We report the case of a thalassemic patient with asymptomatic malaria in which the infection became clinically manifest only after blood transfusion, mimicking a febrile non haemolytic transfusion reaction. The patient was a 19 yr old thalassemic girl from Togo regularly and uneventfully transfused every 60-90 days since the age of 5 months and splenectomised at 13 yrs. Two malaria episodes in 1995 and 1997 were treated with quinine and halofantrin respectively. In February 2008 the transfusion interval shortened (15 days) and blood transfusions were constantly followed after 30-40 hours by high fever (39-4028C) and hypotension. The patient was referred to our Hospital to clarify and overcome the transfusion problems. Malaria attacks were excluded by the referring clinic.
At admission, Hb was 5.9 g/dL, Hct 18.3%, MCV 71.8 fL, MCH 23.1 pg, MCHC 32.2%, reticulocytes 0.82%. WBC 13.1 × 109/L platelet count 953 × 109/L erythroblasts 12.7% of nucleated cells. Molecular analysis of β and α genes revealed double heterozygosity for β IVS1-1 G>A and β IVS2-849 A>G, associated with deletion 3.7 (-α3.7) at the heterozygous state. G6PD 6.29 IU/g Hb (ref.values 5.97±1), Pyruvate kinase 25.1 IU/gHb (ref. v. 11.9-16.1). Red cell osmotic fragility was decreased. The cytofluorimetric analysis of red cells labelled with eosin 5 maleimide gave normal results. Direct antiglobulin test was negative and red cell alloantibodies were not detected. The patient's blood group assessed by molecular biology testing was: genotype O1A2, phenotype A2; ccDee; K-k+; Jk(a+b-); Fy(a-b+); M+N+S+s-. The patient was given 2 crossmatch negative, filtered O neg units: the post-transfusion Hb values were 9.9 g/dL. Thirty-two hours later the patient developed fever (40°C) and hypotension followed by disseminated intravascular coagulation, metabolic acidosis and anuria. Direct and indirect antiglobulin tests were negative on a post-transfusion sample. Because of the rapid worsening of clinical conditions she was admitted to the Intensive Care Unit of our Hospital. Septic shock was excluded on the basis of negative blood cultures and infectious diseases testing. Microscopic examination of thick blood smear was negative for malaria parasites on 2 consecutive days and the malaria rapid diagnostic test (RDT) (Core Malaria Pan-PV-PF®, Core Diagnostics, U.K.-Effegiemme, Nerviano, Milano, Italy) gave inconsistent results. Anti Plasmodium total antibodies (Malaria EIA New Market Laboratories U.K.- Bio-Rad Italia) were detected in the serum at high levels (odd sample/cut off 22). Vital functions were supported by mechanical ventilation, amine administration and continuous venous-venous hemofiltration (CVVH). Broad spectrum antibiotic therapy was started. Fresh frozen plasma and two units of PRC were transfused on day 1 and 2 without increment of Hb level. Three days later, the examination of the peripheral blood smear for counting schistocytes revealed the presence of parasites in a very small number of red cells. This finding was almost simultaneous to the availability of PCR testing results that were positive for P. Falciparum. The differential agglutination with anti A antibody performed on a blood sample collected at admission to ICU allowed to separate patient's and donors' red cell. Counting the number of parasitized red cells in total blood and in the donor fraction blood revealed that the parasitized cells were almost exclusively those of donors (14.4 % vs 0.029%).
Treatment with quinine chlorhydrate 500 mg i.v. every 8 hr for 3 days followed by oral quinine sulphate 500 mg every 8 hr for 3 days was successfully undertaken without significant side effects leading to dramatic improvement of clinical conditions and to eradication of P. falciparum. Two RBC units were effectively transfused without any reaction, and in the following two weeks the patient maintained stable haemoglobin values. After discharge, the transfusion interval returned to the previous values (60-90 days) without any post-transfusion reaction.
We therefore think that the transfusion of normal, non malaria-resistant red cells fuelled the P. falciparum infection causing fever, DIC and acidosis giving rise to a very severe, atypical febrile non haemolytic transfusion related reaction.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.