Morbidity and mortality in the antiphospholipid syndrome during a 10-year period: a multicentre prospective study of 1000 patients.

OBJECTIVES: To assess the prevalence of the main causes of morbi-mortality in the antiphospholipid syndrome (APS) during a 10-year-follow-up period and to compare the frequency of early manifestations with those that appeared later. METHODS: In 1999, we started an observational study of 1000 APS patients from 13 European countries. All had medical histories documented when entered into the study and were followed prospectively during the ensuing 10 years. RESULTS: 53.1% of the patients had primary APS, 36.2% had APS associated with systemic lupus erythematosus and 10.7% APS associated with other diseases. Thrombotic events appeared in 166 (16.6%) patients during the first 5-year period and in 115 (14.4%) during the second 5-year period. The most common events were strokes, transient ischaemic attacks, deep vein thromboses and pulmonary embolism. 127 (15.5%) women became pregnant (188 pregnancies) and 72.9% of pregnancies succeeded in having one or more live births. The most common obstetric complication was early pregnancy loss (16.5% of the pregnancies). Intrauterine growth restriction (26.3% of the total live births) and prematurity (48.2%) were the most frequent fetal morbidities. 93 (9.3%) patients died and the most frequent causes of death were severe thrombosis (36.5%) and infections (26.9%). Nine (0.9%) cases of catastrophic APS occurred and 5 (55.6%) of them died. The survival probability at 10 years was 90.7%. CONCLUSIONS: Patients with APS still develop significant morbidity and mortality despite current treatment. It is imperative to increase the efforts in determining optimal prognostic markers and therapeutic measures to prevent these complications.

Does the type of fluid affect rapidity of shock reversal in an anaesthetized-piglet model of near-fatal controlled haemorrhage? A randomized study.

BACKGROUND: The optimal resuscitation fluid for the early treatment of severe bleeding patients remains highly debated. The objective of this experimental study was to compare the rapidity of shock reversal with lactated Ringer (LR) or hydroxyethyl starch (HES) 130/0.4 at the early phase of controlled haemorrhagic shock. To assess the influence of vascular permeability in this model, we measured plasma vascular endothelial growth factor (VEGF) levels during the experiment. METHODS: Thirty-six anaesthetized and mechanically ventilated piglets were bled (<30 ml kg(-1)) to hold mean arterial pressure (MAP) at 40 mm Hg for more than 30 min and were resuscitated in two randomized groups: LR (n=14) or HES (n=14) at 1 ml kg(-1) min(-1) until MAP reached its baseline value of ±10%. MAP was maintained at its baseline value for 1 h. The time and fluid volume necessary to restore the baseline MAP value were measured. RESULTS: The time to restore the baseline MAP value of ±10% was significantly lower in the HES group (P<0.001). During the initial resuscitation phase, the infused volume was 279 (119) ml in the HES group and 1011 (561) ml in the LR group (P<0.0001). During the stabilization phase, the infused volume was 119 (124) ml in the HES group and 541 (506) ml in the LR group. Biological data and plasma VEGF levels were similar between the groups. CONCLUSIONS: Restoration of MAP was four times faster with HES than with LR in the early phase of controlled haemorrhagic shock. However, there was no evidence of increased vascular permeability.

Thrombotic microangiopathy, DIC-syndrome and COVID-19: link with pregnancy prothrombotic state.

For last months, humanity has faced a formidable unknown enemy, which is presented as a new coronavirus infection. Despite the fact that the causative agents of new diseases appear at a certain frequency and that the virus SARS-CoV-2 has certain common properties with its predecessors, at the moment we are dealing with a new unknown pathogenesis of the development of severe complications in patients with risk factors. A final understanding of pathological process mechanisms is the goal of the scientific community. Summarizing research data from different countries, it became obvious that in severe cases of viral infection, we are dealing with a combination of the systemic inflammatory response syndrome, disseminated intravascular coagulation and thrombotic microangiopathy (TMA). Thrombotic microangiopathy is represented by a group of different conditions in which thrombocytopenia, hemolytic anemia, and multiple organ failure occur. The article reflects the main types of TMA, pathogenesis and principles of therapy. The main participants in the process are described in detail, including the von Willebrand factor and ADAMTS-13. Based on the knowledge available, as well as new data obtained from patients with COVID-19, we proposed possible models for the implementation of conditions such as sepsis, TMA, and DIC in patients with severe new coronavirus infection. Through a deeper understanding of pathogenesis, it will be possible to develop more effective diagnosis and therapy.

Management of cancer-related thrombosis in the era of direct oral anticoagulants: A comprehensive review of the 2019 ITAC-CME clinical practice guidelines. On behalf of the Groupe Francophone Thrombose et Cancer (GFTC).

Venous thromboembolism (VTE) is a common disease complication in cancer patients and the second cause of death after cancer progression. VTE management and prophylaxis are critical in cancer patients, but effective therapy can be challenging because these patients are at higher risk of VTE recurrence and bleeding under anticoagulant treatment. Numerous published studies report inconsistent implementation of existing evidence-based clinical practice guidelines (CPG), including underutilization of thromboprophylaxis, and wide variability in clinical practice patterns across different countries and various practitioners. This review aims to summarize the 2019 ITAC-CME evidence-based CPGs for treatment and prophylaxis of cancer-related VTE, which include recommendations on the use of direct oral anticoagulants specifically in cancer patients. The guidelines underscore the gravity of developing VTE in cancer and recommend the best approaches for treating and preventing cancer-associated VTE, while minimizing unnecessary or over-treatment. Greater adherence to the 2019 ITAC guidelines could substantially decrease the burden of VTE and improve survival of cancer patients.

Morbidity and mortality in the antiphospholipid syndrome during a 5-year period: a multicentre prospective study of 1000 patients.

OBJECTIVES: To identify the main causes of morbidity and mortality in patients with antiphospholipid syndrome (APS) during a 5-year period and to determine clinical and immunological parameters with prognostic significance. METHODS: The clinical and immunological features of a cohort of 1000 patients with APS from 13 European countries who had been followed up from 1999 to 2004 were analysed. RESULTS: 200 (20%) patients developed APS-related manifestations during the 5-year study period. Recurrent thrombotic events appeared in 166 (16.6%) patients and the most common were strokes (2.4% of the total cohort), transient ischaemic attacks (2.3%), deep vein thromboses (2.1%) and pulmonary embolism (2.1%). When the thrombotic events occurred, 90 patients were receiving oral anticoagulants and 49 were using aspirin. 31/420 (7.4%) patients receiving oral anticoagulants presented with haemorrhage. 3/121 (2.5%) women with only obstetric APS manifestations at the start of the study developed a new thrombotic event. A total of 77 women (9.4% of the female patients) had one or more pregnancies and 63 (81.8% of pregnant patients) had one or more live births. The most common fetal complications were early pregnancy loss (17.1% of pregnancies) and premature birth (35% of live births). 53 (5.3% of the total cohort) patients died. The most common causes of death were bacterial infection (21% of deaths), myocardial infarction (19%) and stroke (13%). No clinical or immunological predictor of thrombotic events, pregnancy morbidity or mortality was detected. CONCLUSION: Patients with APS still develop significant morbidity and mortality despite current treatment (oral anticoagulants or antiaggregants, or both).

[Acquired autoimmune haemophilia: Where is the place of rituximab in the treatment strategy? Reflection from a monocentric series of 8 patients and literature review]. / Hémophilie acquise auto-immune : quelle est la place du rituximab dans la stratégie thérapeutique ? Réflexion à partir d'une série monocentrique de 8 patients et revue de la littérature.

INTRODUCTION: Autoimmune acquired haemophilia is a rare autoimmune disease. The purpose of immunosuppressive therapy is to stop the production of autoantibodies that inhibit clotting factors VIII or IX. A corticosteroids-cyclophosphamide combination is recommanded as first-line therapy. From our experience at the University Hospital of Nîmes, we discuss the place of rituximab in the therapeutic arsenal. METHODS: We report a monocentric observational retrospective study. Our data are discussed in light of literature data, in particular cohorts EACH2 and SACHA. RESULTS: Eight patients (7 with FVIII anibodies) were consecutively included from 2005. The average age was 68.5 years with a male predominance (62.5%). Bleeding manifestations were usually spontaneous and superficial. A pathology, mostly autoimmune or neoplastic, was associated in 5/8 patients. A "by-pass" haemostatic treatment was prescribed for 3/8 patients. Rituximab was prescribed for 5/8 patients, three times as first-line therapy, and always associated with corticosteroids. Three patients received a cyclophosphamid/cortisone combination, two were treated exclusively with oral corticosteroids. Remission was obtained in all patients, without subsequent relapse. The average time to obtain remission under rituximab (after the first injection) was 32.5 days (10-143). The results observed in our series of patients are consistent with the data from the literature. CONCLUSIONS: Rituximab appears to be an effective and well-tolerated treatment for autoimmune acquired haemophilia. However, its place remains to be specified.

Associations between tumor necrosis factor-alpha and lymphotoxin-alpha polymorphisms and idiopathic recurrent miscarriage.

Heightened expression of tumor necrosis factor (TNF)-alpha and lymphotoxin-alpha (LT-alpha) was associated with pregnancy complications, including idiopathic recurrent miscarriage (RM). Whereas TNF-alpha and LT-alpha gene polymorphisms affect serum cytokine concentrations, their contribution to RM is controversial. The single nucleotide polymorphisms (SNPs) TNF-alpha (-238G/A, -308G/A) and LT-alpha (+252A/G) were investigated in 350 RM women and 200 control women. Higher frequency of the TNF-alpha -238A, but not the TNF-alpha -308A or the LT-alpha+252G, allele was seen in patients, with comparable frequencies of TNF-alpha -238G/A, TNF-alpha -308G/A, and LT-alpha+252A/G genotypes seen between both groups, except for TNF-alpha -238G/G, which was lower in patients. Regression analysis confirmed the association of the TNF-alpha -238G/A SNP with idiopathic RM, and both TNF-alpha -308A/TNF -238G/LT-alpha+252G and TNF-alpha -308G/TNF-alpha -238A/LT-alpha+252G haplotypes played a susceptible role in idiopathic RM. TNF-alpha -238G/A and -238A/A, and LT-alpha+252G/G genotypes were positively associated only with exclusively early RM. This supports the concept of the association of TNF-alpha (-238G/A) and LT-alpha (+252A/G) polymorphic variants in idiopathic RM.

[A new automated haematology analyser: the Excell 2280]. / Un nouvel automate de cytologie hématologique: l'Excell 2280.

Excell 2280 analyser is a new automated haematology analyser manufactured by Drew Scientific Inc, Texas, USA, and distributed in France by MAXMAT S.A., Montpellier. It can achieve 80 complete blood cell counts per hour, with leukocyte differential counts. Three sampling possibilities are included: a direct one (open tubes, 180 microL), a blood saver one (80 microL) and an automatic, through-the-cap one (180 microL). The analytic principles are: electrical impedance for cell counting (WBC, RBC, platelets, MCV) and RBC/platelet sizing; and a new multidimensional optical system using a laser light scattering flow cytometer for WBC counting and classification. We evaluated the Excell 2280 in our laboratory: we quantified intra-run and within-run variations, correlations between the automatic and the direct sampling method, stability of the results over time, linearity of the detections and finally correlation between results obtained with this analyzer and the Gen'S one from Beckman-Coulter Inc. The obtained results were within the theoretical ranges given by the manufacturer. The presence of any abnormal result, or of any flag, must systematically lead to check the blood smear. This new automated haematology analyser appears to be convenient for emergency room-related laboratories, and for routine small-to-medium laboratories.

Reliability of hemostasis biomarkers is affected by time-dependent intra-patient variability.

Essentials Nucleosomes and free DNA are two newly described biomarkers in venous thromboembolism (VTE). Reliability of nucleosomes, plasma free DNA and conventional hemostasis markers were studied. Hemostasis biological parameters vary over a short time-frame in VTE patients. Hemostasis biological parameters also vary over a short time-frame in healthy controls. SUMMARY: Background Previous studies have associated neutrophil-derived circulating nucleosomes and plasma free DNA with venous thromboembolism (VTE). However, there are few data concerning these two biomarkers and no studies have compared the reliability of nucleosomes and plasma free DNA against that of conventional hemostasis markers. Objectives We performed a 3-year prospective study of nucleosomes and plasma free DNA levels in comparison with conventional hemostatic biomarkers and blood cells. Patients/Methods Fifteen healthy controls and 22 randomly selected patients with a history of VTE were followed monthly for 6 months. The reliability of these markers was evaluated by the intraclass correlation coefficient (ICCs). Results and Conclusions In healthy controls and patients, we found a low reliability for nucleosomes and plasma free DNA, with ICCs at 0.538 (95% confidence interval [CI], 0.334-0.764) and 0.091 (95% CI, -0.026-0.328), respectively, in the healthy controls, and at 0.213 (95% CI, 0.042-0.463) and 0.161 (CI 95%, 0.008-0.398) in the patient group. For the conventional hemostasis biomarkers and for blood cells, reliability ranged from poor to good in the healthy volunteers and from poor to acceptable in the patient group. Our study shows for the first time that hemostasis biological parameters spontaneously vary over a short time-frame in VTE patients and, more surprisingly, in normal individuals. The clinical value of such intra-individual variations is currently unknown. This variability might mean reinterpreting diagnostic or prognostic models based on static evaluation of individuals. Studying the intrinsic value of individual patterns of markers' variability is warranted.

Homozygosity for the C46T polymorphism of the F12 gene is a risk factor for venous thrombosis during the first pregnancy.

BACKGROUND: A first thromboembolic event during pregnancy and puerperium is predisposed to by polymorphisms G1691A in the factor V gene (F5) (F5G1691A) and G20210A in the prothrombin gene (F2) (F2G20210A). OBJECTIVES: To study another potentially frequent thrombogenic polymorphism, C46T in the factor XII gene (F12) (F12C46T). PATIENTS AND METHODS: The 32 463 previously asymptomatic women included in the NOHA First cohort in their first pregnancy were investigated for these three polymorphisms. No other constitutional or acquired thrombophilic risk factor was studied. RESULTS: The overall incidence--absolute risk--of venous thromboembolic events (VTE) was 127 per 100,000 woman-years and was reduced to 22 per 100,000 women-years in women negative for the three polymorphisms (P < 0.0001). Homozygosity for F12C46T was associated with a significant relative risk (RR) of VTE [RR: 5.99, 95% confidence interval (95% CI): 2.1-17.3, P = 0.001], as was heterozygosity for F5G1691A (RR: 18.7, 95% CI: 8.3-42, P < 0.0001), heterozygosity for F2G20210A (RR: 14.3, 95% CI: 6.2-33.2, P < 0.0001), maternal age (RR: 1.18, 95% CI: 1.07-1.29, P = 0.0006), maternal body mass index (RR: 1.31, 95% CI: 1.11-1.55, P = 0.002), conceptus weight (percentiles adjusted for term of delivery; RR: 0.90, 95% CI: 0.88-0.93, P < 0.0001) and pre-eclampsia (RR: 3.03, 95% CI: 1.06-8.69, P = 0.039). CONCLUSIONS: Homozygosity for the C46T polymorphism of the F12 gene is associated with venous thrombosis during the first pregnancy/puerperium in previously asymptomatic women.

Evaluation of the non-compliance with grouping guidelines which may lead to "wrong blood in tube", an observational study and risk factor analysis.

BACKGROUND: In France, blood group determination requires the completion of two samples collected at two different times to detect identity mistake and "wrong blood in tube". The aims of the present study were: (1) to evaluate the compliance with guidelines and (2) to identify risk factors of non-compliance. MATERIALS AND METHODS: Samples for ABO group determination collected between January 1st and December 15th, 2013 in the University hospital of Nîmes, France were analyzed. An ABO group determination demand was considered non-compliant if more than one tube arrived in the laboratory within ten minutes apart. Between May 1st and June 30th 2014, a self-administered questionnaire was offered to the nurses of the hospital on a random day for each service during this period. The aim was to validate the non-compliance criterion and the identification of risk factors using logistic regression. RESULTS: Among the 16,450 analyzed blood samples, the overall compliance rate was 65.1%. Lower compliance rates were found in the surgical services. Independent risk factors for wrong practice were work overload, surgical service and individual intermediate transfusion frequency. DISCUSSION: More than one third of ABO group determinations did not follow national recommendations, which induces a substantial risk of "wrong blood in tube" and group error. The study revealed major variations among hospital services. Identification of risk factors allows targeted corrective actions.

Antiphospholipid antibodies and the risk of severe and non-severe pre-eclampsia: the NOHA case-control study.

BACKGROUND: pre-eclampsia (PEecl) can be defined as non-severe (NS-PEecl) or severe (S-PEecl). Our study aimed to determine the incidence of antiphospholipid antibodies (aPLs) in women with a past history of NS-PEecl or S-PEecl. PATIENTS AND METHODS: This case-control study includes 195 control women, 199 NS-PEecl patients and 143 S-PEecl patients whose plasma samples were collected 6 months after their first delivery. Each plasma was tested for lupus anticoagulant (LA), anticardiolipin (aCL) and antiß2GP1 antibodies, as well as antibodies against phosphatidylserine/prothrombin complex (aPS/PT) and domain I of the ß2GP1. RESULTS: When compared with the control group no significant associations were found for the NS-PEecl group after adjustment of confounding variables. For the S-PEecl group, there was an association with antiß2GP1 immunoglobulin G (IgG) (OR 16.91, 95% CI 3.71-77.06), as well as age, obesity, smoking and multiparity. Antiß2GP1-domain I IgG was associated with aCL, antiß2GP1 and aPS/PT IgG in the three groups. aPS/PT IgG was associated with aCL IgG, and aPS/PT IgM was associated with aCL and antiß2GP1 IgM in the three groups. CONCLUSION: S-PEecl is a distinct entity from NS-PEecl and is mainly associated with the presence of antiß2GP1 IgG. Antiß2GP1 domain I correlates with other aPL IgG tests, and aPS/PT may be promising in patients for whom LA tests cannot be interpreted.

Role of allelic variants Gly972Arg of IRS-1 and Gly1057Asp of IRS-2 in moderate-to-severe insulin resistance of women with polycystic ovary syndrome.

To assess the role of insulin receptor, insulin receptor substrate (IRS)-1, and IRS-2 genes in insulin resistance, we explored the genomic DNA in women with polycystic ovary syndrome (PCOS) and a variable degree (mean +/- SE) of insulin resistance (homeostasis model assessment index for insulin resistance [HOMA(IR)] 3.2 +/- 0.6, n = 53; control subjects 1.56 +/- 0.34, n = 102) using direct sequencing. Whereas no novel mutations were found in these genes, gene-dosage effects were found on fasting insulin for the Gly972Arg IRS-1 variant and on 2-h plasma glucose for the Gly1057Asp IRS-2 variant. The Gly972Arg IRS-1 variant was more prevalent in insulin-resistant patients compared with non-insulin-resistant individuals or control subjects (39.3 vs. 4.0 and 16.6%, P < 0.0031, respectively). A multivariate model that included BMI as a variable revealed significant effects of the Gly1057Asp IRS-2 variant on insulin resistance (P < 0.016, odds ratio [OR] 7.2, 95% CI 1.29-43.3). HOMA(IR) was higher in carriers of both IRS variants than in those with IRS-2 mutations only or those with wild-type variants (6.2 +/- 2.3, 2.8 +/- 0.5, and 1.8 +/- 0.2, respectively; P < 0.01), and it was significantly associated with this genotype (P < 0.0085, OR 1.7, 95% CI 1.09-2.99). We conclude that polymorphic alleles of both IRS-1 and IRS-2, alone or in combination, may have a functional impact on the insulin-resistant component of PCOS.

Factor V Leiden and prothrombin G20210A polymorphisms as risk factors for miscarriage during a first intended pregnancy: the matched case-control 'NOHA first' study.

Factor V Leiden (FVL) and prothrombin G20210A (FIIG20210A) mutations are associated with a higher risk of miscarriage: we sought to understand whether this association differs by clinical time of unexplained miscarriage, and by ethnic origin, among women with no previous thrombotic episode, during the first intended pregnancy. We performed a case-control study nested in a cohort of 32 683 women. We analyzed 3496 pairs of women matched for classical confounding factors. The FVL and FIIG20210A mutations were associated with an increased risk of miscarriage in Caucasian women [odds ratio (OR) 3.19, 95% confidence interval (CI) 2.37-4.30, P < 0.001 and OR 2.36, 95% CI, 1.72-3.24, P < 0.001, respectively]. Among non-Caucasian women, the mutations were rare and the associations with risk of miscarriage less clear. FVL and FIIG20210A mutations were independent risk factors for miscarriages only for women with related clinical signs occurring from the 10th week of gestation on (OR 3.46, 95% CI 2.53-4.72, P < 0.001 and OR 2.60, 95% CI 1.86-3.64, P < 0.001, respectively). These results indicate that FVL and FIIG20210A mutations are associated with a significant risk of spontaneous abortion which clinical signs occur from the 10th week on of the first intended pregnancy.

Recombinant human FVIIa for reducing the need for invasive second-line therapies in severe refractory postpartum hemorrhage: a multicenter, randomized, open controlled trial.

BACKGROUND: Case reports on recombinant human factor VIIa (rhuFVIIa) use in women with severe postpartum hemorrhage (PPH) showed encouraging results, but no randomized controlled trial (RCT) is available. PATIENTS AND METHODS: Eighty-four women with severe PPH unresponsive to uterotonics were randomized to receive one early single rhuFVIIa infusion (n = 42) or standard care (no rhuFVIIa; n = 42). The primary efficacy outcome measure was the reduction of the need for specific second-line therapies, such as interventional hemostatic procedures, for blood loss and transfusions. The primary safety outcome measure was the number of deaths and thrombotic events during the 5 days following rhuFVIIa infusion. RESULTS: rhuFVIIa was associated with a reduction in the number of patients who needed second-line therapies compared with controls (standard care). Specifically, 39/42 (93%) patients in the standard care arm received second-line therapies and 22/42 (52%) patients in the rhuFVIIa arm (absolute difference, 41%; range, 18-63%; relative risk RR, 0.56 [0.42-0.76]). The delivery mode (vaginal or Cesarean section) did not affect the primary outcome. No death occurred. Two venous thrombotic events were recorded in the rhuFVIIa arm: one ovarian vein thrombosis and one deep vein thrombosis with a non-severe pulmonary embolism. CONCLUSION: This open RCT in women with severe PPH refractory to uterotonics shows that rhuFVIIa reduces the need for specific second-line therapies in about one in three patients, with the occurrence of non-fatal venous thrombotic events in one in 20 patients.

Hypoxia/reoxygenation stimulates endothelium to promote neutrophil adhesion.

An in vitro model was designed to study the role of ischemia/reperfusion and endothelium-derived oxygen free radicals on neutrophil adhesion, with particular interest in the endothelial adhesion molecules involved. Human umbilical vein endothelial cells were submitted to 5 h hypoxia followed by various times (20 min to 24 h) of reoxygenation. Human resting neutrophils were added to monolayers for the last 15 min of reoxygenation. Adherence was evaluated by myeloperoxidase assay. Under these conditions, we found an increased adhesion of neutrophils with two peaks after 20 min and 4 h reoxygenation. This was correlated with the respective expression of the preformed granule membrane protein 140 (GMP-140) and of the de novo synthesized endothelial leukocyte adhesion molecule 1 (ELAM-1) on endothelial surface. Superoxide dismutase and/or catalase, or oxypurinol added to cultures before hypoxia efficiently prevented neutrophil adhesion. These results underline the crucial role played by endothelial oxy radicals at reoxygenation in adhesion of leukocytes, which could lead to an amplification of the oxidative stress injury. The protection offered by free radical scavengers emphasizes the potential therapeutic use of antioxidants in postischemic vascular disorders.

Thrombophilic families with inheritably associated high levels of coagulation factors VIII, IX and XI.

We describe six families in which associated high levels of coagulation factors (F) XI, FIX and FVIII (each with a plasma concentration higher than the 95th percentile found in a control group of 500 asymptomatic individuals: respectively, 135, 145 and 155 IU dL-1) were inherited as a dominant autosomic genetic traits. In these six families, this syndrome is associated with venous thromboembolic events (Odds ratio 41 [4.9-353], P = 0.0006). It seems to predispose to idiopathic events and, as age increases, is often associated with recurrence. First thrombotic episodes occur in young patients (50% of the carriers are symptomatic at the age of 32 years) and in women, can be unmasked by hormonal treatments, mainly oral contraceptives. The association of high levels of coagulation FXI, FIX and FVIII is thus a new rare high-risk inherited thrombophilia syndrome.

Venous occlusion and chronic cigarette smoking: dose-dependent decrease in the measurable release of tissue-type plasminogen activator and von Willebrand factor.

This study was aimed at examining the effect of chronic cigarette smoking on a venous occlusion test. Two groups of young healthy men, a control group of 20 non-smoking subjects and a group of 21 smoking subjects having an average consumption of 17.6 packages.day-1.years (SD 8.6) were studied. Venous occlusion performed in smokers did not induce a significant measurable release of von Willebrand factor (vWF). The release of tissue-type plasminogen activator (t-PA) was significantly weaker for the smokers than for the control group (P less than 0.02). An inverse correlation was found between the cumulative parameter of tobacco consumption and the measurable amount of t-PA Ag or vWF Ag released during venous occlusion (r' = -0.994 and r' = -0.889). Cigarette smoking is thus associated with disturbances of the biological response to this venous occlusion test.

Use of a low-molecular weight heparin (enoxaparin) or of a phenformin-like substance (moroxydine chloride) in primary early recurrent aborters with an impaired fibrinolytic capacity.

An impaired fibrinolytic capacity, defined as an insufficient venous occlusion-induced shortening of the plasma euglobulin clot lysis time, is a common feature in women suffering from primary early recurrent unexplained miscarriages. We investigated the therapeutic effect of a low-molecular-weight heparin and of a phenformin-like substance. In a prospective, randomized trial, 30 consecutive patients initially received either enoxaparin, 20 mg per day during one month, or moroxydine chloride, 1200 mg per day during one month. In case of fibrinolytic status normalization, they were treated during 6 months by the beneficial treatment which was planned to be continued during eventual pregnancies. Patients with hypofibrinolysis persistence received the alternative treatment during another month and a new evaluation was performed. No treatment was given when a persistent abnormal response to the venous occlusion test was evidenced. In case of positive response, the treatment was continued during 6 months. The primary study end-points consisted of any of the following: effect of the treatments on the fibrinolytic response; number of patients becoming pregnant during the 6 months following the last venous occlusion test; number of full-term pregnancies. Concerning the effects on the fibrinolytic system, 20 out of 29 women responded to the first or second-line enoxaparin treatment whereas only 1 woman out of 19 responded to moroxydine chloride (p = 0.00002). Concerning the effects on fertility, responders to LMWH were more likely to initiate a new pregnancy than non-responders (16/20 vs 2/10, p = 0.002). In patients conceiving, LMWH responders were more likely to obtain live births than nonresponders (13/16 vs. 0/2, p = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)