thromboplastin and Liver-Diseases

The liver is the primary source of a number of circulating coagulation factors, and acute liver injury and chronic liver disease are each associated with alterations in blood coagulation. Current views of the connection between liver injury and coagulation extend beyond the impact of liver disease on synthesis of coagulation factors to include a role for coagulation factor activity in the initiation and progression of liver disease. Mechanisms of coagulation initiation in liver disease are not completely understood. Compared to other tissues, liver expresses very low levels of tissue factor (TF). Recent studies indicate that expression of TF by hepatocytes comprises the majority of liver procoagulant activity, and that hepatocyte TF activates coagulation induced by liver injury. This review will briefly cover the expression and regulation of TF by hepatocytes, the role of TF in coagulation triggered by liver toxicity, and the contribution of coagulation activity to the progression of liver disease.

Topics: Animals; Blood Coagulation; Gene Expression; Hepatocytes; Humans; Liver; Liver Diseases; Thromboplastin

The Prothrombin Time (PT) test is used for monitoring of treatment with Vitamin K-antagonists (VKA). The result of the PT test should be expressed as the International Normalized Ratio (INR). Calculation of INR is based on the availability of International Standards (IS) for thromboplastin and a calibration model. Calibration of a new PT test system is performed with the appropriate IS and fresh plasma samples of healthy (normal) volunteers and patients treated with VKA. The calibration model is based on the assumption of a linear relationship between the log(PT)'s obtained with the new PT system and the reference IS for both normal and patients' samples. Patients' samples for calibration should be selected by rejecting samples beyond the 1.5-4.5 INR range. Outliers should be rejected defined as points with a perpendicular distance greater than three residual standard deviations from the line of relationship. Selection of patients' samples and rejection of outliers result in a reduction of the between-laboratory variation of calibration. In addition to monitoring of VKA, the PT is used for management of patients with chronic liver disease. Likewise, INR(liver) should be based on calibration with an IS using samples from patients with chronic liver disease.

Topics: Calibration; Humans; International Normalized Ratio; Liver Diseases; Prothrombin Time; Reference Standards; Sensitivity and Specificity; Thromboplastin

To review the state of the art of laboratory monitoring of oral anticoagulant therapy, as reflected by the medical literature and the consensus opinion of recognized experts in the field, and to make recommendations for improvement in laboratory monitoring of oral anticoagulant therapy.. Review of the medical literature, primarily from the last 10 years, and current laboratory practices by a panel of 8 international experts in the field of oral anticoagulant monitoring.. After an initial assessment of the literature, key points were identified. Experts were assigned to do an in-depth review of the literature and current practices relevant to each of the key points and to prepare a summary of their findings and recommendations. A draft manuscript was prepared and circulated to every participant in the College of American Pathologists Conference XXXI on Laboratory Monitoring of Anticoagulant Therapy prior to the conference. Each of the key points and associated recommendations was then presented for discussion at the Conference. Recommendations were accepted if a consensus of the 26 experts attending the Conference was reached. The results of the discussion were used to revise the manuscript into its final form.. Consensus was reached on 12 recommendations concerning the laboratory monitoring of oral anticoagulant therapy. Detailed discussion of the rationale for each of these recommendations is found in the text of this article. Discussion of points on which consensus was not reached is also included in the text. It is hoped that widespread adoption of these recommendations will further improve the laboratory monitoring of oral anticoagulant therapy.

Topics: Administration, Oral; Anticoagulants; Blood Coagulation Tests; Calibration; Drug Monitoring; Heart Failure; Heparin; Humans; Liver Diseases; Lupus Coagulation Inhibitor; Pathology, Clinical; Point-of-Care Systems; Reference Values; Self Care; Sensitivity and Specificity; Thromboplastin; United States

Extrinsic pathway inhibitor (EPI) is a Kunitz type serine protease inhibitor. EPI is a potent inhibitor of the factor VIIa/thromboplastin (TP) complex in the presence of factor Xa and is also a direct inhibitor of factor Xa. The inhibitory mechanism is complex and is currently thought to involve, in a first step, the formation of a EPI-factor Xa complex, and, in a second step, the formation a quaternary EPI-factor Xa-factor VIIa-TP complex. In the blood vessels, EPI is confined to three different pools. A major pool of EPI is bound to the endothelial surface, and this fraction may be released by heparin. Plasma contains a second, but smaller pool of EPI (approximately 10-50% of the endothelial surface pool) at a concentration of 50-100 ng/ml. This pool consists mostly of EPI-lipoprotein complexes and only less than 10% is carrier-free EPI. A third pool of EPI is confined to platelets (less than 10% of the plasma pool). The biological role of these pools has not yet been clarified, but some evidence suggest that the carrier-free EPI is biologically most active. In patients, disseminated intravascular coagulation may continue despite normal or even elevated EPI levels. However, evidence has now been provided to indicate that EPI can inhibit factor VIIa/TP complexes formed in vivo to prevent the effect of limited amounts of TP. Taken together, the present knowledge of EPI indicates that EPI functions as a key inhibitor to feedback control of blood coagulation initiated by TP.

Topics: Blood Coagulation; Blood Platelets; Disseminated Intravascular Coagulation; Endothelium, Vascular; Factor VII; Factor VIIa; Factor Xa Inhibitors; Feedback; Heparin; Humans; Lipoproteins; Liver Diseases; Neoplasms; Recombinant Proteins; Reference Values; Sepsis; Thromboplastin

Factor VII appears to be the key regulatory protein in the initiation of both the intrinsic and extrinsic systems of coagulation. The single chain, or zymogen form, of factor VII possesses enzymatic activity which makes it an ideal candidate for the initiation of coagulation following vascular injury. A number of interactions between the intrinsic and extrinsic systems of coagulation have been identified. It appears that factor VII is capable of directly activating factor IX and vice versa. The study of factor VII variants with associated thromboembolic complications may provide a number of answers regarding the initiation and regulation of the blood coagulation process.

Topics: Blood Coagulation; Blood Coagulation Tests; Cerebral Hemorrhage; Enzyme Activation; Factor IX; Factor VII; Factor VII Deficiency; Hemarthrosis; Hemophilia A; Humans; Lipoproteins; Liver Diseases; Neutralization Tests; Partial Thromboplastin Time; Radioimmunoassay; Thromboplastin; Thrombosis; Vitamin K Deficiency

Topics: Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Calcium; Factor IX; Factor V; Factor VIII; Factor X; Factor XII; Fibrin; Fibrinogen; Humans; Liver Diseases; Phospholipids; Prothrombin; Prothrombin Time; Thromboplastin; Vitamin K Deficiency

Topics: Anemia, Hemolytic; Blood Coagulation Tests; Disseminated Intravascular Coagulation; Factor XII; Fibrinogen; Fibrinolysis; Heparin; Humans; Liver Diseases; Meningitis, Meningococcal; Phospholipids; Thrombin; Thromboplastin

The INR system was developed to standardize PT reporting in patients on oral anticoagulants. We prospectively collected blood samples from 29 patients with liver impairment (INR 1.5-3.5). Control patients were on warfarin (n = 31). PT's were measured on an ACL-300 with three thromboplastin reagents. INR's were calculated using instrument specific ISI's. Other tests performed were FDP's, fibrinogen, aPTT, factors II, V, VII and X. The INR's for each patient in the study population using the three thromboplastin reagents were significantly different (p = 0.0001). Those for the control population were not (p = 0.0658). Fibrinogen, factors V, II and X were different at the 5% level of significance between the populations. FDP's were detected in 17 study subjects. The INR system is not valid for comparison of patients with liver impairment because different reagents do not give the same INR for the same sample. It is, however, no less valid than the use of PT with different thromboplastin reagents. Further study is recommended.

Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Indicators and Reagents; Liver Diseases; Male; Middle Aged; Prospective Studies; Prothrombin Time; Reference Standards; Reproducibility of Results; Thromboplastin; Warfarin; World Health Organization

Coronavirus disease 2019 (COVID-19) is a global pandemic which has caused numerous deaths worldwide. The present study investigated the roles of hypoproteinemia in the clinical outcome and liver dysfunction of COVID-19 patients. In this retrospective study, we extracted data from 2,623 clinically confirmed adult COVID-19 patients (>18 years old) between January 29, 2020 and March 6, 2020 in Tongji Hospital, Wuhan, China. The patients were divided into three groups-non-critically ill, critically ill, and death groups-in accordance with the Chinese Clinical Guideline for COVID-19. Serum albumin, low-density lipoproteins cholesterol (LDL-C), and high-density lipoproteins cholesterol (HDL-C) concentrations and inflammatory cytokines levels were measured and compared among these three groups. The median age of these 2,623 patients was 64 years old (interquartile range (IQR), 52-71). Among the patients enrolled in the study, 2,008 (76.6%) were diagnosed as non-critically ill and 615 (23.4%) were critically ill patients, including 383 (14.6%) critically ill survivors and 232 (8.8%) critically ill deaths in the hospital. Marked hypoalbuminemia occurred in 38.2%, 71.2%, and 82.4% patients in non-critically ill, critically ill, and death groups, respectively, on admission and 45.9%, 77.7%, and 95.6% of these three groups, respectively, during hospitalization. We also discovered that serum low-density lipoprotein (LDL) and HDL levels were significantly lower in critically ill and death groups compared to non-critically ill group. Meanwhile, the patients displayed dramatically elevated levels of serum inflammatory factors, while a markedly prolonged activated partial thromboplastin time (APTT) in critically ill patients reflected coagulopathy. This study suggests that COVID-19-induced cytokine storm causes hepatotoxicity and subsequently critical hypoalbuminemia, which are associated with exacerbation of disease-associated inflammatory responses and progression of the disease and ultimately leads to death for some critically ill patients.

Topics: Aged; China; Cholesterol, HDL; Cholesterol, LDL; Coronavirus Infections; COVID-19; Critical Illness; Cytokines; Female; Humans; Liver Diseases; Male; Middle Aged; Prognosis; Retrospective Studies; Risk Factors; SARS-CoV-2; Serum Albumin, Human; Thromboplastin; Time Factors

Platelets play a pivotal role in stimulating liver regeneration after partial hepatectomy in rodents and humans. Liver regeneration in rodents is delayed when platelets are inhibited. However, the exact mechanisms whereby platelets accumulate and promote liver regeneration remain uncertain. Thrombin-dependent intrahepatic fibrin(ogen) deposition was recently reported after partial hepatectomy (PHx) in mice, but the role of fibrin(ogen) deposits in liver regeneration has not been investigated. We tested the hypothesis that fibrin(ogen) contributes to liver regeneration by promoting intrahepatic platelet accumulation and identified the trigger of rapid intrahepatic coagulation after PHx. PHx in wild-type mice triggered rapid intrahepatic coagulation, evidenced by intrahepatic fibrin(ogen) deposition. Intrahepatic fibrin(ogen) deposition was abolished in mice with liver-specific tissue factor deficiency, pinpointing the trigger of coagulation after PHx. Direct thrombin activation of platelets through protease-activated receptor-4 did not contribute to hepatocyte proliferation after PHx, indicating that thrombin contributes to liver regeneration primarily by driving intrahepatic fibrin(ogen) deposition. Fibrinogen depletion with ancrod reduced both intrahepatic platelet accumulation and hepatocyte proliferation after PHx, indicating that fibrin(ogen) contributes to liver regeneration after PHx by promoting intrahepatic platelet accumulation. Consistent with the protective function of fibrin(ogen) in mice, low postoperative plasma fibrinogen levels were associated with liver dysfunction and mortality in patients undergoing liver resection. Moreover, increased intrahepatic fibrin(ogen) deposition was evident in livers of patients after liver resection but was remarkably absent in patients displaying hepatic dysfunction postresection. The results suggest a novel mechanism whereby coagulation-dependent intrahepatic fibrin(ogen) deposition drives platelet accumulation and liver regeneration after PHx.

Topics: Adult; Aged; Aged, 80 and over; Animals; Blood Coagulation; Female; Fibrinogen; Follow-Up Studies; Hepatectomy; Humans; Liver Diseases; Liver Regeneration; Male; Mice; Mice, Inbred C57BL; Middle Aged; Platelet Activation; Prognosis; Prospective Studies; Receptors, Thrombin; Thrombin; Thromboplastin

Coagulation is a critical component in the progression of liver disease. Identification of key molecules involved in the intrahepatic activation of coagulation (IAOC) will be instrumental in the development of effective therapies against liver disease. Using a mouse model of concanavalin A (ConA)-induced hepatitis, in which IAOC plays an essential role in causing liver injury, we uncovered a procoagulant function of chitinase 3-like 1 (Chi3l1). Chi3l1 expression is dramatically elevated after ConA challenge, which is dependent on ConA-induced T cell activation and the resulting interferon γ and tumor necrosis factor α productions. Compared with wild-type mice, Chi3l1. Our data demonstrate that Chi3l1, through induction of TF via mitogen-activated protein kinase activation, promotes IAOC and tissue injury. (Hepatology 2018;67:2384-2396).

Topics: Animals; Blood Coagulation; Cells, Cultured; Chitinase-3-Like Protein 1; Female; Liver; Liver Diseases; Male; Mice; Thromboplastin

In patients with chronic liver diseases, hypercoagulability can contribute to the progression of fibrosis and complications of cirrhosis. Tissue factor (TF) is a transmembrane glycoprotein that initiates the extrinsic pathway of blood coagulation. Recent investigations have established that TF is elevated in patients with pancreatic cancer, blood disorders, diabetes, and cardiovascular disease. Alternatively spliced tissue factor (asTF), a secreted form of TF, induces angiogenesis and exhibits low-level procoagulant activity. The aim of this study was to investigate whether the circulating levels of asTF are elevated in the plasma of patients with liver disease.. In a single-center study, we retrospectively analyzed asTF plasma levels in healthy participants and patients having stage F0-F3 liver fibrosis, liver cirrhosis, as well as hepatocellular carcinoma (HCC). AsTF plasma levels were measured using a sandwich enzyme-linked immunosorbent assay. Values were expressed as median with interquartile range (IQR).. The lowest median plasma asTF concentration (94 pg/ml, IQR: 33-275) was found in the healthy control group. The patients with low-grade liver fibrosis (F0-F1 group) displayed the highest median asTF concentration (404 pg/ml, IQR: 277-789). Significant differences between the asTF levels in the plasma of healthy participants and those in patients with grade F0-F1 fibrosis (P<0.001), patients with grade F2-F3 fibrosis (P=0.019), patients with cirrhosis (P=0.004), and patients with HCC (P<0.001) were found using a Wilcoxon rank-sum test. Treatment-naive patients with HCC had significantly higher asTF levels (P=0.018) than those receiving treatment. AsTF levels were found to increase with worsening Child-Pugh scores and heightened liver disease activity.. AsTF levels are elevated in patients with chronic liver diseases, which increase with worsening Child-Pugh scores and decrease following HCC therapy.

Topics: Adult; Alternative Splicing; Biomarkers; Carcinoma, Hepatocellular; Chronic Disease; Female; Humans; Liver Cirrhosis; Liver Diseases; Liver Neoplasms; Male; Middle Aged; Retrospective Studies; Severity of Illness Index; Thromboplastin

This study aims to investigate the molecular mechanisms underlying the pathogenesis of severe acute pancreatitis (SAP) and SAP-associated liver injury, we performed an association analysis of the functions of tissue factor (TF) and blood coagulation system in both SAP patients and mouse SAP model. Our results showed that serum TF and tissue factor-microparticle (TF-MP) levels were highly up-regulated in both SAP patients and SAP mouse model, which was accompanied by the dysfunction of blood coagulation system. Besides, TF expression was also highly up-regulated in the Kupffer cells (KCs) of SAP mouse model. After inhibiting KCs in SAP mouse model, the amelioration of blood coagulation system functions was associated with the decrease in serum TF and TF-MPs levels, and the reduction of SAP-associated liver injury was associated with the decrease of TF expression in KCs. In conclusion, the dis-regulated TF expression and associated dysfunction of blood coagulation system are critical factors for the pathogenesis of SAP and SAP-associated liver injury. TF may serve as a potential and effective target for treating SAP and SAP-associated liver injury.

Topics: Aged; Animals; Blood Coagulation; Female; Gadolinium; Humans; Kupffer Cells; Liver Diseases; Male; Mice; Mice, Inbred C57BL; Middle Aged; Pancreatitis; RNA, Messenger; Thromboplastin; Up-Regulation

Patients with chronic liver disease and cirrhosis have a dysregulated coagulation system and are prone to thrombosis. The basis for this hypercoagulable state is not completely understood. Tissue factor (TF) is the primary initiator of coagulation in vivo. Patients with cirrhosis have increased TF activity in white blood cells and circulating microparticles. The aim of our study was to determine the contribution of TF to the hypercoagulable state in a mouse model of chronic liver injury.. We measured levels of TF activity in the liver, white blood cells and circulating microparticles, and a marker of activation of coagulation (thrombin-antithrombin complexes (TATc)) in the plasma of mice subjected to bile duct ligation for 12days. We used wild-type mice, mice with a global TF deficiency (low TF mice), and mice deficient for TF in either myeloid cells (TF(flox/flox),LysMCre mice) or in hepatocytes (TF(flox/flox),AlbCre).. Wild-type mice with liver injury had increased levels of white blood cell, microparticle TF activity and TATc compared to sham mice. Low TF mice and mice lacking TF in hepatocytes had reduced levels of TF in the liver and in microparticles and exhibited reduced activation of coagulation without a change in liver fibrosis. In contrast, mice lacking TF in myeloid cells had reduced white blood cell TF but no change in microparticle TF activity or TATc.. Hepatocyte TF activates coagulation in a mouse model of chronic liver injury. TF may contribute to the hypercoagulable state associated with chronic liver diseases in patients.

Topics: Animals; Cells, Cultured; Chronic Disease; Disease Models, Animal; Hepatocytes; Humans; Liver Diseases; Male; Mice; Mice, Inbred C57BL; Thrombophilia; Thromboplastin

The international normalized ratio (INR) may not be directly applicable to patients with liver disease. We aimed to establish an alternative INR calibration system for patients with liver disease and to evaluate the effect of their use in chronic liver disease patients. Eighty-two patients with liver cirrhosis (LC) were included, and their prothrombin times (PTs) were measured by using 5 commercial thromboplastins. Each of the thromboplastins was also assigned an international sensitivity index (ISIliver) by the plasmas from LC patients. INRvka, INRliver, model for end-stage liver disease (MELD)vka, MELDliver, Child-Pugh (Child)vka, and Childliver scores were calculated. The coefficient of variance of INRvka was significantly larger than that of INRliver (P < 0.01). The mean difference in INRvka between the thromboplastins was also significantly larger than that in INRliver (P < 0.01). The total mean MELDliver score was higher than the total mean MELDvka score. The mean difference between the MELDvka and MELDliver scores (MELD score ≥15) was 3.2 %. We reconfirmed that the use of the alternative calibration system described herein for patients with liver disease may resolve the variability of INR measurement. Our data suggest that we would need to reevaluate the correlation between Child-Pugh class, MELD score, and clinical prognosis by using INRliver for patients with LC.

Topics: Aged; Chronic Disease; Female; Humans; International Normalized Ratio; Liver Cirrhosis; Liver Diseases; Male; Middle Aged; Prothrombin Time; Reference Values; Thromboplastin

Gestational alloimmune liver disease is the main cause of the neonatal hemochromatosis phenotype, wherein severe neonatal liver disease is associated with iron overload and extrahepatic tissue siderosis. How fetal liver disease produces extrahepatic siderosis is not known. We hypothesized that fetal liver injury causes deficient hepcidin production and poor regulation of placental iron flux. Under the resulting conditions of iron overload, the tissue pattern of extrahepatic siderosis is determined by the normal expression of proteins involved in the import of non-transferrin-bound iron and the export of cellular iron.. Liver and extrahepatic tissues from infants with gestational alloimmune liver disease were examined and compared to normal age-appropriate tissues.. Serum iron indices indicate iron overload and excess non-transferrin bound iron in gestational alloimmune liver disease. The diseased liver showed significantly reduced hepcidin, hemojuvulin, and transferrin gene expression compared to the normal fetal and neonatal liver. Those extrahepatic tissues that are typically involved in pathological siderosis in neonatal hemochromatosis, whether from normal or diseased newborns, consistently expressed solute carrier family 39 (zinc transporter), member 14 (ZIP14) for non-transferrin-bound iron uptake and expressed little ferroportin for iron export.. Excess non-transferrin-bound iron in gestational alloimmune liver disease may result from fetal liver injury that causes reduced synthesis of key iron regulatory and transport proteins. Whereas, the pattern of extrahepatic siderosis appears to be determined by the normal capacity of various tissues to import non-transferrin-bound iron and not export cellular iron.

Topics: Antimicrobial Cationic Peptides; Female; GPI-Linked Proteins; Hemochromatosis; Hemochromatosis Protein; Hepcidins; Humans; Infant, Newborn; Iron; Isoantigens; Liver Diseases; Pregnancy; Pregnancy Complications; Siderosis; Thromboplastin

Severe acute pancreatitis (SAP)-associated liver injury is systematically one of main pathophysiological events due to SAP development. The aim of the study was to investigate whether fgl2 prothrombinase is involved in SAP-associated liver injury.. Microthrombosis in the liver of rats with SAP was observed by Masson staining. Fgl2 prothrombinase expression in the liver of rats with SAP was analyzed by real-time PCR and immunohistochemistry methods.. Fgl2 prothrombinase gene and protein expression in SAP group were significantly up-regulated compared to sham-operation (SO) group. Immunohistochemistry staining showed that fgl2 prothrombinase was localized speci?cally to the endothelial cells of intrahepatic veins and hepatic sinusoids. Furthermore, Masson staining demonstrated that the proportion of hepatic microthrombotic capillaries in SAP group were evidently increasing in comparison to SO group and closely correlated with fgl2 expression (r=0.948, p<0.01 ). In addition, there was a positive correlation between fgl2 expression and the severity of hepatocellular injury as indicated by hepatic pathological grade (r=0.704, p<0.01).. Fgl2 prothrombinase may contribute to microthrombosis in SAP-associated liver injury, thus resulting in hepatic microcirculatory disturbance and measurement of fgl2 may be used as a helpful biomarker in the prognosis of the severity of hepatic pathological injury in SAP.

Topics: Acute Disease; Alanine Transaminase; Animals; Aspartate Aminotransferases; Immunohistochemistry; Liver; Liver Diseases; Male; Pancreatitis; Rats; Rats, Sprague-Dawley; Thromboplastin; Thrombosis

Patients with liver disease often show substantial changes in their hemostatic system, which may aggravate further during liver transplantation. Recently, thrombin generation in patients with stable disease was shown to be indistinguishable from controls provided thrombomodulin, the natural activator of the anticoagulant protein C system, was added to the plasma. These results indicated that the hemostatic balance is preserved in patients with liver disease, despite conventional coagulation tests suggest otherwise.. Here we examined thrombin generation profiles in serial plasma samples taken from ten consecutive patients undergoing liver transplantation.. At all time points, the endogenous thrombin potential (ETP) was slightly lower compared to healthy volunteers, despite substantially prolonged PT and APTT values. However, when thrombin generation was tested in the presence of thrombomodulin, the ETP was equal to or even higher than that in healthy subjects. In fact, thrombin generation was hardly affected by thrombomodulin, while thrombin generation in healthy subjects decreased profoundly upon the addition of thrombomodulin. In patients undergoing liver transplantation, efficient thrombin generation in the presence of thrombomodulin may be explained by decreased levels of protein C, S, and antithrombin, and by elevated levels of FVIII.. Thrombin generation in patients undergoing liver transplantation is equal or even superior to thrombin generation in healthy volunteers when tested in the presence of exogenous thrombomodulin. These results support the recently advocated restrictive use of plasma during liver transplantation and warrants further study of the prophylactic use of anticoagulants to reduce thromboembolic complications after transplantation.

Topics: Adult; Blood Coagulation Tests; Case-Control Studies; Cholangitis, Sclerosing; Factor VIII; Female; Hepatitis C; Humans; Liver Cirrhosis; Liver Diseases; Liver Transplantation; Male; Middle Aged; Prothrombin Time; Thrombin; Thrombomodulin; Thromboplastin; Time Factors

The International Normalised Ratio (INR)/International Sensitivity Index (ISI) system was developed as a way to standardise the prothrombin time during the monitoring of patients undergoing oral anti-coagulant therapy with vitamin K antagonists. The wide acceptance of the INR has led to its use as one of three parameters used in the Model for End stage Liver disease (MELD) scoring system to aid the prioritisation of patients for liver transplant. Literature published recently has highlighted the potential inadequacy of the INR system in this context. Our aim was to investigate the degree of difference between INR values calculated using an ISI derived from warfarinised patients and those calculated using an ISI derived from patients with liver disease. Prothrombin times from 60 patients with liver disease were determined using three working thromboplastin reagents; Innovin, Thromborel S and Thromboplastin C and two reference thromboplastins; rTF/95 and RBT/05. All thromboplastin reagents tested had standard international sensitivity indices (ISIs) assigned following calibration with patients on oral anticoagulant therapy (ISIvka). As a result of the new calibration each of the working thromboplastin reagents was assigned a specific "liver patient" ISI. Two INR values were calculated for each thromboplastin patient involved in the calibration. A comparison of the mean INRliver with INRvka showed a statistically significant difference between the two values (p<0.0001). A similar relationship existed for INRs on a further 20 patients with liver disease whose plasmas were not used to derive the ISIliver. This difference led to a change in the final MELD score and could therefore affect the prioritisation and management of these patients.

Topics: Acute Disease; Administration, Oral; Anticoagulants; Blood Coagulation; Calibration; Chronic Disease; Humans; International Normalized Ratio; Liver; Liver Diseases; Liver Transplantation; Predictive Value of Tests; Prothrombin Time; Recombinant Proteins; Severity of Illness Index; Thromboplastin; Warfarin

Platelets have been implicated in the pathogenesis of liver damage after orthotopic liver transplantation (OLT). Early graft dysfunction is frequently caused by reperfusion injury subsequent to cold ischemia (IRI). Therefore, we investigated activation of the pivotal haemostatic cells, platelets and monocytes, from patients with elevated markers of IRI and from patients with uneventful course (control-group), respectively during the first week after OLT. Flow cytometry analysis of citrate anticoagulated blood samples revealed that platelets from IRI patients became significantly activated within 48 h after OLT in vivo, with increased surface presentation of P-selectin, CD40L, thrombospondin-1 and tissue-factor. Platelet activation in IRI patients on post-transplant day 2 was accompanied by significantly enhanced tissue-factor expression on peripheral blood monocytes, significant elevated levels of C-reactive protein and hepatocellular damage. Towards post-transplant day 4, levels of platelet-derived microparticles rose significantly in IRI patients if contrasted to control patients. Thus, activated cellular haemostasis is involved in the early inflammatory response of hepatocellular damage subsequent to reperfusion of the transplanted liver. Targeting distinct activation patterns of platelets and monocytes in an early phase of hepatic grafting may counteract the extent of IRI via inhibition of micro-thrombus formation and inflammation without exacerbating the existing bleeding risk.

Topics: Adult; Blood Platelets; Case-Control Studies; Female; Humans; Inflammation; Liver; Liver Diseases; Liver Transplantation; Male; Middle Aged; Monocytes; Platelet Activation; Prospective Studies; Reperfusion Injury; Thromboplastin

The prothrombin time (PT) assay is the most clinically ordered coagulation test and is most often used for monitoring of vitamin K antagonist (VKA) therapy (e.g., warfarin), where results are expressed as an international normalized ratio (INR). The INR is in essence the patient's PT "mathematically adjusted" to a standardized value by taking into account the peculiarities of the test system through applying two "correction factors" defined by an international sensitivity index (ISI) and mean normal prothrombin time (MNPT). Although some manufacturers provide assigned ISI values for specific PT reagents and instrumentation, it is still recommended practice that laboratories check or locally validate these ISIs, as well as estimate the MNPT based on the population being tested. Where a manufacturer does not provide an ISI, the laboratory needs to define its own (local ISI) value. Current recommendations suggest the use of commercial reference-plasma calibration sets, but there is limited information to validate their performance in laboratory practice. We report our personal experience with use of some of these materials, as well as review alternate or supplementary procedures for calibration and/or validation of ISI and for determination and validation of MNPT. In brief, our data and experience suggests that further verification checks should be performed prior to acceptance of ISI and MNPT estimates generated from commercial reference-plasma calibration sets. We detail various strategies to ensure that laboratory practices are optimized to provide INRs that accurately reflect a patient's true anticoagulant status and to thus assist their clinical therapeutic management.

Topics: Anticoagulants; Calibration; Humans; International Normalized Ratio; Liver Diseases; Prothrombin Time; Reference Standards; Thromboplastin

Nodular regenerative hyperplasia (NRH) of the liver is a local hyperplastic response of hepatocytes, probably due to vascular abnormalities. Since it was shown in a few case reports that NRH may be associated with antiphospholipid antibodies (APA) we wanted to analyze the relevance of APA in patients with this disease. Sera from 13 patients with histologically defined NRH were tested for APA by an in-house ELISA using as antigens cardiolipin (CL), beta2-glycoprotein I (beta2-gp I), phosphatidylserine (PS), and thromboplastin (TP), a mixture of different phospholipids and phospholipid-binding proteins. As controls, sera from patients with serologically and histologically defined autoimmune liver diseases (primary biliary cirrhosis n = 14; autoimmune hepatitis n = 14) without histological evidence for NRH as well as from 14 healthy blood donors were analyzed. 77% of the NRH patients had APA. In 46% they were directed against CL. In contrast, only 14% of the patients with autoimmune liver diseases and 14% of the healthy controls had anti-CL antibodies (p < 0,05). Antibodies to beta2-gp I and TP did not discriminate between NRH and autoimmune liver diseases. Anti-PS antibodies were not observed. These data indicate that determination of anti-CL antibodies in NRH may help to identify a subgroup of patients in whom an 'organ-specific antiphosholipid syndrome' of the liver may be involved in the pathogenesis.

Topics: Adult; Aged; Antibodies, Antiphospholipid; beta 2-Glycoprotein I; Cardiolipins; Enzyme-Linked Immunosorbent Assay; Female; Glycoproteins; Humans; Hyperplasia; Liver; Liver Diseases; Liver Regeneration; Male; Middle Aged; Phosphatidylserines; Thromboplastin

Patients receiving maintenance hemodialysis (HD) present with hemostatic abnormalities, which may be aggravated by comorbid conditions, especially liver disease. The factors that influence plasma levels of thrombomodulin (TM), an initiator of the anticoagulant protein C pathway, and those of tissue factor (TF), which triggers the extrinsic coagulation pathway, were assessed. In 63 HD patients, TM and TF levels were higher than those in healthy controls. In bivariate analysis, TF positively correlated with TM, and both were directly associated with the presence of viral hepatitis B or C marker, serum liver enzymes, use of erythropoietin therapy, hemoglobin levels, and duration of HD therapy, and inversely correlated with body mass index. TF was also positively associated with plasma von Willebrand factor (vWF) antigen, and inversely associated with activated partial thromboplastin time. In multivariate analysis, increased vWF, alanine aminotransferase, and use of erythropoietin independently predicted both TF and TM levels. HD patients with vWF and ALT levels lower than middle, and not treated with erythropoietin had normal TF but increased TM concentrations compared with levels in healthy controls. Increased plasma levels of TM and TF in patients on maintenance HD are surrogates of vascular endothelial injury. Liver disease and use of erythropoietin treatment are also important determinants of these markers, and should be considered in further studies.

Topics: Adult; Aged; Aged, 80 and over; Analysis of Variance; Biomarkers; Case-Control Studies; Clinical Enzyme Tests; Cross-Sectional Studies; Endothelium, Vascular; Erythropoietin; Female; Hepatitis, Viral, Human; Humans; Liver Diseases; Male; Middle Aged; Prevalence; Renal Dialysis; Thrombomodulin; Thromboplastin; von Willebrand Factor

Wide acceptance of the international normalised ratio (INR) and thromboplastins with low international sensitivity indices (ISIs) has inadvertently led to the application of the INR to patients other than those on anticoagulation treatment. I examined the degree of factor deficiency for a given INR in patients with liver disease and controls receiving stable-dose warfarin. The degree of factor V and VII, but not prothrombin, deficiencies for a given INR were greater in liver patients than controls. The INR measured with a low-ISI thromboplastin can quantify the coagulation status of patients with liver disease, but should not be interpreted as having the same meaning as the INR in patients receiving warfarin.

Topics: Adult; Case-Control Studies; Factor V; Factor VII; Humans; International Normalized Ratio; Liver Diseases; Prothrombin; Prothrombin Time; Thromboplastin; Warfarin

Monocyte tissue factor expression was evaluated in 67 patients with hepatosplenic Schistosomiasis. They were classified as Child A (n = 15), Child B (n = 15), Child C (n = 12) and Bleeders (n = 10), in addition to 15 healthy controls. Mononuclear cells were cultured in vitro with and without lipopolysaccharide (LPS) to assess monocyte tissue factor (TF) antigen (Ag) and activity (Act) in cell lysate, in addition to measurement of prothrombin fragment 1 + 2 (F1 + 2) as a marker of in vivo thrombin generation. A significant increase in monocyte TF Ag and TF Act was noted in all stages of the disease compared with the control group, with marked accentuation during an acute attack of variceal bleeding. This enhanced monocyte expression was noted before the addition of LPS and became more obvious with addition of LPS. An increasing level of F1 + 2 was similarly noted. These findings constitute further evidence for an existing prothrombotic state in hepatosplenic Schistosomiasis, and also that monocytes are closely implicated in the haemostatic diathesis characterizing the disease.

Topics: Adult; Case-Control Studies; Hemorrhagic Disorders; Humans; Lipopolysaccharides; Liver Diseases; Monocytes; Peptide Fragments; Prothrombin; Schistosomiasis; Severity of Illness Index; Splenic Diseases; Thrombophilia; Thromboplastin

Topics: Factor V; Factor VII; Factor X; Humans; International Normalized Ratio; Liver Diseases; Prothrombin; Prothrombin Time; Thromboplastin

Gut-derived substances can activate Kupffer cells to provoke hepatic necrosis after partial hepatectomy in rats. A similar situation may occur during orthotopic liver transplantation (OLT), as congestion in the intestinal wall, caused by portal vein occlusion, is inevitable during the operation. The contribution of such substances to liver injury following OLT was investigated in rats. Oral administration of polymyxin B sulfate for 7 days significantly altered intestinal bacterial flora in rats; Enterobacteriaceae diminished and anaerobes such as Bifidobacterium , Lactobacillus, Bacteroides, and Eubacterium increased in number, compared with the control rats. Also, this treatment significantly reduced endotoxin concentration in the portal blood 30 minutes after blood reflow following portal vein occlusion. When OLT was performed in rats using the liver preserved in cold University of Wisconsin solution for 18 hours, tissue factor activity in Kupffer cells (KC) isolated from the transplanted liver 1 hour after the operation was significantly higher than in that of normal rats. This increase was significantly reduced by pretreatment of the recipients with polymyxin B sulfate. In these recipients, serum alanine aminotransferase activity, tumor necrosis factor alpha (TNF alpha) concentration, and histological extent of liver necrosis were significantly attenuated at 24 hours after the operation compared with those of control rats. We conclude that the substances derived from bacilli sensitive to polymyxin B sulfate in the gut may be a contributing factor to liver injury following OLT in rats; we feel that this probably occurs by entering of the substances into the portal blood during the ahepatic phase of the operation to activate KC. Selective bowel decontamination of recipients with polymyxin B sulfate would be a candidate for protection against early graft failure following OLT.

Topics: Animals; Anti-Bacterial Agents; Bacteria; Endotoxins; Intestines; Kupffer Cells; Liver; Liver Diseases; Liver Transplantation; Male; Polymyxin B; Portal System; Postoperative Complications; Preoperative Care; Rats; Rats, Inbred F344; Thromboplastin; Tumor Necrosis Factor-alpha

A simple chromogenic substrate assay for the quantitation of tissue factor pathway inhibitor (TFPI) activity in plasma or serum samples was developed. After immobilization on microtiter plates for 20 hours at 4 degrees C, a commercial thromboplastin was incubated for 1 hour at room temperature with 1 U/mL of a prothrombin complex concentrate (Protromplex). After washing, solid-phase Factor Xa activity was measured by a chromogenic substrate (S-2222). Factor Xa generation was progressively inhibited when increasing amounts (1-12 microL) of heated serum or plasma, and recombinant TFPI (1-5 ng/mL), were coincubated with Protromplex. Inhibition by serum or plasma was abolished by anti-TFPI polyclonal antibodies. Plasma levels of TFPI in 25 healthy volunteers were found to be 0.98 +/- 0.19 U/mL (range 0.71-1.52), with an intra- and inter-assay coefficient of variation of 10.7 and 11.1%, respectively. The use of a recombinant human thromboplastin improved the sensitivity and reproducibility of the assay. Plasma levels of TFPI were found to be normal in 10 women at the end of their pregnancies, in 10 patients receiving oral anticoagulant therapy, and in 10 diabetic patients. Significantly higher levels were detected in 10 patients with chronic liver disease and in 10 patients with unexplained juvenile thrombosis. In patients with cardiovascular disease, a 7-day treatment with subcutaneous standard heparin increased TFPI activity. The availability of a simple and rapid assay to measure TFPI that does not require purified coagulation proteins may facilitate studies of the pathophysiologic relevance of this inhibitor.

Topics: Adolescent; Adult; Cardiovascular Diseases; Chromogenic Compounds; Factor Xa Inhibitors; Female; Humans; Lipoproteins; Liver Diseases; Male; Middle Aged; Plasma; Recombinant Proteins; Reference Values; Sensitivity and Specificity; Serine Proteinase Inhibitors; Thromboplastin

Topics: Animals; Biomarkers; Brain Chemistry; Calibration; Humans; Indicators and Reagents; Liver Diseases; Placenta; Protein Precursors; Prothrombin; Prothrombin Time; Rabbits; Recombinant Proteins; Reference Standards; Reproducibility of Results; Sensitivity and Specificity; Thromboplastin; World Health Organization

The recent introduction of thromboplastin reagents with low international sensitivity index (ISI) values into the US market for the purpose of generating a more precise international normalized ratio than high ISI thromboplastins could has necessitated an evaluation of the impact of the low ISI reagents on prothrombin time (PT) testing in general. In this study, PT testing with three thromboplastin reagents, one of which (presently used in our laboratory) has an ISI of 2.10 and the other two ISI values of 0.92 and 1.06, respectively, was performed on normal individuals, on quality control reference plasma specimens and single-factor-deficient plasma specimens, and on patients with liver disease, intravascular coagulation, and receiving oral anticoagulant therapy. We found that PTs of normal individuals determined by all three thromboplastins were virtually identical. The thromboplastins with a low ISI generated much longer PTs on abnormal reference plasma specimens than did the high ISI product. Low ISI reagents also produced longer PTs in all three groups of patients. However, the degree of prolongation was far greater for patients receiving warfarin than for the other two groups of patients. Conversion of the PT to an international normalized ratio minimized the discrepancy seen in the PT ratio in patients receiving oral anticoagulants. The two low ISI thromboplastins did not produce near-identical values of PT, PT ratio, or international normalized ratio on plasma specimens obtained from patients who received warfarin therapy. The critical value set for PT with a high ISI thromboplastin would not be adequate if the reagent is to be replaced with a low ISI product.

Topics: Administration, Oral; Disseminated Intravascular Coagulation; Humans; Liver Diseases; Prothrombin Time; Quality Control; Reference Standards; Regression Analysis; Sensitivity and Specificity; Thromboplastin; Warfarin

The purpose of the present study was to compare the results obtained with a human recombinant thromboplastin (Innovin, Baxter) (IN) and a high-sensitivity rabbit brain reagent (Thromboplastin IS, Baxter) (IS), on the performance of prothrombin time (PT) test and the functional assay of factors included in the extrinsic coagulation system, in order to establish possible differences on imprecision, diagnostic accuracy and sensitivity to the oral anticoagulant defect, between the two products.. Six Spanish hospital took part in the study. Plasma samples from 221 healthy subjects, 100 patients with severe liver disease, 27 with dysfibrinogenaemia, 10 with lupus anticoagulant and from 13 individuals propositus and their relatives with congenital deficiencies of the extrinsic coagulation pathway, and their relatives were studied; 188 patients stabilized on oral anticoagulant therapy and 82 on heparin therapy were also included. The in vitro effect of heparin was tested by addition of increasing amounts of heparin (0.3 to 10.0 IU/mL) to aliquots of normal plasma.. Both in the intra-assay and in the inter-assay imprecision study, a better coefficient of variation was obtained with IN when the PT was performed on abnormal samples. Prothrombin time ratio from patients with liver disease had significantly higher values with IS. On the contrary, IN had a higher sensitivity in samples from patients with dysfibrinogenaemia or from those stabilized on oral anticoagulant therapy. In showed a very low sensitivity to heparin at concentrations corresponding to the therapeutic range.. The results of this field study indicate that IN, compared with a high-sensitivity rabbit brain thromboplastin, is a suitable reagent for PT determination in normal subjects, patients with liver disease or with congenital deficiencies of clotting factors. It shows a higher sensitivity in cases of dysfibrinogenaemia and in patients on oral anticoagulant therapy. In addition, the recombinant reagent had better reproducibility when the PT was performed on abnormal samples, and it was hardly affected by heparin within the therapeutic range.

Topics: Afibrinogenemia; Animals; Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Heparin; Humans; Indicators and Reagents; Liver Diseases; Lupus Coagulation Inhibitor; Phospholipids; Prothrombin Time; Rabbits; Recombinant Fusion Proteins; Reproducibility of Results; Sensitivity and Specificity; Thromboplastin

A new PT reagent based on recombinant human tissue factor and synthetic phospholipids (phosphatidyl choline and phosphatidyl serine) with defined fatty acid side chains was calibrated against BCT/253 and CRM 149R. A small but consistent bias in the International Sensitivity Index (ISI) value was obtained using either the human or rabbit brain reference material. ISI values were around 1.0 or slightly lower depending on the respective instrument. Mixing studies with factor deficient plasmas showed a high factor sensitivity especially for factor VII as compared to commercial rabbit brain or human placenta thromboplastin. In an international field trial the reagent was tested using fully or semi automated Electra coagulometers in 4 different laboratories. Results with normal samples were in excellent agreement among the different laboratories. Mean values were 10.9, 10.9, 11.0, 11.2 s with a range of 9.5 to 12.5 s. Results of males and females were not different. In patients with liver disease very similar PT activities were found as compared to sensitive rabbit brain or human placental thromboplastins. In normals and patients with oral anticoagulation INR values correlated very well against BCT (r = 0.98, regression line y = -0.07 + 0.9 x). The distribution of samples was linear over the whole range. In the comparison against sensitive rabbit brain thromboplastin or human placental thromboplastin similar correlations were found. In a few cases higher INR values were observed for the recombinant reagent especially in patients with intensive treatment. Factor assays in those patients showed at least the strong reduction of one vitamin K-dependent coagulation factor.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Brain Chemistry; Calibration; Coumarins; Evaluation Studies as Topic; Female; Heparin; Humans; Indicators and Reagents; Liver Diseases; Male; Phospholipids; Placenta; Pregnancy; Prothrombin Time; Rabbits; Recombinant Proteins; Reference Standards; Thromboplastin

Relipidated recombinant tissue factor (r-TF) has been assessed in comparison with conventional rabbit brain thromboplastin (Manchester Reagent) for its suitability for measurement of prothrombin time (PT). The International Sensitivity Index (ISI) of r-TF calibrated against the International Reference Preparation BCT/253 (human plain) was found to be 0.96 and 1.12 with instrumental and manual techniques. Our study of plasmas from patients with congenital deficiencies of clotting factors covering a wide range of severity demonstrates that r-TF is able to detect even minor deficiencies of factors involved in the extrinsic and common coagulation pathways. Patients with liver diseases were correctly diagnosed with a prevalence of abnormal results comparable for both reagents. Between-assay reproducibility expressed as coefficient of variation was 2.3% and 3.9% at normal and abnormal PT levels. In conclusion, our evaluation shows that relipidated r-TF possesses the necessary requisites of sensitivity, diagnostic accuracy and reproducibility which make it a suitable candidate for PT determination both for monitoring oral anticoagulant therapy and diagnosing congenital and acquired clotting factor deficiencies. Moreover, being a highly defined reagent it may constitute a step forward in the standardization of PT testing.

Topics: Anticoagulants; Blood Coagulation Disorders; Evaluation Studies as Topic; Humans; Indicators and Reagents; Liver Diseases; Prothrombin Time; Recombinant Proteins; Reference Standards; Reproducibility of Results; Thromboplastin

Topics: Humans; Liver Diseases; Prothrombin Time; Reference Standards; Thromboplastin

Plasma or serum extrinsic pathway inhibitor (EPI) activity was measured in 24 patients with disseminated intravascular coagulation (DIC) and in 23 patients with severe hepatocellular disease. EPI was measured as activity in a test sample that inhibited factor VIIa/tissue factor (TF)-catalyzed activation of 3H-factor IX (activation peptide release) in the presence of factor X. Of the 24 patients with DIC, 13 had sepsis and five had metastatic carcinoma, disorders in which tissue factor is believed to initiate DIC. EPI activity ranged from 68% to 300% (mean 134% +/- 50%). Serial measurements in nine patients failed to show depletion of EPI activity coincident with worsening DIC. DIC induced by tissue factor or other activating materials may progress despite normal EPI levels. In the patients with liver disease, of whom 15 had decompensated chronic hepatocellular disease (two fatal cases) and eight had acute fulminant liver failure (seven fatal cases), plasma or serum EPI activity varied from less than 20% to 194%. Values were distributed in a bimodal fashion. EPI activity could not be correlated with either the etiology of the liver disease or the degree of prolongation of the prothrombin time. Patients with chronic hepatocellular disease who survived had normal or elevated EPI activity. Patients with fatal hepatic dysfunction had low, normal, or high values for EPI activity. This must mean that secretion of EPI from cells other than hepatocytes can maintain normal plasma EPI levels.

Topics: Acinetobacter Infections; Adult; Chronic Disease; Disseminated Intravascular Coagulation; Factor VII; Factor VIIa; Female; Humans; Liver Diseases; Male; Mediastinitis; Middle Aged; Stomach Neoplasms; Thromboplastin

Inhibition of Factor VIIa-tissue factor activity by a plasma component(s) that requires factor Xa has been described recently. In this communication, we have developed a specific radiometric assay (which utilizes 3H-Factor IX and is sensitive to less than 1% of plasma level) for this inhibitor and have measured its activity in various disease states. Strikingly, the levels of this inhibitor were found to be normal in patients with advanced chronic hepatocellular disease but low in patients with disseminated intravascular coagulation (DIC). When endotoxin was used to induce DIC in rabbits, the levels of this inhibitor fell by 25-90%. Human umbilical vein endothelial cells (HUVE), bovine pulmonary artery endothelial cells, and a human hepatoma cell line (HepG2) all synthesized and secreted this inhibitor, whereas a promyelocytic cell line (HL-60) did not and a monocytic cell line (U937) appears to synthesize only small amounts. When ammonium sulfate-fractionated human plasma and serum-free conditioned media from both HUVE and HepG2 cells were electrophoresed on sodium dodecyl sulfate acrylamide gels, two activity peaks corresponding to Mr approximately 45,000 and Mr approximately 33,000 were eluted in each case. These observations suggest that (a) the inhibitor is consumed in DIC and that (b) endothelial cells (or other cells) synthesize sufficient amounts of this inhibitor in vivo to compensate for any decreased production by liver cells.

Topics: Animals; Carcinoma, Hepatocellular; Cattle; Cells, Cultured; Chronic Disease; Disseminated Intravascular Coagulation; Factor VII; Factor VIIa; Humans; Infant, Newborn; Leukemia, Myeloid, Acute; Liver Diseases; Liver Neoplasms; Lymphoma, Large B-Cell, Diffuse; Pulmonary Artery; Rabbits; Thromboplastin; Umbilical Veins

In five centres a new sensitive standardized thromboplastin from human placenta (Thromborel S) for determination of prothrombin time (PT) was evaluated on plasmas from healthy subjects, from patients on oral anticoagulant therapy and from patients with different diseases, especially of the liver. The standardization of the human placenta thromboplastin (HPT) for prothrombin time determination was performed by comparison with a lot of the Reference Preparation British Comparative Thromboplastin (BCT). The obtained International Sensitivity Index (ISI) for 14 differents lots of the new thromboplastin varied between 1.04 and 1.29 (mean value: 1.16). The reagent is highly sensitive to the factors of the extrinsic coagulation pathway and is not affected by heparin at least up to 0.6 IU/ml. From the comparison with the British Comparative Thromboplastin lot No. 235, a therapeutical range for the stable phase of the oral anticoagulation of 2.4-4.0 prothrombin ratio or 15-27% of normal, respectively, was obtained. Comparison of prothrombin time determination using the Human Placental Thromboplastin and the British Comparative Thromboplastin lot No. 235 in 330 patients on oral anticoagulation showed good correlations either in "percent normal" or in prothrombin ratio.

Topics: Anticoagulants; Blood Coagulation Tests; Evaluation Studies as Topic; Humans; Liver Diseases; Placenta; Reference Standards; Thromboplastin

A method for photometric determination of prothrombin time (PT) with a chromogenic peptide as substrate is described. The reagent contains human placental thromboplastin, a chromogenic substrate, calcium, a heparin antagonist and buffer. The new prothrombin time method has been calibrated against international reference preparations for thromboplastin. The reagent is sensitive to deficiency of all coagulation factors of the extrinsic pathway. However, it is not sensitive for heparin up to 1 IU/ml. The precision of this fast and simple method is comparable to that of mechanised assays for clinical chemistry.

Topics: Blood Coagulation; Fibrin; Heparin; Humans; Indicators and Reagents; Liver Diseases; Photometry; Prothrombin Time; Reference Values; Thromboplastin

Topics: Animals; Anticoagulants; Cattle; Chromogenic Compounds; Factor VII; Factor X; Humans; Liver Diseases; Methods; Oligopeptides; Thromboplastin

20 coagulation parameters were investigated in 144 patients with different liver diseases. The groups of acute hepatitis, chronic active hepatitis and liver cirrhosis were compared and the prognostic value of the coagulation analyses investigated. It is clear that the determination of the factor V activity is a good and easy test for detection of actual liver function. Repeated controls over several weeks revealed with a statistical significance (p less than 0.0005) that all patients with a factor XIII below 35% and a plasminogen below 19% will die in liver coma, if they have not died beforehand from acute gastrointestinal haemorrhage, acute infection or cardiac arrest. Plasminogen is also lower in the group of non-survivors but the values of the two groups are overlapping and of no prognostic help in a single case. The possible causes of the diminution of factor XIII activity are discussed.

Topics: Adolescent; Adult; Aged; Blood Coagulation Tests; Factor V; Factor XIII; Female; Fibrin Fibrinogen Degradation Products; Hepatitis; Humans; Liver Cirrhosis; Liver Diseases; Male; Middle Aged; Plasminogen; Prognosis; Prothrombin; Thromboplastin; Time Factors

Activated partial thromboplastin times (APTT's) performed with a semi-automated electrical-conductivity type of clot timer on plasmas from patients with hepatic disease and intravascular coagulation, and on warfarin or heparin therapy, were significantly lower than when done on the same plasmas with either a manual optical method or an automated optical-endpoint instrument. Results of APTT's done on normal plasmas by the three methods were not significantly different. Substitution of different activator-phospholipid reagents resulted in some variability in results, but these differences were less than those between the different done with both the electrical clot timer and the automated optical instrument on prepared plasmas containing 5.0 or 1.0% of factor II, V, VIII, IX, OR X revealed shorter times with the electrical clot timer only in the case of factor II- and factor V-deficient plasmas. APTT's done on normal plasmas to which 0.1 or 0.3 units per ml. of heparin had been added vitro also were shorter with the electrical clot itmer than the automatic optical instrument. Prothrombin times done on normal and abnormal control plasmas and on a series of plasmas from patients on warfarin therapy showed no significant difference between the two methods.

Topics: Autoanalysis; Blood Chemical Analysis; Blood Coagulation Tests; Erythrocyte Aggregation; Factor V Deficiency; Factor X Deficiency; Hemophilia A; Hemophilia B; Heparin; Hydrogen-Ion Concentration; Hypoprothrombinemias; Liver Diseases; Optics and Photonics; Phospholipids; Prothrombin Time; Thromboplastin; Time Factors; Warfarin

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Humans; Liver Diseases; Prothrombin; Thromboplastin

Topics: Antithrombins; Blood Coagulation Tests; Caseins; Factor V; Factor VIII; Fibrinogen; Fibrinolysis; Hepatitis; Humans; Liver Cirrhosis; Liver Diseases; Liver Neoplasms; Mushroom Poisoning; Plasminogen; Prothrombin Time; Thromboplastin

Topics: Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Coumarins; Evaluation Studies as Topic; Factor V; Factor VII; Factor X; Humans; Liver Diseases; Prothrombin; Thromboplastin; Time Factors

Topics: Blood Coagulation Tests; Blood Platelets; Disseminated Intravascular Coagulation; Factor V Deficiency; Factor VIII; Fibrinogen; Heparin; Humans; Liver Diseases; Prothrombin Time; Thromboplastin; Vitamin K; Vitamin K Deficiency

Topics: Adolescent; Adult; Afibrinogenemia; Blood Cell Count; Blood Coagulation Tests; Blood Platelets; Child; Child, Preschool; Disseminated Intravascular Coagulation; Factor V; Factor VIII; Female; Fibrinogen; Humans; Infant; Liver; Liver Diseases; Male; Middle Aged; Prothrombin; Prothrombin Time; Serum Globulins; Solubility; Thromboplastin

Liver biopsy was performed in 38 patients with fulminant hepatitis and coma and repeated in 22. Stereological estimation of hepatocyte volume was correlated with levels of clotting factors. Early liver biopsy allowed prognosis in 55% of the cases. All patients with a hepatocyte volume of <35% and thromboplastin time /=35% and thromboplastin time >10% recovered consciousness (n = 9) or at least showed evidence of marked liver regeneration (n = 2). On serial liver biopsy a significant increase in hepatocyte volume and clotting factors was only observed in patients who recovered consciousness. The estimated liver cell mass after regeneration in patients who recovered consciousness was >/=45% and <45% in the patients who did not.

Topics: Acute Disease; Biopsy; Factor V; Hepatic Encephalopathy; Hepatitis; Hepatitis A; Humans; Liver; Liver Diseases; Prognosis; Thromboplastin; Time Factors

Topics: Blood Coagulation; Blood Platelets; Fibrinogen; Gold Colloid, Radioactive; Humans; Indium; Kidney Diseases; Liver Diseases; Mercury Isotopes; Platelet Adhesiveness; Prothrombin; Radiation Effects; Radioisotopes; Radionuclide Imaging; Thromboplastin; Time Factors

Topics: Blood Cell Count; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelets; Fibrinogen; Hemorrhagic Disorders; Hemostasis; Humans; Liver Diseases; Prothrombin Time; Thrombin; Thrombocytopenia; Thromboplastin

Topics: Adult; Aged; Arthritis; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelets; Carcinoma; Factor VIII; Female; Fibrinolysin; Hepatitis; Humans; Liver Diseases; Male; Middle Aged; Necrosis; Rectal Neoplasms; Thrombin; Thromboplastin; Vaginal Neoplasms

Topics: Adult; Aged; Bile Duct Neoplasms; Biliary Tract Diseases; Female; Humans; Liver Diseases; Liver Neoplasms; Male; Middle Aged; Thromboplastin

Coagulation studies were carried out on 30 patients with chronic liver disease. The clotting defect was complex and involved factors V, VII, IX (Christmas factor), and prothrombin. Some patients showed a significant depression of factor IX in the presence of a normal one-stage prothrombin time. Thrombotest was found to be a good indicator of factor IX deficiency in this group of patients and may be of use as an additional liver function test. The screening of patients with liver disease for surgery or liver biopsy should assess the coagulation factors involved in both intrinsic and extrinsic thromboplastin generation.

Topics: Adult; Aged; Blood Coagulation Disorders; Chronic Disease; Factor IX; Factor V; Factor VII; Female; Humans; Liver Diseases; Liver Function Tests; Male; Middle Aged; Prothrombin; Prothrombin Time; Thromboplastin

Topics: Blood Coagulation Factors; Erythrocyte Count; Factor V; Factor VII; Factor X; Fibrinogen; Fibrinolysis; Gastrointestinal Diseases; Humans; Kidney Diseases; Liver Diseases; Lung Neoplasms; Lymph; Prothrombin; Prothrombin Time; Thoracic Duct; Thromboplastin

Topics: Antithrombins; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Humans; Lipoproteins; Liver Cirrhosis; Liver Diseases; Liver Neoplasms; Pathology; Thrombin; Thromboplastin

Topics: Amyloidosis; Blood Coagulation Tests; Factor V; Factor VII; Factor X; Humans; Hypoprothrombinemias; Liver Diseases; Prothrombin Time; Thromboplastin

Topics: Anemia; Blood Coagulation; Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelets; Calcium; Factor IX; Factor V; Factor VII; Factor VIII; Factor X; Factor XI; Factor XII; Fibrinogen; Hemolysis; Humans; Kidney Diseases; Liver Diseases; Prothrombin; Thromboplastin

Topics: Humans; Liver Diseases; Thromboplastin; Vascular Diseases

Topics: Adhesiveness; Blood Coagulation Tests; Blood Platelets; Humans; Liver Diseases; Platelet Aggregation; Platelet Function Tests; Thromboplastin

Topics: Humans; Liver Diseases; Thromboplastin

Topics: Blood Coagulation Tests; Blood Platelets; Humans; Liver Diseases; Platelet Activation; Platelet Function Tests; Thromboplastin

Topics: Factor VIII; Liver Diseases; Menstruation; Thromboplastin