Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Prothrombin”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,297 records · Page 72Linked to original sources
PubMed1999

Factor Xa and prothrombin: mechanism of action of FEIBA.

A complex consisting of activated factor X (FX) (enzyme) and prothrombin (substrate), both highly purified from human plasma and virus inactivated, was formulated, characterised biochemically as well as in animal studies, and given the name Partial Prothrombinase (PPT). In vitro, PPT shortened the clotting time of a high-titre human factor VIII (FVIII) inhibitor plasma in a manner similar to that of the activated prothrombin complex concentrate FEIBA and triggered coagulation in plasma samples in which factor V (FV) is present. In vivo, the ability of PPT to activate coagulation in both chimpanzees and baboons was equivalent to that of FEIBA. PPT also triggered coagulation in a von Willebrand factor(vWF)-deficient dog and controlled bleeding in rabbits with antibody-induced haemophilia A. Thus, studying the mechanism of action of PPT also explains the therapeutic principle of FEIBA.

Animals↗
PubMed2003

A critical evaluation of the prothrombin time for monitoring oral anticoagulant therapy.

The Quick prothrombin time is the most common clotting test performed, principally for monitoring oral anticoagulant therapy. The International Normalized Ratio (INR) for comparing patient results from prothrombin time measurements and the International Standardized Index (ISI) for achieving greater consistency of results using different thromboplastins have made it possible to compare the results of vitamin K antagonist drug therapy that was impossible before the introduction of the INR and ISI. However, INR values obtained from the same patient plasma sample using different thromboplastins are significantly different. This is so even when the thromboplastins have nearly the same ISI values. We suggest that investigation of patient-specific differences can provide a means by which the INR discrepancies can be identified and understood and thus lead to better methods for monitoring oral anticoagulant therapy.

Administration, Oral↗
PubMed1993

Changes in plasma levels of prothrombin fragment F 1 + 2 in cases of disseminated intravascular coagulation.

Plasma levels of prothrombin fragment F 1 + 2 (PTF) and thrombin-antithrombin III complex (TAT) were assayed in 86 cases of disseminated intravascular coagulation (DIC). A significant elevation of both parameters was observed in most cases of DIC, which suggested that the in vivo generation of thrombin is highly accelerated by the cleavage of the prothrombin molecule by factor Xa. On the contrary, no significant elevation of plasma levels of PTF was observed in cases of DIC with severe hepatic failure or fulminant hepatitis in spite of significant elevation of TAT. Plasma levels of PTF were directly proportional to those of TAT in 86 cases of DIC as a whole (r = 0.682, p < 0.001). The measurement of both parameters was considered to be useful to estimate the hemostatic activation in DIC.

Antithrombin III↗
PubMed1974

Pre- and post-operative studies of fibrinolysis and prothrombin in cyanotic congenital heart disease.

Multiple components of the fibrinolytic mechanism (plasminogen, plasmin, antiplasmin, fibrinogen, fibrin degradation products) and factor II (prothrombin) levels were studied in 40 children with cyanotic congenital heart disease (CCHD) prior to corrective surgery. Seven of these were also studied post-operatively. A further 17 children were studied after corrective surgery only. Pre-operatively, increased fibrinolysis could bedemonstrated in only 7.5-12% of patients, and there was no correlation between the levels of fibrinolytic components and the severity of polycythemia or post-operative blood loss. There was no evidence of fibrinolysis post-operatively. Pre-operatively, low prothrombin levels were common (25%), were correlated with the amount of post-operative bloodloss and were restored to normal by corrective surgery. Hypoprothrombinaemia is one of the most significant haematological abnormalities in CCHD.

Child↗
PubMed1989

Variations of prothrombin time, factor VII and protein C with a single daily dose of acenocoumarol. Preliminary results.

In 11 patients on steady anticoagulation with a daily dose of acenocoumarol, prothrombin time, factor VII and protein C were measured 2 and 16 h after the daily intake of acenoumarol. Prothrombin time (expressed as International Normalised Ratio) increases significantly, factor VII and protein C decrease between the two samples. These results suggest that a daily dose of acenoumarol is associated with fluctuation of the anticoagulant effect.

Acenocoumarol↗
PubMed1993

Prothrombin fragment 1 + 2 and thrombin-antithrombin complex measurements indicate continuous and progressive intraoperative thrombin generation in liver transplantation.

Prothrombin fragment 1 + 2 (F1 + 2) and thrombin-antithrombin complex (TAT) have been measured in the different surgical phases in 40 patients undergoing 43 orthotopic liver transplantations (OLT), in order to study thrombin generation throughout the surgical procedure. F1 + 2 and TAT progressively rose from preoperative values (1.47 +/- 0.92 nmol/l and 22.41 +/- 19.15 ng/ml, respectively) to the end of anhepatic phase (5.97 +/- 2.20 nmol/l, 64.24 +/- 11.30 ng/ml), whereas changes in circulating antithrombin III (ATIII) were negligible in this period. Thrombin generation continued to slightly but significantly increase immediately after liver graft reperfusion (F1 + 2 6.87 +/- 1.65 nmol/l, TAT 89.32 +/- 7.54 ng/ml), and ATIII levels decreased from 70.61 +/- 12.28 to 57.16 +/- 9.57%. Higher preoperative values of F1 + 2 were associated with larger requirements of both packed red blood cells and fresh frozen plasma (FFP) in the host liver explantation phase, whereas the lowest basal levels of ATIII were related to a higher plasma expense in the whole OLT procedure. The activation of circulating prothrombin begins early in OLT, and adequate FFP infusion is capable of maintaining appropriate circulating thrombin-inhibitory activity.

Adolescent↗
PubMed1997

Morning hypercoagulability and hypofibrinolysis. Diurnal variations in circulating activated factor VII, prothrombin fragment F1+2, and plasmin-plasmin inhibitor complex.

BACKGROUND: Diurnal fluctuations of blood coagulation and fibrinolysis activity are thought to play a role in the observed circadian variation in the frequency of onset of acute cardiovascular events. In the present study, the diurnal variations in blood coagulation and fibrinolysis activity were investigated in 10 young, healthy control subjects by use of specific molecular activation markers. METHODS AND RESULTS: The plasma levels of activated factor FVII (FVIIa), the active portion of the main coagulation activator, decreased during the day (8 AM: 2.03 ng/mL, CI 1.16 to 2.88 ng/mL; 8 PM: 1.16 ng/mL, CI 0.81 to 1.5 ng/mL; P = .005), whereas FVII antigen did not change significantly. In parallel with the diurnal variations of FVIIa, we found a decrease of prothrombin fragment F1+2 (8 AM: 0.97 nmol/L, CI 0.79 to 1.15 nmol/L; 8 PM: 0.78 nmol/L, CI 0.64 to 0.93 nmol/L; P = .005), a molecular marker of intravasal thrombin generation. Evidence for a possible functional relevance of circulating FVIIa was found because this parameter was significantly correlated with prothrombin fragment F1+2 in 72 fasting healthy individuals (r = .29, P = .011). Plasminogen activator inhibitor-1 levels decreased (8 AM: 9.9 ng/mL, CI 7.7 to 12.1 ng/mL; 8 PM: 5.4 ng/mL, CI 3.8 to 6.9 ng/mL; P < .005), whereas plasmin-plasmin inhibitor complex levels, representing the degree of intravascular plasmin generation, concomitantly increased (8 AM: 235 micrograms/L, CI 198 to 272 micrograms/L; 8 PM: 449 micrograms/L, CI 391 to 507 micrograms/L; P = .008). CONCLUSIONS: Our data suggest that the diurnal changes in the plasma levels of activators and inhibitors of coagulation and fibrinolysis lead to corresponding changes in the activity state of these systems, leading to morning hypercoagulability and hypofibrinolysis.

Adult↗
PubMed1975

Binding of the products of prothrombin activation to human platelets.

Binding of prothrombin and activation intermediates 1 and 2 to human platelets was tested with 125-I-labeled protein preparations. None of these precursors of thrombin bound to platelets under conditions in which high affinity binding of thrombin was observed,nor did they cause platelet aggregation or serotonin release. The molecular conformation required for binding to platelets as well as for induction of platelet aggregation and release is present, therefore, only after the final step in prothrombin activation.

Binding Sites↗
PubMed1993

The activation of factor X and prothrombin by recombinant factor VIIa in vivo is mediated by tissue factor.

The human coagulation system continuously generates very small quantities of Factor Xa and thrombin. Current evidence suggests that basal level activation of the hemostatic mechanism occurs via Factor VIIa-dependent activation of Factor X, but direct proof has not been available for the participation of tissue factor in this pathway. To examine this issue, we infused relatively high concentrations of recombinant Factor VIIa (approximately 50 micrograms/kg body wt) into normal chimpanzees and observed significant increases in the plasma levels of Factor IX activation peptide, Factor X activation peptide, and prothrombin activation fragment F1+2. Metabolic turnover studies with radiolabeled Factor IX activation peptide, Factor X activation peptide, and F1+2 indicate that elevated levels of the activation peptides are due to accelerated conversion of the three coagulation system zymogens into serine proteases. The administration of a potent monoclonal antibody to tissue factor, which immediately neutralizes function of the Factor VIIa-tissue factor complex in vitro, abolishes the activation of Factor X and prothrombin mediated by the infused recombinant protein, and also suppresses basal level activation of Factor IX and Factor X. The above results suggest that recombinant Factor VIIa functions as a prohemostatic agent by interacting with endogenous tissue factor sites, but definitive proof will require studies in hemophilic animals using relevant hemostatic endpoints.

Animals↗
PubMed1999

Paget-Schroetter syndrome associated with FV:Q506 and prothrombin 20210A--a case report.

Effort thrombosis of the axillary-subclavian vein (Paget-Schroetter syndrome) develops usually secondary to heavy arm exertion. An underlying chronic venous compressive anomaly at the thoracic outlet or intimal damage of the axillary vein following forceful hyperabduction, external rotation of the shoulder joint has been proposed to explain the pathophysiology of this thrombosis. This condition is usually not attributed to an underlying hypercoagulability such as deficiency of natural coagulation inhibitors. Here, the authors present a case with thrombosis of the axillary-subclavian vein following an effort, with factor V Leiden and prothrombin 20210A mutations. Both factor V Leiden and the genetic variant in the prothrombin gene have been shown to confer an increased risk for venous thrombosis. Although rare, effort thrombosis may develop in a patient with hereditary thrombophilia, so laboratory evaluation should include the common causes of thrombosis.

Adult↗
PubMed1998

Brown snakes (Pseudonaja genus): venom yields, prothrombin activator neutralization and implications affecting antivenom usage.

The recent high prevalence of fatal bites by Brown snakes (Pseudonaja genus) has led to this study of venom yields from 66 brown snake milkings over 15 months. The amount of venom obtained from all species was higher than reported previously. Electrophoretic and Western blotting analyses of their venoms showed significantly lower avidity of Brown snake antivenom (BS-AV) for the prothrombin activator (PA) component (190 kD) than for other venom components, including the neurotoxins. The LD50 of P. inframacula has been determined for the first time. SDS-PAGE (sodium dodecyl sulphate-polyacrylamide gel electrophoresis) and Western blotting studies have shown that the Pseudonaja venoms contained proportionately more PA component than venoms of the Taipan (Oxyuranus scutellatus) or the Fierce snake (O. microlepidotus). Neutralization of the prothrombin activator of the Common Brown snake (P. textilis) (Pt-PA) by BS-AV was found to be time dependent and 40% remained unneutralized after 30 minutes incubation. Adult rats administered quantities of Pt-PA (IV) died with acute disseminated intravascular coagulation. Rats were made resistant to Pt-PA by preheparinization or by induction of tolerance to increasing quantities of Pt-PA. There is no evidence that Pt-PA has intrinsic toxicity apart from being a procoagulant. The improvement of BS-AV by addressing its deficiencies should be canvassed.

Animals↗
PubMed1999

Factor V1691 G-A, prothrombin 20210 G-A, and methylenetetrahydrofolate reductase 677 C-T variants in Turkish children with cerebral infarct.

Inherited gene defects related to the coagulation system have been reported as risk factors for ischemic stroke. These gene defects include a G-A transition at nucleotide 1691 in exon 10 of the Factor V gene causing activated protein C resistance; a G-A transition in the 3' untranslated region of the prothrombin gene at nucleotide position 20210 (G-A), which is associated with increased levels of prothrombin activity; and a C-T polymorphism at nucleotide 677 in the methylenetetrahydrofolate reductase gene responsible for an alanine to valine substitution, resulting in the synthesis of a thermolabile form of methylenetetrahydrofolate reductase that causes increased levels of homocysteine. The case-control study included 28 patients with cerebral infarction; all were 18 years of age or younger (range, 10 months to 18 years). Seven (25%) of the 28 patients were heterozygous for the FV1691 mutation. Five (17.8%) of the patients carried the PT20210A mutation. Two (7.1%) of the patients carried both mutations. When compared to controls, the difference was significant for both mutations (P = .007; .04). The frequency of allele T of methylenetetrahydrofolate reductase 677 was 0.3214, which was not significant when compared to controls (0.231; P = .3). A total of 12 (42.8%) patients carried one or both of the mutations FV1691 G-A and PT20210 G-A. From our data, it appears that FV1691 G-A and PT20210 G-A are associated with cerebral infarct risk independently. Risk assessment of double prothrombotic gene alterations did not reveal synergy between these mutations. In conclusion, the presence of FV1691 A and PT20210 A mutations but not the methylenetetrahydrofolate reductase 677 TT mutation correlate with the occurrence of cerebral infarction in children.

Adolescent↗
PubMed1998

Anti-prothrombin antibodies and their relation with thrombosis and lupus anticoagulant.

Antiphospholipid antibodies are a heterogeneous group of antibodies, comprising antibodies with different antigen specificity. Prothrombin is one of the antigens which can be detected by antiphospholipid antibodies and therefore anti-prothrombin antibodies belong to the antiphospholipid antibody family. The presence of antiphospholipid antibodies correlates strongly with thromboembolic complications; however a mechanism by which these autoantibodies induce a thrombotic complication in vivo is not understood. The classic assays for the detection of antiphospholipid antibodies (LAC and anticardiolipin ELISAs) aim to measure all the antiphospholipid antibodies present in the samples without making a distinction between the different subspecificities of the antibodies present in one single sample. Moreover, most of the in-vitro studies performed were carried out with total IgGs, which contain a mixture of antibodies. The absence of an accurate characterization of the plasma samples and the lack of specificity of the IgGs used in in-vitro tests makes it difficult to determine the contribution of antiprothrombin antibodies to the thrombotic complications. Here we review and critically analyse the literature regarding the clinical relevance of the presence of antiprothrombin antibodies and the possible participation of these antibodies in the pathogenesis of the thrombotic complications.

Animals↗
PubMed2000

Review and management of patients with the prothrombin G20210A polymorphism.

A single mutation in the 3'-untranslated region of the prothrombin gene, resulting in a G to A substitution, was recently reported. This finding added to the growing list of genetic disorders thought to be responsible for familial thrombophilia. Although most studies are in general agreement about the elevated risk of venous thrombosis in individuals carrying this mutation, its role in the first event of venous thromboembolism and recurrent events is unclear. Even less clear is the role that this mutation plays in the formation of arterial thrombosis (including coronary artery disease and cerebral ischemia), as studies show contradicting results. Because of this, it is not recommended as part of the routine screening of patients with venous thromboembolism. However, there are certain subgroups of patients who should undergo testing. The discovery of this prothrombin mutation has important clinical implications because it is the second most common cause of genetic thrombophilia, second only to the factor V Leiden. Moreover, its discovery likely will augment the clinician's ability to systematically risk-stratify an individual's likelihood of developing spontaneous thrombosis.

3' Untranslated Regions↗
PubMed2001

G20210A prothrombin gene mutation: prevalence in a recurrent miscarriage population.

Many recurrent pregnancy losses appear to have a thrombotic etiology. We have investigated the prevalence of the G20210A prothrombin gene mutation in 122 women with a history of three or more early (< or = 12 weeks gestation; n = 91), late (> 12 weeks gestation: n = 2), or mixed (n = 29) consecutive pregnancy losses. A control group of 66 healthy parous women with no history of thrombosis or miscarriage was also studied. Four heterozygotes that suffered only early pregnancy losses were detected in the patient group giving a prevalence of 3.3%. Three of the control group women were heterozygous for the mutation. giving a prevalence of 4.5% (p = 0.32: odds ratio 0.71: 95% confidence interval [CI] 0.15-3.27). When only Caucasians were analyzed, a prevalence of 3.9% (4/103) was observed in the patient group and 4.2% (2/48) in the control group (p = 0.28; odds ratio 0.89; 95% CI 0.16-5.05). The prevalence of the G20210A prothrombin gene mutation is not increased in women with recurrent miscarriage, although it was only found in women who had suffered early pregnancy losses. However, it remains possible that this mutation is relevant in a selected subgroup of women with recurrent miscarriage, additional thrombophilic defects, and in whom fetal loss is associated with placental infarction and thrombosis.

Abortion, Habitual↗
PubMed2004

Factor V Leiden and prothrombin G20210A mutations and the risk of atherothrombotic events in systemic lupus erythematosus.

Because genetic predisposition to atherothrombosis in systemic lupus erythematosus (SLE) remains to be determined, the most common genetic prothrombotic factors, prothrombin G20210A and factor V Leiden mutations, were studied. Seventy-four SLE patients with vascular ischemia (SLE cases) were studied and stratified into myocardial infarction and/or cerebrovascular accident subgroup (MI/CVA), and coronary heart disease subgroup without overt arterial thrombotic events (CHD). Seventy-one SLE patients without atherothrombosis were investigated as SLE controls. Factor V Leiden was detected in six cases (five in MI/CVA, one in CHD group) and three controls (OR 2.00, 95%CI 0.48-8.32). Two cases (both CHD patients) had prothrombin G20210A mutation vs. three controls (OR 0.63, 95%CI 0.1-3.88). Anticardiolipin antibodies (aCL) were increased in cases vs. controls (39/74 vs. 27/71); however, this was not statistically significant (OR 1.82, 95%CI 0.94-3.52). Neither univariate nor multivariate analysis indicated that investigated mutations are risk factors for atherothrombosis in SLE cases, MI/CVA, or CHD subgroups. Overall, disease activity was the strongest risk factor for atherothrombosis (p=0.0014) in SLE cases. Combination of disease activity+gender was the best predictor of atherothrombotic process (p=0.00045) in this cohort. In MI/CVA subgroup, disease activity was the only predictor (p=0.0058). In CHD patients, the best predictive value was conferred by combination of hypertension+gender+disease activity (p=0.00077). No other investigated risk factor (including aCL) conferred an increased risk individually or potentiated the other risk factors. The results deny the role of investigated mutations in atherothrombosis in SLE, but they underscore the importance of disease activity (i.e., ongoing inflammation) in pathogenesis of atherosclerosis and arterial thrombosis.

3' Untranslated Regions↗
PubMed2004

The prothrombin 3'end formation signal reveals a unique architecture that is sensitive to thrombophilic gain-of-function mutations.

The functional analysis of the common prothrombin 20210 G>A(F2 20210(*)A) mutation has recently revealed gain of function of 3'end processing as a novel genetic mechanism predisposing to human disease. We now show that the physiologic G at the cleavage site at position 20210 is the functionally least efficient nucleotide to support 3'end processing but has evolved to be physiologically optimal. Furthermore, the F2 3'end processing signal is characterized by a weak downstream cleavage stimulating factor (CstF) binding site with a low uridine density, and the functional efficiency of F2 3'end processing can be enhanced by the introduction of additional uridine residues. The recently identified thrombosis-related mutation (F2 20221(*)T) within the CstF binding site up-regulates F2 3'end processing and prothrombin biosynthesis in vivo. F2 20221(*)T thus represents the first example of a likely pathologically relevant mutation of the putative CstF binding site in the 3'flanking sequence of a human gene. Finally, we show that the low-efficiency F2 cleavage and CstF binding sites are balanced by a stimulatory upstream uridine-rich element in the 3'UTR. The architecture of the F2 3'end processing signal is thus characterized by a delicate balance of positive and negative signals. This balance appears to be highly susceptible to being disturbed by clinically relevant gain-of-function mutations.

3' Untranslated Regions↗
PubMedDate not supplied

Accuracy, clinical correlation, and patient acceptance of two handheld prothrombin time monitoring devices in the ambulatory setting.

OBJECTIVE: To evaluate the accuracy, clinical correlation, ease of use, and patient acceptance of the Coaguchek and the ProTime Microcoagulation System as compared with standard laboratory methods for prothrombin time determination. METHODS: A total of 30 prothrombin times, expressed as international normalized ratios (INRs), were determined by each handheld device for comparison with standard laboratory testing. Accuracy was evaluated by calculating the absolute difference for each pair of INR values. Clinical correlation was defined as an INR obtained by the handheld monitor that would have resulted in the same therapeutic decision as the INR obtained by the standard laboratory method. Subjects were surveyed to determine which method of INR determination they preferred and their reasons for that preference. RESULTS: Accuracy was superior with the Coaguchek monitor. The absolute difference (mean +/- SD) in the laboratory and Coaguchek INRs was 0.28+/-0.23 (p = 0.96). The absolute difference (mean +/- SD) in the laboratory and the ProTime Microcoagulation System INRs was 0.56+/-0.34 (p < 0.001). For clinical correlation, two out of 24 (8.3%) INRs with the Coaguchek were sufficiently different from the laboratory INR to have resulted in a different therapeutic decision, compared with 12 out of 24 (50%) with the ProTime Microcoagulation System (p < 0.005). Of subjects surveyed, 77.8% preferred the finger stick method. CONCLUSIONS: The Coaguchek was superior to the ProTime Microcoagulation System in accuracy, clinical correlation, and ease of use. The study also showed that patients preferred capillary blood sampling by finger puncture over venipuncture for INR monitoring.

Anticoagulants↗