vitamin-k-semiquinone-radical and Liver-Failure

Topics: Abdominal Pain; Acute Disease; Ankle Injuries; Arthralgia; Aspirin; Child; Consciousness Disorders; Diagnosis, Differential; Fatigue; Female; Hemorrhagic Disorders; Humans; Hyperammonemia; Hypoglycemia; Hypotension; Lactulose; Liver Failure; Reye Syndrome; Rheumatic Fever; Vitamin K

Regarding anticoagulant therapies there has been a remarkable shift in recent years. The objective of this brief overview is to provide relevant information and guidelines on the advantages and disadvantages of novel anticoagulants addressing specifically the surgical disciplines. Hitherto, conventional anticoagulant therapy in patients with a high thrombosis risk was largely limited to heparins and vitamin-K antagonists (VKA). Their modes of action, the difficulties in managing VKAs (e.g., bridging therapy) and the risk of HIT (heparin-induced thrombocytopenia) associated with heparins are briefly discussed. Novel anticoagulants supposedly eliminate these obstacles. Fondaparinux (Arixtra®) is a fully synthetic pentasaccharide which acts like a heparin but has an increased half life. Fondaparinux has a diminished risk of HIT. However, no specific antidote is currently available for Fondaparinux. The novel oral anticoagulants (NOAC) dabigatran etexilat (Pradaxa®), rivaroxaban (Xarelto®) and apixaban (Eliquis®), also known as "direct" anticoagulants, act independently from antithrombin by inhibiting thrombin, as in the case of dabigatran, or by inhibiting factor Xa, as in the case of rivaroxaban and apixaban. It is assumed that they are suitable for long-term use and do not require laboratory monitoring. Nevertheless, clinical experience is very limited and caution rather than quick conclusions is necessary. Two major drawbacks are on the one hand the risk of drug accumulation in kidney and/or liver disease and, on the other hand, the lack of specific antidotes. In addition, interactions with other medication may have unexpected effects on serum drug levels. Therefore, the analysis of drug levels in the plasma may become necessary in subgroups of patients.. Studies establishing clear recommendations for the desirable and measurable reference range are needed. Similarly, evidence-based recommendations regarding perioperative prevention of thrombosis are required ("bridging": yes or no?). Irrespective of these issues, the authors predict a further expansion of the use of NOACs.

Topics: Administration, Oral; Anticoagulants; Benzimidazoles; Blood Coagulation Tests; Dabigatran; Drug Interactions; Factor Xa Inhibitors; Fondaparinux; Heparin; Humans; International Normalized Ratio; Liver Failure; Metabolic Clearance Rate; Morpholines; Perioperative Care; Polysaccharides; Pyrazoles; Pyridines; Pyridones; Renal Insufficiency; Rivaroxaban; Thiophenes; Thrombocytopenia; Thrombosis; Vitamin K

Prothrombin complex concentrates (PCCs) are purified drug products with hemostatic activity derived from a plasma pool. Today, PCCs contain a given and proportional amount of four non-activated vitamin K-dependent coagulation factors (II, VII, IX, and X), a variable amount of anticoagulant proteins (proteins C and S, and in some antithrombin) and low-dose heparin. In some countries PCC products contained only three clotting factors, II, IX, and X. Dosage recommendations are based on IU of F-IX, so that one IU of F-IX represents the activity of F-IX in 1 mL of plasma. Reversion of the anticoagulant effect of vitamin K antagonists (VKAs) in cases of symptomatic overdose, active bleeding episodes, or need for emergency surgery is the most important indication for PCCs and this effect of PCCs appears to be more complete and rapid than that caused by administration of fresh frozen plasma. They may be considered as safe preparations if they are used for their approved indications at the recommended dosage with adequate precautions for administration, and have been shown to be effective for reversing the effect of VKAs. Their adequate use based on decision algorithms in the perioperative setting allows a rapid normalization of International Normalized Ratio (INR) for performing emergency surgery, minimizing bleeding risk. This review aims to propose two algorithms for the use of PCCs in the perioperative setting, one to calculate the PCCs dose to be administered in a bleeding patient and/or immediately before urgent surgery, based on patient's clinical status, prior INR and INR target and another for reversing the action of oral anticoagulants depending on urgency of surgery.

Topics: Algorithms; Anticoagulants; Antidotes; Blood Coagulation Factors; Blood Coagulation Tests; Blood Loss, Surgical; Disseminated Intravascular Coagulation; Drug Monitoring; Emergencies; Evidence-Based Medicine; Hemorrhage; Hemostatics; Humans; Liver Failure; Perioperative Care; Postoperative Hemorrhage; Randomized Controlled Trials as Topic; Thromboembolism; Vitamin K

Biliary atresia (BA) is a rare disease, characterized by progressive and obliterative cholangiopathy, and is one of the major causes of secondary vitamin K deficiency in infancy. We describe 15 infants (10 female, 5 male) with BA, presenting with intracranial hemorrhage (ICH), including 10 subdural hemorrhages, 4 subarachnoid hemorrhages, 2 intraventricular hemorrhages, and 1 intraparenchymal hemorrhage. The age at onset of ICH ranged from 26 to 79 (mean 54.2) days. Eight patients underwent successful surgical evacuation of ICH, following administration of vitamin K. All 15 patients underwent Kasai portoenterostomy for BA 8-30 days after onset. During a mean follow-up period of 86.8 (range 2-352) months, 4 patients died of liver failure despite lack of neurological sequelae. Two patients underwent living-related donor and 1 patient living-unrelated donor liver transplantation. Only 2 patients suffered neurological signs and symptoms, including mental retardation and epilepsy, whereas 3 were noted to have temporary hemiparesis which recovered completely during the follow-up period. The possibility of BA should be considered in the treatment of ICH due to vitamin K deficiency, since it is reported to be one of the major causes of secondary vitamin K deficiency. Urgent surgical intervention for ICH can be performed successfully following sufficient administration of vitamin K or fresh frozen human plasma. Moreover, early performance of Kasai portoenterostomy is possible even for patients who have undergone craniotomy.

Topics: Biliary Atresia; Epilepsy; Female; Follow-Up Studies; Humans; Infant; Infant, Newborn; Intellectual Disability; Intracranial Hemorrhages; Liver Failure; Liver Transplantation; Male; Paresis; Vitamin K; Vitamin K Deficiency; Vitamins

We aimed at evaluating the performance of a new prothrombin time (PT) reagent (STA-NeoPTimal) with two other PT reagents (STA-Neoplastine R and STA-Neoplastine CI Plus) and the reference PT reagent used in our laboratory (ReadiPlasTin).. Evaluation consisted in intra- and interassay precision assessment, determination of sensitivity to unfractionated heparin (UFH) or enoxaparin in spiked samples and to direct oral anticoagulants (DOACs) in patients (n = 43). Method comparison of the 4 PT reagents, factor II, V, VII and X assays was tested on normal (n = 20) and abnormal samples: VKA (n = 47), preoperative (n = 23), liver failure (n = 12) and burned patients (n = 37).. Analytical performance met manufacturers' criteria for all reagents. All PT reagents gave correlation coefficients >0.8 and even >0.9 in many situations. In some VKA samples, differences ≥ 0.5 INR units were found in samples within and above therapeutic ranges. For burned patients, PT correlations were good but with some minimal bias (<5.0%) while factor assays gave very consistent results (R > .8 and mainly >0.9). As expected, poor responsiveness of the PT to DOAC concentrations was observed with all four assays.. The STA-NeoPTimal showed comparable performance to ReadiPlasTin, making it suitable for VKA control, detection of factors II, V, VII, X deficiency and assessment of liver disease coagulopathy. However, for patients receiving VKA, some significant differences were observed. We confirmed the inability of the PT assay to detect residual DOAC concentrations. Finally, burned patients results showed that recombinant thromboplastins were less sensitive to factor deficiencies in comparison to extraction thromboplastins.

Topics: Blood Coagulation; Blood Coagulation Tests; Humans; International Normalized Ratio; Liver Failure; Preoperative Period; Prothrombin Time; Reproducibility of Results; Sensitivity and Specificity; Thromboplastin; Vitamin K

Plasma transfusion is commonly used to correct elevated international normalized ratio (INR) before invasive procedures. A 54-year-old woman presented to the emergency department with abdominal pain. Workup revealed Streptococcus pneumoniae peritonitis. Her hospitalization was complicated by respiratory failure, fluid overload, atrial fibrillation, and acute kidney injury. Patient underwent 2 paracentesis (9 L removed). Four units of plasma were transfused to correct an INR of 3.0 (goal 1.5) for a transjugular intrahepatic portosystemic shunt procedure. INR remained at 1.9, and she developed acute pulmonary edema and died within 24 hours. Prothrombin complex concentrates may have been a more appropriate treatment option in this case.

Topics: Antifibrinolytic Agents; Blood Transfusion; Female; Humans; International Normalized Ratio; Liver Failure; Middle Aged; Portasystemic Shunt, Transjugular Intrahepatic; Transfusion Reaction; Vitamin K

The optimal initial treatment of splanchnic vein thrombosis is uncertain. Anticoagulant therapy has been shown to be associated with vessel recanalization and decreased recurrence. Furthermore, information regarding potential predictors of chronic complications is not well understood.. A retrospective cohort study involving consecutive patients diagnosed with first-episode noncirrhotic splanchnic vein thrombosis referred to the thrombosis clinic of the authors' institution between 2008 and 2011 was conducted. Demographic and clinical information was collected. The response to initial anticoagulant therapy was evaluated by determining radiographic recanalization of vessels and clinical resolution (defined as the absence of ongoing splanchnic vein thrombosis symptoms or complications requiring treatment beyond anticoagulant therapy).. Twenty-two patients were included. Anticoagulant therapy alone resulted in vessel recanalization in 41% of patients and 68% achieved clinical resolution. Two patients experienced bleeding events. Factors associated with a lack of clinical resolution included signs of portal hypertension⁄liver failure on presentation, complete vessel occlusion at diagnosis, presence of a myeloproliferative disorder or JAK2V617F tyrosine kinase mutation and the absence of a local⁄transient predisposing factor.. Anticoagulant therapy appeared to be an effective initial treatment in patients with splanchnic vein thrombosis. Clinical factors may help to identify patients who are at risk for developing complications thus requiring closer monitoring. These findings were limited by the small sample size and need to be explored in larger prospective studies.

Topics: Abdominal Pain; Adult; Aged; Anticoagulants; Female; Heparin, Low-Molecular-Weight; Humans; Hypertension, Portal; Janus Kinase 2; Liver Failure; Male; Middle Aged; Mutation; Myeloproliferative Disorders; Portal Vein; Retrospective Studies; Splanchnic Circulation; Splenic Vein; Treatment Outcome; Venous Thrombosis; Vitamin K

The association between acquired aplastic anemia (AA) and hepatitis/acute liver failure has been well characterized as AA temporally after the presentation of acute hepatitis. In this case series we report 2 cases of patients who present with AA occurring simultaneously with the development of acute liver failure. This is among only a few reported cases known to date in which AA occurs simultaneously with impending liver failure. More importantly, this is the first report that demonstrates the feasibility of administering immunosuppressive therapy before complete resolution of the hepatic dysfunction and with excellent results. Both of our cases avoided orthotopic liver transplantation through the use of timely immunosuppressive therapy, demonstrating the potential role of medical management to avoid transplantation in these patients. Previous studies have suggested a link between an unidentified viral process and immune dysregulation that may lead to the development of AA after acute hepatitis. These 2 cases support the rationale that in our patients the 2 disease processes may share a common etiology and encourage further research into the complex pathogenic mechanism affecting these 2 different organ systems at varying points in time.

Topics: Acute Disease; Adolescent; Anemia, Aplastic; Antilymphocyte Serum; Biopsy; Blood Coagulation Tests; Blood Transfusion; Bone Marrow; Child, Preschool; Cyclosporine; Feasibility Studies; Female; Granulocyte Colony-Stimulating Factor; Humans; Immunosuppressive Agents; Liver Failure; Liver Function Tests; Male; T-Lymphocytes; Vitamin K

Topics: Biopsy; Carnitine; Cholagogues and Choleretics; Female; Hemochromatosis; Humans; Immunoglobulins, Intravenous; Infant, Newborn; Infant, Premature; Iron; Lip; Liver Failure; Liver Regeneration; Mouth Mucosa; Salivary Glands, Minor; Ursodeoxycholic Acid; Vitamin K; Vitamins

International Normalized Ratio (INR), which standardizes prothrombin time (PT) during oral anticoagulation, has been extended to standardize PT in liver diseases and is included in prognostic models such as the Model for End stage Liver Disease (MELD). However, mechanisms of PT prolongation in liver diseases differ from those involved in oral anticoagulation, and the thromboplastin reagents differ in their sensitivities to these 2 mechanisms. Our aim was to determine whether, in the calibration model for thromboplastins proposed by the World Health Organization, the use of plasmas from patients with liver diseases instead of plasmas from patients on oral anticoagulation could lead to a new INR specific for liver diseases (INR "LD"), achieving a real standardization of PT. First, 5 thromboplastins were calibrated against an international reference using 60 plasmas of patients with liver failure and, in a second step, the variation of PT reported as seconds, the ratio of patient PT to normal PT, INR, and INR"LD" was assessed in 34 other patients. MELD scores were calculated with the INR values obtained with the 5 thromboplastins. Only INR"LD" eliminated variability in PT results observed with the different thromboplastins. The discrepancy between MELD scores were up to 4 and 7 points in 52% and 17% of the patients, respectively.. INR "LD" may provide a common international scale of PT reporting in hepatology. Its adoption would be an important step because of the significant impact on MELD score induced by interlaboratory variability in INR determination.

Topics: Adult; Aged; Calibration; Female; Humans; International Normalized Ratio; Liver Failure; Male; Middle Aged; Prothrombin Time; Severity of Illness Index; Thromboplastin; Vitamin K

Acute hepatic failure has been reported in the presence of Epstein-Barr virus (EBV) infection. Autoimmune hemolytic anemia may also occur in the course of this infection. We report a rare case of fulminant hepatic failure and autoimmune hemolytic anemia associated with Epstein-Barr virus. A seven-year-old girl was admitted with the complaints of abdominal pain, vomiting and jaundice. She was irritable, confused and had mild hepatomegaly with marked splenomegaly. Serum aminotransferase levels were moderately elevated, while direct and indirect bilirubin levels were markedly elevated. Prothrombin time was prolonged. Hemoglobin was 3.9 g/dl. Anti-HAV IgM, HbsAg, anti-HBc IgM, anti-HCV and anti-CMV IgM were negative, while IgM VCA EBV, IgG VCA EBV and anti-CMV IgG were positive. Serum copper and ceruloplasmin levels were normal. The patient received supportive therapy for hepatic failure. Meanwhile, the cause of the deep anemia was investigated and autoimmune hemolytic anemia was ascertained by means of increased reticulocyte count and positive Coombs test. Corticosteroid therapy was administered. The prognosis was good. Although not reported before, the combination of acute hepatic failure and autoimmune hemolytic anemia may complicate the course of EBV infection. Physicians need to be aware of this association.

Topics: Adrenal Cortex Hormones; Anemia, Hemolytic, Autoimmune; Anti-Bacterial Agents; Antifibrinolytic Agents; Blood Transfusion; Child; Epstein-Barr Virus Infections; Female; Gastrointestinal Agents; Herpesvirus 4, Human; Humans; Lactulose; Liver Failure; Neomycin; Plasma; Vitamin K

Despite advances in left ventricular assist device (LVAD) design that permit support without anticoagulation, LVAD recipients often suffer profound bleeding complications. This bleeding diathesis may be attributable to pre-operative right-ventricular failure with concomitant hepatic dysfunction. The purpose of this study was to characterize coagulation abnormalities in LVAD recipients and determine the impact of pre-operative vitamin K administration on the incidence of postoperative bleeding.. Hemostatic and liver function profiles were obtained in 66 recipients of the Heartmate LVAD; 39 of these patients received perioperative vitamin K.. During LVAD support, hepatic synthetic function improved as evidenced by increases in clotting factors II, V, VII, XI. There was ongoing fibrinolysis with elevation of fibrinopeptide A and D-dimers and diminution of fibrinogen; however, plasminogen levels did not decline suggesting that systemic disseminated intravascular coagulation (DIC) did not occur. Bleeding requiring re-exploration more than 48 hours postimplantation occurred in 9 of 66 patients (13.6%). Prior to implantation, patients that bled had decreased levels of factor II (52.2 +/- 27.1% vs 69.7 +/- 26.6%; p = 0.048) and prolonged prothrombin times (16.5 +/- 2.4 seconds vs 13.8 +/- 3.1 seconds; p = 0.005) compared to patients that did not bleed. Seven of 27 patients (25.9%) not treated with vitamin K bled, while only 2 of 39 (5.1%) patients treated with vitamin K required re-exploration for bleeding (p = 0.026).. We conclude that: (1) Liver synthetic function improves during LVAD support resulting in increased levels of circulating coagulation factors; (2) ongoing fibrinolysis occurs but likely only represents remodeling of fibrin on the LVAD surface; (3) perioperative vitamin K reduces nonsurgical bleeding in LVAD recipients.

Topics: Disseminated Intravascular Coagulation; Factor V; Factor VII; Factor XI; Female; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysis; Fibrinopeptide A; Heart-Assist Devices; Hemostasis; Humans; Incidence; Liver; Liver Failure; Male; Middle Aged; Plasminogen; Postoperative Hemorrhage; Premedication; Prothrombin; Prothrombin Time; Reoperation; Ventricular Dysfunction, Right; Ventricular Function, Left; Vitamin K

Topics: Administration, Oral; Diet; Humans; Injections, Intramuscular; Liver Cirrhosis; Liver Failure; Vitamin K