Hereditary Persistence of Fetal Hemoglobin Presenting With 100% Fetal Hemoglobin and Recurrent Thrombotic Events

TL;DR

A 30-year-old man with 100% fetal hemoglobin experienced repeated blood clots, challenging the belief that high fetal hemoglobin is harmless.

Contribution

First reported case of 100% fetal hemoglobin in an adult with recurrent thrombotic events.

Findings

Patient had 100% fetal hemoglobin and multiple thrombotic events like splenic thrombosis and pulmonary embolism.

Genetic testing identified a homozygous deletion-inversion in the β-globin cluster.

Case challenges the traditional view of hereditary persistence of fetal hemoglobin as a benign condition.

Abstract

Fetal hemoglobin (HbF) is the predominant hemoglobin during fetal development, typically replaced by adult hemoglobin after birth. Elevated HbF levels in adulthood are rare and often associated with genetic conditions such as hereditary persistence of fetal hemoglobin (HPFH) or hemoglobinopathies. We present the case of a 30-year-old Pakistani male with 100% HbF, recurrent thrombotic events, including splenic thrombosis and unprovoked pulmonary embolism, and chronic systemic symptoms. Despite extensive evaluation, including bone marrow biopsy, advanced imaging, and multidisciplinary consultations, establishing a definitive diagnosis remained challenging. Genetic testing revealed a homozygous Asian-Indian deletion-inversion in the β-globin cluster. The patient’s clinical course was complicated by persistent leukocytosis and compensated hemolysis. To our knowledge, this represents the first reported case in the literature of an adult with 100% HbF presenting with recurrent thrombotic complications. This case highlights the diagnostic complexity of rare hematological conditions and the potential association between 100% HbF and thrombotic complications, challenging the traditional view of HPFH as a benign condition.

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