[Heparin-induced thrombocytopenia: Update]. / La thrombopénie induite par héparine : mise au point.

Heparin-induced thrombocytopenia (HIT) is a serious complication of heparin therapy. It is due to the synthesis of antibodies most often directed against platelet factor 4 (FP4) modified by heparin (H). HIT is manifested by a platelet count fall, associated with a high risk of venous or arterial thrombosis. The diagnosis of HIT is based on the assessment of clinical probability (4Ts score or change in platelet count after cardiac surgery) and the demonstration of heparin-modified anti-FP4 antibodies (FP4/H). If the immunological tests are positive, functional tests should be performed. In case of suspicion of HIT, it is necessary to urgently stop heparin therapy, to perform a doppler ultrasound of the lower limbs, and to prescribe an alternative anticoagulation agent at a curative dose. Currently, danaparoid sodium and argatroban are authorized. The diagnosis and management of HIT remain complex and requires multidisciplinary collaboration.

Ultrasound arterial anomalies in patients exposed to nilotinib therapy for chronic myeloid leukemia.

INTRODUCTION: Patients exposed to nilotinib for chronic myeloid leukemia (CML) appear to be at risk of arterial complication. The prevalence and aspect of ultrasound asymptomatic arterial lesions are unknown. OBJECTIVE: To describe prevalence and characteristics of ultrasound arterial anomalies in patients treated with nilotinib for CML. METHODS: Patients treated with nilotinib from 2006 to 2015 in the department of the Paoli-Calmettes Institute, Marseille, were included retrospectively. A vascular ultrasound screening was carried out from 2010. The arterial lesions at the first examination were described: plaque and its echogenicity, stenosis or occlusion. A vascular arterial anomaly (VAA) was defined by the presence of a clinical and/or ultrasound anomaly. Patients with or without VAA at initial vascular examination were compared using bivariate and multivariate analysis. RESULTS: 74 patients were included (51.4% men, mean age 54.5 years); 25 patients had ultrasound arterial anomalies (33.8%). Carotid bulb was the most involved territory (44%). Arterial anomalies were: 88% plaques, 44%>50% stenosis and 12% occlusion. 72.7% plaques were echolucent or hypoechogenic. A VAA was present in 25 patients with initial vascular evaluation (33.8%). Patients with VAA at baseline were significantly older (64.9 vs 49.3, P<0.001), older at nilotinib initiation (60.8 vs 46.5, P<0.001), with more arterial hypertension (40% vs 12.2%, P=0.01), with more cardiovascular risk factors (P=0.03). In patient with no cardiovascular risk factor 12.5% had VAA (n=24). CONCLUSION: Nilotinib seems to be associated to arterial lesions of unstable lipid-like appearance. The most involved arterial territory was the carotid bulb and the most common lesion was echolucent or hypoechogenic plaque. VAA can occur in patients without cardiovascular risk factors. This result encourages us to systematically screen and follow all patients exposed to nilotinib even those without cardiovascular risk factors.

Descriptive study of the general practitioners' perception of direct oral anticoagulants and the risk of genital bleeding in women of childbearing age.

AIM OF THE STUDY AND PATIENTS: Direct oral anticoagulants (DOA) tend to replace antivitamins K (VKA). The incidence of major and minor hemorrhages is higher in women, a difference potentially linked to genital hemorrhages. The objective is to assess the practices and perception of general practitioners of the use of oral anticoagulant therapy in women of childbearing age. MATERIALS AND METHODS: Descriptive, observational, transversal and monocentric study. An 11-items questionnaire was sent to 900 randomized general practitioners, assessing the type of patient, the type of anticoagulant prescribed, the management of genital bleeding, and the assessment of the quality of life of anticoagulated patients. RESULTS: DOA were the most prescribed anticoagulants. Genital hemorrhage was the second leading cause of minor hemorrhage. Most doctors (60.6%) believed they were due to VKAs. 25% reported an alteration in the quality of life of patients following these genital hemorrhages and 47.5% addressed this subject in consultation. CONCLUSION: Our study suggests that, according to the general practitioners interviewed, genital hemorrhage is more frequent on VKA than on DOA in women of reproductive age, which is contradictory with the data in the literature. The probably taboo subject is rarely mentioned in consultation and is responsible for a deterioration in the quality of life in these young patients. No recommendation exists on the management of this type of genital hemorrhage in these women. An algorithm is proposed for their management.

[Bilateral adrenal hemorrhage under apixaban in primary antiphospholipid syndrome]. / Nécrose hémorragique bilatérale des surrénales sous apixaban : penser au syndrome des antiphospholipides ?

INTRODUCTION: Adrenal hemorrhage is a classical but rare complication of antiphospholipid syndrome, revealing diagnosis in one third of the cases. Anti-vitamin K therapy is the standard treatment but direct oral anticoagulants are discussed as an alternative. In the latest recommendations, it is advised not to use direct oral anticoagulants in the setting of antiphospholipid syndrome. CASE REPORT: We present a case of bilateral adrenal hemorrhage revealing primary antiphospholipid syndrome with triple positive antibody profile, in a 47-year-old man treated by apixaban for previous venous thromboembolism. CONCLUSION: To our knowledge, it is the first case of adrenal hemorrhage occurring during apixaban treatment in a patient with antiphospholipid syndrome. This case illustrates the inefficacy of direct oral anticoagulants to prevent thrombotic events in antiphospholipid syndrome, in accordance with the latest recommendations.

[Impact of menstrual blood self-representation on contraceptive choice of women]. / Impact des représentations du sang menstruel sur le choix contraceptif des femmes.

OBJECTIVES: To study the psychic self-representations and experiences of menstrual blood in women and their impact on the choice of a contraceptive method, with or without amenorrhea. METHODS: Qualitative study based on semi-structured interviews with French women over age 18, under contraception. RESULTS: Twenty-three interviews were conducted with women of various ages and socio-economic classes. Three themes have been studied: the menarche experience, the representation and experience of menstrual blood, and the representation and experience of amenorrhea induced by contraception. Menarche has been a negative experience for most of them, and menarche is known to influence menstrual self-representation. About menstrual bleeding, two profiles of women could be described. Those with a positive self-representation of menstrual blood considered it necessary for the purification of their bodies as well as for procreation and were reluctant to the idea of amenorrhea induced by their contraception. Those with a negative representation of menstrual blood considered it as a source of physical and mental suffering and accepted the idea of having amenorrhea induced by their contraception, amenorrhea being considered as a treatment or a release. CONCLUSION: The choice of a contraception with or without a induced-amenorrhea seems to be specific to every woman and depends on there self-psychic representation of menstrual blood, independently from their socio-economic class. The results of this study highlighted the effect of women's psychic representations and experience of menstrual blood on their contraceptive choice.

[Evaluation of an "Emergency Thrombosis" care system in a university-hospital department of general emergencies]. / Évaluation de la mise en place d'une filière de soins « Urgence Thrombose ¼ dans un service hospitalo-universitaire d'Urgences générales.

GOAL: Describe the use of diagnostic, prognostic and therapeutic algorithms for venous thromboembolism (VTE), derived from the 2014 European guidelines, in a teaching hospital's emergencies department and compare two groups: the 2015 group "without a care path" and the 2017 group "with a care path". METHOD: Comparative and retrospective study of the characteristics of emergencies department patients admitted for VTE from January to June 2015 for the 2015 group and from January to June 2017 for the 2017 group. RESULTS: Seventy-nine patients were included in the 2015 group and 62 patients in the 2017 group. In 24% of cases a clinical probability rule was calculated in the 2017 group (vs. no score in 2015, P<0.05). In the 2015 group, 10% of patients did not have a D-Dimer measurement in case of low clinical probability (vs. 0% in 2017, P<0.05). For both groups, the severity score sPESI was not noted in the medical record. All patients with pulmonary embolism were hospitalized in both groups. A total of 36% of patients with deep vein thrombosis (DVT) were hospitalized in the 2015 group (vs. none in 2017, P<0.05). A total of 52.5% of patients were treated with direct oral anticoagulants (DOAS) in the 2017 group vs. 32.5% in the 2015 group (P<0.05). In 18% of cases DOAS were prescribed by emergency physicians in the 2017 group vs. 2.5% in the 2015 group (P<0.05). Mean hospital stay was 7.4 days in the 2017 group and 9.4 days in the 2015 group (P<0.05). CONCLUSION: We observed a change in clinical practices and prescriptions after the establishment of an "Emergency Thrombosis" care system. Indeed, improvement in the calculation of the clinical probability score, increase in the outpatient management of DVT, increase in prescribing DOAS and reducing the length of hospital stay were the main revisions. The implementation of standardized digitally calculated clinical and prognostic probability scores would optimize this care path, as well as allow a better distribution of the post-emergency consultations created for outpatients.

Minor allele of the factor V K858R variant protects from venous thrombosis only in non-carriers of factor V Leiden mutation.

Factor V serves an important role in the regulation of blood coagulation. The rs6025 (R534Q) and rs4524 (K858R) polymorphisms in the F5 gene, are known to influence the risk of venous thrombosis. While the rare Q534 (factor V Leiden) allele is associated with an increased risk of venous thrombosis, the minor R858 allele is associated with a lower risk of disease. However, no study has deeply examined the cumulative impact of these two variations on venous thrombosis risk. We study the association of these polymorphisms with the risk of venous thrombosis in 4 French case-control populations comprising 3719 patients and 4086 controls. We demonstrate that the Q534 allele has a dominant effect over R858. Besides, we show that in individuals not carrying the Q534 allele, the protective effect of the R858 allele acts in a dominant mode. Thrombin generation-based normalized activated protein C sensitivity ratio was lower in the 858R/R homozygotes than in the 858K/K homozygotes (1.92 ± 1.61 vs 2.81 ± 1.57, p = 0.025). We demonstrate that the R858 allele of the F5 rs4524 variant protects from venous thrombosis only in non-carriers of the Q534 allele of the F5 rs6025. Its protective effect is mediated by reduced factor VIII levels and reduced activated protein C resistance.

[Risk factors for thromboembolic disease in young women-the role of hormones]. / Facteurs de risque de maladie veineuse thromboembolique chez les jeunes femmes en contexte hormonal: Risque de survenue d'une maladie thromboembolique veineuse chez les membres de la famille au 1er degré de femmes ayant une maladie veineuse thromboembolique en contexte hormonal : étude « FIT ­ H ¼.

Hormonal exposure in young women increases the risk of venous thromboembolic disease (VTE). Thrombophilia testing is often proposed in women of childbearing age before the initiation of contraception. However, the presence of a familial history of VTE has the potential to be more accurate than the presence of inherited thrombophilia. OBJECTIVE: To demonstrate an association between the risk of VTE in young women with hormonal exposure (pregnancy or oral contraceptive use) and the presence of a previous episode of VTE in their first-degree relatives, according to whether or not a detectable inherited thrombophilia was present. METHODS: We will perform a multicenter case-control cross-sectional study. The main risk factor is defined by the presence of a symptomatic VTE in young women with hormonal exposure. The principle variable is the presence of an objectively diagnosed episode of VTE in first-degree relatives. We will need to include 2,200 family members in 440 cases. EXPECTED RESULTS: We expect to improve understanding of the thrombotic risk in first-degree relatives of patients in hormonal context with or without a past history of VTE.

Protein S Heerlen mutation heterozygosity is associated with venous thrombosis risk.

Hereditary Protein S (PS) deficiency is a rare coagulation disorder associated with an increased risk of venous thrombosis (VT). The PS Heerlen (PSH) mutation is a rare S501P mutation that was initially considered to be a neutral polymorphism. However, it has been later shown that PSH has a reduced half-life in vivo which may explain the association of PSH heterozygosity with mildly reduced levels of plasma free PS (FPS). Whether the risk of VT is increased in PSH carriers remains unknown. We analyzed the association of PSH (rs121918472 A/G) with VT in 4,173 VT patients and 5,970 healthy individuals from four independent case-control studies. Quantitative determination of FPS levels was performed in a subsample of 1257 VT patients. In the investigated populations, the AG genotype was associated with an increased VT risk of 6.57 [4.06-10.64] (p = 1.73 10-14). In VT patients in whom PS deficiency was excluded, plasma FPS levels were significantly lower in individuals with PSH when compared to those without [72 + 13 vs 91 + 21 UI/dL; p = 1.86 10-6, mean + SD for PSH carriers (n = 21) or controls (n = 1236) respectively]. We provide strong evidence that the rare PSH variant is associated with VT in unselected individuals.

Genetic risk factors for venous thrombosis in women using combined oral contraceptives: update of the PILGRIM study.

Identifying women at risk of venous thrombosis (VT) under combined oral contraceptives (COC) is a major public health issue. The aim of this study was to investigate in COC users the impact on disease of genetic polymorphisms recently identified to associate with VT risk in the general population. Nine polymorphisms located on KNG1, F11, F5, F2, PROCR, FGG, TSPAN and SLC44A2 genes were genotyped in a sample of 766 patients and 464 controls as part of the PILGRIM (PILl Genetic Risk Monitoring) study. Cases were women who experienced an episode of documented VT during COC use, while controls were women with no history of VT using COC at the time of inclusion. Among the studied polymorphisms, only F11 rs2289252 was significantly associated with VT. The F11 rs2289252-A allele was associated with a 1.6-fold increased risk of VT (p < 0.0001). Besides, the combination of the rs2289252-A allele with non-O blood group, present in 52% of the cohort, was associated with an odds ratio of 4.00 (2.49-6.47; p < 10-4 ). The consideration of this genetic risk factor could help to better assess the risk of VT in COC users.

Single nucleotide polymorphisms in an intergenic chromosome 2q region associated with tissue factor pathway inhibitor plasma levels and venous thromboembolism.

Essentials Tissue factor pathway inhibitor (TFPI) regulates the blood coagulation cascade. We replicated previously reported linkage of TFPI plasma levels to the chromosome 2q region. The putative causal locus, rs62187992, was associated with TFPI plasma levels and thrombosis. rs62187992 was marginally associated with TFPI expression in human aortic endothelial cells. Click to hear Ann Gil's presentation on new insights into thrombin activatable fibrinolysis inhibitor SUMMARY: Background Tissue factor pathway inhibitor (TFPI) regulates fibrin clot formation, and low TFPI plasma levels increase the risk of arterial thromboembolism and venous thromboembolism (VTE). TFPI plasma levels are also heritable, and a previous linkage scan implicated the chromosome 2q region, but no specific genes. Objectives To replicate the finding of the linkage region in an independent sample, and to identify the causal locus. Methods We first performed a linkage analysis of microsatellite markers and TFPI plasma levels in 251 individuals from the F5L Family Study, and replicated the finding of the linkage peak on chromosome 2q (LOD = 3.06). We next defined a follow-up region that included 112 603 single nucleotide polymorphisms (SNPs) under the linkage peak, and meta-analyzed associations between these SNPs and TFPI plasma levels across the F5L Family Study and the Marseille Thrombosis Association (MARTHA) Study, a study of 1033 unrelated VTE patients. SNPs with false discovery rate q-values of < 0.10 were tested for association with TFPI plasma levels in 892 patients with coronary artery disease in the AtheroGene Study. Results and Conclusions One SNP, rs62187992, was associated with TFPI plasma levels in all three samples (ß = + 0.14 and P = 4.23 × 10-6 combined; ß = + 0.16 and P = 0.02 in the F5L Family Study; ß = + 0.13 and P = 6.3 × 10-4 in the MARTHA Study; ß = + 0.17 and P = 0.03 in the AtheroGene Study), and contributed to the linkage peak in the F5L Family Study. rs62187992 was also associated with clinical VTE (odds ratio 0.90, P = 0.03) in the INVENT Consortium of > 7000 cases and their controls, and was marginally associated with TFPI expression (ß = + 0.19, P = 0.08) in human aortic endothelial cells, a primary site of TFPI synthesis. The biological mechanisms underlying these associations remain to be elucidated.

α1 -antitrypsin Pittsburgh and plasmin-mediated proteolysis.

Essentials Patients with α-1-antitrypsin (α1-AT) Pittsburgh exhibit a mild bleeding tendency. A new case of α1-AT Pittsburgh with suspected high antifibrinolytic potential was studied. We showed that α1-AT Pittsburgh inhibits tissue plasminogen activator and plasmin. The antifibrinolytic potential of the variant contributes to explaining the mild bleeding phenotype. SUMMARY: α1 -Antitrypsin (α1 -AT) Pittsburgh has a Met358 to Arg substitution at the reactive Met-Ser site of α1 -AT, which enables the protein to act as a potent thrombin inhibitor. Four patients with α1 -AT Pittsburgh have been described to date. An additional young girl was recently diagnosed with α1 -AT Pittsburgh in our center after presenting with a large hematoma in the forearm. Interestingly, all of these patients showed a potent thrombin inhibitor in the plasma and a mild bleeding phenotype. This observation suggests that the in vivo consequences of the mutation may contribute to the maintenance of normal hemostatic balance. We assessed inhibition of the fibrinolytic system by the variant protein by evaluating the fibrinolysis inhibitory potential of the patient's plasma, purified wild-type α1 -AT and purified Pittsburgh α1 -AT with an electrophoretic zymography system, western blotting, and clot fibrinolysis. Our results indicate that the patient's plasma and purified α1 -AT Pittsburgh have strong potential to inhibit tissue-type plasminogen activator and plasmin.

Is there still room for additional common susceptibility alleles for venous thromboembolism?

UNLABELLED: Essentials Genetic architecture of venous thromboembolism (VTE) remains to be fully disentangled. 11 newly discovered candidate polymorphisms were genotyped in 3019 VTE cases and 2605 controls. None of the 11 polymorphisms were significantly associated with VTE risk. Additional major efforts are needed to identify VTE-associated genetic variants. SUMMARY: Background Through a meta-analysis of 12 genome-wide association studies, the International Network against VENous Thrombosis (INVENT) consortium identified two novel susceptibility loci for venous thromboembolism (VTE). This project has also generated other candidates that need to be confirmed. Objectives To assess the association with VTE of common single-nucleotide polymorphisms (SNPs) that demonstrated strong statistical, but not genome-wide, significance in the INVENT cohorts. Patients/methods Eleven SNPs were genotyped and tested for association with VTE in three case-control studies totaling 3019 patients and 2605 healthy individuals. Results and conclusions None of the tested SNPs showed evidence for association with VTE. Different strategies are needed to decipher the whole spectrum of common and rare genetic variations associated with VTE risk.

Genetic determinants of tissue factor pathway inhibitor plasma levels.

Tissue factor pathway inhibitor (TFPI) impedes early stages of the blood coagulation response, and low TFPI plasma levels increase the risk of thrombosis. TFPI plasma levels are heritable, but specific genetic determinants are unclear. We conducted a comprehensive review of genetic risk factors for TFPI plasma levels and identified 26 studies. We included 16 studies, as well as results from two unpublished genome-wide studies, in random effects meta-analyses of four commonly reported genetic variants in TFPI and its promoter (rs5940, rs7586970/rs8176592, rs10931292, and rs10153820) and 10 studies were summarised narratively. rs5940 was associated with all measures of TFPI (free, total, and activity), and rs7586970 was associated with total TFPI. Neither rs10931292 nor rs10153820 showed evidence of association. The narrative summary included 6 genes and genetic variants (P151L mutation in TFPI, PROS1, F5, APOE, GLA, and V617F mutation in JAK2) as well as a genome-wide linkage study, and suggested future research directions. A limitation of the systematic review was the heterogeneous measurement of TFPI. Nonetheless, our review found robust evidence that rs5940 and rs7586970 moderate TFPI plasma levels and are candidate risk factors for thrombosis, and that the regulation of TFPI plasma levels involves genetic factors beyond the TFPI gene.

Economic analysis of thrombo inCode, a clinical-genetic function for assessing the risk of venous thromboembolism.

BACKGROUND: Patients with venous thromboembolism (VTE) commonly have an underlying genetic predisposition. However, genetic tests nowadays in use have very low sensitivity for identifying subjects at risk of VTE. Thrombo inCode(®) is a new genetic tool that has demonstrated very good sensitivity, thanks to very good coverage of the genetic variants that modify the function of the coagulation pathway. OBJECTIVE: To conduct an economic analysis of risk assessment of VTE from the perspective of the Spanish National Health System with Thrombo inCode(®) (a clinical-genetic function for assessing the risk of VTE) versus the conventional/standard method used to date (factor V Leiden and prothrombin G20210A). METHODS: An economic model was created from the National Health System perspective, using a decision tree in patients aged 45 years with a life expectancy of 81 years. The predictive capacity of VTE, based on identification of thrombophilia using Thrombo inCode(®) and using the standard method, was obtained from two case-control studies conducted in two different populations (S. PAU and MARTHA; 1,451 patients in all). Although this is not always the case, patients who were identified as suffering from thrombophilia were subject to preventive treatment of VTE with warfarin, leading to a reduction in the number of VTE events and an increased risk of severe bleeding. The health state utilities (quality-adjusted life-years [QALYs]) and costs (in 2013 EUR values) were obtained from the literature and Spanish sources. RESULTS: On the basis of a price of EUR 180 for Thrombo inCode(®), this would be the dominant option (more effective and with lower costs than the standard method) in both populations. The Monte Carlo probabilistic analyses indicate that the dominance would occur in 100 % of the simulations in both populations. The threshold price of Thrombo inCode(®) needed to reach the incremental cost-effectiveness ratio (ICER) generally accepted in Spain (EUR 30,000 per QALY gained) would be between EUR 3,950 (in the MARTHA population) and EUR 11,993 (in the S. PAU population). CONCLUSION: According to the economic model, Thrombo inCode(®) is the dominant option in assessing the risk of VTE, compared with the standard method currently used.

Safety and effectiveness of the association ezetimibe-statin (E-S) versus high dose rosuvastatin after acute coronary syndrome: the SAFE-ES study.

BACKGROUND: Statin therapy is a cornerstone therapy for secondary prevention after acute coronary syndrome (ACS). However, the use of these drugs can be limited by side effects, mainly muscular pain. Ezetimibe is a newer lipid-lowering agent, with fewer side effects. AIMS: The present study was designed to compare a commercially available association of ezetimibe and simvastatin (E-S) to high dose Rosuvastatin on cholesterol and muscular enzyme levels and occurrence of muscular pain. METHODS: All consecutive ACS statin-naïve patients with LDL cholesterol (LDL-C)>100mg/dL randomly received either high dose statin (Rosuvastatin 20mg) or E-S 10/40-mg. All patients had one-month follow-up with biological testing and clinical examination. We compared the two groups on the biological efficiency and incidence of muscular pain. RESULTS: One hundred and twenty-eight patients were randomized; 64 received E-S and 64 Rosuvastatin. In the two groups, the lowering of LDL-C level (Δ=51%) at one month was significant (P<0.01) without any difference in the rate of lowering on LDL-C or HDL-C suggesting that E-S is as effective as high dose Rosuvastatin (P=0.77 and P=0.99). The rate of patients reaching the objective of LDL-C<100mg/dL (45%) and LDL-C<70mg/dL (51%) was not different in the two clusters (P=0.65). Incidence of muscular pain was 15% higher in patients treated with Rosuvastatin (P=0.01) without any difference on CPK level (P=0.6). CONCLUSION: Using an association of E-S in an effective alternative strategy to high dose Rosuvastatin with a lower incidence of muscular pain, which might impact adherence to medication after ACS.

Risk assessment of venous thrombosis in families with known hereditary thrombophilia: the MARseilles-NImes prediction model.

BACKGROUND: Although predicting the risk of venous thrombosis (VT) in an individual from a family with inherited thrombophilia is of major importance, it is often not feasible. OBJECTIVES: To develop a simple risk assessment model that improves prediction of the risk of VT for individuals of families with inherited thrombophilia. PATIENTS/METHODS: 1201 relatives from 430 families with inherited thrombophilia (deficiencies of antithrombin, protein C or protein S, and the factor V Leiden and F2 20210A mutations) were recruited at the referral center for thrombophilia in Marseilles, France, from 1986 to 2008. One hundred and twenty-two individuals had a personal history of VT. Sixteen preselected clinical and laboratory variables were used to derive the VT risk score. RESULTS: The scores based on the 16 variables and on the five most strongly associated variables performed similarly (areas under receiver operating characteristic curves of 0.85 and 0.83, respectively). For the five-variable score, named the MARNI score, derived from family history score of VT, von Willebrand factor antigen levels, age, severity of thrombophilia, and FGG rs2066865, the risk of VT ranged from 0.2% for individuals with a score of 0 (n = 186) to > 70% for individuals with a score of ≥ 7 (n = 27). The model was validated with an internal bootstrap method. CONCLUSIONS: With the use of a simple scoring system, assessment of the risk of VT in subjects from families with inherited thrombophilia can be greatly improved. External validation is now needed to replicate these findings.

Risk assessment of venous thrombosis in families with known hereditary thrombophilia: the MARseilles-NImes prediction model.

BACKGROUND: Although predicting the risk of venous thrombosis (VT) in an individual from a family with inherited thrombophilia is of major importance, it is often not feasible. OBJECTIVES: To develop a simple risk assessment model that improves prediction of the risk of VT for individuals of families with inherited thrombophilia. PATIENTS/METHODS: 1201 relatives from 430 families with inherited thrombophilia (deficiencies of antithrombin, protein C or protein S, and the factor V Leiden and F2 20210A mutations) were recruited at the referral center for thrombophilia in Marseilles, France, from 1986 to 2008. One hundred and twenty-two individuals had a personal history of VT. Sixteen preselected clinical and laboratory variables were used to derive the VT risk score. RESULTS: The scores based on the 16 variables and on the five most strongly associated variables performed similarly (areas under receiver operating characteristic curves of 0.85 and 0.83, respectively). For the five-variable score, named the MARNI score, derived from family history score of VT, von Willebrand factor antigen levels, age, severity of thrombophilia, and FGG rs2066865, the risk of VT ranged from 0.2% for individuals with a score of 0 (n = 186) to > 70% for individuals with a score of ≥ 7 (n = 27). The model was validated with an internal bootstrap method. CONCLUSIONS: With the use of a simple scoring system, assessment of the risk of VT in subjects from families with inherited thrombophilia can be greatly improved. External validation is now needed to replicate these findings.