The long-term objective of this porposal is to define the underlying immunologic mechanisms responsible for fetal thrombocytopenia associated with autoimmune thrombocytopenic purpura (ATP) and pregnancy-induced hypertension (PIH). ATP and PIH frequently result in thrombocytopenia, which may be associated with significant maternal morbidity. Whether the cause of platelet destruction is immunologically similar in both conditions is unknown, but fetal thrombocytopenia is a complication of ATP and PHI. Since fetal thrombocytopenia is associated with serious neonatal complications including intracranial bleeding during vaginal delivery, obstetric management of these patients could be selectively altered if the thrombocytopenic fetus could be identified. However, to date, no antepartum maternal characteristics have been identified that can reliably predict fetal thrombocytopenia. Four questions are posed in this application concerning maternal and fetal platelet-associated and circulating antibody, and experiments are detailed to provide the answers: (1) is the antibody specifically directed against a platelet antigen? (2) If specific binding is occurring, which platelet antigen is being recognized? (3) Do ATP and PIH patients produce antibodies against the same platelet components and do all specificities of antibody cross the placenta? (4) What is the relationship between antibody in the cord blood and those in the maternal circulation? Antibody specificity will be determined by several methods; our principal approach will be the use of transblotting, but a pattern of antibody reactivity will also be determined by adsorbing samples containing antibody with a battery of typed donor platelets. Using papain and pepsin digests of the antibody, binding via Fc versus Fab will also be determined. The information in this study will facilitate the understanding of the basic immunologic mechanisms of thrombocytopenia in pregnancy and possibly the development of a reliable antepartum technique to predict fetal platelet destruction. This would allow the selection of appropriate obstetric management and route of delivery in each instance and may lead to the identification and active treatment of fetal thrombocytopenia prior to labor.
| Scott, J R; Rote, N S; Branch, D W (1987) Immunologic aspects of recurrent abortion and fetal death. Obstet Gynecol 70:645-56 |
| Rote, N S; Harrison, M R; Scott, J R (1987) Platelet-binding immunoglobulins in pregnancy-induced hypertension. II. Origin of circulating IgG and IgM antiplatelet antibodies in the umbilical cord serum. J Reprod Immunol 10:273-84 |
| Rote, N S; Lau, R J; Harrison, M R et al. (1987) Platelet-binding immunoglobulins in pregnancy-induced hypertension. I. Platelet-associated IgM on fetal platelets: evidence of a fetal autoimmune reaction? J Reprod Immunol 10:261-72 |
