[Physicians' Opinion on Health Care in Oral Anticoagulation]. / Einschätzung von Ärzten zur medizinischen Versorgung mit oralen Antikoagulanzien.

BACKGROUND: The introduction of direct oral anticoagulants (DOAC) in addition to the established Vitamin K antagonist (VKA) has increased the complexity of antithrombotic therapy leading to numerous treatment options. Studies of the medical evaluation of the current treatment situation by health care providers, which are of great importance for the development of treatment strategies in addition to studies on pharmacovigilance, are limited in the literature. METHODS: 11 700 physicians (Rhineland-Palatinate, Germany) were contacted to participate in the web-based survey on health care with oral anticoagulation (OAC). After detailed quality control, the study was analysed in synopsis with routine care data of VKA patients of the thrombEVAL study programme (N = 2.011). RESULTS: In total, 512 physicians (mean age: 48.0 ±â€Š9.6 years; 74.0 % male) participated in the study. In general, quality of OAC therapy was rated as "average/satisfactory" (2.9 ±â€Š0.9). Comparison of physicians' perception with data from routine care highlighted marked differences regarding time in therapeutic range (+ 6.4 % [95 %-CI 2.7 %; 9.5 %]), duration of control intervals (- 35.0 % [28.0 %; 41.4 %]) and rate of OAC-related complications (+ 61.8 [37.8 %; 83.3 %], which differed additionally and statistically-significant between physician groups. The willingness to use DOAC was approximately 50 % lower in general physicians as compared to specialists (36.6 % [25.4 %; 47.8 %] vs. 72.4 % [66.0 %; 78.9 %]; p < 0.0001). Regarding management of OAC therapy, 73.8 % [69.7 %; 77.9 %] advocated the establishment of a service hotline and 67.3 % [62,9 %; 71.6 %] a specialized coagulation service. DISCUSSION: The present survey among physicians reveals a need for optimization of OAC therapy in daily practice. Specialized care models might facilitate optimized OAC therapy with both VKAs and DOACs.

Direct oral anticoagulants in patients with chronic kidney disease: patient selection and special considerations.

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.

Haemostasis in chronic kidney disease.

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.

Anticoagulation in a Neurosurgical Patient with Heparin-Induced Thrombocytopenia Type II with Argatroban and Fondaparinux after Clipping of an Intracranial Aneurysm.

BACKGROUND: Therapeutic anticoagulation in patients after a major neurosurgical procedure remains critical because of the risk of a major intracranial bleed. Novel drugs could play a beneficial role in this setting. CASE REPORT: We describe a patient with heparin-induced thrombocytopenia type II and pulmonary embolism who was anticoagulated with argatroban and, later, with fondaparinux. No intracranial bleeding was detected when anticoagulation was performed with argatroban and, later, fondaparinux. CONCLUSION: Both substances could have therapeutic potential in this context.

Risk stratification and heparin prophylaxis to prevent venous thromboembolism in pregnant women.

Women with a history of venous thromboembolism (VTE), thrombophilia or both may be at increased risk of thrombosis during pregnancy, but the optimal management strategy is not well defined in clinical guidelines because of limited trial data. A strategy of risk assessment and heparin prophylaxis was evaluated in pregnant women at increased risk of VTE. In a prospective trial (Efficacy of Thromboprophylaxis as an Intervention during. Gravidity [EThIG]), 810 pregnant women were assigned to one of three management strategies according to pre-defined risk factors related to history of VTE and thrombophilic profile. Low-risk women (group I), received 50-100 IU dalteparin/kg body weight/day for 14 days postpartum, or earlier when additional risk factors occurred. Women at high (group II) or very high risk (group III) received dalteparin from enrollment until six weeks postpartum (50-100 IU and 100-200 IU/kg/day, respectively). Objectively confirmed, symptomatic VTE occurred in 5/810 women (0.6%; 95% confidence interval [CI], 0.2 to 1.5%) (group I, 0 of 225; II, 3/469; III, 2/116). The rate of serious bleeding was 3.0% (95 % CI, 1.9 to 4.4%); 1.1% (95 % CI, 0.5 to 2.2%) was possibly dalteparin-related. There was no evidence of heparin-induced thrombocytopenia, one case of osteoporosis, and rates of miscarriage and stillbirth were similar to previous, retrospective studies. Risk-stratified heparin prophylaxis was associated with a low incidence of symptomaticVTE and few clinically important adverse events. Antepartum heparin prophylaxis is, therefore, warranted in pregnant women with idiopathic thrombosis or symptomatic thrombophilia.

Method comparison of cardiac marker assays on PATHFAST, StratusCS, AxSYM, Immulite 2000, triage, elecsys and cardiac reader.

The purpose of this evaluation was to perform a method comparison of the assays for cardiac troponin I (cTnl), CK-MB, myoglobin, and NT-proBNP on the automated PATHFAST Immuno-Assay Analyzer with respective immunoassays on other commercially available immunoanalyzers. The PATHFAST assays are immunochemiluminescent assays (in single reagent cartridges) employing two mono- or polyclonal antibodies in a sandwich test format. The calibration materials for cTnI and CK-MB are standardized to the reference materials NIST SRM 2921 (troponin CIT complex) and IRMM-IFCC 455 (CK-MB mass). The PATHFAST assays for cTnI, CK-MB, myoglobin, and NT-proBNP on the PATHFAST Analyzer were compared using 118 (NT-proBNP: 90) plasma samples from patients with different cardiovascular diseases with those on the Dade Behring StratusCS Analyzer, on the Abbott AxSYM System, on the DPC IMMMULITE 2000 Analyzer, on the Biosite Triage Meter Plus System, on the Roche Elecsys Immuno Analyzer 2010 and Roche Cardiac Reader System, respectively. The correlation coefficients for the comparison of cTnI methods ranged from 0.953 to 0.982, those for the comparison of myoglobin methods ranged from 0.776 to 0.992, and those for the comparison of CK-MB methods ranged from 0.835 to 0.999, with the Triage System giving in all comparisons the lowest correlation. Also the comparison of PATHFAST NTproBNP against the Roche Elecsys assay yielded a very good correlation (r = 0.992). The slopes of the regression line among methods showed considerable variation indicating that standardization efforts by international groups are indispensable to achieve harmonization of results. In summary, this evaluation study confirms the overall good correlation of the results obtained with assays for cardiac markers developed on the PATHFAST analyzer with those on other immunoassay platforms and thus the analytical reliability of the developed methods.

Anticoagulation with low-molecular-weight heparin (dalteparin) in plasmapheresis therapy: initial experience.

BACKGROUND: In contrast to other extracorporeal treatments no established regime exists for anticoagulation with low-molecular-weight heparin (LMWH) in plasmapheresis therapy. A study was conducted to investigate whether LMWH (dalteparin-Na) is suitable as an effective anticoagulant in plasmapheresis therapy. STUDY DESIGN AND METHODS: Eleven patients with autoimmune neurological diseases and the necessity for a plasmapheresis therapy were enrolled. A capillary membrane filter was used. A total of 2000 mL of human plasma was isovolumetrically exchanged per plasmapheresis cycle. The anticoagulation was accomplished with a single bolus of LMWH (dalteparin) of 80 to 90 IU per kg of body weight. The system was visually monitored. Anti-factor (F)Xa activity, thrombin-antithrombin III complex (TAT), and prothrombin fragment 1+2 (F 1+2) were determined at regular intervals. Samples were taken from the collected plasma pool to determine the loss of LMWH during the plasmapheresis procedure. RESULTS: All plasmapheresis cycles with LMWH were successful without complications. Approximately 40 percent of the initially administered LMWH bolus was lost by the large porous filter during the plasmapheresis. The anti-FXa values were determined to be 0.5 IU per mL during the entire plasmapheresis. TAT values were elevated (TAT median, 14.3 microg/L). F 1+2 values measured before the filter cartridge remained within the normal range for the entire plasmapheresis cycle (<1.2 nmol/L) and were increasingly elevated after the filter. CONCLUSION: Our initial experiences with LMWH for anticoagulation in plasmapheresis indicate that a body weight adjusted dose of LMWH (dalteparin) is suitable for anticoagulation in plasmapheresis therapy. No complications were observed. The data are encouraging. Further investigations will show if and how the present anticoagulation regime could be further optimized.

Glycogen phosphorylase BB in acute coronary syndromes.

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.

[Prevention of thromboembolism with low molecular weight heparin (Dalteparin-Na) in risk pregnancy]. / Thromboembolieprophylaxe mit niedermolekularem Heparin (Dalteparin-Na) bei Risikoschwangerschaften.

BACKGROUND: Venous thrombotic events still remain the leading cause of maternal morbidity and mortality. During pregnancy as well as post partum, hemostasis changes also in normal pregnant women. Coagulation is activated and fibrinolysis suppressed, the concentration of particular coagulation factors is increased, while inhibitor potential is decreased. Additionally, the venous blood stream is mechanically hampered by the gravid uterus. As a result of these physiologic changes, the risk of thromboembolism is elevated. The risk increases frequently in women with previous thromboembolic episodes, a family history of thromboembolism, hereditary or acquired thrombotic disorders as well as the appearance of additional exposure prothrombogenic factors such as immobilization, inflammation, and operation. Simultaneous presence of combined prothrombogenic factors conducts a potentiation of the risk of thromboembolism. To avoid thromboembolism or rethromboembolism during pregnancy or puerperium, an individual risk-adapted heparin prophylaxis is indicated. PATIENTS AND METHODS: 17 pregnant women with inherited and/or acquired prothrombogenic disorders, eleven of them with previous thromboembolism episodes, were treated with low molecular weight heparin (LMWH; dalteparin-Na). The daily dose of 5,000-10,000 IU LMWH was applied subcutaneously by self-injection during pregnancy and up to 8 weeks post partum. Every 4 weeks clinical and laboratory monitoring was performed. Basic parameters as well as the special coagulation marker TAT (thrombin-antithrombin complex) and D-dimer were analyzed. RESULTS: Under the therapy with LMWH (dalteparin-Na), no thromboembolic events during pregnancy or post partum could be observed. No serious bleeding complications, except small subcutaneous local hematomas, occurred. Bolus applications of LMWH by self-injection were easy to practice, gained a good acceptance and high compliance. Increased TAT values above normal at the actual state of pregnancy could be suppressed to normal values by raising the LMWH dose. CONCLUSION: The individual thromboembolic prophylaxis with LMWH represents an effective and safe therapy in risk pregnancy with previous thromboembolic events and/or thrombotic disorders. TAT seems to be an effective marker for monitoring of the coagulation activity during pregnancy and puerperium. Under this management, thromboembolic prophylaxis can be optimized.