Thrombin generation in two families with MYH9-related platelet disorder

Abstract

MYH9-related platelet disorders are inherited macrothrombocytopenias with additional clinical manifestations including renal failure, hearing loss, pre senile cataract and inclusion bodies in leucocytes that are present in different combinations. The MYH9 gene codes for the cytoplasmic contractile protein non-muscular myosin heavy chain IIA, present in several tissues. The bleeding tendency is usually mild to moderate but rarely, thrombotic complications are also seen. We report on the thrombin generation potential (ETP) in patients with MYH9-related disease with and without arterial thrombosis.In family A, four affected members (c.5521G>A mutation causing p.(Glu1841Lys)) were evaluated. Three of them had a moderate bleeding tendency and in two renal insufficiency and hearing loss were already present. These two patients had an arterial thrombosis (myocardial infarction and pons infarction, respectively) before 50 years of age. In family B two members were affected (c.4679T>G, resulting in p.(Val1560Gly)). Their bleeding tendency was mild (bleeding scores 4 and 3, respectively). Thrombelastography (ROTEM) was normal in all six individuals. ETP was below the normal range in family B. However, in family A, the two members affected by thrombosis had a normal ETP, indicating that other factors compensated for the low platelet count and might have contributed to the arterial thrombosis.

Idiopathic pulmonary embolism in a case of severe family ANKRD26 thrombocytopenia

“…This hypothesis could not be totally applied to MYH9 syndrome or our case because these two IPDs have no functional defect. A recent, interesting report found no difference in thrombin potential generation in MYH9 patients with or without arterial thrombotic events, indicating that other factors than the low platelet count might have contributed to the thrombosis 5. However, few patients were tested in this study.…”

“…Thrombotic events described in the literature are mostly arterial: nine MYH9 patients1,4–5 and three BSS patients developed myocardial infarction, coronary arterial disease, and pons infarction stroke. In contrast, ten Glanzmann patients developed venous thrombosis,1,6 mas did two MYH9 patients 1.…”