A patient with Fechtner syndrome successfully treated with romiplostim.

doi:10.1160/TH11-07-0474 Thromb Haemost 2012; 107: 590–591 Dear Sirs, Fechtner syndrome (1) is a rare autosomaldominant disorder characterised by thrombocytopenia, giant platelets and features of Alport syndrome, i.e. nephritis, cataract and sensorineural hearing loss. It is one entity of a group of giant platelet disorders caused by mutations of the MYH9 gene, encoding the heavy chain of nonmuscle myosin IIA (NMMHC-A) (2, 3). NMMHC-A is supposed to play a key role in the cytoskeleton function and contractile system of platelets and leukocytes (3). Most patients are asymptomatic or have a mild bleeding tendency. However, during major interventions or in case of ongoing bleeding symptoms, it might be desirable to increase the platelet count temporarily. In 2010, Pecci et al. reported an observational study on the effect of eltrombopag, a thrombopoietin receptor agonist, in 12 patients with MYH9 related platelet disorders (4). In most of these patients bleeding tendency decreased or vanished. We present the case of a patient with Fechtner syndrome suffering from recurrent bleeding episodes during haemodialysis who was initially successfully treated with the thrombopoietin receptor agonist romiplostim, but in whom the effect on the platelet count decreased over time. A 30-year-old Caucasian male patient presented with a history of thrombocytopenia diagnosed at the age of two. At the age of 12, he received the first platelet transfusion. None of his relatives had a history of thrombocytopenia. In December 2005, he developed progressive renal failure with severe hypertension, and an unselective urinary protein loss of 3.2 g/day. He remained severely thrombocytopenic. Wiskott-Aldrich syndrome was excluded, but invasive investigations of the renal disease were deferred due to low platelet count. Bone marrow examination showed a normal amount of megakaryocytes leading to the diagnosis of chronic immune-mediated thrombocytopenia (ITP) despite the absence of antiplatelet antibodies and no evidence for splenic platelet sequestration by scintigraphy. Treatments with dexamethasone, high-dose immunoglobulines and mycofenolate mofetil 1g/day twice daily failed to increase the platelet count. Haemodialysis was started in March 2007. Because of repetitive bleeding incidents from venous access during haemodialysis under regular co-medication with heparin, the patient was treated with weekly platelet transfusions by his nephrologist, reducing his chances of successful kidney transplantation through alloantibody formation. In February 2008, the diagnosis of MYH9-related macrothrombocytopenia was made based on the presence of large platelets in the peripheral blood and Döhle-like inclusion bodies in the granulocytes (5). Mutation analysis revealed a mutation in exon 1: S96L of the MYH9 gene. Because the patient presented with moderate sensorineural hearing difficulties, presenile cataract, and renal failure, the diagnosis of Fechtner syndrome was made (1). The patient displayed a de novo mutation as none of his first degree relatives were affected. There were no antecedents of thrombotic events. On the basis of the initial diagnosis of ITP, the patient was included in an AMG 531 clinical trial funded by Amgen (Thousand Oaks, CA, USA). Weekly subcutaneous treatment with romiplostim was started at a dose of 1 μg/kg body weight in October 2007 at a platelet count of 7,000/μl and was increased weekly to a maximum of 10 μg/kg body weight. This resulted in an increase of the platelet count to 66,000 platelets/μl in April 2008 ( Fig. 1). No bleeding events or serious side effects such as thromboembolic events occurred. Followup bone marrow biopsies did not show evidence of any reticulin or collagen increase. However, despite continuous application of the maximum dose of 10 μg/kg body weight, platelet counts decreased again