Thrombocytosis

Thrombocytosis (or thrombocythemia) is the presence of high platelet counts in the blood, and can be either primary (also termed essential and caused by a myeloproliferative disease) or reactive (also termed secondary). Although often symptomless (particularly when it is a secondary reaction), it can predispose to thrombosis in some patients. Thrombocytosis can be contrasted with thrombocytopenia, a loss of platelets in the blood.

In a healthy individual, a normal platelet count ranges from 150,000 and 450,000 per mm³ (or microlitre) (150–450 x 10⁹/L).^[1] These limits, however, are determined by the 2.5th lower and upper percentile, and a deviation does not necessary imply any form of disease. Nevertheless, counts over 750,000 (and especially over a million) are considered serious enough to warrant investigation and intervention.

Signs and symptoms

High platelet levels do not necessarily signal any clinical problems, and are picked up on a routine full blood count. However, it is important that a full medical history be elicited to ensure that the increased platelet count is not due to a secondary process. Often, it occurs in tandem with an inflammatory disease, as the principal stimulants of platelet production (e.g. thrombopoietin) are elevated in these clinical states as part of the acute phase reaction.

High platelet counts can occur in patients with polycythemia vera (high red blood cell counts), and is an additional risk factor for complications.

A very small segment of patients report symptoms of erythromelalgia, a burning sensation and redness of the extremities that resolves with cooling and/or aspirin use.^[2]

Scientific literature sometimes excludes thrombocytosis from the scope of thrombophilia by definition,^[3] but practically, by the definition of thrombophilia as an increased predisposition to thrombosis,^[4][5] thrombocytosis (especially primary thrombocytosis) is a potential cause of thrombophilia. Conversely, secondary thrombocytosis very rarely causes thrombotic complications.^[6]

Diagnosis

Laboratory tests might include: full blood count, liver enzymes, renal function and erythrocyte sedimentation rate.

If the cause for the high platelet count remains unclear, bone marrow biopsy is often undertaken, to differentiate whether the high platelet count is reactive or essential.

Causes

Increased platelet counts can be due to a number of disease processes:

• Essential (primary)
  • Essential thrombocytosis (a form of myeloproliferative disease)
  • Other myeloproliferative disorders such as chronic myelogenous leukemia, polycythemia vera, myelofibrosis
• Reactive (secondary)
  • Inflammation
  • Surgery (which leads to an inflammatory state)
  • Hyposplenism (decreased breakdown due to decreased function of the spleen)
  • Splenectomy
  • Asplenia (absence of normal spleen function)
  • Iron deficiency anemia or hemorrhage

Over-medication with drugs that treat thrombocytopenia, such as eltrombopag or romiplostim, may also result in thrombocytosis. Other causes include the following

• Kawasaki disease
• Soft tissue sarcoma
• Osteosarcoma
• Dermatitis (rarely)
• Inflammatory bowel disease
• Rheumatoid arthritis
• Nephritis
• Nephrotic syndrome
• Bacterial diseases, including pneumonia, sepsis, meningitis, urinary tract infections, and septic arthritis.^[6]

The vast majority of causes of thrombocytosis are acquired disorders, but in a few cases, they may be congenital, such as thrombocytosis due to congenital asplenia.^[7]

Treatment

Often, no treatment is required or necessary for reactive thrombocytosis. In cases of reactive thrombocytosis of more than 1,000x10⁹/L, it may be considered to administer daily low dose aspirin (such as 65 mg) to minimize the risk of stroke or thrombosis.^[8]

However, in primary thrombocytosis, if platelet counts are over 750,000 or 1,000,000, and especially if there are other risk factors for thrombosis, treatment may be needed. Selective use of aspirin at low doses is thought to be protective. Extremely high platelet counts in primary thrombocytosis can be treated with hydroxyurea (a cytoreducing agent) or anagrelide (Agrylin).^[9]

In Jak-2 positive disorders, ruxolitinib (Jakafi) can be effective.

References

• Schafer AI (March 2004). "Thrombocytosis". N. Engl. J. Med. 350 (12): 1211–9. PMID 15028825. doi:10.1056/NEJMra035363. 

1. ↑ Kumar & Clark (2005). "8". Clinical Medicine (Sixth ed.). Elsevier Saunders. p. 469. ISBN 0-7020-2763-4. 
2. ↑ van Genderen, P. J.; Lucas, I. S.; van Strik, R.; Vuzevski, V. D.; Prins, F. J.; van Vliet, H. H.; Michiels, J. J. (1996-09-01). "Erythromelalgia in essential thrombocythemia is characterized by platelet activation and endothelial cell damage but not by thrombin generation". Thrombosis and Haemostasis. 76 (3): 333–338. ISSN 0340-6245. PMID 8883266. 
3. ↑ "Management of patients with thrombophilia". Drug and Therapeutics Bulletin. 33 (1): 6–8. 1995. PMID 7587981. doi:10.1136/dtb.1995.3316. 
4. ↑ Mitchell RS, Kumar V, Abbas AK, Fausto N (2007). "Chapter 4". Robbins Basic Pathology (Eighth ed.). Philadelphia: Saunders. ISBN 1-4160-2973-7. 
5. ↑ Heit JA (2007). "Thrombophilia: common questions on laboratory assessment and management". Hematology Am. Soc. Hematol. Educ. Program. 2007 (1): 127–35. PMID 18024620. doi:10.1182/asheducation-2007.1.127. 
6. 1 2 Pediatric Thrombocytosis at eMedicine
7. ↑ Chanet, V.; Tournilhac, O.; Dieu-Bellamy, V.; Boiret, N.; Spitz, P.; Baud, O.; Darcha, C.; Travade, P.; Laurichesse, H. (2000). "Isolated spleen agenesis: A rare cause of thrombocytosis mimicking essential thrombocythemia". Haematologica. 85 (11): 1211–1213. PMID 11064471. 
8. ↑ Secondary Thrombocytosis~treatment at eMedicine
9. ↑ Harrison, CN; Campbell PJ; Buck G; Wheatley K; East CL; Bareford D; Wilkins BS; van der Walt JD; Reilly JT; Grigg AP; Revell P; Woodcock BE; Green AR; United Kingdom Medical Research Council Primary Thrombocythemia 1 Study (2005). "Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia.". NEJM. 353 (1): 33–45. PMID 16000354. doi:10.1056/NEJMoa043800.