Macrothrombocytopenia in DiGeorge Syndrome (del 22q11.2)

Macrothrombocytopenia in DiGeorge Syndrome (del 22q11.2)
Author: Udhayvir S Grewal, MD; Kai J Rogers, MD, PhD; Usha Perepu, MD
Category: Hemostasis and coagulation > Bleeding disorders > Platelet abnormalities
Published Date: 03/16/2023

A 20-year-old male with a known diagnosis of DiGeorge Syndrome (DGS) presented for evaluation of long-standing thrombocytopenia. Records indicated chronic stable mild-moderate thrombocytopenia ranging from 91k to 154k/cu. mm (reference range 150k-450k), with no history of episodes of spontaneous bleeding or bleeding/bruising with minimal trauma. The peripheral smear showed several large platelets interspersed with few normal-sized platelets, consistent with a diagnosis of macrothrombocytopenia (figure). A platelet function assay was unremarkable.

DGS or 22q11.2 syndrome is a rare congenital disorder characterized by broad phenotypic variability. Macrothrombocytopenia has been frequently observed in patients with DGS, which is characterized by a significant drop in platelet count with a concurrent increase in the size and volume of the platelets. However, this is not accompanied by an increased risk of bleeding. Macrothrombocytopenia in patients with DGS has been linked to heterozygosity for a deletion of the GPIb gene, which is also associated with the autosomal recessive coagulation disorder Bernard-Soulier syndrome (BSS). However, the degree of thrombocytopenia in DGS is not as profound as in BSS, which is also characterized by clinically significant bleeding and the presence of giant platelets (larger than the size of the average red blood cell in the field). Macrothrombocytopenia appears to be the most common cause of thrombocytopenia in patients with DGS. Some studies indicate that it may also be used as a potential clinical marker of the disease. The current case highlights the importance of peripheral smear evaluation for prompt diagnosis and prevent unnecessary testing for thrombocytopenia in these patients.