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 1,333 records · Page 74Linked to original sources
PubMedDate not supplied

[Prevalence of genetic prothrombotic factors (factor V Leiden and II20210 prothrombin mutation) in glomerular nephropathies with or without thrombosis].

The presence of genetic prothrombotic factors (factor V Leiden and the prothrombin II20210 mutation) was investigated in 38 patients with glomerulonephritis with or without a history of thrombotic events and/or nephrotic syndrome. We found an increased prevalence (36%) of heterozygous factor V Leiden in those patients with a history of thrombotic events. This is ten times the prevalence in the normal Spanish population. Carrier status for this mutation may be a determining factor in the development of thrombotic events along with the acquired disorders of coagulation to which these patients are prone. We found only one patient who was a carrier of the G-A II20210 mutation of the prothrombin gene; this patient had no history of venous thrombosis or embolism. Our findings suggest the need to measure activated protein C resistance and to look for the most frequent genotype causing it, Factor V Leiden, in patients with glomerulonephritis to identify those at risk who may benefit from prophylaxis against thrombosis.

Activated Protein C Resistance↗
PubMed1999

[Coincidence of 20210A prothrombin variant and factor V Leiden predisposing to venous thromboembolism].

Coexistence of inherited and environmental risks leads to the high hazard of venous thromboembolism. In such cases, there might be difficulties in the diagnosis and treatment of recurrent episodes. The importance of Factor V Leiden and prothrombin variant 20210A in the pathogenesis of venous thromboembolic disease, is widely accepted, but the carriership of thrombophilic genes' variants is usually not sufficient for the development of the disease. We report two cases of familial thrombophilia with concurrent presence of prothrombin variant 20210A and factor V Leiden. In a 28-year-old woman: pregnancy, immobilization, obstetric intervention appeared to precipitate the thromboembolic complication. In the second patient, the genetic studies revealed both thrombophilic mutations which could predispose to the recurrent venous thromboembolism, previously thought to be idiopathic. We discuss diagnostic and therapeutic difficulties in such patients.

Adult↗
PubMed2001

[Continuously perfused cultivation of genetically-engineered CHO cells producing prothrombin in a modified Super-Spinner].

A Super-Spinner was Modified by mounting a stainless steel filter(pore size 75 microns) to the impeller shaft to retain cells while fresh nutrient is perfused. Using Macroporous microcarrier Cytopore 1, continuously perfused cultivation of a recombinant CHO cell line, CHO2DS producing prothrombin was performed with the perfusion of a protein-free medium DF6S. The cell retention rate was more than 90% during the 24 days continuously perfused cultivation. The viable cell density of CHO2DS and prothrombin concentration reached 4.62 x 10(6)(cells.m/L) and 11.3(mg/L) respectively after 9 days culture.

Animals↗
PubMed2001

Quantification of lupus anticoagulants in clinical samples using anti-beta2GP1 and anti-prothrombin monoclonal antibodies.

Quantification of lupus anticoagulant (LA) in clinical samples is hampered by the lack of a suitable standard of activity. We evaluated the use of mAbs displaying LA activity for this purpose. As most patient samples contain both beta2Glycoprotein I (beta2GP1) and prothrombin dependent LA, a combination of two mAbs, one of each specificity, was added to normal plasma in a concentration from 0 to 60 microg/ml. Eight assay systems using different reagents and instruments were used. The calibration curves were linear for all but one, with marked differences between the responsiveness to each mAb. A panel of plasmas from 69 patients with persistent LA diagnosed using the SSC-ISTH criteria was tested. An antiphospholipid syndrome (APS) was present in 40, whereas 29 were asymptomatic. LA activities of individual plasmas varied between assays (p < 10(-4)), but homogeneous subgroups were identified. In a majority of samples, LA activity displayed a prothrombin-dependent profile, with a variable contribution of beta2GP1-dependent activity. The latter was associated to beta2GP1 antibodies detected by solid-phase immunoassay. By using 3 dilute Russell viper venom time assays, higher LA titers were found in APS, compared to asymptomatic patients (p <0.05).

Adult↗
PubMed2001

[Spinal cord infarction and recurrent venous thrombosis in association with estrogens and the 20210A allele of the prothrombin gene].

The acute spinal cord infarction is a rare cause of acute-onset paraplegia. Furthermore, it is specially uncommon that the infarction occurs in patients with apparent low predisposition to vascular disease. The 20210A allele of the prothrombin gene (causing a threefold-increased risk in venous thromboembolism) was recently associated with unexplained spinal cord infarction in young women under treatment with estrogens (contraceptive pill). We report a case of anterior spinal artery syndrome resulting from an ischaemic infarction at the anterior aspect of the spinal cord in a healthy 50-year-old woman, carrying this mutation, being the first published case under treatment with transdermal estradiol. She referred the typical sudden-onset back pain associated to clinical anterior spinal artery syndrome with sphincter dysfunction and nontraumatic paraplegia. A possible multiple sclerosis was ruled out and the steroids or immunoglobulin therapy induced no clinical improvement. Cerebrospinal fluid and other investigations were all negative. Sequential MRI scans revealed development of spinal cord infarction from T10 to T11, with increased signal in T2-weighted image (T2). Because she referred a previous thrombophlebitis and suffered a deep-vein thrombosis one month after paraplegia, a complete coagulation study was performed. Antithrombin, proteins C and S, homocysteine, factor V Leiden, lupus anticoagulant and anticardiolipin antibodies were all normal or negatives. In opposite, the 20210A variation was positive (heterozygous) and the factor VIIIc level was very high (280 U/dl eight months later). We argue the relative importance of both findings. The patient had no a substantial recovery over a period of 20 months.Certainly, the prothrombin 20210A seems to be associated with unexplained ischemic myelopathy among the young women with estrogens.

Alleles↗
PubMed2002

The prothrombin 20210A allele influences clinical manifestations of hemophilia A in patients with intron 22 inversion and without inhibitors.

BACKGROUND AND OBJECTIVES: The modulation of disease severity in hemophilia A (HA) patients may be related to the co-inheritance of mutations in genes with a known thrombotic effect such as factor V Leiden (FVL) and prothrombin. In the Spanish population, the prothrombin 20210A (PT20210A) allele is the most prevalent genetic risk factor for venous thromboembolism. DESIGN AND METHODS: We investigated the presence of both mutations in a cohort of 265 hemophiliac patients divided into two groups: I) 140 unrelated patients with moderate and mild HA and II) 125 unrelated patients with severe HA (83 carrying an inversion of intron 22). RESULTS: In group I, 4 patients had the FVL (2.8% vs. 2.98% controls) and 5 had the PT20210A (3.6% vs. 6.46% controls). In group II, two patients with inversion had the FVL (1.6%) and PT20210A was found in 10 patients (8%), five of them with inversion of intron 22 without inhibitors. One of these patients had the FVL and PT20210A mutations concomitantly. In the subgroup of patients with inversion who were carriers of the PT20210A, three parameters i.e. spontaneous bleeding (p=0.008), factor VIII utilization (p=0.016) and number of hemophilic arthropathies (p<0.0005) were significantly lower than in a subgroup of 11 age-matched non-PT20210A severe HA patients with inversion and without inhibitors. INTERPRETATION AND CONCLUSIONS: These results indicate that the inheritance of PT20210A could be a protective factor that mitigates the clinical severity of HA.

Adolescent↗
PubMed2002

[Prothrombin time and its standardization: a potentiality to introduce INR method in criteria for disseminated intravascular coagulation].

Prothrombin time (PT) is widely utilized for evaluation of diseases with single or multiple coagulation factors disorders, such as severe liver dysfunction and disseminated intravascular coagulation (DIC). However, its standardization of reagent and method is not established yet for universal purpose except International Normalized Ratio (INR) for control of oral anticoagulant therapy (OAT). Neither Prothrombin time ratio adapted in Japanese criteria for DIC nor seconds method in criteria reported by the last SSC meeting is corrected between assays, therefore much dependence on these criteria causes risk of misdiagnosis. In order to resolve incoherence of method of PT, we performed this study for introducing INR method to diagnostic criteria for DIC. In our results, sensitivities of two reagents from human tissue factor (TF) to DIC model plasma with middle to low activities of multiple coagulation factors almost equal to plasma from patients with OAC, although other two reagents from rabbit TF show discrepancy of sensitivities between DIC and OAT plasma. These suggest a potentiality to introduce INR system to diagnosis of DIC when human TF is used as a PT reagent. Based on standardization of method, significance of PT in DIC criteria should be reevaluated in worldwide.

Disseminated Intravascular Coagulation↗
PubMed2002

Levels of F(1+2) prothrombin fragments and thrombin - antithrombin III (TAT) complexes in patients with dermatitis herpetiformis.

BACKGROUND: Dermatitis herpetiformis (DH) is a rare bullous disease of autoimmune etiology. It is an intestinocutaneous syndrome, in which vesicopapular cutaneous lesions are accompanied by gluten-dependent enteropathy. The diagnosis of DH is based on immunopathological investigation of unaffected skin fragment (granular IgA deposits present at the tops of dermal papillae and IgA - EmA present in the serum). MATERIAL/METHODS: The studied group consisted of 33 patients with dermatitis herpetiformis - 23 males and 10 females aged 22-78 (mean age 44.7). In all the patients, the following parameters of blood coagulation systems were determined in the plasma Levels of prothrombin fragments 1+2 (F(1+2)), levels of thrombin - antithrombin III (TAT) complexes, antithrombin III activity (AT III). RESULTS: In patients with dermatitis herpetiformis, the main level of F(1+2) fragments amounted to 9.08 nmol/l, as compared with 1.14 nmol/l in the control group (the difference statistically significant, p<0.0001). In DH patients, the levels of TAT complexes were over twice higher than among the controls and that difference also reached statistical significance (p<0.0001). Mean antithrombin III activity (AT III) in patients with DH reached 102.60% and was similar to that observed in the control group (104.68%). CONCLUSIONS: In patients with dermatitis herpetiformis, increased levels of F(1+2) prothrombin fragments and TAT complexes indicate enhanced in vivo thrombinogenesis. No statistically significant differences of F(1+2), TAT and AT III levels in DH patients related to their sex, age and duration of the disease were observed.

Adult↗
PubMed2000

[Frequency of prothrombin gene G20210A variant in the 3'-untranslated region in Chinese people with ischemic stroke].

OBJECTIVE: To ascertain the frequency of prothrombin(F II) gene 3'-untranslated region(3'-UT) G20210A variant and to explore whether this mutation is related to arterial thrombosis in Chinese people. METHODS: We studied 49 patients with thrombosis and 46 healthy Chinese persons. The patients had a first ischemic stroke. The G20210A mutant allele of the prothrombin gene in all blood specimens was investigated by DNA extraction, polymerase chain reaction amplification, Hind III digestion and polyacrylamide gel electrophoresis (PAGE). RESULTS: The patients and normal control subjects were all homozygous for the normal G20210G allele, and there was no any F II G20210A variant. CONCLUSION: Factor II gene 3'-UT G20210A mutant allele is absent in Chinese patients with ischemic stroke and normal subjects; its mutation may not be a major risk factor for thrombogenesis in Chinese people.

3' Untranslated Regions↗
PubMedDate not supplied

[Cerebral venous thrombosis in a girl carrier of the prothrombin gene mutation 20210G--> A treated by local fibrinolysis of the superior sagittal sinus].

CASE REPORT: Girl, aged 4, without antecedents who was admitted to our hospital for drowsiness and progressive sensorial depression. Within 24 hours the clinical picture deteriorated with partial seizures of the right hand side of the body and right hemiparesis. A brain CAT scan showed a left temporoparietal parenchymatous haematoma with collapse of the left lateral ventricle and moderate obliteration of the basal cisterns. MR angiography and cerebral arteriography displayed images that were compatible with thrombosis of the superior sagittal, the left transverse and the sigmoid sinuses. The patient was heterozygotic for the G A mutation in position 20210 of the prothrombin gene, which is linked with a high risk of thrombosis. She was given heparin intravenously, but continued to display endocranial hypertension and tissue ischemia with partial response to hyperosmolar agents and barbituric coma. She was therefore submitted to selective catheterization of the superior sagittal sinus and continuous local fibrinolysis with urokinase for 72 hours. The outcome was satisfactory, with repermeabilisation of the thrombosed sinuses and a good clinical response with no complications. At present the patient has functional paresis of the right hand and receives treatment with oral anticoagulants. CONCLUSIONS: We advocate the use of early local fibrinolytic treatment with urokinase in children affected by thrombosis of the venous sinuses who do not respond to treatment with sodium heparin. We consider it necessary to include the molecular study of the G20210A mutation of the prothrombin gene in screening for prothrombotic risk factors in small children

Child, Preschool↗
PubMed2002

[Primary antiphospholipid syndrome in combination with heterozygous mutation in prothrombin (G20210A) gene: a case report].

A 47-year-old man had residual effects of acute disorders of cerebral circulation in the territory of the median cerebral artery. Computer tomography confirmed the presence of the postischemic focus in the area of the head of the caudate nucleus. Also, thrombosis of small branches of the coronary arteries with development of postinfarction cardiosclerosis and arrhythmia, thrombosis of deep veins in the left leg gave grounds for verification of primary antiphospholipid syndrome (PAS). The diagnosis was serologically confirmed by the presence of anticardiolipin antibodies and the presence of lupus anticoagulant. A genetic examination detected heterozygous mutation G20210A in prothrombin gene but failed to identify G1691A (Leiden) mutation in gene of factor V and C677T in gene 5,10-methylentetrahydrofolatreductase. A family history was collected. Thrombotic complications were found in grandmother and aunt (by mother), in sister and brother. The latter had also a heterozygous mutation of prothrombin gene. Genetic mutations in PAS patients are an additional risk factor of recurrent thrombosis.

Antiphospholipid Syndrome↗
PubMed2002

A fully recombinant partial prothrombin complex effectively bypasses fVIII in vitro and in vivo.

The development of inhibitory antibodies is a serious complication in hemophilic patients, severely compromising therapeutic success. Bleeding episodes in affected patients are controlled by treatment with a plasma-derived prothrombin complex concentrate (PCC), activated PCC (APCC) or recombinant activated factor VII. We hypothesized that a recombinant two-component agent consisting of recombinant prothrombin (rfII) and activated factor X (rfXa) would have substantial fVIII bypassing activity and could be a safe alternative therapeutic option. To test this hypothesis we assembled an agent in vitro solely consisting of rfII and rfXa at a molar ratio of 37,500:1. These factors are believed to be responsible for the activity of APCC preparations. Recombinant fX, used as the source for fXa generation, and rfII were purified from serum-free and protein-free conditioned media of stably transfected CHO and BHK tissue culture cells, respectively. Activation of rfX to rfXa was accomplished by the plant protease ficin, obviating the need for a protease derived from a human or animal source. We found that in vitro the complex reduced the abnormally prolonged activated partial thromboplastin time (APTT) of a high-titer fVIII inhibitor plasma similar to an APCC preparation. Furthermore, addition of increasing amounts of rfII/rfXa to inhibitor plasma resulted in a linear dose-dependent increase in the rate of thrombin generation. In a rabbit fVIII inhibitor model, treatment with rfII/rfXa statistically significantly reduced the intensity of the abnormal cuticle bleeding. In the Wessler test, rfII/rfXa showed no thrombogenicity. These data show that a well-defined, particularly safe and efficacious agent with fVIII bypassing activity can be generated from recombinant fII and fXa.

Animals↗
PubMed1976

Use of prothrombin complex concentrates in the treatment of a hemophilic patient with an inhibitor of factor VIII.

The course and treatment of a life-threatening hemorrhagic episode in a patient with hemophilia A whose plasma contained a high concentration of an inhibitor of factor VIII activity is presented. The inhibitor of factor VIII was localized to the most anodal fractions of immunoglobulin G on electrophoresis, and was thus presumed to be an antibody directed against factor VIII. No therapeutic benefit occurred with infusions of massive amounts of fresh blood and factor VIII concentrates, or with a brief course of immunosuppressive therapy. Administration of standard and activated prothrombin complex concentrates resulted in reduction of the partial thromboplastin time to almost normal values and control of hemorrhage. Eight months later, another hemorrhagic episode occurred. Although a higher titer of inhibitor of factor VIII activity was still present in the patient's plasma, a beneficial therapeutic response was again achieved with standard prothrombin complex infusions.

Adult↗
PubMed1977

Prothrombin complex concentrates: potentially thrombogenic materials and clues to the mechanism of thrombosis in vivo.

Factors affecting the coagulant activity of two different prothrombin complex concentrates have been investigated using a sensitive in vitro assay developed in this laboratory. One concentrate contained substantial amounts of potentially thrombogenic material, while the other, which was deliberately fortified with antithrombin III and heparin during production, was judged to be relatively nonthrombogenic. The coagulant activity of the thrombogenic concentrate has been partially identified and was due largely to the presence of coagulation factos IXa and Xa. Neither concentrate contained detectable thrombin. However, after incubation with calcium or various polyamines, large amounts of additional coagulant material, including thrombin, appeared. Heparin and antithrombin III not only neutralized the thrombogenic materials present in the thrombogenic concentrate, but also inhibited the de novo generation of coagulant enzymes during incubation with calcium. The implication of these studies on the preparation of prothrombin complex concentrates and on host susceptibility to thrombosis during the clinical use of these concentrates is discussed.

Antithrombins↗
PubMed2001

[The factors that influence the consistency of international normalized ratio of prothrombin time].

OBJECTIVE: To investigate the factors that influence the consistency of international normalized ratio (INR) of prothrombin time. METHODS: Using the same automated blood coagulation analyzer and INR calibration plasma with two different types of prothrombin time (PT) reagent to assay the INR values of 19 controls (group 1), 12 patients who took long-term anticoagulant orally (group 2), 12 patients who took it at the first time (group 3) and 8 patients who took long-term anticoagulant together with cephalosporin N (group 4). RESULTS: The two kinds of reagents gave quite different INR values in all four groups (P < 0.01). The INR difference in group 3 (0.23 +/- 0.07, n = 12) was larger than that in group 2 (0.51 +/- 0.20, n = 12) (P < 0.01). The difference in group 4 (0.61 +/- 0.21, n = 8) was larger than that in group 2 (P < 0.01). CONCLUSIONS: The factors that may influence INR consistency are the source and sensitivity of the reagents, as well as the period of the anti coagulant been taken and the other drugs taken at the same time.

Administration, Oral↗
PubMed2004

[International normalized ratio in the prothrombin test: clinical significance and use].

The safety and efficiency of therapy by peroral anticoagulants (PA) depend on a laboratory monitoring based on the prothrombin test (PT). The test is distinguished through its variability conditioned by different means of results' presentation as well as through the sensitivity of thromboplastin and a type of a device used in coagulation detection. WHO recommended, 1983, to standardize the thromboplastin preparations through adjusting their sensitivity (the so-called International Sensitivity Index--ISI) to blood coagulation defects induced by PA versus the primary international reference thromboplastin. Thromboplastin ISI as well as the mean normal prothrombin time (MNPT) of blood plasma are used to calculate the international normalized ratio (INR). The presentation of PT results as INR is justified exclusively for the PA-therapy stabilized patients. The INR system makes it possible to optimize the PA therapy only if the laboratory expert and clinician can clearly understand the PT standardization essence and observe the key WHO recommendations, i.e. definition of a coagulometer-specific ISI by manufacturing companies, estimation of MNPT by laboratories and use of the correct anticoagulant concentration.

Humans↗
PubMed1992

Pulmonary embolism in total hip and knee arthroplasty. Risk factors in patients on warfarin prophylaxis and analysis of the prothrombin time as an indicator of warfarin's prophylactic effect.

This study was designed to identify those total arthroplasty patients at high risk for embolism even while on a proven warfarin prophylactic regimen and to identify the measure of anticoagulation that would be most efficacious in the prevention of pulmonary embolism (PE). A series of 2348 total arthroplasty patients had a preoperative perfusion scan and a postoperative ventilation/perfusion scan. All patients were placed on a low-dose warfarin protocol. Eighty-one patients were identified as having a PE by pulmonary arteriography (incidence of 3.4%). Of these, 89% were asymptomatic and no case was fatal. A control group of 159 patients without PE was used for comparison. Patients older than 65 years of age with a history of genitourinary infection were identified as being at higher risk of PE while on a proven warfarin prophylactic program. These patients may need additional prophylactic measures to reduce the risk of PE. In contrast, patients with a history of phlebitis, PE, obesity, or varicosities were not at excess risk for PE while on warfarin prophylaxis; therefore, no additional prophylactic measures are required. All prothrombin time profiles were within the prophylactic range. Therefore, the actual prothrombin time may not be the critical determinant of the level of anticoagulation or prophylaxis achieved.

Analysis of Variance↗
PubMed1992

Purified factor IX using monoclonal immunoaffinity technique: clinical trials in hemophilia B and comparison to prothrombin complex concentrates.

Replacement therapy for hemophilia B (factor IX deficiency) using prothrombin complex concentrate (PCC) has been associated with serious complications of thromboembolic events and transmission of viral infections. Monoclonal antibody-purified factor IX (Mononine) provides a highly purified factor IX concentrate, while eliminating other vitamin K-dependent factors (II, VII, and X). Mononine was evaluated for in vivo recovery, half-life, and for its safety and efficacy in 10 patients with hemophilia B. The in vivo recovery of factor IX with Mononine was a 0.67 +/- 0.14 U/dL (mean +/- SD) increase per 1U/kg of infused factor IX, and the biologic half-life (t1/2), determined using the terminal phase of elimination, was 22.6 +/- 8.1 hours. Comparison of in vivo recovery of other vitamin K-dependent factors following a single infusion of either Mononine or PCC showed that, whereas Mononine infusion caused no changes in other vitamin K-dependent factors or in prothrombin activation fragment (F1+2), PCC infusion was associated with significant increases of factors II (2.7 U/dL per 1 U/dL of IX increase) and X (2.2 U/dL for 1 U/dL for 1 U/dL of IX). Patients who used Mononine as their sole therapeutic material during the 12-month period showed an excellent response in hemostasis for their bleeding episodes. Their experience with long-term use of Mononine was at least equivalent to their previous experience with PCC in the frequency and amount of factor usage. No patients developed antibody against mouse IgG or an increase in IX inhibitor during the 12-month period. These results indicate that monoclonal antibody-purified factor IX concentrate provides hemostatically effective factor IX replacement while avoiding extraneous thrombogenic substances.

Antibodies, Monoclonal↗