Platelets, also called thrombocytes, are small cell fragments in the blood that form clots to stop bleeding. A normal platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. When the platelet count is above 450,000, it is considered high or elevated.
There are several blood disorders that can cause high platelets, including:
Essential Thrombocythemia
Essential thrombocythemia (ET) is a rare blood cancer that leads to an abnormal increase in the number of platelets produced. In ET, the bone marrow produces too many platelets due to an acquired mutation in the blood-forming cells. The condition may have no symptoms initially and be detected on a routine blood test. Symptoms that may occur include headaches, dizziness, tingling in the hands and feet, bleeding problems, blood clots, and redness or blushing.
Causes
The cause of ET is not fully understood. About 50% of cases are due to a mutation in the JAK2, CALR, or MPL genes involved in controlling platelet production. These mutations are acquired, meaning they occur after birth and are not inherited. The mutations lead bone marrow stem cells to make too many platelets. In many cases, no gene mutation is found.
Diagnosis
ET is diagnosed with blood tests, genetic testing, and a bone marrow biopsy. Findings include:
- Platelet count over 450,000/microliter
- Enlarged bone marrow with increased numbers of megakaryocytes, the cells that produce platelets
- No identifiable cause for the elevated platelet count such as infection, inflammation, or iron deficiency
- Genetic mutation such as JAK2, CALR, or MPL in about 50% of cases
Treatment
Treatment aims to prevent blood clots, bleeding, and other complications. Options may include:
- Aspirin to reduce blood clotting
- Blood thinners like warfarin if high risk of blood clots
- Hydroxyurea to lower platelet count
- Anagrelide to reduce platelet production
- Phlebotomy to decrease blood thickness
- Interferon alpha if very high risk of blood clots
- Bone marrow transplant in rare cases
Polycythemia Vera
Polycythemia vera (PV) is a rare bone marrow disorder in which the body makes too many red blood cells, and also too many white blood cells and platelets. It is a type of myeloproliferative neoplasm, which are blood cancers that cause overproduction of blood cells.
Causes
Most cases of PV (95%) are caused by a mutation in the JAK2 gene. This mutation causes the bone marrow to make too many blood cells. The cause in other cases without this mutation is unknown.
Diagnosis
PV is diagnosed with:
- Complete blood count showing high red blood cells, hemoglobin, hematocrit, white blood cells and platelet count
- Bone marrow biopsy showing increased production of all blood cell types
- Genetic testing for the JAK2 mutation
- Testing to rule out other causes like heart or lung problems leading to increased red blood cells
Treatment
Treatment options for PV include:
- Phlebotomy (blood removal) to decrease blood volume
- Low-dose aspirin to reduce blood clot risk
- Hydroxyurea to decrease blood cell production
- Interferon to reduce JAK2 mutant cells
- Busulfan or radioactive phosphorus to suppress bone marrow
- Bone marrow/stem cell transplant in some younger patients
Chronic Myeloid Leukemia
Chronic myeloid leukemia (CML) is a type of blood and bone marrow cancer in which the body makes too many white blood cells. It accounts for 15% of newly diagnosed cases of leukemia.
Causes
CML is caused by a genetic abnormality that produces an abnormal gene called BCR-ABL. This gene leads to uncontrolled growth of myeloid cells, which are blood stem cells that develop into red blood cells, other types of white blood cells, and platelets. The BCR-ABL gene is the result of a swapping of genetic material (chromosomal translocation) between chromosomes 9 and 22.
Diagnosis
CML is diagnosed with:
- Blood tests showing high white blood cell count and immature white blood cells called myelocytes
- Often elevated platelet and basophil counts
- Genetic testing showing the Philadelphia chromosome and BCR-ABL gene
- Bone marrow biopsy confirming increased myeloid cells
Treatment
Treatment options for CML include:
- Targeted drugs like imatinib, dasatinib, or nilotinib that block the abnormal BCR-ABL protein
- Stem cell transplant if targeted drugs do not work
- Hydroxyurea or interferon alfa with or without targeted drugs
- Chemotherapy in advanced stages
Primary Myelofibrosis
Primary myelofibrosis is one of the myeloproliferative neoplasms, which are blood cancers associated with overproduction of blood cells. In primary myelofibrosis, scar tissue forms in the bone marrow, impairing normal blood cell production.
Causes
The cause involves abnormal blood stem cells in the bone marrow. About 50% of cases are due to mutations in the JAK2, CALR, or MPL genes. These mutations cause excess growth and replication of blood cells in the bone marrow.
Diagnosis
Primary myelofibrosis is diagnosed with:
- Complete blood count showing varying degrees of low red blood cells, white blood cells, and platelets
- Often high immature blood cells and platelet counts early on
- Bone marrow biopsy showing scar tissue and abnormal megakaryocytes
- Genetic testing for known mutations
Treatment
Treatment aims to manage symptoms and slow disease progression. Options include:
- Targeted therapy with JAK inhibitors like ruxolitinib
- Chemotherapy drugs like hydroxyurea
- Immunomodulators like lenalidomide
- Splenectomy surgery in some cases
- Stem cell transplant in selected cases
- Transfusions and growth factors for low blood cell counts
Reactive Thrombocytosis
Reactive thrombocytosis is increased platelet production due to an underlying inflammatory condition, infection, trauma, surgery, iron deficiency, or malignancy. When the underlying condition resolves, the elevated platelet count returns to normal.
Causes
Reactive thrombocytosis can be caused by:
- Inflammatory diseases like rheumatoid arthritis, inflammatory bowel disease
- Infections including pneumonia, urinary tract infections, abscesses
- Malignancies like lung, breast, ovarian, or colon cancer
- Tissue damage from recent surgery, trauma or burns
- Hemolytic anemia which destroys red blood cells
- Iron deficiency
- Asplenia or hyposplenia (reduced spleen function)
- Certain medications like epinephrine
Diagnosis
Reactive thrombocytosis is a diagnosis of exclusion when high platelets are found and tests rule out other causes like myeloproliferative disorders. Diagnosis involves:
- Complete blood count showing elevated platelets
- Normal red blood cell and white blood cell counts
- Tests to find and treat any underlying condition
- Bone marrow biopsy may be done to exclude myeloproliferative neoplasms
Treatment
Treatment focuses on the underlying disorder causing reactive thrombocytosis. Options may include:
- Treating infections, reducing inflammation, or removing sources of tissue damage
- Managing iron deficiency
- Removing any implicated medications
- Aspirin or hydroxyurea if very high platelet counts substantially increase clot risk
Myelodysplastic Syndromes
Myelodysplastic syndromes (MDS) are a group of disorders caused by abnormal bone marrow stem cells. In MDS, stem cells do not mature properly, leading to low blood cell counts and risk of progression to acute myeloid leukemia.
Causes
MDS can be caused by:
- Prior chemotherapy or radiation therapy
- Exposure to toxic chemicals like tobacco, pesticides, or solvents
- Genetic syndromes like Fanconi anemia
- Blood disorders like aplastic anemia
- No identifiable cause in most cases
Diagnosis
MDS is diagnosed with:
- Complete blood count showing one or more low blood cell types
- Blood smear showing abnormal cell shapes and immature cells
- Bone marrow biopsy showing dysplastic, poorly formed cells
- Cytogenetic analysis for chromosomal abnormalities
Treatment
Treatment options for MDS include:
- Supportive care with blood transfusions and growth factors
- Chemotherapy drugs like azacitidine and decitabine
- Immunosuppressive therapy
- Lenalidomide for MDS with 5q chromosomal deletion
- Stem cell transplant when possible
Conclusion
In summary, several blood disorders can lead to elevated platelet levels. Essential thrombocythemia, polycythemia vera, chronic myeloid leukemia, and primary myelofibrosis are myeloproliferative neoplasms involving abnormal proliferation of blood stem cells. Reactive thrombocytosis occurs secondary to inflammation, infection, or other underlying disorders. Myelodysplastic syndromes involve abnormal hematopoiesis and ineffective blood cell production. Diagnosis involves blood testing, genetic analysis, and bone marrow studies. Treatment aims to prevent complications associated with high platelets and manage any underlying disease.
