Among individuals at risk for developing fetal and neonatal alloimmune thrombocytopenia (FNAIT), evaluating plasma thrombopoietin (TPO) levels among neonates with low platelet counts may help patients be diagnosed sooner.
A thesis authored by Leendert Porcelijn, which appeared recently in the Scholarly Publications of Leiden University (Universiteit Leiden The Netherlands), discussed this issue and others related to the diagnostic advantages of plasma TPO concentrations and platelet autoantibodies among individuals with potential FNAIT and other autoimmune bleeding disorders, including immune thrombocytopenic purpura (ITP).
In the rare immune disorder FNAIT, an infant’s platelets are recognized by the mother as being foreign. Thus, the mother mounts an antibody response against these platelets. In fact, a baby’s platelets may be identified as being foreign when they differ from the mother’s platelets because of genes that have been inherited from the father. Platelets are a type of blood cell that help the blood to clot. An abnormally low level of platelets, which is known as thrombocytopenia, may be associated with easy bleeding and/or the breakdown of blood vessels.
FNAIT has a pathophysiology that is similar to that of hemolytic disease of the fetus and newborn (HDFN) in certain respects. In HDFN, a Rhesus D (RhD)-negative pregnant mother may develop alloantibodies to RhD antigens on fetal/neonatal red blood cells (RBCs) that have been inherited from the father. This, in turn, can lead to the destruction of fetal/neonatal RBCs and to possible anemia.
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In FNAIT, in contrast, maternal platelet alloantibodies are associated with the destruction of fetal/neonatal platelets. The researcher has proposed that if plasma TPO levels are normal among infants who experience FNAIT-associated thrombocytopenia, measuring neonatal TPO levels in the early postpartum period might assist in narrowing down the differential diagnosis and ultimately arriving at the appropriate diagnosis much sooner.
It has been proposed that plasma TPO levels be measured via routine diagnostic laboratory workup to hasten a potential FNAIT diagnosis. The regulation of platelet production is strongly dependent on TPO concentrations. TPO, which is manufactured primarily in the liver, binds to c-mpl-receptors on CD34+ stem cells, platelets, and megakaryocytes In fact, a platelet and megakaryocyte mass that is deemed to be sufficient will be able to eliminate free TPO from the circulation passively.
The investigator of the current analysis sought to establish which of the underlying causes of neonatal thrombocytopenia are associated with elevated levels of plasma TPO, as well as whether the utilization of plasma TPO levels can aid in the early recognition of the underlying cause of neonatal thrombocytopenia.
It is quite complicated to design tests with high accuracy for detecting platelet-bound or circulating autoantibodies against platelet antigens. This is caused chiefly by the fact that, along with specific antibodies, nonspecific antibodies can also bind, which can lead to false-positive reactions. Platelet autoantibodies, in contrast, exhibit a low affinity and thus can be released during the necessary “platelet washing steps in the various tests,” potentially leading to false-negative results.
According to the author, “Although this thesis concerns a relatively small field, some of its findings can be extended to other autoimmune conditions.”
He also stated, “Mapping different groups of patients with apparently the same condition will hopefully lead to insight into differences through such research and thus to an understanding of the optimal therapy for the individual. From the gained insights into immunology and the optimization of diagnostic options so far, we can conclude that the discussed aims for the future in this respect can only be attained by the increasing synergy between clinic and laboratory.”
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