vitamin-k-semiquinone-radical and Necrosis

Vitamin C (VC) and vitamin K(3) (VK(3)) administered in a VC:VK(3) ratio of 100:1 exhibit synergistic antitumor activity and preferentially kill tumor cells by autoschizis, a novel type of necrosis characterized by exaggerated membrane damage and progressive loss of organelle-free cytoplasm through a series of self-excisions. During this process, the nucleus becomes smaller, cell size decreases one-half to one-third of its original size, and most organelles surround an intact nucleus in a narrow rim of cytoplasm. While the mitochondria are condensed, tumor cell death does not result from ATP depletion. However, vitamin treatment induces a G(1)/S block, diminishes DNA synthesis, increases H(2)O(2) production, and decreases cellular thiol levels. These effects can be prevented by the addition of catalase to scavenge the H(2)O(2). There is a concurrent 8- to 10-fold increase in intracellular Ca(2+) levels. Electrophoretic analysis of DNA reveals degradation due to the caspase-3-independent reactivation of deoxyribonuclease I and II (DNase I, DNase II). Redox cycling of the vitamins is believed to increase oxidative stress until it surpasses the reducing ability of cellular thiols and induces Ca(2+) release, which triggers activation of Ca(2+)-dependent DNase and leads to degradation of DNA. Recent experiments indicate that oral VC:VK(3) increases the life-span of tumor-bearing nude mice and significantly reduces the growth rate of solid tumors without any significant toxicity by reactivating DNase I and II and inducing autoschizis. This report discusses the mechanisms of action employed by these vitamins to induce tumor-specific death by autoschizis.

Topics: Animals; Antioxidants; Ascorbic Acid; Cell Death; Humans; Necrosis; Neoplasms; Oxidative Stress; Vitamin K

We report the case of a 57-year old woman whose severe protein C deficiency was revealed soon after oral anticoagulants were introduced into her treatment. Two previous episodes of deep leg vein thrombosis followed by a third episode with suspicion of embolus migration had led to treatment with heparin later replaced by oral anticoagulants. On the 4th day of anticoagulant therapy, she developed skin necrosis of the left calf. A protein C assay showed severe deficiency (19% level as compared with the 70-120% normal levels). The main causes of acquired protein C deficiency were excluded. The first results of a family study demonstrated moderate protein C deficiency in a 30-year old, asymptomatic daughter.

Topics: Adult; Anticoagulants; Deficiency Diseases; Female; Humans; Leg; Middle Aged; Necrosis; Protein C Deficiency; Skin; Thromboembolism; Vitamin K

Oral anticoagulants are used extensively, although their risks are not always fully recognized. The prophylaxis of venous thrombosis after hip surgery, the prevention of deep venous thrombosis and pulmonary emboli after an acute episode of these, the prevention of arterial emboli from the heart in patients at risk, and the prophylaxis of thrombosis in patients with congenital deficiency of antithrombin III, protein C, or protein S are some of the indications for oral anticoagulant use. Warfarin sodium is contraindicated in pregnancy, however. The recommended prothrombin time is 1 1/2 to two times control, lower than previously. The major risk of oral anticoagulant therapy, bleeding, is treated with vitamin K or plasma, depending on its severity. Warfarin necrosis and the "purple-toe" syndrome are seen more frequently than realized.

Topics: Absorption; Administration, Oral; Biological Availability; Drug Interactions; Hemorrhage; Hip Fractures; Humans; Myocardial Infarction; Necrosis; Postoperative Complications; Protein Binding; Prothrombin Time; Pulmonary Embolism; Thrombophlebitis; Thrombosis; Vitamin K; Warfarin

The major clinical importance of plasma protein C is attested to by the strong association between inherited protein C deficiencies of half normal levels and recurrent venous thromboembolic disease. Homozygous protein C deficient individuals do not survive beyond infancy without continuous therapeutic intervention. The spectrum of protein C deficiency is becoming broader and includes patients with both abnormal molecules and half normal levels of functionally active molecules. Rarely, a few young adults with thrombosis have been identified with protein C levels below 25%. Studies of protein C activity have been hampered until the very recent developments of functional assays of plasma protein C. Application of these assays to a wide variety of clinical situations involving thrombotic complications is just beginning and may lead to an explosive proliferation of new data that should prove most fascinating and give much further insight into the contributions of protein C in the regulation of thrombosis.

Topics: Anticoagulants; Blood Coagulation Factors; Disseminated Intravascular Coagulation; Glycoproteins; Half-Life; Humans; Infant, Newborn; Liver Diseases; Male; Necrosis; Protein C; Pulmonary Embolism; Purpura; Skin Diseases; Thromboembolism; Thrombophlebitis; Vitamin K

Topics: Adult; Anti-Bacterial Agents; Fluorouracil; Hemangioma; Hepatic Artery; Humans; Ligation; Liver Cirrhosis; Liver Function Tests; Liver Neoplasms; Male; Necrosis; Neoplasm Metastasis; Serum Albumin; Vitamin K

Anticoagulant-related nephropathy (ARN), a significant but frequently undiagnosed problem in patients receiving anticoagulation, is found to be associated with increased renal morbidity and all-cause mortality. While ARN is mainly associated with warfarin use, recent case reports suggest that it may also occur in patients taking direct oral anticoagulants (DOAC). We report a patient who had a history of alcoholic liver cirrhosis and paroxysmal atrial fibrillation, and received dabigatran 110 mg twice daily for 1 year. He presented with gross hematuria and severe acute kidney injury with an international normalized ratio of 4.09. Dabigatran was stopped and he was put on temporary hemodialysis support. His renal function gradually improved when the hematuria subsided. Renal biopsy later confirmed the presence of red blood cell casts inside the renal tubules with features of IgA nephropathy. Finally, his renal function returned back to baseline level. As DOAC has been increasingly used nowadays for the treatment of various thromboembolic diatheses, regular monitoring of renal function is warranted, especially in patients with underlying glomerular diseases and coagulopathy such as chronic liver diseases.

Topics: Acute Kidney Injury; Administration, Intravenous; Antifibrinolytic Agents; Antithrombins; Dabigatran; Humans; Kidney Tubules; Liver Cirrhosis; Male; Middle Aged; Necrosis; Severity of Illness Index; Treatment Outcome; Vitamin K

Patients treated by vitamin K antagonists (VKA) represent 1% of the population in France. We report a case of atypical necrotic leg ulcers induced by VKA.. A 84-year-old woman was referred to our dermatology department because of necrotic leg ulcers that developed for the past 5weeks, and appeared spontaneously after the introduction of a VKA, fluindione. The etiological assessment was non contributive, in particular the search for thrombophilic factors. The skin biopsy found an aspect compatible with pyoderma gangrenosum. The outcome was favorable after discontinuing the fluindione and the switch to apixaban. A complete healing was obtained in 5months.. We report an original case of necrotic leg ulcers induced by VKA without deficit of protein C or S, with a pyoderma like histology. Reported cases of ulcers induced by VKA are uncommon and the physiopathology is not well known. The involvement of VKA should be evoked in case of necrotic leg ulcer without specific etiology found.

Topics: 4-Hydroxycoumarins; Aged, 80 and over; Female; Humans; Indenes; Leg Ulcer; Necrosis; Protein C Deficiency; Protein S Deficiency; Pyoderma Gangrenosum; Vitamin K

Skin necrosis with vitamin k antagonists are rare. They affect more frequently middle-aged and obese women, often within 10 days after initiating of treatment. They occur most often in a context of thrombophilia.. An 18-year-old obese woman was treated with heparin and fluindione for a lower limb deep venous thrombosis. On day 5, the patient presented fever and skin necrosis, which extended rapidly. We identified an activated protein C resistance and a major inflammatory syndrome related to Mycoplasma pneumoniae infection. The outcome was favorable after discontinuation of the fluindione, introduction of heparin and vitamin K, despite amputation of a toe.. Skin necrosis is due to a transient hypercoagulable state during the initiation of vitamin K antagonist treatment due to an imbalance between pro- and anticoagulant factors. In our case, it was caused by an activated protein C resistance and an inflammatory syndrome.

Topics: 4-Hydroxycoumarins; Adolescent; Amputation, Surgical; Anticoagulants; Breast; Coagulants; Female; Hallux; Heparin; Humans; Indenes; Necrosis; Phenindione; Skin; Vitamin K

Vitamin K antagonists are widely used in thromboembolic diseases. Hemorrhagic complications related to drug overdose represent their main side effect. We report a rare side effect, a severe and unexpected type of skin vasculitis - necrotic leg ulcer - induced by vitamin K antagonist.. A 63-year-old female with a history of diabetes developed hyperalgesic necrotic ulcerations on the lower limbs one month after starting an acenocoumarol-based treatment for ischemic heart disease. Histological examination revealed lymphocytic vasculitis with fibrinoid necrosis. Etiological explorations searching for vasculitis were negative. In the absence of a precise etiology, drug-induced ulcer was suspected. Low molecular weight heparin was prescribed to replace acenocoumarol. The lesions slowly resolved with topical treatment.. The chronological criteria and the negativity of etiological explorations allowed the diagnosis of vitamin K antagonist-induced necrotic skin ulcer. Clinicians should be aware of this rare complication induced by oral anticoagulants because of its practical therapeutic implications. This is the first case of necrotic leg ulcer induced by acenocoumarol corresponding histologically to necrotising lymphocytic vasculitis.

Topics: Acenocoumarol; Anticoagulants; Diabetes Mellitus, Type 2; Drug Substitution; Female; Heparin, Low-Molecular-Weight; Humans; Hyperalgesia; Leg Ulcer; Middle Aged; Necrosis; Vasculitis; Vitamin K

Vitamin K antagonists (VKAs) are widely used in thromboembolic diseases. We report five cases of necrotic leg ulcers having a particularly severe course and in which withdrawal of VKA treatment alone enabled healing.. Five patients presented with necrotic leg ulcers clinically evocative of necrotic angiodermatitis or vasculitis. Histological features were variable, including inconstantly inflammatory lesions (leukocytoclastic vasculitis) and microthrombosis. None of the patients had laboratory signs of autoimmune disease. Healing occurred in all patients only after withdrawal of VKA therapy (fluindione or acenocoumarol). Associated vascular diseases included superficial venous, distal arterial insufficiency and postphlebitic disease. In three cases, thrombotic factors were observed: hyperhomocysteinaemia or heterozygous Factor V Leiden mutation.. Although the causative role of VKAs is based solely on chronological criteria, this potential side effect deserves publication because of its practical therapeutic consequences. The physiopathological mechanisms accounting for the role of VKAs, including immunoallergic phenomena and, above all, microcirculatory thrombotic processes, are hypothetical and not universally accepted.

Topics: Acenocoumarol; Activated Protein C Resistance; Aged; Aged, 80 and over; Anticoagulants; Diabetic Angiopathies; Factor V; Female; Humans; Hyperhomocysteinemia; Leg Ulcer; Male; Necrosis; Phenindione; Polyarteritis Nodosa; Postoperative Complications; Purpura; Thrombophilia; Varicose Ulcer; Vasculitis, Leukocytoclastic, Cutaneous; Vitamin K

Topics: Drug Eruptions; Fatal Outcome; Female; Humans; Infant, Extremely Low Birth Weight; Infant, Newborn; Injections, Intramuscular; Leg Ulcer; Male; Necrosis; Syndrome; Treatment Outcome; Vitamin K

Topics: Aged, 80 and over; Anticoagulants; Cardiac Surgical Procedures; Coumarins; Extremities; Gangrene; Heparin; Humans; International Normalized Ratio; Male; Middle Aged; Necrosis; Thrombocytopenia; Vitamin K; Warfarin

Necrosis, as opposed to apoptosis, is recognized as a nonspecific cell death that induces tissue inflammation and is preceded by cell edema. In non-neuronal cells, the latter has been explained by defective outward pumping of Na(+) caused by metabolic depletion or by increased Na(+) influx via membrane transporters. Here we describe a novel mechanism of swelling and necrosis; namely the influx of Na(+) through oxidative stress-activated nonselective cation channels. Exposure of liver epithelial Clone 9 cells to the free-radical donors calphostin C or menadione induced the rapid activation of an approximately 16-pS nonselective cation channel (NSCC). Blockage of this conductance with flufenamic acid protected the cells against swelling, calcium overload, and necrosis. Protection was also achieved by Gd(3+), an inhibitor of stretch-activated cation channels, or by isosmotic replacement of extracellular Na(+) with N-methyl-D-glucamine. It is proposed that NSCCs, which are ubiquitous although largely inactive in healthy cells, become activated under severe oxidative stress. The ensuing influx of Na(+) initiates a positive feedback of metabolic and electrolytic disturbances leading cells to their necrotic demise.

Topics: Animals; Calcium; Calcium Channel Blockers; Cations; Cells, Cultured; Electric Conductivity; Extracellular Space; Free Radicals; Gadolinium; Ion Channels; Liver; Meglumine; Naphthalenes; Necrosis; ortho-Aminobenzoates; Oxidative Stress; Rats; Sodium; Vitamin K

Calciphylaxis is a rare disorder of small-vessel calcification and cutaneous infarction associated with chronic renal failure. Rare cases of calciphylaxis not associated with chronic renal failure have been reported with breast cancer, hyperparathyroidism, and alcoholic cirrhosis. To our knowledge, we report the first case of calciphylaxis without chronic renal failure associated with cholangiocarcinoma and the first attempt to treat calciphylaxis with vitamin K. A 56-year-old woman presented with necrotic leg ulceration. She was treated initially with low-molecular-weight heparin, with no effect. A coagulation work-up showed vitamin K deficiency. During vitamin K therapy, the patient had fulminant progression of the calciphylaxis. She died, and an autopsy showed metastatic cholangiocarcinoma. Thrombosis and protein C deficiency have been implicated in the pathophysiology of calciphylaxis. Functional protein C deficiency may be one of several factors contributing to the development of calciphylaxis. Vitamin K therapy was ineffective in our patient and may have been detrimental.

Topics: Adenocarcinoma; Anticoagulants; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Biopsy; Calciphylaxis; Cholangiocarcinoma; Fatal Outcome; Female; Heparin, Low-Molecular-Weight; Humans; Leg Ulcer; Liver Neoplasms; Lung Neoplasms; Middle Aged; Necrosis; Neoplasms, Multiple Primary; Prognosis; Sepsis; Vitamin K; Vitamin K Deficiency

Intracellular Na+ accumulation has been shown to contribute to hepatocyte death caused by anoxia or oxidative stress. In this study we have investigated the mechanism by which Na+ overload can contribute to the development of cytotoxicity. ATP depletion in isolated hepatocytes exposed to menadione-induced oxidative stress or to KCN was followed by Na+ accumulation, loss of intracellular K+, and cell swelling. Hepatocyte swelling occurred in two phases: a small amplitude swelling (about 15% of the initial size) with preservation of plasma membrane integrity and a terminal large amplitude swelling associated with cell death. Inhibition of Na+ accumulation by the use of a Na+-free medium prevented K+ loss, cell swelling, and cytotoxicity. Conversely, blocking K+ efflux by the addition of BaCl2 did not influence Na+ increase and small amplitude swelling, but greatly stimulated large amplitude swelling and cytotoxicity. Menadione or KCN killing of hepatocytes was also enhanced by inducing cell swelling in an hypotonic medium. However, increasing the osmolarity of the incubation medium did not protect against large amplitude swelling and cytotoxicity, since stimulated Na+ accumulation and K+ efflux. Altogether these results indicate that the impairment of volume regulation in response to the osmotic load caused by Na+ accumulation is critical for the development of cell necrosis induced by mitochondrial inhibition or oxidative stress.

Topics: Animals; Buffers; Hypertonic Solutions; Intracellular Fluid; Liver; Male; Necrosis; Osmosis; Potassium; Potassium Cyanide; Rats; Rats, Wistar; Sodium; Vitamin K

Simian Virus 40 Large T-antigen expressed in NIH3T3 cells increases p53 level and interacts with this tumor suppressor to form large nuclear complexes. We show here that T-antigen sensitizes NIH3T3 cells to low doses of the oxidative stress inducer menadione. This oxidant increased p53 accumulation and disrupted p53/T-antigen interaction, but not T-antigen/pRb, T-antigen/Hsc70 and p53/Hsc70 complexes; a phenomenon inhibited by the anti-oxidant N-acetyl-cysteine. Analysis of several p53 downstream gene products revealed that the level of Fas receptor, which was sharply reduced by T-antigen expression, was drastically increased in response to menadione treatment. Menadione also induced a T-antigen dependent cleavage of Fas ligand. Analysis performed with Fas receptor antagonist antibody and metalloproteinases inhibitor revealed that menadione triggers a Fas-dependent death of a fraction of T-antigen expressing cells. This Fas pathway does not activate caspase 8 or 3, probably because of the inhibition induced by T-antigen, and leads to a necrotic cell death which contributes at least in part to the hypersensitivity of T-antigen transformed cells to oxidative stress.

Topics: 3T3 Cells; Acetylcysteine; Animals; Antibodies; Antigens, Polyomavirus Transforming; Antioxidants; Apoptosis; Cell Survival; Cell Transformation, Neoplastic; fas Receptor; Mice; Necrosis; Oxidative Stress; Reactive Oxygen Species; Simian virus 40; Tumor Suppressor Protein p53; Vitamin K

Exposure to very intense ionizing irradiation produces acute tissue sequelae including inflammation, pain, and swelling that often results in tissue fibrosis and/or necrosis. Acute tissue necrosis occurs in hours when sufficiently rapid damage to membrane lipids and proteins leads to altered membrane structure, disrupting the vital electrochemical diffusion barrier necessary for cell survival. This damage mechanism is thought to underlie the interphase death of lethally irradiated postmitotic cells such as neurons, but it has also been implicated in the rapid cell death of lymphocytes and acute vascular changes due to capillary epithelium dysfunction. It is not known whether sealing of radiation-permeabilized cell membranes will prolong survival of lethally irradiated cells or perhaps lead to repair of damaged nucleic acids. The purpose of this study is to begin to address the first question.

Topics: Cell Membrane; Cell Membrane Permeability; Ethylenediamines; Gamma Rays; Humans; In Vitro Techniques; Lipid Peroxidation; Lymphocytes; Necrosis; Oxidation-Reduction; Surface-Active Agents; Vitamin K

This study evaluated the action of menadione on cell proliferation and integrity of the rat pancreatic acinar cell line, AR4-2J. Menadione at 1-20 microM dose- and time-dependently inhibited cell proliferation of AR4-2J cells. In contrast, a high concentration of menadione (100 microM) caused rapid cell death (> 90% of cells took up trypan blue within 4-h). While the high concentration of menadione (100 microM) induced DNA smear in electrophoresis indicative of necrosis, lower concentrations (10-20 microM) induced a DNA ladder indicative of apoptosis. Similar results were obtained using a DNA fragmentation ELISA. Glutathione (1 mM), the calcium chelator EGTA (500 microM), and the cysteine protease inhibitor NCO-700 (5 mM) partly inhibited the effect of 1-10 microM menadione on cell proliferation and DNA fragmentation. Menadione at 1-20 microM induced wild-type P53, whereas the 100 microM menadione had a minor effect on wild-type P53. It is concluded that menadione induced necrosis at high concentrations and apoptosis at low concentrations in AR4-2J cells. Apoptosis induced by lower concentrations of menadione may be mediated by wild-type P53, intracellular calcium, and mechanisms which decrease the intracellular concentration of reduced glutathione.

Topics: Animals; Apoptosis; Blotting, Western; Cell Division; DNA Fragmentation; Dose-Response Relationship, Drug; Electrophoresis, Polyacrylamide Gel; Necrosis; Pancreas; Pancreatic Neoplasms; Rats; Tumor Cells, Cultured; Vitamin K

Inducibility of oxidative stress in rat liver in vivo by menadione-associated redox cycling activation under redox enzyme modulating conditions was examined by monitoring hepatocyte injury and 8-hydroxydeoxyguanosine (8-OHdG) levels of liver DNA. In addition, the treatment-associated liver tumor initiating activity was assessed in terms of development of gamma-glutamyl-transpeptidase (GGT)- and glutathione S-transferase placental form (GST-P)-positive foci and hyperplastic nodules. With or without following menadione treatment (50 mg/kg, i.g.), redox enzyme modulations of increased cytochrome P450 reductase activity induced by phenobarbital (PB)-Na (100 mg/kg, i.p. for 5 days), inhibition of DT-diaphorase by dicumarol (25 mg/kg, i.p.) and depletion of glutathione by phorone (200 mg/kg, i.p.), with or without further supplement of iron EDTA-Na-Fe(III) (70 mg/kg, i.p.), caused both substantial hepatocyte necrosis and 8-OHdG production in Fischer 344 male rats. Subsequent feeding with a 0.05% PB diet for 64 weeks resulted in slightly increased development of GGT-positive foci but not GST-P positive lesions or hyperplastic nodules, suggesting a lack of tumor-initiating activity of the oxidative DNA damage associated with redox enzyme modulations with or without menadione.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Body Weight; Cytochrome Reductases; Deoxyguanosine; Dicumarol; DNA; DNA Damage; gamma-Glutamyltransferase; Glutathione; Iron; Ketones; Liver; Liver Neoplasms, Experimental; Male; NAD(P)H Dehydrogenase (Quinone); Necrosis; Neoplasms, Experimental; Organ Size; Oxidation-Reduction; Phenobarbital; Quinone Reductases; Rats; Rats, Inbred F344; Time Factors; Vitamin K

An elderly woman who had been receiving long-term oral anticoagulant therapy developed skin and subcutaneous fat necrosis on five repeated occasions of extreme hypocoagulability, associated with coinciding periods of congestive cardiac failure. In each episode, the skin necrosis developed within days after the prothrombin time (as determined with Thrombotest) exceeded 200 s (International Normalized Ratio greater than 5.4). Widespread thrombosis in the subcutaneous vasculature and interstitial bleeding, as observed in a skin biopsy specimen, were consistent with a diagnosis of coumarin necrosis. On two occasions, an acquired functional protein C deficiency was present. It is hypothesized that an imbalance between anticoagulant and procoagulant vitamin K-dependent factors contributed to the pathogenesis of coumarin-induced skin necrosis. This imbalance was related to repeated periods of congestive heart failure.

Topics: Biopsy; Blood Coagulation Factors; Coumarins; Female; Humans; Middle Aged; Necrosis; Protein C Deficiency; Prothrombin Time; Skin; Vitamin K

The introduction of a new batch of feed to 400 pigs aged five to eight weeks resulted in 38 deaths and further morbidity associated with multiple haemorrhages. Signs abated within two days of withdrawal of the feed. Widespread haemorrhages were present in many tissues including the pancreas. Additional pancreatic lesions comprised focal necrosis, atrophy and fibrosis of exocrine tissue. The condition was reproduced experimentally in pigs and vitamin K protected mice against the injurious effects of the feed. The cause was not determined but it is speculated that more than one toxic factor and an imbalance of nutritional factors may have been present in the diet.

Topics: Animal Feed; Animals; Hemorrhage; Necrosis; Pancreas; Pancreatic Diseases; Swine; Swine Diseases; Vitamin K

A female patient is described who developed skin and subcutaneous fat necrosis on two occasions after intake of acenocoumarol. Several months later identical skin changes occurred during an episode of cholestasis associated with a prolongation of the prothrombin time to an extent comparable with therapeutic anticoagulation; intake of oral anticoagulants could be excluded. This association gives new insights in the pathogenetic mechanisms responsible for the so-called coumarin necrosis and indicates that it may be not due to drug toxicity or allergy.

Topics: Acenocoumarol; Adipose Tissue; Adult; Blood Coagulation Factors; Cholestasis; Drug Therapy, Combination; Female; Heparin; Humans; Necrosis; Recurrence; Skin Diseases; Thrombophlebitis; Vitamin K

Topics: Drug Eruptions; Humans; Necrosis; Vitamin K; Warfarin

Topics: Child; Coumarins; Heparin; Humans; Iliac Vein; Male; Necrosis; Obesity; Prognosis; Skin Diseases; Streptokinase; Thrombosis; Vitamin K

Topics: Adrenal Cortex Hormones; Adult; Anti-Bacterial Agents; Autopsy; Chemical and Drug Induced Liver Injury; Female; Humans; Isoniazid; Necrosis; Tuberculin Test; Tuberculosis; Vitamin K

Topics: Acute Disease; Adult; Alanine Transaminase; Blood Coagulation Tests; Factor IX; Factor V; Factor VII; Factor VIII; Factor X; Female; Fibrin; Fibrinogen; Hepatic Encephalopathy; Hepatitis A; Humans; Middle Aged; Necrosis; Plasmapheresis; Prothrombin; Time Factors; Vitamin K

Topics: Adult; Coumarins; Female; Humans; Middle Aged; Necrosis; Thrombophlebitis; Vitamin K

Topics: Aged; Anticoagulants; Blood Transfusion; Breast Diseases; Buttocks; Coumarins; Diagnosis, Differential; Female; Hemorrhage; Humans; Male; Middle Aged; Necrosis; Thrombophlebitis; Vitamin K; Warfarin

Topics: Aortic Coarctation; Autopsy; Heart Defects, Congenital; Humans; Infant, Newborn; Liver; Liver Diseases; Necrosis; Vitamin K; Vitamin K Deficiency Bleeding

Topics: Adult; Anticoagulants; Female; Hemorrhagic Disorders; Humans; Necrosis; Ovarian Cysts; Rupture; Thigh; Thromboembolism; Vitamin K

Topics: Animals; Carcinoma, Ehrlich Tumor; Dogs; Fatty Liver; Female; Fever; Hemorrhage; Male; Methylene Blue; Mice; Necrosis; Nephrosis; Rats; Sodium; Species Specificity; Sulfites; Vitamin K