Low Protein Z Levels and the Risk of Venous Thrombosis.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1634-1634
Author(s):  
Ida Martinelli ◽  
Tullia Battaglioli ◽  
Cristina Razzari ◽  
Eugenia Biguzzi ◽  
Pier Mannuccio Mannucci
Keyword(s):  
Odds Ratio ◽  
Oral Anticoagulant Therapy ◽  
Factor V Leiden ◽  
Factor Xa ◽  
Protein S ◽  
Lower Limbs ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Protein Z ◽  
Thrombophilia Screening

Abstract Background. Protein Z (PZ) is a vitamin-K dependent protein that serves as cofactor for PZ-dependent protease inhibitor, inactivating factor Xa. Therefore, deficiency of PZ could led to a prothrombotic phenotype. Contrasting data are available on the relationship between PZ and venous thromboembolism (VTE). Patients and Methods. We carried out a case-control study on 443 patients with deep vein thrombosis of the lower limbs and/or pulmonary embolism who discontinued oral anticoagulant therapy and 394 controls, similar for age and sex. PZ was measured with an enzyme immuno-assay (Diagnostica Stago, France). A thrombophilia screening including DNA testing for factor V Leiden and G20210A prothrombin mutation and measurements of plasma antithrombin, protein C, protein S, and homocysteine (fasting and post-methionine load) was performed. Pregnancy, oral contraceptive use, liver or renal disease were exclusion criteria. Results. 443 patients and 394 healthy controls who underwent thrombophilia screening were investigated. Median PZ levels (range) were 1.95 μg/mL (0.22–6.26 μg/mL) in patients and 1.79 μg/mL (0.25–7.82 μg/mL) in controls (p=0.07). The odds ratios (adjusted for age, sex and the presence of thrombophilia) for VTE in patients with PZ levels in the lowest quartile was 0.8 (95% CI 0.5–1.1), and remained statistically non significant considering PZ levels below the 10th percentile. However, low PZ levels (lowest quartile) increased the risk of VTE associated with factor V Leiden (odds ratio 14.6, 95% CI 1.9–113), prothrombin G20210A (odds ratio 3.2, 95% CI 1.0–10.3), and hyperhomocysteinemia (odds ratio 4.7, 95% CI 1.7–17.0). These interactions remained, apart for prothrombin G20210A, when PZ levels below the 10th percentile were considered. Conclusion. Low PZ levels are not an independent risk factor for VTE, but may enhance the relative risk due to already established risk factors, particularly factor V Leiden.

The risk of symptomatic pulmonary embolism due to proximal deep venous thrombosis differs in patients with different types of inherited thrombophilia

2008 ◽  
Vol 99 (06) ◽  
pp. 1030-1034 ◽  
Author(s):  
Elena Rossi ◽  
Tommaso Za ◽  
Angela Ciminello ◽  
Giuseppe Leone ◽  
Valerio Stefano
Keyword(s):  
Pulmonary Embolism ◽  
Factor V Leiden ◽  
Protein S ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Inherited Thrombophilia ◽  
Vein Thrombosis ◽  
Symptomatic Pulmonary Embolism ◽  
Thrombophilia Screening ◽  
Multiple Abnormalities

SummaryIt is uncertain whether the presence of inherited thrombophilia influences the risk of developing symptomatic pulmonary embolism (PE) and whether different thrombophilic alterations are associated with different risks of symptomatic PE. To investigate such issue, we retrospectively studied 920 patients with proximal deep vein thrombosis (DVT) of the legs with or without symptomatic PE referred for thrombophilia screening; patients with overt cancer or antiphospholipid antibodies had been excluded. Three hundred fifty-four patients (38.5%) had deficiency of antithrombin (AT, n=16), protein C (PC, n=26), protein S (PS, n=22), factor V Leiden (FVL, n=168), prothrombin G20210A (PT-GA, n=87), or multiple abnormalities (n=35), and 566 had none of the studied thrombophilic abnormalities. Symptomatic PE complicated the first DVT in 242 patients (26%); the risk of PE was increased in patients with AT deficiency (relative risk [RR] 2.4, 95% confidence interval [CI] 1.6–3.6) or with PT-GA (RR 1.5, 95%CI 1.1–2.0) and decreased in those with FVL (RR 0.7, 95%CI 0.5–1.0) in comparison with those with unknown inherited defect. These data suggest that patients with proximal DVT have different risks of symptomatic PE according to the type of inherited thrombophilia.

The APC-independent anticoagulant activity of protein S in plasma is decreased by elevated prothrombin levels due to the prothrombin G20210A mutation

Blood ◽  
2003 ◽  
Vol 102 (5) ◽  
pp. 1686-1692 ◽  
Author(s):  
Rory R. Koenen ◽  
Guido Tans ◽  
René van Oerle ◽  
Karly Hamulyák ◽  
Jan Rosing ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Protein C ◽  
Anticoagulant Activity ◽  
Factor V Leiden ◽  
Protein S ◽  
Prothrombin G20210a ◽  
Healthy Population ◽  
Factor V ◽  
Thrombotic Risk ◽  
G20210a Mutation

AbstractProtein S exhibits anticoagulant activity independent of activated protein C (APC). An automated factor Xa–based one-stage clotting assay was developed that enables quantification of the APC-independent activity of protein S in plasma from the ratio of clotting times (protein S ratio [pSR]) determined in the absence and presence of neutralizing antibodies against protein S. The pSR was 1.62 ± 0.16 (mean ± SD) in a healthy population (n = 60), independent of plasma levels of factors V, VIII, IX, and X; protein C; and antithrombin, and not affected by the presence of factor V Leiden. The pSR strongly correlates with the plasma level of protein S and is modulated by the plasma prothrombin concentration. In a group of 16 heterozygous protein S–deficient patients, the observed mean pSR (1.31 ± 0.09) was significantly lower than the mean pSR of the healthy population, as was the pSR of plasma from carriers of the prothrombin G20210A mutation (1.47 ± 0.21; n = 46). We propose that the decreased APC-independent anticoagulant activity of protein S in plasma with elevated prothrombin levels may contribute to the thrombotic risk associated with the prothrombin G20210A mutation.

Duration of Anticoagulation: Applying the Guidelines and Beyond

Hematology ◽  
2010 ◽  
Vol 2010 (1) ◽  
pp. 210-215 ◽  
Author(s):  
Kenneth A. Bauer
Keyword(s):  
Anticoagulant Therapy ◽  
Clinical Investigation ◽  
Factor V Leiden ◽  
Protein S ◽  
Bleeding Risk ◽  
Recurrence Risk ◽  
Prothrombin G20210a ◽  
Major Surgery ◽  
First Episode ◽  
Factor V

Abstract Despite an improved understanding of the risk factors underlying venous thromboembolism (VTE), extensive clinical investigation, and detailed clinical guidelines, the decision to extend anticoagulation indefinitely for an individual patient with VTE is often problematic. Patients with VTE in association with major surgery, trauma, immobilization, or pregnancy are at relatively low risk of recurrence and generally do not require more than 3 to 6 months of anticoagulant therapy. For patients with a first unprovoked, or idiopathic, episode of VTE, an individualized approach should be taken in deciding on the duration of anticoagulation based on the patient's recurrence and bleeding risk, as well as their personal preference. Although the presence of genetic thrombophilic disorders (factor V Leiden and prothrombin G20210A gene mutations; deficiencies of antithrombin, protein C, and protein S) predispose patients to a first episode of VTE, there is inconsistent data on whether testing for these defects changes patient outcomes or should alter their management. In patients with a single unprovoked VTE, measurement of D-dimer several weeks following the completion of anticoagulant therapy appears useful in stratifying patients with a first unprovoked episode of VTE with regard to recurrence risk. Through a series of clinical vignettes, the utility of the laboratory in risk-stratifying patients with respect to recurrence risk will be discussed, along with decision making regarding the duration of anticoagulation. The potential impact of having a nonremovable inferior vena caval filter will also be addressed.

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.

Factor V Leiden and Prothrombin G20210A Gene Mutations Should Not Be Routinely Screened among Venous Thromboembolism (VTE) Patients in Singapore - This and Patterns of Other Thrombophilic Conditions among Our VTE Patients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4087-4087
Author(s):  
Heng Joo Ng ◽  
Lai Heng Lee ◽  
Te-Chih Liu ◽  
Lip Kun Tan ◽  
Ponnudurai Kuperan
Keyword(s):  
Gene Mutation ◽  
Antithrombin Iii ◽  
Gene Mutations ◽  
Factor V Leiden ◽  
Anticardiolipin Antibody ◽  
Protein S ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Protein C Deficiency ◽  
G20210a Mutation

Abstract Introduction: Emerging good quality evidence has suggested that the prevalence of VTE among Asians is significant and was largely underestimated previously. Objective and methods: We conducted a study of thrombophilic markers among our population of VTE patients to determine their prevalence and help determine the best screening strategy among our increasing number of VTE patients. Three major hospitals in the country were involved in this study. Results: Of 254 patients recruited, ethnic distribution was as follows: Chinese 68.1%, Malays 17.3%, Indians 12.6%, Others 2%. The ratio of males to females was 2:3. Major risk factors such as surgery, trauma and malignancy was recordedand identified in about 80% of the population. Twenty-one percent of patients had pulmonary embolism. Positive results of thrombophilic markers were as follows: protein C deficiency, 4 patients (1.52%); protein S deficency, 26 (10.24%), antithrombin III deficiency, 11 (4.33%); lupus anticoagulant, 9 (3.54%); anticardiolipin antibody IgG, 3 (1.18%); anticardiolipin antibody IgM, 6 (2.36%); hyperhomocysteinemia, 32 (12.6%); factor V Leiden gene mutation, 0 (0%); prothrombin 20210 gene mutation, 0 (0%). The prevalence of at least one thrombophilic condition was found in about one third of our patients. The relative risks of these thrombophilic conditions will be compared with a healthy control population. Conclusion: Among our VTE patients, the most commonly associated thrombophilic conditions were protein S and antithrombin III deficiencies. The factor V Leiden and prothrombin G20210A mutation did not feature at all in our patient population and is consistent with other studies on Asian populations. These tests should not be included as part of our thrombophilic screening.

Coinheritance of the HR2 Haplotype in the Factor V Gene Confers an Increased Risk of Venous Thromboembolism to Carriers of Factor V R506Q (Factor V Leiden)

Blood ◽  
1999 ◽  
Vol 94 (9) ◽  
pp. 3062-3066 ◽  
Author(s):  
E.M. Faioni ◽  
F. Franchi ◽  
P. Bucciarelli ◽  
M. Margaglione ◽  
V. De Stefano ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Family Members ◽  
Factor V Leiden ◽  
Protein S ◽  
Fold Increase ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Multicenter Cohort Study ◽  
Vein Thrombosis ◽  
Increased Risk

With the aim of establishing whether the HR2 haplotype in factor V affects the risk of venous thromboembolism, a retrospective multicenter cohort study was performed in 810 family members identified through 174 probands who suffered from at least 1 episode of deep vein thrombosis and/or pulmonary embolism and had an inherited defect associated with thrombophilia (antithrombin, protein C, or protein S deficiency; factor V R506Q or prothrombin G20210A). Fifty-eight percent (468/810) of the family members had an inherited defect and 10% (47/468) were symptomatic. The HR2 haplotype was found in association with factor V R506Q more frequently in family members with venous thromboembolism (18%) than in those without (8%). Double heterozygosity for factor V R506Q and HR2 conferred a 3- to 4-fold increase in the relative risk of venous thromboembolism compared with factor V R506Q alone. The median age at first event was lower when the 2 defects were associated (46v 52 years). No increase in risk of venous thromboembolism could be demonstrated when the HR2 haplotype was associated with inherited thrombophilic defects other than factor V R506Q. Because both factor V R506Q and the HR2 haplotype are very frequent, the effect of their coinheritance on the risk of venous thromboembolism might represent a clinically relevant issue, and screening for HR2 in carriers of factor V R506Q should be considered.

Hereditary Thrombophilic Risk Factors and Venous Thromboembolism in Istanbul, Turkey: The Role in Different Clinical Manifestations of Venous Thromboembolism

2008 ◽  
Vol 14 (2) ◽  
pp. 168-173 ◽  
Author(s):  
Gulfer Okumus ◽  
Esen Kiyan ◽  
Orhan Arseven ◽  
Levent Tabak ◽  
Reyhan Diz-Kucukkaya ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Clinical Manifestations ◽  
Factor V Leiden ◽  
Protein S ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Vein Thrombosis ◽  
Significant Difference ◽  
Deep Vein

The aim of this study was to investigate the hereditary thrombophilic risk factors in patients with venous thromboembolism (VTE) and whether these risk factors play a different role in patients with isolated pulmonary embolism (PE) as compared with patients with deep vein thrombosis (DVT) and patients with PE + DVT. The protein C (PC), protein S, antithrombin activities, homocysteine levels, and factor V Leiden (FVL) G1691A and prothrombin G20210A mutations were evaluated in 191 patients with VTE and 191 controls. The prevalence of FVL and PC deficiency were higher in patients ( P = .003 and P = .02, respectively). There was no significant difference for the other risk factors. The combination of thrombophilic risk factors was significantly higher in patients with DVT + PE as compared with patients with isolated PE or DVT ( P = .04). In conclusion, the most important hereditary risk factors for VTE in this study were the FVL mutation and PC deficiency.

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.

Risk Factors in Venous Thromboembolism

2001 ◽  
Vol 86 (07) ◽  
pp. 395-403 ◽  
Author(s):  
Ida Martinelli
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Factor V Leiden ◽  
Protein S ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Nucleotide Substitutions ◽  
Inherited Thrombophilia ◽  
G20210a Mutation ◽  
Increased Risk

SummaryVenous thromboembolism is a serious disorder because of its potential complications, such as pulmonary embolism and the post-thrombotic syndrome. Inherited determinants of venous thromboembolism are only in part known, but in the past decades considerable progress has been made in the understanding of risk factors for the disease and their clinical impact. In particular, the development of molecular biology techniques and the increasing interest in their application, allowed an identification of two causes of inherited thrombophilia, i.e., factor V Leiden and the prothrombin G20210A mutation. Their recent discovery provided a new approach for improving the knowledge of inherited thrombophilia. In contrast to deficiencies of the naturally occurring anticoagulant proteins antithrombin, protein C and protein S, these two mutations cannot be considered true genetic defects, since they are nucleotide substitutions resulting in a more efficient coagulation process. Since they are rather common in the general populations of Caucasian descent and are associated with a moderate increased risk of venous thromboembolism, the effect of the interaction between inherited and environmental risk factors for venous thromboembolism has become an even greater field of interest. Prevention of first events and recurrences of venous thromboembolism can be optimized only through a knowledge of the main risk factors, their effect, and their interaction with environmental factors.

Hypercoagulation Testing in Ischemic Stroke

2007 ◽  
Vol 131 (6) ◽  
pp. 890-901
Author(s):  
Aliyah Rahemtullah ◽  
Elizabeth M. Van Cott
Keyword(s):  
Ischemic Stroke ◽  
Laboratory Testing ◽  
Recurrent Stroke ◽  
Factor V Leiden ◽  
Protein S ◽  
Prothrombin G20210a ◽  
Cerebral Vein ◽  
Factor V ◽  
Cerebral Vein Thrombosis ◽  
Vein Thrombosis

Abstract Context.—The utility of laboratory testing for hypercoagulability in the setting of stroke is uncertain. Objective.—To review the current literature and to make recommendations with regard to laboratory testing for various hypercoagulability risk factors for ischemic stroke. Data Sources.—Published articles studying the utility of various hypercoagulation tests in predicting initial and/or recurrent stroke or transient ischemic attack as well as cerebral vein thrombosis were collected and reviewed, with an emphasis on prospective studies. Conclusions.—Certain tests, such as C-reactive protein, homocysteine, antiphospholipid antibodies, and lipoprotein(a), may be useful in patients with a history of stroke or at high risk for stroke, as evidenced by prospective data. Factor V Leiden, prothrombin G20210A, protein C, protein S, and antithrombin are not recommended for routine testing but may be useful in certain populations, such as in pediatric patients or in patients with cerebral vein thrombosis.

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