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Blood coagulation in falciparum malaria—a review


Falciparum malaria infection influences blood coagulation by various interacting pathobiological mechanisms, the most important being the overwhelming response of the host to sepsis resulting in a cytokine storm. In addition, the parasite infects the red cells leading to changes in the red cell phospholipid composition which supports blood coagulation. Red cells infected with Plasmodium falciparum also adhere to deeper tissue capillary endothelium leading to profound damage to endothelial cells leading to further activation. This results in widespread consumption of platelets and activation of blood coagulation which at times culminates in a clinically and pathologically detectable disseminated intravascular coagulation (DIC). Monocyte–macrophage system also gets activated in this infection compounding the hypercoagulable state. Heavy parasitaemia leading to occlusion of hepatic microcirculation leads to abnormalities in synthesis and secretion of coagulation factors and their inhibitors. Drugs used in the treatment for falciparum malaria can cause thrombocytopaenia, bone marrow suppression and haemolytic anaemia, all of which can interfere indirectly with blood coagulation. Microparticle formation from platelets, red cells and macrophages also causes widespread activation of blood coagulation, and this recently observed mechanism is the focus of intense research in many other inflammatory and neoplastic conditions where there is activation of blood coagulation system. Thus, in severe falciparum malaria, there is activation of blood coagulation system along with thrombocytopaenia, even before widespread DIC and coagulation failure occur.

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  1. Biswas S (1999) Patterns of parasitaemia, antibodies, complement and circulating immune complexes in drug-suppressed simian Plasmodium knowlesi malaria. Indian J Malario 36:33–41

  2. Boehme MW, Werle E, Kommerell B, Raeth U (1994) Serum levels of adhesion molecules and thrombomodulin as indicators of vascular injury in severe Plasmodium falciparum malaria. Clin Investig 72:598–603

  3. Borochovitz D, Crosley AL, Metz J (1970) Disseminated intravascular coagulation with fatal haemorrhage in cerebral malaria. Br Med J 2:71–89

  4. Brentlinger PE (2006) Health, human rights, and malaria control: historical background and current challenges. Health Human Rights 9:10–38

  5. Chaiyaroj SC, Rutta AS, Muenthaisong K, Watkins P, Na Ubol M, Looareesuwan S (2004) Reduced levels of transforming growth factor-beta1, interleukin-12 and increased migration inhibitory factor are associated with severe malaria. Acta Tropica 89:319–327

  6. Clark IA, Budd AC, Alleva LM, Cowden WB (2006) Human malarial disease: a consequence of inflammatory cytokine release. Malaria Journal 5:85

  7. Clemens R, Pramoolsinsap C, Lorenz R, Pukrittayakamee S, Bock HL, White NJ (1994) Activation of the coagulation cascade in severe falciparum malaria through the intrinsic pathway. Br J Haematol 87:100–105

  8. Coltel N, Combes V, Wassmer SC, Chimini G, Grau GE (2006) Cell vesiculation and immunopathology: implications in cerebral malaria. Microbes Infect 8:2305–2316

  9. Combes V, Taylor TE, Juhan-Vague I, Mege JL, Mwenechanya J, Tembo M, Grau GE, Molyneux ME (2004) Circulating endothelial microparticles in Malawian children with severe falciparum malaria complicated with coma. JAMA 291:2542–2544

  10. Combes V, Coltel N, Faille D, Wassmer SC, Grau GE (2006) Cerebral malaria: role of microparticles and platelets in alterations of the blood-brain barrier. International Journal of Parasitology 36:541–546

  11. Day NP, Hien TT, Schollaardt T, Loc PP, Chuong LV, Chau TT, Mai NT, Phu NH, Sinh DX, White NJ, Ho M (1999) The prognostic and pathophysiologic role of pro- and anti-inflammatory cytokines in severe malaria. J Infect Dis 180:1288–1212

  12. de Mast Q, Groot E, Lenting PJ, de Groot PG, McCall M, Sauerwein RW, Fijnheer R, van der Ven A (2007) Thrombocytopenia and release of activated von Willebrand Factor during early Plasmodium falciparum malaria. J Infect Dis 196:622–628

  13. Dugue C, Perraut R, Youinou P, Renaudineau Y (2004) Effects of anti-endothelial cell antibodies in leprosy and malaria. Infect Immunity 72:301–309

  14. Essien EM, Ebhota MI (1981) Platelet hypersensitivity in acute malaria (Plasmodium falciparum) infection in man. Thrombosis Haemostasis 46:547–9

  15. Essien EM, Ebhota MI (1983) Platelet secretory activities in acute malaria (Plasmodium falciparum) infection. Acta Haematologica 70:183–188

  16. Francischetti IM, Seydel KB, Monteiro RQ, Whitten RO, Erexson CR, Noronha AL, Ostera GR, Kamiza SB, Molyneux ME, Ward JM, Taylor TE (2007) Plasmodium falciparum-infected erythrocytes induce tissue factor expression in endothelial cells and support the assembly of multimolecular coagulation complexes. J Thromb Haemostasis 5:155–165

  17. Gimenez F, Barraud de Lagerie S, Fernandez C, Pino P, Mazier D (2003) Tumor necrosis factor alpha in the pathogenesis of cerebral malaria. Cell Mol Life Sci 60:1623–1635

  18. Goodier MR, Lundqvist C, Hammarström ML, Troye-Blomberg M, Langhorne J (1995) Cytokine profiles for human V gamma 9+T cells stimulated by Plasmodium falciparum. Parasite Immunol 17:413–423

  19. Hemmer CJ, Kern P, Holst FG, Radtke KP, Egbring R, Bierhaus A, Nawroth PP, Dietrich M (1991) Activation of the host response in human Plasmodium falciparum malaria: relation of parasitemia to tumor necrosis factor/cachectin, thrombin-antithrombin III, and protein C levels. Am J Med 91:37–44

  20. Hewett PW, Murray JC (1993) Human lung microvessel endothelial cells: isolation, culture, and characterization. Microvasc Res 46:89–97

  21. Horstmann RD, Dietrich M (1985) Haemostatic alterations in malaria correlate to parasitaemia. Blut 51:329–335

  22. Horvat R, Palade GE (1993) Thrombomodulin and thrombin localization on the vascular endothelium; their internalization and transcytosis by plasmalemmal vesicles. Eur J Cell Biol 61:299–313

  23. Inyang AL, Okpako DT, Essien EM (1987a) Platelet reactions in acute Plasmodium berghei infection in Swiss albino mice. Haematologia (Budap) 20:101–108

  24. Inyang AL, Sodeinde O, Okpako DT, Essien EM (1987b) Platelet reactions after interaction with cultured Plasmodium falciparum infected erythrocytes. Br J Haematol 66:375–378

  25. Jadhav UM, Patkar VS, Kadam NN (2004) Thrombocytopenia in malaria correlation with type and severity of malaria. J Assoc PhysIndia 52:615–618

  26. Jakobsen PH, Morris-Jones SD, Hviid L, Theander TG, Høier-Madsen M, Bayoumi A, Greenwood BM (2005) Anti-phospholipid antibodies in patients with Plasmodium falciparum malaria. Ann Rheum Dis 64:1804–1805

  27. Jarvis JN, Planche T, Bicanic T, Dzeing-Ella A, Kombila M, Issifou S, Borrmann S, Kremsner PG, Krishna S (2006) Lactic acidosis in Gabonese children with severe malaria is unrelated to dehydration. Clin Infect Dis 42:1719–1725

  28. Jimmy EO, Saliu I, Okpala I, Walker O, Sowumni A, Ademowo OG, Essien EM (1995) Effect of Plasmodium falciparum malaria on plasma fibrinopeptide-A (FpA) concentration. Cent Afr J Med 41:124–127

  29. Jimmy EO, Saliu I, Ademowo O (2003) Fibrinopeptide-A and fibrinogen fractions in acute, Plasmodium falciparum malaria. Ann Trop Med Parasitol 97:879–881

  30. Kaplan KL, Owen J (1981) Plasma levels of beta-thromboglobulin and platelet factor 4 as indices of platelet activation in vivo. Blood 57:199–202

  31. Lyke KE, Burges R, Cissoko Y, Sangare L, Dao M, Diarra I, Kone A, Harley R, Plowe CV, Doumbo OK, Sztein MB (2004) Serum levels of the proinflammatory cytokines interleukin-1 beta (IL-1beta), IL-6, IL-8, IL-10, tumor necrosis factor alpha, and IL-12(p70) in Malian children with severe Plasmodium falciparum malaria and matched uncomplicated malaria or healthy controls. Infect Immun 72:5630–5637

  32. Mata E, Carcaboso AM, Hernandez RM, Igartua M, Corradin G, Pedraz JL (2007) Adjuvant activity of polymer microparticles and Montanide ISA 720 on immune responses to Plasmodium falciparum MSP2 long synthetic peptides in mice. Vaccine 25:877–885

  33. Meyer CG, May J, Luty AJ, Lell B, Kremsner PG (2002) TNFalpha-308A associated with shorter intervals of Plasmodium falciparum reinfections. Tissue Antigens 59:287–292

  34. Mohanty D, Marwaha N, Ghosh K, Sharma S, Garewal G, Shah S, Devi S, Das KC (1988) Functional and ultrastructural changes of platelets in malarial infection. Trans R Soc Trop Med Hyg 82:369–375

  35. Mohanty D, Ghosh K, Nandwani SK, Shetty S, Phillips C, Rizvi S, Parmar BD (1997) Fibrinolysis, inhibitors of blood coagulation, and monocyte derived coagulant activity in acute malaria. Am J Hematol 54:23–29

  36. Nakamura K, Hasler T, Morehead K, Howard RJ, Aikawa M (1992) Plasmodium falciparum-infected erythrocyte receptor(s) for CD36 and thrombospondin are restricted to knobs on the erythrocyte surface. J Histochem Cytochem 40:1419–1422

  37. Nicolas P, Hovette P, Merouze F, Touze JE, Martet G (1994) Cytokines and malaria. A study of TNF-alpha, IL1-beta, IL6 and IL2R in 28 patients. Bulletin of Society of Pathology Exotica 87:91–95

  38. Omoigberale AJ, Abiodun PO, Famodu AA (2005) Fibrinolytic activity in children with Plasmodium falciparum malaria. East Afr Med J 82:103–105

  39. Pernod G, Polack B, Peyron F, Luisy A, Kolodie L, Ambroise-Thomas P, Santoro F (1992) Monocyte tissue factor expression induced by Plasmodium falciparum-infected erythrocytes. Thromb Haemost 68:111–114

  40. Planche T, Krishna S (2006) Severe malaria: metabolic complications. Current Molecular Medicine 6:141–153

  41. Pradhan V, Badakere SS, Shankarkumar U, Iyer YS, Ghosh K, Karnad D (2002) Anti-neutrophil cytoplasmic antibodies (ANCA) in malaria. Indian J Malariol 39:51–59

  42. Rankin LG, Austin DL (2007) The use of activated protein C in severe Plasmodium falciparum malaria. Anaesth Intensive Care 35:428–432

  43. Rao AK, Willis J, Holmsen H (1984) A major role of ADP in thromboxane transfer experiments: studies in patients with platelet secretion defects. J Lab Clin Med 104:116–126

  44. Srichaikul T, Puwasatien P, Karnjanajetanee J, Bokisch VA, Pawasatien P (1975) Complement changes and disseminated intravascular coagulation in Plasmodium falciparum malaria. Lancet 1:770–772

  45. Srichaikul T, Pulket C, Sirisatepisarn T, Prayoonwiwat W (1988) Platelet dysfunction in malaria. Southeast Asian J Trop Med Public Health 19:225–233

  46. Srinivas R, Agarwal R, Gupta D (2007) Severe sepsis due to severe falciparum malaria and leptospirosis co-infection treated with activated protein C. Malaria Journal 6:42

  47. Stuart J (1978) Intravascular coagulation in falciparum malaria. Br Med J 2:774

  48. Troye-Blomberg M, Sjoholm PE, Perlmann H, Patarroyo ME, Perlmann P (1983) Regulation of the immune response in Plasmodium falciparum malaria. I. Non-specific proliferative responses in vitro and characterization of lymphocytes. Clin Exp Immunol 53:335–344

  49. Troye-Blomberg M, Worku S, Tangteerawatana P, Jamshaid R, Söderström K, Elghazali G, Moretta L, Hammarström M, Mincheva-Nilsson L (1999) Human gamma delta T cells that inhibit the in vitro growth of the asexual blood stages of the Plasmodium falciparum parasite express cytolytic and proinflammatory molecules. Scand J Immunol 50:642–650

  50. Tyagi P, Biswas S (1999) Naturally occurring plasmodia-specific circulating immune complexes in individuals of malaria endemic areas in India. Indian J Malariol 36:12–18

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Correspondence to Kanjaksha Ghosh.

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Ghosh, K., Shetty, S. Blood coagulation in falciparum malaria—a review. Parasitol Res 102, 571–576 (2008). https://doi.org/10.1007/s00436-007-0832-0

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  • Malaria
  • Disseminate Intravascular Coagulation
  • Falciparum Malaria
  • Cerebral Malaria
  • Disseminate Intravascular Coagulation