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Journal Home Page www.bbbulletin.org BRITISH BIOMEDICAL BULLETIN

Original Immune Hemolytic in a Patient with vivax

Deepak Nayak M.*, Sushma V. Belurkar and Anna Joseph Amprayil

Department of , Kasturba Medical College-Manipal, Manipal University. Manipal 576104, India

A R T I C L E I N F O A B S T R A C T

Received 14 May. 2014 Received in revised form 06 June. 2014 Accepted 10 June. 2014 The combination of anemia in malarial infestations has been well documented in literature. But an immune developing within days of treatment for malaria Keywords : Plasmodium vivax; has seldom been reported. We present a case of a patient with Hemolytic anemia; vivax malaria who developed severe anemia and on day Jaundice. seven of initiating treatment with ; necessitating

expedient measures. This case highlights the importance, yet under-reported association of Plasmodium vivax malaria and immune-mediated . Corresponding author:Deepak Nayak M. Department of Pathology, Kasturba Medical College-Manipal, Manipal University. Manipal 576104, India . E-mail address: © 2014 British Biomedical Bulletin. All rights reserved [email protected]

Nayak M. et al______ISSN-2347-5447 Introduction Coomb’s test was advised to ascertain an Malaria continues to be an important immune-mediated hemolysis; which showed disease in India. The varied presentations of a weak positivity for direct antibodies. the disease and its diversity in terms of Clinically, the patient was afebrile but pale. hematological manifestations have been well The biochemical tests showed a raised endowed in literature. By and large, anemia unconjugated (6.3mg/dl) which seen in malaria is multifactorial. This confirmed the pre-hepatic hemolytic anemia. anemia ranges from an accelerated red Other investigations showed a high cell removal by the to ineffective count of 7.18%. The glucose-6- . Drug-induced hemolytic phosphate dehydrogenase (G6PD) enzyme anemia is the other dimension to this aspect. assay was normal; although no bite or blister However, the theory of immune-mediated cells were appreciated in the smear. The hemolysis in malaria has gathered the patient received 2 units of packed red blood attention of researchers in recent years. We cells under steroid cover. On the twelfth describe here a rare case report where day, the stabilized and picked immune-mediated hemolysis developed in up. Plasmodium vivax malaria after completing a course of treatment. Discussion

Case Report Anemia in malaria is not an uncommon association. The prevalence of A 16-year old male patient with a anemia depends on many variables such as two-day history of high grade, intermittent age and nutritional status of the patient and with chills presented to the hospital. endemicity. The mechanism of anemia is Peripheral smear and quantitative buffy coat caused by a variety of pathophysiologic (QBC) test showed both schizonts and ring mechanisms which include accelerated RBC forms of Plasmodium vivax malaria parasite. removal by the spleen, obligatory RBC On admission, his hemoglobin was 9.8g/dl destruction at parasite schizogony (due to and count was 40,000/mm 3. The reduced red cell deformation of parasitized peripheral smear did not show hemolysis. and non-parasitized erythrocytes) and As such, a follow up count for ineffective erythropoiesis. 1 The recent thrombocytopenia was advised. He was advancements have shown that a variety of placed on intravenous artesunate for 5 days. cytokine dysregulations are indeed vital Fever subsided on the third day of treatment. participants in inducing and accelerating the A repeat peripheral smear and QBC test pathogenesis of hemolysis in malaria. They were negative for the parasite. The patient include a significant increase in interferon was subsequently discharged. (IFN) gamma, interleukin (IL)-6, tumour However, the patient appeared for necrosis factor (TNF)-alpha, IL-1, hypoxia follow-up on the seventh day and inducing factor (HIF)-1 and decrease in IL- complained of fatigue and mild lumbar pain. 10 and IL-12 levels. 1 Drug-mediated anemia He was re-admitted and his hemoglobin had has also been postulated. However, the suddenly dropped to 6.3g/dl. The peripheral crucial aspect of treatment in malaria is that smear and QBC test performed were the extent of hemolysis is much greater than negative for the parasite. But the smear that seen in other parasite- induced diseases. showed signs of hemolysis; evidenced by Thus, an underlying immune-mediated spherocytes and polychromasia (figure 1). A pathology has been suggested. 2

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There were similar trends in the reported. To the best of our knowledge, present case. The sudden drop in there have been two single case reports of hemoglobin was noted after the treatment association of malaria and autoimmune course was completed; necessitating a hemolysis, from Korea and Canada. 3,5 packed transfusion. The Despite a high degree of prevalence of peripheral smear and QBC test was negative malaria in India, only sporadic case reports for malarial parasite. Hence, a direct parasite have surfaced. 6,7 This scarcity in literature mediated cell could be ruled out. The may be attributed to the rarity of this raised reticulocyte count along with a weak- phenomenon or due to under-recognition of positive direct Coombs’ test point towards this clinical phenomenon. an immune-mediated cell destruction. Also corroborating these laboratory evidences is Conclusion the clinical response after initiating corticosteroid therapy. A run through the Anemia in P. vivax malaria has been literature reveals that a proportion of assigned to a number of aetiologies. Immune patients suffering from malaria develop hemolytic anemia is probably the least immune hemolysis. 3 The reasons for mentioned one. This case is presented here immune hemolysis are multifactorial. The to highlight the importance of identifying mechanisms include: a) antibodies autoimmune hemolysis if a patient with directed against the parasite antigens malaria develops post treatment hemolysis sticking to red cells b) immune complex or persistent anemia. deposition leading to a by-stander hemolysis due to a parasite antigen or drug antibody Authors’ Contributions: complex, or c) due to oxidative damage and Dr. Deepak Nayak M.: Writing the aggregation of red cell anion channel manuscript draft, consultation and protein, subsequent coating of this denatured correspondence. protein by naturally occurring Dr. Sushma Belurkar: Expert followed by their removal by opinion. in the reticuloendothelial system. 4 Dr. Anna Joseph Amprayil: data In addition, increased levels of collection. cytokines, including TNF-alpha can induce macrophages, which, in a hyperactive stage, References may reduce their threshold for the amount of antibody coating needed for . 1. Ghosh K, Ghosh K. Pathogenesis of anemia Other postulated mechanism includes a loss in malaria: A concise review. Parasit Res of complement regulatory proteins CD-55 2007; 101:1463-1469. and CD-59 in parasitized cells; which are 2. Dhaliwal G, Cornett PA, Tierney LM jr. known to protect RBCs from inadvertent Hemolytic anemia. Am Fam Physician 1979; 69:2599-606. complement-mediated lysis. This coupled 3. Drouin J, Rock G, Jolly E. Plasmodium with increased levels of immune complexes falciparum malaria mimicking autoimmune in malarial infection makes RBCs 1 hemolytic anemia during pregnancy. Can susceptible to complement mediated lysis. Med Assoc J 1985; 132. While hemolysis has been reported 4. Turrini F, Gribaldi G, Carta F, Mannu F, in cases of Plasmodium falciparum malaria; Arse P. Mechanism of band-3 oxidation and both immune and non-immune; an clustering in the phagocytosis of association with P. vivax has seldom been Plasmodium falciparum-infected erythro- cytes. Rodex Report 2003; 8:300-303.

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5. Lee S W, Lee S E Chung B H, Hwang T J, 6. Sharma V, Samant R, Hegde A, Bhaja K. Shin H S. A case of Plasmodium vivax Autoimmune hemolysis in malaria: A report malaria associated with autoimmune of three cases. JAPI 2012; 60:129-130. hemolytic anemia. Infect Chemother 2008; 7. Deshpande RH, Kulkarni RV. Cold 40:63-66. agglutinin disease with malaria – a case report. Int J Pharm Bio Sci 2012 3(3): 800 – 803.

Figure 1. Peripheral smear showing sparse red blood cells, spherocytes and polychromasia (Leishman; x200)

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