Anticoagulant Response to Agkistrodon Contortrix Venom (ACV test): a New Global Test to Screen for Defects in the Anticoagulant Protein C Pathway

1996 ◽  
Vol 75 (04) ◽  
pp. 562-566 ◽  
Author(s):  
A Robert ◽  
V Eschwège ◽  
H Hameg ◽  
L Drouet ◽  
M-F Aillaud
Keyword(s):  
Protein C ◽  
Control Group ◽  
Factor V ◽  
Antithrombin Deficiency ◽  
Global Test ◽  
Vein Thrombosis ◽  
Agkistrodon Contortrix ◽  
Factor V Gene ◽  
Deep Vein ◽  
Anticoagulant Response

SummaryAs specific assays used to identify defects in the protein C (PC) anticoagulant pathway are laborious and expensive, we describe here a global test to screen for these defects. This assay is expressed as the ratio of two activated partial thomboplastin times, one in the absence and one in the presence of 0,125 U/ml of the PC activator of Agkistrodon contortrix venom (ACV). Eight of the 168 healthy volunteers of the control group exhibited an ACV ratio below the lower normal limit of 3.37 [6 subjects with the mutation Arg 506 to Gin in their factor V gene (FV R506Q) and one with PS deficiency]. 128 patients who have had at least one episode of deep-vein thrombosis were retrospectively studied. All patients carrying FV Q506R (n = 48), PC deficiency (n = 14) or combined defects, i. e. FV Q506R and PC deficiency (n = 4) or FV Q506R and PS deficiency (n = 3), had ACV ratios < 3.37. PS deficient plasmas (n = 20) exhibited ACV ratios which overlapped normal range. ACV ratios of one out of seven patients with antithrombin deficiency, and 10% of patients without identified defect in the PC anticoagulant pathway (n = 30) were < 3.37. An ACV ratio raised to 3.70 could lead to a test identifying all patients with a defect in the PC anticoagulant pathway.

FV HR2 Haplotype as Additional Inherited Risk Factor for Deep Vein Thrombosis in Individuals with a High-Risk Profile

2002 ◽  
Vol 87 (01) ◽  
pp. 32-36 ◽  
Author(s):  
Anna Bossone ◽  
Donatella Coalizzo ◽  
Giovanna D’Andrea ◽  
Vincenzo Brancaccio ◽  
Antonio Ciampa ◽  
...  
Keyword(s):  
Risk Factor ◽  
Deep Vein Thrombosis ◽  
Protein C ◽  
Activated Protein C ◽  
Factor V ◽  
Vein Thrombosis ◽  
Estimated Risk ◽  
Factor V Gene ◽  
Fv Leiden ◽  
Deep Vein

SummaryA number of strongly linked polymorphisms within the Factor V gene (FV HR2 haplotype) has been identified as a cause of resistance to activated protein C, and has suggested a modest risk factor for vein thrombosis. We investigated the frequency of the HR2 haplotype in 433 consecutive patients with confirmed deep vein thrombosis and 326 controls. The HR2 haplotype was more frequent in patients (15.2%) than in controls (10.1%). The risk of thrombosis among carriers of this haplotype was significantly increased (odds ratio: 1.6 [95% CI: 1.0-2.5]). The estimated risk associated with the HR2 haplotype was 1.8 (95% CI: 1.1-2.9) in subjects with (n = 255), and 1.4 (95% CI: 0.8-2.4) in those without (n = 178) acquired risk factors for vein thrombosis. After adjustment for sex, FV Leiden and FII A20210 mutations, the estimated risk of vein thrombosis among carriers of the HR2 haplotype was 1.8 (95% CI: 1.1-2.8). Present data indicate that the HR2 haplotype is independently associated with vein thrombosis among individuals with a highrisk profile.

Risk for subsequent venous thromboembolic complications in carriers of the prothrombin or the factor V gene mutation with a first episode of deep-vein thrombosis

Blood ◽  
2000 ◽  
Vol 96 (10) ◽  
pp. 3329-3333 ◽  
Author(s):  
Paolo Simioni ◽  
Paolo Prandoni ◽  
Anthonie W. A. Lensing ◽  
Davide Manfrin ◽  
Daniela Tormene ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Cumulative Incidence ◽  
First Episode ◽  
Factor V ◽  
Thromboembolic Complications ◽  
Vein Thrombosis ◽  
Venous Thromboembolic ◽  
Factor V Gene ◽  
V Gene ◽  
Deep Vein

Abstract Carriers of a mutation in the prothrombin (clotting factor II) or factor V gene have a 2- to 4-fold greater risk for venous thromboembolism than subjects without the mutations. Whether both mutations also predispose to recurrent venous thromboembolism is unclear. Outpatients who had a first episode of proven symptomatic deep-vein thrombosis and a long-term follow-up were studied. The outcome measure was the cumulative incidence of confirmed venous thromboembolic complications. Two hundred fifty-one patients were enrolled in the study. Mean duration of follow-up was 8.3 years. The prothrombin gene mutation was demonstrated in 27 patients (prevalence, 10.8%; 95% CI, 6.9 to 14.6), and the factor V gene mutation was demonstrated in 41 patients (prevalence, 16.3%; 95% CI, 11.8 to 20.9). The cumulative incidence of venous thromboembolic complications after 10 years was 61.3% (95% CI, 35.7 to 87.9), and the hazard ratio was 2.4 (95% CI, 1.3 to 4.7; P = .004) in patients with the prothrombin gene mutation); the cumulative incidence of venous thromboembolic complications after 10 years was 55.2% (95% CI, 36.4 to 74.0), and the hazard ratio was 2.4 (95% CI, 1.4 to 4.1;P = .001) in patients with the factor V gene mutation. In comparison, the cumulative incidence of venous thromboembolic complications after 10 years was 23.1% (95% CI, 16.2 to 30.1) in patients without the mutations. Prothrombin and factor V gene mutations occur frequently in patients with venous thrombosis and are associated with an increased risk for recurrent venous thromboembolic complications

Fibrinolysis in patients with the 1691 G→A mutation in factor V gene and history of deep vein thrombosis

1997 ◽  
Vol 11 (4) ◽  
pp. 201-207 ◽  
Author(s):  
M. Stegnar ◽  
P. Peternel ◽  
P. Uhrin ◽  
T. Cvelbar-Marinko ◽  
K. Goršič-Tomažic ◽  
...  
Keyword(s):  
Deep Vein Thrombosis ◽  
Factor V ◽  
Vein Thrombosis ◽  
History Of ◽  
Factor V Gene ◽  
V Gene ◽  
Deep Vein

scholarly journals Frequency of Thrombophilic Gene Mutations in Patients with Deep Vein Thrombosis and in Women with Recurrent Pregnancy Loss

2017 ◽  
Vol 12 (1) ◽  
pp. 162-166 ◽  
Author(s):  
Mahmoud Mohamed Elgari ◽  
Nadir Ahmed Ibrahim ◽  
Abdel Rahim Mahmoud Muddathir ◽  
Faris Mergheni Eltoom ◽  
Ibrahim M Ibrahim
Keyword(s):  
Deep Vein Thrombosis ◽  
Protein C ◽  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Factor V Leiden ◽  
Protein S ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Vein Thrombosis ◽  
Deep Vein

AbstractThrombophilia may be anticipated by single or combined hereditary defects in encoding genes factor V, Prothrombin, and MTHFR. The aim of this study was to determine the prevalence and associated risks of V Leiden (G1691A), Prothrombin (G20210A), and MTHFR (C677T) mutations in Saudi women with Deep Vein Thrombosis (DVT) and women with recurrent pregnancy loss (RPL). Protein C and protein S activity were measured to determine combined effects, if any. We examined 60 women with a history of DVT and 60 with RPL, extracted DNA from EDTA blood and determined three mutations by using multiplex PCR reactions followed by Strip Assay KIT. Pro C Global assay was used to determine the cutoff value [PCATNR = 0.80]. Protein C/S chromogenic assay was used to estimate protein C and S percentages. Frequency of Factor V Leiden G/A genotype in patients with DVT 7 (11.6%) had a significant association for DVT χ2 (OR = 5.1, P = 0.03). In women with RPL the three mutations did not show any significant association, levels of Protein C, protein S and PCAT-NR in patient groups not different from controls (P > 0.05). In conclusion, we recommend expanding on these data to provide larger-scale studies.

Location and Extent of Deep Vein Thrombosis in Patients with and without FV:R 506Q Mutation

2000 ◽  
Vol 83 (05) ◽  
pp. 648-651 ◽  
Author(s):  
Paul Nilsson ◽  
Jan-Åke Nilsson ◽  
Peter Svensson ◽  
Ola Björgell
Keyword(s):  
Genetic Risk ◽  
Protein C ◽  
Blood Donors ◽  
Activated Protein C ◽  
Control Group ◽  
Vein Thrombosis ◽  
History Of ◽  
Mutation Group ◽  
Deep Vein ◽  
First Time

SummaryResistance to activated protein C due to FV:R 506Q mutation is the most common known genetic risk factor for deep leg vein thrombosis (DVT). The aim of this prospective study was to describe and compare the location and extent of DVT, reflected by a scoring system, in a group of patients with and without FV:R 506Q mutation. Of 247 consecutively included patients undergoing phlebography 105 had a DVT, 36 (35%) in the FV:R 506Q mutation group and 69 (65%) in the non-FV:R 506Q mutation group. Compared to the non-FV:R 506Q mutation group there was a significant increase in the incidence of DVT in the FV:R 506Q mutation group (p = 0.041, OR = 1.79 [1.02–3.15]), a significantly lower mean DVT score of the iliofemoral vein segments (p = 0.0081) and a significantly lower incidence of DVT in the iliofemoral vein segments (p = 0.007, OR = 10.6 [1.3–83.3]), 1/36 (2.8%) compared to 16/69 (23.2%). As controls 288 blood donors were included, with and without FV:R 506Q mutation and with no history of DVT in order to evaluate risk factors of DVT. The odds ratio of an iliofemoral DVT was 0.5 ([0.06–3.90), p = 0.50]) when FV:R 506Q mutation was present, compared to the control group, and at locations below the iliofemoral segments 5.28 ([3.01–9.28], p = less than 0.0001). Our findings provide the basis of a detailed phlebographic description and for the first time, to our best knowledge, shows a specific phlebographic pattern that may be linked to an inherited hypercoagulable state.

Risk for subsequent venous thromboembolic complications in carriers of the prothrombin or the factor V gene mutation with a first episode of deep-vein thrombosis

Blood ◽  
2000 ◽  
Vol 96 (10) ◽  
pp. 3329-3333 ◽  
Author(s):  
Paolo Simioni ◽  
Paolo Prandoni ◽  
Anthonie W. A. Lensing ◽  
Davide Manfrin ◽  
Daniela Tormene ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Cumulative Incidence ◽  
First Episode ◽  
Factor V ◽  
Thromboembolic Complications ◽  
Vein Thrombosis ◽  
Venous Thromboembolic ◽  
Factor V Gene ◽  
V Gene ◽  
Deep Vein

Carriers of a mutation in the prothrombin (clotting factor II) or factor V gene have a 2- to 4-fold greater risk for venous thromboembolism than subjects without the mutations. Whether both mutations also predispose to recurrent venous thromboembolism is unclear. Outpatients who had a first episode of proven symptomatic deep-vein thrombosis and a long-term follow-up were studied. The outcome measure was the cumulative incidence of confirmed venous thromboembolic complications. Two hundred fifty-one patients were enrolled in the study. Mean duration of follow-up was 8.3 years. The prothrombin gene mutation was demonstrated in 27 patients (prevalence, 10.8%; 95% CI, 6.9 to 14.6), and the factor V gene mutation was demonstrated in 41 patients (prevalence, 16.3%; 95% CI, 11.8 to 20.9). The cumulative incidence of venous thromboembolic complications after 10 years was 61.3% (95% CI, 35.7 to 87.9), and the hazard ratio was 2.4 (95% CI, 1.3 to 4.7; P = .004) in patients with the prothrombin gene mutation); the cumulative incidence of venous thromboembolic complications after 10 years was 55.2% (95% CI, 36.4 to 74.0), and the hazard ratio was 2.4 (95% CI, 1.4 to 4.1;P = .001) in patients with the factor V gene mutation. In comparison, the cumulative incidence of venous thromboembolic complications after 10 years was 23.1% (95% CI, 16.2 to 30.1) in patients without the mutations. Prothrombin and factor V gene mutations occur frequently in patients with venous thrombosis and are associated with an increased risk for recurrent venous thromboembolic complications

Factor V Gene Mutation Is a Risk Factor for Cerebral Venous Thrombosis

1996 ◽  
Vol 75 (03) ◽  
pp. 393-394 ◽  
Author(s):  
I Martinelli ◽  
G Landi ◽  
G Merati ◽  
R Cella ◽  
A Tosetto ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Cerebral Venous Thrombosis ◽  
Protein C ◽  
Dna Analysis ◽  
Protein S ◽  
Factor V ◽  
Antithrombin Deficiency ◽  
Apc Resistance ◽  
Factor V Gene ◽  
V Gene

SummaryTo evaluate the association between coagulation defects and cerebral venous thrombosis, a case-control study was conducted in 25 patients who had no autoimmune, neoplastic or infectious disease and 75 healthy individuals. There were no patients with deficiency of protein C or protein S. Four had resistance to activated protein C (APC) and one had APC resistance associated with antithrombin deficiency. APC resistance was investigated by DNA analysis, and diagnosed by the presence of a point mutation in the factor V gene, which predicts replacement of Arg506 with Gin at one of the two APC cleavage sites in activated factor V. The prevalence of APC resistance was 20% in patients and 2.7% in controls. This difference was statistically significant (p = 0.01) and the odds ratio was 9.1. A circumstantial factor predisposing to cerebral venous thrombosis (such as oral contraceptive intake, pregnancy, puerperium, trauma or prolonged immobilization) was reported in 72% of cases. In conclusion, APC resistance is the most frequent coagulation abnormality associated with cerebral venous thrombosis.

Uncertain thrombophilia markers

2016 ◽  
Vol 115 (01) ◽  
pp. 25-30 ◽  
Author(s):  
Massimo Franchini ◽  
Ida Martinelli ◽  
Pier Mannuccio Mannucci
Keyword(s):  
Protein C ◽  
Factor V Leiden ◽  
Coagulation Factor ◽  
High Plasma ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Dna Testing ◽  
Vein Thrombosis ◽  
Thrombophilia Screening ◽  
Deep Vein

SummaryThe development of venous thromboembolism (VTE), which includes deep-vein thrombosis and pulmonary embolism, may be associated with inherited or acquired risk factors that can be measured in plasma or DNA testing. The main inherited thrombophilias include the plasma deficiencies of the natural anticoagulants antithrombin, protein C and S; the gain-of-function mutations factor V Leiden and prothrombin G20210A; some dysfibrinogenaemias and high plasma levels of coagulation factor VIII. Besides these established biomarkers, which usually represent the first-level laboratory tests for thrombophilia screening, a number of additional abnormalities have been less consistently associated with an increased VTE risk. These uncertain causes of thrombophilias will be discussed in this narrative review, focusing on their clinical impact and the underlying pathogenetic mechanisms. Currently, there is insufficient ground to recommend their inclusion within the framework of conventional thrombophilia testing.

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