acenocoumarol and Intracranial-Hemorrhages

Polymorphisms in the vitamin K epoxide reductase complex 1 (VKORC1) and cytochrome P450 2C9 (CYP2C9) genes increase the bleeding risk in anticoagulated atrial fibrillation (AF) patients. Here, we aimed to investigate whether VKORC1 and CYP2C9 polymorphisms improved the predictive performance for major bleeding using the HAS-BLED score.. We recruited 652 consecutive AF patients stable on vitamin K antagonist (INR 2.0-3.0) during at least the previous 6 months. A baseline venous blood sample was obtained for DNA extraction. We gave an extra point to the HAS-BLED score if the patient was a simultaneous carrier of the VKORC1 and CYP2C9 polymorphisms related to bleeding, and we called this modified score "GEN|HAS-BLED." During a median follow-up of 7.6 years (IQR 5.6-8.0), all major bleeding events were recorded.. During follow-up, 106 (16.2%) patients experienced a major bleeding (2.81%/y; 42 intracranial haemorrhages and 44 gastrointestinal bleeding) and 24 (3.7%) died from major bleeding (0.48%/y). Cox regression analyses demonstrated a significant association between HAS-BLED or GEN|HAS-BLED and major bleeds, both as continuous or categorical scores. Comparison of receiver operating characteristic (ROC) curves shows that original HAS-BLED clinical score had better predictive ability than GEN|HAS-BLED (0.660, 95% CI 0.622-0.696 vs 0.645, 95% CI 0.607-0.682; P = .030). Discrimination and reclassification analyses showed that GEN|HAS-BLED did not improve sensitivity compared with the original score and even showed significant negative reclassification.. Adding pharmacogenetic factors (ie polymorphisms of the VKORC1 and CYP2C9 genes) to the HAS-BLED score does not improve the prediction or discrimination performance for major bleeding.

Topics: Acenocoumarol; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cytochrome P-450 CYP2C9; Female; Gastrointestinal Hemorrhage; Genetic Predisposition to Disease; Hemorrhage; Humans; Intracranial Hemorrhages; Male; Pharmacogenetics; Polymorphism, Genetic; Proportional Hazards Models; Risk Assessment; ROC Curve; Stroke; Vitamin K Epoxide Reductases

Nonvitamin K antagonist oral anticoagulants (NOACs) have been proposed as an alternative to vitamin K antagonists in atrial fibrillation (AF) patients but the comparative benefits between NOACs and optimally anticoagulated patients is unknown. We estimated the absolute benefit in clinical outcomes rates of real-world effect of NOACs in optimally anticoagulated AF patients with acenocoumarol. We included 1,361 patients stable on acenocoumarol with time in therapeutic range of 100% and 6.5 years of follow-up. Estimation of clinical events avoided was calculated applying hazard ratio, absolute and relative risk reduction from the real-world meta-analysis. Compared with an optimally anticoagulated population, dabigatran 110 mg had the highest estimated stroke reduction (0.97%/year vs 1.47%/year; p = 0.002), and the benefit was higher than in RE-LY trial. For major bleeding, apixaban showed the highest estimated reduction (1.81%/year vs 2.83%/year; p <0.001). For mortality, the largest estimated reduction was with apixaban (2.68%/year). For gastrointestinal bleeding, only apixaban had a significant reduction compared with acenocoumarol (0.69%/year vs 1.10%/year; p = 0.004), and the reduction was significantly higher than in ARISTOTLE trial. All NOACs showed significantly lower rates for intracranial hemorrhage and had a positive Net Clinical Benefit compared with acenocoumarol. Apixaban showed the highest extended estimated Net Clinical Benefit 2.64 (95%CI 2.34 to 2.96). In conclusion, in optimally acenocoumarol anticoagulated AF patients, estimated reductions in all clinical outcomes with various NOACs are evident, with the best effectiveness and safety profile with apixaban. Indeed, the estimated effect with "real world" NOACs would probably be higher than that seen in phase-III clinical trials.

Topics: Acenocoumarol; Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Atrial Fibrillation; Dabigatran; Factor Xa Inhibitors; Female; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Male; Pyrazoles; Pyridones; Rivaroxaban; Spain; Stroke

The use of antithrombotic medication (ATM) frequently is reported in patients with intracranial hemorrhage (ICH) and is associated with increased mortality. Unfortunately, ATMs sometimes are prescribed and/or used inappropriately. We sought to determine the rate of ATM misprescription/misuse among patients with ICH in a single-center retrospective study.. All patients admitted with ATM-related ICH in 1998-2014 were included. Charts were reviewed and demographic, clinical, and radiologic variables were recorded. The type of ATM, dose, and duration of treatment were analyzed critically. The adequacy of ATM prescription/use was assessed in light of the recommendations and guidelines of the American Heart Association, American Stroke Association, and French National Authority for Health, in effect at the time of admission.. A total of 106 patients with mean age 68 years were identified. Aspirin (53.8%) was the most commonly used drug, followed by oral anticoagulants (31.1%) and clopidogrel (22.6%). In only 80 patients (75.5%), the use of ATM was in line with contemporary guidelines. In the remaining 26 (24.5%), the use of ATMs was inappropriate, including bad drug combination, wrong dose, poor indication, wrong drug class, and/or incorrect treatment duration.. In this Lebanese cohort of patients with ICH, the 24.5% rate of ATM misprescription and/or misuse is highly alarming and the origin of this problem is likely multifactorial. Immediate measures should be undertaken, and efforts should be focused on regaining tight control of ATM prescription and fulfillment, ensuring good patient education, and offering more vigilant oversight on physician licensure.

Topics: Acenocoumarol; Adult; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebral Hemorrhage; Clopidogrel; Coronary Artery Disease; Enoxaparin; Female; Fibrinolytic Agents; Humans; Inappropriate Prescribing; Intracranial Hemorrhages; Lebanon; Male; Middle Aged; Platelet Aggregation Inhibitors; Prescription Drug Misuse; Retrospective Studies; Risk Factors; Stroke; Ticlopidine; Warfarin; Young Adult

Vitamin K antagonists (VKA) are widely used for the prevention and curative treatment of thromboembolic events. This study aims to describe the epidemiological, clinical and evolutionary aspects of overdose in Vitamin K antagonists administration and determine its hemorrhagic factors. We conducted a monocentric cross-sectional descriptive study at the Principal Hospital in Dakar. All patients with an INR greater than 5 were included. We studied patients' gender and age, VKA used, drug use period, indications, INR value, associated drugs, presence of hemorrhage, immediate management and evolution. We enrolled 154 patients. Acenocoumarol was the most prescribed VKA. Sex ratio favoured women. The average age was 63 years. Overdose was asymptomatic in 43% of patients. Hemorrhagic symptoms were mainly represented by gingival bleeding, epistaxis. Major bleeding episodes were found in 8.6% of patients and they were represented by melena in 6 patients (3.9%), deep muscle hematoma in 2 patients (1.3%) and intracerebral parenchymal hematoma in 2 patients. Two patients had cardiovascular collapse associated with deglobulisation. Nonsteroidal anti-inflammatory drugs (NSAIDs) assumption was noted in 21% of patients. VKA assumption was suspended transiently in all patients. Mortality was 2%, due to intracranial hemorrhage. The reduction in VKA overdose requires caregivers to manage overdose factors and provide proper patient education.

Topics: Acenocoumarol; Adult; Aged; Aged, 80 and over; Anticoagulants; Cross-Sectional Studies; Drug Overdose; Female; Hematoma; Hemorrhage; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Middle Aged; Senegal; Vitamin K; Young Adult

The objective of the present study was to investigate the efficacy of a four-factor prothrombin complex concentrate (Prothromplex, PTX) in shortening prolonged international normalized ratio or controlling life-threatening bleeding. The study was a retrospective single-centre study that included 142 patients treated with PTX and allocated in three groups: patients on vitamin K antagonists (VKA) (acenocumarol) and undergoing invasive procedure or presenting with severe bleeding (n = 76), patients treated with VKA presenting with intracranial haemorrhage (n = 22), and patients not on VKA and presenting with uncontrolled bleeding (n = 44). The primary outcome variable was international normalized ratio (INR) return to the norm after PTX infusion. Secondary outcome variables included bleeding control and reduction of transfusion rate. Overall, patients received a median of 1200 IU (≈15 IU/kg) of PTX, and INR decreased from 4 ± 3 to 1.7 ± 1.2 (P < 0.01) in all groups, although it remained at least 1.4 in 38% of patients (29.3% among patients receiving 25 IU/kg vs. 42.6% among those receiving 15 IU/kg; P < 0.05). Patients with initial INR at least 4 benefited the most from treatment. After PTX administration, there was a significant reduction in both transfused blood components units (P < 0.01) and estimated blood loss volume (from 1500 ± 1500 to 200 ± 100 ml; P < 0.01), and only one episode of deep venous thrombosis was observed. Administration of fixed doses of PTX shortened prolonged international normalized ratio and improved life-threatening bleeding in patients with or without VKA therapy. Higher dose attained a more adequate post-infusion INR.

Topics: Acenocoumarol; Adult; Aged; Aged, 80 and over; Anticoagulants; Antifibrinolytic Agents; Blood Coagulation Factors; Female; Humans; Intracranial Hemorrhages; Male; Middle Aged; Retrospective Studies; Treatment Outcome; Vitamin K

There are well defined indications in which chronic anticoagulant treatment has been widely applied. However, complications of this therapy are less discussed, although these complications may lead to serious or even fatal consequences.. The aim of the authors was to analyze data of patients admitted to their multidisciplinary intensive care unit for complications of chronic anticoagulant therapy between January 1, 2006 and December 31, 2011.. Data of 73 patients admitted for serious hemorrhagic complications of chronic anticoagulant therapy were retrospectively analysed.. Of the 73 patients, 63 patients had intracranial bleeding, most of them with traumatic origin. A few patients with other hemorrhagic complications such as spinal hematoma, gastrointestinal bleeding, hemorrhagic cystitis, hemothorax and intraabdominal bleeding were also noted. The INR values were out of therapeutic range in 43 patients. The mortality of patients was very high in spite of complex intensive care; 49 of the 73 patients (75.5%) died due to hemorrhagic complications.. Due to the high proportion of traumatic origin, the large number of out-of-range INR, and the high mortality, the authors strongly believe that regular patient follow-up, transmission of detailed information, and time-to-time reevaluation of the indications and contraindications of chronic anticoagulant therapy could help to decrease the number of serious and fatal complications of chronic anticoagulant therapy.. Bevezetés: A krónikus antikoaguláns kezelést jól körülhatárolt indikációs körrel, széles körben alkalmazzák. Kevesebb szó esik azonban az általa okozott vérzéses szövődményekről, amelyek súlyosak vagy akár halálos kimenetelűek is lehetnek. Célkitűzés: A Szent János Kórház és Észak-budai Egyesített Kórházak Központi Aneszteziológiai és Intenzív Terápiás Osztályán 2006. január 1. és 2011. december 31. között krónikus antikoaguláns kezelés kapcsán kialakult vérzéses szövődményes esetek elemzése. Módszer: A szerzők multidiszciplináris intenzív osztályán a vizsgált hat év alatt összesen 73 betegnél fordult elő intenzív ellátást igénylő vérzéses szövődmény krónikus antikoagulálás kapcsán. Eredmények: Hatvanhárom esetben intracranialis vérzést észleltek, ezen belül leggyakrabban traumás eredetűt. Kisebb számban előfordult még spinalis haematoma, gastrointestinalis vérzés, haemorrhagiás cystitis, haemothorax és hasüregi vérzés. A betegek felvételi INR-értéke 43 esetben a terápiás tartományon kívül esett. A betegek mortalitása igen magas volt, a komplex intenzív kezelés ellenére 49 beteg halt meg a vérzéssel összefüggésben (75,5%). Következtetések: A gyakori traumás eredetre, a terápiás tartományon kívül eső INR-értékek nagy számára és a magas mortalitásra tekintettel a szerzők véleménye szerint rendszeres betegkövetéssel, részletes felvilágosítással, a társbetegségek alakulásával párhuzamosan revideált indikáció/kontraindikáció alapján folytatott krónikus antikoaguláns kezeléssel a vérzéses szövődmények száma csökkenthető lenne. Orv. Hetil., 2013, 154(46), 1829–1835.

Topics: Acenocoumarol; Adult; Aged; Aged, 80 and over; Anticoagulants; Critical Care; Cystitis; Drug Administration Schedule; Female; Gastrointestinal Hemorrhage; Hemorrhage; Hemothorax; Humans; Hungary; Intensive Care Units; International Normalized Ratio; Intracranial Hemorrhages; Male; Middle Aged; Retrospective Studies; Warfarin

Anticoagulant (AC) and antiplatelet (AP) drugs are effectively used in the prevention of thromboembolic events, with the trade-off of bleeding side effects, particularly intracranial. The aim of this study was to determine the incidence of intracranial bleeding in the population of Reggio Emilia and to investigate the potential effect of AC and AP drugs.. We reviewed all the patients admitted for cerebral hemorrhages to our hospital between April 1998 and September 2000. Data were collected with a standardized form. All the patients were followed-up to estimate long-term mortality. Chi(2) and t-tests were used as appropriate. Logistic regression analysis was performed to test predictors of mortality. Pharmaceutical department data were employed to estimate the total number of patients receiving AC and AP drugs.. We found 241 cases (107/134 female/male, mean age 61 years, 133/107 spontaneous/traumatic events, 0.32/1,000/year overall). Twenty-nine and 47 of these patients were being given AC or AP drugs, respectively (4.9/1,000/year and 3.7/1,000/year). The relative risk of intracranial bleeding was 11.5 in AP and 15.3 in AC treated patients. Two patients (one underwent neurosurgery and one thrombolytic treatment) were excluded from mortality and risk factors analysis. Six patients were lost from follow-up and excluded from mortality analysis. Overall mortality was 100/233 (42.9%); mortality in traumatic events was 25/103 (24.2%) versus 75/130 (57.7%) in spontaneous events. Mortality was 19/29 (65.5%), 26/47 (55.3%) and 55/157 (35%) in AC recipients, AP recipients, and untreated patients, respectively. This increased risk was mainly confined to traumatic events (p = 0.06), without difference between AC and AP recipients. At the time of the event, the mean duration of oral AC treatment was 26.3 months (range 1-120). Mean INR was = 3.1 (range 1.6-8.8). Mortality was significantly predicted by the Glasgow Coma Scale Score (GCS) at admission (p < 0.0001), by the type of bleeding (spontaneous versus traumatic) (p = 0.0026), and by age (p < 0.0001).. Careful selection of patients and prevention of traumatic events are the main candidate mechanisms to reduce intracranial bleeding in patients being treated with AC and AP drugs.

Topics: Acenocoumarol; Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Child; Child, Preschool; Female; Humans; Incidence; Infant; Intracranial Hemorrhages; Italy; Male; Middle Aged; Mortality; Platelet Aggregation Inhibitors; Risk Factors; Warfarin

Topics: Acenocoumarol; Adult; Anticoagulants; Aortic Valve; Enoxaparin; Female; Heart Valve Prosthesis; Humans; Intracranial Hemorrhages; Pregnancy; Pregnancy Complications

Over the period 1994-1998, five patients presenting coagulation status impairment in the course of sintrom treatment are hospitalized in the Clinic of Emergency Neurology and Neurosurgery. Three of them are with craniocerebral trauma (2 severe forms--score 5 by the Glasgow Coma Rating scale, and one mild form--score 15), one has spontaneous intracerebral hematoma, and one--acute hydrocephalus against the background of ruptured aneurysm of the basilar artery (score 4). Three patients are given sintrom treatment because of rheumatic heart disease (2 with mitral valve prosthetic replacement and one in the post-commissurotomy period), and two--because of absolute arrhythmia, complicated by systemic emboli in the extremities and/or pulmonary artery. Four patients are subjected to operation--2 with craniocerebral injury, one with intracerebral hematoma and one with acute hydrocephalus of which in two cases the outcome is fatal. One female patient presenting serious craniocerebral trauma is not operated (refusal by the relatives) and dies. The therapeutic approach to this contingent of patients is comprehensively discussed.

Topics: Acenocoumarol; Aged; Anticoagulants; Brain; Craniocerebral Trauma; Female; Humans; Intracranial Hemorrhages; Male; Middle Aged; Tomography, X-Ray Computed