Incidence Of Thromboembolic Events Research Articles

Combined intravenous and intra-articular tranexamic acid administration in total knee arthroplasty for preventing blood loss and hyperfibrinolysis: A randomized controlled trial.

Background:Total knee arthroplasty (TKA) is a surgical procedure to replace the weight-bearing surfaces of the knee joint to relieve pain and disability. However, blood loss and fibrinolytic activity, accounting for a poor prognosis following TKA operation, were relieved by fibrinolytic inhibitor tranexamic acid (TXA). For a better application of TXA function, we explored the effect of intravenous injection (IV) of TXA combined with intra-articular injection (IA) of TXA in patients after TKA.Methods:Patients admitted from Weifang People's Hospital from January 2015 to December 2016 who received TKA were injected with 20 mg/kg TXA by IV before TKA (n = 50), 3.0 g TXA by IA after TKA (n = 50), or combination of 20 mg/kg TXA by IV before TKA and 3.0 g TXA by IA after TKA (n = 50). Knee function was assessed using HSS, KSS, NASS, and ROM. In addition, the total blood loss (TBL), hidden blood loss (HBL), maximum hemoglobin (Hb) drop, fibrinolytic activity, as well as incidence of thromboembolism were measured. The patients were followed up for 6 months. The deadline for follow-up was June 2017 and the incidence of thromboembolism events within 6 months after operation was counted.Results:HSS, KSS, NASS scores, and ROM were elevated after patients receiving TKA. Patients received IV plus IA TXA has decreased TBL, HBL, and maximum Hb drop than those received IV TXA-alone and IA TXA-alone, with reductions in FDP and D-dimer, indicating that IV plus IA TXA injection is superior to prevent blood loss and hyperfibrinolysis during TKA. Age, sex, type of femoral prosthesis, and the injection method of TXA were risk factors for HBL of patients after receiving TKA.Conclusions:The aforementioned results demonstrate that TKA is an effective surgery, and IV plus IA TXA injection functions more effectively in reducing blood loss and fibrinolytic activity in patients, which is a clinical factor of occult hemorrhage.

Serum erythropoietin levels, breast cancer and breast cancer-initiating cells

BackgroundCancer is frequently associated with tumor-related anemia, and many chemotherapeutic agents impair hematopoiesis, leading to impaired quality of life for affected patients. The use of erythropoiesis-stimulating agents has come under scrutiny after prospective clinical trials using recombinant erythropoietin to correct anemia reported increased incidence of thromboembolic events and cancer-related deaths. Furthermore, previous preclinical reports indicated expansion of the pool of breast cancer-initiating cells when erythropoietin was combined with ionizing radiation.MethodsUsing four established breast cancer cell lines, we test the effects of recombinant human erythropoietin and the number of breast cancer-initiating cells in vitro and in vivo and study if recombinant human erythropoietin promotes the phenotype conversion of non-tumorigenic breast cancer cells into breast cancer-initiating cells. In a prospective study, we evaluate whether elevated endogenous serum erythropoietin levels correlate with increased numbers of tumor-initiating cells in a cohort of breast cancer patients who were scheduled to undergo radiation treatment.ResultsOur results indicate that recombinant erythropoietin increased the number of tumor-initiating cells in established breast cancer lines in vitro. Irradiation of breast cancer xenografts caused a phenotype conversion of non-stem breast cancer cells into induced breast cancer-initiating cells. This effect coincided with re-expression of the pluripotency factors c-Myc, Sox2, and Oct4 and was enhanced by recombinant erythropoietin. Hemoglobin levels were inversely correlated with serum erythropoietin levels, and the latter were correlated with disease stage. However, tumor sections revealed a negative correlation between serum erythropoietin levels and the number of ALDH1A3-positive cells, a marker for breast cancer-initiating cells.ConclusionsWe conclude that physiologically slow-rising serum erythropoietin levels in response to tumor-related or chemotherapy-induced anemia, as opposed to large doses of recombinant erythropoietin, do not increase the pool of breast cancer-initiating cells.

Safety of Cold Snare Polypectomy in Patients Receiving Treatment with Antithrombotic Agents.

With the aging of the population and rising incidence of thromboembolic events, the clinical use of antithrombotic agents is also increasing. There are few reports yet on the management of antithrombotic agent use in patients undergoing cold snare polypectomy (CSP). The aim of this study was to evaluate whether continued administration of antithrombotic agents in patients undergoing CSP would be associated with an increased rate of delayed post-polypectomy bleeding (DPPB). A total of 1177 colorectal polyps in 501 patients were resected at Omori Red Cross Hospital between October 2017 and March 2018. The polyps were divided into two groups depending on whether the patients received antithrombotic agent treatment or not: the antithrombotic group (911 polyps) and the no-antithrombotic group (266 polyps). Among the 1177 polyp resections, there was no case of DPPB, including in the antithrombotic group. Immediate bleeding occurred in a total of 63 (5.4%) cases. Polyp location in the rectum (OR (95% CI) 2.64 (1.223-5.679); p = 0.013), polyp size ≥ 6mm (OR (95% CI) 4.64 (2.719-7.933); p < 0.001), polypoid growth pattern (OR (95% CI) 2.78 (1.607-4.793); p < 0.001), and antithrombotic agent use (OR (95% CI) 2.98 (1.715-5.183); p < 0.001) were identified as significant risk factors of immediate bleeding. Continued use of antithrombotic agents does not increase the risk of DPPB, even in those receiving multiple antithrombotic agents. Thus, it is safe to perform CSP even in multiple agent users. Prospective, randomized studies are necessary to confirm our results.

Coagulation Factor Xa (Recombinant), Inactivated-Zhzo (Andexanet Alfa) Hemostatic Outcomes and Thrombotic Event Incidence at an Academic Medical Center.

Andexanet alfa is approved for the reversal of factor Xa inhibitors in patients with major bleeding events. We aimed to review the incidence of effective hemostasis with andexanet alfa in a real-world environment. This retrospective cohort included patients hospitalized for a major bleed that resulted in andexanet alfa administration. The primary outcome was effective hemostasis at 12 hours after andexanet alfa treatment. Thromboembolic events and mortality within 30 days were also assessed. Over a 14-month period, 13 patients received andexanet alfa with a mean age of 69 ± 10 years, 54% male, 69% exposed to apixaban (31% rivaroxaban), and had intracranial (46%) and nonintracranial (54%) bleeding sites. Effective hemostasis was observed in 10 (77%) patients. Four (31%) patients experienced 5 thromboembolic events with a median time to event of 6.5 days (range: 0.5-29). Four thrombotic events occurred during the period in which anticoagulation (prophylaxis or therapeutic) was not restarted. Mortality rate was 15%. Andexanet alfa was effective in obtaining hemostasis in a majority of patients. However, the incidence of thromboembolic events was high and may be attributed to a delay in restarting anticoagulation.

Single Ventricle Physiology Patients and Coagulation Abnormalities: Is There a Relationship With Hemodynamic Data and Postoperative Course? A Pilot Study.

This study evaluates coagulation profiles of single ventricle (SV) patients in relationship to liver function, hemodynamic variables and outcome. Twenty-six children with SV anatomy were included. Advanced coagulation profiles, invasive preoperative hemodynamic parameters and clinical course were retrospectively analyzed. Median (interquartile range) age and weight at the time of blood sampling was 25.5 (31) months and 10.5 (6.9) kg. Sixteen patients (16/26; 62%) showed decreased antithrombin and/or protein C (PC) and/or free protein S (PS) function and/or free PS antigen. Two patients showed abnormal activated PC resistance ratio due to heterozygous factor V Leiden mutation and 1 heterozygous prothrombin G20210A mutation. Group comparison (abnormal coagulation profile [group 1; n = 16] versus normal coagulation profile [group 2; n = 10]) showed longer postoperative hospitalization time (p = .04), longer postoperative catecholamine support (p = .01), a higher incidence of thromboembolic events (p = .04), and chylothoraxes (p = .007) in group 1. In 5 (31%) of 16 group 1 patients, thromboembolic complications occurred: cerebral stroke (n = 1), intestinal ischemia (n = 2), thrombus formation in inferior caval vein (n = 1), and pulmonary vein (n = 1). Abnormalities in coagulation parameters are common in SV patients. Coagulation abnormalities constitute a preoperative risk factor and affect postoperative course.

Pro-coagulant haemostatic factors for the prevention and treatment of bleeding in people without haemophilia.

Pro-coagulant haemostatic factors for the prevention and treatment of bleeding in people without haemophilia.

593: Maternal history of recurrent pregnancy loss and long-term risk of thromboembolic events

Recurrent pregnancy loss (RPL) is a multifactorial disorder with potential underlying maternal hypercoagulability. We aimed to investigate whether a history of RPL poses an independent risk for future maternal long-term thromboembolic morbidity. A population-based study compared the incidence of long-term thromboembolic morbidity in a cohort of women with and without a history of RPL. Data were collected from two tertiary medical center databases that were cross- linked and merged: the computerized hospitalization database and the computerized perinatal database of the obstetrics and gynecology department. Deliveries occurred between the years 1991-2017. The rrisk for long-term thromboembolic morbidity was based on the hospital’s database and a pre-defined set of ICD code list related to thromboembolic hospitalizations. A Kaplan-Meier survival curve was constructed to compare cumulative incidence of significant thromboembolic morbidity in the exposed and unexposed groups, and a Cox proportional hazards model, to control for confounders. During the study period 123,791 parturients met the inclusion criteria; 6.7% (n=8,247) of which experienced previous RPL. The rate of thromboembolic related hospitalizations was significantly higher in exposed women as compared to non-exposed ones (1.1% vs. 0.6%, OR=1.8; 95% 1.4-2.2; p<0.001). Cumulative thromboembolic event incidence, as depicted in the survival curves, was also significantly higher among patients with RPL history (Figure, Log rank p <0.001). The Cox model confirmed RPL history to be an independent risk factor for later maternal thromboembolic morbidity, while controlling for maternal age, ethnicity, and known thrombophilia (aHR 1.26, 95%CI 1.01-1.58, p=0.040; Table). A history of RPL is an independent risk factor for long-term thromboembolic morbidity, even in the absence of known maternal thrombophilia.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Bleeding and Thromboembolism After Traumatic Brain Injury in the Elderly: A Real Conundrum

BackgroundElderly patients presenting with a traumatic brain injury (TBI) often have comorbidities that increase risk of thromboembolic (TE) disease and recurrent TBI. A significant number are on anticoagulant therapy at the time of injury and studies suggest that continuing anticoagulation can prevent TE events. Understanding bleeding, recurrent TBI, and TE risk after TBI can help to guide therapy. Our objectives were to 1) evaluate the incidence of bleeding, recurrent TBI, and TE events after an initial TBI in older adults and 2) identify which factors contribute to this risk. MethodsRetrospective analysis of Medicare claims between May 30, 2006 and December 31, 2009 for patients hospitalized with TBI was performed. We defined TBI for the index admission, and hemorrhage (gastrointestinal bleeding or hemorrhagic stroke), recurrent TBI, and TE events (stroke, myocardial infarction, deep venous thrombosis, or pulmonary embolism) over the following year using ICD-9 codes. Unadjusted incidence rates and 95% confidence intervals (CIs) were calculated. Risk factors of these events were identified using logistic regression. ResultsAmong beneficiaries hospitalized with TBI, incidence of TE events (58.6 events/1000 person-years; 95% CI 56.2, 60.8) was significantly higher than bleeding (23.6 events/1000 person-years; 95% CI 22.2, 25.1) and recurrent TBI events (26.0 events/1000 person-years; 95% CI 24.5, 27.6). Several common factors predisposed to bleeding, recurrent TBI, and TE outcomes. ConclusionsAmong Medicare patients hospitalized with TBI, the incidence of TE was significantly higher than that of bleeding or recurrent TBI. Specific risk factors of bleeding and TE events were identified which may guide care of older adults after TBI.

Clinical Outcome Following Reinstitution of Anticoagulation after Major Gastrointestinal Bleed: A Single Institutional Analysis

Introduction: Arterial and venous thromboembolic events, including stroke and myocardial infarction, are a leading cause of morbidity and mortality in the United States. Anticoagulation therapies are critical in preventing such morbidity and/or mortality. Vitamin K antagonist (VKA) such as warfarin has been the standard therapy for decades until recently with the advent of direct oral anticoagulants (DOACs). These newer agents offer important advantages over warfarin however, the risk of bleeding with these drugs as with all anticoagulants remains an ongoing safety concern. Among the most serious adverse events are intracranial hemorrhages (ICH) and major gastrointestinal bleed (MGIB). For patients who were on anticoagulation prior to these events, there seems to be no consensus on the appropriate timing to resume anticoagulation if at all. Our group reported earlier on the outcome of restarting anticoagulation after ICH (ASH 2017;Oral Abstract #332). Herein, we aim to retrospectively investigate the clinical outcome in terms of recurrent bleeding or thromboembolic events following resumption of anticoagulation post MGIB. Clinical outcome analysis was also extended to compare VKA to DOACs.Method: We retrospectively reviewed medical records of over 800 adults [mean age 68 (22-81)] at Beaumont Hospital, an academic community center from January 2008 to January 2018 with confirmed MGIB. Patients with MGIB who were not on anticoagulation prior to and after the bleeding event were excluded from study. Patients who were on antiplatelet therapy were also excluded. A total of 280 patients met the criteria. MGIB is defined as decrease in hemoglobin by 2 grams below baseline and/or endoscopically confirmed bleeding. Association between restarting anticoagulation (VKA or DOACs) and re-bleeding or thromboembolic event was made using time-to-event adjusted analyses.Results: Demographic distribution of studied patients were 163 (58.2%) white, 89 (31.8%) African Americans and 28 (10%) others. Among these patients, 173 (61.8%) were on VKA, 107 (38.2%) were on one of the DOACs (51.4% rivaroxaban; 29.9% apixaban; 9.3% dabigatran; 2% pradaxa; < 1% edoxaban) (Table 1). Although anticoagulation was not reinstituted in 135 (48.2%) patients following MGIB; 13 (4.6%) patients had anticoagulant restarted within 7 days of diagnosis of MGIB; 42 (15%) patients were restarted between 7-30 days and 88 (31.4%) patients were restarted after 30 days. Majority of patients who restarted anticoagulation within 7 days had severe cardiac dysfunction requiring mechanical valves. Among those who restarted anticoagulation within 2 weeks of MGIB, 21 (7.5%) had recurrent GIB; 18 of those patients were restarted within 7 days whereas 3 were restarted between days 7-12. Majority of the recurrent GIB occurred in the warfarin arm since all patients with mechanical valves were on warfarin. Among the DOACS, rivaroxaban rated highest in terms of recurrent GIB (Table 1). The incidence of thromboembolic event was higher among those whose anticoagulants were discontinued after MGIB compared to those who resumed anticoagulation regardless of timing (86.5% vs 16.2%, p < 0.0001).Conclusion: Given the rising national trend on the use of anticoagulants for various medical necessities, it is imperative that a safe and efficient process be devised on reinstitution of anticoagulation post MGIB to guide Clinicians. Although our study represents a single institutional analysis, it concurs with recent studies that early resumption of anticoagulant following stabilization of MGIB is associated with lower thromboembolic events. Timing for resumption depends largely on the medical reason for anticoagulation; reinstitution by day 7 appear safe for patients on mechanical valve whereas after day 12 maybe appropriate for patients with Atrial fibrillation or venous thromboembolism. Our study further reveals that the risk of recurrent bleed and/or thromboembolism may be less in patients on DOACs when compared to VKA. Among those on DOACs, Rivaroxaban had the highest re-bleeding rate. Nonetheless, randomized clinical trials are needed to evaluate the true risk-benefit profile of anticoagulation resumption after MGIB. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Direct Oral Anticoagulants in Patients with Myeloproliferative Neoplasms: A Single Institution Retrospective Study

Introduction: Myeloproliferative neoplasms (MPN) are associated with an increased risk of venous (VTE) and arterial (ATE) thromboembolic events (TE). Anticoagulation needs to be balanced between the risk of incident and recurrent TE and risk of hemorrhage. While data on outcomes of anticoagulation with warfarin in patients with MPN are available, data on safety and efficacy of direct oral anticoagulants (DOACs) in this subgroup are not. Herein, we present outcomes of use of DOACs in patients with MPN at our institution.Methods: In this retrospective cohort study, we searched the Mayo Clinic clinical databases for patients meeting the WHO criteria for MPN who had been prescribed a DOAC between 2011 and 2017. The MPN diagnosis had to have predated the DOAC prescription. Medical records of consenting patients meeting study criteria were reviewed and data on demographics, diagnosis of MPN, indication for DOAC prescription, and their efficacy (incident or recurrent TE) and safety (hemorrhagic events) were abstracted.Results: Over the study period, 19 patients (female = 10) met inclusion criteria. The median age of patients at MPN diagnosis was 67 years (35-83), and 73 years (53-86) at initiation of DOAC. Prescribed DOACs included rivaroxaban (n=12), apixaban (n=6), and dabigatran (n=2) (one patient received rivaroxaban and was switched to apixaban). MPN diagnoses included polycythemia vera (PV) (n=9), essential thrombocythemia and chronic myeloproliferative neoplasm NOS (3 each), chronic myeloid leukemia and myelofibrosis (2 each). Indications for DOAC included thromboembolism (n=13; 68%) (arterial:2 and venous:11), and atrial fibrillation (afib) (n=6; 31%). The median duration of DOAC therapy was 241.5 days (range 13-1879). Five patients were switched from warfarin to rivaroxaban (n=4) and apixaban (n=1) at patient and/or provider preference; the rest were initiated on the DOAC de novo based on provider preference.Of the 19 patients, one patient each experienced a major hemorrhagic and TE event. One patient with PV who was on rivaroxaban for afib required hospitalization for gastrointestinal hemorrhage due to gastritis; DOAC was discontinued following this episode. One other patient with PV had a non-ST elevation myocardial infarction while on rivaroxaban for afib and prior stroke; DOAC was continued. There were no deaths attributable to DOAC use.Discussion: Our limited data suggests that use of DOACs in patients with MPN is feasible with an acceptable balance between risk of hemorrhage and recurrent thrombosis. Additional data on long term outcomes of DOACs in MPNs are needed. DisclosuresNo relevant conflicts of interest to declare.

Burden of Morbidity Borne By Survivors of Multiple Myeloma (MM) Treated with Autologous Blood or Marrow Transplant (BMT) — Results of the BMT Survivor Study (BMTSS)

Background: Autologous BMT (either as a planned procedure after completion of initial treatment or as salvage therapy for relapse) is considered standard of care for patients with MM. Therapeutic advances have resulted in significant improvement in survival, necessitating an understanding of the burden of morbidity borne by MM survivors - an understudied topic. We addressed this gap by conducting a comprehensive evaluation of chronic health conditions (CHCs) in MM patients treated with autologous BMT using BMTSS.Methods: Patients were eligible if they had undergone autologous BMT for MM between 1974 and 2014 at one of 3 BMT centers, had survived for ≥2y after BMT, and were ≥18y of age at participation. Of the 1,116 subjects approached, 630 (56.5%) participated. A nearest-age sibling was invited to participate in the study, and served as an unaffected comparison group (n=289). Survivors and siblings completed a 231-item BMTSS survey that included questions regarding CHCs, including age at onset of each CHC. Each CHC was scored (CTCAE v 4.03) to determine severity. Using multivariable logistic regression, we determined the risk of any severe (grade 3) or life-threatening (grade 4) CHC in survivors compared with siblings, adjusting for age at study, sex, race/ethnicity, education, annual household income and insurance status. Information on initial pre-BMT treatment exposures, conditioning regimens and post-BMT maintenance treatment was abstracted from medical records. Cumulative incidence of CHCs overall, and by specific types were calculated for BMT survivors, treating death as a competing risk. Cox regression was used to determine clinical, demographic and therapeutic predictors of CHCs in BMT survivors.Results: Mean age at BMT was 57.6±8.5y and at survey was 64.2±7.9y. Mean interval between BMT and study participation was 6.6±3.7y; 58% were males, and 62% were non-Hispanic white. Conditioning was melphalan based in 98%, TBI was used in only 5.5%. Mean age at survey for the siblings was 64±8.08y; 58% were male and 84% were non-Hispanic whites. BMT survivors vs. siblings: Overall, 43.3% of the survivors reported a grade 3-4 CHC, placing them at a 1.4-fold higher odds when compared with siblings (95%CI, 1.0-1.9, p=0.03). The odds of developing the following CHCs were significantly higher in BMT survivors when compared with siblings (Fig 1): cataracts (odds ratio [OR]=2.3; 95%CI, 1.4-3.7, p=0.0006), venous thrombo-embolism (VTE: OR=2.4, 95%CI, 1.2-4.6 p=0.01), and subsequent neoplasms (SNs: OR=4.4, 95% CI, 1.8-10.6, p=0.0009). BMT survivors only: 10y cumulative incidence of any grade 3-4 CHC in BMT survivors was 57.6% ± 3.2% (Fig 2). Cataracts: 10y cumulative incidence of cataracts was 24.8% ± 2.7%. Older age at BMT (≥60y: relative risk [RR]=3.3; 95%CI, 2.2-5.1, p <0.0001); TBI-based conditioning (RR=2.3; 95%CI, 1.1-4.8, p=0.02); and female sex (RR=1.6; 95%CI, 1.1-2.4, p=0.01) were associated with increased risk of cataracts. VTE: 10y cumulative incidence of thrombo-embolic events was 10.5% ± 1.6%. Older age at BMT (≥60y: RR=2.2; 95%CI, 1.2-3.9, p=0.007); non-Hispanic white race/ethnicity (RR=4.8; 95%CI, 2.0-11.2, p=0.0003); and pre-BMT exposure to doxorubicin (RR=2.1; 95%CI, 1.04-4.04, p=0.04) were associated with increased risk for VTE. SNs:10y cumulative incidence of SN was 14.0% ± 2.5%. Older age at BMT (≥60y: RR=2.2; 95%CI, 1.2-4.2, p=0.01), pre-BMT exposure to cyclophosphamide (RR=2.9, 95%CI,1.3-6.5, p=0.01) and IMiDs (thalidomide or lenalidomide: RR=3.8, 95%CI, 1.6-9.2, p=0.003); and non-Hispanic white race/ethnicity (RR=2.3; 95%CI, 1.1-4.8, p=0.03) were associated with increased risk for SNs.Conclusion: The 10y cumulative incidence of a severe/life-threatening chronic health condition approaches 60% in multiple myeloma patients treated with autologous BMT. Cataracts, thrombo-embolic events and subsequent neoplasms constitute the largest burden of morbidity. This study identifies demographic factors and treatment exposures associated with increased risk of chronic health conditions, and provides evidence for close monitoring of these survivors to anticipate and manage morbidity. [Display omitted] DisclosuresWeisdorf:Seattle Genetics: Consultancy; Pharmacyclics: Consultancy; FATE: Consultancy; SL Behring: Consultancy; Equillium: Consultancy. Forman:Mustang Therapeutics: Other: Licensing Agreement, Patents & Royalties, Research Funding.

Use of Direct Oral Anticoagulants Among Patients Undergoing Cardioversion: The Importance of Timing Before Cardioversion.

Cardioversion, whether pharmacological or electrical, is associated with a risk of thromboembolic events on the order of 5% to 7% within 30 days in nonanticoagulated patients.1, 2 The risk of thromboembolism is at its highest within the first 7 days after cardioversion (>80% of events), with the greatest risk within the first 2 days (≈70% of events).3 Thus, the incidence of thromboembolic events within the first week is analogous to the yearly incidence in moderate‐risk nonvalvular atrial fibrillation (NVAF) patients who have not undergone cardioversion. This risk can be mitigated to <1% within 30 days with the use of therapeutic anticoagulation before, during, and after cardioversion.3 Thromboembolic risk is not negated by a low CHADS2 (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke/transient ischemic attack), or CHA2DS2‐VASc (adding vascular disease, age 65–74 years, and female sex) score or by a negative transthoracic esophageal echocardiogram (TEE) because of thrombus formation after cardioversion because of left atrial stunning.3, 4 The single biggest risk factor for thrombus formation is inadequate anticoagulation.4 The conventional approach is to anticoagulate, most commonly with an oral vitamin K antagonist (VKA), for a minimum of 3 weeks before, during, and for a minimum of 4 weeks postcardioversion. The recommendation to anticoagulate for 3 weeks before cardioversion is based on pathophysiologic and observational data, but has not been confirmed by randomized controlled trials.5, 6 In addition, the retrospective analysis by Gallagher et al demonstrated that thromboembolic events were significantly more common at international normalized ratio (INR) 1.5 to 2.4 versus ≥2.5 (0.93% versus 0%, P=0.012), reinforcing the importance of establishing therapeutic anticoagulation before cardioversion.7 Prior studies evaluating parenteral anticoagulation as a means to expedite time to cardioversion over conventional oral VKA therapy have all ensured “therapeutic anticoagulation” at the time of cardioversion. These studies have shown noninferiority between parenteral anticoagulation and conventional therapy, with cardioversion time ranging from 1 to 3 days versus 21 to 30 days, respectively.8, 9 Though the benefits of oral VKAs have long been established in NVAF with respect to stroke reduction, VKAs have the disadvantages of required monitoring and follow‐up, complex drug and food interactions, a narrow therapeutic range, and slow onset of action.10, 11, 12, 13, 14 Since 2010, the US Food and Drug Administration (FDA) has approved the oral direct thrombin inhibitor (DTI) dabigatran (Pradaxa) and 3 oral factor Xa (FXa) inhibitors rivaroxaban (Xarelto), apixaban (Eliquis), and edoxaban (Savaysa) for prevention of stroke and systemic embolism (SSE) in patients with NVAF.15 These agents have all shown either superiority or noninferiority to warfarin in reducing the risk of SSE in this patient population with similar or reduced major bleeding.16, 17, 18, 19 In these clinical trials, all of these agents have shown a reduction in the risk of intracranial hemorrhage as compared with warfarin. Oral DTI and oral FXa inhibitors have the potential advantages of a rapid onset, fixed dosing, no required routine monitoring, and fewer drug/food interactions as compared with VKAs. Of particular interest is the rapid onset of action and the potential to avoid parenteral anticoagulation and the delay in action of VKAs, culminating in faster time to cardioversion, improved maintenance of sinus rhythm, and potentially reduced hospitalization days and health‐system costs.20, 21, 22, 23 As such, these agents offer a potential alternative to conventional anticoagulation strategies for cardioversion. However, there is discordance between the major guidelines pertaining to how best to utilize these agents pericardioversion.5, 20, 24, 25, 26 Given the lack of data, inconsistencies among the guidelines, and the expanding role of oral DTI and oral FXa inhibitor anticoagulants, we reviewed the literature evaluating dabigatran, rivaroxaban, apixaban, and edoxaban in patients requiring cardioversion for atrial fibrillation (AF). Furthermore, we evaluated the pharmacokinetic and pharmacodynamic data for each agent to determine the optimal timing of administration to achieve therapeutic anticoagulation and thus be safely eligible for early cardioversion.

Left Atrial Appendage Occlusion With Left Ventricular Assist Device Decreases Thromboembolic Events

Thromboembolic events (TEs) are common adverse events with continuous-flow left ventricular assist devices (LVADs). Left atrial appendage occlusion (LAAO) is commonly performed at the time of a cardiac operation. The effect of LAAO on TEs in LVAD patients remains unknown. All patients receiving a first LVAD implantation between January 2013 and January 2014 were reviewed. TEs included device thrombosis and ischemic cerebrovascular accidents. The incidence of TEs with respect to LAAO was evaluated using Kaplan-Meier and Cox proportional hazards analyses. The analysis included 102 patients, 36 of whom received LAAO and 66 did not. LAAO patients were an average age of 60 years, and 69.4% were men. Non-LAAO patients were an average age of 59.3 years, and 71.2% were men. There were no significant differences in characteristics other than history of coronary artery bypass grafting (8.3% of LAAO vs 44% of non-LAAO, p= 0.0005). Preoperative atrial fibrillation was present in 19 LAAO patients (52.7%) and in 36 non-LAAO patients (54.5%; p= 1.0). Patients were monitored for a median of 306 days. TEs occurred in 3 LAAO patients (1 device thrombosis and 2 cerebrovascular accidents) compared with 15 non-LAAO patients (5 device thromboses and 11 cerebrovascular accidents, p= 0.049). In a Cox hazards analysis including age, sex, hypertension, and atrial fibrillation, LAAO demonstrated a decreased risk of TE (hazard ratio, 0.27; 95% confidence interval, 0.08 to 0.95; p= 0.04). In patients undergoing LVAD implantation, LAAO is associated with reduced TEs, and this effect may be independent of atrial fibrillation. A prospective randomized study to examine the efficacy LAAO in prevention of TE is needed to confirm these findings.

Thromboembolic events in patients with advanced stage non-small cell lung cancer treated with platinum-based chemotherapy: a prospective observational study

ObjectivesCancer is frequently complicated by thromboembolic events (TEs). We aimed to determine the incidence of TEs in lung cancer patients treated with platinum-based chemotherapy and study patients’ baseline and treatment attributes correlating with its onset.Materials and methodsAdvanced lung cancer patients started on platinum-based chemotherapy were evaluated at baseline and during routine visits for the development of TEs. The duration of follow-up was 4 weeks from the last chemotherapy. A TE occurring between the first dose of chemotherapy and 4 weeks after the last dose was considered to be chemotherapy associated.ResultsOf the 165 patients on platinum chemotherapy who completed follow-up, TEs occurred in 4.8% (8 out of 165) patients. Among these, three patients had developed venous pulmonary thromboembolism and five patients had developed cerebral infarction, out of which four had arterial cerebral infarction and one patient had a superior sagittal sinus thrombosis. The majority of events (7 out of 8) occurred within 100 days of starting platinum chemotherapy. Overall, the median time until occurrence of TE was 48 days (range, 10–130 days). None of the presumed risk factors were found be associated with the occurrence of TEs on univariate analysis.ConclusionsAdvanced lung cancer patients on platinum chemotherapy are predisposed to thromboembolism due to many factors. Despite its lower incidence in our study, exclusion of patients with prior thrombosis suggests the incidence of de novo thrombosis, and hence raises a valid question of the need of thromboprophylaxis in a selected group of patients.

Thromboprophylaxis in Intensive Care Unit Patients: A Literature Review.

Thromboembolism is a major complication in hospitalized patients. Intensive care unit (ICU) patients have a greater risk of thrombotic events due to additional risk factors such as immobilization, mechanical ventilation, and central catheters. The diagnosis and management of deep vein thrombosis (DVT) and pulmonary embolism (PE) in critically ill patients are challenging and these conditions are associated with high mortality. Medical thromboprophylaxis with low molecular weight heparin (LMWH) as well as unfractionated heparin (UFH) has been shown to reduce the incidence of thromboembolic events in such patients. For patients with high risk of bleeding, mechanical thromboprophylaxis can be used. Literature database was conducted on Medline for articles published up to 2018 using particular search terms such as thromboprophylaxis and venous thromboembolism in ICU patients. The following review summarizes the existing data regarding thromboprophylaxis in ICU patients with special consideration to the use of mechanical prophylaxis and pharmacologic prophylaxis using heparin products.

Initial Experience of the Use of 3-Factor Prothrombin Complex Concentrate and Thromboembolic Complications After Cardiac Surgery

3-factor prothrombin complex concentrate (3F-PCC) may provide a valuable treatment option for coagulopathy in cardiac surgery patients. However, it may expose patients to increased risk of thromboembolic events. Accordingly, we compared the incidence of thromboembolic events between patients exposed to 3F-PCC and those receiving conventional therapy. Demographic, operative and postoperative data was obtained in a cohort of consecutive patients exposed to 3F-PCC and a contemporaneous control population. Propensity-score matching was performed for risk adjustment. Unadjusted and adjusted patient demographics and incidence of thromboembolism were compared. Patients receiving 3F-PCC (PCC) were younger (mean age PCC: 64±14.2 vs. No PCC: 67.6±11.6, p=0.022), and less likely to have diabetes or previous myocardial infarction. PCC patients experienced more prolonged aortic cross clamp times (mean time in minutes PCC: 119.9±58.8 vs. No PCC: 92.3±54), more complex cardiac surgeries and were more likely to have received more fresh frozen plasma (FFP), cryoprecipitate and red blood cells. Despite this, both unadjusted and adjusted 30-day mortality and readmission rates were similar between groups. There were 9 (9.2%) and 34 (6.8%) (p=0.40) thromboembolic events in the unadjusted PCC and control groups respectively. Adjusted risk for thromboembolic event rates was also comparable (Odds ratio: 1.512, 95% Confidence Interval 0.401-5.7, p=0.541). 3-factor prothrombin complex concentrate was administered to patients at greater risk of complications including bleeding. Our initial experience suggests that the use of PCC does not appear to increase thromboembolic risks compared to conventional treatment.

Impact of lenalidomide use among non-transfusion dependent patients with myelodysplastic syndromes.

Chemotherapies approved for defined subgroups promise personalized oncologic care, but their off-label impact is unclear. Lenalidomide is approved for lower-risk, transfusion-dependent (TD) myelodysplastic syndromes (MDS) with del(5q), but frequently used in MDS outside this indication. We characterized lenalidomide use and outcomes among non-TD patients with MDS. Patients 65 or older diagnosed with MDS between 2007 and 2013 were identified using SEER; linked Medicare claims were evaluated for transfusions, lenalidomide use, and incident toxicities. TD was ≥2 transfusion episodes within an 8-week period; responses were transfusion independence (TI) and ≥50% transfusion reduction (minor response). We compared overall survival for non-TD patients receiving lenalidomide versus those not receiving lenalidomide, matched on disease and patient characteristics. We identified 676 patients who had received lenalidomide, including 275 (40.7%) TD and 401 (59.3%) non-TD; 18.5% (125/676) had zero claims for RBC transfusion prior to receiving lenalidomide. Incident toxicities among patients prescribed lenalidomide were similar in TD and non-TD groups, except incident thromboembolic events were higher among non-TD patients (10.8% vs. 6.0%, P = .04). Comparing 191 non-TD patients receiving lenalidomide within 6 months of MDS diagnosis to risk-matched MDS controls, lenalidomide was not associated with improved OS (P = .78). Among TD patients (n = 275), 31% achieved TI, and 30% achieved minor hematologic response, with a median time to TI of 4.1 weeks. In conclusion, we confirmed the benefit of lenalidomide among TD patients with MDS; however, many non-TD patients also received lenalidomide. These patients experienced accompanying toxicity without evidence of benefit in terms of transfusion needs or overall survival.

Tranexamic Acid for the Prevention of Blood Loss after Vaginal Delivery

BackgroundThe use of tranexamic acid reduces mortality due to postpartum hemorrhage. We investigated whether the prophylactic administration of tranexamic acid in addition to prophylactic oxytocin in women with vaginal delivery would decrease the incidence of postpartum hemorrhage.MethodsIn a multicenter, double-blind, randomized, controlled trial, we randomly assigned women in labor who had a planned vaginal delivery of a singleton live fetus at 35 or more weeks of gestation to receive 1 g of tranexamic acid or placebo, administered intravenously, in addition to prophylactic oxytocin after delivery. The primary outcome was postpartum hemorrhage, defined as blood loss of at least 500 ml, measured with a collector bag.ResultsOf the 4079 women who underwent randomization, 3891 had a vaginal delivery. The primary outcome occurred in 156 of 1921 women (8.1%) in the tranexamic acid group and in 188 of 1918 (9.8%) in the placebo group (relative risk, 0.83; 95% confidence interval [CI], 0.68 to 1.01; P=0.07). Women in the tranexamic acid group had a lower rate of provider-assessed clinically significant postpartum hemorrhage than those in the placebo group (7.8% vs. 10.4%; relative risk, 0.74; 95% CI, 0.61 to 0.91; P=0.004; P=0.04 after adjustment for multiple comparisons post hoc) and also received additional uterotonic agents less often (7.2% vs. 9.7%; relative risk, 0.75; 95% CI, 0.61 to 0.92; P=0.006; adjusted P=0.04). Other secondary outcomes did not differ significantly between the two groups. The incidence of thromboembolic events in the 3 months after delivery did not differ significantly between the tranexamic acid group and the placebo group (0.1% and 0.2%, respectively; relative risk, 0.25; 95% CI, 0.03 to 2.24).ConclusionsAmong women with vaginal delivery who received prophylactic oxytocin, the use of tranexamic acid did not result in a rate of postpartum hemorrhage of at least 500 ml that was significantly lower than the rate with placebo. (Funded by the French Ministry of Health; TRAAP ClinicalTrials.gov number, NCT02302456.)

Bridging anticoagulation in patients treated with vitamin K antagonists prior to trochanteric and hip fracture surgeries: The current practice.

The strategies of perioperative bridging anticoagulation in orthopedic surgical patients during oral anticoagulation (OAC) therapy with vitamin K antagonists (VKA) vary from center to center. The aim of this single-center study was to assess the risk of bleeding and thromboembolic events (TEs) in bridged patients on VKA who underwent orthopedic surgery due to trochanteric or hip fracture. The retrospective study included 64 patients (mean age: 80 years) who received VKA for at least 3 months prior to orthopedic procedure. All subjects were bridged with enoxaparin (40 mg once a day). The control group (n = 69) comprised of age-, sexand procedure-matched patients operated on for the same indications, but with neither a history of VKA therapy nor perioperative bridging anticoagulation. Severe postoperative bleeding occurred in 19 (29.7%) patients from the VKA group and in 13 (18.8%) controls (p = 0.16). Within the VKA group, intertrochanteric fractures (52.6%) and femoral neck fractures (47.4%) occurred more often in patients with bleeding than other lower extremity fractures (0%; p = 0.03). Severe adverse events (SAEs) were more common in the VKA group than in the controls (12.5% vs 1.5%; p = 0.01). Patients from the VKA group did not differ from the controls in the incidence of TEs (6.3% vs 8.9%; p = 0.31). No intrahospital mortality was documented. Prophylactic administration of enoxaparin is a common strategy of bridging anticoagulation in a hospital setting. This approach does not seem to be associated with an increase in thromboembolic risk nor higher risk of bleeding in orthopedic patients who received VKA preoperatively.

Incidence and risk of thromboembolism associated with bevacizumab in patients with non-small cell lung carcinoma.

Bevacizumab, a recombinant humanized monoclonal antibody against vascular endothelial growth factor (VEGF), is effective for the treatment of advanced non-small cell lung cancer (NSCLC). However, severe adverse events (AEs) have been reported in NSCLC patients treated with bevacizumab. Currently, the contribution of Bevacizumab to thromboembolism is still controversial. We conducted a study to determine the overall risk and incidence of thromboembolism with bevacizumab in NSCLC patients. Electronic databases such as the PubMed, Web of Science and Cochrane Library were searched for related trials. Statistical analyses were conducted to calculate the overall incidence rates, odds ratios (ORs), and 95% confidence intervals (CIs) by using either random-effect or fixed-effect models depending on the heterogeneity. We also used trial sequence analysis (TSA) to verify the pooled result. A total of 3,555 subjects from nine studies were included. The overall incidence of thromboembolism events in NSCLC patients treated with bevacizumab was 4.8% (95% CI: 1.9-7.7%). Without bevacizumab, this incidence was 2.9% (95% CI: 0.6-5.1%). Bevacizumab use was associated with a significantly increased risk in thromboembolism events (OR =1.74; 95% CI: 1.15-2.62; P=0.008). Subgroup analysis based on the doses showed that bevacizumab administered at 15 mg/kg (OR =1.81; 95% CI: 1.14-2.86; P=0.012), but not 7.5 mg/kg (OR =1.32; 95% CI: 0.78-2.24; P=0.296), increased the risk of thromboembolism. Bevacizumab is associated with a significantly increased risk of thromboembolism development in NSCLC patients. It may have dose-toxicity relationship and low dose of bevacizumab may be a better choice for NSCLC patients, with equal efficacy and low hazard of thromboembolism events.