vitamin-k-1 and Hemorrhage

Bleeding is probably the major complication of anticoagulant treatment with vitamin K antagonists represented nowadays mostly by warfarin in the Czech Republic. The main risk factors in hemorrhagic complications of warfarinisation are the intensity and instability of the anticoagulant treatment, individual patient characteristics, warfarin interactions with other drugs and the length of the anticoagulant therapy. Severe bleeding in warfarin patients is most effectively brought about by a fast and complete undoing of the anticoagulation effect of the drug employing the prothrombin complex concentrate and slow i.v. vitamin K1 infusion regardless of the reason for the anticoagulation. This approach can secure the minimalisation of the bleeding's negative consequences. A less severe bleeding or asymptomatic increase in the international normalized ratio can be treated effectively by skipping or decreasing of the warfarin dosage and/or oral administration of vitamin K1 (i.v. administration only in selected higher risk cases) that does result only in a partial consolidation of coagulopathy but of such type that the risk of thrombotic event requires. The article's goal is to contribute to the treatment standardization in patients with warfarin overdose and/or with hemorrhagic complications due to warfarin treatment and it is available at www.thrombosis.cz. The guidelines include a ready-reference chart whose objective is immediate and quick crash course in the clinical practice.

Topics: Anticoagulants; Antifibrinolytic Agents; Blood Coagulation Factors; Drug Monitoring; Factor VIIa; Hemorrhage; Humans; International Normalized Ratio; Plasma; Vitamin K 1; Warfarin

For most warfarin indications, the target maintenance international normalised ratio (INR) is 2-3. Risk factors for bleeding complications with warfarin use include age, history of past bleeding and specific comorbid conditions. To reverse the effects of warfarin, vitamin K(1) can be given. Immediate reversal is achieved with a prothrombin complex concentrate (PCC) and fresh frozen plasma (FFP). Vitamin K(1) is essential for sustaining the reversal achieved by PCC and FFP. When oral vitamin K(1) is used for warfarin reversal, the injectable formulation of vitamin K(1) is preferable to tablets because of its flexible dosing; this formulation can be given orally or injected. To temporarily reverse the effect of warfarin when there is a need to continue warfarin therapy, vitamin K(1) should be given in a dose that will quickly lower the INR to a safe, but not subtherapeutic, range and will not cause resistance once warfarin is reinstated. Prothrombinex-HT is the only PCC approved in Australia and New Zealand for warfarin reversal. It contains factors II, IX and X, and low levels of factor VII. FFP should be added to Prothrombinex-HT as a source of factor VII when used for warfarin reversal. Simple dental or dermatological procedures may not require interruption to warfarin therapy. If necessary, warfarin therapy can be withheld 5 days before elective surgery, when the INR usually falls to below 1.5 and surgery can be conducted safely. Bridging anticoagulation therapy for patients at high risk for thromboembolism should be undertaken in consultation with the relevant experts.

Topics: Administration, Oral; Adult; Anticoagulants; Blood Coagulation Factors; Drug Administration Schedule; Drug Monitoring; Evidence-Based Medicine; Hemorrhage; Humans; International Normalized Ratio; Patient Education as Topic; Patient Selection; Perioperative Care; Plasma; Risk Factors; Thromboembolism; Vitamin K 1; Warfarin

The indications for transfusions are anemia compromising delivery of oxygen, acute blood loss, cardiopulmonary bypass, exchange transfusion, maintenance of hemostasis, and sepsis associated with granulocytopenia. When transfusion therapy is indicated, only that component of whole blood which is needed for correction of the problem should be given. The options for use each component have been discussed.

Topics: Acute Disease; Agranulocytosis; Anemia; Anemia, Aplastic; Blood Cells; Blood Coagulation; Blood Platelets; Blood Transfusion; Blood Transfusion, Autologous; Cardiopulmonary Bypass; Colloids; Erythroblastosis, Fetal; Erythrocytes; Exchange Transfusion, Whole Blood; Factor VIII; Female; Hemophilia A; Hemophilia B; Hemorrhage; Hemostasis; Hepatic Encephalopathy; Humans; Pregnancy; Purpura, Thrombocytopenic; Thrombocytopenia; Vitamin K 1

Warfarin-associated coagulopathy commonly occurs in patients undergoing treatment with this anticoagulant. This trial aimed to determine the efficacy of using low-dose orally administered vitamin K. This was a double-blind, placebo-controlled, randomized trial. Chinese patients with mechanical heart valves who were undergoing warfarin treatment and who had INR values from 4.0 to 10.0 without bleeding were the subjects of this study. These patients were randomized into two treatment groups and were orally administered either vitamin K. In total, 80 patients were enrolled in the present study, and 40 patients each were assigned to the placebo and vitamin K1 treatment groups. Patients administered vitamin K. Low-dose oral vitamin K

Topics: Adult; Anticoagulants; Antifibrinolytic Agents; Blood Coagulation Disorders; China; Dose-Response Relationship, Drug; Double-Blind Method; Female; Heart Valve Prosthesis; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Prospective Studies; Vitamin K 1; Warfarin

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Drug Administration Schedule; Heart Valve Prosthesis; Hemorrhage; Humans; Injections, Intravenous; International Normalized Ratio; Thromboembolism; Vitamin K 1; Warfarin

Treatment of patients with excessive anticoagulation is routinely done by intravenous phytonadione (vitamin K1). Oral administration of phytonadione has been shown to be an effective alternative to the intravenous route, but these methods have never been compared directly. Our objective was to compare efficacy and safety of intravenous vs oral phytonadione treatment in patients with excessive anticoagulation without bleeding.. The study was a prospective randomized controlled trial of consecutive patients presenting with excessive anticoagulation without major bleeding. Patients with a baseline international normalized ratio (INR) of 6 to 10 (n = 44, 47 episodes) received either intravenous or oral phytonadione (0.5 mg or 2.5 mg, respectively), and patients with an INR greater than 10 (n = 17, 19 episodes) received 1 mg or 5 mg, respectively. Efficacy and safety end points were sequential INR changes and the proportion of patients achieving therapeutic range (INR, 2-4), overcorrection (INR<2.0), or undercorrection (INR>4.0) INR values.. Sixty-six episodes of excessive anticoagulation were studied. In patients with baseline INR 6-10 the response to intravenous phytonadione was more rapid than in the oral group, and the proportion of patients reaching therapeutic range INR at 6 hours (11/24 vs 0/23) and at 12 hours (16/24 vs 8/23) was significantly higher. However, mean +/- SD INR values were similar for both groups at 24 hours (2.9 +/- 0.8 vs 2.6 +/- 0.8). Patients in the intravenous group tended to be more often (7/24 vs 2/23) overcorrected (INR<2). In patients with baseline INR values greater than 10 efficacy and safety were comparable for both routes of administration.. Oral administration of phytonadione had similar efficacy and safety as intravenously administered phytonadione and may be suitable for treatment of patients with excessive anticoagulation.

Topics: Administration, Oral; Aged; Anticoagulants; Antifibrinolytic Agents; Blood Coagulation; Female; Hemorrhage; Humans; Infusions, Intravenous; International Normalized Ratio; Male; Middle Aged; Prospective Studies; Safety; Treatment Outcome; Vitamin K 1; Warfarin

There is near-global consensus that all newborns be given parenteral vitamin K. To assess the prevalence of functional VK insufficiency in preterm infants based on elevated under-γ-carboxylated (Glu) species of Gla proteins, factor II (PIVKA-II), and osteocalcin (GluOC), synthesized by liver and bone, respectively.. Preterm infants who remain exclusively or predominantly human breastmilk-fed after neonatal unit discharge are at high risk of developing subclinical VK deficiency in early infancy. Routine postdischarge VK

Topics: Aftercare; Hemorrhage; Humans; Infant; Infant, Newborn; Infant, Premature; Milk, Human; Patient Discharge; Prospective Studies; Vitamin K; Vitamin K 1; Vitamin K Deficiency

Bromadiolone, commonly known as super warfarin, is a long-acting coumarin dicoumarin rodenticide. The mechanism of bromadiolone is mainly to inhibit vitamin K1 epoxide reductase and affect the synthesis of coagulation factors Ⅱ, Ⅶ, Ⅸ and Ⅹ, which causes blood coagulation dysfunction and systemic multiple organ hemorrhage. Here, we report of a case of bromadiolone poisoning patient who had digestive tract, abdominal hemorrhage, as well as secondary paralytic ileus. After blood product transfusion and vitamin K1 supplementation, the patient was discharged after the physical condition was improved. It's suggestied that clinicians should pay attention to rare complications to prevent missed diagnosis when treating other bromadiolone poisoning.. 溴敌隆是一种长效香豆素类抗凝类杀鼠剂，俗称"超级华法林"，其作用机制主要是抑制维生素K1环氧化物还原酶，影响凝血因子Ⅱ、Ⅶ、Ⅸ和Ⅹ的合成，致使机体凝血机能障碍，导致全身多脏器出血。本文报道一例溴敌隆中毒后导致消化道、腹腔出血，同时继发麻痹性肠梗阻的患者，给予输注血制品、补充维生素K1等治疗后，病情好转出院。提示临床医生在救治其他溴敌隆中毒时，要注意少见并发症，以免漏诊。.

Topics: 4-Hydroxycoumarins; Blood Coagulation Factors; Dicumarol; Hemorrhage; Humans; Intestinal Pseudo-Obstruction; Oxidoreductases; Rodenticides; Vitamin K 1; Warfarin

Guidelines exist on the management of supratherapeutic/subtherapeutic international normalized ratio (INR) values for patients on warfarin. However, there is a paucity of the literature relating to an acute overdose of warfarin. This is a retrospective cohort study for all acute and acute-on-chronic (AOC) warfarin overdoses reported to the Maryland Poison Center in patients ≥12 years between January 1st, 2000, until October 31st, 2019, managed in a health care facility. The primary outcome was to determine the time after presentation to peak INR. Secondary outcomes included risk factors associated with INR >10 and describing patient characteristics. A total of 163 overdoses were included, 68 acute and 95 AOC. In patients who did not receive reversal therapies, INR peaked at a median value of 3.8 (interquartile range 2.6-5.5) between 24 and 36 hours. The median time to phytonadione was 22.0 hours. Most patients received phytonadione (62.0%), with fewer receiving blood products (16.6%). The median warfarin dose ingested was 75 mg. The AOC group had a greater mean age (56 vs. 43 years), median INR value (2.4 vs. 1.4), and men (62.1% vs. 41.2%). Factors associated with an INR > 10 included initial INR and reported quantity ingested. Peak INR was greater in the AOC than the acute overdose group (6.1 vs. 3.4), although the bleeding rate was similar. Peak INR values after warfarin overdose occur between 24 and 36 hours after presentation. Initial INRs and reported quantity ingested may be useful to predict those needing treatment.

Topics: Adult; Aged; Anticoagulants; Antidotes; Antifibrinolytic Agents; Blood Coagulation; Drug Overdose; Female; Hemorrhage; Humans; International Normalized Ratio; Male; Maryland; Middle Aged; Poison Control Centers; Predictive Value of Tests; Retrospective Studies; Time-to-Treatment; Vitamin K 1; Warfarin

A large-scale outbreak of life-threatening, inhaled synthetic cannabinoids (Spice/K2)-associated coagulopathy with bleeding complications was recently reported in Illinois. The causative agents were brodifacoum, difenacoum, and bromadiolone, potent, long-acting, 4-hydroxycoumarin anticoagulant rodenticides (LAAR) that were mixed with Spice/K2 products procured and then inhaled by the victims. We report on 3 poisoned patients who reside in underserved, socioeconomically disadvantaged neighborhoods of Chicago that were admitted and treated successfully at two inner-city, tertiary care hospitals in Chicago. The patients were discharged from the hospitals on daily long-term high-dose oral vitamin K

Topics: 4-Hydroxycoumarins; Administration, Inhalation; Adult; Aftercare; Anticoagulants; Antifibrinolytic Agents; Blood Coagulation Disorders; Cannabinoids; Chicago; Female; Hemorrhage; Humans; International Normalized Ratio; Lost to Follow-Up; Male; Medication Adherence; Middle Aged; Patient Compliance; Synthetic Drugs; Vitamin K 1

Patients exposed to long acting anticoagulant rodenticides (LAARs) are typically administered large amounts of oral vitamin K1 (VK1) to counteract life-threatening anticoagulant effects. Although VK1 treatment effectively prevents mortality, additional methods are needed to reduce the long duration of VK1 treatment which can last for months at high expense. We developed a model of brodifacoum (BDF) poisoning, one of the most potent LAARs, in adult male New Zealand White (NZW) rabbits. The LD50 for oral BDF was determined to be 192 μg/kg, similar to that calculated for adult rats. However, in contrast to rats, NZW rabbits exhibited severe internal hemorrhage including in the brain, symptoms which mimic what occurs in cases of human poisoning. Similar to warfarin, BDF and other LAARs undergo enterohepatic recirculation which contributes to their long half-lives. We therefore tested effects of cholestyramine (CSA), an FDA-approved bile sequestrant, on BDF-induced mortality. When given daily (0.67 g/kg, oral) starting the day of BDF administration, CSA reduced mortality from 67% to 11%. At the same CSA prevented the increase in clotting time, and reduced the decrease in core body temperature due to BDF. Given its excellent safety record and that it is approved for children older than 6 years, these findings suggest CSA could be considered as an adjunct to VK1 for treatment of LAAR poisoning.

Topics: 4-Hydroxycoumarins; Animals; Anticoagulants; Bile Acids and Salts; Cholestyramine Resin; Hemorrhage; Lethal Dose 50; Male; Rabbits; Rodenticides; Survival Analysis; Vitamin K 1

To investigate the morbidity of complications and pregnancy outcomes in women with mechanical heart valve replacement who received low-dose oral anticoagulation treatment with warfarin throughout the pregnancy, compare the prognosis and complications of patients who were treated with single oral warfarin treatment or the "bridging" therapy treatment, investigate the influence of using vitamin K1 before emergency cesarean section delivery on postoperative warfarin anticoagulant effect and to explore an appropriate anticoagulant regimen during perioperative period for pregnant women with mechanical heart valve replacement.. 46 pregnant women with mechanical heart valve replacement who received low-dose oral anticoagulation treatment from October 2008 to October 2014 treated at West China Women's and Children's Hospital were retrospectively reviewed. Eight patients received emergency cesarean section (CS), while 38 patients received selective CS, in which 17 patients received single oral warfarin and 21 patients received "bridging" anticoagulation treatment during postoperative period. Morbidity of complications and the time to achieve the target INR after operation were compared.. The mechanical valves were at the mitral position in 35 (76.09 %) patients, at the aortic position in 2 (4.35 %) patient and at both the mitral and aortic position in 9 (19.57 %) patients. 46 full-term healthy babies were delivered and no maternal thromboembolic was observed during pregnancy. There was no significant difference of the amount of uterine bleeding between single oral warfarin group and "bridging" treatment group during postpartum period. In single oral warfarin group, one valve thrombosis was observed and led to sudden death. No periphery thrombosis, hematoma, general hemorrhage or other sign of over-anticoagulation was observed. The INR increased more slowly in the group who received emergency CS with preoperative application of vitamin K1 than other two groups.. The use of vitamin K1 preoperatively might result in warfarin resistance and discontinuation of warfarin therapy before selective CS might be more appropriate than application of vitamin K1. The "bridging" anticoagulation treatment which combines oral warfarin and subcutaneous LMWH might be more effective and safer than single oral warfarin therapy for patients with mechanical heart valve replacement during postoperative period, no matter selective or emergency CS. The safety of low-dose oral warfarin therapy throughout pregnancy is still under controversy.

Topics: Adult; Anticoagulants; Antifibrinolytic Agents; Cesarean Section; China; Delivery, Obstetric; Female; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Morbidity; Perioperative Period; Postoperative Period; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Outcome; Thrombosis; Treatment Outcome; Vitamin K 1; Warfarin; Young Adult

Anticoagulation of patients with cardiac tamponade (CT) complicating catheter ablation of atrial fibrillation (AF) is an ongoing problem. The aim of this study was to survey the clinical practice of periprocedural anticoagulation in such patients. This study analyzed the periprocedural anticoagulation of 17 patients with CT complicating AF ablation. Emergent pericardiocentesis was performed once CT was confirmed. The mean drained volume was 410.0 ± 194.1 mL. Protamine sulfate was administered to neutralize heparin (1 mg neutralizes 100 units heparin) in 11 patients with persistent pericardial bleeding and vitamin K1 (10 mg) was given to reverse warfarin in 3 patients with supratherapeutic INR (INR > 2.1). Drainage catheters were removed 12 hours after echocardiography confirmed absence of intrapericardial bleeding and anticoagulation therapy was restored 12 hours after removing the catheter. Fifteen patients took oral warfarin and 10 of them were given subcutaneous injection of LMWH (1 mg/kg, twice daily) as a bridge to resumption of systemic anticoagulation with warfarin. Two patients with a small amount of persistent pericardial effusion were given LMWH on days 5 and 13, and warfarin on days 6 and 24. The dosage of warfarin was adjusted to keep the INR within 2-3 in all patients. After 12 months of follow-up, all patients had no neurological events and no occurrence of delayed CT. The results showed that it was effective and safe to resume anticoagulation therapy 12 hours after removal of the drainage catheter. This may help to prevent thromboembolic events following catheter ablation of AF.

Topics: Aged; Anticoagulants; Antifibrinolytic Agents; Atrial Fibrillation; Blood Coagulation; Cardiac Tamponade; Catheter Ablation; China; Female; Hemorrhage; Heparin; Humans; Male; Middle Aged; Pericardial Effusion; Pericardiocentesis; Perioperative Period; Protamines; Retrospective Studies; Stroke; Vitamin K 1; Warfarin

Patients treated with warfarin for therapeutic anticoagulation present a challenge for the perioperative management of urgent and emergent surgery. Anticoagulation must be reversed prior to most surgical procedures to prevent intraoperative bleeding. The purpose of this module is to review the options for urgent reversal of warfarin anticoagulation and the indications for each reversal agent. Selection of the appropriate agent is important to reduce unnecessary complications of treatment and to achieve optimal reversal of anticoagulation.. When urgent surgery is required for patients taking warfarin, intravenous vitamin K1 should be used for procedures that can be delayed for six to 12 hr. Vitamin K1 results in the activation of existing clotting factors rather than requiring the synthesis of new proteins, which allows for its relatively rapid onset of action. Intravenous vitamin K1 acts more quickly than oral administration, with reversal of anticoagulation occurring within six to 12 hr vs 18-24 hr, respectively. If surgery cannot be delayed, prothrombin complex concentrates (PCCs) should be given, and intravenous vitamin K1 should be infused concurrently to ensure sustained reversal of anticoagulation. The duration of action of both PCCs and plasma is six hours due to the short half-life of factor VII. Prothrombin complex concentrates contain small amounts of heparin and are contraindicated in patients with heparin-induced thrombocytopenia. Plasma should be used only if PCCs are unavailable or are contraindicated.. Reversal of warfarin anticoagulation can be achieved in a safe and timely manner when the appropriate agent is selected and administered correctly.

Topics: Anticoagulants; Blood Coagulation Factors; Blood Loss, Surgical; Hemorrhage; Humans; Preoperative Care; Time Factors; Vitamin K 1; Warfarin

• Despite the associated bleeding risk, warfarin is the most commonly prescribed anticoagulant in Australia and New Zealand. Warfarin use will likely continue for anticoagulation indications for which novel agents have not been evaluated and among patients who are already stabilised on it or have severe renal impairment. • Strategies to manage over-warfarinisation and warfarin during invasive procedures can reduce the risk of haemorrhage. • For most warfarin indications, the target international normalised ratio (INR) is 2.0-3.0 (venous thromboembolism and single mechanical heart valve excluding mitral). For mechanical mitral valve or combined mitral and aortic valves, the target INR is 2.5-3.5. • Risk factors for bleeding with warfarin use include increasing age, history of bleeding and specific comorbidities. • For patients with elevated INR (4.5-10.0), no bleeding and no high risk of bleeding, withholding warfarin with careful subsequent monitoring seems safe. • Vitamin K1 can be given to reverse the anticoagulant effect of warfarin. When oral vitamin K1 is used for this purpose, the injectable formulation, which can be given orally or intravenously, is preferred. • For immediate reversal, prothrombin complex concentrates (PCC) are preferred over fresh frozen plasma (FFP). Prothrombinex-VF is the only PCC routinely used for warfarin reversal in Australia and New Zealand. It contains factors II, IX, X and low levels of factor VII. FFP is not routinely needed in combination with Prothrombinex-VF. FFP can be used when Prothrombinex-VF is unavailable. Vitamin K1 is essential for sustaining the reversal achieved by PCC or FFP. • Surgery can be conducted with minimal increased risk of bleeding if INR ≤ 1.5. For minor procedures where bleeding risk is low, warfarin may not need to be interrupted. If necessary, warfarin can be withheld for 5 days before surgery, or intravenous vitamin K₁ can be given the night before surgery. Prothrombinex-VF use for warfarin reversal should be restricted to emergency settings. Perioperative management of anticoagulant therapy requires an evaluation of the risk of thrombosis if warfarin is temporarily stopped, relative to the risk of bleeding if it is continued or modified.

Topics: Administration, Oral; Anticoagulants; Antifibrinolytic Agents; Blood Coagulation Factors; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Monitoring; Hemorrhage; Humans; International Normalized Ratio; Plasma; Postoperative Care; Surgical Procedures, Operative; Vitamin K 1; Warfarin

Topics: Administration, Oral; Anticoagulants; Antifibrinolytic Agents; Antithrombins; Benzimidazoles; beta-Alanine; Dabigatran; Hemorrhage; Humans; Morpholines; Plasma; Primary Prevention; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Thromboembolism; Treatment Outcome; Vitamin K 1

To describe the pharmacologic agents and strategies used for urgent reversal of warfarin and the target-specific oral anticoagulants dabigatran, rivaroxaban, and apixaban.. To reverse the anticoagulant effects of warfarin in patients who are bleeding or need surgery, exogenous vitamin K (phytonadione) may be used in combination with another, shorter-acting intervention, such as fresh frozen plasma (FFP), prothrombin complex concentrate (PCC), recombinant factor VIIa, or activated PCC (aPCC). Three-factor PCC contains factors II, IX, and X in an inactivated form, and four-factor PCC also includes factor VII in an inactivated form. No four-factor PCC products are available in the United States, but aPCC, which contains the same four factors with factor VII provided in an activated form, is available. The intervention depends on the International Normalized Ratio, presence of bleeding, and need for and timing of surgery. Research suggests that clotting factor concentrates are more effective than FFP alone for warfarin reversal. These products also may be useful for reversing the effects of target-specific oral anticoagulants, but limited efficacy and safety data are available to support their use. The risks and benefits associated with these products need to be weighed before their use for reversal of dabigatran, rivaroxaban, or apixaban. Additional clinical data are needed to clearly define the role of concentrated clotting factor products in reversal and to determine the optimal clotting factor concentrate product and dose for urgent reversal of oral anticoagulation.. Phytonadione and clotting factor concentrates appear to have a role for reversal of warfarin, and limited evidence suggests that clotting factor concentrates could have a role in reversal of target-specific oral anticoagulants in an emergency situation.

Topics: Administration, Oral; Anticoagulants; Antifibrinolytic Agents; Antithrombins; Benzimidazoles; beta-Alanine; Blood Coagulation Factors; Blood Loss, Surgical; Dabigatran; Drug Therapy, Combination; Emergencies; Hemorrhage; Humans; International Normalized Ratio; Morpholines; Plasma; Pyrazoles; Pyridones; Rivaroxaban; Surgical Procedures, Operative; Thiophenes; Thromboembolism; Treatment Outcome; Vitamin K 1; Warfarin

To describe a process for prompt evaluation and management- including reversal of the effects of warfarin and target-specific oral anticoagulants-of patients with or at high risk for bleeding during oral anticoagulant therapy or when such therapy is interrupted for an urgent invasive procedure or surgery.. The use of pharmacologic interventions for anticoagulant reversal may depend on the measured level of anticoagulation, time since the last anticoagulant dose, target level of coagulation, reliability of laboratory tests of coagulation, severity of or risk for bleeding, the agents' mechanism of action and pharmacokinetics, and pharmacodynamics of the reversal agent. The patient's age, weight, renal function, comorbid conditions, and other drug therapy, as well as the risk for thromboembolism and other adverse effects of the reversal therapies, also enter into therapeutic decisions. Hemodialysis may be used to remove the direct thrombin (factor IIa) inhibitor dabigatran and reverse its anticoagulant effects. Limited experience with clotting factor concentrates suggests that activated prothrombin complex concentrate may be useful for reversing the anticoagulant effects of dabigatran. The activity of oral factor Xa inhibitors (i.e., rivaroxaban and apixaban) is higher up the common pathway of the coagulation cascade and thus may be easier to reverse than that of direct thrombin inhibitors. Additional clinical experience is needed to identify the optimal reversal agents, dosage, and impact on thrombosis or bleeding outcomes for both classes of agents.. A comprehensive plan individualized to each agent should be developed to promptly reverse the effects of oral anticoagulants and optimize outcomes in patients with bleeding or an urgent need for surgery.

Topics: Administration, Oral; Adult; Anticoagulants; Antifibrinolytic Agents; Blood Coagulation Factors; Emergencies; Hemorrhage; Humans; Renal Dialysis; Risk Assessment; Risk Factors; Surgical Procedures, Operative; Treatment Outcome; Vitamin K 1; Warfarin

Early infant (1-60 days of life) male circumcision is being trialed in Africa as a human immunodeficiency virus prevention strategy. Postcircumcision bleeding is particularly concerning where most infants are breastfed, and thus these infants are at increased risk of vitamin K deficiency bleeding.. During a circumcision trial, one infant bled for 90 minutes postprocedure. After discovering he had not received standard prophylactic vitamin K, we gave 2 mg phytomenadione (vitamin K1) intramuscularly; bleeding stopped within 30 minutes.. Vitamin K's extremely rapid action is not commonly appreciated. Neonatal vitamin K has been shown to be cost-effective. To increase availability and promote awareness of its importance, especially in low-resource settings where blood products and transfusions are limited, vitamin K should be included in the World Health Organization's Model List of Essential Medicines for Children.

Topics: Africa; Circumcision, Male; Hemorrhage; Humans; Infant, Newborn; Male; Vitamin K 1; Vitamin K Deficiency; Vitamins

This observational study aimed at evaluating recent superwarfarin intoxication of Korean patients. Ten patients were diagnosed as or highly suspicious for superwarfarin intoxication. Case report forms described by attending hematologists of the patients were collected and analyzed. Bleeding symptoms were varied among the patients. Patients uniformly showed prolonged prothrombin time (PT) and activated thromboplastin time (aPTT) with decreased activity of vitamin K dependent coagulation factors. Positive serum brodifacoum test results in 4 of 5 requested patients contributed to confirmatory diagnosis. Psychiatric interview revealed an attempted ingestion in one patient. High dose vitamin K1 therapy promptly corrected prolonged PT and aPTT, but hasty discontinuation caused repeated bleeding diathesis in 6 patients. Route of intoxication was unknown or not definite among 8 of 10 patients. Three patients had a possibility of environmental exposure considering their occupations: there might be intoxication by transdermal absorption or inhalation. Therefore, high dose and prolonged use of vitamin K1 therapy is necessary for effective detoxification. Further detailed investigation on environmental exposure and efforts to improve availability of the blood level test in clinic are requested.

Topics: 4-Hydroxycoumarins; Adult; Aged; Aged, 80 and over; Anticoagulants; Antifibrinolytic Agents; Environmental Exposure; Female; Hemorrhage; Humans; Male; Middle Aged; Partial Thromboplastin Time; Prothrombin Time; Republic of Korea; Treatment Outcome; Vitamin K 1

Germfree mice died when they were fed a purified diet of AIN-76 formula sterilized by gamma-irradiation. Vitamin K deficiency was suspected and this study was performed to confirm the cause of the death. Germfree mice were fed purified diets of AIN-76 or AIN-93M formula, which were pelleted and sterilized by gamma-irradiation at a dose of 50 kGy. One half of the mice fed the AIN-76 diet died within two weeks and the surviving animals were also in poor health, while 91% of mice fed the AIN-93M diet survived. No hemorrhage was observed grossly in any organs of the surviving animals. Histologically, degeneration with inflammatory cell infiltration was observed as well as hemorrhage and fibrosis in the heart muscles of mice fed the AIN-76 diet. No microscopic lesions were observed in the other organs. Prothrombin time (PT) and activated partial thromboplastin time (APTT) were extremely prolonged when mice were fed the AIN-76 diet. The animals totally recovered when they were intragastrically administered 1 microg/day of vitamin K(3) from the third day of feeding of the AIN-76 diet, except for PT and APTT which were still slightly longer than in mice fed the AIN-93M diet. The concentration of vitamin K(3) supplied in the AIN-76 diet decreased to an undetectable level after gamma-irradiation, while the AIN-93M diet contained 240 microg/kg of vitamin K(1). These results indicate that the deaths of the germfree mice fed the gamma-irradiated AIN-76 diet were caused by vitamin K deficiency. Vitamin K deficiency may cause fatal degeneration of cardiac muscle cells.

Topics: Animal Feed; Animals; Food, Formulated; Gamma Rays; Germ-Free Life; Heart; Heart Ventricles; Hemorrhage; Longevity; Mice; Mice, Inbred BALB C; Myocardium; Partial Thromboplastin Time; Prothrombin Time; Sterilization; Survival Rate; Vitamin K 1; Vitamin K 3; Vitamin K Deficiency

The common bile duct-ligated (CBDL) rat, which is widely used as a model of human cirrhosis, rapidly develops secondary biliary cirrhosis (SBC) within 4 weeks. The CBDL rat shows poor viability, however, a detailed examination of the causes of its death has not been made. In this study, we investigated the outcome of bile duct ligation in detail and attempted to extend the life span of this model by feeding the animals a diet supplemented with nutrients. Survival rate, blood chemistry, blood cell counts, plasma levels of K vitamins and liver histology were compared among CBDL rats fed a standard diet and an enriched diet. Sham-operated rats were used as a control. Six out of 18 CBDL rats fed the standard diet died within 32 days of operation. The cause of death was massive internal hemorrhage in various organs or body cavities. All CBDL rats fed the enriched diet survived more than 31 days, but the viability of CBDL rats was not significant between those fed the standard diet and the enriched diet. The degree of anemia correlated significantly with the prolongation of prothrombin time. Plasma vitamin K1 levels in CBDL rats were significantly lower than those in sham-operated rats, but vitamin K2 levels were similar. We suggest that massive hemorrhage, which was the direct cause of death, is caused by the impairment of hemostasis resulting from vitamin K deficiency. The enriched diet with vitamin K nutritional supplements seemed to contribute to the prolongation of the life span of CBDL rats.

Topics: Animals; Disease Models, Animal; Hemorrhage; Hemostasis; Ligation; Liver Cirrhosis, Biliary; Male; Rats; Rats, Sprague-Dawley; Survival Rate; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency

To investigate the influence of liver lesions and vitamin K1 on bleeding after liver biopsy in patients with chronic renal failure and hepatitis virus infection.. Ninety-two renal transplant recipients on hemodialysis with hepatitis B or C virus infection received percutaneous liver biopsy. The severities of liver inflammation and fibrosis were evaluated by semi-quantitative technique. Thirty-four patients were given intramuscular injection of vitamin K1 before liver biopsy at the dose of 10 mg twice daily for 3 days.. The total incidence of bleeding after liver biopsy was 12.0% (11/92) in these patients, and the use of vitamin K1 did not significantly influence the incidence of bleeding, nor did the degree of liver lesions.. Bleeding occurred with a relatively high incidence after liver biopsy in patients with chronic renal failure and hepatitis virus B or C infection; vitamin K1 before liver biopsy could not reduce the incidence of bleeding, which is not correlated with the degree of liver lesions.

Topics: Biopsy; Hemorrhage; Humans; Incidence; Kidney Failure, Chronic; Liver; Vitamin K 1

The role of erythrocytes in realization of interrelation of the immunomodulating effects of lysozyme and naphthoquinones in normal and under conditions of acute hemorrhage was studied. Interaction of lysozyme and menadione at the level of intact erythrocytes and their stroma resulted in formation of highly efficient immunomodulating factors. The effect of such factors under conditions of acute hemorrhage was mediated by cytokines of the spleen macrophagael cells.

Topics: Acute Disease; Adjuvants, Immunologic; Animals; Drug Synergism; Erythrocytes; Hemorrhage; Leukocytes; Muramidase; Naphthoquinones; Rats; Rats, Wistar; Spleen; Vitamin K 1; Vitamin K 3

To assess compliance with the 2001 consensus guidelines of the American College of Chest Physicians (ACCP) regarding administration of vitamin K1 to reverse the anticoagulant effect of warfarin.. Retrospective chart review.. University teaching hospital.. Fifty-five adult inpatients who received both warfarin and vitamin K1 between September 2001 and January 2002.. The patients' medical records were evaluated; data were collected on patient demographics and on vitamin K1 dosage and route of administration, warfarin dosage, and international normalized ratio (INR) before and after vitamin K1 administration. Administration routes and 87 doses of vitamin K1 prescribed for the 55 patients were assessed for compliance with the ACCP guidelines. Administration routes were subcutaneous (40.2% of doses), intravenous (35.6%), oral (13.8%), and intramuscular (10.3%). The most frequently prescribed dose of vitamin K1 was 10 mg (32.2%), followed by 2 mg (21.8%) and 5 mg (18.4%). Rates of compliance with the ACCP guidelines categorized by INR value were as follows: INR below 5, 12.2%; INR 5-9, 27.8%; INR between 9 and 20, 26.7%; and INR above 20, 0%. Four patients had documented episodes of bleeding and received seven doses of vitamin K1. Twenty-six patients received fresh frozen plasma with vitamin K1. Overall compliance with ACCP-recommended doses and routes of vitamin K1 was only 17.2%.. The most frequently prescribed administration routes for vitamin K1 were subcutaneous and intravenous, indicating that the oral route is often not used as recommended. The vitamin K1 doses prescribed for reversal of warfarin anticoagulation were highly variable, and for most (83%) patients, the recommended guidelines were not followed. The clinical significance of noncompliance with the ACCP guidelines for vitamin K1 administration warrants further study.

Topics: Anticoagulants; Antifibrinolytic Agents; Dose-Response Relationship, Drug; Drug Administration Routes; Drug Antagonism; Drug Utilization Review; Female; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Retrospective Studies; Vitamin K 1; Warfarin

To determine the safety and efficacy of intravenously administered phytonadione (vitamin K1) in patients on routine oral warfarin anticoagulation.. This retrospective cohort study comprised adults who were taking warfarin, were not bleeding, and received intravenous phytonadione anticoagulation therapy before a diagnostic or therapeutic procedure between September 1, 1994, and March 31, 1996. The main outcome measures were adverse reactions to intravenously administered phytonadione, prothrombin-international normalized ratio time values, the incidence of bleeding and thrombosis after the procedure, and the time between the procedure and return to anticoagulation after resumption of warfarin treatment.. Two (1.9%) of the 105 patients studied had suspected adverse reactions to intravenous phytonadione (dyspnea and chest tightness during infusion in both). For the 82 patients who underwent a procedure, the median time from phytonadione to procedure onset was 27 hours (range, 0.7-147 hours), which was significantly less for patients receiving an initial phytonadione dose of more than 1 mg (P=.009). None had thromboembolism after surgery, although 2 (2.4%) of the 82 patients had procedure-associated major bleeding. For the 60 patients resuming warfarin therapy after a procedure, the median time to return to therapeutic anticoagulation was 4.1 days (range, 0.8-31.7 days) and was unaffected by the phytonadione dosage.. Intravenous phytonadione appears to be safe and is effective for semiurgent correction of long-term oral anticoagulation therapy before surgery. In small doses, it does not prolong the patient's time to return to therapeutic anticoagulation.

Topics: Administration, Oral; Adult; Aged; Anticoagulants; Cohort Studies; Hemorrhage; Humans; Injections, Intravenous; International Normalized Ratio; Middle Aged; Preoperative Care; Retrospective Studies; Time Factors; Treatment Outcome; Vitamin K 1; Warfarin

An elevated international normalized ratio (INR) increases the risk for major hemorrhage during warfarin therapy. Optimal management of patients with asymptomatic elevations in INR is hampered by the lack of understanding of the time course of INR decay after cessation of warfarin therapy.. To identify predictors of the rate of INR normalization after excessive anticoagulation.. Retrospective cohort study.. Outpatient anticoagulant therapy unit.. Outpatients with an INR greater than 6.0 were identified from August 1993 to September 1998. Patients in whom two doses of warfarin were withheld and a follow-up INR was obtained on the second calendar day were enrolled. No patient received vitamin K(1).. The INR was measured 2 days after an INR greater than 6.0 was recorded.. Of 633 study patients with an initial INR greater than 6.0, 232 (37%) still had an INR of 4.0 or greater after two doses of warfarin were withheld. Patients who required larger weekly maintenance doses of warfarin were less likely to have an INR of 4.0 or greater on day 2 (adjusted odds ratio per 10 mg of warfarin, 0.87 [95% CI, 0.79 to 0.97]). Other risk factors for having an INR of 4.0 or greater on day 2 included age (odds ratio per decade of life, 1.18 [CI, 1.01 to 1.38]), index INR (odds ratio per unit, 1.25 [CI, 1.14 to 1.37]), decompensated congestive heart failure (odds ratio, 2.79 [CI, 1.30 to 5.98]), and active cancer (odds ratio, 2.48 [CI, 1.11 to 5.57]).. Steady-state warfarin dose, advanced age, and extreme elevation in INR are risk factors for prolonged delay in return of the INR to within the therapeutic range. Decompensated congestive heart failure and active cancer greatly increase this risk.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Antifibrinolytic Agents; Cohort Studies; Female; Half-Life; Heart Failure; Hemorrhage; Humans; International Normalized Ratio; Logistic Models; Male; Neoplasms; Retrospective Studies; Risk Factors; Time Factors; Vitamin K 1; Warfarin

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Antifibrinolytic Agents; Cohort Studies; Female; Heart Failure; Hemorrhage; Humans; International Normalized Ratio; Male; Neoplasms; Retrospective Studies; Risk Factors; Time Factors; Vitamin K 1; Warfarin

The ability of oral vitamin K to eliminate all risk of vitamin K deficiency bleeding during the first three months of life was studied.. Babies (n=182,000) in the north of England judged well enough to be offered milk within 12 hours of birth were given 1 mg of phytomenadione (vitamin K(1)) suspended in a medium chain triglyceride oil by mouth at delivery between 1993 and 1998. The parents of those who were breastfed were given a further three doses to give to the baby once every two weeks after discharge.. Four breastfed babies developed late vitamin K deficiency bleeding. In two, staff failed to follow policy guidelines, and in two there was undiagnosed alpha(1) antitrypsin deficiency. Audit suggested that 93% of breastfed babies had all four doses, as advised.. An oral product that parents can administer themselves would be popular if licensed, but the total dose offered may need to be more than in this study if babies with undiagnosed liver disease are to be protected.

Topics: Administration, Oral; alpha 1-Antitrypsin Deficiency; Bottle Feeding; Breast Feeding; Chemoprevention; Confidence Intervals; Hemorrhage; Humans; Infant, Newborn; Medical Audit; Patient Compliance; Practice Guidelines as Topic; Risk Factors; Self Administration; Vitamin K 1; Vitamin K Deficiency

The anticoagulant and antithrombotic effects of YM-75466 (N-[4-[(1-acetimidoyl-4-piperidyl)oxy]phenyl]-N-[(7-amidino-2-naph thyl)methyl]sulfamoyl acetic acid monomethanesulfonate), a novel orally-active factor Xa (FXa) inhibitor, and warfarin were compared in mice. Both agents were orally administered in all studies. In ex vivo studies, the peak effects of YM-75466 occurred 1 hr after administration while the peak of warfarin activity occurred 18 hr after administration. At each peak, both YM-75466 and warfarin prolonged coagulation time dose-dependently. The dose response curve of warfarin for prothrombin time was steeper than that of YM-75466. In a thromboplastin-induced thromboembolism model, administration of 30 mg/kg YM-75466 or 3 mg/kg warfarin significantly improved the lethality ratio. In blood loss studies, YM-75466 did not increase blood loss from the tail even at 30 mg/kg, while warfarin markedly increased blood loss at 3 mg/kg. Agents that interfere with warfarin action did not interfere with YM-75466 action. In conclusion, this study shows that YM-75466 has advantages over warfarin: i) rapid onset of anticoagulant activity, ii) wide therapeutic range, iii) little effect on bleeding and iv) lack of drug interaction with agents that interfere with warfarin. These results suggest that YM-75466 may be promising as a novel oral anticoagulant agent.

Topics: Administration, Oral; Analgesics, Non-Narcotic; Animals; Anti-Bacterial Agents; Anticoagulants; Anticonvulsants; Antifibrinolytic Agents; Blood Coagulation; Carbamazepine; Cimetidine; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Interactions; Erythromycin; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Male; Mice; Mice, Inbred ICR; Partial Thromboplastin Time; Phenytoin; Piperidines; Prothrombin Time; Rifampin; Sulfonamides; Thromboembolism; Thromboplastin; Vitamin K 1; Warfarin

Topics: Administration, Oral; Anticoagulants; Antifibrinolytic Agents; Hemorrhage; Humans; Injections, Intravenous; Vitamin K 1; Warfarin

Rats received a single subcutaneous dose of the inflammatory agent carrageenin on the top of the skull, followed by oral acenocoumarol for 3 days; in every case, an extensive haematoma was observed on the skull on day 4. The capillary resistance on the depilated dorsal skin was significantly reduced by this combined inflammatory + anticoagulant treatment. Haematoma development was not inhibited by cortisone, non-steroidal anti-phlogistics (piroxicam, proquazone) or benzopyrone derivatives (hesperidin methylchalcone, oligomeric procyanidin). On pretreatment with vitamin K1 for 1 day, followed by daily treatment for 3 days, no haematoma was observed.

Topics: Acenocoumarol; Animals; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Capillaries; Carrageenan; Chromones; Coumarins; Disease Models, Animal; Female; Hematoma; Hemorrhage; Male; Rats; Rats, Inbred Strains; Steroids; Vascular Resistance; Vitamin K 1

Topics: Administration, Oral; Hemorrhage; Humans; Infant, Newborn; Infant, Premature; Prothrombin Time; Risk; Vitamin K 1

Cefoperazone, a beta-lactam antibiotic with a methylthiotetrazole side chain, has been reported infrequently to cause hypoprothrombinemia and hemorrhage. We retrospectively analyzed the records of 80 patients who had been given this drug for more than 72 hours. Nine patients received vitamin K1 (phytonadione) prophylaxis and had no evidence of hemorrhage. Of the remaining 71 patients, 32 had prothrombin times measured; 14 of them had hypoprothrombinemia. Prothrombin times ranged from 14.8 to 97.3 seconds at a mean of 6.2 days after initiation of therapy. Seven of the 14 patients had clinically significant hemorrhage and five required transfusions. Two patients with clinically evident hemorrhage died during or immediately after cefoperazone therapy. Prothrombin times rapidly returned to normal in all patients treated with phytonadione. We believe hypoprothrombinemia is a more common complication of cefoperazone therapy than is generally acknowledged, and is preventable. Unless clinically contraindicated, we recommend that all patients treated with cefoperazone receive phytonadione prophylaxis.

Topics: Aged; Cefoperazone; Costs and Cost Analysis; Hemorrhage; Humans; Hypoprothrombinemias; Middle Aged; Prothrombin Time; Retrospective Studies; Time Factors; Vitamin K 1

Antibiotic therapy, using penicillins or cephalosporins, is frequently required in patients on maintenance hemodialysis. Points to consider are dose adjustment for drugs which are excreted via the kidney, drug dialysability, and cumulation with frequent occurrence of side reactions, neurotoxicity and bleeding being the clinically most important ones. For third-generation cephalosporins with N-methylthiotetrazole side chain, impaired intrahepatic vitamin K metabolism may cause problems of hemostasis which can be avoided by dose adjustment and prophylactic administration of vitamin K1.

Topics: Bacterial Infections; Body Weight; Cephalosporins; Dose-Response Relationship, Drug; Drug Administration Schedule; Hemorrhage; Humans; Kidney Failure, Chronic; Kinetics; Penicillin Resistance; Penicillins; Renal Dialysis; Tetrazoles; Vitamin K 1

Patients on oral anticoagulants who present to the emergency department following trauma pose a special problem. Careful attention must be given to exclude any sites of overt or occult bleeding, particularly in the CNS, where there may be no external evidence of injury. A PT or thrombotest should be obtained as minimum laboratory workup in all cases. In specific situations, emergency reversal of anticoagulation must be undertaken.

Topics: Anticoagulants; Cardiovascular Diseases; Emergencies; Hemorrhage; Humans; Risk; Vitamin K 1; Wounds and Injuries

In a patient taking oral anticoagulants, the complaint of pharyngeal pain, a change in the voice, dysphagia, respiratory difficulty, or a neck mass should prompt a thorough investigation to rule out hemorrhage into the upper airway. This case report describes an anticoagulated patient who experienced precipitous hemorrhagic upper airway obstruction. She was successfully treated with tracheostomy, plasma infusion, and parenteral vitamin K1.

Topics: Airway Obstruction; Emergencies; Female; Hematoma; Hemorrhage; Humans; Middle Aged; Respiratory Tract Diseases; Thrombophlebitis; Tracheotomy; Vitamin K 1; Warfarin

The effects of vitamin K on hemorrhagic death induced by dietary butylated hydroxytoluene (BHT) were studied. Male Sprague-Dawley rats were given BHT or two phenolic antioxidants (2,4,6-tri-tert-butylphenol and 2,5-di-tert-butylhydroquinone) in combination with a 24% casein basal diet. The levels of the phenols were chosen to nearly equal LD50 (40 days). Hemorrhagic death, hemorrhage and a decrease in prothrombin index caused by 1.20% BHT were prevented by simultaneously adding phylloquinone (0.68 mumole/kg/day). Phylloquinone also inhibited the effect of the related phenolic antioxidants. Ten nanomoles of phylloquinone injected into the femoral vein on day 3 of feeding 1.2% BHT increased the prothrombin concentration from 28% of normal to 100% of normal within 18 to 24 hours. Phylloquinone oxide also prevented hypoprothrombinemia due to BHT. These results suggest that BHT-induced hemorrhagic death may be caused by direct and/or indirect vitamin K deficiency, and its mechanism may be different from those of warfarin.

Topics: Animals; Antioxidants; Butylated Hydroxytoluene; Cresols; Diet; Dose-Response Relationship, Drug; Hemorrhage; Hydroquinones; Hypoprothrombinemias; Injections, Intravenous; Male; Phenols; Prothrombin Time; Rats; Vitamin K 1

Successful prevention of the progression of incipient hemorrhagic skin necrosis by timely administration of vitamin K1 in a woman treated with phenprocoumon is presented. From a critical review of the literature strong evidence emerges that coumarin necrosis does only occur in cases with severe initial drug induced hypocoagulability. Non- recognition thusfar of its importance is due to insufficient knowledge of the biological activities of thromboplastin preparations presently used in the laboratory control of oral anticoagulation. All well documented cases with apparently adequate Quick values were monitored with Faktor VIII insensitive thromboplastin. Therefore, such preparations should no longer be used in anticoagulant control.

Topics: 4-Hydroxycoumarins; Female; Hemorrhage; Humans; Middle Aged; Necrosis; Phenprocoumon; Skin; Skin Diseases; Thromboplastin; Vitamin K 1

Topics: Animals; Blood Coagulation; Breast Feeding; Chickens; Female; Fish Products; Hemorrhage; History, 20th Century; Humans; Infant; Medicago sativa; Mycobacterium tuberculosis; Naphthoquinones; Plant Extracts; Pregnancy; Sterols; United States; Vitamin K; Vitamin K 1; Vitamins

Topics: Aged; Chronic Disease; Cystitis; Cystoscopy; Estrogens, Conjugated (USP); Female; Hematuria; Hemorrhage; Humans; Lymphoma, Non-Hodgkin; Urinary Bladder Neoplasms; Vitamin K 1

Topics: Abnormalities, Drug-Induced; Animals; Bone and Bones; Cleft Lip; Cleft Palate; Dose-Response Relationship, Drug; Embryo Implantation; Embryo, Mammalian; Female; Fetal Death; Hemorrhage; Mice; Mice, Inbred Strains; Placenta Diseases; Pregnancy; Prothrombin Time; Sodium Chloride; Time Factors; Vitamin K; Vitamin K 1; Warfarin

Topics: Blood Coagulation Disorders; Czechoslovakia; Drug Utilization; Hemorrhage; Humans; Vitamin K; Vitamin K 1

Topics: Administration, Oral; Animals; Anticoagulants; Blood Coagulation; Coumarins; Hemorrhage; Lethal Dose 50; Rats; Vitamin K 1

Topics: Acute Disease; Age Factors; Anticoagulants; Female; Follow-Up Studies; Hemorrhage; Humans; Male; Sex Factors; Thromboembolism; Time Factors; Vitamin K 1

Topics: Female; Hemorrhage; Humans; Infant, Newborn; Infant, Newborn, Diseases; Pregnancy; Vitamin K 1

Topics: Aged; Ambulatory Care; Anticoagulants; Cardiovascular Diseases; Coumarins; Female; Hemorrhage; Humans; Male; Middle Aged; Vitamin K; Vitamin K 1

Topics: Bile; Bile Duct Neoplasms; Biliary Tract; Biliary Tract Diseases; Cholangiography; Cholelithiasis; Cholestasis; Contrast Media; Diagnosis, Differential; Female; Gallstones; Hemorrhage; Hepatitis; Humans; Liver Diseases; Male; Methods; Neoplasm Metastasis; Pancreatic Neoplasms; Peritonitis; Prothrombin Time; Vitamin K 1

Topics: Administration, Oral; Adult; Aged; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Coumarins; Hemorrhage; Humans; Male; Suicide; Vitamin K 1; Vitamin K Deficiency

Topics: Aged; Coumarins; Diazepam; Drug Synergism; Female; Glutethimide; Hemorrhage; Humans; Male; Middle Aged; Oxyphenbutazone; Phenobarbital; Vitamin K 1

Topics: Blood Cell Count; Blood Coagulation Disorders; Blood Coagulation Tests; Female; Gastrointestinal Hemorrhage; Hemorrhage; Hemostasis; Humans; Liver Cirrhosis; Liver Function Tests; Menorrhagia; Prothrombin Time; Vitamin K 1

Topics: Alcohols; Animals; Blood Coagulation; Blood Coagulation Tests; Dogs; Edema; Estrogens; Female; Hemorrhage; Hemostatics; Male; Malonates; Oxalates; Vitamin K 1; Wounds and Injuries

Topics: Blood Coagulation Factors; Coumarins; Hemorrhage; Humans; Phenylbutazone; Prothrombin Time; Purpura, Thrombocytopenic; Vitamin K 1; Warfarin

Topics: Anticoagulants; Diagnosis, Differential; Duodenal Ulcer; Gastrointestinal Hemorrhage; Hematoma; Hemorrhage; Humans; Intestinal Obstruction; Intestine, Small; Intestines; Radiography; Toxicology; Vitamin K 1

Topics: Antacids; Anti-Bacterial Agents; Antibiotics, Antitubercular; Cathartics; Diet; Diet Therapy; Gastric Lavage; Gastrointestinal Hemorrhage; Hemorrhage; Hepatic Encephalopathy; Humans; Parasympatholytics; Pituitary Hormones; Pituitary Hormones, Posterior; Rest; Serum Albumin; Shock; Shock, Hemorrhagic; Statistics as Topic; Tranquilizing Agents; Vitamin K; Vitamin K 1; Water-Electrolyte Balance

Topics: Adolescent; Hemorrhage; Humans; Surgery, Oral; Vitamin K 1

Topics: Biliary Tract; Female; Hemorrhage; Hemorrhagic Disorders; Humans; Liver Diseases; Postpartum Hemorrhage; Postpartum Period; Vitamin K 1

Topics: Aminocaproates; Aminocaproic Acid; Anemia; Antineoplastic Agents; Blood Transfusion; Busulfan; Central Nervous System; Fever; Hemorrhage; Humans; Leukemia; Mechlorethamine; Mercaptopurine; Nervous System; Physiology; Prednisolone; Thiotepa; Vitamin K 1

Topics: Child; Hemorrhage; Humans; Hypoprothrombinemias; Infant; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature; Infant, Premature, Diseases; Vitamin K; Vitamin K 1

Topics: Antifibrinolytic Agents; Blood Coagulation Tests; Coumarins; Hemorrhage; Hemostatics; Humans; Prothrombin; Vitamin K; Vitamin K 1

Topics: Antifibrinolytic Agents; Ferula; Hemorrhage; Hemostatics; Heparin Antagonists; Vitamin K; Vitamin K 1

Topics: Accidents; Anticoagulants; Antifibrinolytic Agents; Coumarins; Hemorrhage; Humans; Thrombosis; Vitamin K; Vitamin K 1

Topics: Anticoagulants; Antidotes; Coumarins; Female; Genital Diseases, Female; Hemorrhage; Humans; Thrombophlebitis; Vitamin K; Vitamin K 1

Topics: Antifibrinolytic Agents; Coumarins; Hemorrhage; Humans; Naphthoquinones; Phenprocoumon; Retinoids; Vitamin K; Vitamin K 1

Topics: Antifibrinolytic Agents; Coumarins; Dicumarol; Hemorrhage; Naphthoquinones; Poisoning; Retinoids; Vitamin K; Vitamin K 1

Topics: Hemorrhage; Humans; Hypoprothrombinemias; Prothrombin; Vitamin K 1