Autoimmune hemolytic anemia in a patient with Malaria.

Autoimmune Hemolytic Anemia (AIHA), a very infrequent condition which represents a group of disorders in which presence of autoantibodies directed against self-antigens leads to shortened red cell survival. Till date, a very few cases of AIHA in Malaria patients are reported worldwide but still AIHA should be considered a relatively rare cause of anemia in malaria. A 20 year male presented with intermittent fever since seven days and yellowish discoloration of urine and sclera since 5 days. He was transfused three units of blood at a private clinic before one month. On examination, pallor, icterus and spelnomegaly were present. Hemoglobin (Hb) was 3.2 gm% and peripheral smear revealed ring forms of both Plasmodium vivax and Plasmodium falciparum. Serum LDH and Serum billirubin (Indirect and Direct) were high. This patient's blood group was B +ve with positive autocontrol. Indirect Antiglobulin Test (IAT), antibody screening and antibody identification were pan-positive with reaction strength of +4 against each cell. Direct Antiglobulin Test was +4 positive anti IgG and negative with anti C3. He was treated with Artesunate and methylprednisone. Least incompatible, saline washed O Neg and B neg red cells were transfused on the 2(nd) day of starting treatment. Hb was raised to 6.1 gm% on 4(th) day. Patient was discharged on 9th day with Hb 7.0 gm% with oral tapering dose of steroids. In the above case, patient was suffering from high grade malarial parasitemia with co-existing autoimmune RBC destruction by IgG auto-antibodies which led to sudden drop in Hb and rise in serum LDH and indirect billirubin. Least incompatible packed red cells along with antimalarials and steroids led to clinical improvement. So far, one case report each from India, Korea, Canada and Germany and one case series report of three cases from India have been reported. Under-reporting or rarity of this phenomenon may be accountable for this.

Introduction

Autoimmune Hemolytic Anemia represents a group of disorders in which presence of autoantibodies directed against self-antigens leads to red blood cells (RBCs) destruction and ultimately, decreased survival. It is a very infrequent condition, affecting one to three persons per 1,00,000 per year.[1] Anemia occurs in malaria due to invasion and destruction of RBCs by malarial parasite, splenic sequestration and ineffective erythropoiesis.[2] AIHA should be considered a relatively rare cause of anemia in malaria.[3]

Case Report

A 20 year old male patient was admitted at our hospital with chief complaints of intermittent fever with chills since seven days and yellow discoloration of sclera and urine since five days. He was transfused three units of blood at a private clinic for anemia before one month. On Examination, relevant findings were pallor +++, icterus ++ and per abdomen examination showing palpable spleen. On admission, complete blood counts were as follows: Hemoglobin (Hb) 3.2 gm/dL, Mean Corpuscular Volume (MCV) 122 fL, Retic Count 7 %, Total and Differential Count in normal reference range, Platelet count 3.52 lacs/μL. In Peripheral Smear, ring forms of both Plasmodium vivax and P. falciparum were seen with Grade 4 parasitemia. Spherocytes were absent. Other relevant lab findings included Renal Function Tests (RFT): within normal reference range, S. Bilirubin 8.3 mg/dL (Indirect 4.7 mg/dL and Direct 3.6 mg/dL), serum Lactate Dehydrogenase (LDH) 355 U/L, Glucose 6 Phosphate Dehydrogenase (G6PD) enzyme activity: Present, Sickling test: Negative and NESTROFT (Naked Eye Single tube Red Cell Osmotic Fragility Test): Negative.

Blood Bank Investigations: (On admission)

Cell grouping

Serum grouping

This patient’s blood group was determined to be B +ve with positive autocontrol and no auto-clumps with saline. So, fresh sample was obtained which showed the duplicate results as above and further tested as follows:

Indirect Antiglobulin Test (IAT) and Antibody screening with 3 cell panel (DiaMed)

Antibody identification using 11 cell panel (DiaMed) was pan-positive (+4).

Direct Antiglobulin Test (DAT) with Polyspecific and mono-specific Coomb’s sera

Acid Elution of the patient’s sample was performed and the eluate was Pan-positive (+4) in the same 3 cell and 11 cell panels (DiaMed).

On Major Cross Matching, multiple donor units (of the same group and ABO-Rh compatible group) were Grade 4 Incompatible.

These serologic findings are suggestive of auto-antibodies. On 2nd day of admission, Hb dropped further to 1.4 mg/dL.

Patient was treated with intravenous Artesunate (2.4 mg/kg/day). Simultaneously, intravenous Methylprednisone 1 mg/kg/day for five days was started, followed by oral route and dose tapering. On 2nd and 3rd day, patient was transfused one unit O Neg and one unit B Neg Packed Red Cells respectively. Both the units were least incompatible and saline washed with uneventful post-transfusion period. On 4th day, Hb was raised to 6.1 mg/dL and Serum Bilirubin decreased to 4.3 mg/dL suggesting role of antimalarials in clearing parasitemia and steroids in reducing hemolysis by autoantibodies in this case. Patient was discharged on 9th day after admission with Hb 7.0 gm/dL and platelet count 2.5 lacs/μL with tapering dose of oral steroids. On routine follow-up after 15 days of discharge, patient had Hb of 8.1 gm/dL and was asymptomatic throughout this period.

Discussion

Anemia is a frequent association with malaria and usual causes are: destruction of RBCs by parasites, splenic sequestration, dyserythropoiesis, increase in inflammatory cytokines and nutritional deficiency.[2] In the present case, patient was suffering from high grade malarial parasitemia at the time of admission with co-existing autoimmune RBC destruction by IgG auto-antibodies which led to sudden drop in Hb and rise in serum Indirect Bilirubin and LDH.[4] Least incompatible PCV along with antimalarials and steroids led to improvement in this patient as evidenced by increment in Hb and peripheral smear negative for malarial parasite with no rise in temperature after 4th day.[5] So far, one case report each from India, Canada, Korea, Germany and one case series report of three cases have been reported for malaria with AIHA. Under-reporting or rarity of this phenomenon may be accountable for this.[6] The exact mechanism of AIHA in malaria is not well understood but, nevertheless, AIHA should be considered as one of the causes of anemia in malaria.