- The gray platelet syndrome (GPS) is a rare inherited disorder characterized by mild to moderate bleeding tendency, moderate thrombocytopenia, and a marked decrease or absence of platelet alpha-granules and of the proteins contained in alpha-granules.
- The platelets are enlarged, but not giant, and have a gray appearance on light microscopy of Wright-stained peripheral blood smears due to decreased granules.
- GPS is caused by mutations in the NBEAL2 gene and inherited in an autosomal recessive manner.
Hypogranular Platelets – Grey Platelet Syndrome
Signs and Symptoms
- Signs and symptoms usually appear at birth or in early childhood and include low platelet counts, easy bruising, prolonged bleeding, and nose bleeds.
- Affected individuals often have myelofibrosis and splenomegaly. Bleeding tendency is usually mild to moderate in those with mild thrombocytopenia. However, the thrombocytopenia and myelofibrosis are usually progressive in nature.
- GPS may result in fatal hemorrhage (bleeding), especially in adulthood when platelet counts are further decreased especially < 30,000 platelet/microliter blood. Female patients may develop heavy menstrual bleeding.
Lab Diagnosis:
- Low platelet count + Blood smear showing large grey hypogranular platelets
- the bleeding time is prolonged
- also Genetic Testing performed
- Electron Microscopy used to detect absence of alpha-granules in platelets
- ITP come as differential diagnosis with GPD, but in ITP we don’t see large agranular platelets
Electron Microscopy Diagnosis:
- (A) Electron Microscope of thin sections of a platelet showing absence of α-granules and abundant channels of the open canalicular system (labeled as OCS) in comparison with Electron Microscope of a control platelet (B) showing normal alpha granules (labeled as AG).
- DTS: Dense tubule system.
Electron Microscope of thin sections of a platelet
- (C) Light microscopy of the peripheral smear of GPS patient showing a large pale gray platelet (arrow) without the cytoplasmic color of α-granules, in comparison with a normal smear (D)
Grey Platelet Syndrome Patient (Left) and Normal Platelet on the Right
Disease Management:
- There is no specific treatment for grey platelet syndrome (GPS), and this may include Platelet transfusions, Splenectomy and Desmopressin
- Desmopressin: This is a synthetic analogue of vasopressin, which improves bleeding time and clotting (its mechanism of action is unknown).
Important: ITP vs GPS case report
- A 5-year-old girl was treated for 4 years based on a diagnosis of immune thrombocytopenia (ITP). When she presented for a second opinion, she met all criteria for ITP except that inspection of her peripheral blood smear showed large platelets with a complete lack of granulation, indicating a diagnosis of gray platelet syndrome (GPS).
- Electron microscopy subsequently showed absence of α-granules.
- This case illustrates the importance of inspection of the blood smear before making a diagnosis of ITP.
Grey Platelet Syndrome (GPS)- Patient Smear (Large agranular platelets)
References: http://bloodjournal.hematologylibrary.org http://rarediseases.info.nih.gov/
