vitamin-k-semiquinone-radical and Arterial-Occlusive-Diseases

The Multimorbid Patient: Use of New Oral Anticoagulants in Patients with Chronic Kidney Disease Abstract. Increasing life expectancy in Western countries is associated with a high prevalence of multiple chronic diseases which is defined by the term "multimorbidity". Many of these patients suffer from chronic kidney disease (CKD) and thrombogenic comorbidities such as atrial fibrillation with the need for oral anticoagulation. For decades vitamin K antagonists have been exclusively prescribed for oral anticoagulation. However, due to altered pharmacokinetics and bioavailability of these drugs in CKD, a significant risk of bleeding exists. The introduction of direct oral anticoagulants as a new and promising alternative to vitamin K antagonists was -especially for CKD patients - highly anticipated. However, data from randomized studies are missing for older patients with advanced CKD. Consequently, a careful evaluation of the risk-benefit ratio is recommended for this sensitive patient population.. Zusammenfassung. Die zunehmende Lebenserwartung in den westlichen Ländern führt zu einer gleichzeitigen Zunahme chronischer Krankheiten, was mit «Multimorbidität» bezeichnet wird. Viele dieser Patienten leiden an chronischer Niereninsuffizienz (CKD) sowie thrombogenen Komorbiditäten wie z.B. Vorhofflimmern, weshalb eine orale Antikoagulation indiziert ist. Für lange Zeit standen lediglich die Vitamin-K-Antagonisten zur Verfügung. Aufgrund der unter anderem veränderten Pharmakokinetik sowie Bioverfügbarkeit dieser Medikamente bei CKD besteht jedoch gleichzeitig ein deutlich erhöhtes Blutungsrisiko. Die Einführung der direkten oralen Antikoagulanzien als neue und vielversprechende Alternative zu Vitamin-K-Antagonisten wurde daher insbesondere für die Population der CKD-Patienten mit grosser Spannung erwartet. Aufgrund der noch nicht ausreichenden Datenlage insbesondere bei älteren Patienten mit fortgeschrittener Niereninsuffizienz sollte das Risiko-Nutzen-Verhältnis vor Therapiebeginn sorgfältig evaluiert werden.

Topics: Anticoagulants; Arterial Occlusive Diseases; Atrial Fibrillation; Comorbidity; Contraindications; Coronary Disease; Dabigatran; Glomerular Filtration Rate; Kidney Failure, Chronic; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Thromboembolism; Vitamin K

Vitamin K was discovered early last century at the same time as the vitamin K-antagonists. For many years the role of vitamin K was solely ascribed to coagulation and coagulation was thought to be involved only at the venous blood side. This view has dramatically changed with the discovery of vitamin K-dependent proteins outside the coagulation cascade and the role of coagulation factors at the arterial side. Vitamin K-dependent proteins are involved in the regulation of vascular smooth muscle cell migration, apoptosis, and calcification. Vascular calcification has become an important independent predictor of cardiovascular disease. Vitamin K-antagonists induce inactivity of inhibitors of vascular calcification, leading to accelerated calcification. The involvement of vitamin K-dependent proteins such as MGP in vascular calcification make that calcification is amendable for intervention with high intake of vitamin K. This review focuses on the effect of vitamin K-dependent proteins in vascular disease.

Topics: Animals; Anticoagulants; Arterial Occlusive Diseases; Arteries; Blood Coagulation Factors; Blood Proteins; Calcinosis; Humans; Models, Cardiovascular; Vitamin K

The aim of medicinal treatment, during and after femoral and crural interventions is to prevent early or late onset arterial thrombosis of the treated vascular segments. Therefore, unfractionated heparin is administered during the intervention by an intra-arterial or intravenous approach. To avoid late onset thrombosis, administration of platelet function inhibitors is recommended. However, valid data are only available for acetylsalicylic acid (ASA). Therefore, ASA is recommended for long term medication. In several cardiological studies on stent implantation in coronary vessels the combination of ASA and clopidogrel for dual platelet inhibition has been proven to be effective. These results have been transferred to antithrombotic therapy of the lower extremities despite the lack of dedicated studies. There is no evidence for the use of vitamin K antagonists after peripheral interventions.

Topics: Administration, Oral; Anticoagulants; Arterial Occlusive Diseases; Aspirin; Clopidogrel; Drug Therapy, Combination; Heparin; Humans; Infusions, Intravenous; Ischemia; Leg; Long-Term Care; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Secondary Prevention; Thrombocytopenia; Thrombosis; Ticlopidine; Vitamin K

Vitamin K-antagonists and heparin belong to the established indirect acting anticoagulants. For many years these drugs were the only possibility for prophylaxis and treatment of venous and arterial thrombosis. The challenges for the routine laboratory related to the treatment with vitamin K-antagonists and heparin can be regarded as solved. However, in recent years a rapid development of new anticoagulants began. Although they are developed with guidelines for use without monitoring, the control of effective levels may be necessary in selected cases. As a consequence new challenges for the routine laboratory have to be solved. This paper presents an overview concerning monitoring methods.

Topics: Anticoagulants; Arterial Occlusive Diseases; Drug Monitoring; Hemostasis; Humans; Venous Thrombosis; Vitamin K

This chapter about antithrombotic therapy for peripheral arterial occlusive disease is part of the seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence Based Guidelines. Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs, and Grade 2 suggests that individual patients' values may lead to different choices (for a full understanding of the grading see Guyatt et al, CHEST 2004;126:179S-187S). Among the key recommendations in this chapter are the following: For patients with chronic limb ischemia, we recommend lifelong aspirin therapy in comparison to no antiplatelet therapy in patients with clinically manifest coronary or cerebrovascular disease (Grade 1A) and in those without clinically manifest coronary or cerebrovascular disease (Grade 1C+). We recommend clopidogrel over no antiplatelet therapy (Grade 1C+) but suggest that aspirin be used instead of clopidogrel (Grade 2A). For patients with disabling intermittent claudication who do not respond to conservative measures and who are not candidates for surgical or catheter-based intervention, we suggest cilostazol (Grade 2A). We suggest that clinicians not use cilostazol in patients with less-disabling claudication (Grade 2A). In these patients, we recommend against the use of pentoxifylline (Grade 1B). We suggest clinicians not use prostaglandins (Grade 2B). In patients with intermittent claudication, we recommend against the use of anticoagulants (Grade 1A). In patients with acute arterial emboli or thrombosis, we recommend treatment with immediate systemic anticoagulation with unfractionated heparin (UFH) [Grade 1C]. We also recommend systemic anticoagulation with UFH followed by long-term vitamin K antagonist (VKA) in patients with embolism [Grade 1C]). For patients undergoing major vascular reconstructive procedures, we recommend UFH at the time of application of vascular cross-clamps (Grade 1A). In patients undergoing prosthetic infrainguinal bypass, we recommend aspirin (Grade 1A). In patients undergoing infrainguinal femoropopliteal or distal vein bypass, we suggest that clinicians do not routinely use a VKA (Grade 2A). For routine patients undergoing infrainguinal bypass without special risk factors for occlusion, we recommend against VKA plus aspirin (Grade 1A). For those at high risk of bypass occlusion and limb loss, we suggest VKA plus aspirin (Grade 2B). In patients undergoing carotid endarterectomy, we recom

Topics: Arterial Occlusive Diseases; Aspirin; Cilostazol; Clopidogrel; Contraindications; Evidence-Based Medicine; Extremities; Fibrinolytic Agents; Heparin; Humans; Intermittent Claudication; Ischemia; Randomized Controlled Trials as Topic; Risk Assessment; Tetrazoles; Thromboembolism; Ticlopidine; Vitamin K

When warfarin is interrupted for surgery, low-molecular-weight heparin is often used as bridging therapy. However, this practice has never been evaluated in a large prospective study. This study was designed to assess the efficacy and safety of bridging therapy with low-molecular-weight heparin initiated out of hospital.. This was a prospective, multicenter, single-arm cohort study of patients at high risk of arterial embolism (prosthetic valves and atrial fibrillation with a major risk factor). Warfarin was held for 5 days preoperatively. Low-molecular-weight heparin was given 3 days preoperatively and at least 4 days postoperatively. Patients were followed up for 3 months for thromboembolism and bleeding. Eleven Canadian tertiary care academic centers participated; 224 patients were enrolled. Eight patients (3.6%; 95% CI, 1.8 to 6.9) had an episode of thromboembolism, of which 2 (0.9%; 95% CI, 0.2 to 3.2) were judged to be due to cardioembolism. Of these 8 episodes of thromboembolism, 6 occurred in patients who had warfarin deferred or withdrawn because of bleeding. There were 15 episodes of major bleeding (6.7%; 95% CI, 4.1 to 10.8): 8 occurred intraoperatively or early postoperatively before low-molecular-weight heparin was restarted, 5 occurred in the first postoperative week after low-molecular-weight heparin was restarted, and 2 occurred well after low-molecular-weight heparin was stopped. There were no deaths.. Bridging therapy with subcutaneous low-molecular-weight heparin is feasible; however, the optimal approach for the management of patients who require temporary interruption of warfarin to have invasive procedures is uncertain.

Topics: Anticoagulants; Arterial Occlusive Diseases; Aspirin; Atrial Fibrillation; Blood Loss, Surgical; Cohort Studies; Dalteparin; Elective Surgical Procedures; Feasibility Studies; Heart Valve Prosthesis Implantation; Humans; International Normalized Ratio; Intraoperative Complications; Postoperative Complications; Postoperative Hemorrhage; Premedication; Preoperative Care; Prospective Studies; Risk; Thromboembolism; Treatment Outcome; Vitamin K; Warfarin

The safety and effectiveness of non-vitamin K antagonist (VKA) oral anticoagulants, dabigatran or rivaroxaban, were compared with VKA in anticoagulant-naive patients with nonvalvular atrial fibrillation during the early phase of anticoagulant therapy.. With the use of the French medico-administrative databases (SNIIRAM and PMSI), this nationwide cohort study included patients with nonvalvular atrial fibrillation who initiated dabigatran or rivaroxaban between July and November 2012 or VKA between July and November 2011. Patients presenting a contraindication to oral anticoagulants were excluded. Dabigatran and rivaroxaban new users were matched to VKA new users by the use of 1:2 matching on the propensity score. Patients were followed for up to 90 days until outcome, death, loss to follow-up, or December 31 of the inclusion year. Hazard ratios of hospitalizations for bleeding and arterial thromboembolic events were estimated in an intent-to-treat analysis using Cox regression models. The population was composed of 19 713 VKA, 8443 dabigatran, and 4651 rivaroxaban new users. All dabigatran- and rivaroxaban-treated patients were matched to 16 014 and 9301 VKA-treated patients, respectively. Among dabigatran-, rivaroxaban-, and their VKA-matched-treated patients, 55 and 122 and 31 and 68 bleeding events and 33 and 58 and 12 and 28 arterial thromboembolic events were observed during follow-up, respectively. After matching, no statistically significant difference in bleeding (hazard ratio, 0.88; 95% confidence interval, 0.64-1.21) or thromboembolic (hazard ratio, 1.10; 95% confidence interval, 0.72-1.69) risk was observed between dabigatran and VKA new users. Bleeding (hazard ratio, 0.98; 95% confidence interval, 0.64-1.51) and ischemic (hazard ratio, 0.93; 95% confidence interval, 0.47-1.85) risks were comparable between rivaroxaban and VKA new users.. In this propensity-matched cohort study, our findings suggest that physicians should exercise caution when initiating either non-VKA oral anticoagulants or VKA in patients with nonvalvular atrial fibrillation.

Topics: Adolescent; Adult; Aged; Anticoagulants; Antithrombins; Arterial Occlusive Diseases; Atrial Fibrillation; Dabigatran; Databases, Factual; Factor Xa Inhibitors; Follow-Up Studies; Hemorrhage; Hospitalization; Humans; Middle Aged; Risk; Rivaroxaban; Thromboembolism; Thrombophilia; Vitamin K; Warfarin; Young Adult

Topics: Aged; Anticoagulants; Arterial Occlusive Diseases; Humans; Leg Ulcer; Male; Thrombosis; Venous Insufficiency; Vitamin K; Warfarin

Spontaneous arterial dissection in peripheral arteries of the extremities is an extremely rare event. We report a case of a spontaneous dissection of a nonaneurysmal popliteal artery in an otherwise healthy 36-year-old man that came to clinical attention as an acute blue toe syndrome. The diagnosis was primarily made by high-resolution duplex ultrasound that revealed a dissection flap (length: 15.5 mm; thickness: 0.4 mm) together with the partially thrombosed false lumen at the dorsal wall of the left popliteal artery (degree of local diameter reduction: 56%). Further work-up by means of contrast-enhanced MR-A and conventional DSA confirmed a moderate stenosis of the popliteal artery compatible with focal dissection and excluded other causes such as popliteal artery entrapment syndrome. Under full-dose intravenous anticoagulation with unfractionated heparin that was switched to oral anticoagulation with vitamin K antagonists (target INR: 2-3) and conservative management of the blue toe the patient made a gradual, but eventually complete clinical recovery over 8 weeks.

Topics: Adult; Anticoagulants; Aortic Dissection; Arterial Occlusive Diseases; Blue Toe Syndrome; Drug Therapy, Combination; Heparin; Humans; Male; Popliteal Artery; Radiography; Ultrasonography; Vitamin K

Peripheral vascular occlusive disease (PAOD) is frequently seen in patients suffering from coronary heart or cerebrovascular disease and is, considered as a prognostic predictor for the morbidity and mortality of this patient group. Thus, secondary antithrombotic and antiplatelet prophylaxis in these patients is not limited to achievement of long-term patency of the revascularized or recanalized arterial segment, but plays as well a pivotal role for the prevention of myocardial infarction and stroke. Generally, claudicants as well as patients undergoing percutaneous transluminal angioplasty (PTA), supragenicular femoro-popliteal artificial bypass surgery, aortofemoral, iliaco-femoral unilateral bypass, or aortobifemoral Y-graft implantation with unimpaired arterial outflow are treated life-long with low dose acetylsalicylic acid (ASA) 75-250 mg. On the other hand, those undergoing axillo-femoral, femoro-femoral crossover, aorto-profundal or femoro-popliteal infragenicular and femoro-distal venous bypass surgery should be treated with vitamin K antagonists. The role of Clopidogrel in secondary prevention after peripheral revascularization and recanalization still needs to be defined.

Topics: Administration, Oral; Angioplasty, Balloon; Anticoagulants; Arterial Occlusive Diseases; Aspirin; Blood Vessel Prosthesis; Clopidogrel; Confidence Intervals; Dipyridamole; Drug Therapy, Combination; Embolectomy; Fibrinolytic Agents; Heparin; Heparin, Low-Molecular-Weight; Humans; Iloprost; Intermittent Claudication; Leg; Meta-Analysis as Topic; Middle Aged; Multicenter Studies as Topic; Myocardial Infarction; Peripheral Vascular Diseases; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Risk Factors; Stroke; Thrombectomy; Ticlopidine; Time Factors; Vitamin K

Topics: Angina Pectoris; Anticoagulants; Arterial Occlusive Diseases; Arteriosclerosis; Coumarins; Disseminated Intravascular Coagulation; Fibrinolytic Agents; Heparin; Humans; Myocardial Infarction; Pulmonary Embolism; Streptokinase; Thromboembolism; Thrombophlebitis; Thrombosis; Urokinase-Type Plasminogen Activator; Vitamin K

Topics: Adult; Aged; Anticoagulants; Antithrombins; Arterial Occlusive Diseases; Benzyl Compounds; Blood Coagulation Tests; Coumarins; Embolism; Female; Humans; Long-Term Care; Male; Middle Aged; Myocardial Infarction; Thrombophlebitis; Time Factors; Vitamin K