vitamin-k-semiquinone-radical and Peripheral-Vascular-Diseases

Peripheral arterial disease (PAD) is frequently treated by either an infrainguinal autologous (using the patient's own veins) or synthetic graft bypass. The rate of occlusion of the graft after one year is between 12% and 60%. To prevent occlusion, patients are treated with an antiplatelet or antithrombotic drug, or a combination of both. Little is known about which drug is optimal to prevent infrainguinal graft occlusion. This is an update of a Cochrane review first published in 2003.. To evaluate whether antithrombotic treatment improves graft patency, limb salvage and survival in patients with chronic PAD undergoing infrainguinal bypass surgery.. The Cochrane Peripheral Vascular Diseases Group searched their Specialised Register (last searched August 2010) and the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 3).. Randomised, controlled trials; two review authors independently assessed the methodological quality of each trial using a standardised checklist.. Data collected included patient details, inclusion and exclusion criteria, type of graft, antithrombotic therapy, outcomes, and side effects.. A total of 14 trials were included in this review; 4970 patient results were analysed. Four trials evaluating vitamin K antagonists (VKA) versus no VKA suggested that oral anticoagulation may favour autologous venous, but not artificial, graft patency as well as limb salvage and survival. Two other studies comparing VKA with aspirin (ASA) or aspirin and dipyridamole provided evidence to support a positive effect of VKA on the patency of venous but not artificial grafts. Three trials comparing low molecular weight heparin (LMWH) to unfractionated heparin (UFH) failed to demonstrate a significant difference on patency. One trial comparing LMWH with placebo found no significant improvement in graft patency over the first postoperative year in a population receiving aspirin. One trial showed an advantage for LMWH versus aspirin and dipyridamol at one year for patients undergoing limb salvage procedures. Perioperative administration of ancrod showed no greater benefit when compared to unfractionated heparin. Dextran 70 showed similar graft patency rates to LMWH but a significantly higher proportion of patients developed heart failure with dextran.. Patients undergoing infrainguinal venous graft are more likely to benefit from treatment with VKA than platelet inhibitors. Patients receiving an artificial graft benefit from platelet inhibitors (aspirin). However, the evidence is not conclusive. Randomised controlled trials with larger patient numbers are needed in the future to compare antithrombotic therapies with either placebo or antiplatelet therapies.

Topics: Arteriosclerosis; Fibrinolytic Agents; Graft Occlusion, Vascular; Humans; Intermittent Claudication; Ischemia; Leg; Peripheral Vascular Diseases; Randomized Controlled Trials as Topic; Thrombosis; Vitamin K

Because 1.1 million myocardial infarctions occur in the United States alone each year, and 450,000 of them are recurrent infarctions, which carry an inherently greater risk of death and disability than first events, the importance of secondary prevention strategies that can be implemented widely is unparalleled in health care. Antithrombotic therapies, both antiplatelet and anticoagulant, have become the mainstays of these strategies. This article covers the use of chronic antiplatelet and anticoagulation agents after myocardial infarction. It does not include the management of these patients in the acute phase.

Topics: Anticoagulants; Aspirin; Azetidines; Benzylamines; Clopidogrel; Humans; Myocardial Infarction; Peripheral Vascular Diseases; Platelet Activation; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Recurrence; Risk Factors; Thrombolytic Therapy; Thrombosis; Ticlopidine; Vitamin K; Warfarin

Chronic peripheral arterial disease (PAD) is frequently treated by implantation of either an infrainguinal autologous venous or artificial graft. One-year occlusion rates for infrainguinal bypasses vary between 15 and 75%, depending on the site of distal anastomosis, length, quality, and material of the graft, but also on other factors such as proximal inflow and distal outflow conditions. To prevent graft occlusion, patients are usually treated with either an antiplatelet or antithrombotic drug, or a combination of both. Little is known about which drug is optimal to prevent infrainguinal graft occlusion.. To evaluate whether antithrombotic treatment in patients with chronic PAD undergoing infrainguinal bypass surgery improves graft patency, limb salvage and survival by performing a meta-analysis of performed RCTs.. The search strategy was that adopted by the Cochrane Review Group on Peripheral Vascular Diseases. Additional data bases were reviewed (Reference lists of papers resulting from this search, MEDLINE from 1966-onwards and EMBASE from 1980-onwards using the terms 'anticoagulant' and 'arterial surgery'.. The methodological quality of each trial was assessed independently by at least two reviewers using the checklist provided by the Peripheral Vascular Diseases Collaborative Review Group, with emphasis on concealment of randomisation. Each trial was given an allocation score of A (clearly concealed), B (unclear if concealed), or C (clearly not concealed) and a summary score of A (low risk of bias), B (moderate risk), or C (high risk). Trials scoring A were included and those scoring C were excluded. For a trial scoring B, an attempt was made to obtain more information by contacting the author.. For each trial, the number of patients originally allocated to each treatment group was extracted from the data and an 'intention to treat' analysis performed. Data collection on each trial included inclusion and exclusion criteria, patient details, type of graft, type and dose of antithrombotic therapy used, outcome, and side effects. The treatment and control groups were compared for important prognostic factors and differences described. If any of the above data was not available, further information was sought from the author. However, the heterogeneity between trials could not be tested due to inaccessible data. Data were synthesized by comparing group results.. The analysis including four trials which evaluated vitamin K antagonists (VKA) versus no VKA indicate, that oral anticoagulation tendentially favours venous but not artificial graft patency as well as limb salvage and survival. Two other studies comparing VKA with aspirin or aspirin/dipyridamole supported evidence for a positive effect of VKA on the patency of venous but not artificial grafts. Subgroup analysis for artificial grafts as performed in one trial showed a favourable effect of antiplatelet agents on synthetic bypasses. In two trials with a relatively small number of patients low molecular weight heparin treatment was associated with a lower incidence of early postoperative graft thrombosis compared to treatment with unfractionated heparin. In one trial infusion of antithrombin concentrate was reported to have a negative effect on intraoperative graft thrombosis necessitating the study to be stopped before termination. Perioperative administration of ancrod was compared to unfractionated heparin showing no benefit of one drug compared to the other.. Patients operated for an infrainguinal venous graft might benefit from treatment with VKA, whereas patients receiving an artificial graft might profit more from platelet inhibitors (aspirin). However, the evidence is not conclusive. Randomised controlled trials with larger patient numbers comparing antithrombotic therapies with either placebo or antiplatelet therapies are called for in the future.

Topics: Arteriosclerosis; Fibrinolytic Agents; Graft Occlusion, Vascular; Humans; Intermittent Claudication; Ischemia; Leg; Peripheral Vascular Diseases; Postoperative Complications; Randomized Controlled Trials as Topic; Thrombosis; Vitamin K

Nine out of 47 (19%) patients on chronic anticoagulation with warfarin, as secondary prophylaxis after myocardial infarction, initially treated with streptokinase, had thromboembolic complications within 4 weeks after sudden (7/25) or gradual (2/22:NS) warfarin withdrawal. The biochemical effects of warfarin withdrawal were repeatedly studied in 20 of the patients during the first 14 days following drug cessation. During the first 4 days, the levels of coagulation factors VII and IX increased more rapidly than proteins C and S. Thus, a gap was created between the factors provoking and inhibiting the coagulation process. Furthermore, plasma concentrations of fibrinopeptide A (FPA) increased, reflecting activation of the coagulation system. These laboratory findings suggest that withdrawal of warfarin creates a transient hypercoagulable state, imposing a risk of thromboembolic events in patients given anticoagulant treatment as secondary prophylaxis following myocardial infarction.

Topics: Adult; Aged; Angina, Unstable; Blood Coagulation Disorders; Blood Coagulation Factors; Cerebrovascular Disorders; Drug Therapy, Combination; Female; Heparin; Humans; Male; Middle Aged; Myocardial Infarction; Peripheral Vascular Diseases; Streptokinase; Thromboembolism; Treatment Outcome; Vitamin K; Warfarin

Topics: Administration, Intravenous; Humans; Leg Ulcer; Male; Middle Aged; Peripheral Vascular Diseases; Plasma; Vitamin K

Surgical hemostasis may be achieved by using a number of physical, chemical, or biologic methods. One such method is with topical thrombin; however, one member of that class of drugs, bovine-derived thrombin, is associated with potentially serious consequences such as development of immune-mediated coagulopathy. This case report describes a 61-year-old man with peripheral artery disease who presented with a nonhealing ulcer between his toes. Previous exposure to bovine thrombin was unknown but was considered likely because of his extensive surgical history that included procedures in which topical thrombin is commonly used. The patient was admitted and underwent lower extremity revascularization during which he received his first documented exposure to bovine-derived thrombin. By postoperative day 9, he developed a 2.7-cm retroperitoneal hematoma that had progressed to 9.6 cm by postoperative day 13. Evacuation of the hematoma was performed, during which the patient received his second known exposure to topical bovine thrombin. Based on a plasma mixing study on postoperative day 25, presence of factor V and thrombin inhibitors was suspected. A hematology consultation determined that the patient had developed an immune-mediated coagulopathy manifested as exaggerated laboratory coagulation values that continued even after discontinuation of oral anticoagulation, treatment with multiple transfusions of fresh frozen plasma, and intravenous vitamin K administration. The patient was discharged, after no further bleeding episodes had occurred, on postoperative day 29. Although determining previous exposure to bovine-derived thrombin or presence of antibodies can be difficult, a surgeon's index of suspicion should be raised in patients experiencing coagulopathy if they have previously undergone vascular, cardiac, or spinal procedures in which they were most likely exposed to topical thrombin.

Topics: Animals; Antifibrinolytic Agents; Blood Coagulation Disorders; Blood Component Transfusion; Cattle; Hemostasis, Surgical; Hemostatics; Humans; Male; Middle Aged; Peripheral Vascular Diseases; Thrombin; Vitamin K

Topics: Angioplasty, Balloon; Anticoagulants; Atherosclerosis; Combined Modality Therapy; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypolipidemic Agents; Meta-Analysis as Topic; Peripheral Vascular Diseases; Platelet Aggregation Inhibitors; Postoperative Complications; Randomized Controlled Trials as Topic; Risk Factors; Stents; Vascular Patency; Vascular Surgical Procedures; 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