scholarly journals Predictors of Heparin-Induced Thrombocytopenia in Adult Cardiac Surgery Patients

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4705-4705
Author(s):  
Kari Allan ◽  
Jessica Crow ◽  
Jessica Chasler ◽  
Janhavi Athale ◽  
John Lindsley ◽  
...  

Background: The 4Ts, HIT-Expert Probability (HEP), and Post-Cardiopulmonary Bypass (CPB) screening tools for heparin-induced thrombocytopenia (HIT) have not been validated in cardiac surgery patients. Evidence remains unclear regarding which screening tool most accurately predicts HIT in this population. Methods: HIT-positive and HIT-negative patients who underwent on-pump cardiac surgery within a six-year period were matched 1:2 in a case-control design. Each patient was scored with the 4Ts, HEP, and CPB tools. Sensitivities and specificities of each tool were calculated using standard cut-offs. The Youden method was utilized to determine optimal cut-offs in receiver operating characteristic (ROC) curves of each score, then sensitivities and specificities were recalculated. A multivariable logistic regression was performed to determine the association of scoring tool components and relevant clinical characteristics with HIT. Results: Using standard cut-offs for the scoring tools, sensitivities for the CPB, HEP, and 4Ts tools were 100%, 93.9%, and 69.4%, respectively. Specificities were 51%, 49%, and 71.4%, respectively. Using the Youden method-derived optimal cut-offs, sensitivity of the CPB score remained 100% with improved specificity to 88.9%. Sensitivity of the 4Ts score declined to 51% and specificity improved to 93.9%. Pattern of platelet decline, absence of clinically significant bleed, body mass index, coronary artery bypass graft surgery, and postoperative heparin duration were significantly associated with HIT. Conclusions: The 4Ts score has limited utility in cardiac surgery patients, whereas the CPB and HEP scores with standard cut-offs demonstrated high sensitivity but low specificity. A cut-off of 3 points or higher on the CPB score could increase specificity while preserving high sensitivity. Disclosures Crow: Research Point Global: Other: Clinical and coding data review services. Streiff:Pfizer: Consultancy, Honoraria; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Daiichi-Sankyo: Consultancy, Honoraria; Roche: Research Funding; Portola: Consultancy, Honoraria; Bayer: Consultancy, Honoraria.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 267-267
Author(s):  
Adam Cuker ◽  
Ann H Rux ◽  
Jillian L Hinds ◽  
May Dela Cruz ◽  
Serge Yarovoi ◽  
...  

Abstract Abstract 267 Introduction Heparin-induced thrombocytopenia (HIT) is a prothrombotic disorder mediated by platelet, monocyte, and endothelial cell-activating antibodies (Abs) against ultralarge complexes of platelet factor 4 (PF4) and heparin. Laboratory testing plays a key role in the diagnosis of HIT, but is associated with important shortcomings. Immunoassays such as the PF4/heparin ELISA frequently yield false-positive results due to their inability to discriminate cellular activating-Abs from their non-pathogenic counterparts. Functional assays such as the 14C-serotonin release assay (SRA) are more specific, but are unfeasible for most clinical laboratories due to the requirement for radioisotope and fresh platelets from reactive donors. KKO is a monoclonal Ab that causes a HIT-like thrombocytopenic disorder in a mouse model. Binding of KKO to immobilized PF4/heparin is inhibited by human HIT plasma, but not by plasma from patients with non-pathogenic anti-PF4/heparin Abs.1 We exploited this property of KKO to develop a KKO-inhibition (KKO-I) ELISA to detect platelet-activating Abs. We recently described a system to measure cell activation by HIT Abs: DT40 (chicken B lymphocyte) cells transfected with human FcgRIIa coupled to a luciferase reporter.2 We hypothesized that this system (DT40-luc) could be used to identify cell-activating anti-PF4/heparin Abs without need for donor platelets or radioactivity. Here we describe the KKO-I and DT40-luc assays and compare their performance to two commercially available immunoassays and the SRA in samples from 58 patients with suspected HIT and circulating anti-PF4/heparin Abs. Methods Patient samples consecutively referred to a clinical coagulation laboratory for HIT laboratory testing that tested positive by polyspecific anti-PF4/heparin ELISA were included. In addition to the polyspecific ELISA, citrated plasma samples from all patients were tested by an IgG-specific PF4/heparin ELISA, an in-house SRA, and the investigational KKO-I and DT40-luc assays. A 4Ts score to estimate the clinical likelihood of HIT was determined for each subject. The investigator performing 4Ts scoring was blinded to the results of HIT laboratory assays. Investigators performing the KKO-I and DT40-luc assays were blinded to the 4Ts score and the results of the SRA and anti-PF4/heparin ELISA. The KKO-I and DT40-luc assays were performed as previously described.1,2 HIT was defined as the combination of an intermediate or high probability 4Ts score (≥4) and a positive SRA. The performance of each assay with respect to this reference standard was evaluated by receiver-operating characteristic (ROC) analysis. Areas under the ROC curves (AUCs) were calculated and compared using the Delong method for correlated samples. Results Fifty-eight subjects were enrolled, 21 of whom met prespecified criteria for HIT. There were no significant differences in demographic characteristics between the 21 HIT-positive and 37 HIT-negative subjects. The ability of the polyspecific ELISA, IgG-specific ELISA, KKO-I, and DT40-luc assay to discriminate HIT-positive from HIT-negative subjects is shown in Figure 1. HIT-positive plasma showed significantly greater mean inhibition of KKO binding than HIT-negative plasma (70.1%, 95% CI 64.8–75.4 vs. 40.4%, 33.5–47.4, p<0.0001) (Figure 1C). Plasma from HIT-positive subjects also induced significantly greater luciferase activity (3.14, 2.25–4.03 vs. 0.96, 0.85–1.07, p<0.0001) in the DT40-luc assay (Figure 1D). ROC curves for each assay are shown in Figure 2. The AUC for KKO-I (0.92, 0.85–1.00) was significantly greater than the AUC for the polyspecific (0.82, 0.70–0.95) and IgG-specific (0.76, 0.62–0.90) ELISAs (p<0.05 for both comparisons). The AUC for DT40-luc (0.89, 0.79–0.99) was significantly greater than the AUC for the IgG-specific (p=0.046), but not the polyspecific ELISA (p=0.28). Conclusion KKO-I and DT40-luc showed better discrimination than commercially available ELISAs in a small cohort of patients with suspected HIT and anti-PF4/heparin Abs. These assays are simple to perform, do not require donor platelets or radioactivity, and hold promise for improving the specificity and feasibility of HIT laboratory testing. Further evaluation in a larger cohort of patients is required. Disclosures: Cuker: Baxter: Consultancy, Research Funding; Bayer: Consultancy; Canyon: Consultancy; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees; Stago: Research Funding. Arepally:Teva Pharmaceuticals: Research Funding. Cines:Amgen: Consultancy; GSK: Consultancy; Eisai: Consultancy; T2 Biosystems: Research Funding.


Children ◽  
2021 ◽  
Vol 8 (6) ◽  
pp. 521
Author(s):  
Ina Nehring ◽  
Heribert Sattel ◽  
Maesa Al-Hallak ◽  
Martin Sack ◽  
Peter Henningsen ◽  
...  

Thousands of refugees who have entered Europe experienced threatening conditions, potentially leading to post traumatic stress disorder (PTSD), which has to be detected and treated early to avoid chronic manifestation, especially in children. We aimed to evaluate and test suitable screening tools to detect PTSD in children. Syrian refugee children aged 4–14 years were examined using the PTSD-semi-structured interview, the Kinder-DIPS, and the Child Behavior Checklist (CBCL). The latter was evaluated as a potential screening tool for PTSD using (i) the CBCL-PTSD subscale and (ii) an alternative subscale consisting of a psychometrically guided selection of items with an appropriate correlation to PTSD and a sufficient prevalence (presence in more than 20% of the cases with PTSD). For both tools we calculated sensitivity, specificity, and a receiver operating characteristic (ROC) curve. Depending on the sum score of the items, the 20-item CBCL-PTSD subscale as used in previous studies yielded a maximal sensitivity of 85% and specificity of 76%. The psychometrically guided item selection resulted in a sensitivity of 85% and a specificity of 83%. The areas under the ROC curves were the same for both tools (0.9). Both subscales may be suitable as screening instrument for PTSD in refugee children, as they reveal a high sensitivity and specificity.


Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Thiago Augusto Azevedo Maranhão Cardoso ◽  
Gudrun Kunst ◽  
Caetano Nigro Neto ◽  
José de Ribamar Costa Júnior ◽  
Carlos Gustavo Santos Silva ◽  
...  

Abstract Background Recent experimental evidence shows that sevoflurane can reduce the inflammatory response during cardiac surgery with cardiopulmonary bypass. However, this observation so far has not been assessed in an adequately powered randomized controlled trial. Methods We plan to include one hundred patients undergoing elective coronary artery bypass graft with cardiopulmonary bypass who will be randomized to receive either volatile anesthetics during cardiopulmonary bypass or total intravenous anesthesia. The primary endpoint of the study is to assess the inflammatory response during cardiopulmonary bypass by measuring PMN-elastase serum levels. Secondary endpoints include serum levels of other pro-inflammatory markers (IL-1β, IL-6, IL-8, TNFα), anti-inflammatory cytokines (TGFβ and IL-10), and microRNA expression in peripheral blood to achieve possible epigenetic mechanisms in this process. In addition clinical endpoints such as presence of major complications in the postoperative period and length of hospital and intensive care unit stay will be assessed. Discussion The trial may determine whether adding volatile anesthetic during cardiopulmonary bypass will attenuate the inflammatory response. Trial registration ClinicalTrials.gov NCT02672345. Registered on February 2016 and updated on June 2020.


1996 ◽  
Vol 84 (6) ◽  
pp. 1288-1297 ◽  
Author(s):  
James M. Bailey ◽  
Christina T. Mora ◽  
Stephen L. Shafer ◽  

Background Propofol is increasingly used for cardiac anesthesia and for perioperative sedation. Because pharmacokinetic parameters vary among distinct patient populations, rational drug dosing in the cardiac surgery patient is dependent on characterization of the drug's pharmacokinetic parameters in patients actually undergoing cardiac procedures and cardiopulmonary bypass (CPB). In this study, the pharmacokinetics of propofol was characterized in adult patients undergoing coronary revascularization. Methods Anesthesia was induced and maintained by computer-controlled infusions of propofol and alfentanil, or sufentanil, in 41 adult patients undergoing coronary artery bypass graft surgery. Blood samples for determination of plasma propofol concentrations were collected during the predefined study periods and assayed by high-pressure liquid chromatography. Three-compartment model pharmacokinetic parameters were determined by nonlinear extended least-squares regression of pooled data from patients receiving propofol throughout the perioperative period. The effect of CPB on propofol pharmacokinetics was modeled by allowing the parameters to change with the institution and completion of extracorporeal circulation and selecting the optimal model on the basis of the logarithm of the likelihood. Predicted propofol concentrations were calculated by convolving the infusion rates with unit disposition functions using the estimated parameters. The predictive accuracy of the parameters was evaluated by cross-validation and by a prospective comparison of predicted and measured levels in a subset of patients. Results Optimal pharmacokinetic parameters were: central compartment volume = 6.0 l; second compartment volume = 49.5 l; third compartment volume = 429.3 l; Cl1 (elimination clearance) = 0.68 l/min; Cl2 (distribution clearance) = 1.97 l/min1; and Cl3 (distribution clearance) = 0.70 l/min. The effects of CPB were optimally modeled by step changes in V1 and Cl1 to values of 15.9 and 1.95, respectively, with the institution of CPB. Median absolute prediction error was 18% in the cross-validation assessment and 19% in the prospective evaluation. There was no evidence for nonlinear kinetics. Previously published propofol pharmacokinetic parameter sets poorly predicted the observed concentrations in cardiac surgical patients. Conclusions The pharmacokinetics of propofol in adult patients undergoing cardiac surgery with CPB are dissimilar from those reported for other adult patient populations. The effect of CPB was best modeled by an increase in V1 and Cl1. Predictive accuracy of the derived pharmacokinetic parameters was excellent as measured by cross-validation and a prospective test.


2014 ◽  
Vol 97 (5) ◽  
pp. 1488-1495 ◽  
Author(s):  
Michael H. Hall ◽  
Rick A. Esposito ◽  
Renee Pekmezaris ◽  
Martin Lesser ◽  
Donna Moravick ◽  
...  

Perfusion ◽  
2007 ◽  
Vol 22 (4) ◽  
pp. 267-272 ◽  
Author(s):  
D.C. Whitaker ◽  
A.J.E. Green ◽  
J. Stygall ◽  
M.J.G. Harrison ◽  
S.P. Newman

Introduction. The aim of the study was to investigate the relationship between S100b release, neuropsychological outcome and cerebral microemboli. Peri-operative assay of the astroglial cell protein S100b has been used as a marker of cerebral damage after cardiac surgery but potential assay cross-reactivity has limited its specificity. The present study uses an alternative enzyme-linked immunoabsorbant assay (ELISA) for serum S100b that has documented sensitivity and specificity data in patients undergoing coronary artery bypass grafting (CABG). Methods. Fifty-five consecutive patients undergoing routine CABG surgery received serial venous S100b sampling at five time points: i) Pre-operative, ii) At the end of cardiopulmonary bypass (CPB), iii) 6 hrs, iv) 24 hrs and v) 48 hrs post skin closure. A previously described sandwich ELISA with monoclonal anti- S100b was used. This assay has a lower limit of detection of 0.04 μ g/L and < 0.006% reactivity with S100a at a concentration of 100 μg/L S100a. Cerebral microemboli during surgery were recorded by transcranial Doppler monitor over the right middle cerebral artery. Evidence of cerebral impairment was obtained by comparing patients' performance in a neuropsychological battery of 9 tests administered 6—8 weeks post-operatively with their pre-operative scores. Results. There was a significant increase in S100b only at the end of bypass (mean 0.30 μg/L, SD ± 0.33 and range .00 to 1.57). S100b levels at the end of bypass did not correlate with neuropsychological outcome or microemboli counts. Conclusions. The low levels of S100b detected using the present assay, despite its high sensitivity and despite the routine use of cardiotomy suction, suggest that the assay may have higher specificity for cerebral S100b than previously used assays. There was no evidence that this assay is related to neuropsychological change or cerebral microemboli in cardiac surgery. Perfusion (2007) 22, 267—272.


2018 ◽  
Vol 129 (6) ◽  
pp. 1092-1100 ◽  
Author(s):  
Justyna Bartoszko ◽  
Duminda N. Wijeysundera ◽  
Keyvan Karkouti ◽  
Jeannie Callum ◽  
Vivek Rao ◽  
...  

Abstract Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Research into major bleeding during cardiac surgery is challenging due to variability in how it is scored. Two consensus-based clinical scores for major bleeding: the Universal definition of perioperative bleeding and the European Coronary Artery Bypass Graft (E-CABG) bleeding severity grade, were compared in this substudy of the Transfusion Avoidance in Cardiac Surgery (TACS) trial. Methods As part of TACS, 7,402 patients underwent cardiac surgery at 12 hospitals from 2014 to 2015. We examined content validity by comparing scored items, construct validity by examining associations with redo and complex procedures, and criterion validity by examining 28-day in-hospital mortality risk across bleeding severity categories. Hierarchical logistic regression models were constructed that incorporated important predictors and categories of bleeding. Results E-CABG and Universal scores were correlated (Spearman ρ = 0.78, P &lt; 0.0001), but E-CABG classified 910 (12.4%) patients as having more severe bleeding, whereas the Universal score classified 1,729 (23.8%) as more severe. Higher E-CABG and Universal scores were observed in redo and complex procedures. Increasing E-CABG and Universal scores were associated with increased mortality in unadjusted and adjusted analyses. Regression model discrimination based on predictors of perioperative mortality increased with additional inclusion of the Universal score (c-statistic increase from 0.83 to 0.91) or E-CABG (c-statistic increase from 0.83 to 0.92). When other major postoperative complications were added to these models, the association between Universal or E-CABG bleeding with mortality remained. Conclusions Although each offers different advantages, both the Universal score and E-CABG performed well in the validity assessments, supporting their use as outcome measures in clinical trials.


2022 ◽  
pp. jim-2021-001864
Author(s):  
Kanishk Agnihotri ◽  
Paris Charilaou ◽  
Dinesh Voruganti ◽  
Kulothungan Gunasekaran ◽  
Jawahar Mehta ◽  
...  

The short-term impact of atrial fibrillation (AF) on cardiac surgery hospitalizations has been previously reported in cohorts of various sizes, but results have been variable. Using the 2005–2014 National Inpatient Sample, we identified all adult hospitalizations for cardiac surgery using the International Classification of Diseases, Ninth Revision, Clinical Modification as any procedure code and AF as any diagnosis code. We estimated the impact of AF on inpatient mortality, length of stay (LOS), and cost of hospitalization using survey-weighted, multivariable logistic, accelerated failure-time log-normal, and log-transformed linear regressions, respectively. Additionally, we exact-matched AF to non-AF hospitalizations on various confounders for the same outcomes. A total of 1,269,414 hospitalizations were noted for cardiac surgery during the study period. Coexistent AF was found in 44.9% of these hospitalizations. Overall mean age was 65.6 years, 40.9% were female, mean LOS was 11.6 days, and inpatient mortality was 4.5%. Stroke rate was lower in AF hospitalizations (1.8% vs 2.1%, p<0.001). Mortality was lower in the AF (3.9%) versus the non-AF (5%) group (exact-matched OR or emOR=0.48, 95% CI 0.29 to 0.80, p<0.001; 987 matched pairs, n=2423), with similar results after procedural stratification: isolated valve replacement/repair (emOR=0.38, p<0.001), isolated coronary artery bypass graft (CABG) (emOR=0.33, p<0.001), and CABG with valve replacement/repair (emOR=0.55, p<0.001). A 12% increase was seen in LOS in the AF subgroup (exact-matched time ratio=1.12, 95% CI 1.10 to 1.14, p<0.001) among hospitalizations which underwent valve replacement/repair with or without CABG. Hospitalizations for cardiac surgery which had coexistent AF were found to have lower inpatient mortality risk and stroke prevalence but higher LOS and hospitalization costs compared with hospitalizations without AF.


Author(s):  
James G Abel ◽  
Daniel R Wong ◽  
Carmen H Ng ◽  
Lillian Ding ◽  
Andrew Kmetic

Background: Cardiac Services BC (CSBC) is responsible for planning, coordinating, monitoring, and, in some cases, funding cardiac services across British Columbia (BC) in collaboration with senior administrators and physicians from five regional health authorities. CSBC maintains the BC Cardiac Registry (BCCR), a longitudinal clinical registry of all invasive cardiac procedures performed in BC. For over 10 years, CSBC has used BCCR data to evaluate annually quality of care indicators for isolated coronary artery bypass graft (CABG), isolated valve, and CABG+valve surgeries. Methods: In preparation for each annual review, CSBC meets with an established Planning Committee of representative surgeons. BCCR data is linked to provincial Vital Statistics data, to the national Discharge Abstract Database, and for the last 3 yearly analyses to the provincial Central Transfusion Registry which provides robust data on red blood cell (RBC) transfusion. At the annual review, CSBC meets with surgeons who are included in the analyses to present the indicator data. Results: In the 2012 evaluation, the following quality of care indicators were presented for the 2007-2011 period: 30-day mortality and 30-day stroke; 30-day RBC transfusion; and indicators for evidence-based medications at discharge. Risk-adjusted analyses were prepared for the 30-day mortality and 30-day stroke indicators to provide valid comparisons over time and according to hospital and surgeon. Patient characteristics and pre-procedural factors were included in the risk models. The risk-adjusted models performed well with C-statistics for the 30-day mortality models for isolated CABG, isolated valve, and CABG+valve surgeries of 0.86, 0.89, and 0.81, and for the 30-day stroke models 0.80, 0.83, and 0.74, respectively. Expected rates by hospital and by surgeon were determined from each risk model, and observed to expected (O/E) ratios were used for comparison of hospitals and surgeons. Rates of RBC transfusion varied by hospital, and a large reduction in transfusion rates from 69% (378 of 546) in 2007 to 43% (252 of 589) in 2011 was observed at one site with historically higher rates. Conclusion: Presenting quality of care indicators annually has raised awareness of outcome rates and variations which existed across the province. The annual process of engaging surgeons in the evaluation process and linkage with other administrative databases to obtain outcome data has been associated with a reduction in use of RBC transfusion and instigated further investigations into regional variation in mortality rates. The addition of new indicators and other risk-adjusted analyses in the future may further improve quality of care in cardiac surgery in BC.


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