Association of thrombocytopenia with splenomegaly in malaria patients in East Kalimantan: A cross-sectional, retrospective study

Introduction

Malaria is still a serious health problem in Indonesia. The 2007 and 2013 Basic Health Surveys of the Health Ministry show that the prevalence of malaria in Indonesia increased from 2.9% to 6.0%¹.

Data from the East Kalimantan Provincial Health Office indicated that there were 7,045 cases of malaria in 2010. This number fluctuated in the following years, with 3,021 cases in 2011, 9,966 cases in 2012 and 2,603 cases in 2013. In terms of Annual Parasitic Incidence (API), in 2014 East Kalimantan was still above the national average with an API of 2,04 per 1000 population, leading to it being categorized as a low cumulative incidence area².

One common finding in malaria is decreased platelet count or so-called thrombocytopenia. This laboratory finding is often confused with other infectious diseases, especially dengue infection in which thrombocytopenia is a major diagnostic parameter. There are several studies that demonstrate thrombocytopenia in malaria patients^3–5, and this is found in both infection with Plasmodium falciparum and Plasmodium vivax. The results from our previous study demonstrated that from 1041 malaria cases in East Kalimantan, 85% presented with thrombocytopenia of varying degrees⁴. Therefore, thrombocytopenia has been suggested as one important diagnostic parameter in malaria. The mechanism of thrombocytopenia in malaria is still unclear. Several theories, such as mechanical trapping of thrombocytes inside the spleen and immune response that attacks thrombocytes, has been proposed⁵. A study by Coelho et al. found that platelet phagocytosis may contribute to thrombocytopenia in vivax malaria⁶.

Splenomegaly is also one common clinical finding in malaria patients. The spleen is part of the reticuloendothelial system, which becomes active in order to get rid of plasmodium-infected erythrocytes. Splenomegaly can also contribute to increased destruction of thrombocytes due to mechanical trapping. Therefore, the aim of the present study was to determine the association of thrombocytopenia with splenomegaly in malaria patients in East Kalimantan.

Methods

Results

Our study identified a total of 215 malaria patients from January 2015 to July 2018 from four hospitals in East Kalimantan. There were 87.9% (189/215) male and 12.1% (26/215) female patients (Table 1).

The association of thrombocytopenia with splenomegaly in malaria patients shown in Table 2. There were 11 patients with splenomegaly and 204 patients without splenomegaly. There was no association between the presence of splenomegaly and thrombocytopenia in these malaria patients (p=0.661).

Discussion

We found that the incidence of malaria was higher in males than females in this group of patients, and the parasite infecting the majority of patients was Plasmodium vivax (43.2%). This study found that thrombocytopenia affected the majority of malaria patients; thrombocytopenia occurred in 87% of patients, with moderate thrombocytopenia (43.8%) as the majority. This result is in concordance with another study by Arif et al., in India, that found that 79% of patients had moderate thrombocytopenia⁷, while Ansari et al. found 69.18%⁸. In the present study, the degree of thrombocytopenia classified to mild, moderate and severe was 18.2%, 43.8%, 33.0%, respectively. If we compare to study of Arif et al. that found 33.96%, 51.15% and 14.89%, respectively, we find that the moderate thrombocytopenia was the highest percentage in both studies⁷.

A study by Hanson et al. in Vietnam found that thrombocytopenia was a marker of disease severity in adults with Plasmodium falciparum infection, but has limited utility in prognostication, triage and management⁹. On the other hand, Rao et al. in India found that severe thrombocytopenia showed positive correlation with complicated malaria and become a good predictor for poor prognosis¹⁰. Thrombocyte has an important role in haemostasis. However, study by Abro et al. demonstrated that malaria patients with thrombocytopenia rarely presented with any bleeding manifestations even with platelet count as low as 9,000/μL¹¹.

Indeed, splenomegaly is a hallmark of malaria, but the result of this study found that only 11 patients (5.1%) showed splenomegaly. In India, Gupta et al. found that only 20% malaria patients had splenomegaly, but there are no information about thrombocyte count in those malaria patients with splenomegaly¹².

In our study, we describe the thrombocyte count in malaria patients with splenomegaly. We found that there was no association between thrombocytopenia with splenomegaly (p=0.611). Therefore, we propose that thrombocytopenia is not caused by the mechanical trapping of thrombocytes in the spleen. This result suggests another mechanism of thrombocytopenia that involves immune process, as proposed by Coelhoe et al. in 2013⁶. Until now, definitive mechanism of thrombocytopenia in malaria is still unclear. However, some factors that contribute to thrombocytopenia have been reported, such as decreased thrombopoiesis, peripheral destruction induced by P. falciparum and disseminated intravascular coagulation¹¹.

This study has its limitations. Different types of automatic haematology analysers were used in the hospitals and this might contribute to variations in thrombocyte count. Therefore, we suggest the use of a single haematology analyser across hospitals to improve accuracy. In addition, we did not exclude other causes of thrombocytopenia that could coexist with malaria infection, such as viral infection and autoimmune diseases, which would be required to further validate our findings. Finally, the examination of splenomegaly was conducted by different physicians, which might contribute to subjective factors in determining splenomegaly, such as physician’s expertise and thoroughness, especially in cases with minor or subclinical splenomegaly.

Overall, we conclude that splenomegaly, which was a rare clinical finding in this set of malaria patients, was not associated with thrombocytopenia.

Data availability

F1000Research: Dataset 1. Data retrieved from the medical records of malaria patients in East Kalimantan, Indonesia, including age, gender, type of Plasmodium, thrombocyte count, and presence of splenomegaly, https://doi.org/10.5256/f1000research.16606.d225124¹³