Thrombocytosis : Elevated Platelets
Understanding Thrombocytosis : Elevated Platelets
What Are Platelets?
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Platelets are tiny blood cells that help your blood clot to stop bleeding.
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Normal platelet count ranges roughly from 150,000 to 450,000 per microliter of blood.
What Does Elevated Platelets Mean?
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When your platelet count is above 450,000 per microliter, it’s called thrombocytosis.
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It can be mild, moderate, or severe depending on the number.
Types of Elevated Platelets:
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Primary (or Essential) Thrombocytosis:
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Caused by a bone marrow disorder where platelets are produced excessively without a clear reason.
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It's a myeloproliferative neoplasm (a type of blood cancer).
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Requires careful monitoring and sometimes treatment.
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Secondary (or Reactive) Thrombocytosis:
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More common.
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Happens in response to another condition, such as:
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Infection
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Inflammation (arthritis, autoimmune diseases)
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Recent surgery or trauma
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Iron deficiency anemia
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Certain cancers
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Splenectomy (removal of the spleen)
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Usually resolves once the underlying cause is treated.
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Symptoms:
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Often, elevated platelets don’t cause symptoms and are found incidentally.
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If very high, symptoms may include:
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Headaches
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Dizziness
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Visual changes
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Risk of clotting or bleeding (rare)
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Redness or warmth in hands/feet (erythromelalgia)
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Why Does It Matter?
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Very high platelet counts can increase the risk of blood clots, which can cause strokes, heart attacks, or deep vein thrombosis.
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Sometimes, if platelets are dysfunctional, there might be bleeding risks instead.
What Tests Might Follow?
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Repeat platelet counts to confirm persistence.
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Tests for inflammation markers, iron studies.
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Bone marrow biopsy (if primary thrombocytosis suspected).
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Genetic tests (like JAK2 mutation) for myeloproliferative disorders.
Treatment:
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Depends on cause.
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Reactive thrombocytosis usually resolves with treatment of the underlying condition.
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Primary thrombocytosis may require:
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Low-dose aspirin
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Medications to reduce platelet count (hydroxyurea, anagrelide)
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Regular monitoring by a hematologist.
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Is Elevated Platelets Hereditary?
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Reactive (secondary) thrombocytosis — the most common kind — is not hereditary. It’s a response to things like infections, inflammation, iron deficiency, or surgery, which aren’t inherited.
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Primary (essential) thrombocytosis can have some genetic components:
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It’s caused by mutations in bone marrow cells, such as the JAK2, CALR, or MPL genes.
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These mutations usually happen spontaneously (called somatic mutations), not inherited from parents.
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So, it’s not typically passed down through families, though very rarely, there can be familial forms.
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What About Family History?
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While the exact mutations aren’t inherited, a family history of blood cancers or myeloproliferative disordersmight slightly increase risk.
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But overall, essential thrombocytosis is mostly a sporadic condition.
Summary:
| Condition Type | Hereditary? |
|---|---|
| Reactive (secondary) | No |
| Primary (essential) | Usually no; caused by acquired mutations |
| Rare familial cases | Very uncommon |
What Are JAK2, CALR, and MPL Genes?
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These genes provide instructions for making proteins involved in blood cell production regulation inside the bone marrow.
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Mutations in these genes can cause overproduction of blood cells, including platelets.
1. JAK2 (Janus kinase 2) Gene
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Most common mutation in MPNs.
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The mutation (usually called JAK2 V617F) causes the JAK2 protein to be constantly active, telling the bone marrow to produce too many blood cells.
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Found in about:
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50-60% of essential thrombocythemia cases
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95% of polycythemia vera (another MPN)
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50-60% of primary myelofibrosis
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Causes increased platelet, red blood cell, and sometimes white blood cell production.
2. CALR (Calreticulin) Gene
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Mutation in CALR is the second most common cause of essential thrombocythemia and primary myelofibrosis.
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Found in about 20-30% of ET cases without JAK2 mutation.
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CALR mutations affect a protein involved in calcium signaling and cell proliferation.
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Usually associated with a lower risk of blood clots compared to JAK2 mutations.
3. MPL (Myeloproliferative leukemia virus oncogene) Gene
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MPL mutations affect the thrombopoietin receptor which regulates platelet production.
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Present in 3-5% of ET cases and some cases of primary myelofibrosis.
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Causes abnormal signaling leading to excessive platelet production.
Why Are These Mutations Important?
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They help diagnose specific MPNs.
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They guide treatment decisions and risk assessment (e.g., risk of clotting).
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They are somatic mutations — acquired during life, not inherited.
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Testing for these mutations is standard when evaluating high platelet counts or suspected MPN.
Summary Table:
| Gene | Mutation Effect | Common In | Frequency in ET | Clotting Risk |
|---|---|---|---|---|
| JAK2 | Constant activation of signaling | ET, PV, MF | ~50-60% | Higher |
| CALR | Alters calcium signaling | ET, MF | ~20-30% | Lower |
| MPL | Activates thrombopoietin receptor | ET, MF | ~3-5% | Variable |
How Are JAK2, CALR, and MPL Mutations Detected?
1. Sample Collection
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A blood draw (usually from a vein) is the most common sample.
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Sometimes a bone marrow aspirate may be used, especially if diagnosis is unclear.
2. DNA Extraction
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Lab technicians isolate DNA from white blood cells in the sample.
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This purified DNA contains the genetic code where mutations might exist.
3. Polymerase Chain Reaction (PCR)
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PCR is a method to amplify (make many copies) of specific gene regions—like JAK2 exon 14 (where the V617F mutation is), CALR exon 9, or MPL exon 10.
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Amplifying these parts makes it easier to detect mutations, even if only a small number of cells have them.
4. Mutation Detection Techniques
There are several ways to detect mutations after PCR:
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Allele-Specific PCR (AS-PCR):
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Designed to detect a specific known mutation (e.g., JAK2 V617F).
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Very sensitive and fast.
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Sanger Sequencing:
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Reads the nucleotide sequence of the amplified gene region.
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Useful for detecting known and unknown mutations.
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More detailed but slower and costlier.
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Next-Generation Sequencing (NGS):
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Can analyze multiple genes and mutations simultaneously.
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High sensitivity and comprehensive.
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Increasingly used in complex cases.
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Fragment Analysis (for CALR):
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Since CALR mutations are often insertions or deletions, fragment size analysis after PCR can detect these changes.
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5. Result Interpretation
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The lab reports whether the mutation is present or absent.
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Some tests also quantify the mutation burden (percentage of mutated cells).
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Positive results support a diagnosis of a myeloproliferative neoplasm.
Turnaround Time
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Typically, results take 1–2 weeks, depending on the lab and method used.
Summary Table of Methods:
| Mutation | Common Detection Method | Notes |
|---|---|---|
| JAK2 V617F | Allele-Specific PCR | Highly sensitive, common test |
| CALR | Fragment Analysis, PCR + Sequencing | Detects insertions/deletions |
| MPL | PCR + Sequencing or AS-PCR | Less common; tests exons 10 |
References
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Kaushansky, K. (2005). The molecular mechanisms that control thrombopoiesis. Journal of Clinical Investigation, 115(12), 3339–3347. https://doi.org/10.1172/JCI26891
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Tefferi, A., & Barbui, T. (2019). Polycythemia vera and essential thrombocythemia: 2021 update on diagnosis, risk-stratification, and management. American Journal of Hematology, 94(1), 133–143. https://doi.org/10.1002/ajh.25290
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McCrae, K. R. (2022). Thrombocytosis: Clinical manifestations, evaluation, and management. UpToDate. Retrieved from: https://www.uptodate.com
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Arber, D. A., et al. (2016). The 2016 WHO classification of myeloid neoplasms and acute leukemia. Blood, 127(20), 2391–2405. https://doi.org/10.1182/blood-2016-03-643544
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Harrison, C. N., et al. (2022). Essential thrombocythemia: Pathogenesis, diagnosis, and management. Hematology/Oncology Clinics of North America, 36(5), 869–886. https://doi.org/10.1016/j.hoc.2022.05.002
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Spivak, J. L. (2017). Myeloproliferative neoplasms. New England Journal of Medicine, 376(22), 2168–2181. https://doi.org/10.1056/NEJMra1406186
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Campbell, P. J., & Green, A. R. (2006). The myeloproliferative disorders. New England Journal of Medicine, 355(23), 2452–2466. https://doi.org/10.1056/NEJMra052528
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Tefferi, A. (2016). Primary thrombocythemia: 2021 update on diagnosis, risk stratification, and management. American Journal of Hematology, 91(3), 300–310. https://doi.org/10.1002/ajh.24273
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World Health Organization (WHO). (2022). WHO Classification of Tumours: Haematolymphoid Tumours, 5th Edition. IARC Press.
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American Society of Hematology (ASH). (2023). What is thrombocytosis? Patient FAQs. Retrieved from: https://www.hematology.org