A case of Plasmodium vivax malaria associated with severe autoimmune hemolytic anaemia


Anemia in malaria is multifactorial. Autoimmune hemolysis is an extremely rare cause of anemia in malaria and more so in vivax malaria. A 35-year-old female presented to us with fever and anemia. She was diagnosed as vivax malaria with autoimmune hemolytc anemia by a positive Direct Coomb’s test. We treated her with antimalarial durgs, corticosteroids, and transfused her with the least incompatible blood. The patient recovered and was discharged. Hence, we suggest that autoimmune hemolysis be considered an important cause of anemia in Plasmodium vivax (P. vivax) malaria.

Keywords: Anemia, autoimmune hemolytic anemia, coomb′s test, malaria

How to cite this article:
Singh D, Gupta V, Acharya S, Mahajan SN, Verma A. A case of Plasmodium vivax malaria associated with severe autoimmune hemolytic anaemia. Ann Trop Med Public Health 2012;5:133-6
How to cite this URL:
Singh D, Gupta V, Acharya S, Mahajan SN, Verma A. A case of Plasmodium vivax malaria associated with severe autoimmune hemolytic anaemia. Ann Trop Med Public Health [serial online] 2012 [cited 2021 Mar 4];5:133-6. Available from: https://www.atmph.org/text.asp?2012/5/2/133/95972

Malaria is a protozoal disease that still remains a challenge to clinicians worldwide due to its multisystem involvement, protean manifestations, and devastating consequences. Despite all the advances in the field of infectious diseases mankind has still found it difficult to control the menace of malaria particularly in the tropical countries.

In 2008, there were 247 million cases of malaria and nearly one million deaths-mostly among children living in Africa. [1] Malaria has been a potent force to reckon with even in South East Asia. It is estimated that the number of cases in the Region should be approximately 20 million per year, while the number of deaths should be 100,000. [2] Among the WHO regions, the South-East Asia Region has a malaria burden second only to Africa. [2] India reported the highest number of malaria cases in the Region and the second highest number of deaths due to malaria. [2] Another often underestimated fact about the epidemiology of malaria is the enormous economic burden it imposes on the developing nations which includes both personal and public expenditures on prevention and treatment. It decreases gross domestic product by as much as 1.3% in countries with high disease rates. [1]

The complications associated with malaria are an important factor contributing to the burden of malaria. Anemia is one of the most significant and common complications associated with malaria. Anemia in this infection is caused by a variety of pathophysiologic mechanisms, and in areas where malaria infection is endemic, co-morbidities like other parasitic infestations, iron, folate, and vitamin B 12 deficiency, deficiency of other nutrients, and anemia, which is aggravated by anti-malarial drugs both through immune and non-immune mechanisms, are important considerations. The pathogenesis of anemia in malaria is multifactorial [Table 1].

Table 1: Showing the pathophysiological causes of anemia in malarial infection[3],[4],[5]

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The role of autoimmune hemolysis in malaria is unresolved as well as rare/uncommon. [3],[4],[5] The burden of autoimmune hemolysis has traditionally been very high in falciparum malaria, but and its contribution to anemia in vivax malaria still remains an enigma to clinicians. Thus, to reduce the overall burden of morbidity and mortality of malaria a clinician needs to be vigilant and acquainted even with the rarest of rare pathophysiological aspects of various complications of malaria.

We present a case of Plasmodium vivax malaria associated with severe acute autoimmune hemolytic anemia who presented to our hospital.

Case Report

A 35-year-old female patient presented with a H/O fever with chills since 7 days with yellowish discoloration of eyes and urine since 4 days with breathlessness and fatigability on minimal exertion since 2 days. The patient had been investigated by a private practitioner and was diagnosed as vivax malaria on peripheral smear and treated with Tablet chloroquine. The patient was referred to our hospital as her fever did not subside; she became breathless and yellowish discoloration of her eyes increased.

On admission, patient was febrile, conscious, and oriented. Her pulse was 96/min BP was 100/70 mm of Hg and respiratory rate was 30/min. The patient was icteric, pale with minimal edema feet. Her JVP was normal. On systemic examination, cardiovascular system and respiratory system were found to be normal. On abdomen examination, spleen was palpable 4 cm below the left costal margin. No hepatomegaly or lymphadenopathy was evident. We reinvestigated her and compared her reports with the investigations done 3 days prior to admission.

We kept the diagnosis as vivax malaria with hemolytic anemia and started the patient on injection artesunate and capsule doxycycline and planned blood transfusion for her. Her blood group was AB+ve. We got an intimation from our blood bank that her blood samples sent for cross match were not compatible with any AB+ve blood bag/O-ve blood bag. We asked them to perform Direct Coomb’s test which was positive [Figure 1]. So the cause of anemia was revised to autoimmune hemolytic anemia. We decided to start injection methyl prednisolone 500 mg daily for 3 days and at the same time transfused her with O negative blood which showed least incompatibility with her blood group. She was transfused 4 units of O negative whole blood with a full course of anti-malarial durgs and also oral tablet prednisone 40 mg/d till her stay in hospital after injectable steroids. The patient recovered and on discharge after 10 days of hospitalization her hemoglobin was 9 gm/dl. Serum bilirubin returned to normal, reticulocyte count came down to 1%, and serum LDH was 140 U/L. She was discharged on tablet prednisone in tapering doses over 2 weeks along with folic acid. [Table 2] shows the comparison of laboratory investigations done 3 days prior to admission in our institute and on admission in our institute [Table 2]. [6]

Figure 1: Direct antiglobulin test (DAGT) showing Grade 4+ (positive) reaction (tube no.6); with DiaMed-ID Micro Typing gel cards (LISS/ Coomb’s cards). The gel card contains Anti Ig G and C3d.

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Table 2: Comparison of lab reports within a span of 3 days

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Anemia has been a common accompaniment of malarial fever. P. falciparum-induced anemia is considered more frequent and more severe as compared to anemia caused by other plasmodium species. [7] However, recent evidence shows that P. vivax-induced anemia is more frequent and more severe. [8],[9],[10] According to various theories factors contributing to anemia in vivax malaria are same as those mentioned in [Table 1] but the role of immune-mediated hemolysis has been better attributed to anemia in falciparum malaria. [11]

In autoimmune hemolytic anemia, antibodies are directed against antigens on the surface of RBC. Lab features of autoimmune hemolytic anemia are shown in [Table 3].

Table 3: Showing laboratory features of autoimmune haemolytic anemia[12],[13],[14],[15]

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The direct Coomb’s test demonstrates the presence of antibodies or complement on the surface of RBCs. In our case, all the above criteria that help us to diagnose AIHA were positive except S. haptoglobin which was not performed. The Coomb’s reagent used was a broad spectrum reagent. The treatment of AIHA is given in [Table 4].

Table 4: Treatment options in AIHA[15],[16]

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In our case, we used the least incompatible blood unit for transfusion along with prednisolone; injectable initially and then orally as the patient improved.

However, the role of antibodies (i.e. Coomb’s +ve hemolysis) in anemia associated with malaria is unresolved. [4],[5],[17] The majority of studies till date do not show increased RBC immunoglobulin binding in malaria, but in the presence of a lowered recognition threshold for splenic clearance these immunoglobulins might be difficult to detect. The splenic threshold is lowered because of antibody coating or reduced RBC deformability. [18],[19] This probably explains why positive results in DAGT have been found in only a minority of patients with malaria where immunoglobulin or complement mediated immune complex formation leads to hemolysis in malaria.

The extent of hemolysis in P. falciparum malaria is much greater as compared to other species and the combined mechanism with immune-mediated hemolysis has been suggested. But only a single case of P. vivax-mediated autoimmune hemolytic anemia with a positive DAGT has been reported.

This second case of vivax associated AIHA highlights the fact that although rare, autoimmune hemolysis can be one of the important and often overlooked factors contributing to anemia in vivax malaria. Also AIHA is probably the only indication in malaria where corticosteroids have a beneficial effect. A high degree of suspicion along with rapid and intelligent interpretation of investigations can go a long way in treating life-threatening hemolysis and thus reduce morbidity and mortality due to vivax malaria.

1. Malaria Fact Sheet 2010 by WHO.
2. Estimation of Malaria Disease Burden in India Report of an Informal Consultative Meeting New Delhi, India, 21-23 Nov 2007 convened by WHO Regional office South East Asia.
3. Sina B. Focus on plasmodium vivax. Trends Parasitol 2002;18:287-9.
4. Facer CA, Bray RS, Brown J. Direct Coomb’s antiglobulin reactions in Gambian children with p.falciparum malaria. I. Incidence and class specificity. Clin Exp Immunol 1979;35:119-27.
5. Facer CA. Direct Coomb’s antiglobulin reactions in Gambian children with Plasmodium falciparum malaria. II. Specificity of of erythrocyte bound IgG. Clin Exp Immunol 1980;39:279-88.
6. Malaria rapid Diagnostic Performance: Results of WHO products testing of malaria RDTs. 2008:17.
7. Severe falciparum malaria. World Health Organization, Communicable Diseases Cluster. Trans R Soc Trop Med Hyg 2000;94(suppl 1):S1-90.
8. Selvam R, Baskaran G: Hematological impairments in recurrent P.Vivax infected patients. Jpn J Med Sci Biol 1996;49:151-65.
9. Collins WE, Jeffery GM, Roberts JM. A retrospective examination of anaemia during infection of humans with Plasmodium vivax. Am J Trop Med Hyg 2003;68:410-2.
10. Song HH, O SO, Kim SH, Moon SH, Kim JB, Yoon JW, et al. Clinical features of Plasmodium Vivax malaria. Korean J Intern Med 2003;18:220-4.
11. Drouin J, Rock G, Jolly EE. Plasmodium falciparum malaria mimicking autoimmune haemolytic anaemia during pregnancy. Can Med Assoc J 1985;132:265-7.
12. Dhaliwal G, Cornett PA, Tierney LM Jr. Hemolytic anaemia. Am Fam Physician 2004;69:2599-606.
13. Maedel L, Sommer S. Morphologic Changes in erythrocytes. slides 50,52,66. Chicago: Am Society for Clinical Pathology Press; 1993. p. 4.
14. Marchand A, Galen RS, Van Lente F. The predictive value of serum haptoglobin in haemolytic disease. JAMA 1980;243:1909-11.
15. Hemolytic Anaemias and anaemias due to acute blood loss. Lucio Luzzatto: Harrisson’s Principles of Internal Medicine. 17 th ed. USA: The McGraw Hill Companies, Inc.; 2008. p. 652
16. Autoimmune Hemolytic Anaemia: The Merck Manual’s Online Medical Library. Whitehouse Station, N.J., U.S.A. Available from: http://www.merckmanuals.com. [Last Accessed on 2011 Feb 20].
17. Merry AH, Looareesuwan S, Phillips RE, Chanthavanich P, Supanaranond W, Warrell DA, et al. Evidence against immune hemolysis in falciparum malaria in Thailand. Br J Haematol 1986;64:187-94.
18. Lee SH, Looareesuwan S, Wattanagoon Y, Ho M, Wuthiekanun V, Vilaiwanna N, et al. Antibody dependent red cell removal during P. falciparum malaria: The clearance of red cells sensitised with IgG anti D. Br J Haematol 1989;73:396-402.
19. Ho M, White NJ, Looareesuwan S, Wattanagoon Y, Lee SH, Walport MJ, et al. Splenic Fc receptor function in host defence and anaemia in falciparum malaria. J Infect Dis 1990;161:555-61.

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1755-6783.95972


[Figure 1]


[Table 1], [Table 2], [Table 3], [Table 4]

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