Authors: Mark A. Marinella, MD, FACP, FACN, CNSP


Thrombocytosis is typically symptomless, discovered as an incidental laboratory abnormality when the complete blood count is obtained for an unrelated reason. A normal platelet count ranges between 150,000 and 450,000 per mm3. Thrombocytosis is typically either is a reactive process (secondary thrombocytosis) or is caused by a clonal bone marrow (myeloproliferative) disorder; the latter category includes essential thrombocythemia. It is often exceedingly difficult to differentiate between the two on the basis of clinical findings or laboratory test results. Yet there are fundamental differences between them in terms of cause, pathophysiological features, and clinical implications.

Platelet Physiology

The bone marrow pluripotent hematopoietic stem cell serves as the progenitor cell for all hematopoietic cellular elements. Through differentiation of this stem cell through subsequent cell divisions, megakaryoyctes are formed under the trophic influence of the hormone thrombopoietin (TPO) which serves as the ligand for the megakaryocyte growth factor receptor, c-mpl (1). Serum levels of thrombopoietin vary inversely with the circulating platelet count. For instance, patients with thrombocytopenia exhibit elevated serum levels of thrombopoietin due to reduced binding of the hormone to c-mpl receptors; this elevation in thrombopoietin serves as a stimulator of megakaryocytopoiesis (1). Conversely, thrombocytosis results in depressed serum levels of thrombopoietin. Various cytokines such as interleukin (IL)-1, IL-3, and IL-6 are also important for platelet maturation at various stages of development (1-3).

Any inflammatory process such as bacterial infection, neoplasia, sepsis, multiple trauma, burns, or pancreatitis that elevates serum IL levels (especially IL-6), may increase the circulating platelet count (2,3).  Elevated serum IL-6 levels correlate with thrombocytosis in various conditions such as tuberculosis, complicated urinary tract infections, and trauma, for instance (4-6).  Additionally, C-reactive protein may serve as a correlate to IL-6 since hepatic synthesis increases in response to acute inflammation. One study revealed that 81% of patients with thrombocytosis had elevated serum levels of either IL-6 or C-reactive protein (7).  Thrombocytosis associated with underlying inflammation or infection is known in clinical parlance as “reactive thrombocytosis” and constitutes the vast majority of cases encountered in practice (8,9). Clonal thrombocytosis, such as essential thrombocytosis or resulting from other myeloproliferative disorders, is a neoplastic process resulting from expansion of an abnormal marrow stem cell and will not be discussed further.

back to top

Etiologies of Thrombocytosis

For practical purposes, thrombocytosis can be divided into clonal (primary) thrombocytosis associated with myeloproliferative disorders or reactive (secondary) thrombocytosis which occur in association with an underlying disease, which is often infectious in nature. Table 1 displays major etiologies of thrombocytosis that a busy clinician may encounter. With regards to infection-related thrombocytosis, increased serum levels of IL-6 released by mononuclear cells play a central role in megakaryocytic proliferation and platelet production (1-3). Elevated catecholamine levels secondary to medical or surgical stress may induce splenic release of platelets, further contributing to thrombocytosis (1). An important, albeit uncommon, cause of persistent thrombocytosis is prior splenectomy.

Complications of thrombocytosis

In general, even extreme thrombocytosis (e.g., >1,000,000 cells/mm3) in the setting of an inflammatory condition is rarely associated with thrombotic events, which generally occur only in patients with underlying malignancy or recent surgery in most studies (10,11).


Since reactive thrombocytosis rarely causes venous or arterial thrombosis, no specific anti-platelet therapy is indicated in most patients. Treatment of the underlying illness, such as infection, is the key to therapy.

back to top


1. Schafer AI. Thrombocytosis and essential thrombocythemia. In: Williams Hematology. 6th ed. Beutler E, Coller BS, Lichtman MA, et al., eds. New York: McGraw-Hill, 2001, pp. 1541-1549.

2. Alexandrakis A, MG, Passam FH, Perisinakis K, et al. Serum proinflammatory cytokines and its relationship to clinical parameters in lung cancer patients with reactive thrombocytosis. Respir Med 2002;96:553-558. [PubMed]  

3. Araneda M, Krishnan V, Hall K, et al. Reactive and clonal thrombocytosis: proinflammatory and hematopoietic cytokinesand acaute phase proteins. South Med J 2001;94:417-420. [PubMed]  

4. Unsal E, Aksaray S, Koksal D, et al. Potential role of interleukin-6 in reactive thrombocytosis and acute phase response in pulmonary tuberculosis. Postgrad Med J 2005;81:604-607. [PubMed]  

5. Baynes RD, Bothwell TH, Flax H, et al. Reactive thrombocytosis in pulmonary tuberculosis. J Clin Pathol 1987;40:676-679. [PubMed]  

6. Gofrit ON, Shapiro A, Rund D, et al. Thrombocytosis accompanying urinary tract infection suggests obstruction or abscess. Am J Emerg Med 2006;24:118-121. [PubMed]  

7. Tefferi A, Ho TC, Ahmann GJ, et al. Plasma interleukin-6 and C-reactive protein levels in reactive versus clonal thrombocytosis. Am J Med 1994;97:374-378. [PubMed]  

8. Griesshammer M, Bangerter M, Sauer T, et al. Aetiology and clinical significance of thrombocytosis: analysis of 732 patients with an elevated platelet count. J Intern Med 1999;245:295-300. [PubMed]  

9. Valade N, Decailliot F, Rebufat Y, et al. Thrombocytosis after trauma: incidence, aetiology, and clinical significance. Br J Anaesth 2005;94:18-23. [PubMed]  

10. Buss DH, Cashell AW, O’Connor ML, et al. Occurrence, etiology, and clinical significance of extreme thrombocytosis: a study of 280 cases. Am J Med 1994;96:247-53. [PubMed]  

11. Aydogan T, Kanbay M, Alici O, et al. Incidence and etiology of thrombocytosis in an adult Turkish population. Platelets 2006;17:328-331. [PubMed]

12. Seth AK, Gunson BK, Mirza DF, et al. Thrombocytosis in liver transplant recipients: prevalence, natural history, and impact. Liver Transpl 2007;13:1598-1602. [PubMed] 

13. Miguez-Burbano MJ, Burbano X, Rodriguez A, et al. Development of thrombocytosis in HIV+ drug users: impact of antiretroviral therapy. Platelets 2002;13:183-185. [PubMed] 

14. Finsterer J, Kotazilias N. Thrombocytosis under ciprofloxacin and tazobactam/piperacillin. Platelets 2003;14:329-331. [PubMed]

back to top



Table 1:  Etiologies of Thrombocytosis

Primary (clonal) thrombocytosis

Secondary (reactive) thrombocytosis

Myeloproliferative disorders

Ø      Essential thrombocytosis

Ø      Polycythemia vera

Ø      Chronic myelogenous leukemia

Ø      Myeloid metaplasia with myelofibrosis


Ø      Pneumonia/Empyema

Ø      Complicated urinary tract infection

Ø      Soft tissue infection

Ø      Intraabdominal infection


Ø      Musculoskeletal infection

Ø      Tuberculosis


Ø      Gastrointestinal/ Hepatobiliary/Pancreas


Ø      Lung

Ø      Kidney

Ø      Gynecologic

Ø      Sarcoma

Ø      Lymphoma/leukemia


Ø      Splenectomy

Ø      Liver transplantation (12)

Tissue trauma/Necrosis

Ø      Multiple trauma

Ø      Myocardial infarction

Ø      Mesenteric infarction

Ø      Rhabdomyolysis

Acute hemorrhage

Hemolytic anemia

Iron deficiency anemia

Rebound phenomenon after bone marrow suppression


Collagen vascular diseases

Inflammatory bowel disease



Ø      Catecholamine analogues (e.g., epinephrine, norepinephrine)


Ø      Vincristine

Ø      Highly active anti-retroviral therapy (HAART) (13)


Ø      Piperacillin-tazobactam andciprofloxacin in combination (14)

Guided Medline Search For Recent Reviews


Clinical Manifestations




Guided Medline Search For Historical Aspects