Essential Thrombocytosis Workup

  • Author: Asheesh Lal, MBBS, MD; Chief Editor: Emmanuel C Besa, MD   more...
 
Updated: Jan 10, 2012
 

Laboratory Studies

  • Complete blood cell (CBC) count
    • This panel is essential for the diagnosis of essential thrombocytosis (primary thrombocythemia).
    • The hallmark of essential thrombocytosis (primary thrombocythemia) is a sustained, unexplained thrombocytosis.
    • Leukocytosis, erythrocytosis, and mild anemia may be found.
    • The peripheral blood may show occasional immature precursor cells (eg, myelocytes, metamyelocytes). Large platelets (thrombocytes) are typically identifiable on routine peripheral blood smear.
    • Mild basophilia and eosinophilia may be found.
  • JAK2 V617F mutation: Present in 50% of patients with essential thrombocytosis (primary thrombocythemia).[18] V617F -positive patients displayed multiple features resembling polycythemia vera, with significantly higher hemoglobin levels, neutrophil counts, bone marrow erythropoiesis and granulopoiesis, more venous thromboses and a higher incidence of polycythemic transformation.
    • Teofili et al noted that specific JAK2 mutations activate the JAK-STAT pathway in polycythemia vera and essential thrombocytosis (primary thrombocythemia), with the presence of biologic markers such as endogenous erythroid colony (EECs) growth or PRV-1 RNA overexpression.[19] Because these finding are also found in JAK2 wild type patients, the authors hypothesized that a deregulation of the suppressor of cytokine signaling (SOCS) protein system in these cases could produce the activation of the JAK-STAT pathway.
    • Teofili et al evaluated 81 patients with polycythemia vera and essential thrombocytosis (primary thrombocythemia) (53 adults and 28 children) for the methylation status of the SOCS-1, SOCS-2 and SOCS-3 CpG islands and for several myeloproliferative markers (including JAK2 and MPL mutations and clonality of hematopoiesis). The authors identified SOCS-1 or SOCS-3 hypermethylation in 23 patients, which was associated with a significant decrease of SOCS-1 or SOCS-3 RNA and protein levels, and demonstrated that the gene expression was restored by exposing cells to the demethylating agent 2-deoxyazacytidin.[19] The investigators concluded that "SOCS-1 or SOCS-3 hypermethylation can activate the JAK-STAT signaling pathway in alternative or together with JAK2 mutations," which may "represent a potential therapeutic target."[19]
    • Ohyashiki et al studied JAK2 mutational status with cytogenetic analysis in 54 patients with essential thrombocythemia (primary thrombocythemia) to obtain evaluate the correlation between clinicohematologic features and genetic abnormalities.[20, 21] These investigators found that recurrent der(9;18) in essential thrombocythemia (primary thrombocythemia) with JAK2 V617F is highly linked to myelofibrosis development.
    • Of 6 patients with essential thrombocytosis (primary thrombocythemia) who developed myelofibrosis, 4 had JAK2 V617F mutation. In addition, 3 of 4 patients with JAK2 V617F had add(18)(p11). However, the remaining 2 patients with essential thrombocytosis (primary thrombocythemia) who developed myelofibrosis did not have JAK2 V617F or add(18)(p11), and none of the patients with essential thrombocytosis (primary thrombocythemia) and JAK2 V617F and chromosome changes other than add(18)(p11) developed myelofibrosis. The authors concluded that "add(18)(p11), possibly due to der(9;18), may contribute a link to myelofibrosis in" JAK2 V617F -positivity in patients with essential thrombosis (primary thrombocythemia), whereas "those with wild-type JAK2 may use another pathway toward myelofibrosis."[20]
  • Bone marrow
    • Approximately 90% of patients with show an increase in bone marrow cellularity.
    • Megakaryocytic hyperplasia is common.
    • Giant megakaryocytes are often observed. Clusters of megakaryocytes may be present; significant dysplasia of the megakaryocytes is unusual.
    • Hyperplasia of granulocyte and reticulocyte precursors is common.
    • Bone marrow reticulin is usually increased,[22] but collagen fibrosis is uncommon.
    • Iron stores may be absent in the bone marrow. This may be due to gastrointestinal tract bleeding or menorrhagia. However, inessential thrombocytosis (primary thrombocythemia), as in other myeloproliferative disorders, bone marrow iron stain results may be negative even when other studies do not support the presence of iron deficiency.
  • Platelet aggregation studies
    • The results of the prothrombin time (PT) and activated partial thromboplastin time (aPTT) studies are usually within reference ranges. The bleeding time may or may not be prolonged.
    • Platelet aggregation study findings are abnormal and show impaired platelet aggregation to epinephrine, adenosine diphosphate, and collagen but not to ristocetin and arachidonic acid.
    • Some patients may present with spontaneous platelet aggregation.
  • Chemistries
    • Chemistry studies reveal elevated uric acid (UA) levels in 25% of patients at diagnosis.
    • Pseudohyperkalemia may occur, and falsely elevated phosphorus (P) and acid phosphatase levels may be noted.
    • Pseudohypoxemia may develop from extreme thrombocytosis.
    • Vitamin B-12 levels are increased in 25% of patients with essential thrombocytosis (primary thrombocythemia).
  • Cytogenetic study results are usually normal. Molecular studies (eg, polymerase chain reaction [PCR], Southern [genomic] blotting) may be used as sensitive means of excluding chronic myelogenous leukemia.
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Imaging Studies

Computed tomography (CT) scanning or ultrasonography of the spleen may reveal splenomegaly in patients with essential thrombocytosis (primary thrombocythemia) even when this condition is not physically detectable.

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Other Tests

  • Elevation of C-reactive protein (CRP), fibrinogen, and IL-6 levels suggests the presence of secondary thrombocytosis, because these are acute-phase reactants.
  • Conduct a red blood cell (RBC) mass study to exclude polycythemia vera. In essential thrombocytosis (primary thrombocythemia), the RBC mass is without abnormality.
  • Conduct a sensitivity test to IL-3, which shows an increase in the formation of endogenous erythroid and/or megakaryocytic colonies and indicates the presence of abnormal hematopoietic progenitor cells (primarily a research tool).
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Procedures

  • Bone marrow aspirate and biopsy
    • A bone marrow aspirate and biopsy are useful. Use specialized needles to obtain the aspirate and biopsy material over the posterior iliac crest.
    • Obtaining an aspirate over the sternum may also be helpful, although most physicians prefer the posterior iliac crest.
    • Do not attempt to obtain a biopsy from the sternum.
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Histologic Findings

Approximately 90% of patients with essential thrombocytosis (primary thrombocythemia) show an increase in bone marrow cellularity. Megakaryocytic hyperplasia is present. Giant megakaryocytes are frequently observed, and clusters of megakaryocytes may be present. Significant dysplasia of the megakaryocytes is unusual. Hyperplasia of granulocyte and reticulocyte precursors is common. Bone marrow reticulin is usually increased, but collagen fibrosis is uncommon.

In essential thrombocytosis (primary thrombocythemia), as in other myeloproliferative disorders, bone marrow iron stain results may be negative when other studies do not support the presence of iron deficiency. For practical purposes, a ferritin level that is within the reference range or increased, along with an RBC mean corpuscular volume (MCV) that is within the reference range, is sufficient to exclude reactive thrombocytosis secondary to iron deficiency and the possibility of polycythemia vera masked by iron deficiency.

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Contributor Information and Disclosures
Author

Asheesh Lal, MBBS, MD  Physician, Department of Internal Medicine, Lexington Medical Center

Asheesh Lal, MBBS, MD is a member of the following medical societies: American Society of Clinical Oncology and American Society of Hematology

Disclosure: Nothing to disclose.

Specialty Editor Board

Wadie F Bahou, MD  Chief, Division of Hematology, Hematology/Oncology Fellowship Director, Professor, Department of Internal Medicine, State University of New York at Stony Brook

Wadie F Bahou, MD is a member of the following medical societies: American Society of Hematology

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Marcel E Conrad, MD  Distinguished Professor of Medicine (Retired), University of South Alabama College of Medicine

Marcel E Conrad, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for the Advancement of Science, American Association of Blood Banks, American Chemical Society, American College of Physicians, American Physiological Society, American Society for Clinical Investigation, American Society of Hematology, Association of American Physicians, Association of Military Surgeons of the US, International Society of Hematology, Society for Experimental Biology and Medicine, and Southwest Oncology Group

Disclosure: No financial interests None None

Rajalaxmi McKenna, MD, FACP  Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems

Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis

Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD  Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Clinical Oncology, American Society of Hematology, and New York Academy of Sciences

Disclosure: Nothing to disclose.

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Peripheral blood smear in essential thrombocytosis showing increased platelet numbers. Courtesy Wei Wang, MD, and John Lazarchick, MD; Department of Pathology, Medical University of South Carolina.
Bone marrow biopsy in essential thrombocytosis showing increased megakaryocytes. Courtesy Wei Wang, MD, and John Lazarchick, MD; Department of Pathology, Medical University of South Carolina.
 
 
 
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