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 Table of Contents  
Year : 2021  |  Volume : 11  |  Issue : 1  |  Page : 46-48  

Pancytopenia with hemophagocytic lymphohistiocytosis in Plasmodium falciparum: A unusual presentation

1 Cell Biology Laboratory and Malaria Parasite Bank, ICMR-National Institute of Malaria Research, Ministry of Health and Family Welfare, New Delhi, India
2 Department of Microbiology, VMMC and Safdarjung Hospital, New Delhi, India
3 Department of Pediatrics, VMMC and Safdarjung Hospital, New Delhi, India

Date of Submission31-Mar-2020
Date of Acceptance30-Sep-2020
Date of Web Publication13-May-2021

Correspondence Address:
Shyam Sundar Meena
Department of Pediatrics, VMMC and Safdarjung Hospital, New Delhi - 110 029
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/tp.TP_34_20

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Hematological manifestations such as anemia and thrombocytopenia are known complications in malaria. Here, we report two cases presented as pancytopenia with hepatosplenomegaly and initial diagnosis kept as hematological malignancy like leukemia but later on its diagnosed as malaria-associated hemophagocytic lymphohistiocytosis which is a rare entity. The aim of this report is to draw the attention of physicians, especially in tropical countries such as India and Sub-Saharan nations to keep in mind this uncommon presentation of malaria, though the exact pathophysiological mechanism still remains obscure.

Keywords: hemophagocytic lymphohistiocytosis, malaria, pancytopenia

How to cite this article:
Chaudhry S, Arya A, Matlani M, Singh V, Meena SS. Pancytopenia with hemophagocytic lymphohistiocytosis in Plasmodium falciparum: A unusual presentation. Trop Parasitol 2021;11:46-8

How to cite this URL:
Chaudhry S, Arya A, Matlani M, Singh V, Meena SS. Pancytopenia with hemophagocytic lymphohistiocytosis in Plasmodium falciparum: A unusual presentation. Trop Parasitol [serial online] 2021 [cited 2023 Feb 4];11:46-8. Available from: https://www.tropicalparasitology.org/text.asp?2021/11/1/46/315930

   Introduction Top

Anemia is commonly reported in Plasmodium falciparum (Pf) malaria infection cases and majorly responsible for mortality as well as directly or indirectly responsible for morbidity in endemic areas for children and pregnant women.[1],[2] Many different types of pathophysiological mechanisms of severe anemia (hemoglobin concentration of <5 g/dL) involved in Pf malaria infection and least understood. Here, we are reporting the two cases presented as pancytopenia with hepatosplenomegaly.

   Case Report Top

Index case 1

A 6-year-old female child admitted to pediatrics emergency with high-grade fever without chills and rigors past 7 days, progressive pallor past 5 days, and bluish spots over the whole body for 2 days. In detailed history, she had a fever without any symptoms of vomiting, jaundice, or hematuria. There was no history oft previous hospitalization. At admission, a child was lethargic, febrile (102°F), severely pallor, petechial rashes, cervical lymphadenopathy, and body pain (paroxysms) with the features of shock. In the systemic examination, hepatosplenomegaly in per abdomen examination and respiratory, cardiovascular finding (except hemic murmur) were within normal limits. In the central nervous system examination, she was in altered sensorium without meningeal signs or focal deficits. Initially, we kept as lymphoreticular malignancy with febrile neutropenia and start supportive as well as symptomatic treatment and malignancy workup planed. After stabilization, bone marrow aspiration as well as biopsy was done. Bone marrow aspiration and biopsy revealed hemophagocytosis [Figure 1]. Due to persistent high-grade fever, fever workup, including rapid malarial antigen test, peripheral smear for malaria parasite, serology for typhoid and rickettsial infection, blood culture, etc., as well as a supportive workup for hemophagocytic lymphohistiocytosis (HLH) (liver transaminases, lactate dehydrogenase, triglyceride, serum ferritin, and fibrinogen) were sent [Table 1]. In peripheral smear, malaria parasite was seen as trophozoites for Pf malaria and revised the diagnosis as malaria-associated secondary HLH (sHLH) and the anti-malarial drug was started. On 3rd day of antimalarial therapy, the child fever responded and 5th-day fever was subsided and discharged the child.
Figure 1: Photomicrograph showing hemophagocytosis in bone marrow

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Table 1: Laboratory parameters of the malarial cases

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Case 2

There was another 11-year-old male child admitted to pediatrics emergency with the complaint of fever (15 days), red color urine, black terry color stool, and nasal bleeding past 3 days for whom peripheral smear for Pf malaria came out to be positive. Hematological as well other laboratory parameters were suggestive as HLH and child respond to anti-malarial therapy.

In both cases, sHLH is the cause of pancytopenia. After anti-malarial therapy, both children responded very well and hematological parameters starting to improve within a week of therapy [Table 1]. All these cases are in regular follow-up and till the last follow-up at 6 weeks of discharge there both children were doing well and were hematological parameters also improved.

   Discussion Top

Pancytopenia is mainly identified by decreased level of red blood cell, white blood cell, and platelet count is called pancytopenia. Pancytopenia caused by the sequestration of peripheral tissue and bone marrow destruction.[3] In both cases, sHLH is the cause of pancytopenia. HLH is present in two forms one is primary (familial HLH) and the second one is sHLH. There are several viruses which cause metabolic disease, malignancies, and severe infection associated with HLH. In which severe infection associated is caused by the EpsteinBarr virus. Few cases have been published with malaria and sHLH.[4]

Strong immunological activation of cytokines and other factors activation of T lymphocytes and macrophages are mainly responsible for severe infections of HLH. Increased levels of cytokines mainly tumor necrosis factor alpha (TNFα) and interleukin-18 have been studied in malaria infection cases also could cause HLH. High level of TNFα decreases the amount of antibody coating, which is necessary of phagocytosis and also may responsible for the release of oxygen free radical by causing oxidative cell damage.[5] In the presence of malaria, parasite HLH continues individually by activating of cytokine cascade.

For the treatment of sHLH includes, treat influencing factors and the use of immunosuppressant drugs, steroids, and intravenous immunoglobulin (IVG). For immunodeficient, autoimmune, and sepsis patient, polyclonal IVG antibodies are used.[6] Several studies showed that malaria-HLH patients treated by anti-malaria drugs only without the use of any immunosuppressive drug and other steroids.[7],[8]

In this case, the report highlights the unusual presentation of malaria. Malaria-associated HLH is very rare and few studies have been reported related to this disease, so it is important to assess the cases and history of sHLH, especially in tropical countries like India.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Haldar K, Mohandas N. Malaria, erythrocytic infection, and anemia. Hematology Am Soc Hematol Educ Program 2009;1:87-93.  Back to cited text no. 1
Calis JC, Phiri KS, Faragher EB, Brabin BJ, Bates I, Cuevas LE, et al. Severe anemia in Malawian children. The New Engl J Med Orig 2008;358:888-99.  Back to cited text no. 2
Gudina EK, Amare H, Benti K, Ibrahim S, Mekonnen G. Pancytopenia of unknown cause in adult patients admitted to a tertiary hospital in Ethiopia: Case series. Ethiop J Health Sci 2018;28:375-82.  Back to cited text no. 3
Bhagat M, Kanhere S, Kadakia P, Phadke V, George R, Chaudhari K. Haemophagocytic lymphohistiocytosis: A cause of unresponsive malaria in a 5-year-old girl. Paediatr Int Child Health 2015;35:333-6.  Back to cited text no. 4
Ohnishi K, Mitsui K, Komiya N, Iwasaki N, Akashi A, Hamabe Y. Falciparum malaria with hemophagocytic syndrome. Am J Trop Med Hyg 2007;76:1016-8.  Back to cited text no. 5
Ramos-Casals M, Brito-Zerón P, López-Guillermo A, Khamashta MA, Bosch X. Adult haemophagocytic syndrome. Lancet 2014;383:1503-16.  Back to cited text no. 6
Vinoth PN, Thomas KA, Selvan SM, Suman DF, Scott JX. Hemophagocytic syndrome associated with Plasmodium falciparum infection. Indian J Pathol Microbiol 2011;54:594-6.  Back to cited text no. 7
[PUBMED]  [Full text]  
Kumar TR, Baghmar S. Plasmodium vivax malaria complicated by neurological, jaundice and haemophagocytic syndrome. J Nepal Paediatr Soc 2010;30:168-70.  Back to cited text no. 8


  [Figure 1]

  [Table 1]

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