Arterial and venous thromboembolism with fatal outcome and resistance to activated protein C

The Lancet ◽  
1994 ◽  
Vol 343 (8902) ◽  
pp. 917 ◽  
Author(s):  
B. Lindblad ◽  
Pj Svensson ◽  
B. Darhlbäck
Keyword(s):  
Venous Thromboembolism ◽  
Protein C ◽  
Fatal Outcome ◽  
Activated Protein C

scholarly journals A Factor V Genetic Component Differing From Factor V R506Q Contributes to the Activated Protein C Resistance Phenotype

Blood ◽  
1997 ◽  
Vol 90 (4) ◽  
pp. 1552-1557 ◽  
Author(s):  
F. Bernardi ◽  
E.M. Faioni ◽  
E. Castoldi ◽  
B. Lunghi ◽  
G. Castaman ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Protein C ◽  
Activated Protein C ◽  
Functional Assay ◽  
Factor V ◽  
Resistance Phenotype ◽  
Apc Resistance ◽  
Genetic Components ◽  
Factor V Gene ◽  
V Gene

AbstractFactor V gene polymorphisms were investigated to detect components that may contribute to the activated protein C (APC) resistance phenotype in patients with venous thromboembolism. A specific factor V gene haplotype (HR2) was defined by six polymorphisms and its frequency was found to be similar in normal subjects coming from Italy (0.08), India (0.1), and Somalia (0.08), indicating that it was originated by ancestral mutational events. The relationship between the distribution of normalized APC ratios obtained with the functional assay and haplotype frequency was analyzed in patients heterozygous for factor V R506Q (factor V Leiden). The HR2 haplotype was significantly more frequent in patients with ratios below the 15th percentile than in those with higher ratios or in normal controls. Moreover, the study of 10 patients with APC resistance in the absence of the factor V R506Q mutation showed a 50-fold higher frequency of HR2 homozygotes. The HR2 haplotype was associated with significantly lower APC ratios both in patients with venous thromboembolism and in age- and sex-matched controls. However, the two groups showed similar HR2 haplotype frequencies. Plasma mixing experiments showed that an artificially created double heterozygote for the factor V R506Q mutation and the HR2 haplotype had an APC ratio lower than that expected for a simple R506Q heterozygote. Time-course experiments evaluating the decay of factor V in plasma showed the normal stability of the molecule encoded by the factor V gene marked by the HR2 haplotype, which ruled out the presence of a pseudo-homozygous APC resistance mechanism. Our results provide new insights into the presence of factor V genetic components other than the factor V R506Q that are able to contribute to the APC resistance phenotype in patients with venous thromboembolism.

scholarly journals Oral Contraceptive Types in Relation to ABO Blood Groups Among Saudi Women of Different Reproductive Age Groups and Impact on Venous Thromboembolism

2020 ◽  
Vol 26 ◽  
pp. 107602962096605
Author(s):  
Abdulrahman B. O. Mohamed ◽  
Nabeel Al-Ama ◽  
Huda Al Kreathy ◽  
Khalid H. B. Ahmed ◽  
Turki Al Amri ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Blood Group ◽  
Protein C ◽  
Second Generation ◽  
Activated Protein C ◽  
Blood Groups ◽  
Fourth Generation ◽  
Third Generation ◽  
Abo Blood Groups ◽  
Saudi Women

Saudi women have recently started using oral contraceptives (OCs), which has led to risk of venous thromboembolism (VTE). The risk varies with the type of OC generations used, and with OC use the risk for VTE increases by 2- to 6-fold. This study evaluated the effect of OC types in relation to ABO blood group on the risk of VTE among Saudi women. Thrombin generation (TG) was measured in the plasma of the women in the presence and absence of platelet rich plasma, platelet poor plasma and thrombomodulin or activated protein C. OC usage increased TG parameters ETP and Peak height by 9.81% and 16.04%, respectively. An increased risk of VTE was seen among women on third generation OCs as compared to those on second generation products. Within OC generations, we found that for women using fourth generation OCs, their ETP increased by 36.18% as compared to those using second generation and by 6.07% in those using third generation compared to those using second generation. There was significant difference with respect to ABO blood groups and OC generation types, but larger sample size is required. Women who are 40 years and older and using third generation OC had a higher risk of having thrombosis (11.84%), as compared to those using second generation OC (8.79%) and to those using fourth generation OC (5.03%). An association between different OC groups and non-O blood group in thrombosis generation was noted. TG parameters were significantly increased in relation to BMI when comparing to OC users versus non-users. In addition, inhibition of TG parameters in the presence of recombinant human thrombomodulin (TM) and activated protein C (APC) were significantly increased.

scholarly journals A Rapid Activated Protein C Sensitivity Test as a Diagnostic Marker for a Suspected Venous Thromboembolism in Pregnancy and Puerperium

2011 ◽  
Vol 72 (1) ◽  
pp. 55-62 ◽  
Author(s):  
Motoi Sugimura ◽  
Ryota Ohashi ◽  
Kazunao Suzuki ◽  
Hiroaki Itoh ◽  
Kazuhiro Sugihara ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Protein C ◽  
Diagnostic Marker ◽  
Activated Protein C ◽  
Sensitivity Test ◽  
In Pregnancy

Contribution of polymorphisms in the endothelial protein C receptor gene to soluble endothelial protein C receptor and circulating activated protein C levels, and thrombotic risk

2004 ◽  
Vol 91 (05) ◽  
pp. 905-911 ◽  
Author(s):  
Pilar Medina ◽  
Silvia Navarro ◽  
Amparo Estellés ◽  
Amparo Vayá ◽  
Barry Woodhams ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Protein C ◽  
Receptor Gene ◽  
Activated Protein C ◽  
Soluble Form ◽  
Cell Protein ◽  
Endothelial Protein C Receptor ◽  
Thrombotic Risk ◽  
Increased Risk ◽  
The Relationship

SummaryEndothelial cell protein C receptor (EPCR) enhances the generation of activated protein C (APC) by the thrombin-thrombomodulin complex. A soluble form of EPCR (sEPCR), which is generated by metalloprotease activity, is present in plasma. The distribution of sEPCR levels in healthy populations is bimodal. Previously, we described two polymorphisms in exon 4 of the EPCR gene, 4600A/G that encodes the substitution of Ser219 by Gly in the transmembrane region of EPCR and 4678G/C in the 3’-UT region. The aim of this study was to investigate the relationship between these two polymorphisms and plasma sEPCR and APC levels and risk of venous thrombosis. We genotyped 401 healthy controls from the Spanish population and measured their plasma sEPCR and APC levels. Carriers of the 4600AG genotype had significantly higher sEPCR levels than those with the AA genotype, while the 4678CC genotype was associated, to a lesser extent, with elevated APC levels. To assess the effect of these polymorphisms on the risk of thrombosis, we genotyped 405 patients with venous thromboembolism. The frequency of the 4600AG genotype was very similar in patients and controls (p=0.975), whereas the 4678CC genotype was significantly more frequent in controls than in patients (p=0.008). In multivariate analysis, carriers of the 4678CC genotype had a decreased risk of thrombosis (OR=0.61, p=0.009). These data indicate that individuals carrying the 4600AG genotype have high sEPCR levels but do not have an increased risk of thrombosis, whereas individuals carrying the 4678CC genotype have higher APC levels and lower risk of venous thromboembolism.

Coagulation, inflammation, and apoptosis: different roles for protein S and the protein S–C4b binding protein complex

Blood ◽  
2004 ◽  
Vol 103 (4) ◽  
pp. 1192-1201 ◽  
Author(s):  
Suely Meireles Rezende ◽  
Rachel Elizabeth Simmonds ◽  
David Anthony Lane
Keyword(s):  
Venous Thromboembolism ◽  
Complement Activation ◽  
Protein C ◽  
Binding Protein ◽  
Anticoagulant Activity ◽  
Activated Protein C ◽  
Protein S ◽  
Increased Risk ◽  
Established Role ◽  
Structure And Functions

AbstractProtein S (PS) has an established role as an important cofactor to activated protein C (APC) in the degradation of coagulation cofactors Va and VIIIa. This anticoagulant role is evident from the consequences of its deficiency, when there is an increased risk of venous thromboembolism. In human plasma, PS circulates approximately 40% as free PS (FPS) and 60% in complex with C4b-binding protein (C4BP). Formation of this complex results in loss of PS cofactor function, and C4BP can then modulate the anticoagulant activity of APC. It had long been predicted that the complex could act as a bridge between coagulation and inflammation due to the involvement of C4BP in regulating complement activation. This prediction was recently supported by the demonstration of binding of the PS-C4BP complex to apoptotic cells. This review aims to summarize recent findings on the structure and functions of PS, the basis and importance of its deficiency, its interaction with C4BP, and the possible physiologic and pathologic importance of the PS-C4BP interaction.

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