PubMed Health⌕ Search

Biomedical subjects

J Goudemand

Publications and source records attributed to J Goudemand.

At least 37 records · Page 2Linked to original sources
PubMed2000

[Platelet transfusion and allergic transfusion reactions: experiences at Lille Hospital over a four year period].

Among the immediate transfusion reactions caused by the utilization of blood products, those suggesting immuno-allergic mechanisms posed problems for frequency, gravity, laboratory diagnosis and safety. We report here the Lille Hospital's experience over a four-year period concerning these manifestations after platelet concentrate transfusion. Eight hundred and fifty-two immediate transfusion reactions have been declared, of which 230 were allergic, which appeared in 181 patients (27%). Among the most frequent clinical signs, rash was often described (158 cases: 68.7%); less frequent were respiratory problems such as dyspnea (34 cases: 14.8%) and hypotensive reactions (18 cases: 7.8%). Seven patients presented severe reactions (3%). Twenty percent of them presented multiple allergic reactions and in 43.2%, the recurrence was more serious than the initial problem in spite of preventive medication; the use of washed blood components was necessary. The age of platelet concentrates does not appear to play a part in provoking these events (67% of platelet concentrates had been collected within four days). These allergic transfusion reactions posed problems for those who prescribe medication, because they are frequent, sometimes serious, can recur and at present, the proposed medication prevention is not always efficient.

Adolescent↗
PubMed1999

[Low prevalence of anti-annexin V antibodies in antiphospholipid syndrome with fetal loss].

PURPOSE: Annexin V, a protein with potent anticoagulant activity has a calcium-dependent binding affinity for phospholipids. Annexin V is distributed in many organs, especially in the placenta and endothelium. Various studies have shown that placental annexin V is decreased in women with anti-phospholipid syndrome. It has been suggested that annexin V might be a target of anti-phospholipid antibodies and that the subsequent decrease in annexin V might be associated with obstetrical complications. We investigated the presence of anti-annexin V antibodies in the plasma of women with anti-phospholipid syndrome and obstetrical complications. METHODS: Twenty-three patients with at least one spontaneous abortion were included in the study. Anti-cardiolipin antibodies and lupus anticoagulant were present in 87% and 30% of the patients, respectively. A group of 40 healthy women were included in the control group. Anti-annexin V IgG and IgM antibodies were measured by ELISA. RESULTS: The IgG mean OD was 0.07 +/- 0.013 in patients and 0.042 +/- 0.06 in the control group. There was no significant difference between the two groups (P = NS). Only two out of the 23 patients and two out of the 40 healthy women were positive for IgG (OD > 0.25). The sensitivity of the assay was poor (8.7%). Even when the threshold was adjusted according to the mean OD in control subjects +2 SD, the sensitivity was still poor, reaching only 13%. CONCLUSION: The prevalence of anti-annexin V was low in patients with anti-phospholipid syndrome and repetitive spontaneous abortions. Anti-annexin V assay does not appear to be sensitive enough for the identification of anti-phospholipid antibodies that might be involved in the decrease in annexin V leading subsequently to thrombosis risk.

Abortion, Spontaneous↗
PubMed1999

[Diagnostic difficulties of transfusion incidents due to bacterial contamination: report of two cases].

The French hemovigilance system has recently underlined the relative frequency of transfusion-associated bacterial sepsis and the necessity to remain constantly aware of this eventuality. We describe the experience of a hematology unit over a 18-month period: 189 acute transfusion reactions were registered and bacterial cultures of the implicated cellular blood products realized in 82 of them. A positive result was obtained in two cases. For both cases, clinical symptoms of transfusion reaction were limited to a lasting fever, and a skin rash occurred in aplastic patients with preexisting signs of sepsis. The causal relationship between this contamination and the transfusion reaction is difficult to establish. Clinical manifestations justifying a bacterial inquiry must therefore be more precisely defined, particularly in multitransfused patients.

Adult↗
PubMed1999

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. Nine of the 11 patients were high responders ¿>10 Bethesda units (BU) with peak inhibitor levels ranging from 10 to 566 BU. The other two were low responders with peak levels between 0.7 and 2 BU. Before inhibitor detection, the patients had been receiving products of various purities. The IIT regimens were very heterogeneous, and the treatment schedule varied from a short period with 50 IU kg-1 every 2 days, followed by 100 IU kg-1 every 2 days and then 220 IU kg-1 daily. The outcome was considered successful when the inhibitor level fell to 0.6 BU or lower after IIT treatment. The outcome overall was successful in nine out of 11 patients (81.8%), with the nine successful cases comprising seven of the nine high responders (77.8%) and the two low responders. Definite failure of IIT was observed in one high responder after two different IIT regimens. A second high responder is still on IIT treatment. All patients in whom IIT was successful are currently receiving r-FVIII on demand or prophylactically at various dosages. Despite the variability of the patient characteristics and the IIT schedules, this study demonstrates that r-FVIII represents an effective alternative for the eradication of inhibitors through IIT.

Adolescent↗
PubMed1999

Hemophilia. Treatment of patients with inhibitors: cost issues.

The management of bleeding episodes and surgery in haemophilia patients who develop inhibitors is specially difficult and also has major impact on therapeutic costs. We assessed the costs of coagulation factors in noninhibitor haemophilia A and B patients (0 Inh; n=103), patients with low responding inhibitors (LR; n=24), patients with high responding inhibitors (HR; n=17) in our centre between 1988 and 1998 during two periods: 1988-1995 and 1996-1998, before and after the introduction of recombinant factor VIIa in France (1996). From 1988 to 1995 the mean annual cost of 0 inh and LR patients was 43 234 and 49 422, respectively, with more than 90% as home treatment, whereas the mean cost of HR patients was 56 262 (1.3 time more than 0 Inh), half of this cost being related to treatment administered in hospital. From 1996 to 1998, the mean cost of HR patients was 186 482, approximately three times more than that of 0 Inh (59 887) and LR patients (54 226) with half of the cost due to treatment administered in hospital. So rFVIIa seems to exert a major economic effect on both the cost of home treatment and treatment administered in hospital. It must be pointed out that particularly severe bleeding episodes were effectively treated with rFVIIa during this period and that rFVIIa allowed surgery to be undertaken: including two elective orthopaedic surgeries. So there is no doubt that rFVIIa offers new perspectives in the therapeutic management of HR patients, but creates a new economic situation which needs further evaluation.

Adolescent↗
PubMed1998

A novel mutation in the D3 domain of von Willebrand factor markedly decreases its ability to bind factor VIII and affects its multimerization.

In type 2N von Willebrand disease (vWD), von Willebrand factor (vWF) is characterized by normal multimeric pattern, normal platelet-dependent function, but a markedly decreased affinity for factor VIII (FVIII). In this report, we describe the case of a vWD patient who has an abnormal vWF multimers distribution associated with a markedly decreased vWF ability to bind FVIII. Sequencing analysis of patient's vWF gene showed, at heterozygous state, a G-->A transition resulting in the substitution of Asn for Asp at position 116 of the mature vWF subunit and a C-->T transition, changing the codon for Arg 896 into a stop codon. His sister who has a subnormal vWF level, but a normal FVIII/vWF interaction, was found to be heterozygous for the Arg896ter mutation only. Recombinant vWF (rvWF) containing the candidate (Asn116) missense mutation was expressed in COS-7 cells. The expression level of Asn116rvWF was significantly decreased compared with wild-type rvWF. The multimeric pattern of Asn116rvWF was greatly impaired as shown by the decrease in high molecular weight forms. The FVIII binding ability of Asn116rvWF was dramatically decreased. These data show that the Asp116Asn substitution is the cause of both the defective FVIII/vWF interaction and the impaired multimeric pattern observed in the patient's vWF. The monoclonal antibody 31H3 against D' domain of vWF (epitope aa 66-76) that partially inhibits the FVIII binding and recognizes only nonreduced vWF, showed a decreased ability to bind Asn116rvWF when used as capture-antibody in enzyme-linked immunosorbent assay (ELISA). This result suggests that a potential conformation change in the D' domain is induced by the Asp116Asn substitution, which is localized in the D3 domain.

Amino Acid Substitution↗
PubMed1998

[Recombinant activated factor VII: a new treatment for hemophilia].

Recombinant factor VIIa (NovoSeven, NovoNordisk) initiates coagulation in inhibitor patients who either develop alloantibodies to clotting factors or those with acquired haemophilia. The human gene for FVII was transfected into a baby hamster kidney (BHK) cell line which secretes FVII in a single-chain form. Recombinant FVII is purified from the medium by four chromatographic steps including immunoaffinity chromatography with a monoclonal anti-FVII. During this process rFVII undergoes autoactivation to rFVIIa. NovoSeven does not contain any stabilising protein including human albumin. The SA is 50 KU/mg, the concentration is 0.6 mg/mL. Recovery is 45%, clearance is 31 mL/h/kg, the half-life was estimated between 2 and 3 hours. Combined to tissue factor rFVIIa directly activates factor X without implication of FVIIIa and FIXa. There is no systemic coagulation activation. Efficacy was assessed from data derived largely from the Compassionate Use Programme and clinical studies using rFVIIa as first line therapy. Various situations were proven to be efficiently resolved with rFVIIa including surgeries. Usual dosages are 90-120 mcg/kg administered every 2-3 hours. There were no side effects even in cases of prolonged administration. Drawbacks are the short half-life and the cost of the product.

Animals↗
PubMed1998

Clinical management of patients with von Willebrand's disease with a VHP vWF concentrate: the French experience.

Part of the French clinical experience using the solvent/detergent (S/D) treated VHP von Willebrand factor (vWF) concentrate (LFB, Les Ulis, France) characterized by a high vWF:RCoF specific activity and a low factor VIII (FVIII) content is reported. Since 1989 this concentrate has been routinely used in clinical practice taking into account the vWF:RCoF given by the manufacturer. Seventy-five patients with von Willebrand disease (type 1: 42, 2A: 11, 2B: 5, 2N: 6, 3: 4, acquired: 7) were treated on 99 occasions either to control spontaneous bleedings (15) or to prevent haemorrhagic risks associated with minor (< 5 days of treatment) (48) or major (5 days of treatment) (36) surgery including seven knee or hip-replacements. Forty lots of concentrate were used containing 58 +/- 13 U mL-1 vWF:RCoF with less than 10 units of FVIII per 100 units vWF:RCoF. Patients with type 2N were analysed separately. With the exception of gastro-intestinal bleedings, spontaneous bleedings were generally stopped after few infusions of 40-47 U kg-1 vWF:RCoF. Patients having more than 20 U dL-1 FVIII were treated on 54 surgical occasions with one preoperative infusion (51-55 U kg-1 vWF:RCoF) which allowed an increase in FVIII concentration to a mean level of 67-88 U dL-1. Patients with less than 20 U dL-1 were either treated with two preoperative infusions of vWF, 12 or 24 h apart (11 cases) or received a FVIII injection immediately after the preoperative infusion of vWF (10 cases). During the postoperative period vWF alone (30-35 U kg-1 vWF:RCoF) allowed FVIII to be kept at a mean level of 118-138 U dL-1 not exceeding 180 U dL-1. Patients with type 2N were treated taking in account only their baseline FVIII concentration. No haemorrhagic complications occurred in any of the patients. Thus it was found to be feasible and practical to manage replacement therapy in patients with von Willebrand disease (whatever the type or the circumstances) on the basis of the vWF:RCoF activity of the concentrate.

France↗
PubMed1998

Antithrombin, protein C and protein S levels in 127 consecutive young adults with ischemic stroke.

OBJECTIVES: The aim of our study was to evaluate the prevalence of antithrombin, protein C and protein S deficiencies in consecutive ischemic stroke patients under 45. MATERIAL AND METHODS: We studied 127 consecutive patients with a mean age of 34.4 years admitted for an ischemic stroke, over a 2-year period, after exclusion of those with arterial dissection. Antithrombin, protein C and protein S levels were measured in all patients at the acute stage of the ischemic stroke and measurements were repeated in case of abnormality. RESULTS: We found abnormal levels in 9 patients. Seven had an acquired cause of deficiency (pregnancy, oestrogen, acute inflammation). Two had no obvious acquired cause of deficiency but further controls were normal. CONCLUSIONS: Hereditary deficiencies of coagulation inhibitors are rare in ischemic stroke patients under 45 and their systematic detection seems to be of poor interest.

Adolescent↗
PubMed1998

Pharmaco-economic aspects of inhibitor treatment.

The management of bleeding episodes and surgery in haemophilia patients who develop inhibitors is especially difficult. Haemostasis is typically achieved using high doses of factor VIII (FVIII) or FIX to overcome the inhibitor, or by using activated products, or by inhibitor eradication by immune tolerance induction. We assessed the costs of coagulation factors for non-inhibitor haemophilia A and B patients (ACneg; n = 104), patients with low responding inhibitors (LR; n = 24) and patients with high responding inhibitors (HR; n = 17) in our centre between 1988 and 1995. In ACneg and LR patients, > 90% of costs were attributed to home treatment, compared with 54% for HR patients. The costs of treatment were $US 36.8 m total, $US 41,000 mean per patient for ACneg patients; $US 10 m total, $US 46,000 mean per patient for LR patients; and $US 7.6 m total, $US 59,000 mean per patient for HR patients. The mean cost of hospital treatment per HR patient was more than 10 times that for ACneg or LR patients and this was influenced by the occurrence of 4 very severe bleeding episodes in these patients. This analysis highlights the different costs and treatment patterns for inhibitor patients and should enable us to evaluate the impact of new treatments such as recombinant activated rFVII (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark) on treatment at our centre in the future.

Antibodies↗
PubMed1998

Experiences with continuous infusion of recombinant activated factor VII.

A questionnaire was sent to 28 haemophilia treatment centres known to have used recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark), to collect data on continuous infusion of this product. This mode of administration was recently introduced for rFVIIa but there are several questions which remain to be answered in order to optimize this technique. Of the 26 responding centres, 14 had used rFVIIa in continuous infusion for 40 treatment episodes over a total of 283 days. In most of the cases the treatment was targeted at a factor VII level of 10 IU/ml, monitored by the one-stage clotting assay. This seemed to be adequate for most of the haemorrhagic and surgical procedures. Pretreatment pharmacokinetic evaluation was performed in only a minority of the cases but is probably of great importance given the wide variation observed in the clearance values. A strategy was necessary to prevent local thrombophlebitis, at least for infusions in peripheral veins; parallel infusion of heparin, saline or dextrose-saline proved effective. The question of optimal monitoring needs further attention. Haemorrhagic complications were significantly less frequent when treatment was combined with the antifibrinolytic tranexamic acid.

Drug Monitoring↗
PubMed1998

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.

Child↗
PubMed1998

A cross-over pharmacokinetic study of a double viral inactivated factor IX concentrate (15 nm filtration and SD) compared to a SD factor IX concentrate.

A double blind randomized cross-over multi-center study has been conducted to compare the pharmacokinetic and coagulation activation markers of high-purity factor IX concentrate subjected to both solvent/ detergent (SD) treatment and 15 nm-filtration (FIX-SD-15) with the licensed product subjected only to solvent-detergent (FIX-SD). This filtration process allows the elimination of small particles, such as non-enveloped viruses (i.e., hepatitis A and parvovirus B19). Eleven severe hemophilia B patients (FIX coagulant activity <2 IU/dl) received one infusion of 60 IU/kg of FIX-SD and one infusion of 60 IU/kg of FIX-SD-15 at least at 10 days interval. Blood samples were obtained before and at various time up to 72 h after infusion. The decay curves of factor IX (FIX:C and FIX:Ag) were evaluated by a model independent method. Bioequivalence was found between the two concentrates using the Schuirmann test. The mean FIX:C and FIX:Ag recovery of FIX-SD-15 was 1.08 and 0.89 IU/dl/IU/kg respectively with a mean half-life of 33.3 h for FIX:C and 25.6 h for FIX:Ag. Six months after initial enrollment, pharmacokinetic parameters were similar in the 7 patients tested. There was no significant variation of prothrombin fragment 1+2 and thrombin-antithrombin complexes measured up to 6 h after infusion, indicating that there was no activation process after administration of FIX. In conclusion, these data demonstrate that the introduction of a 15 nm filtration does not alter the pharmacokinetic profile of a well characterized SD FIX concentrate while providing additional viral safety.

Adolescent↗
PubMed1997

[Endothelium and hemorrhages].

Normal endothelium, as well as megakaryocytes, produces and secretes von Willebrand factor which plays a pivotal role in haemostasis. It mediates platelet adhesion and shear-stress-induced aggregation at the site of vessel wall injury and also serves as a carrier protein of factor VIII, an essential cofactor in coagulation. The quantitative or qualitative abnormalities of von Willebrand factor lead to von Willebrand disease, the most common congenital bleeding disorder. Over the past few years major progress in the knowledge of the synthesis, structure and functions of von Willebrand factor have led to improve the diagnosis and treatment of the different molecular forms of von Willebrand disease.

Animals↗
PubMed1997

Thrombocytopenia induced by vancomycin-dependent platelet antibody.

BACKGROUND AND OBJECTIVES: Many drugs are associated with thrombocytopenic purpura through immune-mediated platelet destruction. The case of a woman who suffered life-threatening thrombocytopenia during vancomycin treatment for Staphylococcus aureus septicemia is reported. MATERIALS AND METHODS: Conventional clinical and laboratory methods, including flow cytometry. RESULTS: After treatment of septicemia with vancomycin, severe thrombocytopenia and bleeding occurred, without detection of drug-dependent platelet antibodies (DDPA). This was followed by vegetative endocarditis, whereupon antibiotics were withdrawn so as to isolate the organism. The thrombocytopenia was corrected. On day 34, antibiotics including vancomycin were reinstituted, and three days later thrombocytopenia recurred. With a change in antibiotics, the platelet count corrected itself within four days. CONCLUSIONS: Vancomycin may induce potentially severe immunological thrombocytopenia.

Aged↗