What diseases cause giant platelets? A guide to macrothrombocytopenia

October 1, 2025 •

5 min read

Giant platelets, known as macrothrombocytes, are platelets with a diameter greater than 7 microns, significantly larger than normal platelets. The presence of these abnormally large blood cells, a condition called macrothrombocytopenia, can indicate several underlying diseases, both inherited and acquired.

Quick Summary

Giant platelets, or macrothrombocytes, are abnormally large blood cells that can signal a range of underlying health conditions. These diseases are broadly categorized into inherited and acquired disorders, affecting blood clotting ability and increasing bleeding risks. Examples include genetic syndromes like Bernard-Soulier and conditions such as myelodysplastic syndrome.

Key Points

Diverse Etiologies: Giant platelets can be caused by both inherited genetic mutations and acquired medical conditions, including autoimmune disorders and blood cancers.
Hereditary Disorders: Inherited causes include rare syndromes such as Bernard-Soulier syndrome, May-Hegglin anomaly, and Gray Platelet Syndrome, which often result in both large and low numbers of platelets.
Acquired Conditions: Acquired causes include Immune Thrombocytopenia (ITP), where the immune system destroys platelets, and Myelodysplastic Syndrome (MDS), a bone marrow cancer.
Impaired Clotting: Due to their large size or functional defects, giant platelets may not clot effectively, increasing the risk of abnormal bleeding.
Comprehensive Diagnosis: Diagnosis typically involves a blood smear review, followed by platelet function tests, flow cytometry, and potentially genetic testing or a bone marrow biopsy, to differentiate the various potential causes.
Misdiagnosis Risk: Inherited giant platelet disorders can sometimes be misdiagnosed as acquired conditions like ITP, leading to inappropriate treatment, highlighting the need for careful evaluation.

Understanding giant platelets and macrothrombocytopenia

Platelets are tiny, irregularly shaped cells that help the body form clots to stop bleeding. A healthy adult typically has a platelet count of 150,000 to 450,000 platelets per microliter of blood. Giant platelets, or macrothrombocytes, are platelets that are abnormally large in size, often accompanied by a low overall platelet count, a combination known as macrothrombocytopenia. When present, these oversized platelets can indicate a significant medical condition and may not function as effectively as normal-sized platelets, leading to impaired blood clotting and an increased risk of bleeding. The reasons behind the formation of giant platelets can be broadly divided into inherited and acquired causes.

Inherited diseases causing giant platelets

Many of the conditions causing giant platelets are rare genetic disorders passed down through families. These inherited conditions often arise from mutations in specific genes that affect platelet development or function.

Bernard-Soulier Syndrome (BSS)

BSS is a rare, inherited bleeding disorder caused by mutations in the GP1BA, GP1BB, or GP9 genes.

The syndrome results in a deficiency of the glycoprotein Ib-IX-V complex on the platelet surface, which prevents platelets from adhering properly to blood vessel walls.
Key features include giant platelets, moderate to severe thrombocytopenia, and a prolonged bleeding time.
Symptoms often include easy bruising, nosebleeds, and heavy menstrual bleeding.

MYH9-related disorders

This is a family of autosomal dominant disorders caused by mutations in the MYH9 gene, which provides instructions for a protein called non-muscle myosin heavy chain IIA.

May-Hegglin Anomaly: This classic MYH9 disorder features giant platelets, thrombocytopenia, and distinctive inclusions (Döhle-like bodies) in the cytoplasm of white blood cells. Most individuals experience mild or no bleeding.
Sebastian Syndrome: Similar to May-Hegglin anomaly, but with more subtle inclusions in white blood cells and without the associated non-hematological symptoms seen in other MYH9 disorders.
Fechtner Syndrome: This is a more severe variant that combines the hematological features of May-Hegglin anomaly with systemic issues like nephritis, hearing loss, and cataracts.
Epstein Syndrome: Another MYH9-related disorder, characterized by the presence of giant platelets, thrombocytopenia, nephritis, and deafness.

Gray Platelet Syndrome

This is a rare inherited platelet disorder resulting from mutations in the NBEAL2 gene.

It is characterized by a deficiency of alpha-granules, which gives the platelets a distinctive gray appearance under a microscope.
Patients have giant platelets, moderate thrombocytopenia, and a mild to moderate lifelong bleeding tendency.

Other inherited causes

Jacobsen Syndrome: A congenital disorder caused by a deletion on chromosome 11, which includes the FLI1 gene. It is associated with macrothrombocytopenia and a variety of other physical abnormalities.
Platelet-Type Bleeding Disorder 16 (BDPLT16): An autosomal dominant form of congenital macrothrombocytopenia with platelet anisocytosis.
Harris Platelet Syndrome: Also known as asymptomatic constitutional macrothrombocytopenia, this is a common inherited disorder in some populations.

Acquired diseases causing giant platelets

Besides inherited syndromes, several acquired conditions can also lead to the formation of giant platelets, sometimes in an attempt to compensate for low platelet counts.

Immune Thrombocytopenia (ITP)

ITP is an autoimmune condition where the body’s immune system mistakenly attacks and destroys its own platelets.

The bone marrow often responds by producing more platelets, but these are often larger and less mature (megathrombocytes), resulting in the presence of giant platelets.
ITP can be acute (following a viral infection) or chronic and is a common cause of thrombocytopenia with large platelets.

Myelodysplastic Syndrome (MDS)

MDS is a group of blood and bone marrow cancers where blood cells fail to mature properly.

This can lead to significant numbers of giant platelets alongside other blood cell abnormalities, such as anemia.
MDS is a more serious cause, and the prognosis depends on the specific type and severity.

Other acquired causes

Myeloproliferative Neoplasms (MPNs): These are cancers of the bone marrow that cause the body to produce too many blood cells. The platelets produced can be abnormally large.
Chronic Liver Disease or Cirrhosis: This can lead to an enlarged spleen, which traps and sequesters platelets. The remaining circulating platelets can sometimes appear larger.

Comparison of selected giant platelet disorders


Feature	Bernard-Soulier Syndrome	May-Hegglin Anomaly	Gray Platelet Syndrome	Immune Thrombocytopenia (ITP)
Etiology	Inherited (recessive/dominant)	Inherited (autosomal dominant)	Inherited (autosomal recessive/dominant)	Acquired (autoimmune)
Underlying Defect	Glycoprotein Ib-IX-V complex deficiency	MYH9 gene mutation affecting myosin	Alpha-granule deficiency (due to NBEAL2 gene mutation)	Autoantibodies against platelets
Other Cell Findings	Normal white and red blood cells	Döhle-like bodies in white blood cells	Normal white and red blood cells	Normal white and red blood cells (usually)
Associated Symptoms	Easy bruising, prolonged bleeding	Often asymptomatic, mild bleeding risk	Moderate bleeding tendency, bruising	Bruising, petechiae, gum bleeding
Treatment Approach	Proactive bleeding management, transfusions if needed	Generally no treatment needed for mild cases	Bleeding management, transfusions if severe	Immunosuppressants, IVIG, steroids

Diagnosis and clinical significance

Diagnosing the underlying cause of giant platelets begins with a complete blood count (CBC), which may show a low platelet count (thrombocytopenia) and an elevated mean platelet volume (MPV). A detailed review of a peripheral blood smear is essential for a hematologist to visually inspect the platelet size and morphology, as well as look for associated features like the Döhle-like inclusions seen in May-Hegglin anomaly.

Further diagnostic steps can include:

Platelet function tests: To evaluate how well the platelets are working.
Flow cytometry: To measure the expression of specific platelet surface proteins, such as the glycoprotein complex implicated in BSS.
Genetic testing: To identify specific gene mutations associated with inherited giant platelet disorders.
Bone marrow biopsy: May be necessary, especially if myelodysplastic syndrome or other bone marrow disorders are suspected.

Conclusion

In summary, the presence of giant platelets, or macrothrombocytopenia, can stem from a variety of inherited and acquired conditions, ranging from relatively benign syndromes to more serious blood cancers. Inherited causes often include Bernard-Soulier syndrome, Gray Platelet Syndrome, and the MYH9-related disorders, while acquired causes include Immune Thrombocytopenia and Myelodysplastic Syndrome. The presence of giant platelets is often a significant diagnostic clue that guides further testing to determine the underlying disease. Proper diagnosis is crucial to ensure appropriate management, especially to distinguish between chronic, inherited conditions and more acute or progressive acquired disorders, thereby preventing unnecessary treatments. Regular monitoring and proactive strategies, particularly for those with a bleeding tendency, are essential for managing these conditions.

For more information on platelet disorders and their management, visit the National Heart, Lung, and Blood Institute (NHLBI) website at https://www.nhlbi.nih.gov/health/platelet-disorders.

Frequently Asked Questions

Inherited diseases are genetic disorders present from birth, caused by mutations passed down through families, such as Bernard-Soulier syndrome. Acquired giant platelet conditions, like Immune Thrombocytopenia (ITP), develop later in life due to other medical issues.

Giant platelets can be a sign of a serious underlying condition, but the severity varies greatly. Some inherited disorders cause only mild symptoms, while other causes, like myelodysplastic syndrome, are more serious.

Bernard-Soulier syndrome (BSS) is a rare inherited bleeding disorder characterized by very large, dysfunctional platelets and a low platelet count. It results from a defect in a platelet surface protein complex essential for clotting.

May-Hegglin Anomaly is an inherited disorder with giant platelets and leukocyte inclusions (Döhle-like bodies) in the white blood cells. While it features large platelets and low count, bleeding symptoms are often mild compared to other syndromes.

Yes, ITP is an acquired autoimmune disease that can cause giant platelets. The bone marrow attempts to compensate for platelet destruction by producing more, but these newer, immature platelets (megathrombocytes) are often larger.

Diagnosis typically involves a complete blood count (CBC) followed by a visual examination of a peripheral blood smear. Specialized tests like flow cytometry, platelet function studies, or genetic testing are used to pinpoint the specific cause.

Treatment for giant platelet disorders depends on the underlying cause. For many inherited syndromes, management focuses on preventing and treating bleeding episodes rather than curing the genetic defect. Some acquired conditions, like ITP, can be managed with medication.