Patients with sickle cell disease (SCD) have a high prevalence of RBC alloimmunization.However, underlying mechanisms are poorly understood. Given that proinflammatory type 1 interferons (IFNα/β) and interferon stimulated genes (ISGs) promote alloimmunization in mice, we hypothesized that IFNα/β may contribute to the increased frequency of alloimmunization in patients with SCD. To investigate this, expression of ISGs in blood leukocytes and peripheral blood mononuclear cells (PBMCs) of previously transfused SCD patients with or without alloimmunization and race-matched healthy controls were quantified, and IFNα/β gene scores were calculated. IFNα/β gene scores of SCD leukocytes and plasma cytokines were elevated, compared to controls (gene score, p < 0.01). Upon stimulation with IFNβ, isolated PBMCs from patients with SCD had elevated ISGs and IFNα/β gene scores (p < 0.05), compared to stimulated PBMCs from controls. However, IFNβ-stimulated and unstimulated ISG expression did not significantly differ between alloimmunized and non-alloimmunized patients. These findings indicate that patients with SCD express an IFNα/β gene signature, and larger studies are needed to fully determine its role in alloimmunization. Further, illustration of altered IFNα/β responses in SCD has potential implications for IFNα/β-mediated viral immunity, responses to IFNα/β-based therapies, and other sequelae of SCD.

Lupus anticoagulant hypoprothrombinemia syndrome (LAHPS) comprises lupus anticoagulant, acquired hypoprothrombinemia, and often mild thrombocytopenia or normal platelets. It is usually associated with autoimmunity or postviral illness. We describe a case of a 10-year-old boy with oral bleeding and severe thrombocytopenia initially suggestive of immune thrombocytopenia. Secondary to bleeding, evaluation demonstrated prolonged coagulation tests and subsequently revealed the presence of lupus anticoagulant and hypoprothrombinemia, along with marked autoimmunity, suggestive of LAHPS. He was treated with intravenous immunoglobulin and hydroxychloroquine. This case report and discussion highlight the diagnostic and therapeutic challenges associated with LAHPS and coincident severe thrombocytopenia.

Trisomy 21 is a common congenital disorder with well documented clinical manifestations, including an increased risk for transient myeloproliferative disorder as a neonate and leukemia in childhood and adolescence. Children with mosaic trisomy 21 can have a similar risk for hematological malignancies. We present a non-dysmorphic neonate, with negative noninvasive prenatal screening of maternal blood for trisomy 21, who came to medical attention because of ruddy skin. He was found to have mild polycythemia, thrombocytopenia and developed peripheral blasts. His clinical presentation was concerning for transient myeloproliferative disorder, which is only seen in trisomy 21 patients. Cytogenetic studies were positive for mosaic trisomy 21.

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