We report the first case of severe intractable thrombocytopenia in a patient with adenosine deaminase deficiency, Severe Combined Immune Deficiency (SCID), necessitating hematopoietic stem cell transplant. This patient developed severe thrombocytopenia from polyethylene glycol adenosine deaminase and needed a hematopoietic stem cell transplant as an adolescent. She did well afterwards, overall. Although rare, thrombocytopenia can result from polyethylene glycol adenosine deaminase. Hematopoietic stem cell transplant may be an option in SCID patients with intractable thrombocytopenia, even at a later age.