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.

Serologic Results in >1000 Patients With Suspected Heparin-Induced Thrombocytopenia

2007 ◽  
Vol 14 (4) ◽  
pp. 410-414 ◽  
Author(s):  
Suresh G. Shelat ◽  
Anne Tomaski ◽  
Eleanor S. Pollak
Keyword(s):  
Laboratory Diagnosis ◽  
Serotonin Release ◽  
Enzyme Linked Immunosorbent Assay ◽  
Functional Assay ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia ◽  
Life Threatening ◽  
Release Assay ◽  
Pathogenic Antibodies

Heparin-induced thrombocytopenia (HIT) can lead to life-threatening and limb-threatening thrombosis. HIT is thought to be initiated by the interaction of pathogenic antibodies toward a complex platelet factor 4 (PF4) and heparin (PF4:H), which can activate platelets and predispose to thrombosis. As such, the laboratory diagnosis of HIT includes antigenic and functional assays to detect antibodies directed at PF4:H complexes. We performed a retrospective analysis of 1017 consecutive samples tested by serotonin-release assay and by enzyme-linked immunosorbent assay (ELISA). Most samples showed no serologic evidence of HIT, whereas 4% to 5% of samples demonstrated both antigenic and functional serological evidence for HIT. Approximately 12% to 18% of samples showed immunologic evidence of anti-PF4:H antibodies but without functional evidence of serotonin release in vitro. Interestingly, a small minority of samples (0.7%) caused serotonin release but were negative in the ELISA. The results are presented using cutoff values established at our hospital and for the ELISA manufacturer. This study provides a pretest probability of the serologic results from an antigenic assay (ELISA) and a functional assay (serotonin-release assay) in patients clinically suspected of having HIT.

scholarly journals P.038 Bilateral carotid thrombi and cerebral infarction as a manifestation of heparin-induced thrombocytopenia with normal platelet count: a case report

2019 ◽  
Vol 46 (s1) ◽  
pp. S24 ◽  
Author(s):  
P Malla
Keyword(s):  
Platelet Count ◽  
Sudden Onset ◽  
Serotonin Release ◽  
Heparin Induced Thrombocytopenia ◽  
Platelet Counts ◽  
Normal Platelet ◽  
Bilateral Carotid ◽  
Upper And Lower Extremities ◽  
Release Assay ◽  
Discharge From Hospital

Background: This is the first report of Heparin induced thrombocytopenia (HIT) presenting as bilateral carotid thrombi and multiple cerebral infarcts. Methods: 54 year old woman presented with sudden onset of right arm numbness and weakness two days after discharge from hospital. During her hospitalization 9 days prior, she underwent colovesicular fistula repair, received heparin subcutaneously for DVT prophylaxis and had normal platelet counts. Results: On this admission, MRI Brain showed scattered multiple acute infarcts within the cortex of bilateral cerebral hemispheres. CT angiography head /neck showed non-occlusive thrombi at the carotid bifurcations bilaterally. Platelet count on admission was 267 K/uL q which decreased to 125 K/uL the next day, after which heparin was started for the carotid thrombi. The platelet count rapidly decreased further to 79 K/uL leading to suspicion for HIT and switching to Argatroban. HIT and serotonin release assay were positive confirming the diagnosis of HIT. CT chest and tranthoracic echocardiogram was normal. Venous Duplex of bilateral upper and lower extremities were negative for DVTs.Hypercoaguable evaluation was negative. Conclusions: This case highlights the importance of identifying HIT as a cause of arterial thrombosis and stroke even with normal platelet counts in the clinical setting of recent heparin use.

Prevalence and Overtesting of True Heparin-Induced Thrombocytopenia in a 591-Bed Tertiary Care, Teaching Hospital

2017 ◽  
Vol 34 (6) ◽  
pp. 464-471 ◽  
Author(s):  
Stephen Farley ◽  
Caitlyn Cummings ◽  
William Heuser ◽  
Shan Wang ◽  
Rose Calixte ◽  
...  
Keyword(s):  
New York ◽  
Tertiary Care ◽  
Retrospective Chart Review ◽  
Elisa Test ◽  
Serotonin Release ◽  
University Hospital ◽  
Enzyme Linked Immunosorbent Assay ◽  
Heparin Induced Thrombocytopenia ◽  
Release Assay ◽  
Hospital Stays

Heparin-induced thrombocytopenia type II (HIT) is a rare but potentially fatal antibody-mediated reaction to all forms of heparin (unfractionated heparin, low-molecular weight heparin, heparin flushes, and heparin-coated catheters), which can lead to HIT with thrombosis. Two tests commonly used to screen for HIT include the enzyme-linked immunosorbent assay (ELISA) and serotonin release assay (SRA). This is a retrospective chart review study conducted from January 1, 2013, through December 31, 2014, to estimate the rate of true HIT in critical care patients at Winthrop-University Hospital, located in Mineola, New York. Patients are classified as positive for HIT if both ELISA and SRA immunoassays are positive. We reviewed 507 heparin immunoassays, excluding 64 who had an inappropriate ELISA test sent due to no administration of heparin, enoxaparin, or heparin lock flush at this or previous hospital stays at Winthrop. Of the 443 heparin immunoassays, ELISA results were positive for 66 patients (15.1%), and only 11 (2.5%) patients had true cases of HIT with a 95% confidence interval of 1.3% to 4.4%. The 4T score for those with true HIT (median: 5.0) was statistically higher compared to those without true HIT (median: 2.0; P < .001). Despite guidelines in place, overtesting for HIT is still a prevalent issue.

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.

Prevalence of Heparin-Dependent Platelet Antibodies in Children after Cardiopulmonary Bypass Surgery.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3019-3019
Author(s):  
Rowena C. Punzalan ◽  
Sheila J. Hanson ◽  
Nancy Ghanayem ◽  
Brian R. Curtis ◽  
Kathleen Murkowski ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
Unfractionated Heparin ◽  
Pediatric Intensive Care ◽  
Serotonin Release ◽  
Platelet Factor 4 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia ◽  
Platelet Antibodies ◽  
Release Assay

Abstract Heparin is used during cardiopulmonary bypass (CPB) surgery in children. Upon exposure to heparin, heparin-dependent platelet antibodies (HDPA) may form against complexes of platelet factor 4 and heparin on platelet surfaces. Heparin-induced thrombocytopenia (HIT) or heparin-induced thrombocytopenia and thrombosis (HITT) may then ensue. Among adult CPB patients, up to 50% demonstrate HDPA, although only 2% develop HIT and 1% develop HITT. In previous studies done among non-CPB newborns and pediatric intensive care patients, the incidence of HDPA has been zero to minimal. Objective: To determine prevalence of HDPA among children undergoing CPB who are exposed to unfractionated heparin for &gt;120 hours after CPB. Methods: We designed a prospective pilot study. All patients ≤ 12 years old who were to receive heparin during CPB were eligible. The presence of HDPA was assessed by heparin-platelet factor 4 enzyme-linked immunosorbent assay (ELISA); positive and equivocal results were confirmed by serotonin release assay. Blood samples were obtained at the time of cessation of heparin or after 10 days on heparin, whichever came first. Results: Thirty patients were enrolled: 15 were aged 2–19 days (median 6 days); 15 were aged 1.2 to 50 months (median 4.5 months). One patient had borderline positive and 1 had positive results by heparin-platelet factor 4 ELISA; both had negative results by serotonin release assay; neither developed clots. Eighteen patients developed thrombocytopenia, which is common after CPB, including the 2 with equivocal results by ELISA. Six patients, all with negative ELISAs, developed symptomatic thromboses. Conclusion: There were no HDPA identified among children who received unfractionated heparin for CPB. The specificity of heparin-platelet factor 4 ELISA among children should be assessed.

scholarly journals Staged Management of Heparin-Induced Thrombocytopenia for Renal Cavo-Atrial Cancer Removal on Cardiopulmonary Bypass

2021 ◽  
Author(s):  
Salim Aziz ◽  
Shailendra Sharma ◽  
Jenna Aziz ◽  
James Gould ◽  
Xiomara Fernandez
Keyword(s):  
Cardiopulmonary Bypass ◽  
Platelet Reactivity ◽  
Circulatory Arrest ◽  
Serotonin Release ◽  
Successful Outcome ◽  
Enzyme Linked Immunosorbent Assay ◽  
Platelet Activity ◽  
Heparin Induced Thrombocytopenia ◽  
Platelet Receptor ◽  
Release Assay

Management of patients with acute heparin-induced thrombocytopenia (HIT) with cavo-atrial renal cancer requiring surgery on cardiopulmonary bypass (CPB) and possible deep hypothermia circulatory arrest is a challenge. A staged approach using Bivalirudin, plasmapheresis, and intravenous immunoglobulin (IVIG) was used to preoperatively de-escalate HIT guided by enzyme-linked immunosorbent assay (ELISA) and serotonin release assay (SRA). Intraoperatively heparin was used as the anticoagulant for CPB as DHCA was likely to be used to remove the atrio-caval tumor. Heparin is effective in preventing clots in the circuit during DHCA. To prevent HIT upon re-exposure to heparin during CPB, a bolus of a Cangrelor (reversible P2Y12 platelet receptor inhibitor) was given before heparin and during CPB whilst platelet activity was monitored using platelet reactivity units (PRU). Postoperatively, to prevent recurrence of HIT, plasmapheresis was used until SRA and optical density (OD) resulted. The patient had a successful outcome.

Incidence of antibodies to protamine sulfate/heparin complexes in cardiac surgery patients and impact on platelet activation and clinical outcome

2013 ◽  
Vol 109 (06) ◽  
pp. 1141-1147 ◽  
Author(s):  
Dorothée Leroux ◽  
Jérome Rollin ◽  
Jean Amiral ◽  
Marc-Antoine May ◽  
Claire Pouplard ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Serotonin Release ◽  
Platelet Lysate ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia ◽  
Normal Platelet Count ◽  
Normal Platelet ◽  
Heparin Complexes ◽  
Release Assay

SummaryA new ELISA (Zymutest HIA®), based on incubation of diluted plasma with protamine/heparin (PRT/H) complexes without and with platelet factor 4 (PF4) provided by a platelet lysate, was used to detect heparindependent antibodies in a cohort of 232 cardiac surgery (CS) patients and in 47 patients with heparin-induced thrombocytopenia (HIT). Significant binding of IgG/A/M to PRT/H complexes was demonstrated in 59 CS patients (25.4%), with similar absorbances whether platelet lysate was added to the plasma or not, and significant reactivity to PF4/H in 29 of them. Antibodies to PRT or heparin alone were present in 15 and two of these patients, respectively. Importantly, antibodies to PRT/H were detected in only three of the 47 HIT patients, who had also undergone recent CS. The Zymutest HIA® was positive in another 41 CS patients (17%), but only or mainly when their plasma was tested with platelet lysate, with significant levels of antibodies to PF4/H in 40 of them without detectable reactivity to PRT or heparin alone. Slight antibody binding to PRT/H complexes was also measured in six of these 41 patients. Therefore, a total of 35 CS patients exhibited dual antibody reactivity towards PRT/H and PF4/H complexes. Serotonin release assay performed with PRT alone was positive in 17 CS patients with antibodies to PRT/H, but all had normal platelet count evolution without thrombosis postoperatively. In conclusion, antibodies to PRT/H are frequently present in CS patients postoperatively (25.4%), and can activate platelets in vitro, but their clinical impact remains questionable.

scholarly journals Heparin-induced thrombocytopenia in patients on extracorporeal membrane oxygenation and the role of a heparin-bonded circuit

Perfusion ◽  
2019 ◽  
Vol 34 (7) ◽  
pp. 584-589 ◽  
Author(s):  
Dirk Pabst ◽  
Jacqueline B Boone ◽  
Behzad Soleimani ◽  
Christoph E Brehm
Keyword(s):  
Overall Survival ◽  
Platelet Count ◽  
Retrospective Study ◽  
Extracorporeal Membrane Oxygenation ◽  
Serotonin Release ◽  
Single Center ◽  
Heparin Induced Thrombocytopenia ◽  
Membrane Oxygenation ◽  
Release Assay

Background: In patients supported with extracorporeal membrane oxygenation, and who develop heparin-induced thrombocytopenia, there is no clear evidence to support changing to a non-heparin-coated extracorporeal membrane oxygenation circuit. Our goal was to evaluate clinical outcomes of patients who were continued on heparin-bonded circuits despite diagnosed heparin-induced thrombocytopenia. Methods: We completed a single-center retrospective study of all patients who underwent extracorporeal membrane oxygenation support from July 2008 to July 2017 and were tested heparin-induced thrombocytopenia positive while on extracorporeal membrane oxygenation support. After diagnosis of heparin-induced thrombocytopenia, mean platelet count (k/µL) was measured on consecutive days for 14 days. Results: Out of 455 patients, 14 (3.1%) had a diagnosis of heparin-induced thrombocytopenia by serotonin release assay and systemic heparin treatment was discontinued in every case. In total, 11 of the heparin-induced thrombocytopenia patients (78.6%) survived to discharge. The overall survival of all 455 extracorporeal membrane oxygenation patients was 54.1%. Platelets counts after discontinuation of systemic heparin in the heparin-induced thrombocytopenia patients increased from a mean of 59.8 k/µL at time of heparin-induced thrombocytopenia diagnosis to a mean of 280.2 k/µL at 14 days after discontinuation of heparin despite continuation of the heparin-bonded circuit. Platelet count increased in heparin-induced thrombocytopenia patients on extracorporeal membrane oxygenation support after discontinuation of systemic heparin even if maintained on the heparin-bonded circuit. Conclusion: Discontinuation of systemic heparin but continuation of heparin-coated extracorporeal membrane oxygenation circuits appeared to be an appropriate response for our extracorporeal membrane oxygenation–supported patients who developed heparin-induced thrombocytopenia. Survival in this group was not significantly different to those patients on extracorporeal membrane oxygenation without heparin-induced thrombocytopenia. Larger studies should evaluate the safety of heparin-bonded extracorporeal membrane oxygenation systems in heparin-induced thrombocytopenia patients.

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.

Sign in / Sign up

Export Citation Format

Share Document