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PubMed2006

[Factor V Leiden (G1691A) and prothrombin-G20210A alleles among patients with deep venous thrombosis and in the general population from Spain].

BACKGROUND: Factor V leiden and the -G20210A variant of prothrombin gene are associated to a higher risk of deep venous thrombosis. AIM: To assess the frequency of factor V Leiden (G1691A) and prothrombin -G20210A alleles in patients with deep venous thrombosis (DVT) and in the general population from Spain. MATERIAL AND METHODS: Factor V Leiden (g1691a) and prothrombin-g20210a alleles were genotyped in 493 individuals from the Spanish general populations and in 131 patients with DVT. The presence of DVT was confirmed by phlebography. Allelic frequencies and the DVT risk associated with these variants were estimated. RESULTS: Allelic frequencies for the factor V Leiden (G1691A) allele were 0.019 in patients with DVT and 0.010 in the general population (p=0.235). The frequencies for the prothrombin-G20210A allele were 0.027 and 0.026 (p=0.975). After adjustment for age and gender, the odds ratio for DVT, associated with the presence of G1691A allele was 2.41, but not statistically significant (95% confidence intervals 0.63-9.19). CONCLUSIONS: Prothrombin-G20210A allele was more prevelant than factor V Leiden (G1691A) allele in the Spanish population. However, the magnitude of the association between the G20210A and DVT risk is very low. On the contrary, the G1691A allele is associated by itself with a two fold increase in DVT risk in this population although without reaching statistical significance due to its low frequency.

Factor V↗
PubMed2002

Prevalence of the 20210 G-->A prothrombin variant and its association with coronary artery disease in a Middle Eastern Arab population.

BACKGROUND: No reports are available on the distribution of the 20210 G-->A prothrombin variant among Middle Eastern Arabs. Additionally, to date, studies that attempt to establish this polymorphism as an independent risk factor or as a predictor for coronary artery disease (CAD) have yielded conflicting results. OBJECTIVE: To determine the prevalence of the 20210 G-->A prothrombin variant among Middle Eastern Arabs and to evaluate the potential relevance of this variant to Arab patients with angiographically documented CAD. METHODS AND RESULTS: We used the polymerase chain reaction and restriction enzyme digestion to determine the prevalence of this polymorphism in 613 individuals from Arabic ethnic origin with CAD and from 593 healthy blood donors (BDs) from an identical ethnic background. Within the BD group (n = 593), 10 individuals (1.7%) were heterozygous, 583 individuals (98.3%) were normal, and none were homozygous for the 20210 G-->A prothrombin variant. Within the CAD group (n = 613), 13 individuals (2.1%) were heterozygous, 600 individuals (97.9%) were normal, and none were homozygous for the 20210 G-->A prothrombin variant. A chi(2) analysis was used to evaluate any significance in the distribution of genotypes. A value of 1.23 was obtained. Values less than 3.84 indicate no statistically significant difference between the heterozygous carriers of the 20210A allele in both study groups. CONCLUSIONS: In our population of Middle Eastern Arabs, the presence of the 20210 G-->A prothrombin variant is not associated with patients with angiographically documented CAD. Therefore, this variant cannot be considered as an independent risk factor or as a predictor for CAD in this population.

Adult↗
PubMed2002

Clinical and laboratory management of the prothrombin G20210A mutation.

OBJECTIVE: To make recommendations regarding the appropriate evaluation for the prothrombin G20210A mutation, as reflected by published evidence and the consensus opinion of recognized experts in the field. DAT SOURCES: Review of the medical literature, primarily since 1996. DATA EXTRACTION AND SYNTHESIS: After an initial assessment of the literature, key points defining the condition, and review of the clinical study design, a draft manuscript was prepared and circulated to every participant in the College of American Pathologists Conference on Diagnostic Issues in Thrombophilia before the meeting. Each of the key points and associated recommendations were then presented for discussion at the conference. Recommendations were accepted if a consensus of 70% of experts attending the conference was reached. The results of the discussion were used to revise the manuscript into its final form. CONCLUSIONS: Consensus was reached on several recommendations concerning the criteria for testing for the prothrombin G20210A mutation and for the method of testing. First, a major point of consensus was that the prothrombin G20210A mutation is a significant risk factor for venous thromboembolism (VTE) and that testing should be considered in the initial evaluation of suspected inherited thrombophilia. Second, although several analytic methods are commonly used for genetic testing for the prothrombin mutation, all are generally robust and reliable. The recommendations for testing for the prothrombin mutation parallel those for the factor V Leiden mutation and include patients with a history of recurrent VTE, a first episode of VTE before the age of 50 years, a history of an unprovoked VTE at any age, thromboses in unusual anatomic sites, or an affected first-degree relative with VTE. A history of VTE related to pregnancy or estrogen use and unexplained pregnancy loss during the second or third trimesters were also considered to be indications for testing. Other scenarios remain controversial or not recommended, including general population screening.

Adult↗
PubMed1999

The prothrombin gene variant 20210A in venous and arterial thromboembolism.

Several hereditary disorders affecting coagulation factors have been identified as prothrombotic risk factors. Recently, the prothrombin 20210 A/G mutation has been identified as a second important polymorphism involved in venous thrombosis. This article reviews all published information about this new procoagulant mutation. Our group has been involved in a number of studies about the role and importance of polymorphisms in thromboembolic disease, including the analysis of the prothrombin 20210 A/G mutation. Moreover, an extensive Medline literature search was made to complete the review using the key words: prothrombin mutation, 20210, venous or arterial thrombosis. The combination of environmental and genetic risk factors determines the relative risk that any individual has of suffering a thrombotic episode. Some genetic mutations affecting coagulation factors have been described. Recently, Poort et al. described a new mutation in the 3'-untranslated region of the prothrombin gene. The prothrombin 20210 G/A mutation, associated with elevated levels of factor II in plasma, significantly increases the risk of developing venous thrombosis. In fact, this polymorphism is the second most important genetic risk factor for venous thrombosis in Caucasian populations. Moreover, and supporting the multifactorial feature of thromboembolic diseases, this mutation greatly increases the possibility of developing a thrombotic episode when combined with other environmental or genetic risk factors. The role of this procoagulant mutation in arterial vascular disease is, however, unclear.

Humans↗
PubMed2000

High prevalence of the prothrombin gene mutation in women with intrauterine growth retardation, abruptio placentae and second trimester loss.

BACKGROUND: It has been reported recently that obstetric complications are associated with thrombophilias. Our objective was to investigate the association between pregnancy complications and the guanine 20210 adenine (G20210A) mutation in prothrombin gene. METHODS: Two hundred and twenty-two women (study group) with obstetric complications were tested for the prothrombin mutation. Indications for testing were: severe preeclampsia, mild preeclampsia, intrauterine growth retardation, severe abruptio placentae, unexplained stillbirth, second trimester loss, and three or more consecutive spontaneous abortions. We also tested 156 healthy women who had at least one normal pregnancy and comprised the control group. RESULTS: Demographic data of the study and control groups were similar. Twenty-eight women of the study group (13%) were found to be heterozygous carriers of the 20210 variant of the prothrombin gene compared to five (3.2%) of the control group, p=0.001, odds ratio (OR) 2.9; 95% confidence interval (CI) 1.3-6.5. Compared to the control women, the prothrombin gene mutation was significantly more prevalent in women with IUGR, abruptio placentae, and second trimester loss but not in women with mild or severe preeclampsia, stillbirth and habitual abortion. CONCLUSIONS: Our data demonstrate that the mutation in the prothrombin gene is associated with specific pregnancy complications.

Abortion, Spontaneous↗
PubMed1975

Activation of human prothrombin by highly purified human factors V and X-a in presence of human antithrombin.

In this communication we describe the first method for isolating human Factor V. The final product contains no other coagulation components as judged by functional assays and is physically homogeneous as shown by isofocusing gel electrophoresis. In addition, we present a means for obtaining intrinsically activated human Factor X-a. This preparation is usually homogeneous as judged by isofocusing gel electrophoresis. However, on occasion, an additional minor electrophoretic species with Factor X-a activity is observed. Furthermore, we describe the use of isoelectric focusing in sucrose density gradients to free human prothrombin from contamination by coagulation factors and other components. These homogeneous human proteins are employed to examine the conversion of prothrombin to thrombin in the presence and absence of human antithrombin. The latter component is responsible for virtually all of the plasm's capacity to neutralize Factor X-a and thrombin. In the absence of antithrombin, prothrombin (67,800) is converted to the precursor P-2 (51,600) and the fragment F-a (19,500). Subsquently, P-2 is cleaved to form the precursor P-3 (37,000), and the fragment F-b (11,500). Finally, P3 IS proteolyzed to form the heavy chain T-h (29,500) and the light chain T-L (6,500) of active thrombin. In the presence of antithrombin, an additional prothrombin conversion pathway is observed in which the zymogen is directly cleaved to form P-3 and F-A + B (30,000) prior to thrombin generation. Trace amounts of free thrombin remain uninhibited by antithrombin and could bias the zymogen activation pathway. Hirudin is known to neutralized thrombin instantaneoulsly. We demonstrate that the purified leech protein also binds to P-3 and prevents thrombin formation. When hirudin is added to activation mixtures at concentrations sufficient to virtually suppress P-3 conversion to thrombin, molecular species from both activation pathways are observed. Thus two human prothrombin conversion sequences appear to be initiated by Factor X-3 and may be of physiological significance.

Antithrombins↗
PubMed2001

Association between the prevalence of antibodies to beta(2)-glycoprotein I, prothrombin, protein C, protein S, and annexin V in patients with systemic lupus erythematosus and thrombotic and thrombocytopenic complications.

BACKGROUND: Anti-phospholipid (aPL) antibodies (Abs) frequently found in the plasma of patients with systemic lupus erythematosus (SLE) have been associated with thrombotic complications. Our aim was to clarify the roles in thrombosis of aPL Abs that react with complexes of phospholipids and plasma proteins such as beta(2)-glycoprotein I (beta(2)-GPI), prothrombin, protein C, protein S, and annexin V. METHODS: We determined the prevalence of aPL Abs to various phospholipid-binding plasma proteins in SLE patients with arterial thrombosis (30 cases), venous thrombosis (19 cases), thrombocytopenia (14 cases), fetal loss (14 cases), and patients without complications (91 cases). The aPL Abs were measured by an ELISA system in which human plasma proteins (beta(2)-GPI, prothrombin, protein C, protein S, and annexin V) were immobilized on gamma-irradiated or plain polystyrene plates. RESULTS: All types of aPL Abs were frequently observed in the patients with SLE when gamma-irradiated polystyrene plates were used (51 of 168 cases positive for anti-beta(2)-GPI, 94 of 168 cases positive for anti-prothrombin, 36 of 168 cases positive for anti-protein C, 47 of 168 cases positive for anti-protein S, and 50 of 168 cases positive for anti-annexin V), whereas no Abs to these plasma proteins were detected when plain polystyrene plates were used. Multivariate analysis confirmed that both anti-beta(2)-GPI and anti-prothrombin Abs were significant risk factors for arterial thrombosis [odds ratios (ORs), 8.8 and 14.5, respectively; 95% confidence intervals (CIs), 3.2-25 and 1.8-116, respectively] but not for venous thrombosis. The presence of anti-protein S Abs was a significant risk factor for venous thrombosis (OR, 30.4; CI, 3.3-281) but not for arterial thrombosis. The only significant risk factor for fetal loss was the presence of anti-annexin V Abs (OR, 5.9; CI, 1.4-14.8). CONCLUSIONS: Patients with SLE frequently have some aPL Abs to beta(2)-GPI, prothrombin, protein C, protein S, and annexin V. Thrombotic complications in SLE may depend on the antigenic specificities of these Abs, alone or in combination.

Adolescent↗
PubMed2001

Phenotypic APC resistance in carriers of the A20210 prothrombin mutation is associated with an increased risk of venous thrombosis.

We hypothesized that increased prothrombin levels associated with G20210A prothrombin gene mutation could affect the results of activated protein C (APC) resistance phenotype and increase the risk of venous thrombosis (VT). The increasing addition of purified prothrombin in plasma of 90 normal subjects resulted in a parallel significant increase of APC resistance. Significantly different mean n-APC-SR in 879 GG20210 subjects compared to 27 heterozygous carriers of isolated G20210A mutation was observed (1.0 +/- 0.12 vs. 0.95 +/- 0.11; P = 0.02) in a random sample of 906 normal population subjects. Twenty-seven families with VT and isolated G20210A mutation consecutively diagnosed during 1998-1999 were evaluated. Mean n-APC-SR was significantly lower in the 80 G20210A carriers compared to 58 GG 20210 relatives investigated, even after sex and age adjustment (0.92 +/- 0.08 vs. 1.05 +/- 0.13; P < 0.0001). A strong relationship between plasma prothrombin level and n-APC-SR was observed in the families. When n-APC-SR values were grouped in tertiles, the odds ratio for VTE, after exclusion of the index cases and adjustment for 20210 status, for subjects in the lowest tertile (n-APC-SR 0.73-0.90) was 4.58 (95% CI 0.78-26.88) compared to upper tertile (n-APC-SR 1.01-1.30). In conclusion, in subjects with G20210A mutation APC resistance is significantly increased, correlates with plasma prothrombin level and the carriers with the lowest APC resistance values have an increased risk of VTE.

3' Untranslated Regions↗
PubMed2001

[From gene to disease; risk factors for venous thrombosis: factor V Leiden and prothrombin 20210A].

Venous thromboembolic disease is an important clinical entity, in which both acquired and genetic risk factors play a causative role. Genetic factors which increase thrombotic risk consist of rare heterogeneous loss-of-function mutations in coagulation-inhibitory factors, such as antithrombin, protein S and C, and more common, but unique, gain-of-function mutations in coagulation factors V and II, so-called factor V-Leiden and prothrombin 20210A. The genetic defect underlying factor V-Leiden is a guanine (G) to adenine (A) mutation in the factor V gene, causing substitution of arginine at position 506 by glutamine, thereby providing resistance to proteolytic cleavage by activated protein C (APC). In the prothrombin 20210A allele a G to A mutation at nucleotide 20210 in the 3'-untranslated region of the prothrombin gene is associated with increased prothrombin levels. The APC-resistance assay is used to screen for the presence of factor V-Leiden. Both factor V-Leiden and prothrombin 20210A are diagnosed by DNA analysis.

Activated Protein C Resistance↗
PubMed2001

[Relationship between cholinesterase, prothrombin activity and albumin and the pathology of the liver].

BACKGROUND: To investigate the relationship between serum cholinesterase, albumin and plasma prothrombin activity and the pathology of the liver in patients with viral hepatitis. METHODS: Totally 135 patients diagnosed as chronic hepatitis, cirrhosis and/or severe hepatitis with needle biopsy of liver were enrolled in this study. Serum cholinesterase and albumin of the patients were detected with enzyme rate method; meanwhile, their plasma prothrombin activity was detected with turbidimetry test. RESULTS: The percentage of decrease of the level of serum cholinesterase was higher than that of albumin and plasma prothrombin activity in chronic mild and moderate hepatitis; the level of serum cholinesterase, albumin and plasma prothrombin activity decreased gradually followed by the exacerbation of inflammatory reaction (P<0.001) and by the elevation of degree of fibrosis of the liver (P <0.001) their correlation coefficient was 0.720 to 0.778 (P<0.001). CONCLUSION: The level of serum cholinesterase could better a nd more sensitively reflect the synthetic function and the damage of the pathology of the liver than that of albumin and plasma prothrombin activity could do, they all negatively correlated with the pathology of the liver.

Adolescent↗
PubMed2002

Factor V Leiden, prothrombin gene mutation, and thrombosis risk in patients with antiphospholipid antibodies.

OBJECTIVE: To determine if the prevalence of 2 prothrombotic genetic factors, factor V Leiden and prothrombin gene mutation, is increased in patients with antiphospholipid (aPL) antibodies with a history of venous/arterial thrombosis compared to patients with aPL antibodies with no history of thrombosis. METHODS: One hundred fifty-seven patients with aPL antibodies were studied. The occurrence of venous and arterial thrombotic events since the time of antibody detection was determined retrospectively, using appropriate clinical and diagnostic criteria. Clinical risk factors for thrombosis were documented and included hypertension, hyperlipidemia, cigarette smoking, diabetes, positive family history, use of oral contraceptive, pregnancy, trauma, hospitalization, varicose veins, and malignancy. Genomic DNA was extracted from blood cells for determination of factor V Leiden mutation G1691 --> A and prothrombin mutation G20210 --> A by polymerase chain reaction and restriction fragment length polymorphism analysis. RESULTS: Of 157 patients, 69 had a history of thrombosis (venous 37, arterial 32); 147 (94%) patients had anticardiolipin (aCL) antibodies; 69 (45%) had lupus anticoagulant (LAC). The prevalence of factor V Leiden in patients with thrombosis was 13% compared to 4.6% in patients without thrombosis (OR 3.11, CI 0.92-10.6). In patients with aCL antibodies, 15% of patients with arterial thrombosis had factor V mutation compared to 3.5% of patients without thrombosis (OR 4.9, CI 1.2-19.3). The prothrombin gene mutation was identified in 5 patients, none of whom had thrombosis. Stepwise logistic regression analysis indicated that LAC (p = 0.005), male sex (p = 0.04), and hypertension (p = 0.03) were the strongest risk factors for developing thrombosis and that no additional risk was conferred by factor V Leiden (p = 0.13) and prothrombin gene mutation. CONCLUSION: Although the prevalence of factor V Leiden is modestly increased in patients with autoimmune aPL antibodies and thrombosis, these results suggest that its detection does not significantly increase the risk of a thrombotic event, once other clinical risk factors have been considered. Prothrombin gene mutation is not associated with thrombosis in patients with aPL antibodies.

Adult↗
PubMed2002

[Prothrombin time and its standardization].

This review regarding prothrombin time and its standardization is described around some recent topics as the followings. 1. History of standardization for prothrombin time and revised WHO guideline for thromboplastin; A short history of standardization is summarized to understand a scheme of International Normalized Ratio (INR) based on International Sensitivity Index (ISI) that is calibrated by International Reference Preparation (IRP) for thromboplastin, and some key points in revised WHO guideline for thromboplastin and plasma used to control oral anticoagulant therapy are interpreted for research and practical use. 2. Point-of-care prothrombin time monitoring; A portable device to measure prothrombin time with whole blood sample, such as CoagChek (Roche), contributes to self-management by patients required long-term oral anticoagulation. Some investigators reported clinical agreement to use this monitoring system and improvement of patient's QOL and cost-effectiveness in overseas. 3. New types of thromboplastins; Two new types of thromboplastins have been available since the last year in Japan. One is a human plain thromboplastin, Simplastin HTF (Bioméreux) from extract of cultured human lung cancer cell, and another is IL test PT-Fibrinogen Recombinant (Iatron) from recombinant rabbit tissue factor relipidated in a synthetic phospholipid blend. For control of oral anticoagulation, good performance are expected in either thromboplastins because of their sufficient low ISI values. 4. INR methodology for other diseases; INR/ISI system is designed as a standardized methodology for control of oral anticoagulation. Prothrombin time, however is utilized as a global coagulation test for diagnosis or criteria of other disorders, such as congenital coagulation factor deficient, severe liver dysfunction and disseminated intravascular coagulation. Previous our study indicated that discrepancy of sensitivities to plasma absorbed multiple coagulation factors and plasma from patients under oral anticoagulation was revealed in rabbit brain thromboplastins, but not in human origins. Discrepancy of sensitivities observed in rabbit thromboplastins was emphasized in convert to INR values. These results suggested that the use of human thromboplastin of which ISI is close to 1.0 leads possibility for introducing INR methodology to evaluate PT of other disorders.

Environmental Monitoring↗
PubMed2003

Different circumstances of the first venous thromboembolism among younger or older heterozygous carriers of the G20210A polymorphism in the prothrombin gene.

BACKGROUND AND OBJECTIVES: The G20210A polymorphism in the prothrombin gene is a common cause of inherited thrombophilia. Scarce information is available about the circumstances of the heralding thrombotic manifestation at different ages. The aim of this study was to determine the risk of spontaneous or secondary venous thromboembolism (VTE) among younger and older carriers of the G20210A prothrombin polymorphism. DESIGN AND METHODS: We performed a case-control study, investigating 650 patients with a first objectively documented deep venous thrombosis of the legs or pulmonary embolism and 703 individuals with no history of vascular disease. In all of them we carried out laboratory screening for antithrombin III, protein C and protein S deficiencies, and for the presence of the factor V Leiden and the G20210A prothrombin polymorphisms. RESULTS: After adjustment for other inherited causes of thrombophilia (deficiency of antithrombin III, protein C or S, factor V Leiden) the overall risk for VTE associated with the prothrombin polymorphism was 3.4 times higher than in the controls (95% CI, 2.0 to 5.8). Stratification according to the age and to the circumstances of the first event revealed an increased risk of spontaneous VTE only among the patients older than 45 years in comparison with age-matched controls (odds ratio 4.4, 95% CI 1.8 to 10.6); among the younger individuals the risk was increased for secondary VTE (odds ratio 4.8, 95% CI, 2.3 to 9.8) but not for spontaneous VTE. INTERPRETATION AND CONCLUSIONS: The clinical penetrance of the thrombotic tendency associated with the G20210A prothrombin polymorphism is more expressed in the presence of a circumstantial risk factor (oral contraceptives, pregnancy, surgery, trauma) and in the presence of older age, which acts as an additional circumstantial risk factor. Accordingly, such situations should not discourage from carrying out laboratory screening.

Adult↗
PubMed2002

Factor V Leiden and prothrombin G20210A mutations in Thai patients awaiting kidney transplant.

Renal transplantation provides the best long-term treatment for chronic renal failure, but thrombosis of the transplanted renal artery or renal vein is one of the causes of kidney failure in the early postoperative period. Factor V Leiden (FVL) and prothrombin G20210A mutation are the most frequent genetic abnormalities associated with venous thrombosis. We investigated the prevalence of FVL and prothrombin G20210A by polymerase chain reaction with restriction fragment length polymorphism in 75 Thai patients awaiting renal transplant, and a control group of 106 healthy blood donors. Of those awaiting renal transplant, none was found to carry FVL or prothrombin G20210A mutations. Neither the heterozygous nor the homozygous FVL mutation nor the prothrombin G20210A mutation was detected in the 106 healthy volunteers. Although we failed to detect FVL and prothrombin G20210A mutation among those waiting for a kidney transplant, the population size was small. Further studies need to be performed in order to ascertain if these coagulation mutations are of relevance in predicting patients at risk of early transplant failure.

Adolescent↗
PubMed1992

Detection of a single base substitution of the gene for prothrombin Tokushima. The application of PCR-SSCP for the genetic and molecular analysis of dysprothrombinemia.

The genetic and molecular basis of a mutant prothrombin of 'prothrombin Tokushima' was studied by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and PCR-restriction fragment length polymorphism (PCR-RFLP) analyses. The abnormal gene was detected by altered migration by PCR-SSCP and by the loss of an MspI site by PCR-RFLP. The gene for prothrombin Tokushima was shown to be inherited from the mother of the proband. Sequencing analysis using PCR-amplified genomic DNA clarified a substitution of thymine (T) for cytosine (C) at position 9,490, changing arginine (Arg) to tryptophan (Trp) at position 418 of the polypeptide chain. This point mutation is assumed to be the molecular basis of prothrombin Tokushima, firstly, because of the absence of distinct changes in Southern blot analysis of the proband's DNA (using a full-length human prothrombin cDNA as a probe), secondly, because it has the same molecular weight as the abnormal gene product, and, thirdly, because of the absence of other amino acid abnormalities in the proteolytic peptide-fragments. It is concluded that PCR-SSCP and PCR-RFLP were useful for detecting the abnormal gene and for directly diagnosing the carrier status of dysprothrombinemia. This is the first report of gene analysis of dysprothrombinemia.

Amino Acid Sequence↗
PubMed1977

[Changes of prothrombin activity by plasmin immobilized on L-lysine Sepharose 4B].

It is demonstrated that the method of immobilization of human plasmin by its adsorption on L-lysine-Sepharose 4B can be successfully applied for bovine plasmin isolation. Proteolysis of bovine prothrombin by bovine prothrombin by bovine plasmin preparations of high caseinolytic activity results in the increase of prothrombin level. Prothrombin proteolysis by bovine plasmin preparations of high caseinolytic activity results in the decrease of prothrombin level.

Animals↗
PubMed2003

[Control of anticoagulant therapy with portable prothrombin time device in patients with mechanical heart valve prostheses: two-year follow-up].

BACKGROUND: Monitoring patients on oral anticoagulation is essential to prevent haemorrhage and recurrent thrombosis, but it is still difficult. We studied a group of 348 patients with mechanical heart valve prostheses to verify whether the use of a new portable prothrombin time device might improve the management of oral anticoagulant therapy. METHODS AND MATERIAL: We used a new portable prothrombin time device to check the anticoagulation therapy in a group of 348 patients with mechanical heart valve prostheses to validate its results by comparing to routine I.N.R. determinations (28 pts) and verify its user-friendliness by a face-to-face interview. Furthermore, the incidence of haemorrhagic and thromboembolic events has been studied by a two-year follow-up. RESULTS: Pearson correlation indicated an R2 = 0.9 between I.N.R. values determined by routine or by a new portable prothrombin time device. All patients agreed to replace the routine I.N.R. determinations with those by the new procedure, particularly female, young and those with usually difficult blood collections. During the two-year follow-up period, 21 haemorrhagic (2.6/100/patients/year) and 5 thromboembolic events (0.6/100/patients/year) occurred; but neither replaced valves' thrombi nor fatal events were found out. CONCLUSIONS: I.N.R.s determined using a new portable prothrombin time device are convincing as routine determinations. Such new procedure improves the quality of life, and the therapeutical range of anticoagulation is maintained safer and longer than by routine determinations. These results suggest that the control of anticoagulation in patients to a set I.N.R. therapeutic range is improved by using portable prothrombin time device in expert anticoagulation clinics, such improvement may result in reducing mortality as well as morbidity in patients treated with oral anticoagulants.

Anticoagulants↗
PubMed2004

Cleavage of prothrombin bound in immune complexes results in high thrombin enzymatic activity.

Thrombin plays a pivotal role in blood clotting as well as in the regulation of vascular remodeling and oxidative stress. Recent evidence suggests that auto-antibodies directed against prothrombin, may play an important role in the pathogenesis of atherosclerosis. It is however not clear, if prothrombin bound in an immune complex retains its clotting and regulatory properties or acts solely by increasing vascular inflammation. In order to answer this question, we used a newly developed stain for the detection of thrombin activity of such complexes. Plasma and serum samples were subjected to rocket immunoelectrophoresis in an anti-prothrombin antiserum containing agarose gel. Gel plates, covered with a nitrocellulose membrane were soaked with chromogenic thrombin substrate. The product of thrombin activity was diazotized to red azo dye bound to nitrocellulose. Activity stain revealed barely discernible rockets in plasma, but heavily stained ones in serum. Pre-incubation with trypsin enhanced activity of immunoprecipitates deriving from plasma, but not from serum. Densitometric analysis showed, that the trypsin-enhanced activity in plasma derived immune complexes was twice as high as in serum derived immunoprecipitates. Thrombin active centre is not blocked by anti-prothrombin antiserum allowing to retain thrombin activity. Moreover, prothrombin in immunoprecipitate is readily cleaved by proteolytic enzymes. This cleavage could potentially be enhanced by antibody binding, although these results need to be confirmed using different antibodies.

Antigen-Antibody Complex↗