[Mortality and morbidity conference: A tool for quality and safety of care continuous improvement]. / La Revue de mortalité et morbidité : une méthode d'amélioration continue de la qualité et la sécurité des soins.

OBJECTIVE: The mortality and morbidity conference (MMC) is one of the keystones in the evaluation of quality of care. The objective of this work was to describe a MMC by presenting a case report. CASE REPORT: A 16-year old man suffering from chronic anaemia had to be transfused with two units of red blood cells in an outpatient unit. Although the transfusion went well for the first unit, the patient presented haemolysis during the transfusion of the second unit because the nurse administered the wrong unit. The incident was analysed during a mortality and morbidity conference with the attendance of the hemovigilance local correspondent. Immediate causes of the event were the failure to respect the transfusion procedure: in advance compatibility testing, failure to check the patient and blood component identification just before the transfusion. Factors contributing to the event were the deviation of transfusion practices, poor working conditions of nurses, linked to inadequate staff in relation to the activity. The discussion of the incident led to develop an action plan. DISCUSSION: This case shows the interest for staff members to discuss an adverse event. However, a well-defined methodology for conducting mortality and morbidity conferences is lacking and leads to a wide heterogeneity between teams. Major differences refer to criteria for case selection and quality of participants. This heterogeneity is likely to have an impact of the efficacy of mortality and morbidity conferences regarding the quality and safety of care.

Continuous infusion of B-domain deleted recombinant factor VIII (ReFacto) in patients with haemophilia A undergoing surgery: clinical experience.

This retrospective, open-label, non-comparative study evaluated continuous infusion of recombinant factor VIII (ReFacto), B-domain deleted recombinant FVIII (BDDrFVIII), in patients with haemophilia A undergoing surgery and requiring >5 consecutive days of treatment. Sixteen patients from eight centres underwent a total of 20 procedures. Haemostatic outcome was assessed as 'excellent' or 'good' in 75% of procedures, and target FVIII:C levels were maintained throughout the continuous infusion period. The reported volume of blood loss during surgery was also within the normal range for non-haemophilic patients for the type of surgery performed. Red blood cell transfusions were required to balance excessive blood loss during BDDrFVIII continuous infusion in eight (40%) procedures (seven patients), five with bleeding or requiring volume replacement and three to treat anaemia secondary to blood loss. Non-serious adverse events considered by investigators as possibly or probably related to BDDrFVIII continuous infusion were infrequent (n = 5) considering the duration of treatment (n =239 cumulative days of continuous infusion), and all of these were mild-to-moderate in severity. No thromboembolic complications were reported except for one case of thrombophlebitis occurring at the infusion site. Only two patients (four events) experienced serious adverse bleeding; BDDrFVIII was otherwise well-tolerated. These data show that continuous infusion of BDDrFVIII provides reliable haemostasis and is an effective and well-tolerated regimen for patients with haemophilia A undergoing surgery.

A blinded in vitro study with Refacto mock plasma samples: similar FVIII results between the chromogenic assay and a one-stage assay when using a higher cephalin dilution.

Assay of factor VIII (FVIII) in patient samples is routinely carried out using the one-stage assay rather than the chromogenic substrate assay. The introduction of new FVIII preparations for the treatment of haemophilia A, including immunopurified FVIII and particularly, recombinant FVIII (rFVIII) concentrates, has led to discrepancies between the results obtained with the two assays. In patients treated with rFVIII concentrates, FVIII levels measured with the one-stage assay can be 20-50% lower than those measured with the chromogenic assay. In this study, the one-stage assay was performed with cephalin dilutions higher than those recommended by the manufacturer. B-domain-deleted recombinant FVIII, Refacto, was diluted to eight different concentrations, ranging from 1-100 IU dL(-1), in FVIII-deficient plasma and the FVIII activity of the eight solutions was determined by the chromogenic method in a central laboratory. Aliquots were then assayed by the one-stage method in the four participating laboratories, using different dilutions of CK-Prest. When CK-Prest was reconstituted according to the manufacturer's recommendations (dilution 1 : 1), the difference between the one-stage and chromogenic methods was close to 30%. CK-Prest cephalin dilutions of 1 : 5 and 1 : 8 gave very similar results with the two methods, without increasing the interlaboratory coefficient of variation. These findings confirm the influence of phospholipids on the one-stage assay, particularly the importance of using a phospholipid concentration close to the physiological value in platelets. This modified one-stage method may therefore offer an alternative to the use of a concentrate-specific standard.

French previously untreated patients with severe hemophilia A after exposure to recombinant factor VIII : incidence of inhibitor and evaluation of immune tolerance.

Fifty French previously untreated patients with severe hemophilia A (factor VIII < 1%), treated with only one brand of recombinant factor VIII (rFVIII), were evaluated for inhibitor development, assessment of risk factors and outcome of immune tolerance regimen. The median period on study was 32 months (range 9-74) since the first injection of rFVIII. Fourteen patients (28%) developed an inhibitor, four of whom (8%) with a high titer (> or = 10 BU). All inhibitor patients but one continued to receive rFVIII either for on-demand treatment or for immune tolerance regimen (ITR). Among these patients, inhibitor was transient in 2 (4%), became undetectable in 6 and was still present in 6. The prevalence of inhibitor was 12%. Presence of intron 22 inversion was found to be a risk factor for inhibitor development. Immune tolerance was difficult to achieve in our series despite a follow-up period of 16 to 30 months: immune tolerance was complete in only one out of the 3 patients undergoing low dose ITR and in one out of the 5 patients with high dose ITR.

Varicella and thrombotic complications associated with transient protein C and protein S deficiencies in children.

We report six cases of protein S deficiency secondary to varicella. Five cases were complicated by thrombotic and vascular events, namely purpura fulminans and necrotic vasculitis, deep vein thrombosis and stroke. Two cases were associated with protein C deficiency and one case revealed a heterozygous factor XII deficiency. The underlying mechanism of this acquired protein S deficiency is unclear but could be related to a direct effect of zoster virus.

Platelet activating properties of murine monoclonal antibodies to beta 2-glycoprotein I.

Previously developed murine monoclonal antibodies (MAbs) to human beta 2-glycoprotein I (beta 2 GPI), a plasma protein required for the binding of anti-phospholipid antibodies, were studied for anti-platelet reactivity and influence on platelet function. The six MAbs (IgG1 isotype) tested interacted with both intact and fixed platelets in a beta 2 GPI-dependent manner. Carbamylated beta 2 GPI was still recognized by MAbs but was unable to mediate platelet-antibody binding. MAbs induced aggregation and secretion responses of platelets in platelet-rich plasma (PRP) and whole blood, provided subthreshold concentrations of weak agonists (i.e. ADP or adrenaline) were added. When aggregation in PRP was evaluated by a counting technique instead of turbidometrically, the sole addition of MAbs led to a rapid fall in single platelets. Triggering gel-filtered platelets with MAbs together with beta 2 GPI, but not its carbamylated form, led to platelet activation after a lag time, as monitored by aggregometry, measurements of ATP and beta-thromboglobulin secretion and calcium mobilization. F(ab')2 fragments of one of the MAbs failed to activate platelets but inhibited the responses to the whole antibody. This process thus depends on MAbs binding to platelets through both Fab and Fc domains, as confirmed by the suppression of platelet responses upon pretreatment with the anti-Fc gamma RII MAb IV.3. Aggregation and secretion induced by MAbs plus beta 2 GPI did not require exogenous fibrinogen and were variably inhibited in the presence of acetyl salicylic acid, apyrase or Ca2+, depending on the concentrations used for the two proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

Lupus-like anticoagulant properties of murine monoclonal antibodies to beta 2-glycoprotein I.

The lipid-binding inhibitor of coagulation, beta 2-glycoprotein I (beta 2GPI), has been shown to form the antigen to which some autoantibodies against anionic phospholipids (aPL) are directed. Six murine monoclonal antibodies (MAbs) of the IgG1 isotype were raised against human beta 2GPI and could be subdivided into three groups on the basis of mutual competition experiments. MAbs 9G1 and 8C3 (group A) markedly inhibited the binding of immunoglobulins from aPL-positive sera to beta 2GPI-coated wells. Using a lipid-based solid-phase radioimmunoassay, the MAbs interacted with both anionic phospholipids and phosphatidylethanolamine, but not phosphatidylcholine, in a beta 2GPI-dependent manner. A cross-reaction between beta 2GPI from several (including bovine) species was seen with one of the MAbs (9G1). All six MAbs induced dose-dependent prolongation of the DAPTT, DRVVT, KCT and TTI clotting times of human plasma, whereas 9G1 was the sole antibody to be inhibitory with plasma from bovine origin. Synergistic inhibitory effects were observed with MAbs used in pairs provided that they did not compete with each other for beta 2GPI binding. The anticoagulant activity of the MAbs was fully neutralized by the addition of freeze-thawed platelets. The MAbs described here resemble lupus anticoagulants in several respects which makes them valuable to study the involvement of beta 2GPI in the autoimmune thrombotic pathophysiology.

[Treatment of deep venous thrombosis. Comparative study of a low molecular weight heparin fragment (Fragmin) by the subcutaneous route and standard heparin by the continuous intravenous route. A multicenter study]. / Traitement des thromboses veineuses profondes constituées. Etude comparative d'un fragment d'héparine de bas poids moléculaire (Fragmine) administrée par voie sous-cutanée et de l'héparine standard administrée par voie intraveineuse continue. Etude multicentrique.

This open, randomised multicenter trial compares the efficacy and safety of Fragmin administered subcutaneously twice daily with standard heparin administered by continuous infusion in the treatment of deep vein thrombosis (DVT). The initial dose of Fragmin is 100 U anti-Xa/kg/12 h and the further doses are adjusted according to the anti-Xa activity between 0.5 and 0.8 U/ml, 3 hours after the morning injection. The initial dose of standard heparin is 240 UI/kg/12 h. The dose adjustments are based on the daily results of APTT (1.5 - 3 times the control). Treatments efficacy are appreciated when comparing the venography performed before and after 10 days of treatment. The safety is evaluated on clinical parameters and iterative biological tests. Sixty-six patients have been included in this study. Efficacy of the two treatments is equivalent with a phlebographic improvement in respectively 79.3 p. 100 (Heparin Group) and 71.0 p. 100 (Fragmin Group) of the cases and an aggravation in 3.4 p. 100 and 6.4 p. 100 (NS) respectively. The frequency of dosage adjustments is lower and the stability of biological tests is better in the Fragmin group. In conclusion, the administration of Fragmin twice daily by subcutaneous route seems to be equivalent at least to standard heparin continuous infusion in the treatment of recent DVT. The better convenience and safety of Fragmin have to be verified on a larger panel of patients.

[Enoxaparin in the prevention of thrombosis of extracorporeal circulation during dialysis of patients with chronic renal failure]. / L'enoxaparine dans la prévention de la thrombose du circuit extracorporel de dialyse des insuffisants rénaux chroniques.

Chronic renal failure patients under haemodialysis are exposed to two dangers: haemorrhage and clotting of the extracorporeal circulation circuit. This problem can be solved by using low molecular weight heparins. Two studies were conducted to evaluate the effectiveness and safety of a low molecular weight heparin: enoxaparin. The first study, which involved 42 chronic renal failure patients under haemodialysis without any particular risk, enabled the optimum dosage (1 mg/kg bodyweight) to be determined. The second study, which concerned 46 patients at high risk of haemorrhage who received enoxaparin 0.5 mg/kg or 0.75 mg/kg depending on the vascular approach, confirmed that enoxaparin was highly effective (clotting of the extracorporeal circuit in only 0.6 p. 100 of the cases) and well tolerated (bleeding in only 0.2 p. 100 of the cases).

[Thrombosis and antiprothrombinase in children. Apropos of 2 cases]. / Thrombose et antiprothrombinase chez l'enfant. A propos de deux observations.

Two cases of arterial and venous thrombosis associated with lupus anticoagulant are reported. The first case was observed in the context of a systemic lupus erythematosus. In the second case, no underlying disease was found. From these 2 cases and a review of the literature, the particularities of this association in children is discussed.

[The use of enoxaparine for anticoagulation in extracorporeal circulation in hemodialysis at high risk for hemorrhage]. / Utilisation de l'énoxaparine pour l'anticoagulation du circuit extracorporel des hémodialyses à haut risque hémorragique.

After evaluation of efficacy of a low molecular weight heparin (LMWH), enoxaparine (Lovenox), in patients on continuous hemodialysis without a particular known hemorrhagic risk, this same LMWH was administered during 493 dialysis sessions to 46 patients presenting various degrees of risk of hemorrhage. Lower doses of 0.5 mg/kg or 0.75 mg/kg as bolus injections were administered at the start of the 4 or 5 hourly session. Clotting in the extracorporeal circulation (ECC) was noted in 0.6% treatments, the product being effective in all other sessions. Only one case of bleeding can be imputed to the LMWH injected during hemodialysis (0.2% of sessions). Although an open trial, the superiority of enoxaparine both for antithrombotic activity in ECC, and its simple management, as well as the small number of hemorrhages noted, has led to the routine use of this method in all patients at hemorrhagic risk.

[Biological activity of enoxaprine (PK 10169) in hemodialysis. A dose study]. / Activités biologiques de l'éjnoxaparine (PK 10,169) en hémodialyse. Etude de dose.

Anti-Xa and anti-IIa activity were evaluated in 42 patients with chronic renal insufficiency, in an open randomized trial, to determine optimal dose of PK 10169 for prevention of coagulation in extracorporeal circuit during hemodialysis sessions. PK 10169 was given as single doses of 0.75, 1 and 1.25 mg/kg at start of dialysis, into the arterial line. All dialysis sessions were continued over the 4 hours provided for without the need for further injections. A linear relation existed between anti-Xa and anti-IIa activity measured at end of dialysis and the dose injected (p less than 0.001). Efficacy and tolerance were assessed clinically and biologically and were rated excellent at the 3 dose levels, the best tolerance/efficacy ratio being at the 1 mg/kg dosage.

[Acute chorea, systemic lupus erythematosus and antiphospholipid antibodies. Apropos of a case]. / Chorée aiguë, lupus érythémateux disséminé et anticorps antiphospholipides. A propos d'une observation.

A case of acute chorea in a 10 years old girl complicating a systemic lupus erythematosus associated with antiphospholipid antibodies is reported. The lupus anticoagulant was detected with a coagulation assay and the false serological reaction for syphilis by the RPR test. The child recovered with Prednisone therapy. The place of chorea in the context of neurological complications of SLE and the particularity of its association with anti-phospholipid antibodies are discussed.

[Thrombocytosis and reduced levels of factor VIII in rheumatoid purpura in children]. / L'hyperplaquettose et la baisse du facteur XIII dans le purpura rhumatoïde de l'enfant.

Thirty three patients with Henoch-Schoenlein purpura were studied at various developmental stages of this disease: specially platelet counts and factors XIII and VIII. During the development phases: 40,6% of the patients have a slight but regressive thrombocytosis (greater than 400 G/l); and 75% a reduced factor XIII, well correlated with the severity of the clinical status (level as low as 60% can be considered as a "gravity threshold"), and corrected during the improvement of the disease. This reduced factor XIII is probably linked to the local inflammation in the vessels. Factor VIII studies (specially VIII A: Ag) were normal.

[Consumption coagulopathies following peritoneojugular bypass. Prevention by a heparin-antithrombin III combination]. / Les coagulopathies de consommation après dérivations péritonéo-jugulaires. Prévention par l'association héparine-antithrombine III.

Consumption coagulopathy (CIVD) is a frequent complication of peritoneojugular bypass operation. Preventive treatment applied involves low-dose heparin (1.5 mg/kg/d) to maintain an antithrombin III concentration of at least 65%. Results are evaluated in 6 patients treated by 7 bypass operations. A biologic CIVD developed in 2 cases (29%) but no clinical coagulopathy was observed. This incidence is less than that usually reported, a literature review indicating a biologic coagulopathy in 65% of cases, with clinical evidence in 12.5%. Furthermore, patients with spontaneously elevated AT III levels did not develop CIVD while, in contrast, sufficiently high concentrations of AT III could not be maintained in the 2 patients with coagulopathy. These findings suggest the interest of prevention of a CIVD by the use of this procedure.

Structural genes of coagulation factors VII and X located on 13q34.

From 7 cases of abnormalities involving chromosome 13, the structural gene(s) coding for coagulation factors VII and X were located in the region 13q34-13qter. Gene-dosage effects for these coagulation factors seem to act in both directions, causing a decrease when there is monosomy of segment 13q34, but also, as has not been demonstrated before, an increase when there is trisomy of this same segment.

Protein C level at birth.

The protein C level was determined, on cord blood, for 30 healthy newborns by electro-immuno assay using a monospecific antiserum. For the newborns the mean level of protein C related antigen is about one third of normal adults' mean level. There is a good correlation between Protein C related antigen and prothrombin related antigen. The low level of these vitamin-K-dependent proteins is probably a consequence of partial liver immaturity at birth. Using two-dimensional immuno-electrophoresis we were unable to detect subcarboxylated forms of protein C. However these abnormal forms could be seen in vitamin-K deficiencies of neonates.