Journal of Thrombosis and Thrombolysis

Professionals voice confusion between the distinctions of board certification and educational certificate courses, and note barriers and motivators in obtaining national anticoagulation board certification. To identify barriers vs. motivators in obtaining board certification and detail the differences in board certification and educational certificate courses, an IRB-approved electronic survey was sent to professionals completing the University of Southern Indiana (USI) Anticoagulation Therapy educational certificate course (n = 491) and existing Certified Anticoagulation Care Providers (CACP, n = 622). A total of 1049 surveys were delivered successfully, with a 26% response rate (USI = 62, CACP = 211.) Respondents identified as a nurse (n = 52, 19%), advanced practice nurse (n = 14, 5.1%), pharmacist (n = 206, 75.5%) or physician (n = 5, 1.8%). Overall, respondents indicated board certification via CACP has significant impact on patient/organizational outcomes (n = 118, 43.2%). Top motivators for board certification include personal accomplishment (n = 147, 53%) and professional growth (n = 139, 50.9%). Top barriers include lack of time to prepare (n = 102, 37.3%,) board certification exam cost (n = 95, 34.8%), and for CACP recertification, and requirement to recertify by examination (n = 74, 35.1%). Of board-certified respondents, 45.4% indicated they were not employed at an Anticoagulation Center of Excellence (ACE), 34.8% employed at an ACE and 16.8% were unsure of ACE status. Narrative comments were obtained and evaluated. Significant personal and professional barriers exist in completing, and subsequently maintaining, board certification in anticoagulation. This offers great insight for NCBAP to invoke changes to support clinicians and healthcare organizations in seeking and maintaining CACP credentialing, a component of ACE attainment.

The ultimate goal of warfarin therapy, to prevent thromboembolism with the lowest possible risk of major bleeding complications, is most likely to be realized when therapeutic anticoagulation as measured by the international normalized ratio (INR) is quickly achieved and maintained in appropriate candidates. Realizing this goal requires optimal functioning of various anticoagulation management system components. The extent to which these components function smoothly together determines the quality of warfarin therapy management. A quality measure is used to ascertain the degree to which a given system is successfully coordinating care to accomplish a particular therapeutic goal. The quality of care can be evaluated at different levels such as outcomes (e.g. INR results, major bleeding, thromboembolism, death), processes (e.g. method used to adjust warfarin doses), and structures (e.g. clinic organization structure, workload statistics). There is great need for a structured program of quality measurement for warfarin therapy management. The arrival of new options for oral anticoagulation medications increases the need for credible information regarding the site-specific quality of warfarin therapy management because the potential advantages over warfarin therapy associated with some of these agents are in part dependent upon the quality of warfarin therapy management.

Infection increases the risk of thrombosis through the activation of inflammation and coagulation. Edoxaban, a direct oral factor Xa inhibitor, is used for the prevention and treatment of thrombotic diseases. The aim of this study was to determine the effects of edoxaban on microvascular thrombus formation in a rat model of lipopolysaccharide (LPS)-induced coagulopathy. Rats were intravenously injected with 7.5 mg/kg of LPS (Escherichia coli 055:B5). Immediately after LPS injection, the rats were treated with subcutaneous injection of edoxaban. At 2 and 6 h after the injection of LPS, biomarkers of coagulation and organ damages and inflammatory cytokines were measured. Microvascular thrombus formation in organs was evaluated using 125I-fibrinogen (human) or by the pathological analysis. Mortality was examined 24 h after LPS injection. After the injection of LPS, D-dimer and thrombin-antithrombin complex increased and platelet numbers decreased, indicating the activation of coagulation. Microvascular thrombi were found in the liver. Markers of liver injury (aspartate aminotransferase and alanine aminotransferase) also increased. Treatment with edoxaban attenuated the changes in the coagulation markers and microvascular thrombus formation in the liver. Edoxaban suppressed the increase in the liver injury markers and reduced the mortality. Edoxaban did not affect the levels of inflammatory cytokines. In conclusions, edoxaban significantly inhibited the activation of coagulation, the formation of microvascular thrombus in the liver and the liver damage, and reduced mortality in rats injected with LPS. These results suggest that the FXa inhibition by edoxaban might be a beneficial therapy for the management of infection-associated thrombosis.

Under pressure to provide cost-effective healthcare, many healthcare systems have adopted Therapeutic Interchange (TI) programs—the interchange of therapeutically equivalent but chemically unique drugs—to reduce the total cost of therapy without compromising patient care. To be appropriate and feasible, a TI program for any class of drugs must meet certain rigorous criteria and undergo medical, financial, tactical, and legal reviews. Moreover, once a TI program is implemented, a process to monitor its success should be established. Application of the TI criteria to low-molecular-weight heparins (LMWHs) reveals that a blanket TI program for LMWHs does not appear advisable at this time.

Venous thromboembolism (VTE) carries significant morbidity and mortality and affects a large portion of hospitalized patients. VTE prophylaxis is rated by the Agency for Healthcare Research and Quality as the most effective of 79 patient safety practices it assessed in 2001. Since 1997, Blue Cross Blue Shield of Michigan/Blue Care Network (BCBSM/BCN) have partnered with Michigan hospitals and providers in statewide registry-based collaborative quality improvement initiatives (CQI) aimed at improving the safety and quality of surgical and medical care; many of these collaborative have a particular focus on VTE prevention. The CQIs are uniquely structured to catalyze hospitals and practitioners to become self-optimizing. In this review, we describe the model BCBSM/BCN and participating Michigan hospitals have developed to improve the prevention and diagnosis of VTE for patients in the state of Michigan.

Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice, accounting for approximately one-third of hospitalizations for cardiac rhythm disturbances. The highest incidence of AF is in patients 70–80 years old and other high-risk populations. Although the diagnosis of AF is usually straightforward, effective treatment strategies are less well implemented. This is particularly true for antithrombotic therapy, which is very effective at preventing thromboembolic complications of AF. Stroke is the most significant morbidity in AF patients. The yearly risk of stroke increases from 1.5% for AF patients aged 50–59 to 23% for those aged 80–89. Ischemic strokes secondary to AF carry twice the risk of death when compared with strokes from other causes. We provide a practical and useful review of the most recent American College of Cardiology/American Heart Association/European Society of Cardiology guidelines-based care and future directions of antithrombotic therapy for patients with AF.

During recent years it has become increasingly recognized that the plasmin activation system is involved in the development of atherosclerosis and restenosis. Responsible pathophysiologic mechanisms, however, remain elusive. This review focuses primarily on the clinicians, point of view, suggesting that increases in plasminogen activator inhibitor type-1 (PAI-1) plasma levels after balloon angioplasty or permanently elevated lipoprotein (a) (Lp(a)) plasma levels might be helpful in the prediction of restenosis after coronary angioplasty. In contrast, tissue-type plasminogen activator (tPA) plasma levels appear unrelated to restenosis, and data regarding a possible role of urokinase-type plasminogen activator (uPA) in circulation are not available at present. Furthermore, a new hypothesis on the pathophysiological role of local PAI-1 overexpression as a beneficial negative feedback mechanism to limit excess cellular proliferation in atherogenesis and restenosis is presented.

Enoxaparin is a hydrophilic drug with obesity having little effect on its apparent volume of distribution, therefore patients with obesity receiving standard 1 mg/kg dosing may be at a higher risk of supratherapeutic dosing. Conversely, dose reducing patients with obesity could place already at risk patients at higher risk of a thrombotic event. Data and recommendations are variable for the most appropriate weight-based dose of therapeutic enoxaparin in obese patients, particularly those a weight > 100 kg or a body mass index (BMI) ≥ 40 kg/m2. The purpose of this systematic review was to globally evaluate these data to surmise optimal dosing recommendations for patients with obesity. A systematic review of English language studies was conducted and identified articles via Pubmed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) searches. Studies were included if they reported therapeutic enoxaparin use in adult patients with a BMI ≥ 40 kg/m2 or body weight > 100 kg and the percentage of patients achieving a therapeutic anti-Xa based on a weight-based dose or the weight-based dose required to produce a therapeutic anti-Xa level. Therapeutic attainment of anti-Xa levels were assessed across enoxaparin weight-based dosing categories including a very low dose group: < 0.75 mg/kg, low dose group: 0.75–0.85 mg/kg, and standard dose group: ≥ 0.95 mg/kg. Rates of bleeding and thrombosis were also evaluated. A total of eight studies were included. For anti-Xa level assessment, 682 patients were included. A total of 62% of anti-Xa levels were therapeutic in the very low dose group, 66% in the low dose group, and 42% in the standard dose group. Overall rates of total bleeding and thrombosis were assessed in 798 patients. A total of 29 bleedings (3.6%) occurred, and 27 reported a relationship to dose. Most bleedings, 85.2% (n = 23/27), occurred with doses in the standard dose group (≥ 0.95 mg/kg). Thrombosis occurred in 5 patients (0.6%). Utilization of a reduced weight-based dosing strategy for therapeutic enoxaparin in obese patients may increase the percentage of patients with a therapeutic anti-Xa level. 1. Current evidence for therapeutic enoxaparin use in obese patients mainly consists of small, retrospective data, but inappropriate dosing may lead to bleeding or thrombotic events. 2. This review identified eight studies that assessed therapeutic enoxaparin dosing in patients with a BMI ≥ 40 kg/m2 or > 100 kg and determined that patients with a reduced dosing regimen (0.75–0.85 mg/kg) achieved goal anti-Xa levels 66% of the time compared to 43% of the time with full weight-based dosing (≥ 0.95 mg/kg). 3. Rates of bleeding occurred in 3.6% of patients, most of which (> 85%) were in the full weight-based dosing group. 4. Use of a reduced weight-based dose of enoxaparin (0.75–0.85 mg/kg) may result in more obese patients with a BMI ≥ 40 kg/m2 or body weight > 100 kg achieving goal anti-Xa levels than full weight-based dosing. 5. Prospective randomized-controlled trials are required to verify clinical outcomes in this population.

Atrial fibrillation (AF) is a common cardiac arrhythmia. Dabigatran etixalate (DE) is one of the new oral anticoagulant drugs being used in nonvalvular AF (NVAF). There is no adequate real world data in different populations about DE. The aim of this registry was to evaluate the efficacy and safety of DE Consecutive NVAF patients treated with warfarin or both DE doses were enrolled during 18 months study period. The patients were re-evaluated at regular 6-month intervals during the follow-up period. During the follow-up period outcomes were documented according to RELY methodology A total of 555 patients were analyzed. There was no significant difference in ischemic stroke rates (p = 0.73), death rates (p = 0.15) and MI rates (p = 0.56) between groups. The rate of major bleeding was significantly higher in warfarin and dabigatran 150 mg group than dabigatran 110 mg (p < 0.001). Intracranial bleeding rate and relative risk were significantly lower in dabigatran 110 mg group than warfarin group (p = 0.004). Dyspepsia was significantly higher in both DE doses than warfarin (p = 0.004) Both DE doses are as effective as warfarin in reducing stroke rates in NVAF patients, without increasing MI rates. Intracranial bleeding rates are significantly lower in warfarin than both doses of DE and gastrointestinal bleeding risk increases with increased DE doses.