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BACKGROUND: Hemophilia is a inherited bleeding disorder that is characterized by intra-articular bleeding (hemarthrosis). The aim of the study was to evaluate the state of the satellite tendons of the target joints in the patient with hemophilic arthropathy and propose rehabilitation treatment with eccentric exercises. METHODS: The tendons of the joints mainly affected by hemophilic arthropathy were evaluated by ultrasound. The ultrasound evaluation is associated with the use of evaluation clinical scales, such as the Hemophilia Joint Health Score (HJHS), the Functional Independence Score in Hemophilia (FISH), the Hemophilia Activity List (HAL), the DASH, the VISA-A, the VISA-P, and the VAS scale. RESULTS: In 20 patients with hemophilic arthropathy, the thickness of the tendons that were examined was normal. In six subjects with severe joint damage, echostructural alterations were present, and signs of hyperemia and neo-vascularization were detected on color Doppler, as well as the presence of intratendinous calcifications. CONCLUSIONS: The tendons of the target joints in patients with hemophilic arthropathy are compromised by the indirect biomechanical damage caused by the joint disease, and rehabilitation treatment with eccentric exercises can be considered safe and effective in improving the tenso-elastic properties of the tendons.
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INTRODUCTION: Haemophilias are X-linked inherited bleeding disorders, due to de novo F8/F9 gene variants in 30-50% of cases. The identification of causative variant in index cases (IC) is crucial for genetic counselling in related women. Over the last 20 years the Emilia-Romagna Regional Haemophilia Registry documented high proportions of sporadic severe haemophilia. AIM: To clarify if carriers' reproductive choices influence the sporadic/familial ratio of severe haemophilia. METHODS: Genetic counselling and genotyping in 221 relatives of severe IC were retrospectively reviewed, retrieving reproductive choices and pregnancy history of childbearing-age carriers from familial and sporadic pedigrees and according to the IC degree of relationship (mothers, daughters, II/other). RESULTS: Carriers' identification rates were lower in sporadic women and in other-degree relatives. Among childbearing age women (n = 140), carriers were 37/48 (77%) and 57/92 (62%) of familial and sporadic relatives, respectively. Forty-five/57 sporadic carriers experienced 67 pregnancies, while 21/37 familial carriers had 39 pregnancies (four voluntary terminations), with a significantly higher number of affected sons in the former (40/67 vs. 12/35, P = .025). Prenatal diagnosis was chosen by 40% and 47% of sporadic and familial aware carriers, respectively. Sporadic mothers often avoided further pregnancies (17/38, 45%) after a firstborn affected child, while familial mothers tended to face pregnancies without prenatal approaches (6/10, 60%). CONCLUSION: In this cohort sporadic offspring account for more than 70% of severe haemophilia cases. This increasing proportion is likely to reflect the influence in reproductive choices of awareness of carriers' status, particularly in sporadic mothers, and of prenatal diagnosis options.
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Tomada de Decisões , Hemofilia A , Gravidez , Feminino , Hemofilia A/diagnóstico , Hemofilia A/epidemiologia , Hemofilia A/genética , Heterozigoto , Humanos , Gravidez/psicologia , Sistema de Registros , História Reprodutiva , Estudos RetrospectivosRESUMO
BACKGROUND: In older people, multiple chronic ailments lead to the intake of multiple medications (polypharmacy) that carry a number of negative consequences (adverse events, prescription and intake errors, poor adherence, higher mortality). Because ageing patients with haemophilia (PWHs) may be particularly at risk due to their pre-existing multiple comorbidities (arthropathy, liver disease), we chose to analyse the pattern of chronic drug intake in a cohort of PWHs aged 60 years or more. PATIENTS AND METHODS: S + PHERA is a multicentre observational study, with the broad goal to evaluate prospectively the health status and medication intake in 102 older patients with severe haemophilia A or B compared with 204 age- and residence-matched controls chosen randomly from the same general practices of PWHs. The rate of potential drug-drug interactions (PDDI) was evaluated as a proxy of prescription appropriateness. RESULTS: After excluding replacement therapies and antiviral drugs, PWHs took in average less daily drugs than controls (2.4 ± 2.5 vs 3.0 ± 2.4) and had a lower rate of polypharmacy. Moreover, their prevalence of PDDI was lower (16.7% vs 27%). CONCLUSIONS: The rate of polypharmacy and the appropriateness of medications other than those for haemophilia and related comorbidities are acceptable in Italian PWHs, and better than those in their age peers without haemophilia, perhaps owing to drug tailoring and deprescribing by the specialized haemophilia centres at the time of regular visits. However, the PWHs investigated herewith were relatively young and the rate of polypharmacy and related PDDIs may become more prominent and crucial when older ages are reached, suggesting the need of continuous surveillance on prescribed drugs and the risk of drug-drug interactions.
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Hemofilia A/tratamento farmacológico , Polimedicação , Fatores Etários , Feminino , Hemofilia A/patologia , Humanos , Masculino , Prevalência , Fatores de RiscoRESUMO
BACKGROUND: Laboratory investigation with specific factor XIII (FXIII) assays plays a crucial role in diagnosis of FXIII deficiency. According to the International Society on Thrombosis and Hemostasis (ISTH), it is necessary a blank sample with iodoacetamide, provided by the kit or locally prepared, when the ammonia release assays are used, to avoid FXIII activity overestimation. METHODS: In this study we set up a modification of the Berichrom FXIII chromogenic assay, in which iodoacetamide was added by the BCS analyzer in the reaction mixture of the blank sample, without modifications of the original reagents. We analyzed 100 plasma samples of outpatients with clinical symptoms suggestive of a bleeding diathesis (20 samples had FXIII activity <20%). RESULTS: In all samples blank subtraction significantly reduced FXIII activity, mostly in the low activity range group (from 10.1% to 2.4%, p<0.0001). In this group correction with iodoacetamide also increased the agreement with the immunoassay and allowed FXIII activity measure up to 0%. CONCLUSIONS: Despite the low number of samples included in the study, the described automatic procedure seemed to decrease FXIII activity overestimation and, especially for low activity range samples (<20%), to improve the agreement between FXIII activity and concentration. Our data suggested that iodoacetamide correction could allow the detection of severe FXIII deficiencies (activity <5%) otherwise undiagnosed using the original method.
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Amônia/química , Automação , Análise Química do Sangue , Deficiência do Fator XIII/diagnóstico , Fator XIII/análise , Iodoacetamida/química , Adulto , Fator XIII/metabolismo , Deficiência do Fator XIII/sangue , Feminino , Humanos , MasculinoRESUMO
Rigorous evidence is lacking on long-term outcomes of factor VIII (FVIII) prophylaxis initiated in adolescent or adult patients with severe haemophilia A. The prospective, open-label Prophylaxis versus On-demand Therapy Through Economic Report (POTTER) study (ClinicalTrials.gov NCT01159587) compared long-term late secondary prophylaxis (recombinant FVIII-FS 20-30 IU/kg thrice weekly) with on-demand treatment in patients aged 12 to 55 years with severe haemophilia A. The annual number of joint bleeding episodes (primary endpoint), total bleeding episodes, orthopaedic and radiologic (Pettersson) scores, health-related quality of life (HRQoL), pharmacoeconomic impact, and safety were evaluated over a > 5-year period (2004-2010). Fifty-eight patients were enrolled at 11 centres in Italy; 53 (27 prophylaxis, 26 on demand) were evaluated and stratified into 2 age subgroups (12-25 and 26-55 years). Patients receiving prophylaxis experienced a significantly lower number of joint bleeding episodes vs the on-demand group (annualised bleeding rate, 1.97 vs 16.80 and 2.46 vs 16.71 in younger and older patients, respectively; p=0.0043). Results were similar for total bleeding episodes. Prophylaxis was associated with significantly fewer target joints (p< 0.001), better orthopaedic (p=0.0019) and Pettersson (p=0.0177) scores, better HRQoL, and fewer days of everyday activities lost (p< 0.0001) but required significantly higher FVIII product consumption. The POTTER study is the first prospective, controlled trial documenting long-term benefits of late secondary prophylaxis in adolescents and adults with severe haemophilia A. The benefits of reduced bleeding frequency, improved joint status, and HRQoL may offset the higher FVIII consumption and costs.
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Fator VIII/administração & dosagem , Hemartrose/prevenção & controle , Hemofilia A/tratamento farmacológico , Hemostáticos/administração & dosagem , Adolescente , Adulto , Fatores Etários , Criança , Análise Custo-Benefício , Esquema de Medicação , Custos de Medicamentos , Fator VIII/efeitos adversos , Fator VIII/economia , Hemartrose/sangue , Hemartrose/diagnóstico , Hemartrose/economia , Hemofilia A/sangue , Hemofilia A/diagnóstico , Hemofilia A/economia , Hemostáticos/efeitos adversos , Hemostáticos/economia , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE: Warfarin dosing is affected by clinical and genetic variants, but the contribution of the genotype associated with warfarin resistance in pharmacogenetic algorithms has not been well assessed yet. We developed a new dosing algorithm including polymorphisms associated both with warfarin sensitivity and resistance in the Italian population, and its performance was compared with those of eight previously published algorithms. METHODS: Clinical and genetic data (CYP2C9*2, CYP2C9*3, VKORC1 -1639 G > A, and VKORC1 3730 G > A) were used to elaborate the new algorithm. Derivation and validation groups comprised 55 (58.2% men, mean age 69 years) and 40 (57.5% men, mean age 70 years) patients, respectively, who were on stable anticoagulation therapy for at least 3 months with different oral anticoagulation therapy (OAT) indications. RESULTS: Performance of the new algorithm, evaluated with mean absolute error (MAE) defined as the absolute value of the difference between observed daily maintenance dose and predicted daily dose, correlation with the observed dose and R(2) value, was comparable with or slightly lower than that obtained using the other algorithms. The new algorithm could correctly assign 53.3%, 50.0%, and 57.1% of patients to the low (≤25 mg/week), intermediate (26-44 mg/week) and high (≥ 45 mg/week) dosing range, respectively. Our data showed a significant increase in predictive accuracy among patients requiring high warfarin dose compared with the other algorithms (ranging from 0% to 28.6%). CONCLUSIONS: The algorithm including VKORC1 3730 G > A, associated with warfarin resistance, allowed a more accurate identification of resistant patients who require higher warfarin dosage.
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Anticoagulantes/administração & dosagem , Oxigenases de Função Mista/genética , Varfarina/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Hidrocarboneto de Aril Hidroxilases/genética , Hidrocarboneto de Aril Hidroxilases/metabolismo , Citocromo P-450 CYP2C9 , Relação Dose-Resposta a Droga , Resistência a Medicamentos , Etnicidade , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Oxigenases de Função Mista/metabolismo , Polimorfismo de Nucleotídeo Único , Vitamina K Epóxido Redutases , Adulto JovemRESUMO
Intracranial haemorrhage (ICH) is the most serious bleeding symptom in haemophiliacs, resulting in high rates of mortality and disabling sequelae. The Association of Italian Haemophilia Centres carried out a retrospective survey (1987-2008) of ICH occurring in haemophiliacs with the goals to establish: (i) incidence, location of bleeding, death rate and disabling sequels; (ii) risk factors for ICH; and (iii) treatment used during the acute phase of ICH and for recurrence prevention. A total of 112 ICH episodes had occurred in 88 patients (78 haemophilia A, 10 haemophilia B), 24 of whom experienced recurrences. The cumulative hazard of ICH for the whole cohort over the entire follow-up period was 26.7 per 1000 patients, and the annualized rate of ICH was 2.50 events per 1000 patients (95% CI 1.90-3.31). The risk of ICH was higher in the youngest children (24.4 per 1000, 95% CI 12.7-47.0 in the first year of age and 14.9, 95% CI 7.1-31.4 in the second year of age) and then progressively rose again after the age of 40. Univariate, bivariate (age-adjusted) and multivariate analysis investigating the effects of patient characteristics on ICH occurrence showed that haemophilia severity and inhibitor status were strongly associated with ICH [severe vs. mild, HR 3.96 (2.39-6.57); inhibitor vs. non-inhibitor 2.52 (1.46-4.35)]. HCV infection was also associated with the risk of ICH [HR 1.83 (1.25-2.69)]. Therapeutic suggestions based upon our experience to control ICH recurrence are provided.
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Hemofilia A/complicações , Hemofilia B/complicações , Hemorragias Intracranianas/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Autoanticorpos/sangue , Fatores de Coagulação Sanguínea/uso terapêutico , Criança , Pré-Escolar , Estudos de Coortes , Hemofilia A/imunologia , Hemofilia B/imunologia , Humanos , Incidência , Lactente , Recém-Nascido , Hemorragias Intracranianas/prevenção & controle , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Inquéritos e Questionários , Adulto JovemRESUMO
INTRODUCTION: Though thrombin-activatable fibrinolysis inhibitor (TAFI) may contribute to hypercoagulability during pregnancy, limited data are available on the role of TAFI in women with recurrent fetal loss. MATERIAL/METHODS: We performed a case-control study aimed at evaluating any possible association between TAFI levels and early recurrent fetal loss (≥ 3, or 2 with at least one normal fetal karyotype, before the 10th week of gestation). 140 women with early recurrent fetal loss and 140 age-matched healthy controls with at least one normal pregnancy were included. The number of miscarriages was 2.59 and occurred at gestational age 6.89 weeks. TAFI levels were determined by a chromogenic assay measuring total potential activatable TAFI. RESULTS: TAFI levels were significantly lower in early recurrent fetal loss women (12.2 ± 2.3 µg/ml vs 13.2 ± 2.6 µg/ml in healthy controls, p=0.001). ORs of early recurrent fetal loss (crude and adjusted for possible confounding variables) were calculated after stratification of TAFI levels into quartiles. 25/140 (17.8%) early recurrent fetal loss women had TAFI levels above 14.0 µg/ml (4th quartile) vs 44/140 (31.3%) in healthy women (p=0.014). Crude and adjusted ORs of early recurrent fetal loss in women with TAFI levels in the 4th quartile vs those in the reference category (1st quartile=below 11.0 µg/ml) were 0.42 (95%CI: 0.22-0.82) and 0.39 (95%CI: 0.19-0.80), respectively. CONCLUSIONS: Our study provides evidence that high TAFI levels are associated with reduced risk of early recurrent fetal loss. Further studies are needed to better understand the actual role of TAFI in recurrent fetal loss.
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Aborto Habitual/sangue , Carboxipeptidase B2/sangue , Aborto Habitual/epidemiologia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Gravidez , Fatores de RiscoAssuntos
Fator IX , Fator VIII , Hemofilia A , Hemofilia B , Fator IX/administração & dosagem , Fator IX/economia , Fator VIII/administração & dosagem , Fator VIII/economia , Feminino , Hemofilia A/economia , Hemofilia A/prevenção & controle , Hemofilia B/economia , Hemofilia B/prevenção & controle , Humanos , Itália , Masculino , Inquéritos e QuestionáriosRESUMO
The natural history of calf deep-vein thrombosis (DVT) is still uncertain and it is debated whether it warrants to be diagnosed and treated. We aimed to investigate the complication rate of untreated isolated calf DVT (ICDVT). Symptomatic outpatients were prospectively managed with serial compression ultrasonography (SCUS). Those without proximal DVT and with likely pre-test clinical probability (PCP) or altered D-dimer received immediate subsequent complete examination of calf deep veins (CCUS) by a different operator. The result of CCUS was kept blind both to the managing doctor and the patient and disclosed after three months. Primary outcome was the rate of venous thromboembolism at three months. We examined 431 subjects (196 males; median age 68.0 years) in whom five outcomes were recorded (1.2%; 95% confidence intervals [CI]: 0.4-2.7). If CCUS results had been available, outcomes would have been recorded in 3/424 patients (0.7%; 95% CI: 0.2-2.1) with two events in subjects negative at both serial and complete CUS. ICDVT was diagnosed in 65 subjects (15.3%; 95% CI: 12-19); of whom 59 remained uneventful (one was lost to follow-up). A significant higher rate of outcomes was recorded in subjects with than without ICDVT (5/64; 7.8%; 95% CI: 3-17 vs. 3/351; 0.8%; 95% CI: 0-2; p=0.003). However, after excluding two events picked at serial CUS in subjects with ICDVT, the difference became barely significant (3/64; 4.7%; 95% CI: 1-13; p=0.049). Thrombotic evolution of untreated ICDVT in high-risk subjects may be relevant. Larger studies are needed to address this issue.
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Perna (Membro)/irrigação sanguínea , Tromboembolia Venosa/etiologia , Trombose Venosa/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Distribuição de Qui-Quadrado , Progressão da Doença , Método Duplo-Cego , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Imunoensaio , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Ultrassonografia Doppler em Cores , Tromboembolia Venosa/sangue , Tromboembolia Venosa/diagnóstico por imagem , Trombose Venosa/sangue , Trombose Venosa/diagnóstico por imagem , Adulto JovemRESUMO
BACKGROUND: Congenital thrombophilia is a risk factor for venous thromboembolism (VTE). Whether it is associated with increased risk of arterial disease is today a matter of debate. We aimed to look for early signs of atherosclerotic alterations in carriers of inherited thrombophilic alterations (ITA). METHODS: Between January 2006 and September 2008 ultrasonography assessment of the carotid arteries with measurement of intima-media thickness (IMT), and determination of the ankle/brachial pressure index (ABI), was performed in: a) 161 carriers of ITA (deficiency of antithrombin, protein C or S, factor V Leiden or prothrombin G20210A mutations), 84 of whom with previous VTE, and b) 180 subjects without ITA, matched for age, sex and previous VTE. All subjects were <66 year old. RESULTS: Carotid plaques were found in 8 subjects [3 (1.9%) with ITA]. Increased IMT values (>1mm) were detected in 6 subjects with and 1 without thrombophilia (p=0.055). The prevalence of IMT values>90(th) percentile was not different in subjects with/without thrombophilia (15.2% vs 11.6%, p=0.416). At multivariate analysis only age was significantly associated with increased odds ratios for IMT values>90(th) percentile. No subjects had abnormal (<0.9) ABI values. CONCLUSIONS: The present study, the first to investigate the presence of atherosclerotic markers in relatively young subjects with inherited thrombophilia, did not find a particular prevalence of signs of early atherosclerotic markers in these subjects.
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Aterosclerose/etiologia , Heterozigoto , Trombofilia/complicações , Idoso , Aterosclerose/genética , Aterosclerose/patologia , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Fatores de Risco , Estatísticas não Paramétricas , Trombofilia/genética , Trombofilia/patologia , UltrassonografiaRESUMO
BACKGROUND: Venous thromboembolism (VTE) is a major complication of myeloma therapy recently observed with the increasing use of up-front thalidomide and dexamethasone (thal-dex). The pathogenesis of thal-induced VTE is not well recognized, and the role of prothrombotic factors, especially of thrombophilic abnormalities, is not yet determined. MATERIAL AND METHODS: Two hundred and sixty-six patients with newly diagnosed multiple myeloma (MM) were primarily treated with thal-dex in preparation for subsequent high-dose therapy and autologous stem-cell transplantation. Out of these 266 patients, 190 were evaluated for thrombophilic alterations at baseline, and 125 of them were also re-assessed after thal-dex therapy. RESULTS: The presence of genetic thrombophilic polymorphisms among patients with MM was superimposable to that of normal controls and was associated with a twofold increase in the relative risk of VTE. aAPCR and elevated factor VIII levels were frequent, albeit transient, alterations and were not associated with a significant increase in the risk of VTE. Two hundred and forty-six patients received a thromboprophylaxis with fixed low-dose warfarin (1.25 mg/day) during thal-dex therapy. Of these patients (or 10.6%), 26 had symptomatic VTE events. Their patients-years rate of VTE (35.5%) was significantly lower in comparison with the 86.2% rate recorded among the first 19 patients who initially entered the study and did not receive any kind of thromboprophylaxis (P = 0.043). CONCLUSIONS: On the basis of these data, a baseline thrombophilic work up is not recommended in patients with receiving up-front thal-dex. For these patients, fixed low-dose warfarin may be a valuable prophylaxis against VTE.
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Dexametasona/administração & dosagem , Mieloma Múltiplo/tratamento farmacológico , Talidomida/administração & dosagem , Trombofilia/induzido quimicamente , Trombose/induzido quimicamente , Trombose/prevenção & controle , Resistência à Proteína C Ativada/genética , Adulto , Idoso , Anticoagulantes/administração & dosagem , Estudos de Casos e Controles , Dexametasona/efeitos adversos , Fator V/genética , Fator VIII/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Protrombina/genética , Fatores de Risco , Talidomida/efeitos adversos , Trombofilia/sangue , Trombofilia/genética , Tromboembolia Venosa/induzido quimicamente , Tromboembolia Venosa/prevenção & controle , Varfarina/administração & dosagemRESUMO
Atrial fibrillation (AF) is a common arrhythmia that results in a high risk of cerebral and peripheral embolism. Factor V Leiden and factor II G20210A variant are two leading conditions for venous thrombosis. The aim of our study was to find out whether these two common prothrombotic mutations play a role in the occurrence of embolic events in AF patients. We investigated 336 non-valvular AF patients and 336 healthy control subjects. Factor II G20210A variant was found in 24/336 patients (7.14%) and in 11/336 of control subjects (3.3%). At a multivariate analysis, factor II G20210A variant was independently associated to AF (OR 2.4 95% CI 1.1-5.2; p<0.05). No significant difference was observed in the prevalence of factor V Leiden in the two groups investigated [6/304 (2.0%) in patients vs 13/336 (3.9%) in controls (p=0.24)]. AF patients were separately analyzed in relation to the occurrence or absence of a cerebral or peripheral embolic event (200 with and 136 without embolic event). The prevalence of the two mutations among AF patients with and without an embolic event was similar [factor II G20210A polymorphism (7% and 7.3% respectively) and factor V Leiden (1.2% and 2.9%, respectively)]. No differences were found in relation to the type of embolic event. Our results suggest a possible relationship between the presence of prothrombin gene variant and AF per se.
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Fibrilação Atrial/complicações , Fibrilação Atrial/genética , Mutação , Polimorfismo de Nucleotídeo Único , Protrombina/genética , Tromboembolia/genética , Trombofilia/genética , Fibrilação Atrial/sangue , Estudos de Casos e Controles , Análise Mutacional de DNA , Fator V , Prevalência , Fatores de Risco , Tromboembolia/epidemiologia , Tromboembolia/etiologiaRESUMO
BACKGROUND: We have shown that normal D-dimer levels obtained after the discontinuation of oral anticoagulant treatment (OAT) has a high negative predictive value for recurrent venous thromboembolism (VTE). The aim of the present study was to assess the predictive value of D-dimer for recurrent VTE in subjects with a previous unprovoked event who are either carriers of inherited thrombophilia or not. METHODS AND RESULTS: We prospectively evaluated 599 patients (301 males) with a previous VTE episode. They were repeatedly examined for D-dimer levels after OAT withdrawal and were screened for inherited thrombophilic alterations. Alterations were detected in 130 patients (21.7%), factor V Leiden (70 patients; 2 of whom were homozygotes) and prothrombin mutation (38 patients) were the most prevalent ones. Recurrent events were recorded in 58 subjects (9.7%) during a follow-up of 870.7 patient-years. Altered D-dimer levels at 1 month after OAT withdrawal were associated with a higher rate of subsequent recurrence in all subjects investigated, especially in those with an unprovoked qualifying VTE event (hazard ratio, 2.43; 95% confidence interval, 1.18 to 4.61) and in those with thrombophilia (hazard ratio, 8.34; 95% confidence interval, 2.72 to 17.43). The higher relative risk for recurrence of altered D-dimer was confirmed by multivariate analysis after adjustment for other risk factors. The negative predictive value of D-dimer was 92.9% and 95.8% in subjects with an unprovoked qualifying event or with thrombophilia, respectively. CONCLUSIONS: D-dimer levels measured 1 month after OAT withdrawal have a high negative predictive value for recurrence in subjects with unprovoked VTE who are either carriers or not carriers of congenital thrombophilia.