A 56-year-old construction worker presents to his primary care clinician for a routine physical examination. He has no specific complaints, although he mentions that his hearing is slowly getting worse. An audiometry exam confirms bilateral mild to moderate hearing loss at 40 dB. His physical examination is otherwise unremarkable.

The patient’s medical history includes a >30-year history of a low platelet count but is otherwise unremarkable. When asked about his low platelet count, the patient states that he was told “not to worry about it.” He could not remember any specific laboratory values or when his most recent blood work was done. He denies having a history of petechiae, spontaneous bleeding or bruising, gum or nose bleeding, or increased bleeding with dental procedures or minor injuries.

The patient’s medical history also includes bilateral cataract surgery 2 years ago, with no postoperative bleeding complications. He reports that he consumes approximately 2 to 4 beers per week and does not smoke cigarettes or use recreational drugs. The patient is married with 2 grown children. Neither of his parents, both of whom died from a heart attack when they were in their 70s, had any known bleeding disorders, and he has no siblings.

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Given the patient’s history, a complete blood count (CBC) was ordered. White blood count, red blood count, and indices were within normal limits. His platelet count was low at 26,000/μL (reference range, 150,000/μL to 400,000/μL).

May-Hegglin Anomaly

May-Hegglin anomaly (MHA) is a rare, congenital, autosomal-dominant disorder first identified by German physician Richard May in the early 1900s and then later described in more detail by Swiss physician Robert Hegglin in the mid-1940s.1 The disorder is characterized by thrombocytopenia, abnormally large and misshapen (giant) platelets, and a defect of leukocytes consisting of the presence of inclusion bodies, also known as Döhle bodies, in the cytoplasm.1 Some individuals with this disorder are asymptomatic, whereas others may have various bleeding disorders and other abnormalities, such as sensorineural hearing loss, cataracts, and renal insufficiency or failure.2,3

MHA is 1 of 4 overlapping syndromes that belong to a group of inherited giant platelet disorders caused by mutations in the MYH9 gene. The other 3 disorders are Epstein syndrome, Fechtner syndrome, and Sebastian platelet syndrome.3 Common to all 4 syndromes are giant platelets and thrombocytopenia (macrothrombocytopenia). The 4 syndromes are distinguished from one another by the presence or absence of the leukocyte inclusion bodies. MHA is the only syndrome to demonstrate large leukocyte cytoplasmic inclusion bodies, whereas small leukocyte cytoplasmic inclusion bodies are observed in Fechtner syndrome and Sebastian platelet syndrome. Inclusions cannot be observed via standard light microscopy in Epstein syndrome.3

Although MHA was first identified more than a century ago, it has been only 20 years since the genetic basis of MHA was established as a mutation in MYH9, the gene that encodes for the nonmuscular myosin heavy chain IIA (NMMHC-IIA).2-4 A study revealed that the MYH9 mutation causes a loss of myosin IIA function, thus promoting proplatelet formation and possibly triggering premature platelet release, which may result in macrothrombocytopenia.2 Glomerulonephritis, sometimes seen in MHA, also is thought to be caused by defects in the myosin IIA structure. Manifestations of this syndrome (ie, renal disease, hearing loss, and presenile cataracts) are dependent on the position of the mutations within the gene.2

Signs and Symptoms

Although thrombocytopenia occurs in 50% of patients with MHA, severe bleeding is unusual. Individuals may experience easy bruising, recurrent epistaxis, gingival bleeding, menorrhagia, and excessive bleeding associated with surgical procedures.5 In women, iron deficiency anemia caused by menorrhagia is a major problem. In addition, high-tone hearing loss, renal involvement, and cataracts are, in decreasing order of frequency, clinical features of MHA.6 Petechiae are rare and usually only occur if the already depressed platelet count decreases further due to comorbidities.

Platelet counts may vary between <30,000/μL and 100,000/μL.5 In an individual patient, the platelet count may remain rather stable over time. However, a transient decrease in platelet count may occur after a viral infection or other risk factors for thrombocytopenia.7

Even though giant platelets are present from birth in all individuals with an MYH9-related platelet disorder, mild conditions may remain undetected even in adulthood. For those individuals, distinguishing between a congenital or inherited thrombocytopenia and an acquired or secondary thrombocytopenia, such as an immune thrombocytopenia purpura, is essential to avoid unnecessary and potentially harmful treatments, including corticosteroid therapy and splenectomy.6

Identification of patients with probable MYH9-related disorders is possible through the analysis of blood cell count, mean platelet volume, platelet histogram, and platelet morphology in the blood smear.7 The diagnosis of MHA occurs through the identification of characteristic leukocyte inclusion bodies on stained blood smears. If suspected, the disease may be confirmed by the immunofluorescence test for NMMHC-IIA distribution within neutrophils.

In the case of MYH9-related diseases, the test will demonstrate cytoplasmic aggregates or clusters.6 However, it is not always easy to detect the leukocyte inclusion bodies on stained blood smears, which can lead to a misdiagnosis of immune thrombocytopenia purpura and incorrect treatment.8