Saturday, 10 June, 1995, 13:00-16:00
Chair: Cecile Kaplan, France
Co-Chairs: D. Beardsley, USA; J. Bussel, USA; T. Kunicki; USA; S. Shattil, USA
Minutes prepared by D. Beardsley and C. Kaplan.
This committee had a working session.
Mainly three topics were discussed:
- Autoimmunity
- Alloimmunity
- Heparin-induced thrombocytopenia
The tasks for the coming years are as follow:
1) Autoimmunity:
Detection and characterization of platelet autoantibodies and antigenic targets:
Recent studies of platelet autoantibodies in AITP have included a multicenter international workshop organized by Drs. P. Berchtold and P. Imbach. There was excellent correlation between results obtained by participating laboratories, particularly with regard to platelet associated antigen capture results. It could now be interesting to include in such workshop a standardization of monoclonal antibodies to be used. This is in order to have a standard that could be recommended to the majority of the laboratories active in the field. Platelet glycoprotein-specific antibody methods are superior to the measurement of platelet- associated IgG in the diagnosis of AITP. Direct assays gave more consistent results than indirect assays and were more valuable in diagnosing AITP. The reasons why it is important to determine the platelet bound antibodies include: 1) many false negatives can occur with indirect assays, especially if there is not a large amount of antibody present, 2) some antibodies may represent antibodies formed as a result of the AITP, rather than causing the disease, and 3) alloantibodies formed as a result of transfusion or pregnancy could co-exist with autoantibodies making it sometimes difficult to ascertain their origin.
A goal of this field should be to minimize the amount of blood needed to accomplish the direct assay of platelet-associated glycoprotein-specific antibodies. This can currently be done by the immunobead technique on 1x107platelets, but this amount can probably be reduced further. The minimum number of platelets needed for direct MAIPA testing has to be determined. Concerning circulating autoantibodies, C. Kaplan reported that in special conditions, i.e. neonatal thrombocytopenias associated with "hidden maternal autoimmunity," the mothers had no detectable platelet-associated antibodies and that the only possibility for such a diagnosis was the characterization of circulating autoantibodies. It will be important to evaluate the feasibility of utilizing recombinant peptides for diagnostic assays for platelet antibodies. There is a great deal of work going on at present to identify the precise epitopes which are commonly the targets of platelet autoantibodies (N.R. Shulman's GPIb epitope is one example).
At the moment there is no current consensus regarding optimum management of pregnancy associated with anti-platelet autoimmunity. The question of whether fetal blood samplings must be performed at the end of pregnancy has been addressed by several groups. For the coming year, it could be of interest to compare the results obtained by different teams in terms of number of thrombocytopenic fetuses and infants at birth or during the first days of life in order to evaluate
more precisely the fetal/neonatal risks with the same criteria.
It is important to have a follow-up examination of the mother in the six month post-partum period, and when possible a platelet life span study, to accurately diagnose immune platelet destruction.
2) Alloimmunity:
- Nomenclature. There remains considerable controversy regarding a nomenclature system for platelet alloantigens. The possibility of a World Health Organization forum working out this issue was brought up in 1994 at the SSC meeting. The cooperation of the SSC as well as the ISBT should be incorporated to reach the best solution to this problem.
- Fetal/Neonatal Alloimmune Thrombocytopenia. Prospective studies have recently shown that alloimmunization is more frequent that previously thought. Results reported by W. Ouwehand (Great Britain), L. Marshall (Australia), and C. Kaplan (France) are concordant: immunization could occur in 1/500 pregnancies and 50% of the fetuses could be affected. A central registry for antenatal therapy comparison is a new concept presented by C. Kaplan of the European registry. Extending this to an international base should be explored. Statistical analysis must be done in order to have the same criteria for the definition of therapeutic effectiveness or failure. Proposals for the design and operation of such a registry should be brought forward for the 1996 SSC Platelet Immunology meeting.
3) Heparin-associated/induced Thrombocytopenia:
- Testing standardization
At the moment many laboratories hesitate between functional and antigen testing for the diagnosis. A standardization could be evaluated this coming year before the next meeting and could be discussed then.
- Therapy
The therapy of Heparin-induced thrombocytopenia is still a matter of concern. It could be worse than HIT by itself. For that purpose, T. Warkentin and A. Greinacher will prepare propositions after the clinical trials conducted this coming year.