macrothrombocytopenia

Macrothrombocytopenia is a laboratory and clinical term for conditions in which platelets are abnormally large (macrothrombocytes) and the platelet count is reduced (thrombocytopenia). The disorder is most often congenital and presents with bleeding symptoms ranging from mild to significant. The large platelets can be seen on a peripheral blood smear and may be associated with a normal or reduced platelet function depending on the underlying cause.

Two well-described inherited causes are Bernard-Soulier syndrome and MYH9-related disease. Bernard-Soulier is autosomal recessive and results from deficiency of the GPIb-IX-V receptor complex on platelets, producing giant platelets and mucocutaneous bleeding with markedly reduced ristocetin-induced aggregation. MYH9-related disease, caused by mutations in the MYH9 gene, encompasses a spectrum including May-Hegglin anomaly, Epstein and Fechtner syndromes, and Sebastian syndrome; it features macrothrombocytopenia with Döhle-like inclusions in neutrophils and may be associated with nephropathy, sensorineural hearing loss, and liver involvement.

Rarely, macrothrombocytopenia can occur in other congenital contexts or as an acquired phenomenon during certain hematologic disorders or as an artifact. The common mechanism in congenital forms is abnormal megakaryocyte development leading to large platelets and reduced numbers.

Diagnosis relies on complete blood count showing thrombocytopenia with enlarged platelets, review of peripheral smear, and targeted genetic testing (for GPIb-IX-V defects in Bernard-Soulier or MYH9 mutations). Flow cytometry can help assess platelet surface glycoprotein expression and function. Bone marrow examination is rarely required but may show megakaryocytic abnormalities.

Management is tailored to the underlying cause and bleeding risk. Patients with Bernard-Soulier or MYH9-related disease may require platelet transfusions for major procedures or bleeding. Avoidance of antiplatelet drugs and careful perioperative planning are recommended. Prognosis depends on the syndrome; many individuals have mild bleeding, while MYH9-related disease can involve renal or auditory complications.