acenocoumarol and Gastrointestinal-Hemorrhage

Acute gastrointestinal bleeding represents the most common adverse event associated with the use of oral anticoagulant therapy. Due to increasing prescription of anticoagulants worldwide, gastroenterologists are more and more called to deal with bleeding patients taking these medications. Their management is challenging because several issues have to be taken into account, such as the severity of bleeding, the intensity of anticoagulation, the patient's thrombotic risk and endoscopy findings. The recent introduction into the marketplace of new direct oral anticoagulants, for whom specific reversal agents are still lacking, further contributes to make the decision-making process even more demanding. Available evidence on this topic is limited and practice guidelines by gastroenterology societies only marginally address key issues for clinicians, including when and how to reverse coagulopathy, the optimal timing of endoscopy and when and how to resume anticoagulation thereafter. The present paper reviews the evidence in the literature and provides practical algorithms to support clinicians in the management of patients on anticoagulants who present with acute gastrointestinal bleeding.

Topics: Acenocoumarol; Acute Disease; Algorithms; Anticoagulants; Coagulants; Dabigatran; Endoscopy, Gastrointestinal; Gastrointestinal Hemorrhage; Humans; Rivaroxaban; Vitamin K; Warfarin

Atrial fibrillation is a major cause of death and disability due to stroke. Vitamin K antagonist drugs are effective for prevention, but they have a narrow therapeutic range and multiple pharmacological interactions. In recent years, new therapeutic alternatives have been searched to minimize complications. The main objective is to evaluate the risk of gastrointestinal bleeding in anticoagulated patients and compare the classic treatment with new anticoagulants.. We conducted a retrospective cohort study to determine the risk of gastrointestinal bleeding in patients treated with acenocoumarol/dabigatran/rivaroxaban, between 2012 and 2016. We compared the classic with the new anticoagulant group, and a multivariate logistic regression analysis was used to determinate the risk factors of gastrointestinal bleeding.. A total of 1213 patients were selected, 52.7% male patients, a mean age of 72.6 years old (± 14.563). 73.6% had atrial fibrilation. 14.5% of patients used acetylsalicylic acid, and 4% clopidogrel. 67.2% had a high-risk CHADS-2 Score, and 36.9% a high-risk HAS-BLED Score. We determined a 5.6% (68) of gastrointestinal bleeding, without differences according to anticoagulant used. The multivariate model showed a greater risk for digestive hemorrhage in patients with a previous hemorrhagic event (odds ratio [OR] = 2.422 95% confidence interval [CI]: 1.101-5.327) and the concomitant therapy with clopidogrel (OR = 2.373 95% CI: 0.996-5.652).. No differences were found in the risk of gastrointestinal bleeding between the different anticoagulants. A previous gastrointestinal bleeding were considered independent risk factor. The HAS-BLED score should be taken into account to make clinical decisions about to prescribe anticoagulant treatment.

Topics: Acenocoumarol; Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Clopidogrel; Dabigatran; Female; Gastrointestinal Hemorrhage; Humans; Male; Retrospective Studies; Rivaroxaban; Warfarin

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

Topics: Acenocoumarol; Anticoagulants; Biopsy, Needle; Colonoscopy; Combined Modality Therapy; Constriction; Gastrointestinal Hemorrhage; Hemostatic Techniques; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Prostate; Rectal Diseases; Rectum; Sclerosing Solutions; Sclerotherapy; Ulcer; Ultrasonography, Interventional

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

A drug interaction between capecitabine and coumarin may result in an increased INR and bleeding complications.. We describe an 80-year-old woman who presented with rectal bleeding and an increased INR due to the concomitant use of acenocoumarol and capecitabine for atrial fibrillation and metastatic cecal cancer, respectively.. In patients with a compelling indication for treatment with capecitabine and anticoagulant therapy, conversion to low-molecular weight heparin should be considered.

Topics: Acenocoumarol; Aged, 80 and over; Anticoagulants; Antimetabolites, Antineoplastic; Atrial Fibrillation; Capecitabine; Deoxycytidine; Drug Interactions; Erythrocyte Transfusion; Female; Fluorouracil; Gastrointestinal Hemorrhage; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Rectal Neoplasms

Topics: Acenocoumarol; Aged; Anticoagulants; Female; Gastrointestinal Hemorrhage; Hematoma; Humans; Radiography; Stomach Diseases

Topics: Acenocoumarol; Adenocarcinoma; Anticoagulants; Biopsy, Needle; Colonoscopy; Epinephrine; Erythrocyte Transfusion; Gastrointestinal Hemorrhage; Heart Valve Prosthesis; Hemostatics; Heparin, Low-Molecular-Weight; Humans; Hypotension; Male; Polidocanol; Polyethylene Glycols; Prostate; Prostatic Neoplasms; Rectal Diseases; Rectum; Sclerosing Solutions

The VKORC1 c.-1639G>A and CYP2C9 c.430C>T and c.1075A>C polymorphisms have been associated with increased sensitivity to oral anticoagulants. However, their role in gastrointestinal bleeding is unknown. We studied the risk of gastrointestinal bleeding associated with these polymorphisms, and how this risk was influenced by the anticoagulant dose and the use of common drugs. Eighty-nine patients with gastrointestinal bleeding during acenocoumarol therapy and 177 patients free of bleeding during acenocoumarol therapy were studied. None of the three polymorphisms constituted a serious gastrointestinal bleeding risk factor. However, patients bearing at least one of these polymorphisms were at high risk, when they simultaneously met one of the following conditions: a weekly dose of acenocoumarol higher than 15 mg [adjusted Odds Ratio (OR) (95% confidence interval (CI) = 4.19 (1.59-11.04)]; amiodarone use [adjusted OR (95% CI) = 9.97 (1.75-56.89)]; or aspirin use [adjusted OR (95% CI) = 8.97 (1.66-48.34)]. The consumption of statins was associated with a lower risk of gastrointestinal bleeding [adjusted OR = 0.50 (0.26-0.99)]. The risk of gastrointestinal bleeding during acenocoumarol therapy in carriers of any of the studied polymorphisms is severely increased with exposure to weekly doses of acenocoumarol higher than 15 mg or the use of amiodarone or aspirin.

Topics: Acenocoumarol; Aged; Aged, 80 and over; Amiodarone; Anti-Arrhythmia Agents; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Aspirin; Case-Control Studies; Cytochrome P-450 CYP2C9; Drug Administration Schedule; Female; Gastrointestinal Hemorrhage; Genetic Predisposition to Disease; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; International Normalized Ratio; Male; Mixed Function Oxygenases; Odds Ratio; Polymorphism, Genetic; Risk; Vitamin K Epoxide Reductases

Treatment with vitamin K antagonists (coumarins) is associated with an increased risk of bleeding. In order to elucidate the bleeding risk of users of antiplatelet drugs among users of coumarins, we assessed the odds ratio of major bleeding associated with use of antiplatelet drugs in users of the coumarins acenocoumarol and phenprocoumon. We used data from a Dutch record linkage system, including pharmacy and linked hospitalization records for approximately two million subjects, to conduct a nested case control study in a cohort of new users of coumarins. Cases were patients who were hospitalized with a primary diagnosis of major bleeding while taking coumarin and were matched with up to four control subjects. Conditional logistic regression analysis was used to determine ORs and 95% confidence intervals (CI). We identified 1848 case patients who were matched to 5818 controls. Users of clopidogrel or aspirin showed a significantly increased risk of hospitalization because of major bleeding (OR 2.9, 95% CI 1.2-6.9 and OR 1.6, 95% CI 1.3-1.9, respectively), whereas users of dipyridamole and combinations of antiplatelet drugs showed a strong trend (OR 1.5, 95% CI 1.0-2.3 and OR 1.8, 95 % CI 1.0-3.3, respectively). In all cases, the risks were greater for upper gastrointestinal bleedings than for other bleedings. In conclusion, the use of any antiplatelet drug increases the risk of hospitalization for major bleeding among users of coumarins. Concurrent use of clopidogrel or dipyridamole and coumarins is probably not safer than concurrent use of aspirin and coumarins.

Topics: Acenocoumarol; Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Blood Coagulation; Case-Control Studies; Clopidogrel; Coumarins; Dipyridamole; Drug Therapy, Combination; Female; Gastrointestinal Hemorrhage; Hemorrhage; Hospitalization; Humans; Logistic Models; Male; Medical Records Systems, Computerized; Middle Aged; Netherlands; Odds Ratio; Phenprocoumon; Platelet Aggregation Inhibitors; Risk Assessment; Ticlopidine; Vitamin K

Topics: Acenocoumarol; Anticoagulants; Diverticulum; Fatal Outcome; Female; Gastrointestinal Hemorrhage; Humans; Jejunal Diseases; Middle Aged

Topics: Acenocoumarol; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Cerebral Hemorrhage; Female; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Male; Retrospective Studies; Risk Factors; Rural Population; Spain

Topics: Acenocoumarol; Aged; Aryl Hydrocarbon Hydroxylases; Benzodiazepines; Cytochrome P-450 CYP2C9; Drug Interactions; Gastric Mucosa; Gastrointestinal Hemorrhage; Genetic Predisposition to Disease; Homozygote; Humans; Inactivation, Metabolic; Indomethacin; Ischemic Attack, Transient; Male; Polymorphism, Genetic

Carcinoid tumors arise from enterochromaffin or enterochromaffin-like cells that are present in the gastrointestinal tract, ovaries, and lungs. Over 90% of carcinoids originate in the gastrointestinal tract with the most common sites in order of frequency being the appendix, terminal ileum, rectum, and the remainder of the colon. Gastroduodenal and pancreatic carcinoids are infrequent. Carcinoid syndrome is associated with small intestine carcinoids in about 40%. Common symptoms include intermittent intestinal obstruction with crampy abdominal pain and vomiting, and weight loss. Upper gastrointestinal bleeding with melaena or hematochezia is a relatively rare early symptom of patients with small intestine carcinoid tumors. We report on a 69-year-old man, treated with acenocoumarol for previous thromboembolic complications of hereditary protein S deficiency. He was admitted to hospital because of an acute episode of hematochezia followed by melaena. Endoscopic evaluation of esophagus, stomach, duodenum and colonoscopy revealed no apparent source of bleeding. Selective angiographic evaluation of mesenterial arteries showed pathologic vasculature approximately in mid jejunum. Laparotomy revealed bleeding from a small submucosal malignant carcinoid tumor in small intestine and multiple large metastases within mesenteric tissue. Segmental resection of small intestine and exstirpation of the metastatic masses was performed. Postoperative period was uneventful. Cytotoxic chemotherapy in this adjuvant setting has not been recommended. Small intestinal carcinoid tumor has to be considered as a rare cause of gastrointestinal bleeding with melaena or hematochezia. Nevertheless, bleeding is a relatively rare early symptom of patients with small intestine carcinoid tumor.

Topics: Acenocoumarol; Aged; Blood Transfusion; Carcinoid Tumor; Diagnosis, Differential; Gastrointestinal Hemorrhage; Humans; Intestinal Neoplasms; Intestine, Small; Male; Protein S Deficiency; Recurrence

The development of abdominal pain in the patient receiving anticoagulant therapy is more likely to pose a diagnostic dilemma. A group of intra-abdominal bleeding syndromes, which are extremely rare in patients with normal haemostasis, have been described in patients on anticoagulant therapy. Theses syndromes are of particular interest to surgeons because they simulate acute surgical conditions of the abdomen. We herein report the preoperative diagnosis of a spontaneous intramural hematoma of the small bowel by computed tomography. The authors conclude that CT should be used early in the diagnostic evaluation of abdominal pain and of acute abdomen in patients receiving anticoagulant therapy. Indications for the operative management of these patients include active bleeding, pneumoperitoneum, failure to improve with conservative management within 72 hours, worsening of symptoms, and uncertain diagnosis.

Topics: Acenocoumarol; Anticoagulants; Gastrointestinal Hemorrhage; Hematoma; Humans; Ileal Diseases; Male; Middle Aged

Topics: Acenocoumarol; Adult; Aged; Epidemiologic Methods; Gastrointestinal Hemorrhage; Humans; Middle Aged; Selection Bias

In spite of a 10-13 fold increased risk of bleeding, standard doses of coumarin with a target prothrombin time of 2.7-4.5 INR (International Normalized Ratio) are chronically used in the Netherlands by 4-5% of the adult population forty to eighty years old, mainly for the secondary prevention of myocardial infarction. The Dutch Thrombosis Services, who monitor these patients, use less rigorous criteria than the standard studies do. It would not, therefore, be too much of a surprise if the numbers of bleeding complications in practice would be much higher than expected from the standard papers so far. To answer this question the authors studied emergency intestinal bleedings in a population-based cohort study of chronic acenocoumarin users (813 person years) and their age-matched and population-based controls (17,620 person years). Of 142 first bleedings serious enough to require immediate sigmoidoscopy, 35 were connected with acenocoumarin (25%). The overall incidences in the acenocoumarin cohort and the age-matched controls were, respectively, 4.3 and 0.6 bleedings/100 person years, RR (relative risk) 7.09, p < 0.0001. Relative Risk (RR) = Incidence Among Exposed/Incidence Among Nonexposed The acenocoumarin bleeders and their controls had symmetric clinical diagnoses and levels of hemoglobin. However, acenocoumarin bleeders were significantly older and more frequently males. The sex- and age-adjusted RRs were, however, only slightly different from the crude data, suggesting no major influence of these asymmetries on the overall results. Prothrombin times in the acenocoumarin bleeders were frequently higher than the target range.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acenocoumarol; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Case-Control Studies; Cohort Studies; Dipyridamole; Female; Gastrointestinal Hemorrhage; Humans; Incidence; Intestinal Diseases; Male; Middle Aged; Prothrombin Time; Risk Factors

Topics: Acenocoumarol; Blood Coagulation Disorders; Drug Interactions; Gastrointestinal Hemorrhage; Hernia, Hiatal; Humans; Male; Middle Aged; Piroxicam

A patient developed an intramural hematoma of cecum as a result of indirect anticoagulant treatment. The case is remarkable with respect to the symptomatology and the very restricted extension of the lesion, these features probably resulting from a process of secondary infection.

Topics: Acenocoumarol; Bacterial Infections; Cecal Diseases; Gastrointestinal Hemorrhage; Hematoma; Humans; Inflammation; Intestinal Mucosa; Male; Middle Aged

Topics: Acenocoumarol; Adult; Aged; Anticoagulants; Gastrointestinal Hemorrhage; Hematoma; Humans; Intestine, Small; Male; Middle Aged; Prothrombin; Vitamin K

The authors present a case of intramural hematoma of the small intestines during anticoagulant treatment. With reference to this case, they study the frequency, etiopathogenesis and anatomy of this hematoma and particularly look at the radiological manifestations. In this respect they distinguish three stages in the evolution. The first, when the straight X-ray of the abdomen and barium followthrough demonstrate an axial stenosis of the small intestines with dilation of the proximal loops; the second (between the 7th and 20th days) when the loop affected by the hematoma takes on a characteristic "palissade" or "spring" -like sausage appearance; finally the third (after the 3rd week), when only thickening of the haustrations persists with progressive return to normal. The radiological diagnosis is discussed, not only with intramural hematomas of the small intestines of other etiologies (traumatic, during pancreatitis, during disorders in hemostatis), but also with conditions giving rise to similar radiological pictures: malabsorption, inflammatory conditions, etc.

Topics: Acenocoumarol; Adult; Anticoagulants; Clofibrate; Gastrointestinal Hemorrhage; Hematoma; Humans; Jejunum; Male; Radiography

Topics: Acenocoumarol; Aged; Drug Synergism; Gastrointestinal Hemorrhage; Glycolates; Hemorrhage; Humans; Male; Phenoxyacetates; Thiophenes

Anticoagulation therapy with acenocoumarin or with anticoagulants plus aspirin was given to 65 and 57 patients, respectively, with cardiac valve replacement. The follow-up was 1,462 months (22.5 months per patient) for the first group and 1,411 months (24.7 months per patient) for the second group. The frequency of embolic accidents was significantly lower in the group taking aspirin: Thirteen thromboembolic accidents were detected in patients receiving the anticoagulant and 3 in the group receiving the anticoagulant plus aspirin. These figures represent a 20.3 per cent incidence (one each 9.3 years of treatment) for the anticoagulant group and a 5.2 per cent incidence (one accident each 39.1 years of treatment) for the other group. The statistical significance between groups is p less than 0.005. There was no difference in the hemorrhagic risk between the two groups. We conclude that the use of an anticoagulant plus aspirin is a good and safe therapy for the prevention of thromboembolism in these patients.

Topics: Acenocoumarol; Anticoagulants; Aspirin; Blindness; Drug Therapy, Combination; Female; Gastrointestinal Hemorrhage; Heart Valve Prosthesis; Humans; Intracranial Embolism and Thrombosis; Male; Myocardial Infarction; Postoperative Complications; Thromboembolism