Difference In Thromboembolic Events Research Articles

An Evaluation of the Use of Topical Tranexamic Acid in Total Knee Arthroplasty

The purpose of this study was to evaluate the effectiveness of topical tranexamic acid in primary TKA from a clinical and economic standpoint. We retrospectively reviewed 683 primary total knee arthroplasties performed at a single institution over a 2-year period. We compared 373 cases performed in 2010 without tranexamic acid to 310 cases performed in 2011 with tranexamic acid. Demographic data, hemoglobin levels, transfusion rates, hospital length of stay, cost, and perioperative complications during the first 3 months were collected. Statistical analysis was performed using two sample t-tests and Fisher's exact tests. There was no difference in age, sex, height, or pre-operative hemoglobin between the two groups. The tranexamic acid group had significantly higher post-operative hemoglobin (P<0.0001), lower transfusion rate (P<0.0001), decreased length of stay (P<0.0001), decreased blood bank costs (P<0.0001), increased pharmacy cost (P<0.0001), and decreased total direct cost to the hospital (P<0.0001). The average savings was approximately $1500 per patient. There were no differences in thromboembolic events or infection. The use topical tranexamic acid in primary TKA is safe, effective, and results in significant cost savings.

Recombinant Activated Factor VII Use in Critically III Patients: Clinical Outcomes and Thromboembolic Events

Hemorrhage and coagulopathy are associated with morbidity and mortality in critically ill patients. Recombinant activated factor VII (rFVIIa) is frequently used in these situations to control bleeding; however, few controlled clinical trials have demonstrated clinical benefit and prolonged survival. To compare clinical outcomes and thromboembolic events in intensive care unit (ICU) patients who received rFVIIa versus ICU patients who did not between 2000 and 2005. A total of 2918 nonhemophiliac adult ICU patients, which included 1459 who received at least 1 dose of rFVIIa and 1459 matched controls who did not, were included in a retrospective database study. Data were extracted from the Solucient ACTracker database, which included 550 hospitals across the US. Measures included patient demographics, rFVIIa prescribing, death, thromboembolic events, discharge disposition, length of stay, and transfusion data. The most common primary diagnoses for patients receiving rFVIIa included traumatic brain injury, cirrhosis, and nontraumatic intracranial hemorrhage. Patients receiving rFVIIa were more likely to have comorbidities, including mechanical ventilation, acute kidney injury, sepsis, hemodialysis, and gastrointestinal bleeding (p < 0.0001). The average rFVIIa dose was 4.8 mg and 82% of patients received 1 dose. Compared to controls, patients receiving rFVIIa had greater odds of death (OR 2.1, 95% CI 1.8-2.6, p < 0.0001), transfusion (OR 2.1, 95% CI 1.8-2.5, p < 0.0001), and longer length of stay (p < 0.001). There was no significant difference in thromboembolic events between groups. While we cannot show direct causality between rFVIIa and the poor clinical outcomes documented in ICU patients, they provide important insight for critical care clinicians.

Periprocedural Heparin Bridging in Patients Receiving Vitamin K Antagonists

Background— Periprocedural bridging with unfractionated heparin or low-molecular-weight heparin aims to reduce the risk of thromboembolic events in patients receiving long-term vitamin K antagonists. Optimal periprocedural anticoagulation has not been established. Methods and Results— MEDLINE, EMBASE, and Cochrane databases (2001–2010) were searched for English-language studies including patients receiving heparin bridging during interruption of vitamin K antagonists for elective procedures. Data were independently collected by 2 investigators (κ=0.90). The final review included 34 studies with 1 randomized trial. Thromboembolic events occurred in 73 of 7118 bridged patients (pooled incidence, 0.9%; 95% confidence interval [CI], 0.0.0–3.4) and 32 of 5160 nonbridged patients (pooled incidence, 0.6%; 95% CI, 0.0–1.2). There was no difference in the risk of thromboembolic events in 8 studies comparing bridged and nonbridged groups (odds ratio, 0.80; 95% CI, 0.42–1.54). Bridging was associated with an increased risk of overall bleeding in 13 studies (odds ratio, 5.40; 95% CI, 3.00–9.74) and major bleeding in 5 studies (odds ratio, 3.60; 95% CI, 1.52–8.50) comparing bridged and nonbridged patients. There was no difference in thromboembolic events (odds ratio, 0.30; 95% CI, 0.04–2.09) but an increased risk of overall bleeding (odds ratio, 2.28; 95% CI, 1.27–4.08) with full versus prophylactic/intermediate-dose low-molecular-weight heparin bridging. Low-thromboembolic-risk and/or non–vitamin K antagonist patient groups were used for comparison. Study quality was poor with heterogeneity for some analyses. Conclusions— Vitamin K antagonist–treated patients receiving periprocedural heparin bridging appear to be at increased risk of overall and major bleeding and at similar risk of thromboembolic events compared to nonbridged patients. Randomized trials are needed to define the role of periprocedural heparin bridging.

HIT Antibody Seropositivity and Thromboembolic Events After Cardiac Surgery

Abstract 1159▪▪This icon denotes a clinically relevant abstract Background.Heparin induced thrombocytopenia (HIT) is an immune disorder where platelets are activated by antibodies to a complex of platelet factor 4 antigen and heparin (PF4/H), leading to thrombocytopenia (HIT) and, potentially, thrombosis (HITT). Documentation of anti-PF4/H antibodies in addition to the appropriate clinical findings is essential for making a diagnosis of HIT. In the post-cardiac bypass surgery setting, however, the frequency of elevated anti-PF4/H antibodies is high, whereas the frequency of clinical HIT or HITT is relatively uncommon. Several studies have shown that the presence of anti-PF4/H antibodies may be associated with an increased frequency of adverse outcomes, even in the absence of clinical HIT. The primary objective of this study was to determine the relationship between a positive PF4/H antibody in the postoperative setting with adverse thromboembolic events occurring up to 3 months after cardiac surgery. Methods.Patients undergoing cardiac surgery who were not going to be treated with chronic anticoagulation postoperatively were eligible for this multi-center prospective cohort study. Data were collected daily during hospitalization, and then at 30 and 90 days after surgery using a structured interview format with a standardized questionnaire that included all thrombotic as well as hemorrhagic events, platelet counts, and utilization of antithrombotics in the postoperative setting. The primary outcome variable was a composite endpoint comprising arterial and venous thrombotic events and other miscellaneous events compatible with HIT, as well as death attributable to an event compatible with HIT. Citrated plasma was collected at baseline, pre-discharge (∼4–5 days after surgery), and the 30 day follow-up visit, processed, and stored at −80°C for testing. Laboratory analyses included an anti-PF4/H antibody ELISA (GTI, Waukesha, WI) on all samples, a high-heparin confirmatory test on samples with an OD reading >0.40, and a serotonin release assay (SRA) on all postoperative samples with an OD reading >0.40. A sample size of 800 patients was estimated in order to detect a 3% difference in thromboembolic events assuming a 2 to 10-fold increase risk attributable to seropositivity. Chi-squared testing was used to test the relationship between the primary outcome and postoperative anti-PF4/H levels. Results.Informed consent was obtained from 1030 eligible patients between August 2006 and May 2009, and laboratory and follow-up data were analyzable for 1016 patients. Thirty-day antibody data were available for 888 patients, and fully complete laboratory and 90-day follow-up data were available for 815 patients. The average age was 62 ± 12 years, and 73% of participants were male. A total of 769 patients underwent coronary artery bypass grafting and 237 underwent valve repair or replacement. During the entire study period, there were 17 (1.7%) deaths, 46 thromboembolic events in 44 patients (4.3%), and 25 hemorrhagic events in 24 patients (2.4%). Using an OD cutoff of 0.40 for the ELISA, 339 patients (33.4%) were positive for anti-PF4/H antibodies at the time of discharge, and 630 patients (62%) were positive by day 30. There was no correlation between seropositivity for anti-PF4/H antibodies at the day of discharge or at day 30 and the primary outcome (p=0.47 and 0.73, respectively). Incorporating the high-heparin confirmatory step did not improve the relationship between positive antibody results and the primary outcome. Using a higher cut-off value for the anti-PF4/H antibody ELISA of 1.0 decreased the number of patients with positive results (96 patients at the time of discharge [9.4%] and 221 patients at the 30-day follow-up visit [21.8%]), but this did not improve the relationship between antibody positivity at the day of discharge or day 30 and the primary clinical endpoint, since most patients with the primary endpoint had an ELISA OD below 1.0 (75th percentile of 0.90; 90th percentile of 1.22). Similarly, using the SRA did not identify a relationship between assay results and outcome. Conclusions.The presence of anti-PF4/H antibodies in the postoperative setting following cardiac bypass surgery is not associated with an increased risk for thromboembolic complications. Positive anti-PF4/H results in this clinical setting should be interpreted with caution and only in the context of clinical suspicion for HIT. Disclosures:Ortel:Instrumentation Laboratory: Consultancy; Eisai: Research Funding; GSK: Research Funding. Welsby:CSL Behring: Speaker; CSL Behring: Membership on an entity's Board of Directors or advisory committees; NovoNordisk: Principal Investigator. Heit:Daiichi Sankyo: Honoraria; Ortho-McNeil Janssen: Honoraria; Covidien: Honoraria.

Perioperative Heparin Bridging in Patients Receiving Oral Anticoagulation: Meta-Analysis of Bleeding and Thromboembolic Rates

Abstract 545 Background:Periprocedural bridging using unfractionated heparin (UFH) or low molecular weight heparin (LMWH) in patients receiving chronic oral anticoagulation (OAC) is often utilized with the view to reduce the risk of thromboembolic (TE) events. Optimal perioperative anticoagulant methods have not been established. Methods: Systematic review and meta-analysis of published English-language studies from 2001 to 2010 examining bleeding and TE events in patients receiving bridging therapy during temporary OAC interruption for elective procedures. Results: A search of MEDLINE, EMBASE and Cochrane Collaboration databases yielded 32 studies on 6760 bridged patients. Studies were reviewed by 2 independent data collectors (k=0.869). Study quality was generally poor with risk of bias. Thirty-one studies were observational with 1 randomized controlled trial. Low TE risk and/or non-OAC patient groups were used for comparison in 12 observational studies. Major (22/32, 68.8%) and non-major (27/32, 84.4%) procedures were represented. TE events occurred in 67 of 6760 bridged (0.87%; 95% CI 0.40%–1.35%) and 29 of 4897 non-bridged (0.77%; 95% CI 0.24%–1.30%) patients. Using a random effects model, there was no difference in the risk of TE events in bridged versus non-bridged patients (OR 1.02, 95% CI 0.53–1.95). Bridged patients had a significantly increased risk of overall bleeding (OR 5.47, 95% CI 3.89–7.70) and major bleeding (OR 3.43, 95% CI 1.13–10.4) compared to non-bridged patients. There was no difference in TE events (OR 2.44, 95% CI 0.34–17.4) or overall bleeding (OR 2.40 95% CI 0.72–8.05) in patients receiving full versus intermediate/low dose LMWH. Summary: Patients receiving heparin bridging during OAC interruption appear to be at increased risk of bleeding and similar risk of TE events compared to non-bridged patients. Studies of high methodologic quality are needed to develop an optimal anticoagulation strategy and inform clinical decision-making. Disclosures:Lim:Leo Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Consultancy; Pfizer: Honoraria. Kaatz:Boehringer-Ingelheim: Consultancy, Research Funding, Speakers Bureau; Bristol Myer Squibb: Consultancy, Research Funding; Bayer: Research Funding; National Institute of Health: Research Funding; Canadian Institute of Health Research: Research Funding; Pfizer: Consultancy; Johnson and Johnson: Consultancy; Ortho-McNeil: Consultancy; GlaxoSmithKline: Speakers Bureau; AC Forum: Membership on an entity's Board of Directors or advisory committees; National Certification Board of Anticoagulation Providers: Membership on an entity's Board of Directors or advisory committees; National Blood Clot Alliance: Membership on an entity's Board of Directors or advisory committees.

Postcesarean thromboprophylaxis with two different regimens of bemiparin.

Objectives. To compare the effectiveness of postcesarean thromboprophylaxis with two different regimens of bemiparin. Material and Methods. The study included 646 women with cesarean delivery in our hospital within a 1-year period, randomly assigned to one of two groups for prophylaxis with 3500 IU bemiparin once daily for 5 days or 3500 IU bemiparin once daily for 10 days. Results. There was one case of pulmonary embolism (first day following cesarean). An additional risk factor was present in 98.52% of the women, most frequently emergency cesarean, anemia, or obesity. The only risk factors for thromboembolic disease significantly related to pulmonary thromboembolism were placental abruption and prematurity. There were no differences in thromboembolic events among the two thromboprophylaxis regimens. Conclusions. Cesarean-related thromboembolic events were reduced in our study population due to the thromboprophylactic measures taken. Thromboprophylaxis with 3500 IU bemiparin once daily for 5 days following cesarean was sufficient to avoid thromboembolic events.

Warfarin Sensitivity Genotyping: A Review of the Literature and Summary of Patient Experience

The antithrombotic benefits of warfarin are countered by a narrow therapeutic index that contributes to excessive bleeding or cerebrovascular clotting and stroke in some patients. This article reviews the current literature describing warfarin sensitivity genotyping and compares the results of that review to the findings of our study in 189 patients at Mayo Clinic conducted between June 2001 and April 2003. For the review of the literature, we identified relevant peer-reviewed articles by searching the Web of Knowledge using key word warfarin-related adverse event. For the 189 Mayo Clinic patients initiating warfarin therapy to achieve a target international normalized ratio (INR) in the range of 2.0 to 3.5, we analyzed the CYP2C9 (cytochrome P450 2C9) and VKORC1 (vitamin K epoxide reductase complex, subunit 1) genetic loci to study the relationship among the initial warfarin dose, steady-state dose, time to achieve steady-state dose, variations in INR, and allelic variance. Results were compared with those previously reported in the literature for 637 patients. The relationships between allelic variants and warfarin sensitivity found in our study of Mayo Clinic patients are fundamentally the same as in those reported by others. The Mayo Clinic population is predominantly white and shows considerable allelic variability in CYP2C9 and VKORC1. Certain of these alleles are associated with increased sensitivity to warfarin. Polymorphisms in CYP2C9 and VKORC1 have a considerable effect on warfarin dose in white people. A correlation between steady-state warfarin dose and allelic variants of CYP2C9 and VKORC1 has been demonstrated by many previous reports and is reconfirmed in this report. The allelic variants found to most affect warfarin sensitivity are CYP2C9*1*1-VKORC1BB (less warfarin sensitivity than typical); CYP2C9*1*1-VKORC1AA (considerable variance in INR throughout initiation); CYP2C9*1*2-VKORC1AB (more sensitivity to warfarin than typical); CYP2C9*1*3-VKORC1AB (much more sensitivity to warfarin than typical); CYP2C9*1*2-VKORC1AB (much more sensitivity to warfarin than typical); CYP2C9*1*3-VKORC1AA (much more sensitivity to warfarin than typical); and CYP2C9*2*2-VKORC1AB (much more sensitivity to warfarin than typical). Although we were unable to show an association between allelic variants and initial warfarin dose or dose escalation, an association was seen between allelic variant and steady-state warfarin dose. White people show considerable variance in CYP2C9 allele types, whereas people of Asian or African descent infrequently carry CYP2C9 allelic variants. The VKORC1AA allele associated with high warfarin sensitivity predominates in those of Asian descent, whereas white people and those of African descent show diversity, carrying either the VKORC1BB, an allele associated with low warfarin sensitivity, or VKORC1AB or VKORC1AA, alleles associated with moderate and high warfarin sensitivity, respectively.

Current Evidence Based Guidelines for Factor VIIa Use in Trauma: The Good, the Bad, and the Ugly

Recombinant factor VII (rFVIIa) has arisen as an option for the control of life-threatening traumatic bleeding unresponsive to other means. The timing of administration, dosage, mortality, units of blood transfusion saved, risk of thrombotic events, and risk/benefits ratio are presently poorly defined. A Medline search from 1995 through March 2008 was conducted. All English language articles containing the terms "trauma" and "factor VII" or its variants were retrieved. Letters to the editor, animal studies, and general reviews were excluded. A total of 19 articles met inclusion criteria. These articles were then reviewed and stratified into three classes of evidence according to the quality assessment instrument developed by the Brain and Trauma Foundation. Levels of recommendation were developed. A total of 118 articles were identified. Only one Class I study was identified. This study demonstrated that three doses of rFVIIa given in blunt traumatic hemorrhage yielded a significant reduction of 2.6 of red blood cells used. These findings were not statistically significant for penetrating trauma patients. There was no reduction in mortality and no increase in thromboembolic events. Four Class II studies were identified; three showed a significant decrease of blood product usage and one demonstrated significant reductions in 24-hour and 30 day death from hemorrhage in patients receiving rFVIIa. The remaining 14 studies were Class III reviews of databases, registries, case series, and case reports. No identified study specifically addressed the cost/benefit analysis of rFVIIa usage in trauma hemorrhage. Utility of rFVIIa in trauma-associated hemorrhage remains controversial. There is Level I supporting the use of rFVIIa for blunt trauma patients only. There is no Class I evidence supporting decreased mortality or differences in thromboembolic events. Minimal effective dosing regimens and cost/benefit analyses have not yet been examined.

Renal transplantation in r-HuEPO-treated patients

After sporadic reports of renal graft artery thromboses, prophylaxis against thrombosis (PAT) was given to all of our r-HuEPO-treated patients (n = 35) during a period of 2 years. No thromboembolic events (TEE) occurred in the r-HuEPO-treated group receiving PAT. However, the PAT-protocol (500 ml dextran on days 0, 1, 3 and 5, followed by low doses of aspirin, 160–250 mg daily) resulted in a 54.3% incidence of bleeding complications, of which 22.9% were major (i. e., necessitating multiple transfusions or invasive procedures). A group of renal graft recipients (n = 83), who were not treated with r-HuEPO and were not given PAT, showed a 10.8% incidence of bleeding complications of which 2.4% major. Two cases of TEE were noted in the untreated group. The difference in bleeding complications between the two groups was statistically significant (0.025 > P > 0.01). The difference in TEE between the groups was not significant. We found no difference between the groups with regard to early and late graft function and the incidence of acute rejections. In summary, r-HuEPO treatment did not influence the prognosis in renal graft recipients. The use of PAT in the r-HuEPO-treated group resulted in a high incidence of bleeding complications. In consequence, we have abandoned the routine use of PAT in this patient group.