The coagulation system has gained much interest again as new anticoagulatory substances have been introduced into clinical practice. Especially patients with renal failure are likely candidates for such a therapy as they often experience significant comorbidity including cardiovascular diseases that require anticoagulation. Patients with renal failure on new anticoagulants have experienced excessive bleeding which can be related to a changed pharmacokinetic profile of the compounds. However, the coagulation system itself, even without any interference with coagulation modifying drugs, is already profoundly changed during renal failure. Coagulation disorders with either episodes of severe bleeding or thrombosis represent an important cause for the morbidity and mortality of such patients. The underlying reasons for these coagulation disorders involve the changed interaction of different components of the coagulation system such as the coagulation cascade, the platelets and the vessel wall in the metabolic conditions of renal failure. Recent work provides evidence that new factors such as microparticles (MPs) can influence the coagulation system in patients with renal insufficiency through their potent procoagulatory effects. Interestingly, MPs may also contain microRNAs thus inhibiting the function of platelets, resulting in bleeding episodes. This review comprises the findings on the complex pathophysiology of coagulation disorders including new factors such as MPs and microRNAs in patients with renal insufficiency.

Many patients with chronic kidney disease (CKD) receive anticoagulation or antiplatelet therapy due to atrial fibrillation, coronary artery disease, thromboembolic disease, or peripheral artery disease. The treatment usually includes vitamin K antagonists (VKAs) and/or platelet aggregation inhibitors. The direct oral anticoagulants (DOAC) inhibiting factor Xa or thrombin represent an alternative for VKAs. In patients with acute and chronic kidney disease, caution is warranted, as DOACs can accumulate as they are partly eliminated by the kidneys. Thus, they can potentially increase the bleeding risk in patients with CKD. In patients with an estimated glomerular filtration rate (eGFR) above 60 mL/min, DOACs can be used safely with greater efficacy and safety as compared to VKAs. In patients with CKD 3, DOACs are as effective as VKAs with a lower bleeding rate. The more the renal function declines, the lower is the advantage of DOACs over VKAs. Thus, use of DOACs should be avoided in patients with an eGFR below 30 mL/min, particularly, the compounds with a high renal elimination. Available data suggest that DOACs can also be used safely in older patients. In this review, use of DOACs in comparison with VKAs, heparins, and heparinoids, together with special considerations in patients with impaired renal function will be discussed.

The diagnosis of myocardial damage is preferably based on measurement of the cardiac-specific troponins. However, there is an emerging need for early, specific cardiac markers. One potential candidate is the glycogen phosphorylase BB isoenzyme (GPBB). We investigated the use of a new, commercially available GPBB ELISA assay in 61 patients presenting with an acute coronary syndrome (37 acute myocardial infarction, 24 unstable angina pectoris) in comparison to established cardiac markers such as troponin T, creatine kinase isoenzyme MB (CKMB) mass, and myoglobin. Blood samples were obtained on arrival, as well as 1, 2, 3, 4, 8, 12 and 24 h later. GPBB plasma concentrations were elevated in 90.9% of patients 1 h after onset of chest pain and increased to 100% at 4-5 h. Within the first 6 h, GPBB showed the highest sensitivity (95.5-100%) and high specificity (94-96%) compared to myoglobin (85-95% sensitivity) and CKMB mass (71.4-91.3% sensitivity). As expected, troponin T showed high specificity (100%) and sensitivity >95% later in the time course (>or=3 h). In un-stable angina pectoris patients, a very high rate of elevated GPBB was observed (93.9% at 3 h) compared to myoglobin (66.7%). Cardiac troponin T and CKMB were only elevated in 33.8% and 55.0% of these patients, respectively. In conclusion, GPBB is a promising marker for the early diagnosis of acute coronary syndromes and could probably act as a marker of ischemia. However, further studies on specificity and development of a fast, automated assay are necessary before GPBB can be recommended as a routine diagnostic tool.

Background Management of oral anticoagulation (OAC) therapy is essential to minimize adverse events in patients receiving vitamin K-antagonists (VKAs). Data on the effect of e-health-based anticoagulation management systems on the clinical outcome of OAC patients are limited. Objectives To compare the clinical outcome of OAC patients managed by an e-health-based coagulation service (CS) with that of patients receiving regular medical care (RMC). Methods The prospective multicenter cohort study thrombEVAL (NCT01809015) comprised 1558 individuals receiving RMC and 760 individuals managed by a CS. Independent study monitoring and adjudication of endpoints by an independent review panel were implemented. Results The primary study endpoint (composite of thromboembolism, clinically relevant bleeding and death) occurred in 15.7 per 100 patient-years (py) with RMC and in 7.0 per 100 py with the CS (rate ratio [RR], 2.3; 95% confidence interval [CI], 1.7-3.1). Rates for major and clinically relevant bleeding were higher with RMC than with the CS: 6.8 vs. 2.6 and 10.1 vs. 3.6 per 100 py, respectively. Thromboembolic events showed an RR of 1.5 (95% CI, 0.8-2.6) comparing RMC with the CS. Hospitalization (RR, 2.6; 95% CI, 2.3-3.0) and all-cause mortality (RR, 4.6; 95% CI, 2.8-7.7) were markedly more frequent with RMC. In Cox regression analysis with adjustment for age, sex, cardiovascular risk factors, comorbidities, treatment characteristics and sociodemographic status, hazard ratios (HR) for the primary endpoint (HR, 2.2; 95% CI, 1.5-3.4), clinically relevant bleeding (HR, 3.1; 95% CI, 1.7-5.5), hospitalization (HR, 2.2; 95% CI, 1.8-2.8) and all-cause mortality (HR, 5.6; 95% CI, 2.9-11.0) favored CS treatment. Conclusions In this study, e-health-based management of OAC therapy was associated with a lower frequency of OAC-specific and non-specific adverse events.