What is the May-Hegglin Anomaly?
May-Hegglin anomaly (MHA) is a rare, hereditary blood disorder characterized by abnormalities in the blood's cellular components, specifically platelets and leukocytes (white blood cells). The condition was first described by German physician R. May in 1909 and later by Swiss hematologist Robert Hegglin in 1945, who identified the complete diagnostic triad. As an autosomal dominant disorder, it results from a mutation in the $MYH9$ gene, meaning only one copy of the altered gene is needed to cause the condition. The gene encodes for non-muscle myosin heavy chain IIA, a protein crucial for normal cell function, including the formation of platelets.
Breaking Down the Triad of May-Hegglin
The diagnostic triad is typically identified through a routine blood test and a subsequent examination of a peripheral blood smear. The three key features are:
- Thrombocytopenia: This is a lower-than-normal platelet count in the blood, which can be mild to moderate in severity. Platelets are small, disc-shaped cell fragments essential for blood clotting. In MHA, thrombocytopenia occurs because of defective platelet formation from megakaryocytes in the bone marrow, leading to fewer circulating platelets.
- Giant Platelets: While the overall number of platelets is low, many of the remaining platelets are abnormally large and misshapen, also known as macrothrombocytopenia. These large platelets may have impaired function in small blood vessels, which can contribute to the bleeding tendency. The presence of these giant platelets can also cause automated blood cell counters to inaccurately report an even lower platelet count, making a manual examination of the blood smear crucial for correct diagnosis.
- Döhle-like Inclusions in Leukocytes: This is a distinct morphological feature where large, basophilic (blue-staining) cytoplasmic inclusions are found in granulocytes, such as neutrophils, as well as monocytes. These inclusions, often described as Döhle-like bodies, are composed of aggregated myosin heavy chain filaments due to the $MYH9$ gene mutation. They are typically spindle-shaped and easily visible on a Wright-stained peripheral blood smear.
Clinical Manifestations and Patient Experience
While the blood abnormalities are always present, the clinical symptoms can vary greatly among individuals with MHA. Many patients are completely asymptomatic, and their condition is only discovered incidentally during a routine blood test. For those who do experience symptoms, they are generally related to the degree of thrombocytopenia and can include:
- Easy bruising
- Frequent nosebleeds (epistaxis)
- Bleeding gums
- Heavy menstrual bleeding (menorrhagia)
- Prolonged or excessive bleeding after surgery, dental procedures, or injury
It is important to note that unlike other related disorders, MHA specifically is not typically associated with non-hematological issues like hearing loss, cataracts, or kidney disease. The bleeding risk is generally considered mild, but can be a concern during surgical procedures or severe trauma.
Diagnosis and Differential Diagnosis
Diagnosis of MHA begins with a standard complete blood count (CBC), which reveals the low platelet count and often indicates a higher-than-normal mean platelet volume (MPV) due to the presence of giant platelets. The definitive diagnosis relies on a manual peripheral blood smear examination to visually confirm the triad: thrombocytopenia, giant platelets, and the characteristic Döhle-like inclusions in leukocytes. Genetic testing for a mutation in the $MYH9$ gene can confirm the diagnosis and distinguish it from other related conditions.
It is critical to correctly differentiate MHA from other platelet disorders, especially immune thrombocytopenia (ITP), which it is frequently mistaken for. Misdiagnosis can lead to inappropriate treatments like corticosteroids, immunosuppressants, or splenectomy, which are ineffective for MHA and can cause unnecessary side effects.
Comparison of MYH9-Related Disorders
May-Hegglin anomaly is part of a family of autosomal dominant macrothrombocytopenias caused by mutations in the $MYH9$ gene. While all share the core feature of giant platelets and thrombocytopenia, the key differentiator is the presence of leukocyte inclusions and additional systemic features.
| Feature | May-Hegglin Anomaly (MHA) | Sebastian Syndrome | Fechtner Syndrome | Epstein Syndrome |
|---|---|---|---|---|
| Giant Platelets | Yes | Yes | Yes | Yes |
| Thrombocytopenia | Yes | Yes | Yes | Yes |
| Leukocyte Inclusions | Yes (Linear Döhle-like) | Yes (Small, spherical) | Yes (Small, spherical) | Absent or faint |
| Hearing Loss | No | No | Yes | Yes |
| Cataracts | No | No | Yes | No |
| Nephritis (Kidney Disease) | No | No | Yes | Yes |
Management and Prognosis
For most individuals with MHA, who are often asymptomatic or experience only mild bleeding, no specific treatment is necessary. Management primarily involves precautionary measures to minimize bleeding risk.
- Avoid certain medications: Individuals should avoid drugs that inhibit platelet function, such as aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs).
- Dental and surgical procedures: For patients undergoing surgery or dental work, a hematologist should be consulted. Pre-operative intravenous desmopressin (DDAVP) may be administered to reduce bleeding risk, or platelet transfusions may be required in cases of severe bleeding or trauma.
- Pregnancy: Pregnant women with MHA require careful monitoring by a multidisciplinary team to manage bleeding risks during delivery for both mother and newborn.
MHA is a lifelong condition, but for the majority of people, the prognosis is excellent, and it does not significantly impact their daily lives. Patients with MHA should be educated about their condition and necessary precautions to manage bleeding risk effectively.
Conclusion
What is the triad of May-Hegglin? It is the distinctive combination of thrombocytopenia, giant platelets, and Döhle-like leukocyte inclusions. This inherited blood disorder is caused by a mutation in the $MYH9$ gene and is part of a broader family of related conditions. While its clinical severity varies, with many individuals remaining asymptomatic, the key to proper management is accurate diagnosis, primarily through a peripheral blood smear. Avoiding misdiagnosis as other platelet disorders and taking precautions during procedures or trauma are vital for ensuring a good long-term outcome. With proper medical guidance, most people with MHA can lead healthy, normal lives despite their genetic condition.
Medscape's comprehensive article on May-Hegglin Anomaly provides further clinical details.
