Prognostic factors of hemorrhagic complications after oxaliplatin-based hyperthermic intraperitoneal chemotherapy: Toward routine preoperative dosage of Von Willebrand factor?

BACKGROUND: Oxaliplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC-ox) induces specific morbidity with hemorrhagic complications (HC). The aim of this study was to identify preoperative, intraoperative and postoperative HC predictive factors after HIPEC-ox. METHODS: A prospective single center study that included all consecutive patients treated with curative-intent HIPEC-ox, whatever the origin of peritoneal disease, was conducted. All patients underwent systematic blood tests exploring primary hemostasis and endothelial activation before surgical incision (D0) and on postoperative days 2 (POD2) and 5 (POD5). RESULTS: Between May 2012 and August 2015, 47 patients were enrolled in the study. The overall HC rate was 38%. Major morbidity was significantly higher in patients with HC. Patients presenting HC were significantly more often affected with pseudomyxoma peritonei and had less preoperative chemotherapy. Multivariate analysis showed that a higher plasmatic level of Von Willebrand factor antigen at D0 (D0 VWF:Ag) was a protective predictive factor for HC (p = 0.049, HR: 0.97 CI 95% [0.94-1.00]). A D0 VWF:Ag level below 138% had a sensitivity of 87.5%, a specificity of 67% and an area under the curve of 80.3% (CI 95% [66.5-94], p < 0.01) for predicting HC. CONCLUSIONS: Through the identification of prognostic factors, this study highlighted a subgroup of patients with low risk of HC after HIPEC-ox. Based on these results, we propose a routine preoperative dosage of VWF that would help the surgeon to select the most suitable patients for HIPEC-ox.

Short-term very low-calorie diet in obese females improves the haemostatic balance through the reduction of leptin levels, PAI-1 concentrations and a diminished release of platelet and leukocyte-derived microparticles.

BACKGROUND: In obesity, metabolic stress and inflammation in injured tissues could favour enhanced shedding of procoagulant microparticles (MPs). At sites of endothelium injury, the swift recruitment of procoagulant leukocyte-derived MPs enables the initiation of blood coagulation and thrombus growth. OBJECTIVES: In obese females, we sought to evaluate the impact of a very low-calorie diet (VLCD) on procoagulant MP levels, fibrinolytic status, inflammation and endothelium damage. METHODS: Circulating biomarkers of vascular damage, fibrinolytic status, platelet activation and inflammation were measured before, 30 and 90 days after starting a short-term VLCD. MPs were measured by flow cytometry and capture assays. Their procoagulant potential was quantified using functional prothrombinase assays and their cellular origin were determined using flow cytometry (endothelium, platelet, leukocyte, lymphocyte and erythrocyte-derived MP) or capture assays. RESULTS: A total of 24 obese females (39 ± 10 years) with a mean body mass index of 35 ± 4 kg m(-2) were prospectively enroled. Procoagulant leukocyte-derived MPs were associated with the waist circumference at baseline (r=0.534; P=0.010) and at 90 days follow-up (r=0.487; P=0.021). At 90 days, weight reduction (-9.8%) was associated with a lowering of blood pressure, improvement of metabolic parameters and a significant reduction of plasminogen activator inhibitor-1 (PAI-1) (-38%), procoagulant platelet-derived MPs (-43%), leukocyte-derived MPs (-28%) and leptin (-32%) levels. CONCLUSION: In obese females, a short-term VLCD results in an overall improvement of the haemostatic balance characterized by the reduction of PAI-levels, diminished release of platelet and leukocyte-derived MPs and a reduction in leptin levels, an adipocyte-derived cytokine.

[Value of left atrial dilation in the diagnosis of silent myocardial ischemia in diabetes mellitus patients]. / Facteurs prédictifs de l'existence d'une ischémie myocardique silencieuse chez le patient diabétique. Intérêt de l'évaluation de la surface de l'oreillette gauche.

BACKGROUND: Accelerated atherothrombosis is a common feature in diabetes mellitus patients (DM), which can be related to abnormalities in vascular cell apoptosis and activation leading to the release of procoagulant microparticles (MPs). In DM patients, we hypothesized that circulating levels of biomarkers involved in atherothrombosis processes as well as cardiac and carotid echocardiography variables could be useful in the detection of silent myocardial diagnosed by myocardial perfusion imaging. METHODS AND RESULTS: We investigated, in 55 patients with diabetes (mean age 62+/-10 years) and 15 nondiabetics (46+/-14 years) patients the prevalence of silent myocardial ischemia (SMI) detected by a treadmill exercise or dipyridamole (99m)Tc-sestamibi stress test. Echocardiographic and -carotid variables were obtained using standardized methods. Biomarkers assessing endothelial apoptosis or activation (CD31+-MPs, CD62+-MPs, VCAM-1), inflammatory status (CD11a +/- MPs, MCP-1, CRP), platelet activation (GPIb+/-MPs, CD40-L, P-selectin, GPV) ventricular stretch (BNP) were measured in the plasma. SMI was diagnosed in 23/55 (42%) diabetics patients and in 3/15 (20%) nondiabetics patients. Enhanced inflammatory status and leukocyte damage (CD11a+-MPs) were evidenced in diabetic patients. Within the diabetic population, biomarkers levels of atherothrombosis were not significantly associated to the detection of SMI. In multivariable analyses adjusted for LV hypertophy, left atrial surface (LA) remained independent predictor of silent myocardial ischemia (OR 4.14; IC [1.7-16.13]; P=0.039). CONCLUSIONS: In diabetes mellitus patients, LA surface independently predicted silent myocardial ischemia after adjustment for established echocardiographic, and inflammatory risk factors. This simple measure of LA dilation could be helpful in the identification of diabetes mellitus patients at heightened cardiovascular risk.

[Platelet responsiveness to clopidogrel in patients with coronary syndrome. Comparison of platelet aggregation induced by ADP and flow cytometric analysis of intraplatelet VASP phosphorylation]. / Evaluation de la réponse plaquettaire au clopidogrel au cours des syndromes coronariens. Comparaison de l'agrégométrie à l'ADP et de la méthode VASP.

UNLABELLED: Although antiplatelet therapy with ASA-clopidogrel reduces the risk of cardiovascular episodes after PCI, a substantial number of events occur during follow-up. Sustained platelet reactivity under dual antiplatelet therapy was recently associated with increased risk of recurrent atherothrombotic events after PCI. Whereas it appears significant to determine clopidogrel responsiveness, the accurate platelet function assay is still under investigation. OBJECTIVES: (i) to determine the proportion of "low-responders" or "resistants" patients during coronary syndrome (ii) to identify determinants of interindividual variability response to clopidogrel (iii) to compare aggregometry and VASP phosphorylation measured by flow cytometry. Patients were treated by clopidogrel (300 mg loading dose and 75 mg maintenance dose) and ASA (160 mg) (N=27). Additional treatment by GPIIbIIIa antagonists was given to high-risk patients (N=9). Platelet function was monitored by ADP aggregometry (5, 10, 20 microM) and VASP phosphorylation before any treatment by clopidogrel (d0) and at least five days after (d5). The platelet reactivity index (PRI), expressed as percentage, is the difference in VASP fluorescence intensity between resting (+ PGE1) and activated (ADP) platelets. At d5, low responsiveness to clopidogrel was defined by either (i) a PRI > 67.3% corresponding to the mean value -2SD measured in untreated patients (dO) (ii) or an absolute change (delta d0-d5) in aggregation (ADP 10 microM) < to 30%. RESULTS: PRI, platelet aggregometry to ADP was significantly reduced following clopidogrel treatment (P < 0.01). A wide inter-individual variability to clopidogrel was observed at d5 (PRI from 11 to 83%). Whatever the platelet function used, a large proportion of patients were detected as "low-responders" (37% by VASP, 44% by ADP aggregometry). Absolute change in ADP aggregation was correlated to the variation of PRI (R = 0.559; P = 0.02). Contrary to ADP aggregometry, PRI was not influenced by GPIIbIIIa antagonists or prior administration of ASA. However, the conformity of the two methods to evaluate clopidogrel responsiveness was only 66%. No differences in platelet aggregometry could be observed at d5 between "low" and "good-responders" defined by VASP analysis. At d5, a higher PRI value could be detected in male and patients with history of dyslipemia. CONCLUSION: During coronary syndrome, impaired platelet responsiveness to clopidogrel was observed in a large proportion of patients whatever the platelet function assay used. VASP analysis was found insensitive to GPIIbIIIa or aspirin administration. Possible mechanisms linking clopidogrel "resistance" measured by VASP assay and enhanced thrombogenicity remain to be characterized. Indeed, clopidogrel "resistance" defined by VASP analysis was not associated with higher platelet aggregation.

Circulating procoagulant microparticles in obesity.

AIM: Obesity is a risk factor for cardiovascular diseases and venous thromboembolism. Circulating procoagulant microparticles (MP) have been described in various clinical situations associated with thrombosis and in diabetic patients. The aim of this preliminary study was to evaluate the presence of MP in obese patients without any other vascular risk factor in particular diabetes. METHODS: Fifty-eight obese women <50 year-old without other cardiovascular risk factors were recruited from a single out-patient nutrition clinic. They were compared to 45 age-matched healthy normal weight controls. Main outcome was MP levels in patients and controls. Relationships between MP concentrations and parameters reflecting insulin resistance in patients were also studied. RESULTS: Obese patients were 33.3 +/- 1.2 years old and had a mean BMI of 42.4 +/- 0.9 kg/m2. There vas a greater proportion of smokers in the obese group (34.5 vs 15.6%). Mean MP levels were markedly higher in obese patients compared to controls (10.6 +/- 0.5 vs 3.2 +/- 0.3 nMPSeq, P < 0.001). There was no difference in MP concentrations between smokers and non smokers. In the obese group, there was a negative correlation between MP and BMI (r = -0.265, P < 0.05) but no relationship could be established between MP concentrations and markers of insulin resistance. CONCLUSION: This increase in circulating MP levels reflects cell activation and could account for the increased risk of thrombotic complications in obesity. Further studies are ongoing to explore the relationships between MP levels and coagulation markers and to assess the effect of weight reduction.

[Variable extent of platelet responsiveness to clopidogrel inhibition: "clopidogrel resistance"?]. / Variabilité de la réponse plaquettaire au clopidogrel: "résistance" biologique?

During percutaneous coronary angioplasty, platelet inhibition by clopidogrel and aspirin has drastically decreased the risk of thrombotic occlusion of the stented vessels. However, despite the widespread use of these drugs, the incidence of acute or subacute stent thrombosis remains elevated, concerning 1 to 2% of the treated patients. Considerable differences in the responsiveness to clopidogrel could be observed, suggesting a possible underlying biological resistance. "Clopidogrel resistance" has recently been associated to an increased risk of thrombotic events following coronary angioplasty. Variations in enteric absorption, biotransformation in the liver by the CYP3A4, changes in the ADP receptor P2Y12, abnomalies of intraplatelet signal transduction, extent of platelet activation, class angina, diabetes mellitus may account for the considerable interindividual response variability widely reported. In this view, laboratory tests evaluating "clopidogrel resistance" might be useful tools for the identification and follow-up of patients at higher thrombotic risk. Indeed, in these patients, further platelet inhibition can be achieved by higher doses of clopidogrel.

[The significance of circulating microparticles in physiology, inflammatory and thrombotic diseases]. / Les microparticules circulantes: rôles physiologiques et implications dans les maladies inflammatoires et thrombotiques.

BACKGROUND: In multicellular organisms, apoptosis and subsequent microparticle shedding play a key role in homeostasis. Having long been considered as << cellular dust >>, microparticles released in biological fluids upon cell activation or apoptosis appear as multifunctional bioeffectors involved in the modulation of key functions including immunity, inflammation, hemostasis and thrombosis, angiogenesis. MP constitute reliable markers of vascular damage, accessible to biological detection whilst the cells they originate from remain sequestered in tissues or are promptly submitted to phagocytosis. RECENT FINDINGS: MP modulate biological functions of target cells through the transfer of cytoplasmic content, lipids and membrane receptors. The pharmacological modulation of circulating levels of microparticles could be of particular interest in thrombotic or inflammatory diseases, cancer or hemophilia. CONCLUSION: MP can now be viewed not only as a hallmark of cell damage but also as a true biological tool.

Knee joint arthroplasty in a patient with haemophilia A and high inhibitor titre using recombinant factor VIIa (NovoSeven): a new case report and review of the literature.

Elective orthopaedic surgery is regularly withheld from patients with haemophilia and high inhibitor titre despite the presence of severe arthropathy and urgent medical need. A knee joint arthroplasty was performed in a patient with severe haemophilia A and a high inhibitor titre using recombinant factor VIIa (rFVIIa) as the sole coagulation factor. There was no abnormal bleeding during surgery although an increased blood loss through surgical drains did occur during the first 6 h postoperatively. Rehabilitation was started on day 1 and continued for 3 months. Walking commenced on day 4. After 1 year of follow-up, the clinical outcome of surgery was considered excellent with no pain, knee mobility at 0-5-90 degrees, and an International Knee Society score of 95/100. No rFVIIa-associated side-effects or thrombotic complications were reported. In conclusion, knee joint arthroplasty is now an option for haemophilia patients with a high inhibitor titre. An international review of all available data on elective orthopaedic surgery in inhibitor patients is required so that the optimal treatment regime can be defined and the short- and long-term risk-benefit ratio of surgery compared to that of noninhibitor patients.

Frequent factor II G20210A mutation in idiopathic portal vein thrombosis.

BACKGROUND & AIMS: Despite extensive investigations of portal vein thrombosis, no underlying cause is identifiable in up to 30% of patients. A recently described mutation of the prothrombin gene at nucleotide position 20210 is associated with history of venous thrombosis and was assessed in this study. METHODS: We compared the frequency of factor II G20210A and factor V G1691A (factor V Leiden) mutations in 10 patients with idiopathic portal vein thrombosis, 10 patients with nonidiopathic portal vein thrombosis, 60 patients with deep vein thrombosis of the legs, and 42 control subjects. RESULTS: The frequency of factor II G20210A mutation was increased in patients with idiopathic portal vein thrombosis (40.0%; confidence interval, 3.1%-76.9%) compared with controls (4.8%; confidence interval, 0%-11.5%) or patients with nonidiopathic portal vein thrombosis or deep vein thrombosis (P = 0.0001). In contrast, the frequency of the factor V G1691A mutation was similar in subjects with portal vein thrombosis and in controls but was increased in patients with deep vein thrombosis (P = 0.0001). CONCLUSIONS: The factor II G20210A mutation is frequent in patients with idiopathic portal vein thrombosis and should therefore be assessed under this circumstance.

Significance of diminished factor XIII in Crohn's disease.

OBJECTIVE: Coagulation factor XIII is a plasma transglutaminase involved in crosslinking of fibrin, the last step of the coagulation system and a connective tissue factor contributing to the wound healing process. It circulates as a heterotetrameric molecule consisting of two identical proenzyme subunits (factor XIIIA) and two carrier protein subunits (factor XIIIS). The aim of this study was to determine the disease features associated with the diminution of factor XIII in Crohn's disease. METHODS: Factor XIIIA and factor XIIIS levels were assessed in patients presenting with Crohn's disease, ulcerative colitis, infectious colitis, or diverticulitis, in patients with rheumatoid arthritis, and in control subjects. Prothrombin fragment 1 + 2 assay, as a marker of the generation of thrombin and measurement of C-terminal telopeptide of type I collagen as an estimate of degradation of collagen type I, were performed. RESULTS: Factor XIIIA was significantly decreased in Crohn's disease, in ulcerative colitis, and in infectious colitis by comparison with subjects presenting with diverticulitis, normal, and rheumatoid subjects p = 0.0001). Factor XIIIS was unmodified in patients with Crohn's disease by comparison with controls but was reduced in those presenting with intestinal bleeding (p = 0.0002). In Crohn's disease, the lowest level of factor XIIIA was observed in patients with intestinal bleeding (p = 0.0003). Factor XIIIA was correlated with the Van Hees index (r = -0.5661; p = 0.0001) and with the C-terminal telopeptide of type I collagen (r = -0.4110; p = 0.0011) but not with prothrombin fragment 1 + 2. The multiple regression analysis showed that only Van Hees index and intestinal bleeding were independent variables for explaining the diminution of Factor XIIIA in Crohn's disease. CONCLUSIONS: Factor XIIIA subunit is an indicator of Crohn's disease activity. Our study suggests that a low factor XIIIA level is related to the presence of intestinal lesions and might be linked to intestinal repair mechanisms; loss in intestinal lumen could be also involved, especially in patients with intestinal bleeding.

[Acrosyndromes induced by bleomycin in HIV 1 related Kaposi's disease. 5 cases]. / Acrosyndromes induits par la bléomycine au cours de la maladie de Kaposi associée au VIH 1. 5 observations.

OBJECTIVES: Raynaud's syndromes may be observed in HIV-infected patients, particularly those with Kaposi disease treated with bleomycin. This complication occurs in 10% of patients given bleomycin although only 7 cases have been reported in the literature. The aim of this study was to determine the frequency of certain biological abnormalities observed in HIV patients with Kaposi disease given bleomycin and who develop Raynaud's syndromes. PATIENTS AND METHODS: A survey was conducted from 1989 to 1995 among 1074 patients infected with HIV-1. There were 121 patients with Kaposi disease and 73 of these were treated with bleomycin. The clinical features and laboratory results (cryoglobulinemia, free protein-S, protein-C, anticardiolipin antibodies, von Wille-brand factor (vWF.ag) endothelin-1) were obtained in 5 patients who developed biomycin-induced Raynaud's syndrome. RESULTS: Amont the 73 patients with Kaposi disease treated with bleomycin (total mean dose = 227 mg (120-380 mg)), 5 patients (12.6%) developed a severe Raynaud's synchrome including two who suffered digital necrosis Withdrawal of bleomycin led to improved symptomatology (n = 2) or an aggravation (n = 1) in the 3 patients followed. CONCLUSION: Raynaud's syndromes are frequent (12.6%) in HIV patients with Kaposi disease treated with bleomycin. The vascular toxicity of bleomycin, demonstrated in animals, would appear to be the causal factor among others. Release of endothelial factors (vWF.ag endothelin-1) and perturbed hemostasis related to the HIV infection (protein-S deficiency, anti-cardiolipin antibodies) could be an expression of and aggravate the vascular toxicity of bleomycin.

The treatment of deep vein thrombosis with continuous intravenous low-molecular-weight dermatan sulphate (Desmin). A pilot study.

Eight patients with femoro-popliteal or sural DVT, confirmed by phlebography, were treated with intravenous Desmin (LMW-dermatan sulphate): on the first day, after an initial i.v. injection of 400 mg, all patients received an infusion of 800 mg in 500 ml of saline, during 24 hours; this infusion was repeated in each of the subsequent 9 days (global treatment period: 10 days). To monitor efficacy of the antithrombotic treatment a phlebography, with calculation of Marder score, was repeated at the end of treatment. Laboratory tests monitoring blood coagulation were carried out: aPTT, TT, PT. Factor Xa inhibition (by chronometric and chromogenic method), Stachrom DS, fibrinogen, prothrombin fragments F1 + 2 and TAT. Seven patients completed the ten-day treatment: 6 patients evidenced good improvement of the phlebographic patterns, 1 remained stationary and 1 patient was withdrawn due to adverse events. During the ten days treatment we did not observe any variation of blood coagulation tests. Desmin tolerability was good and no haemorrhagic episodes were registered. The collected results point to a good antithrombotic activity of the new LMW-dermatan sulphate, that deserves to be further evaluated with controlled investigations on larger number of patients.

[Serum cardiolipin antibodies in patients with alcoholic cirrhosis]. / Anticorps sériques anticardiolipides chez les malades atteints de cirrhose alcoolique.

OBJECTIVE: Although portal obstruction is a complication in cirrhosis which is usually associated with hepatocellular carcinoma, its precise neoplastic or thrombotic nature is not easy to determine. Serum antiphospholipid antibodies could be involved in thrombosis-related portal obstruction. PATIENTS AND METHODS: The presence of serum anticardiolipid antibodies was investigated by an immunoenzymatic technique in 129 patients with alcoholic cirrhosis, 47 patients with hepatocellular carcinoma with (n = 18) or without (n = 29) portal obstruction, and 82 patients without hepatocellular carcinoma or portal obstruction. Five control groups were included: patients with non alcoholic cirrhosis (n = 21), non cirrhotic alcoholic liver disease (n = 21), chronic viral hepatitis (n = 14), extra-hepatic cholestasis (n = 9), and hypergammaglobulinemia associated with human immunodeficiency virus infection without liver disease (n = 28). RESULTS: The prevalence of serum anticardiolipid antibodies was 57% in patients with alcoholic cirrhosis, which was significantly different from the prevalence in the control groups which ranged from 0 to 32%. Anticardiolipid antibodies were of IgA isotypes in 90.5% of the cases, mainly related to the degree of liver failure but not to hepatocellular carcinoma or portal obstruction. CONCLUSION: In alcoholic cirrhosis, serum anticardiolipid antibodies do not seem to be related to the pathogenesis of portal obstruction in patients with hepatocellular carcinoma. They could rather reflect liver lesions and immunological dysfunctions.

Prothrombin fragment 1 + 2 and thrombin-antithrombin III complex as markers of activation of blood coagulation in inflammatory bowel diseases.

OBJECTIVES AND METHODS: The aims of the present work were to assess the presence of thrombin generation in Crohn's disease and in ulcerative colitis by using the prothrombin fragment 1 + 2 and the thrombin-antithrombin III complex assays and to study the possible relationships between these markers and disease activity. RESULTS: Prothrombin fragment 1 + 2 and thrombin-antithrombin III complex were significantly raised in patients with Crohn's disease (n = 69) and with ulcerative colitis (n = 25) as compared with healthy controls (n = 50). In Crohn's disease these two markers of thrombin generation were correlated with the Van Hees index (P < 0.05 and P < 0.001, respectively); values were significantly different from controls even in the patient group displaying the lowest disease activity (P < 0.001). No correlation was found with tumour necrosis factor alpha and C-reactive protein; nevertheless patients with C-reactive protein less than or equal to 10 mg/l had significant lower values of prothrombin fragment 1 + 2 (P < 0.03). In ulcerative colitis prothrombin fragment 1 + 2 and thrombin-antithrombin III complex were significantly increased by comparison with controls, were higher in patients with pancolitis and correlated with C-reactive protein (P < 0.002 and P < 0.009, respectively). CONCLUSION: These data show that prothrombin fragment 1 + 2 and thrombin-antithrombin III complex are increased in inflammatory bowel diseases and suggest that thrombin generation might be an early event in their pathogenesis.

Prevalence and significance of anticardiolipin antibodies in Crohn's disease.

Crohn's disease is a chronic inflammatory bowel syndrome in which thrombotic complications occur in the active phase. Phospholipid-binding antibodies such as anticardiolipin antibodies and lupus anticoagulants have been shown to be associated with thrombosis. Their presence has been assessed in a group of 50 patients with Crohn's disease among whom 44 had active disease. The overall prevalence of anticardiolipin antibodies was about 22%, while none of these patients had lupus anticoagulant. Anticardiolipin antibodies have been observed in both active and quiescent CD and their presence does not seem to be related to the site of CD lesions. The presence of phospholipid-binding antibodies could be a sign of vascular alterations that are potentially thrombogenic per se, and their predictive value with respect to the specific inflammatory syndrome of Crohn's disease is discussed.

Variation in von Willebrand's Factor according to the treatment of acute myocardial infarction: physiopathological and clinical implications.

To investigate whether von Willebrand's Factor (vWF) changes as a result of the reperfusion strategy during acute myocardial infarction (AMI), vWF was measured on days 0, 1, 2, 3, 4, 5 and 15 in 34 patients with AMI. Thrombolysis was initiated in 22 patients and followed by a coronary angiogram 90 min later. In 13 patients the infarct-related artery was then patent (THR group). In nine patients the infarct-related artery was occluded and rescue percutaneous transluminal coronary angioplasty was performed (group THR+rPTCA). In 12 patients, primary PTCA was carried out (pPTCA group). Admission values of vWF were similarly high in the three groups, while changes in vWF over the following days were statistically different among the groups. No significant change was observed in THR, whereas a significant and prolonged increase was found after failed thrombolysis with PTCA (peak increase at day 5:1.54 +/- 0.04 U.ml-1). In the pPTCA group, a significant increase could only be found on day 3 (0.96 +/- 0.04 U.ml-1). Absence of a statistical rise in vWF might be a late indicator of successful thrombolysis. The prolonged increase in vWF after failed thrombolysis needing rescue PTCA probably reflects a higher resistance to thrombolysis, while the slight but significant increase in vWF following primary PTCA could be due to vascular injury.

[Von Willebrand factor in coronary disease]. / Le facteur de Willebrand en pathologie coronaire.

The value of studying factors of haemostasis and thrombosis in patients with coronary artery disease is established. The endothelial lesion and evolution of the thrombus play key roles in acute coronary syndromes and coronary angioplasty. The von Willebrand factor (VWF) is known for its participation in primary haemostasis. Deficits of this factor lead to a haemorrhagic syndrome, von Willebrand's disease. This glycoprotein is mainly synthesised by the endothelial cells. Its polymeric composition allows identification of two types of multimeres. The high molecular weight, active multimeres are liberated from the endothelium after stimulation by thrombin. Low molecular weight multimeres are less active and are secreted continuously. The VWF promotes platelet adhesion and facilitates platelet aggregation. Experimental pig models with VWF deficiency show that this factor is essential for the constitution of an occlusive thrombus. Several physiopathological mechanisms interact to increase VWF concentrations during thrombosis: the endothelial lesion, adrenergic stimulation, acute phase reaction. Increased VWF concentrations have been reported in many clinical situations. The results are most demonstrative in coronary artery disease. The VWF is abnormally high from the time of hospital admission in patients with acute myocardial infarction and continues to increase up to the 5th day before falling, without returning to normal values, at the 15th day. It is a sensitive though not specific late diagnostic marker of myocardial infarction. Increased VWF concentrations are not proportional to the severity of coronary atherosclerosis. They are, however, related to the infarct size, to the inflammatory reaction and to the prothrombotic phase.(ABSTRACT TRUNCATED AT 250 WORDS)