110.11.3216.3216 ◽

2007 ◽

Vol 110 (11) ◽

pp. 3216-3216

Author(s):

Resmi Ravindran ◽

Imran Khan ◽

Robert Gosselin ◽

Ted Wun ◽

V.V. Krishnan ◽

...

Keyword(s):

Growth Factors ◽

Adhesion Molecules ◽

Predictive Value ◽

Simultaneous Detection ◽

Diagnostic Methods ◽

Coagulation Disorder ◽

Healthy Controls ◽

Platelet Factor ◽

Heparin Induced Thrombocytopenia ◽

Heparin Administration

Abstract Heparin-induced thrombocytopenia (HIT) is a potentially life-threatening, immune-mediated complication of heparin administration resulting in a hypercoagulable state. The diagnosis is made using clinical scoring systems with confirmatory laboratory testing. However, current diagnostic criteria may lack predictive value for HIT-associated thrombosis and need for alternative anticoagulation. Therefore, there is a need to develop diagnostic methods that will have a better predictive value for HIT diagnosis. The pathogenesis of HIT involves platelet-activating antibodies that recognize platelet factor 4 (PF4) -heparin complex, and may also involve dysregulation of inflammatory mediators and growth factors from platelets and endothelial cells. Luminex multiplex microbead assay allows for the simultaneous detection of multiple serum analytes. The aim of this study is to develop a multiplex method to detect anti-PF4-heparin antibodies and to generate profiles of cytokines, chemokines, growth factors and adhesion molecules with better predictive value for the diagnosis of HIT than current diagnostic methods. In combination with measurement of antibodies to (PF4)-heparin complex, such a panel is expected to enhance the accuracy of HIT diagnosis. To develop the anti-PF4-heparin IgG microbead assay, carboxylated Luminex microbeads were coated at various concentrations with the optimal molar ratio of the PF4/polyvinyl sulfonate (PF4/PVS) complex, the antigenic determinant from the GTI ELISA kit, (provided by GTI, Waukesha WI). The anti-PF4-heparin microbead assay was standardized using plasma samples from patients and healthy controls. Furthermore, we compared the anti-PF4-heparin microbead assay to traditional commercial HIT antibody ELISA kits from GTI, Diagnostica Stago and Aniara. To identify potential plasma biomarkers for HIT, measurements were made on plasma levels of 63 cytokines, chemokines, growth factors and adhesion molecules in patients with and without HIT (as defined by the Chong’s score) and healthy controls using commercial multiplex detection panels (Bio-Rad, Upstate, Linco). Multiplex data were analyzed using multivariate statistical methods and compared with their respective clinical scores. Preliminary anti-PF4-heparin microbead assay results show an overall concordance rate of 80% with GTI (Polyclonal) ELISA; 91% with Diagnostica Stago (Polyclonal); 78% with Aniara Polyclonal and 76% with Aniara IgG ELISA. The anti-PF4-heparin microbead assay results also show good correlation with clinical determination of HIT disease status as determined by Chong’s scoring (72% sensitivity, and 58% specificity). Preliminary biomarker profiling suggest that Il-2Ra, b-NGF, GRO-a, TNF-b, PDGF AB/BB, PDGF AA, and s-ICAM1 are potentially useful markers in further analysis for distinguishing HIT status. We have identified these candidate biomarkers to evaluate in a larger number of patient samples with suspected HIT. Our data show that our novel microbead assay for anti-PF4-heparin antibodies correlate well with the existing conventional ELISA results, and also correlate with HIT diagnosis as determined by the Chong’s score. Furthermore, we have identified a panel of biomarkers that could be useful for improved diagnosis and prognosis of HIT, and will establish a basis for further understanding the pathophysiology of this coagulation disorder.

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

Blood ◽

10.1182/blood.v114.22.1328.1328 ◽

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.

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Performance of 4T score and heparin–platelet factor 4 antibody in the diagnosis of heparin-induced thrombocytopenia (HIT) in cancer

Journal of Thrombosis and Thrombolysis ◽

10.1007/s11239-017-1523-z ◽

2017 ◽

Vol 44 (2) ◽

pp. 261-266 ◽

Cited By ~ 4

Author(s):

Myra Wong ◽

Thein Hlaing Oo ◽

Wei Qiao ◽

Naveen Garg ◽

Cristhiam M. Rojas-Hernandez

Keyword(s):

Platelet Factor 4 ◽

Platelet Factor ◽

Heparin Induced Thrombocytopenia ◽

4T Score

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The Balance Between Thrombin And Plasmin Action On Fibrinogen And The Occurrence Of Venous Thrombosis

10.1055/s-0038-1651990 ◽

1981 ◽

Author(s):

J Owen ◽

D Kvam ◽

H L Nossel ◽

K L Kaplan

Keyword(s):

Positive Predictive Value ◽

Venous Thrombosis ◽

Predictive Value ◽

Plasma Levels ◽

Close Association ◽

The Other ◽

Platelet Factor ◽

Normal Individuals ◽

Serial Measurements ◽

Granule Release

We have studied activation of coagulation, fibrinolysis and platelets in association with venous thrombosis in patients undergoing craniotomy. Serial 125I-fibriongen leg scans were used to detect the presence or onset of venous thrombosis and were confirmed by venography when positive. Serial measurements were made of plasma levels of fibrino- peptide A (FPA), thrombin-increasable fibrinopeptide B (TIFPB), platelet factor 4 (PF4) and beta thromboglobulin (βTG) as indices of thrombin or plasmin proteolysis of fibrinogen and of platelet α-granule release respectively. 17 patients had positive leg scans and 14 had negative leg scans. In normal individuals the FPA level is less than the TIFPB level with a ratio of FPA to TIFPB which is less than 0.5. In 16 of 17 patients with thrombosis FPA levels were elevated and the FPA:TIFPB ratio was markedly increased immediately preceding and overlapping the change of leg scan from negative to positive or with the initial detection of a positive leg scan. In 9 patients the time of onset of thrombosis was documented by the change of the leg scan from negative to positive. In 8 of these patients the FPA level rose and exceeded the TIFPB level preceding and/or overlapping the change in the leg scan. Similar changes in FPA and TIFPB were present in the other 8 patients but since the initial leg scan was positive the time of onset of thrombosis could not be documented. Prior1 to thrombosis $TG but not PF4 levels were elevated. The marked changes in the FPA/TIFPB ratio prior to thrombosis exhibited a significant positive predictive value for thrombosis. The data document a close association between venous thrombosis and imbalance between thrombin and plasmin action on fibrinogen as reflected by plasma levels of FPA and TIFPB.

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