AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Platelets are acute-phase reactants; therefore, they increase in response to various stimuli, including systemic infections, inflammatory conditions, bleeding, and tumors. This is called reactive or secondary thrombocytosis, which is a benign form of thrombocytosis. Clonal thrombocytosis is an unregulated abnormality of platelet production due to a clonal expansion of bone marrow progenitor cells.

Pathophysiology

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

Frequency

United States

Secondary thrombocytosis is a relatively common condition. In a series from a large university hospital that included 280 patients with extreme thrombocytosis, 82% had reactive thrombocytosis. Secondary thrombocytosis is more common than clonal thrombocytosis.

International

Secondary thrombocytosis is common in other countries.

Mortality/Morbidity

Reactive thrombocytosis is generally considered a benign condition. Extremely high platelet elevations may require treatment as a means of minimizing unusual vascular complications.

Race

No race predilection exists.

Sex

No sex predilection exists, except that iron deficiency is more prevalent in females during childbearing years.

Age

No age predilection exists.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

No unique symptoms are suggestive of reactive thrombocytosis.

• Most patients are asymptomatic and are identified on routine blood counts.
• Patients may have symptoms referable to the primary condition that may have precipitated the reactive thrombocytosis.

Physical

No distinguishing features of reactive thrombocytosis are found on physical examination.

• Physical findings reflect the underlying condition.
• In patients who have postsplenectomy thrombocytosis, evidence for prior splenectomy should be evident on physical examination.

Causes

• Etiologic conditions associated with reactive thrombocytosis
• • 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)
  • Idiopathic

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

5q Syndrome
Essential thrombocythemia
Idiopathic myelofibrosis
Idiopathic sideroblastic anemia
Pseudothrombocytosis (chronic lymphocytic leukemia [CLL], thrombotic thrombocytopenic purpura [TTP], hemoglobin H [HbH] disease, microspherocyte)

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Erythrocyte sedimentation rate (ESR), C-reactive protein
• Cytogenetic analysis
• Leukocyte alkaline phosphatase, vitamin B-12
• Antinuclear antibody (ANA), rheumatoid factor
• Iron studies (serum iron, total iron-binding capacity [TIBC], serum ferritin)
• Peripheral blood smear review
• If the clinical presentation does not clearly differentiate reactive and clonal thrombocytosis, further tests may be indicated to exclude or confirm a diagnosis of disorders that cause clonal thrombocytosis.
• • Bone marrow aspiration and biopsy
  • Cytogenetic studies: The presence of the Philadelphia chromosome found in chronic myelogenous leukemia also may be identified using reverse transcriptase-polymerase chain reaction to identify the bcr-abl fusion transcript or 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 "primary thrombocythemia" in Hematology: Basic Principles and Practice, Third Edition. Patients who meet criteria 1-5 and more than 3 of criteria 6-11 are considered to have essential thrombocytosis.
  1. Platelet count greater than 600,000/mm³ on 2 occasions separated by a 1-month interval
  2. Absence of identifiable cause of reactive thrombocytosis
  3. Normal red blood cell mass
  4. Absence of significant marrow fibrosis (ie, less than a third of marrow)
  5. Absence of the Philadelphia chromosome 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 marrow hematopoietic progenitor cells as determined by the growth of endogenous erythroid cells and/or megakaryocyte colonies with increased sensitivity to IL-3
  9. Normal levels of C-reactive protein and IL-6
  10. Absence of iron deficiency anemia documented by either a normal marrow-stainable iron or normal serum ferritin level
  11. In females, demonstration of clonal hematopoiesis by restriction fragment length polymorphism analysis of genes present on the X chromosome

Imaging Studies

• Perform an ultrasound of the abdomen if existence of splenomegaly is uncertain.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

• The primary treatment should address the underlying cause of the thrombocytosis. In general, no treatment is indicated to directly reduce the platelet count.
• For patients with platelet counts in excess of 1,000,000 per µL, aspirin 65 mg daily may be considered to minimize the rare development of stroke or thrombosis.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Drug Category: Antiplatelet agents

Inhibit platelet function by inhibition of the platelet cyclooxygenase system.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Outpatient Care

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

Prognosis

• In general, reactive thrombocytosis is a temporary laboratory anomaly that resolves when the primary causative condition is addressed.
• The overall prognosis reflects that of the underlying associated condition.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• If no reason is identified for the thrombocytosis, patients require regular follow-up examinations to monitor platelet counts. The potential for occult malignant diseases in the appropriate clinical setting warrants attentive follow-up care. If platelet counts continue to rise with no obvious explanation, suspect clonal thrombocytosis and consider platelet-reductive therapy.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Araneda M, Krishnan V, Hall K, et al. Reactive and clonal thrombocytosis: proinflammatory and hematopoietic cytokines and acute phase proteins. South Med J. Apr 2001;94(4):417-20. [Medline].
• Birdane A, Haznedaroglu IC, Bavbek N, et al. The plasma levels of prostanoids and plasminogen activator inhibitor-1 in primary and secondary thrombocytosis. Clin Appl Thromb Hemost. Apr 2005;11(2):197-201. [Medline].
• Chanet V, Tournilhac O, Dieu-Bellamy V, et al. Isolated spleen agenesis: a rare cause of thrombocytosis mimicking essential thrombocythemia. Haematologica. Nov 2000;85(11):1211-3. [Medline].
• Dame C, Sutor AH. Primary and secondary thrombocytosis in childhood. Br J Haematol. Apr 2005;129(2):165-77. [Medline].
• Frye JL, Thompson DF. Drug-induced thrombocytosis. J Clin Pharm Ther. Feb 1993;18(1):45-8. [Medline].
• Hoffman R. Primary thrombocythemia. In: Hoffman R, Benz Jr EJ, Furie B, Cohen HJ,Silberstein LE, McGlave P, eds. Hematology: Basic Principles and Practice. 3rd ed. Philadelphia, Pa:. Churchill Livingstone;2000:1188-204.
• Kutti J, Wadenvik H. Diagnostic and differential criteria of essential thrombocythemia and reactive thrombocytosis. Leuk Lymphoma. Sep 1996;22 Suppl 1:41-5. [Medline].
• Messinezy M, Westwood N, Sawyer B, et al. Primary thrombocythaemia: a composite approach to diagnosis. Clin Lab Haematol. Jun 1994;16(2):139-48. [Medline].
• Pearson TC. Diagnosis and classification of erythrocytoses and thrombocytoses. Baillieres Clin Haematol. Dec 1998;11(4):695-720. [Medline].
• Tefferi A, Ho TC, Ahmann GJ, et al. Plasma interleukin-6 and C-reactive protein levels in reactive versus clonal thrombocytosis. Am J Med. Oct 1994;97(4):374-8. [Medline].
• Vora AJ, Lilleyman JS. Secondary thrombocytosis. Arch Dis Child. Jan 1993;68(1):88-90. [Medline].

Article Last Updated: Dec 19, 2006