|Year : 2012 | Volume
| Issue : 3 | Page : 152-155
Prevalence of thrombocytopenia in a diagnosed case of malaria in rural population of South India
Jaganmani Srikanth, Sunkara Srinivas, Cherukumilli RPS Krishna, Pemira R Ramulu
Department of General Medicine, Bhaskar Medical College Yenkapally, Moinabad, Rangareddy District, Andhra Pradesh, India
|Date of Web Publication||15-Oct-2012|
Bhaskar Medical College, Yenkapally, Moinabad, Rangareddy District, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
Introduction: Malaria is a major health problem in the tropics and poses a significant burden on health expenditure. Malaria is a common disease in rural India with high mortality and morbidity. Falciparum malaria is common in rural India and presents with protean manifestations, involving multiple systems and high mortality. Compared to benign malaria, Plasmodium falciparum malaria progresses to life-threatening complications, more so in rural India. The global case-fatality rate of falciparum infection is around 2 million deaths per year.
Objective: To evaluate the incidence of thrombocytopenia in malaria, its variations in falciparum and vivax; and prognosis of patients with significant thrombocytopenia.
Materials and Methods: Platelet count was done on a fully automated, quantitative, hematology Coulter analyzer (Name: I Count 3, Irish Company, 2010 model) for a sample collected from peripheral smear positive for malaria patient.
Results: The mean platelet count in vivax infections wasis 120454.55/ml ranging from of 36,000 to 263,000 and in falciparum infections the mean platelet count was 118,200 with a range of 13,000-667,000.
Conclusions: Low platelet counts observed in the course of malaria illness are transient and do not necessarily have prognostic implications or platelet infusions more so with the relatively benign course in Plasmodium vivax malaria.
Keywords: Fever, malaria, rural India, thrombocytopenia
|How to cite this article:|
Srikanth J, Srinivas S, Krishna CR, Ramulu PR. Prevalence of thrombocytopenia in a diagnosed case of malaria in rural population of South India. J NTR Univ Health Sci 2012;1:152-5
|How to cite this URL:|
Srikanth J, Srinivas S, Krishna CR, Ramulu PR. Prevalence of thrombocytopenia in a diagnosed case of malaria in rural population of South India. J NTR Univ Health Sci [serial online] 2012 [cited 2020 Apr 6];1:152-5. Available from: http://www.jdrntruhs.org/text.asp?2012/1/3/152/102438
| Introduction|| |
Malaria is a major health problem in the tropics and poses a significant burden on the health expenditure. Malaria is a common disease in rural India with high mortality and morbidity. Falciparum malaria is common in rural India and presents with protean manifestations, involving multiple systems and high mortality. Compared to benign malaria, Plasmodium falciparum malaria progresses to life-threatening complications, more so in rural India. The global case-fatality rate of falciparum infection is around 1.13 million deaths per year. 
Malaria not only presents as acute episodes of fever but also as an important cause of anemia in children and adults. It is responsible for many adverse outcomes like spontaneous abortion, stillbirth, and premature delivery among pregnant women in India and developing countries and also for low birth weight, and overall child mortality. Malaria is also an important cause of economic slowdown, an estimated average annual reduction of 1.3% in the economic growth for those countries with the highest incidence of malaria.  Among the Indian population, many fevers present with thrombocytopenia and malaria is one of the common causes.
Thrombocytopenia has been reported to be associated with malaria,  with an incidence ranging from 24% to 94%, , with some studies reporting a lower incidence in vivax malaria as compared to falciparum malaria.  It is thought to be caused by increased splenic sequestration, immune-mediated destruction, and a shortened platelet survival.
| Materials and Methods|| |
A total of 20 patients with fever, either hospitalized or outpatients, presented from June 2011 in a rural hospital and 20 patients from Bhaskar general hospital were tested for malaria and if peripheral smear was found positive for malaria, they were included in the study. A patient was considered not to have malaria if three consecutive smears were negative. A para check is also done on suspected patients with fever and chills, more so in patients who are smear-negative. The patients with malaria are separated into two groups depending on the platelet counts as patients with thrombocytopenia and those without thrombocytopenia. Platelet count was done on a fully automated, quantitative, hematology Coulter analyzer (Name: I Count 3, Irish Company, 2010 model).
Many acute febrile illnesses in rural areas cause thrombocytopenia, like dengue fever, coxsackie virus, etc., which are excluded by specific tests and patients with chronic liver disease and with a history of recurrent bleeding, bleeding disorder, and also patients with a history of idiopathic thrombocytopenic purpura (ITP) were also excluded. Patients with a history of drug intake like fansidar, septran, thiazides, and chemotherapeutic agents were also excluded.
Thrombocytopenia is defined as a condition with a platelet count below the normal range for the population. Platelet counts of 75,000 to 150,000/L are defined as grade 1 thrombocytopenia, 50,000 to 75,000/L as grade 2, whereas 25,000 to 50,000/L as grade 3, and below 25,000/L as grade 4 thrombocytopenia. 
Baseline platelet counts were done on the day of presentation [Table 1] and [Table 2]. Repeat platelet counts were done in subjects with marked thrombocytopenia until normal or near-normal values were reached with treatment [Table 3]. Patients with associated dengue fever and leptospirosis are excluded from the study after thorough investigation. All the patients were treated with artesunate derivatives and azithromycin followed by primaquine for radical cure of vivax.
|Table 1: Severity of Thrombocytopenia in Plasmodium falciparum and Plasmodium Vivax|
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|Table 2: Severity of Thrombocytopenia in Plasmodium falciparum and Plasmodium Vivax in Relation to Common Hematological Changes Observed|
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| Results|| |
The mean age of patients in the study was 32.625 years. The study involved 65% males and 35% female patients. Fever with chills was the common presentation. A total of 25 patients had P. falciparum malaria and 11 had vivax and four people had both falciparum and vivax. Platelet count less than 150,000/ml was noted in 33 patients (82.5%).
The mean platelet count in vivax was 1,20,454.55/ml ranging from of 36,000 to 2,63,000 whereas falciparum malaria patients had a mean platelet count of 118,200 with a range of 13,000-667,000. Platelet count below 25,000/ml was noted in about 12% of the falciparum malaria patients only. None of the patients with vivax had platelet counts below 25,000. None of the patients with vivax or falciparum malaria had spontaneous bleeding. Two patients had received blood transfusion because of low hemoglobin (Hb 3.3 g/dl, Hb 2.3 g/dl).
About 23% of the patients with falciparum malaria and 50% of patients with vivax malaria had an improvement in platelet count on the 2 nd day of treatment. The raise in platelet count is in along with the disappearance of parasitemia in peripheral smear.
| Discussion|| |
Malaria is a common disease in rural India presenting with multiple complications, more so in the falciparum malaria. Thrombocytopenia is a common feature in acute malaria and occurs both in falciparum and vivax malaria. As seen in this study too, thrombocytopenia is a diagnostic clue to the presence of malaria.  Thrombocytopenia in malaria is rarely associated with bleeding complications and disseminated intravascular coagulation (DIC) and recovery is rapid. , Platelet count can be as low as 13,000/dl seen in only a few cases and moderately in 80% of patients, it highlights that normal platelet counts are unlikely in an acute malaria. 
Grade 4 thrombocytopenia with platelet counts as low as 5000 are reported in Indian literature in vivax malaria.  None of the patients in our study had such low counts, although 12% of falciparum malaria patients had platelet counts below 25,000 with lowest count observed at 13,000. Severe malaria patients may be given platelet transfusions only in the light of bleeding complications.
Thrombocytopenia per se cannot distinguish the type of malaria; there is a significant difference in the incidence of severity of thrombocytopenia in both types of malaria. The frequency of thrombocytopenia (i.e., platelet count below 150,000/mm 3 ) in malaria infection ranges from 24% to 94% in the literature,  but in our study the incidence of thrombocytopenia in both types of malaria is the same (72.73% of cases in vivax and 72% in falciparum malaria). 
The mechanism of thrombocytopenia in malaria is uncertain. Immune-mediated lysis, sequestration in the spleen, and a dyspoietic process in the marrow with diminished platelet production are consequences of malaria, and in rare instances, platelets can be invaded by the malarial parasites themselves. Fajardo and Tallent  in 1974 demonstrated P. vivax within platelets by electron microscopy and suggested a direct lytic effect of the parasite on the platelets. During acute malaria, thrombocytopenia is most probably associated with the binding of parasite antigens to the surface of platelets to which anti-malarial antibodies also bind, leading to the in-situ formation of immune complexes (ICS).  Both non-immunological destruction  as well as immune mechanisms involving specific platelet-associated IgG antibodies that bind directly to the malarial antigen in the platelets have been recently reported to play a role in the lysis of platelets and the development of thrombocytopenia.  In clinical trials, recombinant-macrophage colony stimulating factor (M-CSF) has been known to cause a reversible dose-dependent thrombocytopenia. Elevated M-CSF levels in malaria, by increasing macrophage activity, may mediate platelet destruction in such cases. Oxidative stress damage of thrombocytes has also been implicated in the etiopathogenesis based on the finding of low levels of platelet superoxide-dismutase and glutathione-peroxidase activity and high platelet lipid peroxidation levels in malaria patients, when compared to those of healthy subjects. Specific IgG binds to platelet-bound malaria antigen through the Fab portion of the immunoglobulin molecule.
The fall of platelet count is independent of age, duration of illness, spleen size, and parasite count.
| Conclusions|| |
Low platelet counts observed in the course of malaria illness are transient and may not necessarily have prognostic implications or platelet infusions more so with the relatively benign course in P. vivax malaria. 72% of cases with malaria had thrombocytopenia which is independent of duration of illness, spleen size, and age. Recovery of the platelets seemed to be correlated only with the recovery from the illness [Table 3].
| References|| |
|1.||Murray CJ, Rosenfeld LC, Lim SS, Andrews KG, Foreman KJ, Haring D, et al. Global malaria mortality between 1980 and 2010: A systematic analysis. Lancet 2012;379:413-31. |
|2.||Gallup JL, Sachs JD. The economic burden of malaria. Am J Trop Med Hyg 2001;64:85-96. |
|3.||Jadhav UM, Patkar VS, Kadam NN. Thrombocytopenia in malaria-correlation with type and severity of malaria. J Assoc Physicians India 2004;52:615-8. |
|4.||Lacerda MV, Mourão MP, Coelho HC, Santos JB. Thrombocytopenia in malaria: Who cares? Mem Inst Oswaldo Cruz 2011;106:52-63. |
|5.||Bhandary N, Vikram GS, Shetty H. Thrombocytopenia in Malaria: A clinical study. Biomed Res 2011;22:489-91. |
|6.||Makkar RP, Mukhopadhyay S, Monga A, Monga A, Gupta AK. Plasmodium vivax malaria presenting with severe thrombocytopenia. Braz J Infect Dis 2002;6:263-5. |
|7.||Common terminology criteria for adverse events v 3.0 (CTCAE V.3.0). Available from: http://www.ctep.cancer.gov./reporting/ctc.html. [Last accessed on 2012 Aug 05]. |
|8.||Skudowitz RB, Katz J, Lurie A, Levin J, Metz J. Mechanisms of thrombocytopenia in malignant tertian malaria. Br Med J 1973;2:515-8. |
|9.||Lacerda MV, Mourão MP, Alexandre MA, Siqueira AM, Magalhães BM, Martinez-Espinosa FE, et al. Understanding the clinical spectrum of complicated Plasmodium vivax malaria: A systematic review on the contributions of the Brazilian literature. Malar J 2012;11:12. |
|10.||Abro AH, Saleh AA, Abdou AS, Ustadi AM, Shuri HM, Seliem RM. Thrombocytopenia in adults with acute malaria. RMJ 2009;34:170-2. |
|11.||Kakar A, Bhoi S, Prakash V, Kakar S. Profound thrombocytopenia in Plasmodium vivax malaria. Diagn Microbiol Infect Dis 1999;35:243-4. |
|12.||Fajardo LF, Tallent C. Malaria parasites within human platelets. JAMA 1974;229:1205. |
|13.||Kelton JG, Keystone J, Moore J, Denomme G, Tozman E, Glynn M, et al. Immune-mediated thrombocytopenia of malaria. J Clin Invest 1983;71:832-6. |
|14.||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. |
|15.||Yamaguchi S, Kubota T, Yamagishi T, Okamoto K, Izumi T, Takada M, et al. Severe thrombocytopenia suggesting immunological mechanisms in two cases of vivax malaria. Am J Hematol 1997;56:183-6. |
[Table 1], [Table 2], [Table 3]