With more than 300 families reported in the literature, MYH9-RD is the most frequent form of inherited thrombocytopenia [1,2]. It encompasses four dominant disorders previously considered as distinct disorders (see synonyms).
MYH9-RD is phenotypically variable and characterised by congenital macrothrombocytopenia as well as characteristic leucocyte inclusions (Döhle bodies) in all patients. Some patients may develop additional clinical features such as cataracts, hearing loss and/or progressive kidney disease. This is a rare autosomal dominant inherited disorder caused by mutations of the MYH9 gene encoding for the heavy chain of non-muscle myosin-IIA (myosin9). The bleeding tendency is broadly related to the level of platelet count. The main anaesthetic concerns in the management of patients with MYH9-RD are the development of a strategy to reduce haemorrhagic complications and the screening of associated disorders, particularly renal and hepatic impairment. The possibility of performing neuraxial anaesthesia will depend on platelet levels and normal platelet function.
In 1909, May observed that the blood smear of a woman referred to him showed many leukocytes which contained one or several pale blue inclusion bodies . Thirty-six years later, Hegglin described in three members of the same family the combination of a thrombocytopenia with giant platelets and the presence of Döhle-like bodies in their neutrophils . The name “May-Hegglin anomaly” was used in a case report published by Scholer et al. which Hegglin commented as being identical to his own report. Thereafter, the conjoined eponym “May-Hegglin anomaly” was used.
The disease locus was mapped to chromosome 22q12.3-q132 by linkage analysis [5,6,9]. The gene responsible for this disorder was identified as MYH9, which encodes a large cytoplasmic protein (NMMHC-IIA), expressed in many different tissues including blood cells, kidney, cochlea, hepatocytes. This protein regulates the cytoskeleton and acts as a key component of the activities that drive cell migration, cell-cell interaction and cell matrix adhesion. The pathogenesis of thrombocytopenia is mainly secondary to defective proplatelet formation by increased contractibility.
Several other inherited disorders that were previously considered to be separate entities (see synonyms) were in fact caused by mutations in the MYH9 gene. Therefore, the name MYH9-related disease or MYH9 disorder has been proposed . To date, over 80 different mutations have been identified [8,9]. The majority of patients are heterozygous for missense mutations and some patients for nonsense or frameshift mutations or deletions or duplications. Importantly, 35 % of MYH9-RD cases are sporadic and in half of them a de novo mutation is confirmed by molecular testing in parents.
The thrombocytopenia is characterised by large platelets (i.e. 40 % of platelets > 3.9 µm in diameter) and a platelet count <150x109/l, both detected from birth. Sometimes the platelet count decreased may be more severe < 30x109/l. Platelet aggregation, serotonin release, clot retraction are more often normal or slightly altered. Döhle bodies stained with May-Grunwald-Giemsa are present in 42–84 % of individuals with MYH9-RD, but detectable in all affected patients by immunofluorescence labelling of the non-muscle myosin heavy chain IIA protein in granulocytes .
The severity of bleeding is broadly related to the platelet count but most patients have a low haemorrhagic score as defined by the bleeding assessment tool of the International Society of Thrombosis and Haemostasis (ISTH/BAT) [10,11]. The prevalence of mucocutaneous bleeding was significantly higher in patients with head domain mutations of Myosin-9 . As a result, the diagnosis may wait until adulthood as they are at risk to develop renal failure, deafness or cataract in early or middle life. Easy bruising, spontaneous mucocutaneous bleedings, excessive bleedings after haemostatic challenges, or treatment with drugs interfering with platelet function, are manifestations of thrombocytopenia. In some rare patients with severe bleeding due to menorrhagia or intracranial bleeding, platelet transfusions should be used. Nevertheless, recent progress in the preoperative management by using thrombopoietin (TPO) mimetics must be noticed and are an interesting alternative in adults and children [13,14,15,16].
Differential diagnosis includes other macrothrombocytopenias (MTP) such as Bernard-Soulier syndrome (OMIM 213200/153670) or ACTN1 (OMIM 615193) or ITGA2B ITGB3 (OMIM187800) or TUBB1 (OMIM613112) or DIAPH1 (OMIM124900) related thrombocytopenias .