Biomedical subjects

Rogier M Bertina

Publications and source records attributed to Rogier M Bertina.

24 records · Page 2Linked to original sources

PubMed2002

Protein C inhibitor (plasminogen activator inhibitor-3) and the risk of venous thrombosis.

Protein C inhibitor (PCI), also known as plasminogen activator inhibitor-3, is a serine proteinase inhibitor that can inhibit enzymes in blood coagulation, fibrinolysis and fertility. The role of PCI in regulating the blood coagulation mechanism is not known, as it can inhibit both procoagulant (thrombin, factor Xa, factor XIa) and anticoagulant (activated protein C, thrombin-thrombomodulin, urokinase) enzymes. To determine the relevance of this inhibitor in thrombosis, PCI levels were assessed in the Leiden Thrombophilia Study, a case-control study of venous thrombosis in 473 patients with a first deep-vein thrombosis and 474 age- and sex-matched control subjects. PCI levels above the 95th percentile of the controls (136.1%) increased the risk 1.6-fold compared with PCI levels below the 95th percentile (95% confidence interval 0.9-2.8). There was a gradual increase in risk of thrombosis with further increasing levels of PCI. Adjustment for a number of possible confounders led to a reduction of the risk estimates associated with PCI. However, it is unclear whether adjustment for such factors in the risk models is justified. These results indicate that high levels of PCI may constitute a mild risk factor for venous thrombosis.

Adolescent↗

PubMed2002

The effect of plasma caeruloplasmin levels on the sensitivity for activated protein C.

The effect of caeruloplasmin levels on the sensitivity for activated protein C (APC), measured by a clotting assay based on the activated partial thromboplastin time, was investigated in a large group of healthy individuals without factor V Leiden. A modest inverse association between caeruloplasmin and normalized APC sensitivity ratio was found (regression coefficient beta = -0.33 x 10-2; 95% confidence interval, -0.42 x 10-2 to -0.24 x 10-2). After adjustment for sex and oral contraceptive use, this association weakened (beta = -0.19 x 10-2; 95% CI: -0.34 x 10-2 to -0.05 x 10-2). After additional adjustment for factor VIII levels, which are known to influence the assay, the effect of caeruloplasmin on APC sensitivity completely disappeared.

Activated Protein C Resistance↗

PubMed2002

Factor XIII Val34Leu polymorphism, factor XIII antigen levels and activity and the risk of deep venous thrombosis.

Varying results on the effect of factor XIII (FXIII) Val34Leu on venous thrombotic risk have been reported. The probability of a true association between this polymorphism and venous thrombotic risk would be enhanced by a laboratory phenotype associated with this polymorphism and with the thrombotic risk. The aim of this study was to assess the effect of FXIII Val34Leu, FXIII activity and subunit levels on venous thrombotic risk in a large case-control study, The Leiden Thrombophilia study (LETS). We found higher FXIII activity for 34Leu carriers (Leu/Leu: 158.0, Val/Val: 95.0). FXIII subunit levels were not associated with genotype. Higher FXIII activity was associated with a slightly decreased thrombotic risk [Odds ratio (OR): 0.8, 95% confidence intervals (CI): 0.5-1.3]. This effect was not present for elevated FXIII subunit levels. Higher FXIII activity was also associated with a higher dissociation index (percentage A2B2 complex dissociated after activation by thrombin for a fixed time interval). This index was higher for FXIII 34Leu carriers. The risk of deep venous thrombosis was slightly decreased for carriers of the 34Leu allele [OR: 0.9 (95%CI: 0.7-1.1)]. For homozygous 34Leu carriers the OR was 0.7 (95%CI: 0.4-1.3). This finding, suggesting a weak protective effect, was completely restricted to men. An overall estimate of thrombotic risk was calculated by using earlier reports on the risk of FXIII Val34Leu. The overall risk estimate for homozygous 34Leu carriers was 0.8 (95%CI: 0.6-1.0). In this study, a weak protective effect against venous thrombosis was found, of FXIII 34Leu as well as of increased FXIII activity.

Adolescent↗

PubMed2002

The factor VIII/von Willebrand factor ratio discriminates between reduced synthesis and increased clearance of von Willebrand factor.

It is often stated that a decrease in Von Willebrand factor (VWF), the carrier protein of factor VIII, results in a concordant change in factor VIII. Clinical data suggest that this is not always the case and we hypothesized that the ratio between factor VIII and VWF depends on the genetic defect that causes the VWF deficiency. We have analyzed the ratio between plasma factor VIII and VWF in several subtypes of Von Willebrand Disease and we show that the ratio is increased when VWF synthesis is reduced, but that the ratio remains one when VWF clearance is increased. These observations could be of clinical importance as an increased factor VIII/VWF ratio in combination with a borderline VWF level may indicate the presence of a true genetic defect, possibly a VWF null allele.

Alleles↗

PubMed2002

Effects of (pre-)analytical variables on activated protein C resistance determined via a thrombin generation-based assay.

The normalized activated protein C sensitivity ratio (nAPC-sr) determined with an assay that quantifies the effect of APC on thrombin formation initiated via the extrinsic coagulation pathway identifies hereditary and acquired defects of the protein C system. We investigated the influence of assay conditions (analytical variables) and plasma handling (pre-analytical variables) on nAPC-sr obtained with this APC resistance test. The effect of the analytical variables (CaCl2, phospholipid and APC concentrations and the concentration and source of tissue factor) was determined in pooled normal plasma. Inhibition of thrombin formation by APC was dependent on the APC concentration and was also affected by the tissue factor, Ca2+ and phospholipid concentrations. Thus, strict standardization of reactant concentrations is required to obtain reproducible nAPC-sr. Three different tissue factor preparations were compared by determining nAPCsr in plasma samples obtained from 90 healthy individuals. nAPC-sr were similar for all three tissue factor preparations although, compared with the noncommercially available tissue factor used in earlier studies, values determined with commercial tissue factor preparations showed larger variation. Pre-analytical variables, investigated in plasma of nine volunteers (3 normal individuals and 6 individuals with an APC-resistant phenotype) were: concentration of anticoagulant (3.2% vs. 3.8% trisodiumcitrate), time before processing of blood (0, 4 and 24 h), centrifugation speed, storage temperature of plasma (-20 degrees C vs. -80 degrees C) and sample thawing. Multiple linear regression analysis showed that only the citrate concentration affected the nAPC-sr, which was higher in samples collected in 3.2% trisodiumcitrate than in samples collected in 3.8% trisodiumcitrate.

Activated Protein C Resistance↗

PubMedDate not supplied

Elevated clotting factor levels and venous thrombosis.

Increased plasma levels of fibrinogen, factor VIII (FVIII), factor IX (FIX), factor XI (FXI) and prothrombin all were reported to be independent risk factors of venous thromboembolism (VTE). However there is only limited information on the molecular basis of these plasma phenotypes. In addition some of these plasma phenotypes may form clusters, which may point to defects in common pathways affecting biosynthesis or clearance. Uncertainties as to what should be considered the cut-off for an elevated plasma level and in some cases (FIX, FXI) the lack of published confirmatory and/or prospective studies, have delayed the incorporation of these parameters in thrombophilia screening procedures.

Blood Coagulation Factors↗