warfarin and Hemorrhagic-Disorders

Topics: Anticoagulants; Hemorrhagic Disorders; Heparin; Humans; Thrombosis; Warfarin

Homozygous protein C (PC) deficiency is reported in two siblings (girl and boy) who received their proper diagnoses at the ages of 7 4/12 and 1 3/12 years respectively. The girl had perinatal asphyxia without bleeding. At 1 year of age she developed purpura fulminans. Treatment with heparin and plasma was successful. At 7 4/12 years she developed tender, bluish nonnecrotic skin changes after an orthopedic operation. The PC level was 0.08 U/ml. The boy had had a large intraventricular hemorrhage neonatally and developed severe brain damage. At 1 3/12 years he manifested the same skin changes as his sister and was treated similarly. The PC level was 0.05 U/ml. Both children now receive warfarin continuously and are essentially free of symptoms. The cases represent homozygous phenotypes in a family with a recessive trait of PC deficiency without thrombotic disease. The cases also show that severe PC deficiency may be compatible with life beyond infancy without any specific therapy.

Topics: Blood Transfusion; Female; Hemorrhagic Disorders; Humans; Infant, Newborn; Intellectual Disability; Male; Pedigree; Plasma; Protein C; Protein C Deficiency; Warfarin

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Adult; Blood Coagulation; Blood Platelets; Cell Count; Clofibrate; Drug Interactions; Factor IX; Factor VII; Factor X; Hemorrhagic Disorders; Humans; Hypoprothrombinemias; Male; Phosphoric Monoester Hydrolases; Platelet Adhesiveness; Prothrombin Time; Time Factors; Warfarin

To determine the accuracy of international warfarin pharmacogenetic algorithms developed on large multiethnic cohorts (comprising more than 1000 subjects) to predict therapeutic warfarin doses in Turkish patients.. We investigated two Turkish warfarin-treated cohorts: patients with no history of hemorrhagic or thromboembolic event and patients with major and life-threatening hemorrhagic events.. International pharmacogenetic algorithms showed good performances in predicting the therapeutic dose of patients with no history of bleedings, but they did not significantly detect the incorrect warfarin dose of patients with major and life-threatening hemorrhagic events.. Although genetic information can predict the therapeutic warfarin dose, the accuracy of the international pharmacogenetic algorithms is not sufficient to be used for warfarin screening in Turkish patients.

Topics: Aged; Algorithms; Anticoagulants; Drug Dosage Calculations; Female; Genotype; Hemorrhagic Disorders; Humans; International Normalized Ratio; Male; Middle Aged; Pharmacogenetics; Thromboembolism; Turkey; Warfarin

The first of this series of three articles discussed the dental management of patients with inherited bleeding disorders. This paper will discuss and outline the dental management of patients with acquired bleeding disorders that can result from drug therapy. These may be associated with vascular defects, platelet defects or coagulation defects. In an age when people are living longer, and medical interventions are continually becoming more advanced, clinicians will need to be aware of systemic disorders and treatments that may cause complications in the dental setting. According to National Statistics, the UK population is projected to increase by 0.7% by 2016. This trend is shared with other European countries which also have ageing populations. The proportion of people aged over 65 is predicted to increase from 16% in 2006 to 22% in 2031.. Being able to recognize which drugs may cause bleeding problems at an early stage will lead to good patient management, particularly in planning and delivering treatment following invasive procedures such as dental extractions. Whilst most patients can be successfully treated in general dental practice, the clinician may need to make a decision on whether or not to refer a patient to specialist services for all dental treatment, or to share care between primary care and specialist services for selected procedures.

Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Antineoplastic Agents; Blood Coagulation Disorders; Clopidogrel; Dental Care for Chronically Ill; Drug Therapy; Hemorrhagic Disorders; Hemostasis; Heparin; Humans; Phytotherapy; Platelet Aggregation Inhibitors; Prothrombin Time; Ticlopidine; Warfarin

We report the first case of acute subdural hematoma (SDH) developing after tightening the halo of an osteoporotic 61-year-old woman on warfarin therapy for bilateral traumatic vertebral artery dissection. We discuss literature relevant to this case with an emphasis on identifying warning signs, including recurrent pin loosening, especially in patients with compromised bone structure and high risk of bleeding. Our 61-year-old patient presented to neurosurgery clinic for a 2-month follow-up of a type-III odontoid fracture sustained in a motor vehicle accident. The patient had repeatedly loosened halo pins, and shortly after the pins were tightened, the patient had a syncopal event and struck her head. An emergent computed tomography scan revealed acute SDH requiring emergent craniotomy and evacuation. SDH following pin penetration in a patient with bilateral vertebral artery dissection, osteoporosis, and anticoagulation has not been reported as a complication of the use of the halo vest for stabilization of the cervical spine. The risk of this serious complication can be minimized by giving special consideration to patients with comorbidities and by repositioning problematic pins. This case demonstrates the importance of special attention to bone strength, bleeding risk, and recurrent minor complaints with use of the halo vest.

Topics: Accidental Falls; Accidents, Traffic; Anticoagulants; Bone Nails; Craniocerebral Trauma; Craniotomy; Device Removal; Equipment Failure; Female; Hematoma, Subdural, Acute; Hemorrhagic Disorders; Humans; Immobilization; Middle Aged; Odontoid Process; Osteoporosis, Postmenopausal; Risk Factors; Spinal Fractures; Syncope; Tomography, X-Ray Computed; Vertebral Artery Dissection; Warfarin

An 84-year-old woman under warfarin therapy, who had undergone mechanical valve replacement 29 months previously, developed coagulation abnormalities after antibiotic treatment for pyelonephritis. Laboratory findings included PT at 47.6 sec, activated thromboplastin time (APTT) at 147 sec, factor V (FV) activity of 4% and FV inhibitor of 8 BU. Although overt bleeding was not observed, administration of prednisolone was started. Her coagulation abnormalities were rapidly normalized. It was later determined that the patient had received bovine thrombin at surgery. The presence of a FV inhibitor should be considered in the differential diagnosis in patients demonstrating an unexpected prolongation of PT under warfarin therapy following surgery.

Topics: Aged, 80 and over; Animals; Anti-Bacterial Agents; Anticoagulants; Aortic Valve; Aortic Valve Stenosis; Cattle; Ceftriaxone; Factor V; Female; Heart Valve Prosthesis; Hemorrhagic Disorders; Humans; Immunosuppressive Agents; Partial Thromboplastin Time; Postoperative Complications; Prednisolone; Prothrombin Time; Pyelonephritis; Species Specificity; Thrombin; Warfarin

Familial multiple coagulation factor deficiency (FMFD) of factors II, VII, IX, X, protein C, and protein S is a very rare bleeding disorder with autosomal recessive inheritance. The phenotypic presentation is variable with respect to the residual activities of the affected proteins, its response to oral administration of vitamin K, and to the involvement of skeletal abnormalities. The disease may result either from a defective resorption/transport of vitamin K to the liver, or from a mutation in one of the genes encoding gamma-carboxylase or other proteins of the vitamin K cycle. We have recently presented clinical details of a Lebanese family and a German family with 10 and 4 individuals, respectively, where we proposed autosomal recessive inheritance of the FMFD phenotype. Biochemical investigations of vitamin K components in patients' serum showed a significantly increased level of vitamin K epoxide, thus suggesting a defect in one of the subunits of the vitamin K 2,3-epoxide reductase (VKOR) complex. We now have performed a genome-wide linkage analysis and found significant linkage of FMFD to chromosome 16. A total maximum 2-point LOD score of 3.4 at theta = 0 was obtained in the interval between markers D16S3131 on 16p12 and D16S419 on 16q21. In both families, patients were autozygous for 26 and 28 markers, respectively, in an interval of 3 centimorgans (cM). Assuming that FMFD and warfarin resistance are allelic, conserved synteny between human and mouse linkage groups would restrict the candidate gene interval to the centromeric region of the short arm of chromosome 16.

Topics: Animals; Blood Coagulation Factors; Centromere; Child; Chromosome Mapping; Chromosomes, Human, Pair 16; DNA Mutational Analysis; Drug Resistance; Female; Genes, Recessive; Genetic Markers; Genotype; Germany; Glutathione Transferase; Hemorrhagic Disorders; Humans; Infant, Newborn; Lebanon; Lod Score; Male; Mice; Microsatellite Repeats; Mixed Function Oxygenases; Multienzyme Complexes; Pedigree; Rats; Species Specificity; Vitamin K; Vitamin K 1; Vitamin K Epoxide Reductases; Warfarin

Topics: Administration, Oral; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Cytochrome P-450 CYP2C9; Cytochrome P-450 Enzyme System; Genetic Predisposition to Disease; Haplotypes; Hemorrhagic Disorders; Humans; International Normalized Ratio; Italy; Prevalence; Steroid 16-alpha-Hydroxylase; Steroid Hydroxylases; Warfarin

A 46-year old nurse complaining of multiple hematomas including bleeding into the tongue was referred for hemostasis evaluation. A very low Quick percentage value, i.e. a severely prolonged prothrombin time with severely depressed vitamin K-dependent coagulation factors (FII:C, FVII:C, FX:C) and normal FV:C and fibrinogen level was found. In the absence of cholestasis, malabsorption and broad-spectrum antibiotic therapy, ingestion of vitamin K antagonists was suspected. Three years previously, she had been on oral anticoagulant treatment with phenprocoumon (Marcoumar) for postoperative pulmonary embolism. She denied having voluntarily ingested anticoagulant drugs. A high plasma level of coumarins was found. To exclude accidental ingestion, the patient's son living in the same household was tested as well. Surprisingly, a low level of coumarin was found also in his plasma. We suspect that the patient voluntarily intoxicated herself and gave a low dose of coumarin anticoagulant to her son as well.

Topics: Anticoagulants; Blood Coagulation Tests; Drug Overdose; Female; Hematoma; Hemorrhagic Disorders; Humans; Middle Aged; Phenprocoumon; Tongue Diseases; Warfarin

Topics: Adolescent; Adult; Aged; Analysis of Variance; Anticoagulants; Bleeding Time; Blood Coagulation Tests; Blood Proteins; Child; Female; Hemorrhagic Disorders; Humans; Immunoenzyme Techniques; Male; Middle Aged; Platelet Aggregation; Warfarin

The cause of a fatal condition characterized by hemorrhagic cardiomyopathy, hemothorax, and coagulation defects in hysterectomy-derived male mice was investigated. Microscopic heart alterations included multifocal hemorrhage and necrosis with variable degrees of acute inflammation and fibroplasia that were most severe in the region of the atrioventricular junction. A spontaneous outbreak was arrested by increasing menadione Na-bisulfite (vitamin K) in the feed to 20 ppm. The complete syndrome including hemorrhagic cardiomyopathy was readily reproduced in germ-free male mice given a vitamin K-free diet, and in conventional male and female mice given Warfarin in the diet. We concluded that the cause of this condition was vitamin K deficiency.

Topics: Animals; Blood Coagulation Disorders; Cardiomyopathies; Female; Hemorrhagic Disorders; Hemothorax; Male; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Inbred CBA; Myocardium; Vitamin K; Vitamin K Deficiency; Warfarin

Topics: Adult; Blood Coagulation Factors; Blood Coagulation Tests; Diagnosis, Differential; Female; Hemorrhagic Disorders; Humans; Munchausen Syndrome; Warfarin

Warfarin sodium (Coumadin) has been used as an effective anticoagulating agent in human medicine for many years, although careful monitoring of its effects are necessary to avoid excessive anticoagulation. Previous experience with this drug for chronic anticoagulation therapy in miniature swine has been limited. The effect of warfarin sodium was studied by measuring prothrombin time in twelve 8-month-old Hanford miniature swine. The pigs had been fed a high-cholesterol diet and had undergone a prior coronary artery abrasion procedure for development of an atherosclerotic coronary disease model. Atherosclerosis was induced by feeding a high-cholesterol diet. Baseline prothrombin time ranged from 12.8 to 15.0 s (13.7 s mean). Prothrombin time was determined daily for the first 5 days of treatment and at least twice weekly thereafter until the animals were sacrificed. Animals received warfarin for 37-41 days. Prothrombin time could be increased 33-50% by once daily oral administration of warfarin 0.04-0.08 mg/kg. Oral administration of more than 0.08 mg/kg as a maintenance dose resulted in the death of two pigs. Most animals responded well to 0.08 mg/kg for the first 3 days of treatment followed by a maintenance dose of 0.06 mg/kg. Dosage was adjusted periodically when prothrombin times exceeded 50% above baseline. It is our experience that monitoring prothrombin time at least twice weekly and adjusting the maintenance dose can eliminate death losses due to warfarin intoxication.

Topics: Animals; Arteriosclerosis; Cholesterol, Dietary; Diet, Atherogenic; Disease Susceptibility; Hemorrhagic Disorders; Male; Prothrombin Time; Swine; Swine, Miniature; Warfarin

Although spinal subdural hematoma is a rare condition, it has a higher incidence in persons with a bleeding diathesis and in those with a bleeding diathesis who have had a lumbar puncture. We report a case of a 65-year-old woman on oral anticoagulants presenting with atypical symptoms who developed a spinal subdural hematoma over a six-hour period. This resulted in complete paraplegia of her lower extremities with no improvement after surgical spinal cord decompression.

Topics: Female; Hematoma, Subdural; Hemorrhagic Disorders; Humans; Laminectomy; Middle Aged; Paraplegia; Spinal Cord Compression; Spinal Diseases; Warfarin

In August, 1981, paediatric hospitals in Ho Chi Minh City (formerly Saigon), Vietnam, began to report cases of a haemorrhagic syndrome in infants. The cause of this haemorrhagic phenomenon was identified as talcum powder contaminated with the anticoagulant warfarin. Analysis of talcum powders revealed warfarin in concentrations between 1.7% and 6.5%. 741 cases were detected and 177 patients died. The possibility of accidental contamination or substitution of a perfuming agent by warfarin can be rejected. In an experiment with two baboons, the animal exposed to the contaminated talc died five days later from haemorrhage. The accident and the animal study demonstrate the significant transcutaneous uptake of the anticoagulant.

Topics: Animals; Disease Outbreaks; Drug Contamination; Female; Hemorrhagic Disorders; Humans; Infant; Infant, Newborn; Male; Maternal-Fetal Exchange; Pan troglodytes; Pregnancy; Skin; Skin Absorption; Syndrome; Talc; Vietnam; Warfarin

Topics: Animal Diseases; Animals; Blood Coagulation; Dog Diseases; Dogs; Hemorrhagic Disorders; Indans; Rodenticides; Vitamin K; Warfarin

Topics: Animals; Blood Cell Count; Blood Coagulation Tests; Blood Platelets; Disseminated Intravascular Coagulation; Dog Diseases; Dogs; Female; Fibrin Fibrinogen Degradation Products; Hemophilia A; Hemorrhagic Disorders; Male; Purpura, Thrombocytopenic; von Willebrand Diseases; Warfarin

Topics: Femoral Nerve; Hematoma; Hemorrhagic Disorders; Humans; Iatrogenic Disease; Male; Manipulation, Orthopedic; Middle Aged; Peripheral Nervous System Diseases; Warfarin

Topics: Acetaminophen; Anemia, Aplastic; Anticoagulants; Aspirin; Blood Platelets; Bone Marrow; Capillary Fragility; Drug Hypersensitivity; Drug Synergism; Hemorrhagic Disorders; Hemostasis; Heparin; Heparin Antagonists; Humans; Indenes; Platelet Adhesiveness; Purpura; Thrombocytopenia; Vascular Diseases; Warfarin

Topics: Anticoagulants; Drug Synergism; Hemorrhage; Hemorrhagic Disorders; Humans; Phenylbutazone; Warfarin

Topics: Animals; Benzopyrans; Blood Coagulation Tests; Female; Hemorrhagic Disorders; Incisor; Injections, Intravenous; Ointments; Oral Hemorrhage; Postoperative Complications; Powders; Rats; Thrombosis; Tooth Extraction; Warfarin

Topics: Abdomen; Adult; Animals; Capillaries; Forensic Medicine; Hemorrhagic Disorders; Homicide; Humans; Kidney; Liver; Male; Rats; Rodenticides; Spectrophotometry; Ultraviolet Rays; Warfarin

Coagulation studies were carried out on 10 patients who bled during anticoagulant therapy, in whom no other underlying cause for bleeding could be demonstrated, and 10 patients with similar degrees of hypoprothrombinemia who were not bleeding. The average age and sex distribution of the two groups was similar, and no association was noted between the occurrence of hemorrhage and the type of anticoagulant used, the duration of treatment or the nature of the underlying disease. Comparison of the results revealed no differences in the levels of factors II, VII, IX and X or in the glass and silicone (Siliclad) clotting time, the thromboplastin generation test and Thrombotest. It was concluded that all patients on anticoagulant drugs whose prothrombin time is in the therapeutic range or longer are potential bleeders and that one cannot necessarily predict those who will bleed on the basis of coagulation studies.

Topics: Acenocoumarol; Anticoagulants; Blood Coagulation Tests; Coumarins; Dicumarol; Drug Therapy; Geriatrics; Hemorrhagic Disorders; Humans; Hypoprothrombinemias; Indans; Phenindione; Prothrombin Time; Warfarin

Topics: Analgesics; Analgesics, Non-Narcotic; Anticoagulants; Antipyretics; Atrial Fibrillation; Blood Coagulation Tests; Dicumarol; Drug Synergism; Drug Therapy; Geriatrics; Hemorrhagic Disorders; Muscle Relaxants, Central; Myocardial Infarction; Phenindione; Pyridines; Toxicology; Warfarin

Topics: Blood Coagulation Tests; Criminals; Diagnosis; Factor IX; Factor VII; Factor X; Geriatrics; Hemorrhagic Disorders; Humans; Poisoning; Prothrombin Time; Toxicology; Vitamin K; Warfarin

Topics: Coumarins; Hemorrhagic Disorders; Insecticides; Warfarin