Secondary Thrombocytosis 

Updated: Dec 24, 2018
Author: Koyamangalath Krishnan, MD, FRCP, FACP; Chief Editor: Srikanth Nagalla, MBBS, MS, FACP 

Overview

Background

Platelets are acute-phase reactants; therefore, they increase in response to various stimuli, including systemic infections, inflammatory conditions, bleeding, and tumors.[1, 2, 3] This is called reactive or secondary thrombocytosis, which is a benign form of thrombocytosis. In contrast, clonal thrombocytosis (primary or essential thrombocytosis) is an unregulated abnormality of platelet production due to a clonal expansion of bone marrow progenitor cells.[4, 5]

Pathophysiology

Secondary thrombocytosis (reactive thrombocytosis) may be due to the overproduction of proinflammatory cytokines, such as interleukin (IL)-1, IL-6, and IL-11, that occurs in chronic inflammatory, infective, and malignant states.[6, 7, 8, 9] The presence of elevated IL-1, IL-6, C-reactive protein (CRP), granulocyte colony-stimulating factor (G-CSF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) in individuals with these conditions suggests that these cytokines may be involved in secondary thrombocytosis.

Epidemiology

Secondary thrombocytosis (reactive thrombocytosis) is a relatively common condition. The incidence varies with the underlying condition. The incidence of postsplenectomy secondary thrombocytosis is approximately 75-82%.[10]

Overall, secondary thrombocytosis occurs in 3-13% of hospitalized children. However, in a Greek study of children 10 days to 8 years old who were hospitalized with viral pneumonia,[9] and an Italian study of children 1 to 24 months old who were hospitalized for community-acquired infections,[11] approximately half had thrombocytosis.

Secondary thrombocytosis is more common than primary thrombocytosis. In a series from a large US university hospital that included 280 patients with extreme thrombocytosis (platelet count of 1,000 x 109/L or greater), 82% had secondary thrombocytosis.[12]

Race-, Sex-, and Age-related Demographics

No race predilection exists for secondary thrombocytosis (reactive thrombocytosis). No sex predilection exists for secondary thrombocytosis, except that iron deficiency is more prevalent in females during childbearing years. No age predilection exists for secondary thrombocytosis.[11, 13]

 

Presentation

History

No unique symptoms are suggestive of secondary thrombocytosis (reactive thrombocytosis). Most patients are asymptomatic and are identified on routine blood counts. Patients may have symptoms that are referable to the primary condition that may have precipitated the thrombocytosis.

Physical

No distinguishing features of secondary thrombocytosis (reactive thrombocytosis) are found on physical examination. Physical findings reflect the underlying condition. In patients who have postsplenectomy thrombocytosis, evidence of a previous splenectomy should be eapparent on physical examination.[10]

Causes

Etiologic conditions associated with secondary thrombocytosis (reactive thrombocytosis) include the following:

  • Infection and inflammatory disorders

  • Postsplenectomy or hyposplenism

  • Malignancy

  • Trauma

  • Chronic inflammatory conditions

  • Hemorrhage, blood loss, or both

  • Iron-deficiency anemia

  • Rebound thrombocytosis

  • Asplenia (anatomic or functional)[14]

  • Electric shock[15]

  • Idiopathic

 

DDx

Diagnostic Considerations

Other problems to be considered include the following:

  • Myeloproliferative Disease

  • Polycythemia

  • Pediatric Thrombocytosis

  • Idiopathic myelofibrosis

  • Idiopathic sideroblastic anemia

  • Pseudothrombocytosis

  • Chronic lymphocytic leukemia (CLL)

  • Thrombotic thrombocytopenic purpura (TTP)

  • Hemoglobin H (HbH) disease

  • Microspherocytes

Differential Diagnoses

 

Workup

Laboratory Studies

The laboratory workup in cases of secondary thrombocytosis (reactive thrombocytosis) includes the following:

  • Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP)

  • Cytogenetic analysis

  • Leukocyte alkaline phosphatase, vitamin B-12

  • Antinuclear antibody (ANA), rheumatoid factor (RF)

  • Iron studies (serum iron, total iron-binding capacity [TIBC], serum ferritin)

  • Peripheral blood smear review

If the clinical presentation does not clearly differentiate between primary (clonal) and secondary thrombocytosis, further tests may be indicated to exclude or confirm a diagnosis of disorders that cause clonal thrombocytosis, as follows:

  • Bone marrow aspiration and biopsy

  • Cytogenetic studies: The presence of the Philadelphia chromosome (Ph) found in chronic myelogenous leukemia (CML) may also be identified using reverse transcriptase-polymerase chain reaction (RT-PCR) to identify the bcr-abl fusion transcript or by using Southern blot analysis for identification of bcr-abl genomic rearrangements.

Essential thrombocythemia is a diagnosis of exclusion that is based on the following numeric criteria (adapted from Hoffman R. Primary thrombocythemia. In: Hoffman R, Benz EJ Jr, Shattil SJ, et al, eds. Hematology: Basic Principles and Practice. 3rd ed. Philadelphia, Pa: Churchill Livingstone; 2000:1188-204).[4] Patients who meet criteria 1-5 and more than three of criteria 6-11 are considered to have essential thrombocytosis.

  1. Platelet count greater than 600,000/mm3 on two occasions, separated by a 1-month interval

  2. Absence of an identifiable cause of secondary thrombocytosis

  3. Normal red blood cell mass

  4. Absence of significant bone marrow fibrosis (ie, less than one third of the bone marrow)

  5. Absence of the Philadelphia chromosome (Ph) by karyotyping or absence of the bcr-abl fusion product

  6. Splenomegaly by physical examination or ultrasonography

  7. Bone marrow hypercellularity with megakaryocyte hyperplasia

  8. Presence of abnormal bone marrow hematopoietic progenitor cells as determined by the growth of endogenous erythroid cells and/or megakaryocyte colonies with increased sensitivity to interleukin-3 (IL-3)

  9. Normal levels of CRP and IL-6

  10. Absence of iron deficiency anemia, as documented by either a normal bone marrow–stainable iron or normal serum ferritin level

  11. In females, demonstration of clonal hematopoiesis by restriction fragment length polymorphism (RFLP) analysis of genes present on the X chromosome

Imaging Studies

Perform an ultrasound of the abdomen if the presence of splenomegaly is uncertain.

 

Treatment

Medical Care

The primary treatment of secondary thrombocytosis (reactive thrombocytosis) should address the underlying cause of the thrombocytosis. For example, iron supplementation may normalize platelet counts in patients with thrombocytosis secondary to inflammatory bowel disease.[16] In general, no treatment is indicated to directly reduce the platelet count.[17]

For patients with platelet counts in excess of 1,000,000/μL, aspirin 65 mg daily may be considered to minimize the rare development of stroke or thrombosis.[18]  A case report describes effective use of plateletpheresis for treatment of an internal carotid artery thrombus resulting in a right middle cerebral artery stroke, in a patient with previously undiagnosed reactive thrombocytosis (platelet count of 1,014,000/μL) secondary to iron deficiency anemia.[19]

 

Medication

Medication Summary

The goals of pharmacotherapy are to reduce morbidity and to prevent complications in cases of secondary thrombocytosis (reactive thrombocytosis).

Antiplatelet Agents

Class Summary

Antiplatelet agents inhibit platelet function by inhibition of the platelet cyclooxygenase system.

Aspirin (Anacin, Ascriptin, Bayer Aspirin)

Irreversibly acetylates (and inactivates) platelet and endothelial cell cyclooxygenase. A lower dose (65 mg) preferentially inhibits the platelet cyclooxygenase system (responsible for thromboxane A2 production) while preserving the beneficial effects of endothelial cell prostacyclin production due to difference in sensitivity to the inhibition by aspirin of cyclooxygenases at different sites and due to turnover of the endothelial cell cyclooxygenases.

 

Follow-up

Further Outpatient Care

In patients with secondary thrombocytosis (reactive thrombocytosis) for whom the causal comorbid condition has not been identified, maintain complete careful outpatient monitoring with physical examination and routine laboratory tests to exclude the development of an occult disorder (eg, malignancy).

Prognosis

In general, secondary thrombocytosis (reactive thrombocytosis) is a temporary laboratory anomaly that resolves when the primary causative condition is addressed.

The overall prognosis in patients with secondary thrombocytosis reflects that of the underlying associated condition. With certain disorders, however (eg, chronic obstructive pulmonary disease [COPD],[20] ovarian cancer[21] ), the presence of thrombocytosis indicates a worse prognosis than for patients with the disorder who do not have thrombocytosis. For example, Harrison et al reported that thrombocytosis was an independent risk factor for increased 1-year mortality after COPD exacerbations; however, patients with thrombocytosis who received antiplatelet therapy had significantly lower 1-year mortality.[20]

 

Questions & Answers