Study of thrombocytopenia in patients of malaria.

BACKGROUND: Malaria is a Protozoal disease caused by infection with parasites of the genus Plasmodium and transmitted to man by certain species of infected female Anopheline mosquito. In 2008 there were 1.52 million cases of malaria in India, out of which 0.76 million case of Plasmodium falciparum, comprising 50% of total malaria cases. There were 924 deaths from malaria. Hematological abnormalities have been observed in patients with malaria, with anemia, and thrombocytopenia being the most common.
MATERIALS AND METHODS: We conducted this study to find out the frequency and the degree of thrombocytopenia in patients with malaria. In our study, 230 patients with malaria positive were investigated with platelet count.
RESULTS: In the study group of 230 patients: 130 (56.51%) were positive for Plasmodium vivax, 90 (39.13%) were positive for P. falciparum and 10 (4.34%) had mixed infection with both P. vivax and P. falciparum. Out of 130 cases detected with vivax malaria, 100 cases had thrombocytopenia. Out of 90 cases detected with falciparum malaria, 70 cases had thrombocytopenia. Among 10 cases of mixed infection, 9 cases had thrombocytopenia.
CONCLUSIONS: Presence of thrombocytopenia in a patient with acute febrile illness in the tropics increases the possibility of malaria. The above finding can have therapeutic implications in context of avoiding unnecessary platelet infusion in malaria patients.

INTRODUCTION

Malaria is a Protozoal disease caused by infection with parasites of the genus Plasmodium and transmitted to man by certain species of infected female Anopheline mosquito. Five species of Plasmodium (Plasmodium vivax, Plasmodium falciparum, Plasmodium malariae, Plasmodium ovale, and Plasmodium knowlesi) cause malaria in humans.

In 2008, there were an estimated 243 million cases of malaria world-wide. A vast majority, about 85% were in African Region, followed by the South-East Asia Region (10%) and East Mediterranean (4%). Malaria accounts for an estimated 863,000 deaths, of which 89% were in African Region followed by East Mediterranean (6%) and South-East Asia Region (5%).[1] In India about 27% population lives in malaria high transmission area (more than 1 case per 1000 population) and 58% in low transmission area.[2] In 2008 there were 1.52 million cases of malaria in India, out of which 0.76 million case of P. falciparum, comprising 50% of total malaria cases. There were 924 deaths from malaria.[3]

A typical attack of malaria comprises three distinct stages: Cold stage, hot stage and sweating stage. The clinical features of malaria vary from mild to severe, and complicated, according to the species of parasite present, the patient's state of immunity, the intensity of infection and also the presence of concomitant conditions such as malnutrition and other diseases. Malaria parasite affects multiple organs of the body such as liver, spleen, brain, gastro intestinal tract, gall bladder, pancreas, blood vessels and placenta. Hence the clinical picture could be of wide spectrum ranging from simple malaise to life threatening central nervous symptoms like coma. Hematological abnormalities have been observed in patients with malaria, with anemia, and thrombocytopenia being the most common.[45]

A number of observational studies have confirmed the association of thrombocytopenia to malaria. Both non-immunological as well as immunological destruction of platelets have been implicated in causing thrombocytopenia. The speculated mechanisms are coagulation disturbances, sequestration in spleen, antibody mediated platelet destruction, oxidative stress, and the role of platelets as cofactors in triggering severe malaria. Abnormalities in platelet structure and function have been described as a consequence of malaria, and in rare instances platelets can be invaded by malaria parasites.[678] We conducted this study to find out the frequency and the degree of thrombocytopenia in patients with malaria.

MATERIALS AND METHODS

The blood investigations were carried out in ESIC Model Hospital, Indore, Madhya Pradesh (central part of India) to those patients who were referred to pathology laboratory for malaria test from various departments especially, from internal medicine and pediatrics. Written consent had been taken from the patients. This prospective study was carried out from 01/01/2007 to 31/12/2012. A total 230 patients were included for studies that were found the positive for malaria parasite. Malaria test was carried out by thin and thick smear examination. Thin smear was stained by Leishmen stain and thick smear was stained by field stain. In field stain polychromated methylene blue and eosin stains specifically to basophilic and acidophilic cellular elements to demonstrate blood cells and hemoparasites. All patients undergone for complete blood count by “ABX Pentra Df 120” a fully automated hematology analyzer by Horiba. Data were analyzed by SPSS-20 method. Grading of thrombocytopenia was carried out according to NCI Common Terminology Criteria for Adverse Events Version 3.0.[9] According to that patients with thrombocytopenia have been divided into following five grades:

Grade 0: With in normal limit, platelet count 150,000 or above.

Grade I: Platelet count between 75,000 and 150,000.

Grade II: Platelet count between 50,000 and 75,000.

Grade III: Platelet count between 25,000 and 50,000.

Grade IV: Platelet count less than 25,000.

RESULTS

In our study, 230 patients with malaria positive were investigated with platelet count. Out of 230 patients 150 (65.22%) were males and 80 (34.78%) were female. Age of patients was between 1 year and 60 years with majority of the patients between 15 years and 40 years of age (comprising about 56%). A total 63 (27.39%) patients were belonging to pediatric age group [Table 1]. Mean hemoglobin value was 12.0 ± 2.1 g% (ranging from 6.1 g% to 15.2 g%) and mean white blood cell count was 12,000 ± 1300/cumm (ranging from 2,800 to 19,400/cumm). Mean platelet count was 151,000 ± 50,000/cumm (ranging from 11,000 to 313,000/cumm). All the patients had fever (100%) at the time of presentation, followed by weakness (95%), nausea (90%), vomiting (86%), anorexia (80%) and diarrhea (05%). Most common sign was anemia (80%) followed by splenomegaly (20%), jaundice (10%), and hepatomegaly (02%). One patient was having cerebral malaria. The spontaneous bleeding and mortality was not seen [Table 2].

Table 1

Age and sex distribution of study groups

Table 2

Frequency of clinical features in patients with malaria

In the study group of 230 patients: 130 (56.51%) were positive for P. vivax, 90 (39.13%) were positive for P. falciparum and 10 (4.34%) had mixed infection with both P. vivax and falciparum. Out of 130 cases detected with vivax malaria, 100 cases had thrombocytopenia, 30 (13.04%) cases had normal platelet count. 20 (8.69%) cases had Grade I thrombocytopenia, 25 (10.86%) cases had Grade II thrombocytopenia, 40 (17.39%) cases had Grade III thrombocytopenia and 15 (6.51%) cases had Grade IV thrombocytopenia. Out of 90 cases detected with falciparum malaria, 70 cases had thrombocytopenia, 20 (8.69%) cases had normal platelet count, 15 (6.51%) cases had Grade I thrombocytopenia, 20 (8.69%) cases had Grade II thrombocytopenia, 35 (15.17%) cases had Grade III thrombocytopenia and no patient was detected Grade IV thrombocytopenia. Among 10 cases of mixed infection, 9 cases had thrombocytopenia, 1 (0.43%) case had normal platelet count, 3 (1.30%) cases had Grade I thrombocytopenia, 2 cases had Grade II thrombocytopenia, 3 (1.30%) cases had Grade III thrombocytopenia and 1 (0.43%) case had Grade IV thrombocytopenia.

DISCUSSION

Malaria caused by P. vivax and P. falciparum is endemic in many parts of India. Malaria affects almost all blood components and is a true hematological disease. Thrombocytopenia and anemia are the most frequently malaria associated hematological complications. In endemic areas malaria has been reported as the major cause of low platelet counts. This is so characteristic of malaria, that in some places, it is used as an indicator of malaria in patients presenting with fever. Platelets count of less than 150,000/cumm increases the likelihood of malaria 12-15 times.[101112]

P. vivax was the common species in our study, though many of the patients who were included in our study had infection with P. falciparum (39.13%) and mixed infection (4.34%). Faseela et al.,[7] in her study found similar results. In our study, thrombocytopenia was seen in 78% cases. Colonel et al.,[13] reported thrombocytopenia in 72% of patients with malaria infection. Jamal et al.,[14] in their study on pediatric patient have reported low platelet count in 72% of the patients with malaria infection. However, few studies reported slightly lower incidence of thrombocytopenia like 40%[10] and 58.97%.[15]

Exact mechanism of thrombocytopenia in malaria is unknown. Fajardo and Tallent demonstrated P. vivax within platelets and suggested a direct lytic effect of the parasite on the platelets.[16] Both non-immunological destruction as well as immune mechanism[6] involving specific platelet associated IgG antibodies that bind directly to malarial antigen in the platelets have been recently reported to play a role in the lysis of platelets.[17] Oxidative stress damage of platelets 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.[18] Decreased thrombopoiesis has been ruled out, because platelet forming megakaryocytes in the marrow are usually normal or increased.[10181920] A good tolerance of low platelet count is well-known in malaria. This could be explained by platelet activation and an enhanced agreeability.[12] The hyperactive platelets may enhance hemostatic responses and that is why bleeding episodes are very rare in acute malarial infections, despite significant thrombocytopenia.[21]

In our study, we found more significant thrombocytopenia in P. vivax malaria. More cases of thrombocytopenia in vivax malaria infection may attribute to possible development of a new genotype of P. vivax.[18] Recent studies have shown that thrombocytopenia is equally or even more common in P. vivax malaria contrary to the popular belief that it may be observed in P. falciparum malaria.[22232425262728] More recent data in India has shown how thrombocytopenia exhibited a heightened frequency and severity among patients with P. vivax infections.[29] Recent studies conducted from the Indian subcontinent have found significant thrombocytopenia in P. vivax malaria.[3031] Studies from Qatar and Venezuela had shown the similar results.[3233]

There is no matched control group. This is one of the limitations of this study.

CONCLUSION

Higher frequency of mild to severe thrombocytopenia was observed in-patients suffering from malaria. The above finding can have therapeutic implications in context of avoiding unnecessary platelet infusion in malaria patients. Presence of thrombocytopenia in a patient with acute febrile illness in the tropics increases the possibility of malaria. This may be used in addition to the clinical and microscopic parameters to heighten the suspicion of this disease and prompt initiation of the treatment.