Patient with AIHA and malaria falciparum infection

AIHA along with malaria infection is a rare condition. AIHA can be classified based on the right temperature to detect autoantibodies that bind to erythrocyte membranes to warm antibodies, cold antibodies, and biphasic antibodies. This condition can occur primary or secondary to lymphoproliferative disease, autoimmune diseases, or haematological malignancies. Tropical infectious diseases related to AIHA are a rare condition and cause problems.

History taking and physical examination show the presence of malaria triad, history of travel to endemic areas, anemic, spasms, jaundice, and laboratory tests that are important to show the condition of hemolysis (increased reticulocytes, hyperbilirubinemia, increased LDH) (Chamnanchanunt et al, 2017). Splenomegaly in patients can be a manifestation of hemolytic anemia due to extramedular hematopoiesis or tropical splenomegaly syndrome in patients living in malaria endemic areas. Hyperbilirubinemia in patients predominantly direct bilirubin which shows obstructive jaundice due to the presence of gall bladder sludge formed from bilirubin precipitation in massive hemolytic anemia.

The patient underwent clinical and laboratory examination for his hemolytic condition during malaria therapy. His condition is consistent with severe falciparum infection due to kidney disorders, malaria algids, and severe anemia. A history of travel to endemic areas supports the cause of severe malaria in patients. Blood smear shows microspherocytes and erythrocyte agglutination, which is in accordance with AIHA. Erythrocyte patients showed positive Coombs test results. In the majority of malaria cases, AIHA occurs in the second week after getting malaria therapy (Chamnanchanunt et al, 2017).

AIHA incidence is estimated at 1: 1,000,000 in adults. Warm antibodies are responsible for 87% of cases and cold antibodies are responsible for 13% of cases. Cold antibodies will agglutinate at 4OC and the agglutination process decreases at body temperature. Primary or idiopathic cold antibodies are commonly found in patients around 70 years old in both sexes, with little predominance in women. Secondary cold antibodies occur in transient and chronic forms. This transient form occurs in Mycoplasma pneumonia infection or infectious mononucleosis, especially in adolescents and young adults. Chronic cold antibodies are usually found in patients over 50 years (Yashovardhan et al, 2015). In patients with AIHA cold agglutinin type in which agglutination outside body temperature and hemolysis processes that do not respond to steroids.

The majority of patients do not have underlying disease, the rest have lymphoproliferative disease including CLL, hairy cell leukemia, lymphoma. Cold antibodies can be physiological or pathological depending on the thermal reactivity of these antibodies. Physiological cold antibodies are often found in healthy adults, reactive at temperatures below body temperature and have titer of less than 64. Pathological cold antibodies have high thermal amplitude and manifest as chronic cold antibody disease or transient acute hemolytic anemia associated with respiratory infections. Cold antibodies are IgM, which at low temperatures react with erythrocytes and bind to C1. Only 1 IgM molecule is needed to bind C1 and initiate the activation of the classical pathway complement. C1 sequentially activates C4 and C2, which are bound to erythrocytes and form the C3 convertase enzyme complex. When the blood returns to warm temperatures in the body, cold agglutinins separate from the cell membrane, but complement activation continues. Regulator proteins convert C3 and C4 bound to erythrocytes to C3d, C3dg, and C4d. The anti-C3d components are polyspecific AHG (anti-C3d and anti-IgG) which show direct Coombs test and are indirect negative (Yashovardhan et al, 2015).

Most malaria patients with AIHA receive immunosuppressive therapy (steroids) in iv or oral form. Patients get methylprednisolone and their hemoglobin improves within 1 week. Other studies have shown spontaneous healing without specific therapy for AIHA. The prednisolone dose for AIHA is 1 mg / kg / day and is tapered off if the hemoglobin value is normal without the sign of hemolysis (Chamnanchanunt et al, 2017).

Anemia is associated with malaria and the most common cause is the destruction of erythrocytes by parasites, splenic sequestration, diseritropoiesis, increased inflammatory cytokines, and nutritional deficiencies. In this case, the patient experienced severe parasitemia together with autoimmune erythrocyte destruction by IgG autoantibodies which caused a sudden decrease in Hb and an increase in indirect bilirubin and serum LDH. Reducing incompatibility and administration of antimalarials and steroids causes improvement in patients with negative Hb and blood smears for malaria parasites without increasing temperature after day 4. Furthermore, case reports in India, Canada, Korea, Germany and 3 reports of malaria cases with AIHA. The mechanism of AIHA in malaria is not well understood, but AIHA needs to be considered as one of the causes of anemia in malaria (Sonani et al, 2017).

AIHA patients with malaria infections need to be distinguished whether the hemolysis process that occurs due to an autoimmune process or the course of malaria. In both diseases massive hemolysis and severe anemia can occur. But in AIHA, the fever that arises is only subfebrile and tends to be mild, whereas in malaria there can be a triad of malaria, which is high fever, chills, and sweating.