Thrombocytosis
Authors: Mark A. Marinella, MD, FACP, FACN, CNSP
INTRODUCTION
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.
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).
TREATMENT
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.
REFERENCES
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Tables
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 |
Infection Ø Pneumonia/Empyema Ø Complicated urinary tract infection
Ø Musculoskeletal infection Ø Tuberculosis Neoplasm Ø Gastrointestinal/ Hepatobiliary/Pancreas
Ø Lung Ø Kidney Ø Gynecologic Ø Sarcoma Ø Lymphoma/leukemia Surgery Ø Liver transplantation (12) Tissue trauma/Necrosis Ø Multiple trauma Ø Mesenteric infarction Ø Rhabdomyolysis Acute hemorrhage Hemolytic anemia Iron deficiency anemia Rebound phenomenon after bone marrow suppression
Collagen vascular diseases Inflammatory bowel disease Exercise Drugs Ø Catecholamine analogues (e.g., epinephrine, norepinephrine)
Ø Vincristine Ø Highly active anti-retroviral therapy (HAART) (13)
Ø Piperacillin-tazobactam andciprofloxacin in combination (14) |