RESUMEN
It has recently been hypothesized that vitamin K could play a role in COVID-19. We aimed to test the hypotheses that low vitamin K status is a common characteristic of patients hospitalized with COVID-19 compared to population controls and that low vitamin K status predicts mortality in COVID-19 patients. In a cohort of 138 COVID-19 patients and 138 population controls, we measured plasma dephosphorylated-uncarboxylated Matrix Gla Protein (dp-ucMGP), which reflects the functional vitamin K status in peripheral tissue. Forty-three patients died within 90 days from admission. In patients, levels of dp-ucMGP differed significantly between survivors (mean 877; 95% CI: 778; 995) and non-survivors (mean 1445; 95% CI: 1148; 1820). Furthermore, levels of dp-ucMGP (pmol/L) were considerably higher in patients (mean 1022; 95% CI: 912; 1151) compared to controls (mean 509; 95% CI: 485; 540). Cox regression survival analysis showed that increasing levels of dp-ucMGP (reflecting low vitamin K status) were associated with higher mortality risk (sex- and age-adjusted hazard ratio per doubling of dp-ucMGP was 1.49, 95% CI: 1.03; 2.24). The association attenuated and became statistically insignificant after adjustment for co-morbidities (sex, age, CVD, diabetes, BMI, and eGFR adjusted hazard ratio per doubling of dp-ucMGP was 1.22, 95% CI: 0.82; 1.80). In conclusion, we found that low vitamin K status was associated with mortality in patients with COVID-19 in sex- and age-adjusted analyses, but not in analyses additionally adjusted for co-morbidities. Randomized clinical trials would be needed to clarify a potential role, if any, of vitamin K in the course of COVID-19.
Asunto(s)
COVID-19/mortalidad , Proteínas de Unión al Calcio/metabolismo , Proteínas de la Matriz Extracelular/metabolismo , Hospitalización , Deficiencia de Vitamina K/mortalidad , Vitamina K/sangre , Adulto , Anciano , Biomarcadores/sangre , Coagulación Sanguínea , COVID-19/complicaciones , COVID-19/metabolismo , Proteínas de Unión al Calcio/sangre , Estudios de Cohortes , Proteínas de la Matriz Extracelular/sangre , Femenino , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Análisis de Regresión , SARS-CoV-2 , Trombosis/metabolismo , Deficiencia de Vitamina K/sangre , Deficiencia de Vitamina K/complicaciones , Adulto Joven , Proteína Gla de la MatrizRESUMEN
Patients with chronic kidney disease (CKD) suffer from vitamin K deficiency and are at high risk of vascular calcification (VC) and premature death. We investigated the association of functional vitamin K deficiency with all-cause mortality and whether this association is modified by the presence of VC in CKD stage 5 (CKD G5). Plasma dephosphorylated-uncarboxylated matrix Gla-protein (dp-ucMGP), a circulating marker of functional vitamin K deficiency, and other laboratory and clinical data were determined in 493 CKD G5 patients. VC was assessed in subgroups by Agatston scoring of coronary artery calcium (CAC) and aortic valve calcium (AVC). Backward stepwise regression did not identify dp-ucMGP as an independent determinant of VC. During a median follow-up of 42 months, 93 patients died. Each one standard deviation increment in dp-ucMGP was associated with increased risk of all-cause mortality (sub-hazard ratio (sHR) 1.17; 95% confidence interval, 1.01-1.37) adjusted for age, sex, cardiovascular disease, diabetes, body mass index, inflammation, and dialysis treatment. The association remained significant when further adjusted for CAC and AVC in sub-analyses (sHR 1.22, 1.01-1.48 and 1.27, 1.01-1.60, respectively). In conclusion, functional vitamin K deficiency associates with increased mortality risk that is independent of the presence of VC in patients with CKD G5.
Asunto(s)
Insuficiencia Renal Crónica/complicaciones , Calcificación Vascular/complicaciones , Deficiencia de Vitamina K/complicaciones , Vitamina K/sangre , Adulto , Anciano , Biomarcadores/sangre , Proteínas de Unión al Calcio/sangre , Estudios de Cohortes , Proteínas de la Matriz Extracelular/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/mortalidad , Insuficiencia Renal Crónica/patología , Tasa de Supervivencia , Calcificación Vascular/sangre , Calcificación Vascular/mortalidad , Calcificación Vascular/patología , Deficiencia de Vitamina K/sangre , Deficiencia de Vitamina K/mortalidad , Deficiencia de Vitamina K/patología , Proteína Gla de la MatrizRESUMEN
Patients receiving vitamin K antagonists (VKAs) with an international normalized ratio (INR) between 4.5 and 10 are at increased risk of bleeding. We systematically reviewed the literature to evaluate the effectiveness and safety of administering vitamin K in patients receiving VKA therapy with INR between 4.5 and 10 and without bleeding. Medline, Embase, and Cochrane databases were searched for relevant randomized controlled trials in April 2018. Search strategy included terms vitamin K administration and VKA-related terms. Reference lists of relevant studies were reviewed, and experts in the field were contacted for relevant papers. Two investigators independently screened and collected data. Risk ratios (RRs) were calculated, and certainty of the evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation. Six studies (1074 participants) were included in the review and meta-analyses. Pooled estimates indicate a nonsignificant increased risk of mortality (RR = 1.42; 95% confidence interval [CI], 0.62-2.47), bleeding (RR = 2.24; 95% CI, 0.81-7.27), and thromboembolism (RR = 1.29; 95% CI, 0.35-4.78) for vitamin K administration, with moderate certainty of the evidence resulting from serious imprecision as CIs included potential for benefit and harm. Patients receiving vitamin K had a nonsignificant increase in the likelihood of reaching goal INR (1.95; 95% CI, 0.88-4.33), with very low certainty of the evidence resulting from serious risk of bias, inconsistency, and imprecision. Our findings indicate that patients on VKA therapy who have an INR between 4.5 and 10.0 without bleeding are not likely to benefit from vitamin K administration in addition to temporary VKA cessation.
Asunto(s)
Anticoagulantes/efectos adversos , Hemorragia/prevención & control , Deficiencia de Vitamina K/tratamiento farmacológico , Vitamina K/uso terapéutico , Hemorragia/inducido químicamente , Hemorragia/mortalidad , Humanos , Relación Normalizada Internacional , Medición de Riesgo , Vitamina K/administración & dosificación , Deficiencia de Vitamina K/inducido químicamente , Deficiencia de Vitamina K/mortalidadRESUMEN
Matrix Gla Protein (MGP), a small Gla vitamin K-dependent protein, is the most powerful natural occurring inhibitor of calcification in the human body. To become biologically active, MGP must undergo vitamin K-dependent carboxylation and phosphorylation. Vitamin K deficiency leads to the inactive uncarboxylated, dephosphorylated form of MGP (dpucMGP). We aimed to review the existing data on the association between circulating dpucMGP and vascular calcification, renal function, mortality, and cardiovascular disease in distinct populations. Moreover, the association between vitamin K supplementation and serum levels of dpucMGP was also reviewed.
Asunto(s)
Proteínas de Unión al Calcio/metabolismo , Enfermedades Cardiovasculares/metabolismo , Proteínas de la Matriz Extracelular/metabolismo , Procesamiento Proteico-Postraduccional , Insuficiencia Renal Crónica/metabolismo , Calcificación Vascular/metabolismo , Deficiencia de Vitamina K/metabolismo , Vitamina K/metabolismo , Transporte Biológico , Proteínas de Unión al Calcio/genética , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/mortalidad , Suplementos Dietéticos , Proteínas de la Matriz Extracelular/genética , Regulación de la Expresión Génica , Humanos , Fosforilación , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/genética , Insuficiencia Renal Crónica/mortalidad , Análisis de Supervivencia , Calcificación Vascular/complicaciones , Calcificación Vascular/genética , Calcificación Vascular/mortalidad , Rigidez Vascular , Deficiencia de Vitamina K/complicaciones , Deficiencia de Vitamina K/genética , Deficiencia de Vitamina K/mortalidad , Proteína Gla de la MatrizAsunto(s)
Enfermedades Cardiovasculares/epidemiología , Deficiencia de Vitamina K/epidemiología , Vitamina K/sangre , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Medición de Riesgo , Factores de Riesgo , Deficiencia de Vitamina K/sangre , Deficiencia de Vitamina K/diagnóstico , Deficiencia de Vitamina K/mortalidadRESUMEN
BACKGROUND: Vitamin K modulates calcification by activating calcification inhibitors such as matrix Gla protein (MGP). In kidney transplant recipients, vitamin K insufficiency is common, but implications for long-term outcomes are unclear. STUDY DESIGN: Single-center observational study with a longitudinal design. SETTING & PARTICIPANTS: 518 stable kidney transplant recipients; 56% men; mean age, 51±12 (SD) years; and a median of 6 (IQR, 3-12) years after kidney transplantation. FACTOR: Plasma desphosphorylated-uncarboxylated MGP (dp-ucMGP) levels, reflecting vitamin K status. OUTCOMES: All-cause mortality and transplant failure. RESULTS: At inclusion, median dp-ucMGP level was 1,038 (IQR, 733-1,536) pmol/L, with 473 (91%) patients having vitamin K insufficiency (defined as dp-ucMGP>500pmol/L). During a median follow-up of 9.8 (IQR, 8.5-10.2) years, 152 (29%) patients died and 54 (10%) developed transplant failure. Patients in the highest quartile of dp-ucMGP were at considerably higher mortality risk compared with patients in the lowest quartile (HR, 3.10; 95% CI, 1.87-5.12; P for trend<0.001; P for quartile 1 [Q1] vs Q4<0.001). After adjustment for potential confounders, including kidney function and exclusion of patients treated with a vitamin K antagonist, this association remained significant. Patients in the highest quartile also were at higher risk of developing transplant failure (HR, 2.61; 95% CI, 1.22-5.57; P for trend=0.004; P for Q1 vs Q4=0.01), but this association was lost after adjustment for baseline kidney function (HR, 1.20; 95% CI, 0.52-2.75; P for trend=0.6; P for Q1 vs Q4=0.7). LIMITATIONS: Although MGP exists as various species, only dp-ucMGP was measured. No data were available for vascular calcification as an intermediate end point. CONCLUSIONS: Vitamin K insufficiency, that is, a high circulating level of dp-ucMGP, is highly prevalent in stable kidney transplant recipients and is associated independently with increased risk of mortality. Future studies should address whether vitamin K supplementation may lead to improved outcomes after kidney transplantation.
Asunto(s)
Trasplante de Riñón/mortalidad , Deficiencia de Vitamina K/sangre , Deficiencia de Vitamina K/mortalidad , Vitamina K/sangre , Adulto , Anciano , Biomarcadores/sangre , Proteínas de Unión al Calcio/sangre , Estudios de Cohortes , Proteínas de la Matriz Extracelular/sangre , Femenino , Estudios de Seguimiento , Humanos , Trasplante de Riñón/tendencias , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Mortalidad/tendencias , Deficiencia de Vitamina K/diagnóstico , Proteína Gla de la MatrizRESUMEN
BACKGROUND: Deficiency of vitamin K predisposes to early, classic, or late vitamin K deficiency bleeding (VKDB), of which late VKDB may be associated with serious and life-threatening intracranial bleeding. Late VKDB is characterized with intracranial bleeding in infants aged 2-24 weeks due to severe vitamin K deficiency, occurring primarily in exclusively breast-fed infants. Late VKDB is still an important cause of mortality and morbidity in developing countries. MATERIALS AND METHODS: We presented 120 cases of late VKDB, which were evaluated at Erciyes University Medical Faculty Hospital between June 1990 and June 2006. RESULTS: Signs and symptoms of the patients were bulging fontanels (70%); irritabilities (50%); convulsions (49%); bleeding and ecchymosis (47%); feeding intolerance, poor sucking, and vomiting (46%); diarrhea (34%); jaundice (11%); and pallor (9%), and among these infants, 21% received medication before the diagnosis (10%, antibiotics; 3%, simethicone; 4%, paracetamol; and 4%, phenobarbital). Intracranial hemorrhage in 88 (73%) patients has been observed. The hemorrhage was subdural in 34 (28%) cases, intracerebral in 28 (23%), subarachnoid in 17 (14%), intraventricular in 9 (8%), intracerebral and subdural in 12 (10%), subdural and subarachnoid in 6 (5%), and combination of intracerebral, subdural, and intraventricular in 14 (12%), and the mortality rate was 31%. CONCLUSION: Although late VKDB leads to significant morbidity and mortality, it can be avoided by providing vitamin K prophylaxis to all newborns. Administration of vitamin K (1 mg) at birth can prevent intracranial bleeding and other hemorrhagic manifestations.
Asunto(s)
Hemorragias Intracraneales/diagnóstico , Hemorragias Intracraneales/etiología , Deficiencia de Vitamina K/complicaciones , Deficiencia de Vitamina K/diagnóstico , Femenino , Humanos , Lactante , Recién Nacido , Hemorragias Intracraneales/mortalidad , Masculino , Estudios Retrospectivos , Deficiencia de Vitamina K/mortalidadRESUMEN
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.
Asunto(s)
Alimentación Animal/efectos adversos , Alimentación Animal/efectos de la radiación , Rayos gamma , Esterilización/métodos , Deficiencia de Vitamina K/etiología , Alimentación Animal/análisis , Animales , Alimentos Formulados , Vida Libre de Gérmenes , Corazón/efectos de los fármacos , Ventrículos Cardíacos/efectos de los fármacos , Ventrículos Cardíacos/patología , Hemorragia/inducido químicamente , Hemorragia/patología , Longevidad/efectos de los fármacos , Ratones , Ratones Endogámicos BALB C , Miocardio/patología , Tiempo de Tromboplastina Parcial , Tiempo de Protrombina , Tasa de Supervivencia , Vitamina K 1/análisis , Vitamina K 3/administración & dosificación , Vitamina K 3/análisis , Deficiencia de Vitamina K/mortalidad , Deficiencia de Vitamina K/patologíaRESUMEN
A two-year mechanistic bioassay in male Crl:CD BR rats was initiated with 50 ppm Wyeth-14,643 (WY) to investigate the relationship between peroxisome proliferating compounds and Leydig cell adenoma formation. After 154 days, the survival rate in the WY group decreased below control levels. After 300 days, the dose was lowered to 25 ppm for the remainder of the study. Gross examination of WY-treated rats either found dead or euthanized in extremis revealed hemorrhages at several sites. To investigate this observation, blood was then collected on test day 281 from 10 randomly selected control and WY-treated rats and a clinical pathological examination was performed. The WY-treated rats had significantly decreased red blood cell count, hemoglobin, and hematocrit, and elevated platelet counts. In the WY-treated rats, prothrombin times in undiluted plasma were similar to the controls, but were markedly prolonged in 2 of 10 rats when the plasma samples were diluted to 25%. Subsequently, blood was collected prior to sacrificing WY-treated rats which were exhibiting clinical signs of anemia. These rats had prolonged prothrombin times, activated partial thromboplastin time, and thrombin clot time when compared to laboratory historical control data (116.7 vs 13.3, 116.4 vs 13.7, and 42.4 vs 25.7 seconds, respectively). In a subsequent, ongoing study, Vitamin K was added to control and WY-treated diets (100 ppm). No survival differences between control and WY-treated rats occurred through 260 days in this second study. These new data suggest that deaths in the WY-treated group in our initial study were due to a vitamin K deficiency. The role of increased serum estradiol, its effects on blood coagulation, and enhanced hepatic cell proliferation in the vitamin K-dependent coagulation processes warrant further investigation.
Asunto(s)
Coagulación Sanguínea/efectos de los fármacos , Carcinógenos/toxicidad , Tumor de Células de Leydig/inducido químicamente , Mutágenos/toxicidad , Pirimidinas/toxicidad , Neoplasias Testiculares/inducido químicamente , Análisis de Varianza , Animales , Bioensayo , Recolección de Muestras de Sangre , Relación Dosis-Respuesta a Droga , Recuento de Eritrocitos/efectos de los fármacos , Hematócrito , Hemoglobinas/metabolismo , Tumor de Células de Leydig/sangre , Tumor de Células de Leydig/mortalidad , Masculino , Microcuerpos/efectos de los fármacos , Tiempo de Tromboplastina Parcial , Recuento de Plaquetas/efectos de los fármacos , Tiempo de Protrombina , Pirimidinas/administración & dosificación , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Tasa de Supervivencia , Neoplasias Testiculares/sangre , Neoplasias Testiculares/mortalidad , Trombina/metabolismo , Deficiencia de Vitamina K/sangre , Deficiencia de Vitamina K/inducido químicamente , Deficiencia de Vitamina K/mortalidadRESUMEN
BACKGROUND: The evaluation of the disease of vitamin K deficiency bleeding (VKDB). METHOD: 108 reported cases between 1980 and 1990 from Germany. RESULTS: VKDB occurs preferentially (90%) in fully breastfed infants, males are affected nearly twice as often as females. The peak age is four weeks; the majority (79%) of the infants are between three and seven weeks old. 58% of the patients suffer from intracranial bleeding, which results in a total mortality rate of 19% and in neurological damage in 21%. Generally the VKDB occurred suddenly as no warning signs were noticed or they were so insignificant as not to be heeded. In at least 37% of the patients cholestasis was detected. The Quick value was pathologically low in every case. Vitamin K dependent factors were low and PIVKA was detectable, whereas vitamin K independent hemostatic parameters were normal or even elevated. The combination of low Quick value and normal fibrinogen as well as platelet level is a good diagnostic indicator which can be confirmed by administration of vitamin K, after which the Quick value will rise within 30 minutes. Vitamin K prophylaxis reduces the incidence of VKDB from 5.13 per 100,000 births to a tenth of that; single dose oral prophylaxis reduces the risk by a factor of 3.3 and a single parenteral dose by 14.3. Parenteral prophylaxis is more effective in patients with hepatobiliary disorders. Patients who suffered VKDB despite having received vitamin K prophylaxis are older at onset (without prophylaxis 32 days, with oral prophylaxis 37 days, and with parenteral prophylaxis 63 days) and have less intracranial bleeding (35%) than patients who received none (62%). CONCLUSION: Late form of VKDB is a rare but serious disease which can be prevented by VK-prophylaxis.
Asunto(s)
Sangrado por Deficiencia de Vitamina K/sangre , Deficiencia de Vitamina K/sangre , Pruebas de Coagulación Sanguínea , Daño Encefálico Crónico/sangre , Daño Encefálico Crónico/mortalidad , Daño Encefálico Crónico/prevención & control , Lactancia Materna , Hemorragia Cerebral/sangre , Hemorragia Cerebral/mortalidad , Hemorragia Cerebral/prevención & control , Estudios Transversales , Femenino , Alemania/epidemiología , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Necesidades Nutricionales , Vitamina K/administración & dosificación , Vitamina K/sangre , Deficiencia de Vitamina K/mortalidad , Deficiencia de Vitamina K/prevención & control , Sangrado por Deficiencia de Vitamina K/mortalidad , Sangrado por Deficiencia de Vitamina K/prevención & controlRESUMEN
A coagulopathy due to vitamin K deficiency was discovered in 42 hospitalized patients, most of whom had been misdiagnosed as having disseminated intravascular coagulation. Factors contributing to vitamin deficiency included inadequate diet, malabsorption, failure of physicians to prescribe vitamin K supplements, antibiotic therapy, renal insufficiency, hepatic dysfunction, recent major surgery, and possibly pregnancy. Sixteen patients (34%) bled sufficiently to need red blood cell transfusions and ten patients (24%) ultimately died. Of 18 patients who also had thrombocytopenia, three did have disseminated intravascular coagulation. The deficiency, a contributor to morbidity and mortality, can be prevented by prophylactic administration of vitamin K to severely ill patients who are eating inadequately and receiving antibiotics.
Asunto(s)
Trastornos de la Coagulación Sanguínea/etiología , Deficiencia de Vitamina K/complicaciones , Adolescente , Adulto , Anciano , Trastornos de la Coagulación Sanguínea/mortalidad , Pruebas de Coagulación Sanguínea , Cuidados Críticos , Femenino , Hemorragia/etiología , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Vitamina K/uso terapéutico , Deficiencia de Vitamina K/tratamiento farmacológico , Deficiencia de Vitamina K/mortalidadRESUMEN
PIP: Vitamin K in oral drops and intramuscular injection given at birth to Thai infants were compared to determine whether these routes and doses would influence prothrombin complex activity, mortality or morbidity at 0.5, 1 and 2 months of age. The infants were 321 normal fullterm babies born at Bangkok Adventist Hospital in 1983, exclusively breastfed during the study. Prothrombin complex (PC) was measured by the Owren capillary thrombotest method using a reagent from Nyegaard Co., Oslo. Vitamin K was given in single 1 or 2 mg oral doses, or 1 mg im, within 12 hours of delivery. Judging by the number of PC deficient children, the 1 mg im and 2 mg oral doses of vitamin K maintained clotting factors best at 2 months of age. All formulations were significantly better than no treatment at 1 month at age. No toxicity or side effects were seen. Vitamin K deficiency is a known cause of bleeding disorders, particularly fatal and handicapping intracranial hemorrhage in newborns, in developing countries where injections cannot be given by midwives. These inexpensive oral pediatric drops may provide a practical form of primary health care for routine vitamin K prophylaxis in newborns.^ieng
Asunto(s)
Sangrado por Deficiencia de Vitamina K/prevención & control , Deficiencia de Vitamina K/prevención & control , Vitamina K/administración & dosificación , Administración Oral , Humanos , Lactante , Recién Nacido , Deficiencia de Vitamina K/mortalidad , Sangrado por Deficiencia de Vitamina K/mortalidadRESUMEN
Poultry susceptibility to avitaminosis K-induced granulomatous endocardial lesions was studied in broiler and layer chicks. They were fed either a practical corn-soybean meal diet with and without added vitamin K (vit K), or a 61% raw sugar-isolated soybean protein diet (RS-IS) with no added vit K for 10 weeks. Heart lesions were not found in birds fed any of the experimental diets. Mortality, body weight gain, and prothrombin time did not differ significantly between birds fed the practical diet regardless of vit K supplementation. In contrast, the RS-IS diet significantly increased mortality, prothrombin time, and markedly decreased growth. Furthermore, more than a third of the birds fed the high sugar diet had subcutaneous edema, which resembled exudative diathesis. Compared with swine, poultry are apparently less susceptible to granulomatous endocardial lesions induced by a vit K deficiency.