Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is commonly associated with antibodies against platelet antigens, and alloimmune neonatal neutropenia (ANN) is frequently caused by anti-neutrophil antibodies. Human leukocyte antigen (HLA) antibodies are rarely reported to result in FNAIT or ANN, let alone the combination of FNAIT and ANN. We report here a very unusual case of a first twin pregnancy produced in vitro by donated oocytes where the mother developed markedly elevated HLA antibodies in the absence of anti-platelet or anti-neutrophil antibodies that provoked severe thrombocytopenia and neutropenia in one of the twins. In addition, drug-induced hemolytic anemia (DIHA) that required red blood cell transfusion was detected in this twin. We hypothesize that the complete HLA-incompatible twin pregnancy due to oocyte donation might have contributed to the severity of the clinical manifestations.