Identification of Inherited Macrothrombocytopenias Based on Mean Platelet Volume among Patients Diagnosed with Idiopathic Thrombocytopenia.

Inherited macrothrombocytopenia is a rare illness that is often misdiagnosed as idiopathic thrombocytopenia (ITP), a more widespread acquired disease. The hallmark of a diagnosis of these diseases is the presence of giant platelets. Automated blood cell counters in routine clinical use usually miss giant platelets and underestimate mean platelet volume (MPV). Incorrect diagnoses might expose patients to a risk of unnecessary treatment. The ADVIA 120 hematology counter efficiently detects large platelets based on two-dimensional laser light scatter. This two-dimensional approach provides a more accurate estimation of platelet volume than conventional one-dimensional analysis. The present study measures and re-evaluates MPV using the ADVIA 120 in 112 patients who had initially been diagnosed with ITP.

We identified 11 unrelated patients as having probable macrothrombocytopenia (average MPV of 19.2 ± 3.8 fL; normal range 7.8–10.2). A diagnosis of inherited macrothrombocytopenia was immediately ruled out in 5 of the 11 patients, because their medical records indicated that their platelet counts had once been normal or became normalized (>100x19⁹/L) in response to steroid therapy. Of the remaining 6 patients, platelets aggregated abnormally in response to ristocetin in 3 patients and MYH9-RD was suspected in one patient since Döhle-like bodies were apparent in granulocytes on blood films. DNA analyses confirmed that 3 of these patients had Bernard-Soulier syndrome and 1 had MYH9-related disease, both of which are the most common forms of inherited macrothrombocytopenia. We detected 3 homozygous mutations in the 3 patients with Bernard-Soulier syndrome: A3171T and 4444insT in the GPIbα gene that created new premature termination codons, and the missense mutation, G1913A in the GPIX gene, that caused the loss of GPIX surface expression. In one patient with MYH9-related disease, we found a heterozygous missense mutation of C5797T in exon 40 of the MYH9 gene. We stress that all four patients had received high-dose steroid therapy and/or splenectomy before this study according to a diagnosis of ITP.

Checking MPV using the ADVIA 120 in thrombocytopenic patients is a useful method of correctly diagnosing inherited macrothrombocytopenia, and thus avoiding patient exposure to unnecessary and sometimes toxic treatment.