vitamin-k-semiquinone-radical and Leukemia

Thromboses of abdominal veins outside the iliac-caval axis are rare but clinically relevant. Early deaths after splanchnic vein thrombosis occur in 5-30% of cases. Sequelae can be liver failure or bowel infarction after splanchnic vein thrombosis, renal insufficiency after renal vein thrombosis, ovarian infarction after ovarian vein thrombosis. Local cancer or infections are rare in Budd-Chiari syndrome, and common for other sites. Inherited thrombophilia is detected in 30-50% of patients. Myeloproliferative neoplasms are the main cause of splanchnic vein thrombosis: 20-50% of patients have an overt myeloproliferative neoplasm and/or carry the molecular marker JAK2 V617F. Renal vein thrombosis is closely related to nephrotic syndrome; finally, ovarian vein thrombosis can complicate puerperium. Heparin is used for acute treatment, sometimes in conjunction with systemic or local thrombolysis. Vitamin K-antagonists are recommended for 3-6 months, and long-term in patients with Budd-Chiari syndrome, unprovoked splanchnic vein thrombosis, or renal vein thrombosis with a permanent prothrombotic state such as nephrotic syndrome.

Topics: Anticoagulants; Biomarkers, Tumor; Budd-Chiari Syndrome; Female; Heparin; Humans; Janus Kinase 2; Leukemia; Nephrotic Syndrome; Ovary; Portal Vein; Splanchnic Circulation; Vena Cava, Inferior; Venous Thrombosis; Vitamin K

This review summarizes the current knowledge of the epidemiology, prophylaxis, and treatment of venous thromboembolism (VTE) in patients with lymphoma, multiple myeloma or acute leukemia.. Hematologic malignancies are associated with a high risk of thrombotic complications. The incidence of these events is greatly variable and is influenced by many factors, including the type and the stage of disease, antitumor therapies, and the use of central venous device (CVD). Epidemiological data allow an estimate of the incidence of VTE in acute leukemia, lymphomas, and multiple myeloma. The effect of chemotherapy on the incidence of thrombosis is particularly evident in acute leukemia as it causes the exacerbation of the clotting/bleeding syndrome typical of this disease. The role of chemotherapy is also relevant in lymphoma, and in multiple myeloma, in which the use of immunomodulating agents, in combination with chemotherapy and steroids significantly increases the risk of VTE.. Thrombotic complications have a significant impact on morbidity and mortality of hematological cancer patients, therefore, in this setting, the issue of thromboprophylaxis to prevent VTE is important. However, no clear recommendation in these conditions is available, with the exception of multiple myeloma. Large prospective randomized clinical trials are needed to establish the best practice for prevention and treatment of VTE in these types of malignant diseases.

Topics: Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Incidence; Leukemia; Lymphoma; Multiple Myeloma; Platelet Transfusion; Venous Thromboembolism; Vitamin K

Vitamin K is a fat-soluble vitamin crucial to the production of many proteins involved with the coagulation process. It is integral in the synthesis of coagulants (factors II, VII, IX and X) and anticoagulants (proteins C and S). It is generally recognised that routine administration of vitamin K (phytomenadione) shortly after birth will prevent major neonatal morbidity and mortality related to haemorrhage. Vitamin K supplementation during pregnancy is also recommended if mothers are on anticonvulsant therapy or prolonged treatment with certain antibiotics. These medications, if ingested by pregnant women, predispose the neonate to a bleeding tendency caused by vitamin K deficiency. Vitamin K treatment of pregnant mothers before premature delivery has also been suggested to reduce the incidence of severe intracranial haemorrhage (ICH) in premature neonates. Although further studies are pending, the data to date do not support using antenatal vitamin K for preventing ICH.

Topics: Anticonvulsants; Cerebral Hemorrhage; Epilepsy; Female; Hemorrhage; Humans; Infant, Newborn; Infant, Premature, Diseases; Leukemia; Placenta; Pregnancy; Pregnancy Complications; Vitamin K; Vitamin K Deficiency

Topics: Adult; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Proteins; Female; Fibrinolysis; Glycoproteins; Hemostasis; Humans; Infant, Newborn; Leukemia; Male; Protein C; Protein C Inhibitor; Protein S; Receptors, Cell Surface; Receptors, Thrombin; Thromboembolism; Vitamin K

Topics: Agammaglobulinemia; Blood Protein Disorders; Bromides; Candidiasis, Cutaneous; Carcinoid Tumor; Dermatitis, Exfoliative; Drug Eruptions; Edema; Foot Dermatoses; Hand Dermatoses; Humans; Hypergammaglobulinemia; Keratosis; Leukemia; Lymphatic Diseases; Lymphoma; Penicillamine; Pruritus; Skin Diseases; Skin Manifestations; Vitamin K; Xanthomatosis

Topics: Age Factors; Anemia; Anticoagulants; Antifibrinolytic Agents; Bacterial Infections; Child; Child, Preschool; Disseminated Intravascular Coagulation; Fibrinolysis; Fibrinolytic Agents; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Kidney Diseases; Leukemia; Purpura; Shock; Virus Diseases; Vitamin K; Wounds and Injuries

Prevention of early vitamin K deficiency bleeding (VKDB) of the newborn, with onset at birth to 2 weeks of age (formerly known as classic hemorrhagic disease of the newborn), by oral or parenteral administration of vitamin K is accepted practice. In contrast, late VKDB, with onset from 2 to 12 weeks of age, is most effectively prevented by parenteral administration of vitamin K. Earlier concern regarding a possible causal association between parenteral vitamin K and childhood cancer has not been substantiated. This revised statement presents updated recommendations for the use of vitamin K in the prevention of early and late VKDB.

Topics: Administration, Oral; Health Policy; Hemorrhagic Disorders; Humans; Infant, Newborn; Injections, Intramuscular; Leukemia; Recurrence; Vitamin K; Vitamin K Deficiency

The relationship between neonatal vitamin K received by the intramuscular (i.m.) route and the development of leukaemia or other cancers was investigated as part of a national case-control study of childhood cancer, using data abstracted from obstetric and neonatal records. The analyses included 2530 children diagnosed with cancer before 15 years of age, 1174 of whom had leukaemia and 4487 control children without cancer. Overall, 39% of cases and 42% of controls had records of i.m. vitamin K administration, while 24% of cases and 22% of controls had no record of whether or not they had received vitamin K. Using subjects who received i.m. vitamin K as the baseline group, our analyses found no association between the administration of i.m. vitamin K and either leukaemia or other cancers as a group. We conclude that there is no convincing evidence that neonatal vitamin K administration, irrespective of the route by which it is given, influences the risk of children developing leukaemia or any other cancer.

Topics: Adolescent; Case-Control Studies; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Injections, Intramuscular; Leukemia; Male; Neoplasms; Odds Ratio; United Kingdom; Vitamin K

To investigate the hypothesis that neonates who receive intramuscular vitamin K are at an increased risk of developing cancer, particularly leukaemia, a pooled analysis of individual patient data from six case-control studies conducted in Great Britain and Germany has been undertaken. Subjects comprised 2431 case children diagnosed with cancer before 15 years of age and 6338 control children. The retrospective assessment of whether or not an individual baby received vitamin K is not straightforward. In many cases no record was found in stored medical notes and two types of analysis were therefore conducted; in the first it was assumed that where no written record of vitamin K was found it had not been given, and in the second, where no written record of administration was found, information on hospital policy and perinatal morbidity was used to 'impute' whether or not vitamin K had been given. In the first analysis, no association was found between neonatal administration of intramuscular. vitamin K and childhood cancer: odds ratios adjusted for mode of delivery, admission to special care baby unit and low birth weight were 1.09 (95% confidence interval 0.92-1.28) for leukaemia and 1.05 (0.92-1.20) for other cancers. In the second analysis, the adjusted odds ratios increased to 1.21 (1.02-1.44) for leukaemia and 1.10 (0.95-1.26) for other cancers. This shift did not occur in all studies, and when data from the hypothesis generating Bristol study were excluded, the adjusted odds ratios for leukaemia became 1.06 (0.89-1.25) in the first analysis and 1.16 (0.97-1.39) when data on prophylaxis imputed from hospital policy and perinatal morbidity were used. We conclude that whilst the broad nature of the diagnostic groups and the poor quality of some of the vitamin K data mean that small effects cannot be entirely ruled out, our analysis provides no convincing evidence that intramuscular vitamin K is associated with childhood leukaemia.

Topics: Adolescent; Case-Control Studies; Child; Child, Preschool; Humans; Infant; Infant, Newborn; Injections, Intramuscular; Leukemia; Neoplasms; Vitamin K

We originally reported that vitamin K2 (VK2) analogs, including menaquinone 4 (MK4) but not vitamin K1, effectively induce apoptosis in various types of primary cultured leukemia cells and leukemia cell lines in vitro. It has also been reported by others that VK2 showed the differentiation-inducing activity in leukemia cell lines. To investigate the discrepancy between apoptosis- and differentiation-inductions of leukemia cells by VK2 treatment, we used bcl-2 gene transfected HL-60 cells (HL-60-bcl-2) which resulted in five-fold over-expression of BCL-2 protein, and then compared the effects of MK4 to the control HL-60-neo cells. Seventy-two hours of exposure to various concentrations of MK4 resulted in growth inhibition of these cells in a dose-dependent manner (0.1-50 microM), however, HL-60-bcl-2 was less sensitive against MK4. MK4 potently induced apoptosis of HL-60-neo cells along with the depolarization of mitochondrial membrane potential and caspase-3 activation. Notably, HL-60-bcl-2 was almost completely resistant to apoptosis induction in response to MK4, although cell growth inhibition was still observed. In spite of the abrogation of apoptosis induction, about 90% of HL-60-bcl-2 cells were arrested in the G0/G1 phase within 48 h of exposure to 10 microM of MK4 accompanied by up-modulation of p27KIP1 expression. Concomitantly, HL-60-bcl-2 cells underwent monocytic differentiation. These data suggest that VK2 also shows the differentiation inducing effects on leukemia cells which are resistant against VK2-inducing apoptosis. The dichotomous nature of VK2 against leukemia cells appears to have clinical benefits for the treatment of patients with leukemias and myelodysplastic syndromes.

Topics: Apoptosis; Cell Cycle; Cell Differentiation; HL-60 Cells; Humans; Leukemia; Proto-Oncogene Proteins c-bcl-2; Vitamin K

Topics: Humans; Infant, Newborn; Leukemia; Neoplasms; Risk Factors; Vitamin K; Vitamin K Deficiency Bleeding

To test the hypothesis of an association between neonatal intramuscular vitamin K and childhood leukaemia and other cancers.. Population based case-control study with data abstracted from hospital records.. Scotland.. Children aged 0-14 years resident in Scotland from 1991-4 and diagnosed with leukaemia (150), lymphomas (46), central nervous system tumours (79), a range of other solid tumours (142), and a subset of acute lymphoblastic leukaemia (129). Controls were 777 children matched for age and sex, providing 417 matched sets (360 triplets and 57 pairs) for analysis.. Odds ratios for the risk of childhood leukaemia and cancer and intramuscular vitamin K versus a combined group of oral doses, none, and no record. Results are given for information recorded in medical notes and data supplemented by hospital policy.. Odds ratios based on medical record abstractions showed no significant positive association for leukaemias (odds ratio 1.30; 95% confidence interval 0.83 to 2.03), acute lymphoblastic leukaemia (1.21; 0.74 to 1.97), lymphomas (1.06; 0.46 to 2.42), central nervous system tumours (0.74; 0.40 to 1.34), and other solid tumours (0.59; 0.37 to 0.96). There was no association with acute lymphoblastic leukaemia in children aged 1 to 6 years. Imputation of exposure from hospital policy gave similar results. Adjustment for deprivation and type of delivery moved risk estimates closer to unity for all major diagnostic groups.. The observation of an increased risk of childhood leukaemia and cancer associated with intramuscular vitamin K is not confirmed by this independent population based study.

Topics: Adolescent; Case-Control Studies; Child; Child, Preschool; Humans; Infant; Infant, Newborn; Injections, Intramuscular; Leukemia; Neoplasms; Odds Ratio; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Scotland; Vitamin K; Vitamin K Deficiency

The role of lipid peroxidation, intracellular glutathione and Ca2+ concentration in menadione-mediated toxicity was investigated in human hepatoma cell lines, Hep G2 and Hep 3B, and in human leukemia cell lines, CCRF-CEM and MOLT-3. Incubation of these cells with 80 microM menadione at 37 degrees C resulted in depletion of intracellular glutathione, increased intracellular Ca2+, and increased lipid peroxidation, events leading to cell degeneration. The sensitivity of these cells to menadione, in order, was: Hep G2 cells > Hep 3B cells > CCRF-CEM cells and MOLT-3 cells. The extent of menadione-induced lipid peroxidation in different cell types followed the same order as did their susceptibility to menadione-induced cell degeneration. The menadione-induced depletion in glutathione level was in the following sequence: Hep G2 cells > MOLT-3 and CCRF-CEM cells > Hep 3B cells. The extent of the menadione-induced increase in the intracellular Ca2+ concentration was: Hep G2 cells > Molt-3 cells > CCRF-CEM cells and Hep 3B cells. Pre-treatment of Hep G2 cells with 20 mM deferoxamine mesylate, an iron chelator, reduced both the menadione-induced cell degeneration and lipid peroxidation; however, it did not prevent the menadione-induced increase in intracellular Ca2+ nor the depletion of glutathione. These data suggest that menadione-induced cell degeneration is directly linked to lipid peroxidation, and that it is less related to the rise in intracellular Ca2+ and the depletion in glutathione content. Dicumarol (an inhibitor of DT diaphorase) enhanced the capacity of menadione to induce Hep 3B cell degeneration from 71.3% to 86.2% after 120 min of menadione treatment at 37 degrees C, but did not have this effect in Hep G2, CCRF-CEM or MOLT-3 cells. The activities of DT diaphorase were 52.4, 39.6, 1.5 and 1.8 nmol cytochrome c reduced/min/mg protein in Hep G2, Hep 3B, CCRF-CEM and MOLT-3 cells, respectively. The activity of DT diaphorase was much higher in Hep G2 cells than in the other cells. It seems that DT diaphorase may not, as suggested by others, protect against cell degeneration by quinones, such as menadione.

Topics: Calcium; Carcinoma, Hepatocellular; Cell Death; Chelating Agents; Deferoxamine; Dicumarol; Glutathione; Glutathione Disulfide; Humans; Intracellular Fluid; Leukemia; Lipid Peroxidation; Liver Neoplasms; NAD(P)H Dehydrogenase (Quinone); Neoplasms; Tumor Cells, Cultured; Vitamin K

Topics: Administration, Oral; Drug Administration Schedule; Hemorrhage; Humans; Infant Food; Infant, Newborn; Injections, Intramuscular; Leukemia; Neoplasms; Risk Factors; Vitamin K; Vitamin K Deficiency

Geranylgeraniol, a polyprenylalcohol composing the side chain of vitamin K2 (VK2), was previously reported to be a potent inducer of apoptosis in tumor cell lines (Ohzumi H et al, J Biochem 1995; 117: 11-13). We examined the apoptosis-inducing ability of VK2 (menaquinone 3 (MK3), MK4 and MK5) and its derivatives such as phytonadione (VK1), as well as polyprenylalcohols with side chains of various lengths including farnesol (C15-OH; FO), geranylgeraniol (C20-OH; GGO), and geranylfarnesol (C25-OH; GFO) toward leukemia cells in vitro. MK3, MK4, MK5 and GFO (at 10 microM) showed a potent apoptosis-inducing activity for all freshly isolated leukemia cells tested and for leukemia cell lines such as NB4, an acute promyelocytic leukemia (APL)-derived cell line and MDS92, a cell line derived from a patient with myelodysplastic syndrome, although there were some differences depending on the cells tested. In contrast, VK1 showed no effect on any of the leukemia cells. The combination of MK5 plus all-trans retinoic acid (ATRA) resulted in enhanced induction of apoptosis in both freshly isolated APL cells and NB4 cells as compared to each reagent alone. These data suggest the possibility of using VK2 and its derivatives for the treatment of myelogenous leukemias, including APL.

Topics: Apoptosis; Bone Marrow; Diterpenes; Drug Synergism; Farnesol; Flow Cytometry; Gefarnate; Humans; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Leukemia, Promyelocytic, Acute; Molecular Structure; Myelodysplastic Syndromes; Structure-Activity Relationship; Tretinoin; Tumor Cells, Cultured; Vitamin K; Vitamin K 1; Vitamin K 2

A medical record-based study of leukaemia and non-Hodgkin's lymphoma diagnosed before the age of 30 years was carried out at three hospitals in the south of England. Findings for 177 cases and 354 age- and sex-matched controls are presented here. For documented viral infection in pregnancy, the odds ratio (OR) was 6.0 [95% confidence interval (CI) 1.2-29.7] for leukaemia and infinity (95% CI 1.24-infinity) for non-Hodgkin's lymphoma. Mothers of leukaemic cases were more likely to be anaemic, the OR for a pregnancy haemoglobin below 10 g being 3.8 (95% CI 1.3-11.1). An association with birthweight was found for acute myeloid leukaemia, the OR for birthweights > 3500 g being 6.2 (95% CI 1.3-29.8). Further, the preceding siblings of those diagnosed with any form of leukaemia were also more likely to weigh > 3500 g at birth (OR 2.2; 95% CI 1.1-4.4). Overall, leukaemic cases appeared to be comparatively robust at birth with respect to other indicators of well-being, the ORs for jaundice, phototherapy, admission to special care nursery and neonatal intensive care all being less than 1.0. Further, no relation between childhood leukaemia and neonatal administration of intramuscular vitamin K was noted (OR 0.6, 95% CI 0.3-1.4; for acute lymphoblastic leukaemia diagnosed between the ages of 1 and 6 years).

Topics: Adolescent; Adult; Birth Weight; Case-Control Studies; Child; Child, Preschool; England; Female; Humans; Infant; Leukemia; Lymphoma, Non-Hodgkin; Maternal Age; Maternal-Fetal Exchange; Neonatology; Odds Ratio; Parity; Pregnancy; Pregnancy Complications; Vitamin K

Topics: Erythroblastosis, Fetal; Humans; Infant, Newborn; Leukemia; Neoplasms; Vitamin K; Vitamin K Deficiency

To confirm or refute a possible association of parenteral vitamin K prophylaxis and childhood cancer.. Population based case-control study. Comparison of vitamin K exposure in children with leukaemia or other common tumours with two control groups.. State of Lower Saxony (north western part of Germany); case recruitment from the German childhood cancer registry.. 272 children with leukaemia, nephroblastoma, neuroblastoma, rhabdomyosarcoma, and tumours of the central nervous system diagnosed between 1 July 1988 and 30 June 1993; children were aged between 30 days and 15 years at diagnosis. 334 population based controls without diagnoses of cancer matched to the leukaemia cases for age and sex.. Parenteral vitamin K prophylaxis (intramuscular and subcutaneous) versus oral and no vitamin K prophylaxis.. An association between parenteral vitamin K exposure and childhood cancer (leukaemias and other tumours combined) could not be confirmed (odds ratio 1.04, 95% confidence interval 0.74 to 1.48). For leukaemias the observed odds ratio was only 0.98 (0.64 to 1.50) (comparison of leukaemia cases with local controls 1.24 (0.68 to 2.25); state controls 0.82 (0.50 to 1.36)). These odds ratios remained almost unchanged when several potential confounders were considered in the logistic regression model.. This population based study adds substantial evidence that there is no association between parenteral vitamin K and childhood cancer.

Topics: Adolescent; Case-Control Studies; Central Nervous System Neoplasms; Child; Child, Preschool; Female; Germany; Humans; Infant; Infant, Newborn; Injections, Intramuscular; Injections, Subcutaneous; Kidney Neoplasms; Leukemia; Male; Neoplasms; Neuroblastoma; Population Surveillance; Rhabdomyosarcoma; Risk Factors; Vitamin K; Vitamin K Deficiency; Wilms Tumor

Topics: Child; Child, Preschool; Humans; Infant; Infant, Newborn; Injections, Intramuscular; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Retrospective Studies; Risk Factors; Vitamin K

Topics: Humans; Infant, Newborn; Injections, Intramuscular; Leukemia; Vitamin K; Vitamin K Deficiency Bleeding

Topics: Adolescent; Child; Child, Preschool; Cohort Studies; Denmark; Humans; Incidence; Infant; Infant, Newborn; Leukemia; Lymphoma; Neoplasms; Risk Factors; Vitamin K

Topics: Child, Preschool; Humans; Incidence; Infant, Newborn; Injections, Intramuscular; Leukemia; United States; Vitamin K; Vitamin K Deficiency Bleeding

Topics: Humans; Infant, Newborn; Injections, Intramuscular; Leukemia; Phenols; Vitamin K

Topics: Delivery, Obstetric; Humans; Infant, Newborn; Injections, Intramuscular; Leukemia; Risk Factors; Vitamin K

Topics: Adolescent; Child; Humans; Incidence; Infant, Newborn; Injections, Intramuscular; Leukemia; Risk Factors; Vitamin K

Topics: Administration, Oral; Humans; Infant, Newborn; Injections, Intramuscular; Leukemia; Research Design; Vitamin K

The effect of menadiol (vitamin K3) on fresh specimens of human lymphatic neoplasms (HLN) was tested by means of the differential staining cytotoxicity assay. Menadiol was tested alone and in combination with standard antineoplastic agents. Drug effects were then compared with the effects of the same drugs in normal human lymphocytes and in fresh specimens of human non-small cell lung cancer. By itself, menadiol was moderately toxic to HLN, but not to normal lymphocytes or non-small cell lung cancer. Menadiol, menadione, and two structurally related congeners were equitoxic to HLN cells, but sodium metabisulfite (present in menadiol solutions as a preservative) was nontoxic. Menadiol increased the cytotoxic effects of a number of standard agents in HLN but not in normal lymphocytes. Cell survival times with mechlorethamine, vincristine, and dexamethasone were converted from a range characteristic of drug resistance (ie, range observed in relapsed patients) to a range characteristic of drug sensitivity (ie, range observed in untreated patients) in the presence of menadiol. These effects occurred at a concentration (2.0 micrograms/ml; 4.7 microM) of menadiol which is probably clinically achievable and which did not deplete intracellular glutathione. Menadiol should receive clinical testing as a chemosensitizing agent in HLN.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Colony-Forming Units Assay; Dexamethasone; Drug Evaluation, Preclinical; Glutathione; Humans; Leukemia; Lymphoma; Mechlorethamine; Tumor Stem Cell Assay; Vincristine; Vitamin K

Topics: Alkaloids; Animals; Antifungal Agents; Antineoplastic Agents; Ascites; Colchicine; Demecolcine; Hydrazines; Indicators and Reagents; Iron; Leukemia; Mice; Radiation-Sensitizing Agents; Riboflavin; Triacetin; Triglycerides; Urethane; Vitamin K

Topics: Aminopterin; Antimetabolites; Azaserine; Child; Child, Preschool; Choriocarcinoma; Diazooxonorleucine; Female; Fluorouracil; Folic Acid Antagonists; Humans; Leukemia; Mercaptopurine; Methotrexate; Pregnancy; Pyrimethamine; Toxoplasmosis; Vitamin K; Vitamins

Topics: Alkaline Phosphatase; Blood Transfusion; Bone Marrow Examination; Busulfan; Chromosome Aberrations; Chromosome Disorders; Dexamethasone; Eosinophilia; Eosinophils; Heparin; Humans; In Vitro Techniques; Karyotyping; Leukemia; Male; Middle Aged; Nystatin; Thrombophlebitis; Vitamin K

Topics: Electrophoresis; Humans; Leukemia; Liver Cirrhosis; Neoplasms; Pyridoxine; Vitamin A; Vitamin K; Vitamins

Topics: Adolescent; Anti-Bacterial Agents; Antibiotics, Antitubercular; Blood; Blood Transfusion; Bone Marrow Examination; Child; Drug Therapy; Humans; Leukemia; Mercaptopurine; Properdin; Vitamin K; Vitamins

Topics: Animals; Antifibrinolytic Agents; Characidae; Leukemia; Leukemia, Lymphoid; Naphthoquinones; Neoplasms; Neoplasms, Experimental; Sodium; Tritium; Vitamin K