Heparin-Induced Thrombocytopenia (HIT): A Rural Community Based Experience.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3925-3925
Author(s):  
N. Mullai ◽  
Amanda Brock ◽  
Shona Harper
Keyword(s):  
Rural Community ◽  
Rapid Test ◽  
Heparin Therapy ◽  
Serotonin Release ◽  
Rural Setting ◽  
Thrombin Inhibitor ◽  
Test Results ◽  
Community Based ◽  
Heparin Induced Thrombocytopenia ◽  
Release Assay

Abstract Background: Heparin-induced thrombocytopenia (HIT) is a known complication of heparin therapy. This study was planned to assess the experience of a community based medical practice with HIT in a rural setting. Method: A retrospective study was done from medical records of patients suspected clinically of HIT from January 2006 to January 2007. The data were analyzed with regard to test results of patients, especially those who were positive for the HIT antibody and correlated with national statistics. Result: Fifty-two (52) patients were suspected clinically of having HIT during the study period. All 52 patients received heparin and most of them had cardiac surgery before the onset of thrombocytopenia. Six out of fifty-two (6/52) patients were found to have positive HIT antibody. Two out of six (2/6) also had positive serotonin release assay. Two out of six (2/6) developed heparin-induced thrombocytopenia with thrombosis (HITT). One of the two patients with HITT died of complications. The range of time to obtain test results was 5–7 days. Four out of fifty-two (4/52) patients received thrombin inhibitor lepirudin (Refludan) as alternate anticoagulation. Conclusion: The overall incidences, time of onset, relation to heparin treatment were similar to that of national averages. The time to obtain diagnostic test results ranged 5–7 days and heparin was withheld in all of them, and more expensive anticoagulation was used for some of them while waiting for the test results. This dilemma in diagnosis and treatment could be avoided if a rapid test that can help to assess the risk early in about 12–24 hrs, is possible. Such a test would be very beneficial especially in small, rural community settings where the availability of expensive testing and medications for HIT are limited.

Diagnosis and treatment of heparin-induced thrombocytopenia

Perfusion ◽  
2003 ◽  
Vol 18 (1) ◽  
pp. 47-53 ◽  
Author(s):  
William J DeBois ◽  
Junli Liu ◽  
Leonard Y Lee ◽  
Leonard N Girardi ◽  
Charles Mack ◽  
...  
Keyword(s):  
New York ◽  
Platelet Inhibition ◽  
Heparin Therapy ◽  
Serotonin Release ◽  
Antibody Detection ◽  
Thrombin Inhibitor ◽  
Heparin Infusion ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia ◽  
Life Threatening

Heparin-induced thrombocytopenia (HIT) is a major side effect secondary to the administration of heparin. This syndrome is serious and potentially life threatening. This response is the result of antibodies formed against the platelet factor 4 (PF4)/heparin complex. The incidence of this immune-mediated syndrome has been estimated to be 1-3% of all patients receiving heparin therapy. The occurrence of HIT in patients requiring full anticoagulation for cardiopulmonary bypass (CPB), therefore, presents a serious challenge to the cardiac surgery team. The diagnosis of HIT should be based on both clinical and laboratory evidence. While functional assays, platelet aggregation tests, and the serotonin release assay can be used to support the diagnosis, the negative predictive value of these tests is generally less than 50%. In contrast, although non-functional antibody detection assays are more sensitive, they have a low specificity. HIT can be treated in several ways, including cessation of all heparin and giving an alternative thrombin inhibitor, platelet inhibition followed by heparin infusion, and the use of low molecular weight heparins. In this presentation, the pathology and current diagnostic tests, as well as the successful management of patients with HIT undergoing CPB at New York Presbyterian Hospital, are reviewed.

Class I HLA-Specific Antibodies Can Cause “false-positive” Test Results in the Serotonin Release Assay for Heparin-Induced Thrombocytopenia (HIT).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3506-3506
Author(s):  
Shiu-Ki Hui Rocky ◽  
Thomas M Ellis ◽  
Richard H. Aster ◽  
Brian R. Curtis
Keyword(s):  
Low Dose ◽  
Serotonin Release ◽  
Class I ◽  
High Dose ◽  
True Positive ◽  
Test Results ◽  
Hla Antibodies ◽  
Heparin Induced Thrombocytopenia ◽  
Dose Heparin ◽  
Release Assay

Abstract Abstract 3506 Poster Board III-443 A diagnosis of heparin-induced thrombocytopenia (HIT) is confirmed with support from the laboratory. Antibodies associated with HIT are specific for complexes made up of heparin and platelet factor 4 (PF4) and can be detected in a solid phase ELISA (PF4 ELISA). However, a functional test, the serotonin release assay (SRA) is regarded by many to be the “gold standard” for laboratory investigation of this disorder. In our facility, the SRA is performed by incubating serotonin-labeled platelets (pooled from three different group O donors) with test serum and low dose (0.1 units/ml) or high dose (100 units/ml) heparin and determining the percentage of total serotonin released. Release of serotonin (20-100%) with low dose heparin and inhibition of this release with high dose heparin is considered to be “positive” for platelet-activating HIT antibodies. Sera from some patients cause serotonin release with low dose heparin that is not inhibited with high dose heparin. The significance for these “indeterminate” reactions is unclear, but they are considered not to reflect the presence of “true” HIT antibodies. We studied selected serum samples from 238 patients referred for HIT testing. Of these, 119 tested “true” positive and 117 produced “indeterminate” reactions in the SRA. The same samples were tested for the presence of antibodies reactive with beads coated with various Class I HLA antigens using a flow cytometric bead assay (Flow PRA, One Lambda). Sera producing at least 30% release in SRA and reactive with at least 20% of the bead panel were selected for analysis. As shown in Figure 1, there was a high correlation between the likelihood of an “indeterminate” SRA test result and the presence of Class I HLA antibodies (p << 0.0001). Figure 1 SRA Category No. with PRA >/=20% No. with PRA <20% Total Sample SRA “Indeterminate” (>/=30% Release and Uninhibited by High Dose Heparin) 91 19 110 SRA “True Positive” (>/=30% Release and Inhibited by High Dose Heparin) 36 72 108 As expected, there was a significant correlation between the strength of reactions produced by individual “true positive” sera in the SRA (% release) and in the PF4/heparin ELISA (O.D. value). However, in analyzing 38 sera with “true positive” test results in the SRA, we identified two that were negative in the PF4 ELISA and contained broad Class I HLA reactivity (reactive with 100% and 41% of the panel, respectively). We conclude 1) Class I HLA antibodies are the major cause of “indeterminate” reactions in the serotonin release assay and 2) A subset of these antibodies can be inhibited by high dose heparin and therefore mimics the behavior of “true” HIT antibodies in the SRA. Unless the PF4 ELISA test is used together with the SRA, this type of reaction could lead to an erroneous diagnosis of HIT. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Heparin-Induced Thrombocytopenia in COVID-19

2020 ◽  
Vol 8 ◽  
pp. 232470962094409 ◽  
Author(s):  
Prasanth Lingamaneni ◽  
Sriram Gonakoti ◽  
Krishna Moturi ◽  
Ishaan Vohra ◽  
Maryam Zia
Keyword(s):  
Platelet Count ◽  
Liver Function Tests ◽  
Heparin Therapy ◽  
Serotonin Release ◽  
Coagulation Cascade ◽  
Heparin Induced Thrombocytopenia ◽  
Mechanically Ventilated ◽  
Normal Limits ◽  
Therapeutic Anticoagulation ◽  
Release Assay

COVID-19 (coronavirus disease-2019) infection is a highly prothrombotic state, resulting from a dysregulation of the coagulation cascade. Therefore, thromboprophylaxis is strongly recommended in these patients, with some experts even advocating for therapeutic dosing to prevent thromboembolic events. Heparin-induced thrombocytopenia (HIT) is a well-known complication of heparin therapy. In this article, we report a case of HIT in a patient with COVID-19. A 63-year-old male presented with 1 week of dry cough and diarrhea. He had a positive nasopharyngeal COVID-19 reverse-transcriptase–polymerase chain reaction. On admission, the platelet count and liver function tests were within normal limits. During his hospitalization, he developed a right femoral deep venous thrombosis and was started on therapeutic anticoagulation. Due to worsening respiratory failure, he was intubated and mechanically ventilated. Between days 11 and 12 of hospitalization, platelet count dropped from 304 000 to 96 000 cells/µL. He had a high pretest probability for HIT with a 4T score of 6 and a positive anti-PF4/heparin antibody. Heparin drip was discontinued and was switched to argatroban. The serotonin release assay eventually returned positive, which confirmed the diagnosis of HIT. We also discuss potential overdiagnosis of HIT in COVID-19 through 4 cases with false-positive HIT antibodies.

scholarly journals Heparin-Induced Thrombocytopenia Testing: ELISA Based Anti-Platelet Factor 4 Polyspecific and IgG-Specific Antibody Detection Assays Compared to the Unfractionated Heparin Serotonin Release Assay

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3209-3209
Author(s):  
Edward C.C. Wong ◽  
Laura A. Worfolk ◽  
Caixia Bi ◽  
Lina J. Noh ◽  
Andrew Espinoza ◽  
...  
Keyword(s):  
Unfractionated Heparin ◽  
Specific Antibody ◽  
Serotonin Release ◽  
Test Results ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia ◽  
Specific Antibodies ◽  
Functional Assays ◽  
Antibody Assays ◽  
Release Assay

Abstract Introduction: Antibodies that cause heparin-induced thrombocytopenia (HIT) can be detected with either antigenic or functional assays. Previously, it has been shown that antigenic (ELISA based) assays that detect anti-platelet factor 4 (anti-PF4) IgG, IgM, or IgA (polyspecific) antibodies are more sensitive but less specific than functional assays such as the unfractionated serotonin release assay (UFH SRA), and that the use of anti-PF4 assays that detect IgG antibodies only, would increase the specificity but decrease the sensitivity of these assays for the detection of HIT antibodies that are prothrombotic (associated with positive functional assay). To date large epidemiologic studies have not confirm these findings. To evaluate the relative performance of anti-PF4 polyspecific and IgG-specific antibodies in their ability to detect prothrombotic HIT antibodies, we evaluated results of non-reflexive HIT panels that contained either anti-PF4 polyspecific or IgG-specific assays and unfractionated heparin serotonin release assays over an eight-year period at a U.S. reference laboratory. Methods: Test results for 2 HIT detection panels were compared: 1 panel had UFH SRA plus the polyspecific PF4 ENHANCED® assay (GTI Diagnostics, Waukesha, WI) and 1 panel had UFH SRA plus the IgG-specific Zymutest HIA IgG assay (Hyphen Biomed, France). Test results were from the last 4 years of use for each panel (2009 to 2012 for the polyspecific panel; 2017 to 2020 for the IgG-specific panel). UFH SRA was performed as described by Sheridan et al, (1986) with positivity defined as ≥20% serotonin release by low dose UFH and >50% suppression of release at high dose (100 U/mL) UFH. For each year and assay, test results were stratified by optical density (OD) results, and the percent of results positive by UFH SRA was determined for each OD range. Median yearly UFH SRA positivity rates for each OD interval were compared for anti-PF4 polyspecific vs IgG-specific antibody assays using non-parametric statistical testing, Mann-Whitney U test, two-tailed, with significance defined as <0.05. Results: HIT panels with either ELISA based assays detecting either anti-PF4 polyspecific or IgG specific antibodies demonstrated increasing UFH SRA positivity rates as OD increased. Approximately 50% UFH SRA positivity occurred when OD was in the 2.000 to range. No significant differences in SRA positivity were seen at any positive OD interval when comparing anti-PF4 polyspecific vs IgG-specific assays. A small but significant difference was seen when OD results were considered This observation may have been due to a in the review process (2017-2020): when a UFH SRA result was positive with a negative OD result, repeat UFH SRA testing was performed. Conclusions: Our study demonstrates that the correlations of UFH SRA positivity and OD measurements are similar for anti-PF4 IgG-specific and polyspecific antibody assays. These results suggest the assay types may perform similarly for the detection of HIT and importantly provide important predictive information as to when an optical density value will lead to a positive UFH SRA result. Figure 1 Figure 1. Disclosures Wong: Quest Diagnostics: Current Employment, Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Worfolk: Quest Diagnostics: Current Employment. Bi: Quest Diagnostics: Current Employment. Noh: Quest Diagnostics: Current Employment. Espinoza: Quest Diagnostics: Current Employment. Wu: Quest Diagnostics: Current Employment. Sahud: Quest Diagnostics: Current Employment. Racke: Quest Diagnostics: Current Employment. Dlott: Quest Diagnostics: Current Employment.

The Clinical Usefulness of the Platelet Aggregation Test for the Diagnosis of Heparin-Induced Thrombocytopenia

1993 ◽  
Vol 69 (04) ◽  
pp. 344-350 ◽  
Author(s):  
B H Chong ◽  
J Burgess ◽  
F Ismail
Keyword(s):  
Platelet Aggregation ◽  
Heparin Therapy ◽  
Serotonin Release ◽  
Point System ◽  
Control Groups ◽  
Heparin Induced Thrombocytopenia ◽  
Heparin Concentration ◽  
Release Test ◽  
The Mean ◽  
Normal Controls

SummaryThe platelet aggregation test is widely used for the diagnosis of heparin-induced thrombocytopenia (HIT), a potentially serious complication of heparin therapy. We have evaluated its sensitivity and specificity in comparison with those of the 14C-serotonin release test. The sensitivity of the platelet aggregation test was found to vary with the heparin concentration and the donor of the platelets used in the test. The optimal heparin concentrations were between 0.1 and 1.0 U/ml. Using these heparin concentrations, the mean sensitivity varied from 39% (with the least reactive platelets) to 81% (with the most reactive platelets). In comparison, the sensitivity of the release test ranged from 65% to 94%. The specificities of the platelet aggregation test were 82%, 90% and 100% for the following control groups: (1) non-thrombocytopenic patients given heparin, (2) patients with thrombocytopenia due to other causes, and (3) normal controls not given heparin, respectively. The corresponding specificities for the release test was 94%, 90% and 100%. The specificities can be further increased to 100% for all controls with the adoption of a two-point system which defines a positive result as one in which platelet aggregation occurs with a low heparin concentration (0.5 U/ml) but not with 100 U heparin/ml. For optimal results, a two-point platelet aggregation test should be performed with heparin concentrations of 0.5 and 100 U/ml and using platelets of more reactive donors.

Safety and Efficacy of Argatroban in the Management of Heparin-Induced Thrombocytopenia

2011 ◽  
Vol 4 ◽  
pp. CMBD.S5118 ◽  
Author(s):  
Bernd Saugel ◽  
Roland M. Schmid ◽  
Wolfgang Huber
Keyword(s):  
Arterial Thrombosis ◽  
Pharmacokinetic Profile ◽  
The United States ◽  
Heparin Therapy ◽  
Direct Thrombin Inhibitor ◽  
Thrombin Inhibitor ◽  
Heparin Induced Thrombocytopenia ◽  
Safety And Efficacy ◽  
Increased Risk ◽  
Life Threatening

Heparin-induced thrombocytopenia (HIT) is a life-threatening adverse reaction to heparin therapy that is characterized by thrombocytopenia and an increased risk of venous and arterial thrombosis. According to guidelines, in patients with strongly suspected or confirmed HIT all sources of heparin have to be discontinued and an alternative, nonheparin anticoagulant for HIT treatment must immediately be started. For both the prophylaxis of thrombembolic events in HIT and the treatment of HIT with thrombosis the direct thrombin inhibitor argatroban is approved in the United States. The objective of this review is to describe the mechanism of action and the pharmacokinetic profile of argatroban, to characterize argatroban regarding its safety and therapeutic efficacy and to discuss its place in therapy in HIT.

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.

scholarly journals A diagnostic test for heparin-induced thrombocytopenia

Blood ◽  
1986 ◽  
Vol 67 (1) ◽  
pp. 27-30 ◽  
Author(s):  
D Sheridan ◽  
C Carter ◽  
JG Kelton
Keyword(s):  
High Specificity ◽  
Heparin Therapy ◽  
Positive Test ◽  
Test Results ◽  
Specific Test ◽  
Heparin Induced Thrombocytopenia ◽  
Platelet Release ◽  
High Concentrations ◽  
Low Sensitivity ◽  
Test Result

Heparin-induced thrombocytopenia can be a serious and difficult-to- diagnose complication of heparin therapy. Serum from patients with heparin-induced thrombocytopenia can cause heparin-dependent platelet aggregation, but the low sensitivity and specificity of this test limit its clinical usefulness. In this report we describe an assay for heparin-induced thrombocytopenia that is both sensitive and specific. The improvement in the assay was accomplished by measuring platelet release instead of aggregation and by measuring platelet release at two heparin concentrations. The rationale for the use of two heparin concentrations was that sera from patients with heparin-induced thrombocytopenia caused release at therapeutic but not at high concentrations of heparin. Twenty-eight sera samples from patients suspected of having heparin-induced thrombocytopenia and 573 controls were coded and tested in the assay. The patients with possible heparin- induced thrombocytopenia were ranked according to the likelihood of having this disorder by using prospectively defined criteria. The test had a high specificity (99%); only one of 573 controls showed a positive result. The test was also very sensitive, and the likelihood of a positive test result was directly correlated with the clinical likelihood of the patient having heparin-induced thrombocytopenia. Six of six patients with definitive heparin-induced thrombocytopenia had positive test results, whereas zero of four patients in whom the diagnosis was unlikely had positive test results. The two-point test for heparin-induced thrombocytopenia represents a sensitive and specific test for this disorder. This test may be useful not only in confirming the diagnosis of this disorder but also may provide information about its pathogenesis.

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.

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