May-Hegglin Anomaly Workup

Updated: Feb 28, 2019
  • Author: Vikramjit S Kanwar, MBBS, MBA, MRCP(UK), FAAP; Chief Editor: Hassan M Yaish, MD  more...
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Workup

Approach Considerations

Because of the increased risks of bleeding (particularly intracranial hemorrhage) in young children who have thrombocytopenia, special attention must be paid to pediatric patients with May-Hegglin anomaly (MHA) who have sustained severe head trauma. Imaging studies of the head (computed tomography [CT] or magnetic resonance imaging [MRI]) should be considered in these patients. Because MHA is an autosomal dominant inherited condition, genetic counseling is important.

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Laboratory Studies

The complete blood count (CBC) is essential in assessing MHA. The platelet count is decreased (usually in the range of 40-80 ´ 109/L), but the degree of thrombocytopenia varies. The disorder is also characterized by giant platelets. Platelets are enlarged (>15 µm in diameter), and the mean volume of MHA platelets can be as high as 30 fL. [26] Platelet morphology is otherwise normal.

On electron microscopy, platelets are seen to contain normal organelles (alpha granules, dense granules, lysosomes, and mitochondria). The most conspicuous ultrastructural feature of the platelets is an increased amount of disorganized microtubules.

The Wright-stained peripheral blood smear shows cytoplasmic inclusion bodies (see the image below), particularly in the neutrophils but also in monocytes, eosinophils, and basophils. The inclusions are large (>5 µm), spindle-shaped, pale, blue-staining bodies that consist of ribosomes, segments of endoplasmic reticulum, and microfilaments. They are located in the periphery of the cytoplasm and resemble Döhle bodies. [27]

Blood smear (original magnification ×2000) in pati Blood smear (original magnification ×2000) in patient with May-Hegglin anomaly (MHA) demonstrates characteristic giant platelet with poorly defined granulation. Normal-sized platelet is also present. Trilobed neutrophil contains large, well-defined, basophilic, peripherally placed cytoplasmic inclusion body (resembling Döhle body). Image used with permission from Little, Brown.

Immunocytochemistry can detect NMMHCIIA complexes within the leukocytes and is a useful confirmatory test. [28]

The bleeding time is prolonged in concordance with the degree of thrombocytopenia. Platelets usually aggregate normally in response to various agonists. The glycoprotein composition of the platelet surface is normal. [13]

A study by Rabbolini et al suggested that there would be less likelihood of missing cases of MYH9-related disorders if immunofluorescence and next-generation sequencing were prioritized in diagnostic algorithms during the workup of patients with thrombocytopenia associated with giant platelets. The investigators suggested that such prioritization is necessary even if peripheral blood film does not appear to reveal Döhle-like bodies. [29]

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