Immune Mechanisms of Platelet Refractoriness

1998 ◽  
Vol 21 (6_suppl) ◽  
pp. 103-109
Author(s):  
F. Fischetti ◽  
F. Tedesco

Multiple platelet transfusions may prove ineffective in approximately 40% of patients treated for bone marrow aplasia. This condition is known as platelet refractoriness and is diagnosed by evaluating the corrected count increment following platelet transfusion. Immune factors still represent an important cause of platelet refractoriness and, among these, HLA alloimmunization plays the most relevant pathogenetic role. Less important are other specific and non-specific antigens, that can be detected on platelet surface. Several assays have been developed to reveal anti-platelet antibodies, which include the lymphocyte cytotoxicity test, the platelet immunofluorescence assay and the mixed passive hemagglutination assay. It is now clear that leukocytes contaminating the platelet concentrates represent the main cause of HLA alloimmunization which can be prevented by leukocyte depletion to less than 5 × 106 cells per unit. Transfusion of HLA-matched platelets in alloimmunized platelets may be quite effective, but it can also be fairly expensive considering the large number of donors to be typed for HLA in order to find HLA compatible platelets. A more practical approach would be to select the platelet concentrates on the basis of the negative crossmatch.

Blood ◽  
1981 ◽  
Vol 57 (4) ◽  
pp. 649-656
Author(s):  
AE von dem Borne ◽  
EF van Leeuwen ◽  
LE von Riesz ◽  
CJ van Boxtel ◽  
CP Engelfriet

Platelet immunofluorescence, together with other serologic tests on platelets, lymphocytes, and granulocytes, was used to investigate the sera of 38 mothers with newborns who suffered from thrombocytopenia. In sera of 33 mothers, platelet-specific IgG alloantibodies were demonstrable. Three sera also contained HLA antibodies, of which two were only detectable in the lymphocyte cytotoxicity test. Two other sera contained granulocyte-specific alloantibodies. In sera of 2 mothers, antibodies were found that reacted with all cell types in all tests. However, after further analysis, it became clear that platelet- specific alloantibodies were probably also present in these 2 sera. In 29 cases, the specificity of the platelet alloantibodies was anti-Zwa-- PlA1. One serum contained antibodies directed against a new antigen, Baka. This new antigen was defined after the investigation of the family and a small-scale population study. Two other sera had platelet antibodies with still undefined specificities. In all positive sera, IgG platelet alloantibodies were detected, and sometimes IgM antibodies were also present. The IgG antibodies were mostly of the IgG1 subclasses, but sometimes IgG3 and/or IgG4 was also found. In a few sera, only IgG3 antibodies were detected. In our series, we found no increased frequency of blood group ABO compatibility between mother and child, although it has been described by others and is well known to occur in rhesus alloimmunization. Of all the tests used, the platelet immunofluorescent test, especially the test on paraformaldehyde-fixed platelets in suspension, gave the best results in the detection of platelet antibodies in neonatal alloimmune thrombocytopenia.


Blood ◽  
1981 ◽  
Vol 57 (4) ◽  
pp. 649-656 ◽  
Author(s):  
AE von dem Borne ◽  
EF van Leeuwen ◽  
LE von Riesz ◽  
CJ van Boxtel ◽  
CP Engelfriet

Abstract Platelet immunofluorescence, together with other serologic tests on platelets, lymphocytes, and granulocytes, was used to investigate the sera of 38 mothers with newborns who suffered from thrombocytopenia. In sera of 33 mothers, platelet-specific IgG alloantibodies were demonstrable. Three sera also contained HLA antibodies, of which two were only detectable in the lymphocyte cytotoxicity test. Two other sera contained granulocyte-specific alloantibodies. In sera of 2 mothers, antibodies were found that reacted with all cell types in all tests. However, after further analysis, it became clear that platelet- specific alloantibodies were probably also present in these 2 sera. In 29 cases, the specificity of the platelet alloantibodies was anti-Zwa-- PlA1. One serum contained antibodies directed against a new antigen, Baka. This new antigen was defined after the investigation of the family and a small-scale population study. Two other sera had platelet antibodies with still undefined specificities. In all positive sera, IgG platelet alloantibodies were detected, and sometimes IgM antibodies were also present. The IgG antibodies were mostly of the IgG1 subclasses, but sometimes IgG3 and/or IgG4 was also found. In a few sera, only IgG3 antibodies were detected. In our series, we found no increased frequency of blood group ABO compatibility between mother and child, although it has been described by others and is well known to occur in rhesus alloimmunization. Of all the tests used, the platelet immunofluorescent test, especially the test on paraformaldehyde-fixed platelets in suspension, gave the best results in the detection of platelet antibodies in neonatal alloimmune thrombocytopenia.


1987 ◽  
Vol 115 (2) ◽  
pp. 282-288 ◽  
Author(s):  
Kazuya Zeki ◽  
Takashi Fujihira ◽  
Fumihiko Shirakawa ◽  
Kenichi Watanabe ◽  
Sumiya Eto

Abstract. We investigated the percentage of circulating HLA-DR antigen positive (Ia antigen positive: Ia+) T cells and the additive proliferation by non-specific mitogens and thyroid-specific antigens by means of a cytotoxicity test in autoimmune thyroid diseases. Furthermore, we studied the stimulative function of circulating Ia+T cells in autologous mixed lymphocyte reactions. %Ia+T cells were significantly increased in patients with autoimmune thyroid diseases compared with those in normal controls. They were additionally increased by the stimulation of TSH-receptor or thyroid-microsome in patients with Graves' disease, and by the stimulation of thyroglobulin and thyroid-microsome in patients with Hashimoto's thyroiditis. As to the cellular immune function, circulating Ia+T cells stimulated Ia− T cells in autologous MLR in patients with autoimmune thyroid diseases. These data suggest that some of the T cells are already activated in vivo, that the activation of T cells may be by thyroid-specific antigens, and that these activated (Ia+) T cells may be able sequentially to induce the activation of inactivated (Ia−) T cells in autoimmune thyroid diseases.


Vox Sanguinis ◽  
1989 ◽  
Vol 56 (4) ◽  
pp. 291-292
Author(s):  
J.W.N. Akkerman ◽  
M. van Marwijk Kooy ◽  
L. Borghuis ◽  
H.C. van Prooijen

Vox Sanguinis ◽  
1997 ◽  
Vol 72 (1) ◽  
pp. 20-25 ◽  
Author(s):  
Volker Weisbach ◽  
Alexander Putzo ◽  
Jurgen Zingsem ◽  
Matthias Riewald ◽  
Robert Zimmermann ◽  
...  

1990 ◽  
Vol 60 (8) ◽  
pp. 351-357
Author(s):  
Tsuneo A. Takahashi ◽  
Mari Hosoda ◽  
Sadayoshi Sekiguchi

2018 ◽  
Vol 44 (06) ◽  
pp. 604-614 ◽  
Author(s):  
Roseline d'Oiron ◽  
Man-Chiu Poon

AbstractGlanzmann's thrombasthenia (GT) and Bernard–Soulier's syndrome (BSS) are well-understood congenital bleeding disorders, showing defect/deficiency of platelet glycoprotein (GP) IIb/IIIa (integrin αIIbβ3) and GPIb-IX-V complexes respectively, with relevant clinical, laboratory, biochemical, and genetic features. Following platelet transfusion, affected patients may develop antiplatelet antibodies (to human leukocyte antigen [HLA], and/or αIIbβ3 in GT or GPIb-IX in BSS), which may render future platelet transfusion ineffective. Anti-αIIbβ3 and anti-GPIb-IX may also cross the placenta during pregnancy to cause thrombocytopenia and bleeding in the fetus/neonate. This review will focus particularly on the better studied GT to illustrate the natural history and complications of platelet alloimmunization. BSS will be more briefly discussed. Platelet transfusion, if unavoidable, should be given judiciously with good indications. Patients following platelet transfusion, and women during and after pregnancy, should be monitored for the development of platelet antibodies. There is now a collection of data suggesting the safety and effectiveness of recombinant activated factor VII in the management of affected patients with platelet antibodies.


Blood ◽  
1983 ◽  
Vol 61 (2) ◽  
pp. 311-317 ◽  
Author(s):  
CA Schiffer ◽  
V Young

Abstract An enzyme-linked immunosorbent assay (ELISA) for the measurement of circulating platelet antibody and platelet-associated IgG (PAIgG) is described. The test is done in microtiter plates and rapidly provides quantitative and highly reproducible results. Alloantibodies from 28 of 30 multiple transfused patients and isoantibodies from 3 of 4 patients with immune thrombocytopenic purpura (ITP) were detected. PAIgG was elevated in all 4 patients with ITP, and HLA and platelet-specific antigens were reliably detected using HLA typing sera and anti-PIA1 antibody, respectively. Platelets preserved wither by dessication in the wells of the microtiter plates or in liquid suspension in saline at 4 degrees C gave results comparable to values using fresh platelets. Storage periods ranged from 30 days for dessicated platelets to more than 1 yr for platelets stored in suspension. The ability to utilize preserved platelets may allow relatively convenient screening of large numbers of potential platelet donors for alloimmunized patients.


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