Advertisement

Blood Thrombopoietin Levels in Clonal Thrombocytosis and Reactive Thrombocytosis

      Abstract

      Background: Although the distinction between clonal and reactive thrombocytosis is clinically relevant because clonal thrombocytosis has more thrombohemorragic complications, the differential diagnosis of these two entities can be difficult. Methods such as the detection of unstimulated erythroid or megakaryocyte colony growth are not readily available. Therefore, we measured blood thrombopoietin levels to determine whether these levels can be used to distinguish the two conditions.
      Patients and Methods: Thrombopoietin levels were measured in 73 patients with thrombocytosis (platelet count >500,000/μL), including 39 patients with clonal thrombocytosis (20 patients with essential thrombocythemia, 15 with agnogenic myeloid metaplasia, 1 patient with polycythemia vera, and 3 with undefined myeloproliferative disorders) and 34 patients with reactive thrombocytosis (17 with malignant tumors, 11 with inflammatory diseases, 4 with sickle cell disease, and 2 with iron deficiency anemia). Seventeen normal volunteers were used as controls.
      Results: Thrombopoietin levels were significantly higher (P <0.05) in patients with clonal thrombocytosis (mean ± SD of 555 ± 585 pg/mL), including the subgroup with essential thrombocythemia (505 ± 459 pg/mL), than in patients with reactive thrombocytosis (290 ± 133 pg/mL) who had similar levels as controls (201 ± 112 pg/mL). Thrombopoietin levels in patients with clonal thrombocytosis, including essential thrombocythemia, were not correlated with platelet counts.
      Conclusions: Thrombopoietin levels may be helpful in distinguishing between clonal thrombocytosis and reactive thrombocytosis. Thrombopoietin is probably responsible for the elevated platelet counts in clonal thrombocytosis including essential thrombocythemia, but not in reactive thrombocytosis. High thrombopoietin levels in patients with clonal thrombocytosis cannot be explained solely by platelet megakaryocyte mass.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to The American Journal of Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Morowitz D.A
        • Allen L.W
        • Kirsner J.B
        Thrombocytosis in chronic inflammatory bowel disease.
        Ann Intern Med. 1968; 18: 1013-1021
        • Frenkel E.P
        Southwestern Internal Medicine Conference.
        Am J Med Sci. 1991; 301: 69-80
        • Levin J
        • Conley C.L
        Thrombocytosis associated with malignancy.
        Arch Intern Med. 1964; 114: 497-500
        • Colombi M
        • Radaelli F
        • Zocchi L
        • Maiolo A.T
        Thrombotic and hemorrhagic complications in essential thrombocythemia.
        Cancer. 1991; 67: 2926-2930
        • Cortelazzo S
        • Viero P
        • Finazzi G
        • et al.
        Incidence and risk factors for thrombotic complications in a historical cohort of 100 patients with essential thrombocythemia.
        J Clin Oncol. 1990; 3: 556-562
        • Burkhardt R
        • Bartl R
        • Jager K
        • et al.
        Working classification of chronic myeloproliferative disorders based on histological haematological, and clinical findings.
        J Clin Pathol. 1986; 39: 237-252
        • Kopf I
        • Swolin B
        • Weinfeld A
        Cytogenetic studies on primary thrombocythaemia.
        Hereditas. 1982; 97: 217-220
        • Schafer A.I
        Bleeding and thrombosis in the myeloproliferative disorders.
        Blood. 1984; 64: 1-12
        • Dudley J.M
        • Messinezy M
        • Eridani S
        • et al.
        Primary thrombocythaemia.
        Br J Haematol. 1989; 71: 331-335
        • Fenaux P
        • Simon M
        • Caulier M.T
        • et al.
        Clinical course of essential thrombocythemia in 147 cases.
        Cancer. 1990; 66: 549-556
        • Chistolini A
        • Mazzucconi M.G
        • Ferrari A
        • et al.
        Essential thrombocythemia.
        Haematologica. 1990; 75: 537-540
        • deSauvage F.J
        • Hass P.E
        • Spencer S.D
        • et al.
        Stimulation of megakaryocytopoiesis and thrombopoiesis by the c-mpl ligand.
        Nature. 1994; 369: 533-538
        • Kuter D.J
        • Beeler D.L
        • Rosenburg R.D
        The purification of megapoietin.
        Proc Natl Acad Sci USA. 1994; 91: 11104-11108
        • Bartley T.D
        • Bogenerger J
        • Hunt P
        • et al.
        Identification and cloning of a megakaryocyte growth and develop-ment factor that is a ligand for the cytokine receptor mpl.
        Cell. 1994; 77: 1117-1124
        • Lok S
        • Kaushansky K
        • Holly R.D
        • et al.
        Cloning and expression of murine thrombopoietin cDNA and /timulation of platelet production in vivo.
        Nature. 1994; 369: 565-568
        • Kaushansky K
        • Lok S
        • Holly R.D
        • et al.
        Promotion of megakaryocyte progenitor expansion and differentiation by the c-Mpl Ligand thrombopoietin.
        Nature. 1994; 369: 568-571
        • Wendling F
        • Maraskovsky E
        • Debili N
        • et al.
        cMpl Ligand is a humoral regulator of megakaryocytopoiesis.
        Nature. 1994; 369: 571-578
        • Tefferi A
        • Silverstein M.N
        • Hoagland H.C
        Primary thrombocythemia.
        Semin Oncol. 1995; 22: 334-340
        • Wang J.C
        • Chen C
        • Lou L.-H
        • Mora M
        Blood thrombopoietin, IL-6, IL-11 levels in patients with agnogenic myeloid metaplasia.
        Leukemia. 1997; 11: 1827-1832
        • Nichol J.L
        Serum levels of thrombopoietin in health and disease.
        in: Kuter D.J Hunt P Sheridan W Zucker-Franklin D Thrombopoiesis and Thrombopoietins. Human Press, Totowa, New Jersey1997: 359-375
        • Choe E.I
        • Kasabian A.K
        • Kolker A.R
        • et al.
        Thrombocytosis after major lower extremity trauma.
        Ann Plastic Surg. 1996; 36: 489-494
        • Chang M
        • Yu S
        • Meng G
        • et al.
        Differential mechanisms in the regulation of endogenous levels of thrombopoietin and Interleukin-11 during thrombocytopenia.
        Blood. 1996; 88: 3354-3362
        • Kosugi S
        • Kirata Y
        • Tomiyama Y
        • et al.
        Circulating thrombopoietin level in chronic immune thrombocytopenic purpura.
        Br J Haematol. 1996; 93: 704-706
        • Kuter D.J
        • Rosenberg R.D
        The reciprocal relationship of thrombopoietin (c-MPL ligand) to changes in the platelet mass during busulfan-induced thrombocytopenia in the rabbit.
        Blood. 1995; 85: 2720-2730
        • McCarty J.M
        • Sprugel K.H
        • Fox N.E
        • et al.
        Murine thrombopoietin mRNA levels are modulated by platelet count.
        Blood. 1995; 86: 3668-3675
        • Alexander W.S
        • Roberts A.W
        • Nicola N.A
        • et al.
        Deficiencies in progenitor cells of multiple hematopoietic lineages and defective megakaryocytopoiesis in mice lacking the thrombopoietin receptor c-Mpl.
        Blood. 1996; 87: 2162-2170
        • Cohen-Solal K
        • Villeval J.-L
        • Titeux M
        • et al.
        Constitutive expression of Mpl ligand transcripts during thrombocytopenia or thrombocytosis.
        Blood. 1996; 88: 2578-2584
        • Stoffel R
        • Wiestner S
        • Skoda R.C
        Thrombopoietin in thrombocytopenic mice.
        Blood. 1996; 87: 567-573
      1. Li J, Xia Y, Kuter DJ. Analysis of the thrombopoietin receptor (MPL) on platelets from normal and essential thrombocythemia (ET) patients. Blood 1996;88:545a. Abstract.

      2. Best D, Hornkohl A, Selesi D, et al. Evaluation of biological activity, molecular weight and circulating levels of TO in plasma from normal donors and patients with abnormal platelet numbers. Exp Hematol 1996;24:1069. Abstract.

        • Hollen C.W
        • Henthorn J
        • Koziol J.A
        • Burnstein S.A
        Elevated serum interleukin-6 levels in patients with reactive thrombocytosis.
        Br J Haematol. 1991; 79: 286-290
        • Hollen C.W
        • Henthorn J
        • Koziol J.A
        • Burnstein S.A
        Serum interleukin-6 levels in patients with thrombocytosis.
        Leukem Lymphoma. 1992; 8: 235-241
        • Gastl G
        • Plante M
        • Finstad C.L
        • et al.
        High IL-6 levels in ascitic fluid correlate with reactive thrombocytosis in patients with epithelial ovarian cancer.
        Br J Haematol. 1993; 83: 433-441
        • Tefferi A
        • Ho T.C
        • Ahmann G.J
        • et al.
        Plasma interleukin-6 and C-Reactive protein levels in reactive versus clonal thrombocytosis.
        Am J Med. 1994; 97: 374