[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.

[CRP in the management of bacterial infections in emergency]. / Utilité du dosage de la CRP pour la prise en charge des infections bactériennes aux urgences.

OBJECTIVES: To assess the interest of measuring CRP in emergency for diagnosing bacterial infections and making decisions about antibiotics and to compare its practical usefulness with clinicians' conclusions. METHODS: Systematic CRP measurements in 80 consecutive patients admitted to emergency ward with possible bacterial infection. RESULTS: were not transmitted to the physician in charge. Patients' files were analyzed retrospectively in two phases. In phase 1, two senior physicians assessed the diagnosis and need for antibiotics on the basis of the admission (emergency unit) files. In phase 2, a panel of experts examined the complete files (including discharge notes) to determine the likelihood of infection (obvious or probable, unlikely or excluded) and appropriateness of emergency antibiotics. Their recommendations were used as the standard, against which the usefulness of the laboratory indicators (including CRP) and decisions of the emergency physicians were assessed. ROC curves were used to determine threshold values for CRP and body temperature. We then calculated the sensitivity, positive predictive value and negative predictive value of these cutoffs and compared them with those for the phase 1 clinician recommendations. RESULTS: The study included 76 patients (mean age: 74 years): 28 presented obvious or possible infections and 21 required emergency antibiotic therapy. Mean leukocyte values did not differ between groups. For diagnosis, the threshold value of CRP was 85 mg/L and of body temperature 37.8 degrees C; for prescribing antibiotics, the values were 130 mg/L and 38 degrees C, respectively. The sensitivity, specificity, negative and positive predictive values of CRP were, respectively, 79, 81, 76, and 83% for diagnosis of bacterial infection and 71, 71, 48 and 87% for prescription of an emergency antibiotic. These values were lower than those of clinician's conclusions. CONCLUSION: Because of the variability in the thresholds used in its interpretation, the lack of specificity, and its poor predictive value for treatment decisions, CRP is of little interest in the diagnosis and treatment of patients with bacterial infections in intensive care. The cost generated by this examination is therefore not justified.

Value of autoantibodies to beta(2)-glycoprotein 1 in the diagnosis of antiphospholipid syndrome.

OBJECTIVES: To define the specificity and positive predictive value of anti-beta(2)-glycoprotein 1 (anti-beta(2)GP1) antibodies for the diagnosis of antiphospholipid syndrome (APS). METHODS: We determined the presence of anticardiolipin (aCL) antibodies and anti-beta(2)-glycoprotein 1 (anti-beta(2)GP1) immunoglobulin (Ig) G and IgM in 191 consecutive sera from 191 patients and reviewed clinical data separately. aCL IgG and IgM were detected separately using commercial ELISA kits. Anti-beta(2)GP1 antibodies were detected with an in-house ELISA using beta(2)GP1. RESULTS: Seven patients were diagnosed as having APS and 184 as having other diseases. Thirty-six patients were aCL-positive and 12 were anti-beta(2)GP1-positive, seven of these 12 were APS patients. The specificity for anti-beta(2)GP1 in our population was 97%, with a positive predictive value (PPV) of 58%. Among the aCL-positive patients, specificity was 90% and PPV 70-87%. CONCLUSIONS: This study shows that anti-beta(2)GP1 antibodies have a higher specificity and PPV than aCL for APS. The PPV of anti-beta(2)GP1 was greater in aCL-positive than in all patients. We conclude that screening for anti-beta(2)GP1 antibodies in aCL-positive patients increases the specificity and the PPV of aCL testing. In addition, we show that there is no need to screen for anti-beta(2)GP1 antibodies in the absence of aCL antibodies and in the absence of strong clinical suspicion of APS.

Systemic medium-sized vessel vasculitis associated with chronic myelomonocytic leukemia.

OBJECTIVE: To determine the clinical aspects of systemic vasculitis associated with chronic myelomonocytic leukemia (CMML). METHODS: In this retrospective study, 8 patients suffering from systemic vasculitis associated with CMML are described. The French and English literature on systemic vasculitis associated with myelodysplasia was reviewed. RESULTS: All 8 patients had a systemic medium-sized vessel vasculitis which fulfilled the American College of Rheumatology criteria for polyarteritis nodosa in the setting of active CMML. Antineutrophil cytoplasmic antibodies (ANCA) were negative in 7 patients. One patient had cytoplasmic ANCA by indirect immunofluorescence without antiproteinase 3 or antimyeloperoxydase antibodies on the enzyme-linked immunosorbent assay. At presentation, 6 patients had fever of unknown origin, 5 had polymyalgia rheumatica, 3 had sensory hearing loss, and 4 had eosinophilia. None had viral infection or drug-associated vasculitis. Diagnostic procedures included renal or hepatic angiography in 6 patients which showed microaneurysms in 4, skin and temporal artery biopsy in 2 which showed vasculitis, and 1 postmortem examination which showed gastroduodenal arteritis. All patients were treated with corticosteroids, and 7 received immunosuppressive drugs. Death was attributable to vasculitis in 2 cases, infection in 3, and other vasculitis-related causes in 2. In a review of the French-English literature, we found 11 similar cases of ANCA-negative systemic vasculitis, generally associated with refractory anemia, with or without blast excess. CONCLUSIONS: Systemic ANCA-negative polyarteritis nodosa-type vasculitis seems closely associated to CMML. Clinical presentation is nonspecific, and systemic vasculitis should be suspected when a patient with myelodysplasia develops atypical manifestations. Renal, gastrointestinal, or hepatic angiography are useful diagnostic procedures when more invasive biopsies should be avoided because of low platelet count. The prognosis of CMML-associated systemic vasculitis is poor.

[Horton's disease in elderly patients aged over 75: clinical course, complications of corticotherapy. Comparative study of 164 patients. Towards a reduced initial dose]. / Maladie de Horton du sujet âgé de plus de 75 ans: particularites évolutives, complications de la corticothérapie. Etude comparative sur une série de 164 patients. Vers une dose d'attaque réduite.

PURPOSE: Our study compares clinical and therapeutic courses (corticosteroid response, corticosteroid amount, complications) in people with giant cell arteritis before and over 75 years, during the first year of treatment. METHODS: A series of 164 patients was retrospectively analysed (mean age: 73.3 years) among the two subgroups: before 75 and over 75 years. Patient received (monitoring of reduction in the corticosteroid dosage) a 240 mg intravenous bolus of methylprednisolone followed by 0.5 or 0.7 mg/kg/d of prednisone, or 0.7 mg/kg/d of prednisone without the bolus. RESULTS: Corticosteroid response was identical for the two groups, before and over 75 (patients with corticoresistance: 15% vs 11.4%; NS) and giant cell arteritis-related complications were equivalent (n = 2 vs n = 2; NS). Corticosteroid load was slightly lower in the elderly group (cumulative dose of corticosteroids during the first year of treatment 5.2 g vs 5.8 g; P = 0.03). Patients with rheumatic side effects (collapses of vertebral bodies, mainly) were more frequent in the elderly group (15.5% vs 4.3%; P = 0.01), in spite of a limited mean follow-up period (10.7 months). CONCLUSION: Even if steroid response was identical in the therapeutic course of giant cell arteritis, rheumatic side effects appeared more frequent in the elderly group (over 75 years). In order to obtain a corticosteroid-sparing effect, new studies are necessary to evaluate a reduced initial dosage of corticosteroids.

Systemic antineutrophil cytoplasmic antibody vasculitis associated with lymphoid neoplasia.

Two cases of systemic antineutrophil cytoplasmic antibody (ANCA) vasculitis in the setting of chronic lymphocytic leukaemia and angioimmunoblastic lymphadenopathy type T cell lymphoma are reported. The two patients had fever of unknown origin associated with cutaneous vasculitis and "pulmonary-renal syndrome" with alveolar haemorrhage. Despite anti-infectious treatments, steroids, and chemotherapy, the vasculitis had a fatal paraneoplastic course in several weeks. When infection is excluded in patients with malignancy, atypical features should be promptly investigated for systemic vasculitis, and an ANCA test performed.

A randomized, multicenter, controlled trial using intravenous pulses of methylprednisolone in the initial treatment of simple forms of giant cell arteritis: a one year followup study of 164 patients.

OBJECTIVE: (1) To evaluate the corticosteroid sparing effect of an initial intravenous (i.v.) pulse of methylprednisolone (MP) in the treatment of simple forms of giant cell arteritis (GCA). (2) To analyze corticosteroid response, steroid related side effects, and GCA complications. METHODS: Patients received a 240 mg i.v. pulse of MP followed by 0.7 mg/kg/day oral prednisone (Group 1) or 0.7 mg/kg/day prednisone without an i.v. pulse (Group 2, controls), or a 240 mg i.v. pulse of MP followed by 0.5 mg/kg/day prednisone (Group 3). Corticosteroid dosage was reduced after normalization of 2 biological inflammatory variables to obtain half-dosage after 4 weeks in Groups 1 and 2 and 20 mg/day after 2 weeks in Group 3. Tapering was systematically attempted from the 6th month of treatment. RESULTS: One hundred sixty-four patients were included in the trial (1992-96). Cumulative doses of corticosteroids after one year were identical for all groups (p = 0.39). No significant differences were observed in the time required for normalization of C-reactive protein, corticosteroid resistance (13.5%), and corticosteroid related side effects (39% of patients; p = 0.37). Corticosteroid resistant patients received larger doses and showed a high risk of GCA related complications (p = 0.02). CONCLUSION: MP pulses have no significant longterm, corticosteroid sparing effects in the treatment of simple forms of GCA and should be limited to complicated forms. Moreover, corticosteroid resistance is a real risk factor for GCA complications.

[Treatment of venous thromboembolic disease in the elderly]. / Traitement de la maladie thromboembolique veineuse chez le sujet âgé.

The incidence of deep vein thrombosis and pulmonary embolism is higher in the elderly due to the greater frequency of risk factors among this age group. Classic treatment with heparin and subsequently oral anticoagulant is still the most commonly used. Older patients may be at increased risk for anticoagulant-related bleeding for several reasons: increased anticoagulant effect of warfarin, increased prevalence of comorbidity and incidence of adverse drug reactions. As well as the usual contra-indications to such treatment, the psychological and physical well being of the patient must be assumed before an oral anticoagulant can be given. Careful prescribing is required: a low starting dose, a strict monitoring regime, for a limited duration. The indications for use of an inferior vena cava filter are wider in the older age group, not only for those in whom heparin is contraindicated, or has failed, but also for those who require treatment indefinitely with contra-indications to oral anticoagulant. Careful consideration of risk factors and the use of an individually designed prophylactic treatment are the best way to tackle this difficult problem in the elderly person.

Coagulation activation in patients with an inflammatory syndrome: is there a link with acquired protein S deficiency?

The pathogenic mechanisms of thrombosis during inflammatory syndromes are unknown. The aim of our study was to evaluate coagulation activation and fibrinolysis and to study an acquired protein S deficiency in 58 patients with an inflammatory syndrome of neoplastic (16), infectious (24) or systemic (18) origin and in 54 control subjects. The results indicated that coagulation activation, demonstrated by an increase in the prothrombin fragment 1+2, was present in patients with an inflammatory syndrome regardless of its origin. Free protein S, the only functionally active protein, was not reduced even though C4b-binding protein was increased in inflammatory syndromes. Thus, a prothrombotic state was found in inflammatory syndromes but is not explained by an acquired protein S deficiency. All except five patients had normal plasminogen activator inhibitor-1 levels.

[Mesenteric venous thrombosis and antithrombin III deficiency: diagnosis before an acute digestive hemorrhage]. / Thrombose veineuse mésentérique et déficit en antithrombine III: diagnostic devant une hémorragie digestive aiguë.

Mesenteric venous thromboses are often associated with antithrombin III deficiency. We can suspect this clinical diagnosis in patients with nonspecific abdominal pain syndrome and personal or familial history of mesenteric venous thrombosis. We report the case of a 63-old-male caucasian with antithrombin III deficiency and rectal bleeding who was diagnosed with mesenteric venous thrombosis at exploratory laparotomy. This case emphasizes the necessity of a careful history in all patients without an obvious diagnosis. In this way, we can invoke the diagnosis of mesenteric venous thrombosis quickly and begin the heparin therapy while waiting for the results of further confirmatory tests.

Atrial myxoma mimicking systemic disease. Profile modified by flurbiprofen administration.

A patient had a left atrial myxoma which was modified by flurbiprofen administration. The diagnosis was made 42 months after the first symptoms appeared. Flurbiprofen may have reduced interleukin-6 secretion by the tumor, leading to a delayed diagnosis.

[Pregnancy in primary antiphospholipid syndrome. Proposal for a common management protocol]. / Grossesse dans le syndrome primaire des antiphospholipides. Proposition pour une prise en charge uniciste.

OBJECTIVE: Primary antiphospholipid syndrome (APS) is by definition associated with high obstetric risk. We performed a retrospective study of pregnancies in women with this syndrome in an attempt to define a common means of caring these patients. STUDY DESIGN: Women with APS followed in Internal Medicine Department and in Gynecology Department since 1989 were studied retrospectively. RESULTS: Fifteen women with primary APS had a total of 51 pregnancies, 39 (76%) of which ended in embryonic (n = 24) or fetal (n = 15) loss. Only 6/39 untreated pregnancies led to a live birth, including 2 cases of intrauterine growth retardation. Among the 12 pregnancies treated preventively for obstetric complications, 6 led to a live birth. The treatments used were dissimilar and included aspirin, corticosteroids and heparin, either alone or in association. Four of these 6 live births were obtained by aspirin alone. Gravidic toxemia was observed in one untreated patient. CONCLUSION: The obstetric prognosis for untreated APS is appalling. The benefit of heparin therapy in association with aspirin remains to be demonstrated, ideally in a protocol comparing aspirin alone with aspirin and heparin.

Angiomagnetic resonance imaging of iliofemorocaval venous thrombosis.

Although magnetic resonance imaging has been proposed for the diagnosis of deep venous thrombosis (DVT), its role in diagnostic strategy remains to be defined. We compared prospectively magnetic resonance angiography (MRA) with two-dimensional time-of-flight with contrast venography (CV) and colour duplex sonography (CDS) in 25 patients with DVT of the pelvis confirmed by CV. All patients were examined by CV (gold standard) and MRA and 17 by CDS. These studies were compared for DVT diagnosis in the pelvis and inferior vena cava and analysis of thrombotic spread. MRA was positive in 25 patients whose DVT was diagnosed by CV (100% sensitivity). MRA sensitivity and negative predictive value were 100%, specificity 98.5% and positive predictive value 97.5% for the diagnosis of thrombosis at each anatomic level. There were discrepancies between MRA and CV (2 false-positive results for 2 venous segments) and between CDS and CV (2 false-positive and 3 false-negative results). CV was uninterpretable for 8.8% of segments and CDS was often technically limited to the pelvic level, whereas all venous segments explored were analysable in MRA. MRA gave excellent results for positive diagnosis and DVT spread. MRA is a potentially valuable technique for assessing iliofemorocaval venous thrombosis.

[Diagnosis of venous thrombosis. Evaluation of immunoscintigraphy with 99M technetium labelled antifibrin]. / Diagnostic des thromboses veineuses. Evaluation de l'immunoscintigraphie antifibrine marquée au technétium 99m.

OBJECTIVES: We evaluated the interpretation, reliability and usefulness of 99m technetium labelled antifibrin immunoscintigraphy for the diagnosis of deep vein thrombosis in the lower limbs. METHODS: The diagnostic value of 99m technetium labelled antifibrin immunoscintigraphy was assessed in 44 patients with suspected venous thrombosis. The reference examination was bilateral ascending phlebography; 40 patients had doppler ultrasonography of the veins; 0.5 mg of antibody labelled by 17.5 mCi on average of 99m technetium were injected intravenously, and serial scintigraphic images were collected 1 min, 90 min and 18 hours after injection. RESULTS: The best results were obtained by comparison between the 90 min and the immediate post-injection images, with 86 percent sensitivity, 73 percent specificity and 81 percent accuracy. Heparin therapy and past history of phlebitis had no influence on the results. The doppler ultrasonography/immunoscintigraphy combination had a 100 percent specificity. 99m Technetium labelled antifibrin immunoscintigraphy had about the same diagnostic value as 111 indium labelled antifibrin immunoscintigraphy. CONCLUSION: The introduction of 99m technetium as isotopic marker will make immunoscintigraphy easier and available in numerous nuclear medicine centres. Antifibrin immunoscintigraphy can be an additional diagnostic tool for the difficult diagnosis of deep vein thrombosis.