Irinotecan-induced immune thrombocytopenia.

BACKGROUND: Irinotecan is currently used as second-line chemotherapy for advanced colorectal cancer. We report a case of severe thrombocytopenia after Irinotecan, suggesting an immune mechanism, in a 53-year-old patient. PATIENTS AND METHODS: The patient's sera were screened for platelet antibodies with an indirect platelet immunofluorescence test (PIIFT). The monoclonal antibody immobilization of platelet antigen assay (MAIPA) was used to characterize the antibody target. RESULTS: We detected an IgG platelet antibody in the patient's serum in the presence of Irinotecan by means of PIIFT, and not in the presence of SN-38, its active metabolite. The specificity of the binding was asserted after CD32 MoAb blockade. The platelet binding site could not be strictly identified with MAIPA and immunoblotting but GpIIb/IIIa can be excluded after experiments with Glanzmann platelets. CONCLUSION: This case can be considered the first documented Irinotecan-induced immune thrombocytopenia.

How to stabilize the level of ionized calcium and citrate during plateletpheresis.

BACKGROUND AND OBJECTIVES: Citrate reactions are uncomfortable and potentially dangerous to apheresis donors. Reduction of citrate increases comfort, but may lead to platelet clumping. MATERIALS AND METHODS: We describe a protocol for stepwise reduction of the volume of ACD-A injected during plateletpheresis. This protocol has been carried out in 45 healthy donors with the Cobe 2997 (Cobe) cell separator, and in 35 with the Fenwal-CS 3000 (CS). RESULTS: Using this protocol, during the first hour of platelet collection, ionised calcium decreased on average by 18% for CS and by 18.4% for Cobe. During the second hour, Ca2+ and citrate ion concentration did not change with either Cobe or CS (about 65% of citrate ion load is eliminated). We observed mild signs of neuromuscular hyperexcitability in only 22% and 28% of donors with Cobe and CS, respectively. We also found a significant reduction of phosphate ions (p < 0.0001) at the end of the procedures. CONCLUSIONS: With this stepdown citrate reduction protocol, we obtained a significant reduction of injected citrate without the complication of platelet clumps.

The use of ABO-incompatible grafts in liver transplantation: a life-saving procedure in highly selected patients.

The aim of this study was to assess the long term results of 43 ABO-incompatible liver transplantations performed in 40 patients. The 5-year patient and graft survival rates were 50 and 20%, respectively. In the group of patients transplanted in emergency for fulminant or subfulminant liver failure, ABO incompatibility had no significant impact on patient survival (P = 0.09). Graft survival, however, was significantly impaired (P = 0.0002) through a greater incidence of hyperacute rejection (20%), vascular thrombosis, and biliary injury (56%). Increasing the magnitude of immunosuppression and postoperatively reducing the titer of anti A/B antibodies by plasmapheresis had little influence on the incidence of these complications and were associated with a greater incidence of septic complications. These results indicate that the use of ABO-incompatible liver grafts is a life-saving procedure in patients with life-threatening acute liver failure, but at a high price. Justification for accepting or not accepting an ABO-incompatible graft in these emergency situations depends on the personal choice in giving priority to saving the patient in an acute life-threatening condition or to giving the graft the best chance of success. To avoid this difficult choice, efforts should aim at expanding the pool of grafts available in emergency, at developing artificial support devices that could allow to safely delay transplantation, or at more efficiently controlling the humoral response.

An observational study of 11 French liver transplant recipients infected with human immunodeficiency virus type 1.

We report the clinical and biological course of infection with human immunodeficiency virus (HIV) type 1 in 11 liver transplant recipients who acquired this infection between 1985 and 1987. Eight patients were infected by blood or blood products from graft-related transfusions and one by the graft itself; the remaining two patients were infected after transplantation and had independent risk factors. All patients received a triple-drug immunosuppressive regimen including cyclosporine. The mean duration of follow-up after liver transplantation was 52 months (standard error, +/- 32 months). Chronic graft rejection was documented in four cases. The cumulative incidences of HIV-related complications and HIV-related deaths were 82% and 27%, respectively. Three patients died rapidly of HIV disease. The survival rate 7 years after transplantation was 36% among the 11 HIV-infected patients, whereas it was approximately 70% among HIV-negative liver transplant recipients during the same period. The course of HIV infection in the four survivors did not appear to differ from that in other patients infected by blood transfusion.

Open trial of tacrine therapy in 70 HIV-infected patients.

The purpose of this study consisted in following-up the biological and clinical parameters in HIV infected patients treated with tacrine (THA). THA (150-300 mg/d) was administrated to 70 patients (39 IVC I and 31 IVC II and III). Thirty-five were treated after discontinuation of AZT treatment and 35 as a first intention treatment. Thirty (43%) patients showed an increase in the CD4+ cell count by more than 50% relative to pretreatment levels and fifteen (21%) showed an increase of more than 25%. p24 antigenemia (Ag p24) became negative in eight of the twenty-seven patients who were initially positive, and decreased by 25 and 50% in nine and six patients, respectively. Ag p24 was therefore decreased in 80% of the patients. From a clinical point of view, there were two deaths (3%) and five opportunistic infections (7%). The treatment with THA was stopped in five patients because of side effects (nausea, rash). Neither hepatotoxicity, hematotoxicity, nor pancreatitis was observed during the THA treatment. In group II and III only two patients (6%) developed an opportunistic infection.

[Liver damage induced by the ingestion of a product of phytotherapy containing wild germander. Four cases]. / Atteinte hépatique associée à la prise d'un produit de phytothérapie contenant de la Germandrée petit-chêne. Quatre cas.

We report 4 cases of patients who developed hepatic injury during administration of herbal medicines for loosing weight with Wild Germander. Three developed jaundice and one had fatigue. Aminotransaminase activities were increased in all patients. Outcome was favorable after drug withdrawal in all patients. Liver biopsy showed centrolobular necrosis and portal lymphoplasmocytic infiltration. Another drug than Wild Germander might have been implicated in hepatic injury in two patients. The similarity of these cases suggests, however, that Wild Germander, like other herbal medicines, may be responsible for hepatic injury.

[Liver transplantation and the major histocompatibility complex]. / Transplantation hépatique et complexe majeur d'histocompatibilité.

We have carried out a retrospective study over 308 liver transplant patients (31 of them have had a retransplantation) in Professor Bismuth's Department at Paul Brousse Hospital. The purpose of the study was a search for the possible effect of donor/recipient major histocompatibility complex on the evolution of the transplantation. We chose to study four parameters: early acute rejection; chronic rejection; retransplantation cases and death frequency; graft survival. We observed the following: for HLA A locus: in cases of total or partial compatibility there are more moderate early acute rejections than in the case of incompatibility (p less than 0.02); for HLA B locus: in the case of total compatibility there are more chronic rejections than in cases of partial or total incompatibility (p less than 0.03); for joint A and B locus: the results are similar to those of A locus (p less than 0.03); for HLA class I: we observed no effect either on graft survival or on retransplantation cases or on death frequency; for HLA DR: we did not find any effect on the studied parameters. Considering the low statistical significance of these results and in order to confirm our analysis, we have started a prospective study in collaboration with two other European Transplantation Centers.

[Safety of donors, quality of products, how much to reduce the quantity of citrate]. / Sécurité des donneurs, qualité des produits jusqu'où diminuer la quantité de citrate.

We examined 1,053 blood samples from 48 donors, for the effect of gradual reduction of citrate. We observed that: 1--Platelet count does not show any significant variation between 1/8 to 1/18 ratio. 2--In 13.3% of the cases, platelet clumping starts at 1/18 ratio. 3--There was no significant variation of the thrombin plasma level between 1/8 to 1/16 ratio (by measuring thrombin/ATIII complex). Our results show clearly that we can reduce the citrate ratio to 1/14 without expecting any adverse effect. Therefore we designated 1/14 as the security ratio. Parallel to this we also found that the average level +/- SD of ionized calcium is 100 +/- 10 muMol at 1/14 ratio.

[Delayed autotransfusion associated with the cell-saver method in cardiovascular surgery. Values, methods, initial results]. / Autotransfusion différée associée à la méthode du cell-saver en chirurgie cardio-vasculaire. Intérêts, méthodes, résultats préliminaires.

The aim of deferred autotransfusion associated with the Cell-Saver system, i.e. the recovery of intraoperative blood loss, is to avoid using external homologous blood products. Transfusion-transmitted diseases and immunisation problems can be avoided: normovolumic haemodilution is an advantage in patients with coronary artery disease and economies can be made in the use of homologous blood. This technique has been in use in Professor Cabrol's department since 1987 with the help of the Blood Transfusion Centre of the Pitié Hospital. The contraindications are unstable angina, severe cardiac failure and anaemia of less than 11 g Hb at the first consultation. A review of the first 65 patients included in the protocol showed that deferred autotransfusion was well tolerated in all cases and that only 10 per cent of patients required transfusion with homologous blood. Autotransfusion associated with the Cell-Saver system is therefore a good method which should be extended to the largest possible number of patients referred for elective cardiac surgery.