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Biomedical subjects

J G Eernisse

Publications and source records attributed to J G Eernisse.

At least 19 recordsLinked to original sources

Twenty-two years of intra-uterine intraperitoneal transfusions.

Over a period of 22 years, 154 fetuses were treated with 270 intra-uterine intraperitoneal transfusions. The patients were divided into three groups, according to the period they were treated. The overall percentage of surviving infants increased from 33% during the first period to 58% in the last period. In the group of infants that were not hydropic at the time of the first transfusion, the survival rate increased from 35 to 83%. In the group of children that were hydropic during the first transfusion, the survival rate during the first and last period was 24 and 42%, respectively. The percentage of fetuses that needed their first transfusion before the 26th week of pregnancy increased from 15 to 32% during the study period. Only 13% of these children survived. Lately, the intravascular approach has been introduced. Intravascular transfusions seem to be very effective, especially in early pregnancies and in hydropic fetuses. Application of the two techniques each in the most appropriate situation might offer optimal results for the near future.

Blood Transfusion, Intrauterine↗

Haematopoietic and immunologic abnormalities in severe aplastic anaemia patients treated with anti-thymocyte globulin.

Thirty-five patients with severe aplastic anaemia (SAA) were extensively evaluated 0.3-12.4 years (median 3.8) after anti-thymocyte globulin (ATG) treatment. All but one were transfusion independent. Most patients revealed a normal Hb level and a granulocyte count over 1.5 x 10(9)/l but were still thrombocytopenic due to decreased platelet production. Lymphocytopenia and/or monocytopenia was found in about 30%. Two patients had a monocytosis. Although there was a great range in degree of recovery at various time intervals after ATG, patients tested more than 4 years after ATG tended to have higher cell counts. Lymphocyte counts correlated with the interval between ATG and evaluation, and with haematopoietic recovery. Qualitative abnormalities were found in all cell lines. Most patients showed a homogeneous macrocytic RBC population, and almost 50% a positive sucrose lysis test; only three patients showed evidence of haemolysis and only two of these showed a positive Ham test. Mean platelet volumes were reduced out of proportion to their number. Platelet function, determined by bleeding time and aggregometry, was impaired in over 30%. The granulocytic series showed a shift to the left in about 30%. Hypersegmentation and pseudo Pelger-Huet anomaly were seen in some patients. Lymphocyte subset distribution in blood and bone marrow was within the normal range but absolute blood levels of CD4 cells in particular were slightly decreased, and tended to increase gradually with time after ATG. IgG and IgA levels were significantly decreased. In only one patient cytogenetic analysis of unstimulated bone marrow cells revealed an abnormal karyotype, but in eight of eight patients an increased sensitivity of lymphocytes to X-rays was found. These data suggest impairment at the level of the very early haematopoietic progenitor cell in all patients up to 10 years after ATG. Since similar findings have been reported in clonal (pre-)malignant disease, SAA, improved after ATG treatment, might be prone to clonal (malignant) evolution.

Adolescent↗

Beneficial effect of intravenous gammaglobulin in a patient with complement-mediated autoimmune thrombocytopenia due to IgM-anti-platelet antibodies.

Intravenous gammaglobulin (IV-IgG) was administered to a patient with chronic idiopathic thrombocytopenic purpura due to an unusual IgM platelet autoantibody causing in vitro complement-dependent thrombocytoxicity and in vivo intravascular platelet destruction. After IV-IgG infusion the peripheral platelet count temporarily increased to normal values, the mean platelet survival time increased and the platelet sequestration pattern changed from intravascular to predominantly hepatic destruction. In vivo and in vitro observations in this patient illustrate a transient beneficial effect of gammaglobulin infusion due to interference with the complement-fixing autoantibodies against platelets.

Aged↗

Alloimmunization after leukocyte-depleted multiple random donor platelet transfusions.

In a prospective study we investigated the development and the course of alloimmunization after leukocyte-depleted red cell and multiple random donor platelet transfusions in 335 patients. Of these 335 patients, who had a negative antibody screening on admission and a negative transfusion history, 69 (21%) developed either transient (n = 18) or permanent (n = 51) lymphocytotoxic antibodies, but only 31 patients (9%; 95% confidence limits 6-12%) developed multispecific alloantibodies necessitating HLA-matched platelet transfusions. There was no difference with regard to the development of antibodies and platelet refractoriness between leukemia patients receiving cytostatic treatment and patients with aplastic anemia receiving prednisone and antithymocyte globulin. Females with previous pregnancies developed platelet refractoriness with an increased incidence (Chi 2 13.38; p less than 0.001) compared to females without previous pregnancies, males, and children.

Blood Platelets↗

Severe leukocytoclastic vasculitis of the skin in a patient with essential mixed cryoglobulinemia treated with high-dose gamma-globulin intravenously.

We describe a patient with long-standing severe leukocytoclastic vasculitis of the skin and essential mixed cryoglobulinemia type II, who showed a limited reaction to immunosuppressive drugs, plasmapheresis, and colchicine. Therapy with high-dose gamma-globulin intravenously (IV) for five days resulted in disappearance of vasculitis lesions within three weeks. After gamma-globulin IV treatment there was a decrease in cryoglobulin, circulating immune complexes, and IgM, paraprotein, and a rise in complement levels. No serious side effects were noted during or after gamma-globulin IV treatment. The patient has been in remission for 16 months.

Acute Disease↗

Recovery of hematopoiesis after blood-group-incompatible bone marrow transplantation with red-blood-cell-depleted grafts.

Severe hemolytic transfusion reactions may complicate major blood-group-incompatible bone marrow transplantations (BMT). Probably the most appropriate way to avoid this complication is removal of the incompatible red blood cells (RBC) from the bone marrow graft. In this report we describe a method to eliminate incompatible RBCs that is based on repeated dilution of the graft with donor-and-recipient--compatible third-party erythrocytes. Four patients with ABO incompatibility and one patient with Rh-C incompatibility were transplanted using this technique. After the procedure 86 +/- 8% (mean +/- SD) of the nucleated cells, 95 +/- 14% of CFU-GM, 88 +/- 14% of BFU-e, and 103 +/- 30% of CFU-e were recovered, but only +/- 1% of the incompatible RBCs was left in the transfusate (1-3 ml). No signs of hemolysis were observed. All patients engrafted promptly. The patients with low titers of antibody had normal reticulocyte recoveries. Maturation of erythropoiesis was suppressed only when high titers of antibody were present. However, despite high antibody titers, erythroid progenitor cells (CFU-GEMM, BFU-e, and CFU-e) could be cultured from the bone marrow of the recipient after BMT. Thus, anti-A and anti-Rh-C antibodies give little, if any, inhibition of stem-cell proliferation. The method described to remove incompatible RBCs appears to be simple, safe, and--in most cases--sufficient.

Blood Group Antigens↗

Factors influencing platelet survival during antilymphocyte globulin treatment.

The antiplatelet effect of antilymphocyte globulin (ALG) was studied during 49 courses of therapy of 4-5 d given to 43 patients with severe aplastic anaemia. Concomitant corticosteroid therapy was usually given in moderate ( MDC ) dosages from 10 to 30 mg daily (40 courses); in nine courses the ALG infusions were combined with high dose (20 mg/kg) methylprednisolone (HDC). Clinical side effects were mainly seen during the first ALG infusion. In all MDC -treated patients a decrease of the peripheral-blood leucocyte count to 20-30% of the pretreatment level during the first ALG infusion was associated with a severely shortened platelet survival. During subsequent infusions, which were tolerated much better, the survival of transfused platelets increased considerably. In the HDC-treated patients platelet survival was only slightly shortened on the first day of therapy, but the decrease of the leucocyte count was also less in these patients. Diffuse intravascular coagulation, circulating immune complexes and complement activation were excluded as major causes of the shortened platelet survival. Although ALG reacted with platelets in vitro and in vivo (as detected with indirect immunofluorescence), bystander destruction was likely during the first ALG infusion when massive leucocyte destruction occurred.

Adolescent↗

Anti-thymocyte globulin treatment for aplastic anemia.

20 patients with severe aplastic anemia were treated with anti-thymocyte globulin (ATG), 6 of them in combination with haplo-identical bone marrow. 7 patients (35%) showed a good clinical response within 6 months; they were off transfusions and had greater than or equal to 0.8 x 10(9)/l neutrophils. ATG had the greatest effect on red-cell production and the least on platelet production. The hematological recovery with ATG could not be predicted from the bone-marrow histology, CFU-c growth, or clinical data. However, patients with strong HLA antibodies seemed to respond more often. The actuarial survival was 55% at 5 years. Under intensive supportive care, even 7 out of 12 non-responders were alive after 1 year. ATG appears to be a useful form of therapy for patients with severe aplastic anemia who are not candidates for bone-marrow transplantation.

Adolescent↗

IgG subclasses in rhesus-D immunization. Effects of weekly small volume plasmapheresis.

The IgG subclass composition was determined of the anti-D antibodies present in the serum of 22 women who had a history of severe rhesus-D immunization and who weekly underwent small volume plasmapheresis during their current pregnancy. There was no correlation between the subclass patterns of IgG anti-D antibodies and the degree of illness of the child; the good clinical results obtained with the small volume plasmapheresis could not be explained by a consistent change in the anti-D IgG subclass composition.

Antibodies, Anti-Idiotypic↗

Prevention of platelet refractoriness due to HLA antibodies by administration of leukocyte-poor blood components.

From January 1972 to July 1974, 28 patients with bone marrow depression due to aplastic anemia or cytostatic treatment, were transfused with packed cells and platelet concentrates, both containing 10-20% of the amount of leukocytes present in whole blood. Of these patients, 26 (93%) became refractory to random platelets. Since July 1974, 68 patients have been given red cells filtered through cotton-wool, a procedure which removes over 97% of the leukocytes, and leukocyte-poor platelet suspensions obtained by an additional centrifugation step. Of this latter group, 16 patients (24%) became refractory. Fifty-two recipients were non-refractory to random platelet transfusions after an exposure time of at least 6 weeks and maximally 32 weeks. A possible explanation is that platelets are less immunogenic than leukocytes; on the other hand platelets may not be immunogenic at all with regard to induction of HLA antibodies, and the occurrence of the immunization is purely the result of the contamination with leukocytes in the red cell and platelet preparations.

Adolescent↗

Alloimmunization against the MHC antigens after platelet transfusions is due to contaminating leukocytes in the platelet suspension.

Repeated platelet transfusion to thrombocytopenic patients frequently induce anti HLA antibodies, which are responsible for transfusion refractoriness. As the transfused platelet suspensions usually contain 15-30% of the leukocytes originally present in the blood, it is not known whether these antibodies are raised by the platelets or by the contaminating leukocytes in the platelet suspensions. In the mouse, pure platelet suspensions are not able to induce a primary antibody response, as measured by the NIH test and the indirect immunofluorescence test on platelets and leukocytes, despite repeated injections. However, when the platelet suspensions are contaminated with leukocytes (10(3) or more/injection) an antibody response is induced. This response is higher than the response indiced by an equal amount of leukocytes alone. As in man the use of leukocyte poor platelets postpones the development of refractoriness to random platelets it is concluded that transfusions with leukocyte free platelets will probably prevent immunization against the HLA antigens.

Animals↗