Skip to main content
Top
Published in: BMC Medicine 1/2015

Open Access 01-12-2015 | Research article

The clinical implications of thrombocytopenia in adults with severe falciparum malaria: a retrospective analysis

Authors: Josh Hanson, Nguyen Hoan Phu, Mahtab Uddin Hasan, Prakaykaew Charunwatthana, Katherine Plewes, Richard J Maude, Panote Prapansilp, Hugh WF Kingston, Saroj K Mishra, Sanjib Mohanty, Ric N Price, M Abul Faiz, Arjen M Dondorp, Nicholas J White, Tran Tinh Hien, Nicholas PJ Day

Published in: BMC Medicine | Issue 1/2015

Login to get access

Abstract

Background

Thrombocytopenia is a common finding in adults with severe falciparum malaria, but its clinical and prognostic utility is incompletely defined.

Methods

Clinical and laboratory data from 647 adults with severe falciparum malaria were analysed retrospectively to determine the relationship between a patient’s platelet count on admission to hospital and their subsequent clinical course.

Results

On admission, 614 patients (94.9%) were thrombocytopenic (platelet count <150 × 109/L) and 328 (50.7%) had a platelet count <50 × 109/L. The admission platelet count was inversely correlated with parasite biomass (estimated from plasma PfHRP2 concentrations, rs = −0.28, P = 0.003), the degree of microvascular sequestration (measured with orthogonal polarizing spectral imaging, rs = −0.31, P = 0.001) and disease severity (the number of World Health Organization severity criteria satisfied by the patient, rs = −0.21, P <0.001). Platelet counts were lower on admission in the patients who died (median: 30 (interquartile range 22 to 52) × 109/L versus 50 (34 to 78) × 109/L in survivors; P <0.001), but did not predict outcome independently from other established laboratory and clinical prognostic indices. The 39 patients (6%) with profound thrombocytopenia (platelet count <20 × 109/L) were more likely to die (odds ratio: 5.00, 95% confidence interval: 2.56 to 9.75) than patients with higher platelet counts, but these high-risk patients could be identified more rapidly with simple bedside clinical assessment. The admission platelet count did not reliably identify the 50 patients (7.7%) with major bleeding during the study.

Conclusions

Thrombocytopenia is a marker of disease severity in adults with falciparum malaria, but has limited utility in prognostication, triage and management.
Literature
2.
go back to reference Scott CS, Van Zyl D, Ho E, Ruivo L, Mendelow B, Coetzer TL. Thrombocytopenia in patients with malaria: automated analysis of optical platelet counts and platelet clumps with the Cell Dyn CD4000 analyser. Clin Lab Haematol. 2002;24:295–302.CrossRefPubMed Scott CS, Van Zyl D, Ho E, Ruivo L, Mendelow B, Coetzer TL. Thrombocytopenia in patients with malaria: automated analysis of optical platelet counts and platelet clumps with the Cell Dyn CD4000 analyser. Clin Lab Haematol. 2002;24:295–302.CrossRefPubMed
3.
go back to reference Jadhav UM, Patkar VS, Kadam NN. Thrombocytopenia in malaria–correlation with type and severity of malaria. J Assoc Physicians India. 2004;52:615–8.PubMed Jadhav UM, Patkar VS, Kadam NN. Thrombocytopenia in malaria–correlation with type and severity of malaria. J Assoc Physicians India. 2004;52:615–8.PubMed
4.
go back to reference de Mast Q, de Groot PG, van Heerde WL, Roestenberg M, van Velzen JF, Verbruggen B, et al. Thrombocytopenia in early malaria is associated with GP1b shedding in absence of systemic platelet activation and consumptive coagulopathy. Br J Haematol. 2010;151:495–503.CrossRefPubMed de Mast Q, de Groot PG, van Heerde WL, Roestenberg M, van Velzen JF, Verbruggen B, et al. Thrombocytopenia in early malaria is associated with GP1b shedding in absence of systemic platelet activation and consumptive coagulopathy. Br J Haematol. 2010;151:495–503.CrossRefPubMed
5.
go back to reference Karanikas G, Zedwitz-Liebenstein K, Eidherr H, Schuetz M, Sauerman R, Dudczak R, et al. Platelet kinetics and scintigraphic imaging in thrombocytopenic malaria patients. Thromb Haemost. 2004;91:553–7.PubMed Karanikas G, Zedwitz-Liebenstein K, Eidherr H, Schuetz M, Sauerman R, Dudczak R, et al. Platelet kinetics and scintigraphic imaging in thrombocytopenic malaria patients. Thromb Haemost. 2004;91:553–7.PubMed
6.
7.
go back to reference Kreil A, Wenisch C, Brittenham G, Looareesuwan S, Peck-Radosavljevic M. Thrombopoietin in Plasmodium falciparum malaria. Br J Haematol. 2000;109:534–6.CrossRefPubMed Kreil A, Wenisch C, Brittenham G, Looareesuwan S, Peck-Radosavljevic M. Thrombopoietin in Plasmodium falciparum malaria. Br J Haematol. 2000;109:534–6.CrossRefPubMed
8.
go back to reference Grau GE, Mackenzie CD, Carr RA, Redard M, Pizzolato G, Allasia C, et al. Platelet accumulation in brain microvessels in fatal pediatric cerebral malaria. J Infect Dis. 2003;187:461–6.CrossRefPubMed Grau GE, Mackenzie CD, Carr RA, Redard M, Pizzolato G, Allasia C, et al. Platelet accumulation in brain microvessels in fatal pediatric cerebral malaria. J Infect Dis. 2003;187:461–6.CrossRefPubMed
9.
go back to reference de Mast Q, Groot E, Asih PB, Syafruddin D, Oosting M, Sebastian S, et al. ADAMTS13 deficiency with elevated levels of ultra-large and active von Willebrand factor in P. falciparum and P. vivax malaria. Am J Trop Med Hyg. 2009;80:492–8.PubMed de Mast Q, Groot E, Asih PB, Syafruddin D, Oosting M, Sebastian S, et al. ADAMTS13 deficiency with elevated levels of ultra-large and active von Willebrand factor in P. falciparum and P. vivax malaria. Am J Trop Med Hyg. 2009;80:492–8.PubMed
10.
go back to reference Lowenberg EC, Charunwatthana P, Cohen S, van den Born BJ, Meijers JC, Yunus EB, et al. Severe malaria is associated with a deficiency of von Willebrand factor cleaving protease, ADAMTS13. Thromb Haemost. 2010;103:181–7.CrossRefPubMed Lowenberg EC, Charunwatthana P, Cohen S, van den Born BJ, Meijers JC, Yunus EB, et al. Severe malaria is associated with a deficiency of von Willebrand factor cleaving protease, ADAMTS13. Thromb Haemost. 2010;103:181–7.CrossRefPubMed
11.
go back to reference Severe falciparum malaria. World Health Organization, Communicable Diseases Cluster. Trans R Soc Trop Med Hyg. 2000;94:S1–90. Severe falciparum malaria. World Health Organization, Communicable Diseases Cluster. Trans R Soc Trop Med Hyg. 2000;94:S1–90.
12.
go back to reference Lampah DA, Yeo TW, Malloy M, Kenangalem E, Douglas NM, Ronaldo D, et al. Severe malarial thrombocytopenia: a risk factor for mortality in Papua. Indonesia J Infect Dis. 2014;211:623–34.CrossRefPubMed Lampah DA, Yeo TW, Malloy M, Kenangalem E, Douglas NM, Ronaldo D, et al. Severe malarial thrombocytopenia: a risk factor for mortality in Papua. Indonesia J Infect Dis. 2014;211:623–34.CrossRefPubMed
13.
go back to reference Saravu K, Rishikesh K, Kamath A. Determinants of mortality, intensive care requirement and prolonged hospitalization in malaria - a tertiary care hospital based cohort study from South-Western India. Malar J. 2014;13:370.CrossRefPubMedPubMedCentral Saravu K, Rishikesh K, Kamath A. Determinants of mortality, intensive care requirement and prolonged hospitalization in malaria - a tertiary care hospital based cohort study from South-Western India. Malar J. 2014;13:370.CrossRefPubMedPubMedCentral
14.
go back to reference Tran TH, Day NP, Nguyen HP, Nguyen TH, Pham PL, Dinh XS, et al. A controlled trial of artemether or quinine in Vietnamese adults with severe falciparum malaria. N Engl J Med. 1996;335:76–83.CrossRefPubMed Tran TH, Day NP, Nguyen HP, Nguyen TH, Pham PL, Dinh XS, et al. A controlled trial of artemether or quinine in Vietnamese adults with severe falciparum malaria. N Engl J Med. 1996;335:76–83.CrossRefPubMed
15.
go back to reference Dondorp AM, Ince C, Charunwatthana P, Hanson J, van Kuijen A, Faiz MA, et al. Direct in vivo assessment of microcirculatory dysfunction in severe falciparum malaria. J Infect Dis. 2008;197:79–84.CrossRefPubMed Dondorp AM, Ince C, Charunwatthana P, Hanson J, van Kuijen A, Faiz MA, et al. Direct in vivo assessment of microcirculatory dysfunction in severe falciparum malaria. J Infect Dis. 2008;197:79–84.CrossRefPubMed
16.
go back to reference Maude RJ, Silamut K, Plewes K, Charunwatthana P, Ho M, Abul Faiz M, et al. Randomized controlled trial of levamisole hydrochloride as adjunctive therapy in severe falciparum malaria with high parasitemia. J Infect Dis. 2013;209:120–9.CrossRefPubMedPubMedCentral Maude RJ, Silamut K, Plewes K, Charunwatthana P, Ho M, Abul Faiz M, et al. Randomized controlled trial of levamisole hydrochloride as adjunctive therapy in severe falciparum malaria with high parasitemia. J Infect Dis. 2013;209:120–9.CrossRefPubMedPubMedCentral
17.
go back to reference Hanson J, Lam SW, Mahanta KC, Pattnaik R, Alam S, Mohanty S, et al. Relative contributions of macrovascular and microvascular dysfunction to disease severity in falciparum malaria. J Infect Dis. 2012;206:571–9.CrossRefPubMed Hanson J, Lam SW, Mahanta KC, Pattnaik R, Alam S, Mohanty S, et al. Relative contributions of macrovascular and microvascular dysfunction to disease severity in falciparum malaria. J Infect Dis. 2012;206:571–9.CrossRefPubMed
18.
go back to reference Maude RJ, Hoque G, Hasan MU, Sayeed A, Akter S, Samad R, et al. Timing of enteral feeding in cerebral malaria in resource-poor settings: a randomized trial. PLoS One. 2011;6:e27273.CrossRefPubMedPubMedCentral Maude RJ, Hoque G, Hasan MU, Sayeed A, Akter S, Samad R, et al. Timing of enteral feeding in cerebral malaria in resource-poor settings: a randomized trial. PLoS One. 2011;6:e27273.CrossRefPubMedPubMedCentral
19.
go back to reference Severe and complicated malaria. World Health Organization, Division of Control of Tropical Diseases. Trans R Soc Trop Med Hyg. 1990;84:1–65. Severe and complicated malaria. World Health Organization, Division of Control of Tropical Diseases. Trans R Soc Trop Med Hyg. 1990;84:1–65.
20.
go back to reference Hanson J, Lee SJ, Mohanty S, Faiz MA, Anstey NM, Price RN, et al. Rapid clinical assessment to facilitate the triage of adults with falciparum malaria, a retrospective analysis. PLoS One. 2014;9:e87020.CrossRefPubMedPubMedCentral Hanson J, Lee SJ, Mohanty S, Faiz MA, Anstey NM, Price RN, et al. Rapid clinical assessment to facilitate the triage of adults with falciparum malaria, a retrospective analysis. PLoS One. 2014;9:e87020.CrossRefPubMedPubMedCentral
21.
go back to reference Hanson J, Lee SJ, Mohanty S, Faiz MA, Anstey NM, Charunwatthana P, et al. A simple score to predict the outcome of severe malaria in adults. Clin Infect Dis. 2010;50:679–85.CrossRefPubMedPubMedCentral Hanson J, Lee SJ, Mohanty S, Faiz MA, Anstey NM, Charunwatthana P, et al. A simple score to predict the outcome of severe malaria in adults. Clin Infect Dis. 2010;50:679–85.CrossRefPubMedPubMedCentral
22.
go back to reference Kaung M, Kyi TT, Aung NM, Kyaw MP, Min M, Htet ZW, et al. The prognostic utility of bedside assessment of adults hospitalised with malaria in Myanmar: a retrospective analysis. Malar J. 2015;14:63.CrossRefPubMedPubMedCentral Kaung M, Kyi TT, Aung NM, Kyaw MP, Min M, Htet ZW, et al. The prognostic utility of bedside assessment of adults hospitalised with malaria in Myanmar: a retrospective analysis. Malar J. 2015;14:63.CrossRefPubMedPubMedCentral
23.
go back to reference World Health Organization. WHO guidelines for the treatment of malaria 2010. Geneva: World Health Organization; 2010. World Health Organization. WHO guidelines for the treatment of malaria 2010. Geneva: World Health Organization; 2010.
24.
go back to reference World Health Organization. Guidelines for the treatment of malaria. Geneva: World Health Organization; 2006. World Health Organization. Guidelines for the treatment of malaria. Geneva: World Health Organization; 2006.
25.
go back to reference Dondorp AM, Desakorn V, Pongtavornpinyo W, Sahassananda D, Silamut K, Chotivanich K, et al. Estimation of the total parasite biomass in acute falciparum malaria from plasma PfHRP2. PLoS Med. 2005;2:e204.CrossRefPubMedPubMedCentral Dondorp AM, Desakorn V, Pongtavornpinyo W, Sahassananda D, Silamut K, Chotivanich K, et al. Estimation of the total parasite biomass in acute falciparum malaria from plasma PfHRP2. PLoS Med. 2005;2:e204.CrossRefPubMedPubMedCentral
26.
go back to reference Yeo TW, Lampah DA, Gitawati R, Tjitra E, Kenangalem E, Piera K, et al. Angiopoietin-2 is associated with decreased endothelial nitric oxide and poor clinical outcome in severe falciparum malaria. Proc Natl Acad Sci U S A. 2008;105:17097–102.CrossRefPubMedPubMedCentral Yeo TW, Lampah DA, Gitawati R, Tjitra E, Kenangalem E, Piera K, et al. Angiopoietin-2 is associated with decreased endothelial nitric oxide and poor clinical outcome in severe falciparum malaria. Proc Natl Acad Sci U S A. 2008;105:17097–102.CrossRefPubMedPubMedCentral
27.
go back to reference Erhart LM, Yingyuen K, Chuanak N, Buathong N, Laoboonchai A, Miller RS, et al. Hematologic and clinical indices of malaria in a semi-immune population of western Thailand. Am J Trop Med Hyg. 2004;70:8–14.PubMed Erhart LM, Yingyuen K, Chuanak N, Buathong N, Laoboonchai A, Miller RS, et al. Hematologic and clinical indices of malaria in a semi-immune population of western Thailand. Am J Trop Med Hyg. 2004;70:8–14.PubMed
28.
go back to reference Tagny CT, Mbanya D, Tapko JB, Lefrere JJ. Blood safety in Sub-Saharan Africa: a multi-factorial problem. Transfusion. 2008;48:1256–61.CrossRefPubMed Tagny CT, Mbanya D, Tapko JB, Lefrere JJ. Blood safety in Sub-Saharan Africa: a multi-factorial problem. Transfusion. 2008;48:1256–61.CrossRefPubMed
29.
go back to reference Looareesuwan S, Davis JG, Allen DL, Lee SH, Bunnag D, White NJ. Thrombocytopenia in malaria. Southeast Asian J Trop Med Public Health. 1992;23:44–50.PubMed Looareesuwan S, Davis JG, Allen DL, Lee SH, Bunnag D, White NJ. Thrombocytopenia in malaria. Southeast Asian J Trop Med Public Health. 1992;23:44–50.PubMed
30.
go back to reference Severe malaria. Trop Med Int Health. 2014, 19:7–131. Severe malaria. Trop Med Int Health. 2014, 19:7–131.
31.
go back to reference Chotivanich K, Sritabal J, Udomsangpetch R, Newton P, Stepniewska KA, Ruangveerayuth R, et al. Platelet-induced autoagglutination of Plasmodium falciparum-infected red blood cells and disease severity in Thailand. J Infect Dis. 2004;189:1052–5.CrossRefPubMed Chotivanich K, Sritabal J, Udomsangpetch R, Newton P, Stepniewska KA, Ruangveerayuth R, et al. Platelet-induced autoagglutination of Plasmodium falciparum-infected red blood cells and disease severity in Thailand. J Infect Dis. 2004;189:1052–5.CrossRefPubMed
32.
go back to reference Wassmer SC, Lepolard C, Traore B, Pouvelle B, Gysin J, Grau GE. Platelets reorient Plasmodium falciparum-infected erythrocyte cytoadhesion to activated endothelial cells. J Infect Dis. 2004;189:180–9.CrossRefPubMed Wassmer SC, Lepolard C, Traore B, Pouvelle B, Gysin J, Grau GE. Platelets reorient Plasmodium falciparum-infected erythrocyte cytoadhesion to activated endothelial cells. J Infect Dis. 2004;189:180–9.CrossRefPubMed
33.
go back to reference MacPherson GG, Warrell MJ, White NJ, Looareesuwan S, Warrell DA. Human cerebral malaria. A quantitative ultrastructural analysis of parasitized erythrocyte sequestration. Am J Pathol. 1985;119:385–401.PubMedPubMedCentral MacPherson GG, Warrell MJ, White NJ, Looareesuwan S, Warrell DA. Human cerebral malaria. A quantitative ultrastructural analysis of parasitized erythrocyte sequestration. Am J Pathol. 1985;119:385–401.PubMedPubMedCentral
34.
go back to reference Turner GD, Morrison H, Jones M, Davis TM, Looareesuwan S, Buley ID, et al. An immunohistochemical study of the pathology of fatal malaria. Evidence for widespread endothelial activation and a potential role for intercellular adhesion molecule-1 in cerebral sequestration. Am J Pathol. 1994;145:1057–69.PubMedPubMedCentral Turner GD, Morrison H, Jones M, Davis TM, Looareesuwan S, Buley ID, et al. An immunohistochemical study of the pathology of fatal malaria. Evidence for widespread endothelial activation and a potential role for intercellular adhesion molecule-1 in cerebral sequestration. Am J Pathol. 1994;145:1057–69.PubMedPubMedCentral
35.
go back to reference Lacerda MV, Fragoso SC, Alecrim MG, Alexandre MA, Magalhaes BM, Siqueira AM, et al. Postmortem characterization of patients with clinical diagnosis of Plasmodium vivax malaria: to what extent does this parasite kill? Clin Infect Dis. 2012;55:e67–74.CrossRefPubMed Lacerda MV, Fragoso SC, Alecrim MG, Alexandre MA, Magalhaes BM, Siqueira AM, et al. Postmortem characterization of patients with clinical diagnosis of Plasmodium vivax malaria: to what extent does this parasite kill? Clin Infect Dis. 2012;55:e67–74.CrossRefPubMed
36.
go back to reference Leal-Santos FA, Silva SB, Crepaldi NP, Nery AF, Martin TO, Alves-Junior ER, et al. Altered platelet indices as potential markers of severe and complicated malaria caused by Plasmodium vivax: a cross-sectional descriptive study. Malar J. 2013;12:462.CrossRefPubMedPubMedCentral Leal-Santos FA, Silva SB, Crepaldi NP, Nery AF, Martin TO, Alves-Junior ER, et al. Altered platelet indices as potential markers of severe and complicated malaria caused by Plasmodium vivax: a cross-sectional descriptive study. Malar J. 2013;12:462.CrossRefPubMedPubMedCentral
37.
go back to reference Yeo TW, Lampah DA, Tjitra E, Piera K, Gitawati R, Kenangalem E, et al. Greater endothelial activation, Weibel-Palade body release and host inflammatory response to Plasmodium vivax, compared with Plasmodium falciparum: a prospective study in Papua. Indonesia J Infect Dis. 2010;202:109–12.CrossRefPubMed Yeo TW, Lampah DA, Tjitra E, Piera K, Gitawati R, Kenangalem E, et al. Greater endothelial activation, Weibel-Palade body release and host inflammatory response to Plasmodium vivax, compared with Plasmodium falciparum: a prospective study in Papua. Indonesia J Infect Dis. 2010;202:109–12.CrossRefPubMed
38.
go back to reference Sadler JE. Biochemistry and genetics of von Willebrand factor. Annu Rev Biochem. 1998;67:395–424.CrossRefPubMed Sadler JE. Biochemistry and genetics of von Willebrand factor. Annu Rev Biochem. 1998;67:395–424.CrossRefPubMed
39.
go back to reference Radomski MW, Palmer RM, Moncada S. Endogenous nitric oxide inhibits human platelet adhesion to vascular endothelium. Lancet. 1987;2:1057–8.CrossRefPubMed Radomski MW, Palmer RM, Moncada S. Endogenous nitric oxide inhibits human platelet adhesion to vascular endothelium. Lancet. 1987;2:1057–8.CrossRefPubMed
40.
go back to reference Pober JS, Sessa WC. Evolving functions of endothelial cells in inflammation. Nat Rev Immunol. 2007;7:803–15.CrossRefPubMed Pober JS, Sessa WC. Evolving functions of endothelial cells in inflammation. Nat Rev Immunol. 2007;7:803–15.CrossRefPubMed
41.
go back to reference Dondorp AM, Lee SJ, Faiz MA, Mishra S, Price R, Tjitra E, et al. The relationship between age and the manifestations of and mortality associated with severe malaria. Clin Infect Dis. 2008;47:151–7.CrossRefPubMed Dondorp AM, Lee SJ, Faiz MA, Mishra S, Price R, Tjitra E, et al. The relationship between age and the manifestations of and mortality associated with severe malaria. Clin Infect Dis. 2008;47:151–7.CrossRefPubMed
42.
43.
go back to reference Warrell DA, Looareesuwan S, Warrell MJ, Kasemsarn P, Intaraprasert R, Bunnag D, et al. Dexamethasone proves deleterious in cerebral malaria. A double-blind trial in 100 comatose patients. N Engl J Med. 1982;306:313–9.CrossRefPubMed Warrell DA, Looareesuwan S, Warrell MJ, Kasemsarn P, Intaraprasert R, Bunnag D, et al. Dexamethasone proves deleterious in cerebral malaria. A double-blind trial in 100 comatose patients. N Engl J Med. 1982;306:313–9.CrossRefPubMed
Metadata
Title
The clinical implications of thrombocytopenia in adults with severe falciparum malaria: a retrospective analysis
Authors
Josh Hanson
Nguyen Hoan Phu
Mahtab Uddin Hasan
Prakaykaew Charunwatthana
Katherine Plewes
Richard J Maude
Panote Prapansilp
Hugh WF Kingston
Saroj K Mishra
Sanjib Mohanty
Ric N Price
M Abul Faiz
Arjen M Dondorp
Nicholas J White
Tran Tinh Hien
Nicholas PJ Day
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2015
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-015-0324-5

Other articles of this Issue 1/2015

BMC Medicine 1/2015 Go to the issue