vitamin-k-semiquinone-radical and Cerebral-Infarction

Treatment with vitamin K antagonists are subject to a common iatrogenic mainly characterized by hemorrhagic stroke. Their narrow therapeutic range associated with variability largely explains this phenomenon. New oral anticoagulants (NOAC) are now available. dabigatran (Pradaxa®) is a direct and specific thrombin inhibitor. It is excreted mainly by the kidney and is the only which can be dialyzed. Rivaroxaban (Xarelto®) and apixaban (Eliquis®) are factor X activated direct inhibitors. They are highly bound to plasma proteins and are metabolized mainly by the liver, via CYP3A4. All NOAC are substrates of P-glycoprotein (P-gp). Due to pharmacological changes, some populations at risk were identified: patients with hepatic impairment, renal impairment, elderly patients or low weight. Some pharmacokinetic or pharmacodynamic drug interactions alter the concentration and the expected impact of NOAC. The NOAC does not require biological monitoring. They interfere with the routine coagulation tests which should be interpreted with caution. Specific tests exist and can be used in case of emergencies. Currently, no antidote is available. The new oral anticoagulant look promising in the elderly. However, certain rules must be followed to reduce the risk of iatrogenic.

Topics: Administration, Oral; Aged; Anticoagulants; Benzimidazoles; beta-Alanine; Cerebral Infarction; Dabigatran; Dose-Response Relationship, Drug; Drug Interactions; Drugs, Investigational; Humans; Iatrogenic Disease; Intracranial Hemorrhages; Morpholines; Pyrazoles; Pyridones; Risk Factors; Rivaroxaban; Stroke; Thiophenes; Vitamin K

Dabigatran etexilate is emerging as an alternative for vitamin K antagonists, but evidence-based guidelines for management of intracerebral hemorrhage and acute ischemic stroke in patients taking this drug are nonexistent. This review summarizes current knowledge on key pharmacological features and the assessment of dabigatran activity. Pragmatic approaches are provided for individualized decision taking with regard to hemostatic therapy and reperfusion strategies in acute stroke patients.

Topics: Anticoagulants; Benzimidazoles; Blood Coagulation Disorders; Case Management; Cerebral Hemorrhage; Cerebral Infarction; Dabigatran; Guidelines as Topic; Hemostasis; Hemostatics; Humans; Off-Label Use; Pyridines; Renal Dialysis; Reperfusion; Stroke; Vitamin K

Given the projected rising prevalence of atrial fibrillation in the near future, an increasing number of older patients will have to be treated in order to prevent stroke and systemic embolism. This article summarizes recent developments in antithrombotic treatment and risk stratification for patients with atrial fibrillation and intends to abate the still prevailing reluctance towards anticoagulation in elderly patients.

Topics: Acute Disease; Administration, Oral; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cerebral Infarction; Drug Therapy, Combination; Fibrinolytic Agents; Humans; Risk Factors; Secondary Prevention; Vitamin K

Chronic, nonvalvular atrial fibrillation occurs more frequently with increasing age, together with an increasing risk for ischemic stroke. Guidelines recommend oral anticoagulation with a vitamin K antagonist for patients >65 years without risk factors and patients <65 years with risk factors for cardiac diseases. Advancing age also increases the risk for bleeding complications under oral anticoagulants; thus, only a part of these patients receives anticoagulant therapy. The risk of falls in elderly patients is of advancing relevance for this therapeutic decision. Oral direct thrombin inhibitors like ximelagatran may be an alternative choice for therapy. Ischemic strokes and systemic embolism in the same frequency with 2x36 mg ximelagatran over 18 months (91/3664 patients: 1.6%/year, for study Sportif III and Sportif V) compared with warfarin (93/3665 patients: 1.6%/year for study Sportif III and Sportif V). All bleeding complications occurred less frequently under therapy with ximelagatran. This could be of importance for elderly patients with risk factors for bleeding or risk of falling.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Azetidines; Benzylamines; Cerebral Infarction; Clinical Trials as Topic; Hemorrhage; Humans; Risk Factors; Thromboembolism; Vitamin K; Warfarin

A 65-year-old man, who had been treated with dabigatran for 66 days prior to electrical cardioversion, developed extensive intestinal, renal and cerebral thromboembolism five days after cardioversion. There is limited information available on the treatment of thromboembolism in patients being treated with dabigatran. Routine biochemical monitoring is not available. As is the case for vitamin K antagonists, anticoagulation with dabigatran is not without risks.

Topics: Aged; Antithrombins; Benzimidazoles; beta-Alanine; Cerebral Infarction; Dabigatran; Electric Countershock; Humans; Ileus; Kidney Diseases; Male; Risk Factors; Thromboembolism; Tomography, X-Ray Computed; Vitamin K

Topics: Antifibrinolytic Agents; Cerebral Infarction; Emergency Nursing; Emergency Treatment; Feeding and Eating Disorders; Female; Hematoma, Subdural; Home Childbirth; Humans; Infant; Infant, Newborn; Irritable Mood; Lethargy; Nursing Assessment; Partial Thromboplastin Time; Prothrombin Time; Tomography, X-Ray Computed; Vitamin K; Vitamin K Deficiency Bleeding; Vomiting

Vitamin K is an essential factor for synthesis of plasma clotting proteins and for site-specific carboxylation of bone Gla protein and other bone matrix proteins. Low vitamin K has been associated with reduced bone mineral density. Warfarin therapy, which inhibits vitamin K-dependent blood-clotting, has been demonstrated to reduce the risk of stroke in nonrheumatic atrial fibrillation. We evaluated vitamin K and bone mineral density in nonrheumatic atrial fibrillation patients who had long-term warfarin therapy after an ischemic stroke.. Sera were collected from 64 patients with non-rheumatic atrial fibrillation and ischemic stroke who had been treated with warfarin, 63 stroke patients without warfarin, and 39 control subjects. All stroke patients in both groups had hemiplegia. Sera were assayed for vitamins K1 and K2, bone Gla protein, and 25-hydroxyvitamin D. Bone mineral density was determined in both second metacarpals.. Serum vitamin K1 concentrations (ng/mL) were lower in treated patients (.234 +/- .177 ng/mL) than in untreated patients (.329 +/- .284) or controls (.553 +/- .164). Bone Gla protein was lower in treated patients' sera (1.241 +/- .799 ng/mL) than in untreated patients (4.476 +/- 3.226). Concentrations of 25-hydroxyvitamin D were lower in both patient groups. Bone mineral density was lower on both sides in treated patients than in untreated patients (P < .0001). Vitamin K1 and bone Gla protein were significantly related to bone mineral density bilaterally in treated but not in untreated patients.. Bone mineral density was significantly lower in stroke patients with long-term warfarin treatment than in untreated patients. Both warfarin-induced reduction in vitamin K function and lowered vitamin K1 concentrations are probable causes of this osteopenia.

Topics: Administration, Oral; Aged; Anticoagulants; Antifibrinolytic Agents; Atrial Fibrillation; Bone Density; Cerebral Infarction; Female; Humans; Male; Middle Aged; Regression Analysis; Vitamin K; Vitamin K 1; Vitamin K 2

Topics: Adolescent; Adult; Cerebral Infarction; Female; Humans; Pregnancy; Pregnancy Complications, Hematologic; Pulmonary Embolism; Vegetables; Vitamin K; Warfarin