scholarly journals Clinical and laboratory characteristics associated with a high optical density anti-platelet factor 4 ELISA test

2015 ◽  
pp. 277
Author(s):  
Lawrence Gardner ◽  
Benjamin Lu ◽  
David Kudlowitz
Keyword(s):  
Optical Density ◽  
Elisa Test ◽  
Platelet Factor 4 ◽  
Platelet Factor

scholarly journals Anti-heparin/platelet factor 4 antibody optical density values and the confirmatory procedure in the diagnosis of heparin-induced thrombocytopenia

2008 ◽  
Vol 100 (10) ◽  
pp. 678-684 ◽  
Author(s):  
Stephanie L. Perry ◽  
Thomas L. Ortel ◽  
Nicole L. Whitlatch
Keyword(s):  
Optical Density ◽  
Tertiary Care ◽  
Platelet Factor 4 ◽  
Confirmatory Test ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia ◽  
Highly Sensitive ◽  
Confirmatory Assay ◽  
Density Values ◽  
Test Specificity

SummaryLaboratory testing for heparin-induced thrombocytopenia (HIT) includes the highly sensitive, though less specific, heparin/ platelet factor 4 (PF4) ELISA. A confirmatory test with excess heparin is routinely performed on positive ELISA results to improve test specificity; the significance of a negative confirmatory result is unknown. The aim was firstly to evaluate the clinical utility of the PF4 ELISA confirmatory assay, secondly to examine the relationship between ELISA optical density (OD) value and clinical diagnosis of HIT, and thirdly to assess current practice at a tertiary care medical centre regarding patients with anti-heparin/PF4 antibodies. Patients with anti-heparin/PF4 antibodies detected by commercial ELISA during 2005 were identified. A confirmatory test was performed on positive ELISA results. Patients were labeled confirmatory positive (confirm+) or confirmatory negative (confirm−). Patients were classified as HIT+ (met criteria for HIT), HIT? (HIT possible), and HIT- (did not meet criteria for HIT) utilizing ACCP guidelines. One hundred fifteen patients with anti-heparin/PF4 antibodies were identified. Ninety-eight patients were confirm+;17 were confirm−. The majority of confirm+ patients were HIT+ or HIT?(72%);the majority of confirm− patients were HIT− (81%). Patients who were HIT+/confirm+ had higher ELISA OD values than patients who were HIT?/confirm+ or HIT− /confirm+ (p=0.031, p=0.001). Two confirm− patients were HIT+, one was HIT?; all had high ELISA OD values. Although confirm+ status correlated with clinical HIT, the confirmatory procedure misclassified some patients by yielding a confirm− result despite clinical HIT with high ELISA OD values. Future studies should compare higher ELISA OD values with the confirmatory procedure as strategies to improve ELISA diagnostic specificity for HIT.

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

Blood ◽  
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.

Differential Prevalence of Anti-Heparin-Platelet Factor 4 Antibodies In Elderly Patients with Acute Hip Fracture Undergoing Orthopaedic Surgery and Anticoagulated with Unfractionated Heparin and Enoxaparin

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4217-4217
Author(s):  
Christopher Song ◽  
Josephine Cunanan ◽  
Hussein Kahn ◽  
Debra Hoppensteadt ◽  
Jawed Fareed
Keyword(s):  
Hip Fracture ◽  
Elderly Patients ◽  
Optical Density ◽  
Conflicts Of Interest ◽  
Treated Group ◽  
Progressive Increase ◽  
Platelet Factor 4 ◽  
Platelet Factor ◽  
Surgical Interventions ◽  
Prophylactic Anticoagulation

Abstract Abstract 4217 Orthopaedic surgical interventions pose a high risk of thrombosis (up to 50%) and require prophylactic anticoagulation. Conventionally, UFH and LMWH (enoxaparin) are used for the prophylactic anticoagulation. Both of these agents are capable of generating anti-heparin-platelet factor 4 antibodies. However, the exact prevalence with their use in elderly patients is not known. The purpose of this study was to determine the prevalence of the generation of anti-heparin-platelet factor 4 antibodies in this population with reference to the differences between UFH and LMWH. This study was conducted as a sub-study of PK532, in which 341 patients were recruited with acute hip fracture requiring orthopaedic surgical intervention. Patients were randomized into two groups and received either UFH 5000 units BID or enoxaparin 40 mg OD. Blood samples were drawn the day prior to surgery and on post-op days 1, 3, 5, and 7. Citrated plasma samples were kept frozen at -70 degrees Celsius and were batch analyzed for the presence of anti-heparin platelet factor 4 antibodies using GTI (Milwaukee, Wisconsin) and Aniara (Paris, France) methods. The sub-study was carried out on 94 patients representing 42 enoxaparin and 51 heparin anticoagulation. The prevalence of anti-heparin platelet factor 4 antibody was expressed in terms of antibody titer by measuring optical density in the ELISA method and by determining the positive patients using the criterions established by each kit. Of the 94 patients recruited in this study, both methods showed a progressive increase in optical density starting on post-op day 3 suggesting the generation of anti-heparin platelet factor 4 antibodies. The relative absorbance was lower in the Aniara method. Overall, across all study days, the prevalence of anti-heparin platelet factor 4 antibodies was found to be 18.09% and 10.64% in all patients using the GTI and Aniara methods, respectively. The heparin treated group showed a much higher prevalence (29.41% and 19.61% using GTI and Aniara, respectively) whereas the enoxaparin treated group exhibited a much lower prevalence (2.33% and 0% using the GTI and Aniara methods, respectively). The highest prevalence was found to be on post-op day 7. On post-op day 7, the heparin treated group exhibited 27.59% prevalence using the GTI method and 13.79% prevalence of anti-heparin platelet factor 4 antibodies using the Aniara method (p<0.05). The results of both GTI and Aniara methods correlated well, especially on post-op day 5 and 7. These results suggest that both UFH and enoxaparin are capable of generating anti-heparin platelet factor 4 antibodies, which are more detectable on post-op days 5 and 7. The prevalence of these antibodies is found to be higher in the UFH group compared to the enoxaparin group. However, there are differences in the two methods. The GTI method has a higher sensitivity in detecting these antibodies in contrast to the Aniara method. Based on these results, the GTI method appears to be a more suitable global screening of patients suspected of having anti-heparin platelet factor 4 antibodies. Disclosures: No relevant conflicts of interest to declare.

Assessing the Impact of a Heparin Induced Thrombocytopenia Recognition and Management Protocol

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2080-2080
Author(s):  
John M Koerber ◽  
Trupti P Mehta ◽  
Lisa L Forsyth ◽  
Lindsey Corbets ◽  
Elizabeth Conger ◽  
...  
Keyword(s):  
Optical Density ◽  
Elisa Test ◽  
Thrombin Inhibitor ◽  
Timely Initiation ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia ◽  
Protocol Implementation ◽  
Management Protocol ◽  
The Impact ◽  
Post Period

Abstract Abstract 2080 Heparin-induced thrombocytopenia (HIT) is an immune mediated adverse reaction to heparin which results in significant patient morbidity. Although guidelines for the management of HIT highlight which patients should receive initial therapy, they fall short of directing decisions regarding continuation of therapy after HIT antibody test results return. Using a multidisciplinary approach, a comprehensive HIT Recognition and Management Protocol was developed. Protocol implementation involved a change in HIT testing from a polyspecific platelet factor 4 (PF4)/heparin ELISA to an IgG-specific PF4/heparin ELISA. The use of automatic send out serotonin release assay (SRA) testing for those with a positive PF4/heparin ELISA optical density between 0.4 and 2 was also implemented. The protocol was initiated on October 15th 2010. The overall goal of this project was to assess the impact of protocol implementation on HIT management. A retrospective observational cohort study using a pre – post design was used. Patients started on direct thrombin inhibitor therapy (DTI) from September 1st 2009- February 28th 2010 for suspected/confirmed HIT composed the pre implementation group while those started on DTI therapy from November 1st 2010 – April 30th 2011 composed the post implementation group. Data extraction involved demographic, clinical, laboratory and pharmacy data. DTI initiation within 12 hours of HIT laboratory testing in patients with an intermediate to high 4Ts score was assessed. Additional endpoints included appropriate discontinuation of DTI therapy defined as discontinuation within 12 hours of a negative PF4/heparin ELISA or within 12 hours of a negative SRA in patients with a positive PF4/heparin ELISA with an optical density below 2. Hours of inappropriate continuation of DTI therapy and appropriate warfarin transition were also assessed. T- test, Chi square and Mann Whitney U were used to analyze data with a level of significance set at p <0.05. A total of 61 patients received DTI therapy for suspected/confirmed HIT in the pre period compared to 46 in the post period. DTI initiation within 12 hours of a PF4/heparin ELISA order for those with an intermediate-high 4T score occurred in 8/31 (25.8%) of pre patients and 24/31 (77.4%) of post patients, p <0.0001. Appropriate discontinuation of DTI therapy after a negative PF4/heparin ELISA occurred in 5/23 (21.7%) of pre patients and 12/26 (46.2%) of post patients, p = 0.07. Total hours of inappropriate continuation of DTI therapy after a negative PF4/heparin ELISA test were 2607.8 hours in the pre and 740.5 hours in the post periods. The median number of hours of inappropriate DTI continuation/patient after a negative PF4/heparin ELISA in the pre versus post periods were 99.6 and 25.1 hours respectively, p=0.04. Appropriate discontinuation of DTI therapy after a negative SRA occurred in 2/13 (15.4%) pre and 2/9 (22.2%) post patients, p =0.12. Seventeen patients in the pre and 10 in the post period were transitioned to warfarin for HIT. Initiation occurred after platelet count recovery to 150 × 109/L in 11/17 (64.7%) of pre and 7/10 (70%) of post patients, p = 0.78. The initial warfarin dose was < 5mg in 15/17 (88.2%) of pre and 10/10 (100%) of post patients, p =0.26. A minimum 5 day overlap of DTI and warfarin therapy occurred in 11/16 (68.8%) pre and 8/9 (88.9%) of post patients, p =0.26. Implementation of the HIT protocol improved the timely initiation of DTI therapy in those with an intermediate-high 4Ts score and was successful in promoting appropriate discontinuation of DTI therapy after a negative PF4/heparin ELISA test. Automatic send out SRA testing did not demonstrate a benefit in promoting discontinuation of therapy in those with a positive PF4/heparin ELISA and a negative SRA. Disclosures: No relevant conflicts of interest to declare.

Refractoriness to platelet transfusion in acute myeloid leukemia correlated with the optical density of anti-platelet factor 4/heparin antibodies

2013 ◽  
Vol 98 (4) ◽  
pp. 472-477 ◽  
Author(s):  
Mizuki Aimoto ◽  
Takahisa Yamane ◽  
Kazumasa Shiomoto ◽  
Chikahiko Sakamoto ◽  
Yasuhiro Nakashima ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Optical Density ◽  
Myeloid Leukemia ◽  
Platelet Transfusion ◽  
Platelet Factor 4 ◽  
Platelet Factor ◽  
Acute Myeloid

The level of heparin-induced antibodies in correlation with the result of the flow cytometric functional assay in the patients with suspected HIT

2017 ◽  
Vol 70 (12) ◽  
pp. 1084-1087 ◽  
Author(s):  
Elvira Maličev ◽  
Marjeta Maček Kvanka ◽  
Polona Klemenc ◽  
Primož Rožman
Keyword(s):  
Positive Result ◽  
Platelet Activation ◽  
Optical Density ◽  
Platelet Factor 4 ◽  
Functional Assay ◽  
Flow Cytometric Assay ◽  
Platelet Factor ◽  
Positive Functional ◽  
Flow Cytometric ◽  
Positive Results

Heparin can induce the formation of antibodies against a heparin complex with a platelet factor 4 (PF4), leading to platelet activation and the development of heparin-induced thrombocytopaenia (HIT). Because screening ELISA does not discriminate between platelet activating and non-activating anti-heparin/PF4 antibodies, each positive result is confirmed by an additional functional assay. We analysed 1004 sera of patients with suspected HIT. Optical density (OD) values of ELISA-positive results were correlated with the risk for a positive result with our functional flow cytometric assay. Only 10.7% were ELISA positive and 59.8% of those were positive with the functional assay. The positive functional assay was found in 23.4% of patients with OD<1.0, in 57.7% with 1.0<OD<2.0 and in 94.1% with OD>2.0. Although our results showed that higher ELISA OD values increasethe possibility of the presence of platelet-activating anti-heparin/PF4 antibodies , there is no need for improving ELISA cut-off value for positive result.

Half-Life of Platelet Factor 4 (PF-4) in Plasma and Platelets from Macaca Mulatta

1977 ◽  
Vol 37 (01) ◽  
pp. 073-080 ◽  
Author(s):  
Knut Gjesdal ◽  
Duncan S. Pepper
Keyword(s):  
Macaca Mulatta ◽  
Half Life ◽  
Human Platelet ◽  
Gel Filtration ◽  
Platelet Factor 4 ◽  
Active Protein ◽  
Platelet Factor ◽  
Membrane Bound

SummaryHuman platelet factor 4 (PF-4) showed a reaction of complete identity with PF-4 from Macaca mulatta when tested against rabbit anti-human-PF-4. Such immunoglobulin was used for quantitative precipitation of in vivo labelled PF-4 in monkey serum. The results suggest that the active protein had an intra-platelet half-life of about 21 hours. In vitro 125I-labelled human PF-4 was injected intravenously into two monkeys and isolated by immuno-precipita-tion from platelet-poor plasma and from platelets disrupted after gel-filtration. Plasma PF-4 was found to have a half-life of 7 to 11 hours. Some of the labelled PF-4 was associated with platelets and this fraction had a rapid initial disappearance rate and a subsequent half-life close to that of plasma PF-4. The results are compatible with the hypothesis that granular PF-4 belongs to a separate compartment, whereas membrane-bound PF-4 and plasma PF-4 may interchange.

Beta-Thromboglobulin (βtg) and Platelet Factor 4 (PF4) in Patients with Myeloproliferative Diseases

1994 ◽  
Vol 72 (03) ◽  
pp. 484-485
Author(s):  
Fabrizio Fabris ◽  
Guido Luzzatto ◽  
Maria Luigia Randi ◽  
Giuseppe Cella
Keyword(s):  
Platelet Factor 4 ◽  
Platelet Factor ◽  
Myeloproliferative Diseases
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