Mutations in the fibrinogen aalpha gene account for the majority of cases of congenital afibrinogenemia.

Congenital afibrinogenemia is a rare, autosomal, recessive disorder characterized by the complete absence of detectable fibrinogen. We previously identified the first causative mutations in a nonconsanguineous Swiss family; the 4 affected persons have homozygous deletions of approximately 11 kb of the fibrinogen alpha (FGA) gene. Haplotype data implied that these deletions occurred on distinct ancestral chromosomes, suggesting that this region may be susceptible to deletion by a common mechanism.

Prophylactic antithrombotic therapy for patients with systemic lupus erythematosus with or without antiphospholipid antibodies: do the benefits outweigh the risks? A decision analysis.

Background: A high incidence of both arterial and venous thromboembolic events has been reported in patients with systemic lupus erythematosus (SLE), but the risks and benefits of primary prophylactic antithrombotic therapy have not been assessed. We measured the clinical benefit of 3 antithrombotic regimens in patients with SLE without antiphospholipid antibodies, with anticardiolipin antibodies, or with lupus anticoagulant.

Methods: A Markov decision analysis was used to evaluate prophylactic aspirin therapy, prophylactic oral anticoagulant therapy, and observation.

Inability of serial fibrin monomer measurements to predict or exclude deep venous thrombosis in asymptomatic patients undergoing total knee arthroplasty.

Fibrin monomer (FM) is a highly sensitive marker of venous thromboembolism and can be used to rule out deep venous thrombosis (DVT) and/or pulmonary embolism in symptomatic outpatients. The aim of the study was to investigate the usefulness of serial fibrin monomer determinations to predict or rule out DVT after total knee arthroplasty in asymptomatic patients. One hundred and thirty consecutive patients underwent total knee replacement.

Risk of major bleeding in unselected patients with venous thromboembolism.

Purpose: To evaluate the risk of major bleeding in unselected patients given anticoagulant treatment (heparin overlapped and followed by oral anticoagulants) because of deep vein thrombosis (DVT) or pulmonary embolism (PE).

Subjects And Methods: We screened the database of 1590 outpatients suspected of DVT and PE in prospective diagnostic studies conducted in Geneva between 1992 and 1998.

Results: Four hundred and eleven of 1590 patients (26%) were anticoagulated for confirmed venous thromboembolism (PE, 300; DVT, 111).

Massive thromboembolism due to transcatheter ASD closure with ASDOS device.

Transcatheter occlusion of atrial septal defects (ASD) is currently being investigated as an attractive alternative to surgical correction. Thromboembolic events are rare in both techniques. However, we report a case of massive systemic embolization and residual left atrial thrombus after secundum ASD transcatheter closure by the ASDOS device (Atrial Septal Defect Occlusion System, Dr.

Using clinical evaluation and lung scan to rule out suspected pulmonary embolism: Is it a valid option in patients with normal results of lower-limb venous compression ultrasonography?

Background: In patients with a low clinical probability of pulmonary embolism (PE) and a nondiagnostic lung scan, the prevalence of PE is theoretically very low. We assessed the safety and usefulness of this association for ruling out PE.

Methods: We analyzed data from 2 consecutive cohort management studies performed in 2 university hospitals (Geneva University Hospital, Geneva, Switzerland, and Hospital Saint-Luc, Montreal, Quebec), which enrolled 1034 consecutive patients who came to the emergency department with clinically suspected PE.

Interaction of anti-phospholipid antibodies with late endosomes of human endothelial cells.

Anti-phospholipid antibodies (APLAs) are associated with thrombosis and/or recurrent pregnancy loss. APLAs bind to anionic phospholipids directly or indirectly via a cofactor such as beta(2)-glycoprotein 1 (beta(2)GPI). The lipid target of APLA is not yet established.

Platelet count at term pregnancy: a reappraisal of the threshold.

Objective: To assess the safety of a new platelet count threshold for the definition of maternal thrombocytopenia late in pregnancy.

Methods: A platelet count was performed in 6770 pregnant women late in pregnancy and in 6103 of their newborns as well as in a control group of 287 age-matched nonpregnant healthy women.

Results: The prevalence of maternal thrombocytopenia (platelet count less than 150 x 10(9)/L) was 11.

Induction of immune tolerance with recombinant factor VIII in haemophilia A patients with inhibitors.

We report on 11 patients (nine unrelated and a brother pair) with severe haemophilia A and factor VIII (FVIII) inhibitor, in whom immune tolerance (IIT) was induced with recombinant FVIII (r-FVIII). Their age ranged from 11 months to 47 years. The number of exposure days (ED) at inhibitor detection varied from 11 to 130.

[Menorrhagia, hypermenorrhea and disorders of hemostasis].

Menorrhagia is a common clinical problem. About 10% of women aged between 30 and 49 take medical advice for abnormal uterine bleeding. Underlying bleeding disorders are found in about 20% of women, once pelvic abnormalities are excluded.

Contribution of noninvasive evaluation to the diagnosis of pulmonary embolism in hospitalized patients.

The effectiveness of new diagnostic tools for suspected pulmonary embolism (PE), such as clinical probability assessment, plasma D-dimer (DD) measurement and lower limb venous compression ultrasonography (US), has not been specifically studied in patients with a suspected PE occurring during hospital stay. This study applied a sequential, decision analysis-based strategy adding these instruments to a ventilation/perfusion lung scan in a cohort of 114 consecutive inpatients clinically suspected of PE in order to establish in how many patients a pulmonary angiogram could thereby be avoided. A definitive diagnosis could be established by the noninvasive protocol in 61% of these patients: normal/near-normal lung scan, 14%; high probability lung scan, 19%; clinical probability combined with lung scan result, 18%; and US, 8%.

Performances of the fibrin monomer test for the exclusion of pulmonary embolism in symptomatic outpatients.

Many studies have shown that D-dimer determinations can be used for the exclusion of venous thromboembolism in symptomatic outpatients, depending however on the method of D-dimer measurement. Another related assay, the Fibrin Monomer test which measures soluble fibrin levels in plasma by ELISA, is now available. We have evaluated the performances of this assay for the exclusion of pulmonary embolism (PE) in 426 consecutive outpatients presenting at the emergency ward of our institution.

Maternal antiplatelet antibodies in predicting risk of neonatal thrombocytopenia.

Objective: To determine the incidence of maternal antiplatelet antibodies in cases of thrombocytopenia during pregnancy, using the monoclonal antibody-specific immobilization of platelet antigens assay; and to assess the usefulness of this assay for predicting risk of neonatal thrombocytopenia.

Methods: A total of 6770 pregnant women were included in the study, and the monoclonal antibody-specific immobilization of platelet antigens assay was done when platelet counts were less than 150 x 10(9)/L. Platelet counts were determined in 6103 newborns.

Non-invasive diagnosis of venous thromboembolism in outpatients.

Background: We designed a simple and integrated diagnostic algorithm for acute venous thromboembolism based on clinical probability assessment of deep-vein thrombosis (DVT) or pulmonary embolism (PE), plasma D-dimer measurement, lower-limb venous compression ultrasonography, and lung scan to reduce the need for phlebography and pulmonary angiography.

Methods: 918 consecutive patients presenting at the emergency ward of the Geneva University Hospital, Geneva, Switzerland, and Hôpital Saint-Luc, Montreal, Canada, with clinically suspected venous thromboembolism were entered into a sequential diagnostic protocol. Patients in whom venous thromboembolism was deemed absent were not given anticoagulants and were followed up for 3 months.

Measurement of plasma D-dimer is not useful in the prediction or diagnosis of postoperative deep vein thrombosis in patients undergoing total knee arthroplasty.

Plasma D-dimer, a highly sensitive marker of venous thromboembolism, was measured using an enzyme-linked immunosorbent assay pre-operatively, on the third postoperative day, and at the time of phlebography in 118 patients undergoing elective total knee arthroplasty. Deep venous thrombosis (DVT) was detected using systematic bilateral phlebography between the eighth and 12th postoperative day in 47 (39.8%) patients.

Evaluation of a new antigen capture ELISA for detection and characterization of platelet alloantibodies.

The monoclonal antibody-specific immobilization of platelet antigens (MAIPA) assay is considered as a possible reference method for the detection of maternal alloantibodies when a foetomaternal alloimmunization is suspected. However, this method is tedious. In this study, we have compared the MAIPA results of 54 samples of mothers with (n=34) or without (n=20) alloantibodies with those obtained with a new antigen capture ELISA.

The place of D-dimer testing in an integrated approach of patients suspected of pulmonary embolism.

When a patient is suspected of having pulmonary embolism (PE), the first procedure performed in most institutions is lung scintigraphy. Here we propose an alternative diagnostic strategy based on the following sequential combination of procedures: clinical assessment, D-dimer measurement, ultrasonography of lower limbs, and lung scan. This integrated approach may rule out PE in the majority of outpatients suspected of PE and permits district hospitals without lung-scan facilities to manage approximately 50% of outpatients without referral.