A rare genetic mutation caused a severe case of fetal and neonatal alloimmune thrombocytopenia (FNAIT), a disorder where a pregnant person’s immune system attacks their baby’s platelets, researchers reported in a case study published recently in Transfusion.
In this case, the bleeding disorder was linked to a previously unknown platelet antigen, called Dik, that standard screening failed to detect. FNAITFetal and neonatal alloimmune thrombocytopenia A rare condition in which a mother’s immune system attacks fetal platelets, leading to dangerously low platelet levels before and/or after birth. was suspected shortly after a healthy 33-year-old woman of European ancestry gave birth to a male infant who showed widespread tiny skin bruises called petechiae, mostly on the limbs and groin.
This newborn’s platelet countPlatelet count A measure of how many platelets are in the blood. FNAIT is characterized by severely reduced counts in a fetus or newborn. was critically low at 7 Gpt/L at birth, dropping to just 2 Gpt/L at its lowest point. Other blood tests and infection screens were normal, and there was no family history of bleeding disorders. Treatment with intravenous immunoglobulinIntravenous immunoglobulin A treatment given to pregnant women with a history of FNAIT or known alloantibodies. IVIG reduces the immune reaction against fetal platelets. and six platelet transfusions over five weeks led to improvement.
Read more about FNAIT causes and risk factors
Initial testing revealed incompatibility between the mother and fetus at HPAHuman platelet antigen Proteins found on the surface of platelets. Incompatibility between maternal and fetal human platelet antigens can trigger FNAIT.-1b and HPA-3b, two common platelet markers. But no antibodies showed up in standard screening using an antibody capture assay called the MAIPA method. A crossmatch test, however, revealed the mother’s serum strongly reacted with the father’s platelets. This suggested the presence of an unrecognized platelet antigen.
Further genetic testing found no changes in the ITGB3 gene, but uncovered a new mutation—c.2320C>T—in the ITGA2B gene. This mutation, found in the father and baby but not the mother, caused a single amino acid change (p.Arg743Trp) in the platelet protein GPIIb. Lab studies confirmed that antibodies in the mother’s blood specifically targeted this altered version of GPIIb, but not the normal form.
The mutation, named Dik, was inherited from the baby’s paternal grandmother. It was absent in 1,460 unrelated German blood donors. Public databases report it as extremely rare, with a global frequency of just 2.1 in 100,000. It is more commonly found in people of African descent.
Identifying rare antigens such as Dik can help guide treatment and inform future pregnancies where preventive strategies may be needed to protect the baby.
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