Download PDF
Thromb Haemost 1997; 77(02): 289-293
DOI: 10.1055/s-0038-1655955
Original Article
Schattauer GmbH Stuttgart

Plasma Macrophage Colony-Stimulating Factor and P-Selectin Levels in Malaria-Associated Thrombocytopenia

S H Lee
1   The Division of Haematology, National University Hospital, Singapore
,
S Looareesuwan
2   Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University Bangkok, Thailand
,
J Chan
1   The Division of Haematology, National University Hospital, Singapore
,
P Wilairatana
2   Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University Bangkok, Thailand
,
S Vanijanonta
2   Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University Bangkok, Thailand
,
S M Chong
3   Department of Pathology, National University Hospital, Singapore
,
B H Chong
4   Department of Haematology, Prince of Wales Hospital, Sydney, Australia
› Author Affiliations
Further Information

Publication History

Received 17 June 1996

Accepted after revision 08 October 1996

Publication Date:
10 July 2018 (online)

  PDF Download  Permissions and Reprints

Summary

Thrombocytopenia is a common finding in malaria. In clinical trials, recombinant macrophage colony-stimulating factor (M-CSF) causes a reversible, dose-dependent thrombocytopenia, and high M-CSF has been reported in autoimmune thrombocytopenias. P-selectin, which is secreted into the plasma following platelet/endothelial activation or damage, is elevated in certain consumptive thrombocytopenic disorders. The relationships between thrombocytopenia, M-CSF and P-selectin were analysed in 63 patients with severe (n = 13) or uncomplicated (n = 26) P. falciparum (PF) or P. vivax (PV) malaria (n = 24). On admission, 69% of PF patients and 75% of PV patients were thrombocytopenic (platelets < 150 X 109/1). M-CSF was elevated in PF (3021 ± 1844 pg/ml) and PV (2602 ± 1668 pg/ml) patients, compared to controls (589 ± 200 pg/ml). The platelet count was inversely correlated with M-CSF in PF (r = -0.681), and in PV malaria (r = -0.548). Elevated P-selectin was found in severe PF malaria, but not in PV malaria. Severe PF malaria was associated with marked thrombocytopenia, very high M-CSF, elevated P-selectin and compelling evidence of disseminated intravascular coagulopathy (DIC). Platelet counts, M-CSF and P-selectin returned to control values in 7-14 days. These data suggest that elevated M-CSF in malaria, by enhancing macrophage activity, may result in increased macrophage-mediated platelet destruction. Further, platelet/endothelial activation or damage, as measured by P-selectin, or DIC could intensify thrombocytopenia in severe PF malaria, but does not appear to contribute to thrombocytopenia in uncomplicated PF or PV malaria.

 

  • References

  • 1 Horstmann RD, Dietrich M, Bienzle U, Rasche H. Malaria-induced thrombocytopenia. Blut 1981; 42: 157-164
    CrossrefPubMedGoogle Scholar
  • 2 World Health Organization. Severe and complicated malaria. Warrell DA, Molyneux ME, Beales PF. (eds). Trans Roy Soc Trop Med Hyg 1990; 84 (Suppl. 02) 01-65
    PubMedGoogle Scholar
  • 3 Skudowitz RB, Katz J, Lurie A, Levin J, Metz J. Mechanisms of thrombocytopenia in malignant tertian malaria. Brit Med J 1973; 02: 515-517
    CrossrefPubMedGoogle Scholar
  • 4 Srichaikul T, Panikbutr N, Jeumtrakul P. Bone marrow changes in human malaria. Ann Trop Med Parasitol 1967; 61: 40-51
    CrossrefPubMedGoogle Scholar
  • 5 Knuttgen HJ. The bone marrow of non-immune Europeans in acute malaria infection: a topical review. Ann Trop Med Parasitol 1987; 81: 567-576
    CrossrefPubMedGoogle Scholar
  • 6 Kelton JG, Keystone J, Moore J, Denomme G, Tozman E, Glynn M, Neame PB, Gauldie J, Jensen J. Immune-mediated thrombocytopenia of malaria. J Clin Invest 1983; 71: 832-836
    CrossrefPubMedGoogle Scholar
  • 7 Stanley ER, Guilbert LJ, Tushinski RJ, Bartelmez SH. CSF-1 – a mononuclear phagocyte lineage-specific hemopoietic growth factor. J Cell Biochem 1983; 21: 151-159
    CrossrefPubMedGoogle Scholar
  • 8 Nemunaitis J, Meyers JD, Buckner CD, Shannon-Dorcy K, Mori M, Shulman H, Bianco JA, Higano CS, Groves E, Storb R, Hansen J, Appelbaum FR, Singer JW. Phase I trial of recombinant human macrophage colony-stimulating factor in patients with invasive fungal infections. Blood 1991; 78: 907-913
    PubMedGoogle Scholar
  • 9 Yong K, Salooja N, Donahue RE, Hegde U, Linch DC. Human macrophage colony-stimulating factor levels are elevated in pregnancy and in immune thrombocytopenia. Blood 1992; 80: 2987-3902
    PubMedGoogle Scholar
  • 10 Ziegler ZR, Rosenfeld CS, Nemunaitis JJ, Besa EC, Shadduck RK. Increased macrophage colony-stimulating factor levels in immune thrombocytopenic purpura. Blood 1993; 81: 1251-1254
    PubMedGoogle Scholar
  • 11 Shulman NR, Weinrach RS, Libre EP, Andrews HL, Shannon JA. The role of the reticuloendothelial system in the pathogenesis of idiopathic thrombocytopenic purpura. Trans Assoc Am Physicians 1965; 78: 374-390
    PubMedGoogle Scholar
  • 12 McMillan R, Longmire RL, Tavassoli M, Armstrong S, Yelenovsky R. In vitro platelet phagocytosis by splenic phagocytes in idiopathic thrombocytopenic purpura. New Engl J Med 1974; 290: 249-251
    CrossrefPubMedGoogle Scholar
  • 13 Taliaferro W, Mulligan HW. The histopathology of malaria with special reference to the function and origin of the macrophages in defence. Ind Med Res Mem 29, supplement of the Ind J Med Res 1937: 1-139
    PubMedGoogle Scholar
  • 14 George JN, Shattil SJ. The clinical importance of acquired abnormalities of platelet function. New Engl J Med 1991; 324: 27-39
    CrossrefPubMedGoogle Scholar
  • 15 Larsen E, Celi A, Gilbert GE, Furie BC, Erban JK, Bonfanti R, Wagner DD, Furie B. PADGEM protein: A receptor that mediates the interaction of activated platelets with neutrophils and monocytes. Cell 1989; 59: 305-312
    CrossrefPubMedGoogle Scholar
  • 16 McEver RP. Leukocyte interactions mediated by selectins. Thromb Haemost 1991; 66: 80-87
    Article in Thieme ConnectPubMedGoogle Scholar
  • 17 Dunlop LC, Skinner MP, Bendall LJ, Favoloro EJ, Castaldi PA, Gorman JJ, Gamble JR, Vadas MA, Bemdt MC. Characterisation of GMP-140 (P-selectin) as a circulating plasma protein. J Exp Med 1992; 175: 1147-1150
    CrossrefPubMedGoogle Scholar
  • 18 Chong BH, Murray B, Berndt MC, Dunlop LC, Brighton T, Chesterman CN. Plasma P-selectin is increased in thrombotic consumptive platelet disorders. Blood 1994; 83: 1535-1541
    PubMedGoogle Scholar
  • 19 Essien EM, Ebhota MI. Platelet secretory activities in acute malaria (Plasmodium falciparum) infection. Acta Haemat 1983; 70: 183-188
    CrossrefPubMedGoogle Scholar
  • 20 Looareesuwan S, Vanijanonta S, Viravan C, Wilairatana P, Chaeronlap P. Randomized trial of mefloquine alone and artesunate followed by mefloquine for the treatment of acute uncomplicated falciparum malaria. Ann Trop Med Parasitol 1994; 88: 131-136
    CrossrefPubMedGoogle Scholar
  • 21 World Health Organization Technical Report. Chemotherapy of malaria and resistance to antimalarials. Series No 529. WHO, Geneva. 1973: 01-121
    Google Scholar
  • 22 Lee SH, Crocker P, Gordon S. Macrophage plasma membrane and secretory properties in murine malaria. J Exp Med 1986; 163: 54-74
    CrossrefPubMedGoogle Scholar
  • 23 Looareesuwan S, Ho M, Wattanagoon Y, White NJ, Warrell DA, Bunnag D, Harinasuta T, Wyler DJ. Dynamic alteration in splenic function during acute falciparum malaria. New Engl J Med 1987; 317: 675-679
    CrossrefPubMedGoogle Scholar
  • 24 Lee SH, Looareesuwan S, Wattanagoon Y, Ho M, Wuthiekanul V, Vilayanna N, Weatherall DJ, White NJ. Antibody-dependent red cell clearance during P. falciparum malaria: Studies with an IgG anti-D. Brit J Haematol 1989; 73: 396-402
    CrossrefPubMedGoogle Scholar
  • 25 Sanda MG, Yang JC, Topalian SL, Groves ES, Childs A, Belfort Jr R, deSmet MD, Schwartzentruber DJ, White DE, Lotze MT, Rosenberg SA. Intravenous administration of recombinant human macrophage colony-stimulating factor to patients with metastatic cancer. A Phase I study. J Clin Oncol 1992; 10: 1643-1649
    CrossrefPubMedGoogle Scholar
  • 26 Munn DH, Garnick MB, Cheung N-KV. Effects of parenteral recombinant human macrophage colony-stimulating factor on monocyte number phenotype, and anti-tumour cytotoxicity in nonhuman primates. Blood 1990; 75: 2042-2048
    PubMedGoogle Scholar
  • 27 Mufson RA, Aghajanian J, Wong G, Woodhouse C, Morgan AC. Macrophage colony-stimulating factor enhances monocyte and macrophage antibody-dependent cell-mediated cytoxicity. Cell Immunol 1989; 119: 182-192
    CrossrefPubMedGoogle Scholar
  • 28 Garnick MB, Stoudemire JB. Preclinical and clinical evaluation of recombinant human macrophage colony-stimulating factor (rhM-CSF). Int J Cell Cloning 1990; (Suppl. 01) 08: 356-371
    CrossrefPubMedGoogle Scholar
  • 29 Wang JM, Griffin JD, Rambaldi A, Chen ZG, Mantovani A. Induction of monocyte migration by recombinant macrophage colony-stimulating factor. J Immunol 1988; 141: 575-579
    PubMedGoogle Scholar
  • 30 Bartocci A, Mastrogiannis DS, Migliorati G. et al. Macrophages specifically regulate the concentration of their own growth factor in the circulatio. Proc Natl Acad Sci USA 1987; 84: 6179-6183
    CrossrefPubMedGoogle Scholar
  • 31 Munn DH, Cheung NKV. Preclinical and clinical studies of macrophage colony-stimulating factor. Semin Oncol 1992; 19: 395-407
    PubMedGoogle Scholar
  • 32 Villeval JL, Gearing A, Metcalf D. Changes in hemopoietic and regulator levels in mice during fatal or nonfatal malarial infections. II. Nonerythroid populations. Exp Parasitol 1990; 71: 375-385
    CrossrefPubMedGoogle Scholar
  • 33 Grau GE, Taylor TE, Molyneux MM, Wirima JJ, Vassalli P, Hommel M, Lambert PH. Tumor necrosis factor and disease severity in children with falciparum malaria. New Engl J Med 1989; 320: 1586-1591
    CrossrefPubMedGoogle Scholar
  • 34 Kern P, Hemmer CJ, van DammeJ, Gruss HJ, Dietrich M. Elevated tumor necrosis factor alpha and interleukin-6 serum levels as markers for complicatedPlasmodium falciparummalaria. Am J Med 1989; 87: 139-143
    CrossrefPubMedGoogle Scholar
  • 35 Peyron F, Burdin N, Ringwald P, Vuillez JP, Rousset F, Bancherau J. High circulating levels of circulating IL-10 in human malaria. Clin Exp Immunol 1994; 95: 300-303
    PubMedGoogle Scholar
  • 36 Harpaz R, Edelman R, Wasserman SS, Levine MM, Davis JR, Sztein MB. Serum cytokine profiles in experimental human malaria. Relationship to protection and disease course after challenge. J Clin Invest 1992; 90: 515-523
    CrossrefPubMedGoogle Scholar
  • 37 Ringwald P, Peyron F, Vuillez JP, Touze JE, Le BrasJ, Deloron P. Levels of cytokines in plasma duringPlasmodium falciparummalaria attacks. J Clin Microbiol 1991; 29: 2076-2078
    PubMedGoogle Scholar
  • 38 Cerami A. Inflammatory cytokines. Clin Immunol and Immunopathol 1992; 62: S03-S10
    PubMedGoogle Scholar
  • 39 Johnston GI, Bliss GA, Newman PJ, McEver RP. Structure of the human gene encoding granule membrane protein-140, a member of the selectin family of adhesion receptors for leukocytes. J Biol Chem 1990; 265: 21381-21385
    PubMedGoogle Scholar
  • 40 Inyang AL, Sodeinde O, Okpako DT, Essien EM. Platelet reactions after interaction with culturedPlasmodium falciparuminfected erythrocytes. Brit J Haematol 1987; 66: 375-378
    CrossrefPubMedGoogle Scholar