Thrombin generation in two families with MYH-9-related platelet disorder Eva Zetterberg, MD, PhD1, Margareta S Carlsson Alle, MD, PhD2, Jari Nivala, MD3, Juliane Najm, PhD4, Andreas Greinacher, MD5 1Department of Hematology and Coagulation, Skane University hospital, Malmö, Sweden; 2Department of Hematology, Växjö Central hospital, Växjö, Sweden; 3Department of Pediatrics, Karlstad, Sweden; 4Institute for Human Genetics, Greifswald, Germany; 4 Institute of Immunology and Transfusion Medicine, Greifswald, Germany Corresponding author: Eva Zetterberg, Department of Hematology and Coagulation, Jan Waldenströms gata 14, plan 3b, 205 02, Malmö, Sweden. Phone: +46 40337436; Fax:+46 40336255; e-mail: [email protected] Methods Thrombin generation was performed on frozen platelet rich plasma using the calibrated automated thrombogram (CAT) method (Fig 1). ETP was compared between patients diagnosed with MYH-9 related platelet disorder and a reference material consisting of 40 healthy individuals. Results Figure 3 Plasma samples from 6 members from 2 families (A and B) were analyzed (fig 2). All patients were diagnosed MYH-9 related disease based on the presence of macrothrombocytopenia and inclusion bodies in leucocytes. Two individuals in family A presented with arterial thrombosis before 50 years of age (marked with a star in Fig 3). Thrombin generation analysis revealed that these two members had an ETP within in the normal range despite a low platelet count (Table 1). Members of family B had ETP values below the normal range as expected by the low platelet count . When platelets from a healthy control was added to platelet poor plasma from patients A:1 and A:2 the ETP did not increase significantly. Normal range Introduction MYH-9 related platelet disorders are inherited macrothrombocytopenias where additional clinical manifestations including renal failure, hearing loss, pre senile cataract and inclusion bodies in leucocytes are present in different combinations. The bleeding tendency is usually mild to moderate but rarely, thrombotic complications are also seen . We report on the thrombin generation potential (ETP) in MYH9 patients with and without arterial thrombosis. Figure 2 Table 1 ID nr Sex Age years Plt count 109/L MYH-9 related features Bleed score Throm botic event Mutation ETP A:1 female 51 36 Renal insufficiency Hearing loss 13 Pons infarction N.AD normal • • A:2 male 57 39 Renal insufficiency Hearing loss 4 Myo cardial infarction 5521G>A Glu1841Lys normal A:3 fenale 24 46 none 9 none N.A.D normal A:4 male 30 44 none 3 none N.A.D below normal B:1 female 38 36 none 4 none 4679 T>G below Val1560Gly normal B:2 female 15 46 none 3 none 4679 T>G below Val1560Gly normal • Conclusions Patients MYH-9-related platelet disorder can have a normal ETP despite a low platelet counts We suggest that plasma factors compensated for the low platelet count and clinically even led to a breakthrough of arterial thrombosis We suggest that other centers also assess the ETP in their MYH-9 patients according tour protocol (www.med.lu.se/klinvetmalmo/koagulatio nsforskning/forskningsprojekt) to gather data on the potential association of the ETP with the phenotype.