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PubMedDate not supplied

Abnormal prothrombin: evaluation as a tumour marker and localization in tissues of patients with hepatocellular carcinoma.

In this study, the diagnostic significance of PIVKA-II concentrations in various liver diseases was evaluated, and the use of PIVKA-II as a tumour marker for hepatocellular carcinoma (HCC) was discussed. Also, the location of abnormal prothrombin (PIVKA-II) production in HCC by indirect immunoperoxidase staining was examined. There was a good correlation between plasma and serum PIVKA-II concentrations, indicating that serum samples are adequate for PIVKA-II measurements. Fifty-four of 97 (55.7%) patients with HCC, one of 10 (10%) patients with metastatic liver cancer and two of 47 (4.3%) patients with liver cirrhosis had positive serum PIVKA-II concentrations. Positive serum PIVKA-II concentrations were found more frequently in patients with HCC than in any other liver disease (P < 0.01). Of the 97 patients with HCC, 54 (55.7%) were PIVKA-II positive, 76.3% had serum concentrations of either PIVKA-II or alpha-fetoprotein, indicating the usefulness of both tumour markers in the diagnosis of HCC. Using frozen sections of tissue specimens obtained at autopsy or during surgery, the localization of PIVKA-II was examined by indirect immunoperoxidase staining with specific anti-PIVKA-II antibodies. Tissues from 12 of 22 patients with HCC had positive PIVKA-II indirect immunoperoxidase staining only in the cancer cells. Cells with greater atypia tended to have stronger cytoplasmic staining. No specific staining was observed in non-cancerous cells. These findings suggest that PIVKA-II is synthesized specifically in hepatic cancer cells.

Adult↗
PubMed1979

A randomized study of factor VIII or prothrombin complex concentrate infusions in children with haemophilia and antibodies to factor VIII.

In four children with haemophilia A and antibodies to factor VIII, 18 bleeding episodes were randomized for treatment with factor VIII concentrate (30 units/kg) and 18 for treatment with a prothrombin-complex concentrate (prothrombinex) given in a dose of 30 units of factor IX/kg. Treatment with prothrombinex was associated with a better clinical response, a significantly greater shortening of the kaolin partial thromboplastin time and significantly lower incidence of post-infusion increase of levels of factor VIII antibodies. Although treatment with factor VIII concentrate was clinically successful in 15 episodes, treatment failures occurred in three instances leading to parental request for withdrawal from study in two families.

Antibodies↗
PubMed1999

Increase of serum des-gamma-carboxy prothrombin in alcoholic liver disease without hepatocellular carcinoma.

The purpose of this study is to determine serum des-gamma-carboxy prothrombin (DCP) levels in benign liver diseases by a new sensitive method, and to demonstrate the elevation of serum DCP in alcoholic liver disease (ALD) without hepatocellular carcinoma (HCC). Median values of serum DCP were 16.2 mAU/ml (range: 3.2 to 1570 mAU/ml) in ALD and 16.7 mAU/ml (1.2 to 75.4 mAU/ml) in viral liver disease (VLD). Using the cut-off value of 40 mAU/ml as a tumor marker for HCC, 21% (11/52) was positive in ALD and 2% (1/57) was positive in VLD (p = 0.0014, Fisher's exact probability test), and 27% (9/33) was positive in alcoholic liver cirrhosis and 3% (1/39) was positive in viral liver cirrhosis (p = 0.0042, Fisher's exact probability test). The positive rate of DCP was significantly (p < 0.001, Spearman's rank correlation test) correlated with the severity of liver disease in ALD. Serum vitamin K level was not decreased in cases with ALD. In a demonstrable case, serum DCP was decreased after abstinence and was increased again after the beginning of ethanol intake, suggesting the involvement of ethanol to the elevation of serum DCP in ALD. In conclusion, serum DCP was significantly elevated in ALD, compared with VLD, although the mechanism of the elevation of DCP was not clarified. Ethanol intake may act, in part, on the increase of serum DCP in ALD.

Aged↗
PubMed2006

Effect of fresh-frozen plasma transfusion on prothrombin time and bleeding in patients with mild coagulation abnormalities.

BACKGROUND: Fresh-frozen plasma (FFP) is frequently transfused to patients with mild prolongation of coagulation values under the assumption that FFP will correct the coagulopathy. There is little evidence to support this practice, however. To determine the effect of FFP on coagulation variables and correlation with bleeding in patients with mildly prolonged coagulation values, a prospective audit of all FFP transfusions at the Massachusetts General Hospital between September 2, 2004, and September 30, 2005, was performed. STUDY DESIGN AND METHODS: All patients transfused with FFP for a pretransfusion prothrombin time (PT) between 13.1 and 17 seconds (international normalized ratio [INR], 1.1-1.85) and with a follow-up PT-INR within 8 hours of transfusion were included. Of 1091 units of FFP transfused, follow-up coagulation values within 8 hours were available for 121 patients (324 units). RESULTS: Transfusion of FFP resulted in normalization of PT-INR values in 0.8 percent of patients (95% confidence interval [CI], 0.0020-0.045) and decreased the PT-INR value halfway to normalization in 15.0 percent of patients (95% CI, 0.097-0.225). Median decrease in PT was 0.20 seconds (median decrease in INR, 0.07). Pretransfusion PT-INR, partial thromboplastin time, platelet count, and creatinine values had no correlation with red blood cell loss. CONCLUSION: It is concluded that transfusion of FFP for mild abnormalities of coagulation values results in partial normalization of PT in a minority of patients and fails to correct the PT in 99 percent of patients.

Adolescent↗
PubMed2005

A prospective study of antibodies to beta2-glycoprotein I and prothrombin, and risk of thrombosis.

Antiphospholipid syndrome (APS) is a clinical autoimmune disorder characterized by thrombosis/pregnancy morbidity associated with the persistence of lupus anticoagulant (LA) and/or anticardiolipin (aCL) antibodies. We assessed the contribution of antibodies to beta2-glycoprotein I (anti-beta2GPI) and prothrombin (anti-PT) to the thrombotic risk in a cohort of 194 consecutive patients with persistent LA and/or aCL. Median follow-up was 45 months. A total of 39 patients (20.1%) had one documented episode of thrombosis during follow-up. Eleven of these patients had no previous thrombosis before enrollment in the study and 28 had recurrences of thrombosis. There were 21 venous and 18 arterial thrombotic events and the overall incidence of thrombosis was 5.6% per patient-year. After multivariate analysis, the male sex (P = 0.025), a previous thrombosis (P < 0.01), the presence of anti-beta2GPI (P = 0.001), and the presence of anti-PT (P = 0.03) remained as independent risk factors for recurrent thrombosis. Only IgG anti-beta2GPI and anti-PT were associated with an increased risk of thrombosis (P < 0.01 and P = 0.005). Patients testing positive for anti-beta2GPI had a higher rate of thrombosis than did antiphospholipid patients without anti-beta2GPI (8.0% vs. 3.1% per patient-year). Similarly, a higher rate of thrombosis was found in patients with positive anti-PT compared with patients without anti-PT (8.6% vs. 3.5% per patient-year). Considering only the group of 142 LA positive patients, the highest incidence of thrombosis was found in LA patients positive for both anti-beta2GPI and anti-PT (8.4% per patient-year). In conclusion, the presence of IgG anti-beta2GPI and anti-PT in patients with LA and/or aCL and mainly in those with LA predicts a higher risk of thromboembolic events.

Adolescent↗
PubMed2005

Factor V Leiden and prothrombin G20210A polymorphisms as risk factors for miscarriage during a first intended pregnancy: the matched case-control 'NOHA first' study.

Factor V Leiden (FVL) and prothrombin G20210A (FIIG20210A) mutations are associated with a higher risk of miscarriage: we sought to understand whether this association differs by clinical time of unexplained miscarriage, and by ethnic origin, among women with no previous thrombotic episode, during the first intended pregnancy. We performed a case-control study nested in a cohort of 32 683 women. We analyzed 3496 pairs of women matched for classical confounding factors. The FVL and FIIG20210A mutations were associated with an increased risk of miscarriage in Caucasian women [odds ratio (OR) 3.19, 95% confidence interval (CI) 2.37-4.30, P < 0.001 and OR 2.36, 95% CI, 1.72-3.24, P < 0.001, respectively]. Among non-Caucasian women, the mutations were rare and the associations with risk of miscarriage less clear. FVL and FIIG20210A mutations were independent risk factors for miscarriages only for women with related clinical signs occurring from the 10th week of gestation on (OR 3.46, 95% CI 2.53-4.72, P < 0.001 and OR 2.60, 95% CI 1.86-3.64, P < 0.001, respectively). These results indicate that FVL and FIIG20210A mutations are associated with a significant risk of spontaneous abortion which clinical signs occur from the 10th week on of the first intended pregnancy.

Abortion, Spontaneous↗
PubMed2001

Dural arteriovenous fistula associated with prothrombin gene mutation.

An association between dural arteriovenous fistula and cerebral sinus thrombosis is reported. It is clear in several cases that thrombosis precedes the development of the fistula while it is unclear that it occurs in every case. The authors report a case of a woman with sinus thrombosis and presence of prothrombin gene mutation who subsequently developed a large dural arteriovenous fistula. Various possible factors involved in the pathogenesis of a dural fistula are discussed, with emphasis on underlying thrombophilia and oral contraceptive use in this patient.

Adult↗
PubMed2002

Evaluation of guidelines for ordering prothrombin and partial thromboplastin times.

OBJECTIVES: Existing clinical practice guidelines for ordering prothrombin time (PT) and partial thromboplastin time (PTT) tests in the emergency department (ED) include physician expectation of an invasive procedure as a criterion. This study sought to determine whether this criterion accurately identifies patients who undergo an invasive procedure and whether an amalgam of these guidelines identifies patients at low risk of an adverse medical outcome. METHODS: A prospective observational cohort study of adults treated in a university medical center ED between July 1997 and March 1998. Physicians were surveyed at order placement to determine the presence of guideline criteria. Adverse clinical outcomes defined as an International Normalized Ratio [INR] > 1.3 or PTT > 39.9 seconds combined with consequent directed medical therapy were abstracted from ED and the first 24 hours of inpatient medical records. RESULTS: The sensitivity of ED physician expectation of an invasive procedure was 60.0%; therefore, it was excluded from both the PT and PTT guidelines. There were 553 patients with a PT test order; test order indications were absent in 190 (34.4%), of which one (0.5%, 95% CI = 0.1% to 2.9%) had adverse outcomes. There were 547 patients with a PTT test; test order indications were absent in 226 (41.3%), of which three (1.3%, 95% CI = 0.4 to 3.8%) had adverse outcomes. All three were taking warfarin when they presented to the ED. CONCLUSIONS: Emergency department physician expectation of an invasive procedure for patients with PT or PTT test orders is an insensitive predictor of patients who undergo such procedures. Clinical practice guidelines that exclude this criterion identify ED patients at the time of ED presentation at low risk for adverse medical outcomes in the ED or shortly after admission.

Aged↗
PubMed1999

Serum des-gamma-carboxy prothrombin levels determined by a new generation of sensitive immunoassays in patients with small-sized hepatocellular carcinoma.

OBJECTIVE: Des-gamma-carboxy prothrombin (DCP), also called protein induced by vitamin K absence or antagonist II (PIVKA-II), is a tumor marker complementary to AFP for the diagnosis of hepatocellular carcinoma (HCC). Currently available immunoassays for DCP are not sensitive enough to detect HCC at an early stage. Recently, two new immunoassays with enhanced sensitivity were developed. The aim of this study was to assess the diagnostic values of the new methods in patients with small-sized HCC. METHODS: Coded serum samples obtained from 36 patients with small-sized and single-nodular HCC (< or = 3 cm in diameter) and 49 patients with posthepatitic cirrhosis not carrying HCC were analyzed. DCP levels were determined in three different ways: 1) conventional EIA; 2) a new immunoassay using the electrochemiluminescence (ECLIA) detection system; and 3) a new immunoradiometric assay (IRMA). Lectin-reactive profiles of AFP (AFP-L3) were also determined. RESULTS: In 36 patients with small-sized HCC, the rates of abnormal values obtained by the conventional, ECLIA, and IRMA methods were 2.7%, 27.8%, and 16.7%, respectively. An ROC analysis of the two new methods (ECLIA vs IRMA) revealed a better performance by the ECLIA method (p < 0.05). The true positive rate of AFP-L3 was 22.2%, whereas a combination assay of ECLIA for DCP and AFP-L3 resulted in a 41.7% sensitivity with a specificity of 90%. CONCLUSIONS: Compared with the conventional method, the sensitivity in detecting small-sized HCC was increased in the two new DCP immunoassays (ECLIA and IRMA). The overall performance as evaluated by an ROC analysis was significantly better in ECLIA than in IRMA.

Biomarkers↗
PubMed2006

Sensitivity and specificity of des-gamma-carboxy prothrombin for diagnosis of patients with hepatocellular carcinomas varies according to tumor size.

OBJECTIVES: Serum levels of des-gamma-carboxy prothrombin (DCP) and alpha-fetoprotein (AFP) are known to be useful tumor markers for the diagnosis of hepatocellular carcinoma (HCC). The aim of this study was to examine the diagnostic efficacy of DCP and AFP in differentiating HCC from chronic liver diseases. METHODS: We examined 1,377 HCC patients and 355 patients with chronic hepatitis or cirrhosis (non-HCC) who visited our institute and affiliated hospitals between June 1997 and September 2003. RESULTS: The median values of DCP and AFP were 60 mAU/mL and 34 ng/mL in HCC patients, respectively, and 18 mAU/mL and 3 ng/mL in non-HCC patients, respectively. The areas under the receiver operating characteristic (ROC) curves of DCP and AFP were 0.812 and 0.887, respectively (p < 0.0001). The area under the DCP ROC curve was significantly smaller than that of AFP in tumors less than 3 cm in diameter (p < 0.0001). However, the ROC area of DCP was significantly larger than that of AFP in tumors greater than 5 cm in diameter (p < 0.0001). CONCLUSIONS: The utility of DCP for the diagnosis of HCC was lower than that of AFP for small tumors, but higher than that of AFP for large tumors.

Aged↗
PubMed1979

The varied sensitivity of partial thromboplastin and prothrombin time reagents in the demonstration of the lupus-like anticoagulant.

An acquired inhibitor of blood coagulation, similar to that described in patients with Systemic Lupus Erythematosus (SLE), was detected during routine coagulation screening in 10 patients who did not meet the criteria for a diagnosis of SLE. The lupus-like anticoagulant (LLAC) was diagnosed on the basis of prolonged activated partial thromboplastin time (APTT) and/or prothrombin time (PT) which failed to correct when patient plasma was added to normal plasma; an additional criterion was an abnormal tissue thromboplastin inhibition test. No patient had a specific inhibitor directed against factors VIII and IX. Demonstration of LLAC was highly dependent upon the type of reagents adopted in the APTT and PT: the abnormality was detected consistently by one reagent only. One-stage assays of factors VIII and IX were characteristic of the presence of an inhibitor, showing non-parellel dose-response curves or decreased activity at low dilutions which were partially corrected at higher dilutions. Although 7 patients were free of abnormal bleeding, unequivocal signs of haemorrhagic tendency after a surgery were present in the remaining 3 patients. The findings suggest that LLAC is a non-exceptional cause of prolonged coagulation screening tests, and that it may sometimes be associated with impaired haemostasis.

Adolescent↗
PubMed1996

Effect of a reduced vitamin K supplementation on prothrombin time in prematures and high-risk neonates.

Recommendations for vitamin K supplementation were recently changed to 3 x 1 mg orally in healthy term neonates and 0.2 mg parenterally in prematures and high-risk neonates. Prothrombin times (PT) at reduced vitamin K doses (120 patients, 170 samples) during the first 6 weeks of life were below 40% in 6 patients only; all low PTs were unrelated to vitamin K. In the remaining patients, median PT was 100%; 79% of patients had values above 70%. PT was related to birthweight, gestational age and age. There was no decrease over the observation period. Following reduced oral and parenteral vitamin K regimens PTs were well within published reference values for neonates given larger amounts of vitamin K.

Administration, Oral↗
PubMed2001

Thrombophilic gene mutations and recurrent spontaneous abortion: prothrombin mutation increases the risk in the first trimester.

PROBLEM: Thrombophilic predisposition may be one of the underlying causes of recurrent spontaneous abortions (RSA). We studied the prevalence of five thrombophilic gene mutations in patients with RSA. METHOD OF STUDY: 102 patients with two or more consecutive abortions and 128 women without miscarriage were analyzed for factor V Leiden mutation (FVL), prothrombin G20210A mutation (PTM), C677T mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, glycoprotein IIIa (GPIIIa) C1565T polymorphism, and beta-fibrinogen G-455A polymorphism by polymerase chain reaction (PCR) techniques. RESULTS: No differences in the prevalence of FVL, MTHFR T/T, GPIIIa and 1-fibrinogen polymorphism were detected. Heterozygous PTM occurred more often in patients with RSA. This effect was significant in a subgroup with abortions exclusively in the first trimester (6.7%, vs. 0.8%, P = 0.027, OR 8.5). CONCLUSIONS: In contrast to the other mutations and polymorphisms, heterozygous PTM is more common in patients with abortions in the first trimester. This might reflect an influence of PTM on pathogenesis of early pregnancy loss.

Abortion, Habitual↗
PubMed1968

Human prothrombin activation.

Antiserums to human prothrontbin contain antibodies directed against at least two different antigenic sites. During blood coagulation, prothrombin is cleaved into two major antigenically distinct fragments-thrombin and a "pro" fragment. The latter is present in normal seruim, whereas thrombin loses its immunologic reactivity, presumably because of its combination with the natural thrombin inhibitors in blood.

Antigen-Antibody Reactions↗
PubMed1973

Mechanism of action of vitamin K: demonstration of a liver precursor of prothrombin.

Extracts of sonicated liver microsomes that are prepared from rats deficient in vitamin K or from rats given vitamin K antagonists contain a factor that liberates a thrombin-like activity when it is incubated with venom from Echis carinatus. The amount of this factor is low in control rats and in hypoprothrombinemic rats given vitamin K 1 hour before they were killed. These data indicate that this factor is a protein precursor of prothrombin, which is synthesized in the liver.

Animals↗
PubMed2004

Autoantibodies against phosphatidylserine-prothrombin complex in patients with systemic sclerosis.

OBJECTIVE: To determine the frequency and clinical association of antiphosphatidylserine-prothrombin complex (PS/PT) antibody (Ab) in systemic sclerosis (SSc). METHODS: Anti-PS/PT IgG Ab was examined by enzyme linked immunosorbent assay (ELISA) in 112 patients with SSc. Thirty three healthy volunteers and 30 patients with systemic lupus erythematosus (SLE) were also investigated as controls. RESULTS: Anti-PS/PT Ab was detected in 18/112 (16%) patients with SSc and 10/30 (33%) patients with SLE, whereas it was not detected in any normal controls. Anti-PS/PT Ab was more frequently detected in patients with SSc with peripheral ischaemia and lung disease (pulmonary fibrosis and pulmonary hypertension) than in patients with SSc without the Ab. However, anti-PS/PT Ab was not associated with the severity of skin sclerosis. Importantly, two patients were negative for both lupus anticoagulant and Ab against cardiolipin beta(2)-glycoprotein I complex among six anti-PS/PT Ab positive patients with SSc and a thromboembolic episode. CONCLUSIONS: Anti-PS/PT Ab is associated with thromboembolism, peripheral ischaemia, and lung involvement in some patients with SSc. Examination of this Ab may be useful to recognise the risk of thromboembolism in patients with SSc.

Adult↗
PubMed1976

An evaluation of the Lancer Coagulyzer in the measurement of the one-stage prothrombin time.

An evaluation of a photoelectric clot timer, the Lancer Coagulyzer, in measuring the one-stage prothrombin time has been carried out. The machine is considered to provide reliable results on correctly taken samples without interference by plasma bilirubin, only rarely failing to detect clotting in turbid plasma using a wide range of thromboplastins. The apparatus is useful where there is a sufficient number of samples to be tested.

Bilirubin↗