In families with inherited thrombophilia the risk of venous thromboembolism is dependent on the clinical phenotype of the proband

2011 ◽  
Vol 106 (10) ◽  
pp. 646-654 ◽  
Author(s):  
Elena Rossi ◽  
Angela Ciminello ◽  
Tommaso Za ◽  
Silvia Betti ◽  
Giuseppe Leone ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Universal Screening ◽  
Protein C ◽  
Clinical Phenotype ◽  
Hormonal Contraception ◽  
Factor V Leiden ◽  
Factor V ◽  
Inherited Thrombophilia ◽  
At Deficiency ◽  
Increase In Risk

SummaryThe utility of laboratory investigation of relatives of individuals with inherited thrombophilia is uncertain. To assess the risk of venous thromboembolism (VTE) among the carriers, we investigated a family cohort of 1,720 relatives of probands with thrombophilia who were evaluated because of VTE (n=1,088), premature arterial thrombosis (n=113), obstetric complication (n=257), or universal screening before pregnancy or hormonal contraception or therapy (n=262); 968 relatives were carriers of thrombophilia. A first deep venous thrombosis (DVT) occurred in 44 carriers and 10 non-carriers during 37,688 and 29,548 observationyears from birth, respectively. The risk of DVT among the carriers compared with non-carriers was estimated as a hazard ratio (HR). If the proband had VTE and factor V Leiden (FVL) and/or prothrombin (PT)20210A, the HR for DVT was 2.77 (95%CI 1.21–4.82) in the carriers overall, and 5.54 (95%CI 3.20–187.00) in those homozygous or double heterozygous for FVL and PT20210A. If the proband had VTE and a deficiency of antithrombin (AT), protein C or S, the HR for DVT was 5.14 (95%CI 0.88–10.03) in the carriers overall, and 12.86 (95%CI 2.46–59.90) in those with AT deficiency. No increase in risk was found among the carriers who were relatives of the probands who were evaluated for reasons other than VTE. In conclusion, familial investigation for inherited thrombophilia seems justified for probands with previous VTE, but appears of doubtful utility for the relatives of probands without VTE. This should be taken with caution regarding families with deficiency of natural anticoagulants, given the low number of cases analysed.

scholarly journals Heritable Thrombophilia in Venous Thromboembolism in Northern Pakistan: A Cross-Sectional Study

2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Maria Khan ◽  
Chaudhry Altaf ◽  
Hamid Saeed Malik ◽  
Muhammad Abdul Naeem ◽  
Aamna Latif
Keyword(s):  
Venous Thromboembolism ◽  
Protein C ◽  
Gene Mutations ◽  
Factor V Leiden ◽  
Factor V ◽  
Protein C Deficiency ◽  
Factor V Leiden Mutation ◽  
Inherited Thrombophilia ◽  
At Deficiency ◽  
Prothrombin Gene

Background. Venous thromboembolism (VTE) is referred to as formation of clots in a deep vein or lodging of thrombus towards the lungs which could be fatal yet preventable. The risk of developing VTE can be increased by various factors. Where there are innumerable acquired causes, the possibility of inherited thrombophilia cannot be ignored. In view of this, we have evaluated all patients with venous thromboembolism for inherited thrombophilia. Objective. To evaluate the frequencies of antithrombin (AT) deficiency, protein C and S deficiencies, Factor V Leiden, and prothrombin gene mutations in patients harboring venous thromboembolism. Materials and Methods. A study comprising of 880 patients who were presented with manifestations of venous thromboembolism was conducted from July 2016 to June 2017. A blood sample collected from patients was screened for thrombophilia defects encompassing AT, protein C and S deficiencies, Factor V Leiden, and prothrombin gene mutations. All acquired causes of thrombosis were excluded. Results. Of 880 patients who underwent screening for thrombophilia, 182 patients demonstrated VTE history. Their age ranged from 1 to 58 years. Males constituted a predominant group. About 45 (24.7%) patients had evidence of heritable thrombophilia. Of these, 20 (10.9%) had AT deficiency, 9 (4.9%) had Factor V Leiden mutation, 6 (3.2%) had protein C deficiency, whereas protein S deficiency and prothrombin gene mutation both were found in 5 (2.7%) patients. Conclusion. Our study illustrated the highest frequency of antithrombin deficiency among other investigated thrombophilia defects.

scholarly journals Evaluation of Direct Oral Anticoagulants in the Treatment of Venous Thromboembolism for Inherited Thrombophilia Disorders

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5007-5007 ◽  
Author(s):  
Ali McBride ◽  
Reem Diri ◽  
Ravitharan Krishnadasan ◽  
Pavani Chalasani ◽  
Ivo Abraham ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Protein C ◽  
Factor V Leiden ◽  
Secondary Prophylaxis ◽  
Factor V ◽  
Inherited Thrombophilia ◽  
Dvt Prophylaxis ◽  
Prothrombin Gene ◽  
Baseline Characteristics

Abstract Background Venous thromboembolism can be classified according to the presence of either environmental or genetic risk factors. Risk factors for thrombosis can include activated protein C resistance, and heritable including deficiencies of antithrombin, protein C or protein S. Factor V Leiden deficiency and prothrombin gene mutations are some of the more common thrombophilias, with a slight increased risk for venous thromboembolism (VTE). Current guidelines suggest the use of low-molecular weight heparins for secondary prophylaxis in patients with VTE. However, there is a lack of data on the use of Direct Oral Anticoagulant (DOACs) in patients with inherited thrombophilia. We evaluated our use of rivaroxaban in patients with thrombophilia disorders treated for secondary DVT prophylaxis. Method We performed a retrospective evaluation of patients in our institution with inherited thrombophilia with an active VTE diagnosis who received DOACs for secondary prophylaxis from November 2013 until April 2016. Data collected included patient demographics, inherited thrombophilia mutation, previous history of VTE, prior treatments, and efficacy and safety of anticoagulation with DOACs. Results We had 13 patients with inherited thrombophilia mutation and 4 patients diagnosed with concomitant cancer (non-Hodgkin lymphoma, melanoma, and 2 with breast cancer) (Table 1). Out of 13 patients 3 failed warfarin, and one failed fondaparinux prior to switching to a DOAC. Mutation with heterozygous Factor V Leiden deficiency was reported in 7 patients, while mutations with Protein C and/or S deficiency were found in 4 patients. One patient had both Factor V Leiden and Protein C deficiency mutations. The prothrombin gene mutation was identified in one patient. The median of length of therapy was 2 years with 8/13 still on rivaroxaban in April 2016. The shortest treatment duration was 41 days for a patient who failed rivaroxaban with a second clot and was switched to apixaban without subsequent treatment failure. Two patients experienced 4 non-major episodes of gastrointestinal bleeding, nose bleeding and dark stool. One patient developed rash with noted bruising during their rivaroxaban therapy. Conclusion: This is the first report on outcomes for secondary DVT prophylaxis with DOACs in patients with underlying thrombophilia mutations. Safety and efficacy of DOACs for secondary VTE prophylaxis yielded favorable results; however, future prospective studies in the setting of thrombophilia are warranted. Table 1 Summary of baseline characteristics and outcomes. Table 1. Summary of baseline characteristics and outcomes. Disclosures McBride: Sanofi: Research Funding.

Fundamentals and Patient Evaluation

2006 ◽  
Author(s):  
Richard C. Becker ◽  
Frederick A. Spencer
Keyword(s):  
General Population ◽  
Venous Thrombosis ◽  
Protein C ◽  
Factor V Leiden ◽  
Protein S ◽  
Incidence Rates ◽  
Factor V ◽  
Inherited Thrombophilia ◽  
Occult Malignancy ◽  
History Of

Thrombophilia is the term used to describe a tendency toward developing thrombosis. This tendency may be inherited, involving polymorphism in gene coding for platelet or clotting factor proteins, or acquired due to alterations in the constituents of blood and/or blood vessels. An inherited thrombophilia is likely if there is a history of repeated episodes of thrombosis or a family history of thromboembolism. One should also consider an inherited thrombophilia when there are no obvious predisposing factors for thrombosis or when clots occur in a patient under the age of 45. Repeated episodes of thromboembolism occurring in patients over the age of 45 raise suspicion for an occult malignancy. A summary of inherited thrombophilias are summarized in Table 24.1. This list continues to grow, as new genetic polymorphisms and combined mutations are being detected. The prevalence of common thrombophilias is shown in Figure 24.1. Factor V Leiden (FVL) mutation and hyperhomocysteinemia are present in nearly 5% of the general population and are often found in patients with venous thrombosis, while deficiencies of antithrombin (AT), protein C, and protein S are relatively uncommon. Elevated levels of factor VIII (FVIII) are uncovered frequently in the general population and in patients with thrombosis. This is not surprising as FVIII is an acute-phase reactant that increases rapidly after surgery or trauma; however, prospective studies have shown that FVIII elevation in some patients cannot be attributed to a stress reaction and probably represents mutations in the genes regulating FVIII synthesis or release (Kyrle et al., 2000). The same may be true for factors IX and XI. The relative risks for thrombosis among patients with inherited thrombophilias have been determined. While AT mutations are the least common, they are associated with a substantial risk of venous thrombosis; similar risk is seen with protein C and S deficiency. In contrast, the lifetime risk of having a thromboembolic event in an individual heterozygous for FVL is comparatively low (Martinelli et al., 1998). Incidence rates markedly increase with age, and are highest among those with AT deficiency, followed by protein C and protein S, and least with FVL.

Risk of venous thromboembolism in relatives of symptomatic probands with thrombophilia: a systematic review

2003 ◽  
Vol 90 (07) ◽  
pp. 17-26 ◽  
Author(s):  
Nicole Langlois ◽  
Philip Wells
Keyword(s):  
Venous Thromboembolism ◽  
Relative Risk ◽  
Observational Studies ◽  
Protein C ◽  
Retrospective Studies ◽  
Factor V Leiden ◽  
Protein S ◽  
Clinical Equipoise ◽  
Factor V ◽  
Protein C Deficiency

SummaryClinical equipoise exists regarding whether relatives of individuals with venous thromboembolism (VTE) and thrombophilia should be screened for thrombophilia. There have been no systematic attempts to summarize studies that have assessed the incidence of VTE in relatives. The purpose of this review was to systematically identify and review observational studies with thrombophilic relatives and to summarize their findings with respect to their risk of VTE.We conducted a systematic literature review and included nine observational studies meeting a priori inclusion criteria. Potentially eligible studies evaluated VTE incidence in relatives of index patients (probands) with symptomatic thrombophilia. In the four prospective studies, the incidence of VTE for asymptomatic family members with factor V Leiden ranged from 0.58-0.67% per year, 1.0-2.5% for protein C deficiency, 0.7-2.2% for protein S deficiency, and 4% for antithrombin deficiency. About half of all VTEs occurred during well-known risk periods but incidence rates were decreased by use of prophylaxis. No deaths from pulmonary embolism or fatal hemorrhages from anticoagulants were reported. The incidence of VTE was generally lower in the retrospective studies. The pooled relative risk from four retrospective studies for factor V Leiden carriers was 3.69 (CI 2.27, 6.00) and from two studies the pooled relative risk for deficiencies of protein C, protein S, and antithrombin was 10.58 (CI 5.38, 20.81).In conclusion, the risk of VTE events in asymptomatic relatives is low, but this may be an underestimate. Anticoagulant prophylaxis during risk periods appears to be of benefit but further research in this area is required.

"ProC Global": A functional screening test that predicts recurrent venous thromboembolism

2005 ◽  
Vol 93 (03) ◽  
pp. 600-604 ◽  
Author(s):  
Shannon Bates ◽  
Marilyn Johnston ◽  
Simon McRae ◽  
Jeffrey Ginsberg ◽  
Anne Grand’Maison
Keyword(s):  
Venous Thromboembolism ◽  
Protein C ◽  
Specific Inhibitor ◽  
Factor V Leiden ◽  
First Episode ◽  
Functional Screening ◽  
Factor V ◽  
Increased Risk ◽  
Global Result ◽  
Recurrent Vte

SummaryAbnormalities of the Protein C (PC) pathway are found in the majority of patients with thrombophilia. ProC Global is a coagulation assay that reflects the net effect of the PC pathway by measuring the activated partial thromboplastin time (APTT) of patient and control plasma, before and after activation of endogenous PC by Protac, a snake venom. Previous studies have suggested that abnormalities in this test are associated with an increased risk of venous thromboembolism (VTE). A retrospective analysis was performed using frozen plasma samples from 140 patients with confirmed VTE to determine whether an abnormal ProC Global result (in the presence and in the absence of known abnormalities in the PC pathway) is a predictor of initial and recurrent VTE. Patients were tested for the presence of activated protein C resistance, Factor V Leiden, PC and protein S (PS) deficiency, and non-specific inhibitor positivity. Mean ProC Global results were significantly lower in patients with recurrent VTE than in patients without recurrent VTE. The association between abnormal ProC Global result and recurrent VTE showed a strong trend, before (odds ratio, OR 3.6) and after (OR 3.1) exclusion of known thrombophilic abnormalities. Patients with a first episode of idiopathic VTE also expressed significant lower ProC Global results than those with secondary VTE. After exclusion of known PC pathway abnormalities, there was a statistically significant association between abnormal ProC Global and initial idiopathic VTE (p=0.04). These results suggest that ProC Global may serve as a predictor of recurrent VTE and potentially for first episode of idiopathic VTE. ProC Global may help identify patients at increased risk of initial and recurrent VTE.

scholarly journals Impact of thrombophilia and waist circumference on the risk of venousthromboembolism

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
T B Kondratieva ◽  
L V Popova ◽  
T V Khlevchuk ◽  
M Z Kanevskaya ◽  
M B Aksenova ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Waist Circumference ◽  
Factor V Leiden ◽  
Mthfr C677t ◽  
Prothrombin G20210a ◽  
Factor V ◽  
C677t Polymorphism ◽  
Mthfr C677t Polymorphism ◽  
Inherited Thrombophilia ◽  
Pai 1

Abstract Background Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE) represents a major health problem. In the general population, the absolute risk of any kind of VTE is 0.1%–0.2% per year, and it increases with age. VTE is an important and preventable cause of morbidity and mortality, with almost a third of survivors experiencing long term effects. Obesity is well-known risk factor of VTE. The extent of the effects of obesity on VTE depends not only on total body fat, but also on the distribution of adipose tissue (e.g., central obesity) and the interplay among risk factors for VTE, such as genetic mutations, and other risk factors. Thrombophilia, venous thromboembolism, obesity, waist circumference Purpose The aim of this study is to investigate the impact of waist circumference on the risk of venous thromboembolism Methodology The study involved 68 patients with VTE (33 females and 34 males, mean age 56.8 years ±15.3) and 84 patients without VTE (38 males and 46 females, 44.4 years±18.6). From 2015 to 2017, data have been collected from records of patients admitted to department of internal medicine. All subjects were recruited to the study during their stay in the hospital. The reasons for hospitalization were: acute event of DVT or PE for the main group, the absence of acute event or history of VTE for the control group. DVT was diagnosed by ultrasonic Doppler examination, and PE was confirmed by intravenous radiocontrast computed tomography. Anthropometric measures were performed with subjects wearing short-sleeved garments and no shoes; waist circumference was measured in centimeters at the umbilical line. For all patients genetic testing for inherited thrombophilia – Factor V Leiden G1691A, Prothrombin G20210A, MTHFR C677T polymorphism, PAI-1 (SERPIN1) 4G/5G polymorphism – was performed by real-time PCR technique. Results Factor V Leiden G1691A increase the risk of VTE in 2.11 (CI: 1.79–2.48), p=0.049, prothrombin G20210A in 3.21 (CI: 1.66–6.211), p=0.049. MTHFR C677T polymorphism, PAI-1 (SERPIN1) 4G/5G polymorphism also increase the risk of VTE, but it was no significant. Study have shown that waist circumference >80 cm increase the risk of VTE in 3.19 (CI: 1.35–7.58), p=0.019. Combination of inherited thrombophilia (Factor V Leiden G1691A, Prothrombin G20210A, MTHFR C677T polymorphism, PAI-1 (SERPIN1) 4G/5G polymorphism) and waist circumference >80 cm increase the risk of VTE in 3.51 (CI: 1.76–7.04), p<0.001. Conclusion Previous results of our work indicate influence of waist circumference >80 cm on the risk of VTE, especially risk of thrombosis is higher in patients with combination inherited thrombophilia and waist circumference >80 cm. FUNDunding Acknowledgement Type of funding sources: None.

Prothrombin Fragment F1+2 Is not Predictive for Recurrent Venous Thromboembolism

1997 ◽  
Vol 77 (05) ◽  
pp. 0829-0833 ◽  
Author(s):  
P A Kyrle ◽  
S Eichinger ◽  
I Pabinger ◽  
A Stümpflen ◽  
M Hirschl ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Venous Thrombosis ◽  
Protein C ◽  
Oral Anticoagulants ◽  
Factor V Leiden ◽  
Factor V ◽  
Recurrent Thrombosis ◽  
Prothrombin Fragment ◽  
Recurrent Venous Thromboembolism ◽  
History Of

SummaryIt would be important to estimate in advance the risk of recurrent thrombosis. Deficiencies of antithrombin, protein C or protein S, or resistance to activated protein C are associated with a biochemically detectable prethrombotic state. It is thus far unknown whether in patients with a history of thromboembolism but without a defined clotting abnormality a heightened coagulation activation is detectable.We investigated the value of prothrombin fragment Fl+2 (FI+2) as a predictor of recurrent venous thromboembolism. Furthermore, we compared the Fl+2 levels of thrombosis patients without a defined clotting defect to those of Factor V Leiden patients with a history of venous thrombosis and to those of healthy controls. 180 patients without a defined clotting abnormality and 73 patients with Factor V Leiden were prospectively followed after discontinuation of oral anticoagulants for venous thrombosis and Fl+2 was measured at regular intervals.Recurrent venous thromboembolism occurred in 23 (9%) of the 253 patients. Before or at several time points after oral anticoagulants, no significant difference in Fl+2 levels was found in patients with and without recurrent thrombosis. Fl+2 levels at 3 weeks and prior to recurrence were not significantly different in both patient groups. Over a one-year observation period, Fl+2 levels of both patients with and without Factor V Leiden were higher than those of the controls. No difference in Fl+2 was seen between patients with and without Factor V Leiden.We conclude that monitoring of Fl+2 is not suitable for identification of individuals at risk of recurrent venous thrombosis. Permanent hemostatic system activation is detectable both in patients with a defined abnormality of the clotting system and in patients in whom a particular defect has not (yet) been identified.

Co-inheritance of the 20210A Allele of the Prothrombin Gene Increases the Risk of Thrombosis in Subjects with Familial Thrombophilia

1997 ◽  
Vol 78 (06) ◽  
pp. 1426-1429 ◽  
Author(s):  
M Makris ◽  
F E Preston ◽  
N J Beauchamp ◽  
P C Cooper ◽  
M E Daly ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Protein C ◽  
Factor V Leiden ◽  
Protein S ◽  
Factor V ◽  
Protein C Deficiency ◽  
Antithrombin Deficiency ◽  
Control Subjects ◽  
Increased Risk ◽  
Venous Thromboembolic

SummaryThe presence of the 20210A allele of the prothrombin (PT) gene has recently been shown to be a risk factor for venous thromboembolism. This is probably mediated through increased plasma prothrombin levels. The aim of this study was to compare the prevalence of the prothrombin 20210A allele in control subjects and in subjects with recognised thrombophilia and to establish whether the additional inheritance of the PT 20210A allele is associated with an increased risk of venous thromboembolism. 101 subjects with a history of venous thromboembolism and diagnosed as having either factor V Leiden (R506Q) or heritable deficiencies of protein C, protein S or antithrombin were studied. The prevalence of the PT 20210A allele in this group was compared with the results obtained for 150 control subjects. In addition, the relationships were examined between genetic status and the number of documented thromboembolic episodes, and between plasma prothrombin levels and possession of the PT 20210A allele. 8 (7.9%) of the 101 patients were also heterozygous for the PT 20210A allele. This compares with 0.7% in the control subjects (p = 0.005). After exclusion of patients on warfarin, the mean plasma prothrombin of 113 subjects without 20210A was 1.09 U/ml, as compared with 1.32 U/ml in 8 with the allele (p = 0.0002). Among the 101 patients with either factor V Leiden, protein S deficiency, protein C deficiency or antithrombin deficiency, the age adjusted mean (SD) number of venous thromboembolic episodes at diagnosis was 3.7 (1.5) in those with the PT 20210A allele, as compared with 1.9 (1.1) in those without (p = 0.0001). We have demonstrated that the prevalence of the PT 20210A allele is significantly greater in subjects with venous thrombosis and characterised heritable thrombophilia than in normal control subjects and that the additional inheritance of PT 20210A is associated with an increased risk of venous thromboembolism. We have also confirmed that plasma prothrombin levels are significantly greater in subjects possessing the PT 20210A compared with those who do not.

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