Hemolytic Anemia and Thromobocytopenia Associated with Ischemic Brain Lesions in Patients with Acute Uncomplicated Plasmodium Falciparum Malaria.
Authors: Brittenham Gary M. , Tosti Christina L.V. , Golay Xavier , Van Cauteren Marc , Lekprasert Varinee , Tangpukdee Noppadon , Krudsood Srivicha , Leowattana Wattana , Wilairatana Polrat , Swaminathan Srirama V. , DeLaPaz Robert L. , Brown Truman R. , Looareesuwan Sornchai , Laothamatas Jiraporn 
Published: October 2019

Abstract
To examine the association between hemolysis in Plasmodium falciparum malaria and brain lesions in the absence of severe or cerebral malaria, we prospectively examined patients at the Bangkok Hospital for Tropical Diseases. We conducted standard physical, neurological and laboratory studies on 10 consecutive adult, non-immune patients admitted with acute uncomplicated falciparum malaria. MR studies of the brain, including T2-weighted and diffusion-weighted sequences, were performed within 24 hours of admission and repeated after 4 weeks using a 3.0 Tesla scanner (Gyroscan Intera Master, Philips). Each patient was fully conscious (Glasgow coma score 14 to 15) and had no abnormality detected on standard neurological evaluation. Within 24 hours, initial MR examinations found a restricted diffusion, ischemic, symmetrical midline lesion in the splenium of the corpus callosum of 4 (40%) of the 10 male patients. On admission, the 4 patients with a splenial lesion had a higher median hematocrit (44 vs. 32%, P<0.04), a higher mean serum indirect bilirubin (2.8 vs. 0.7 mg/dL, P<0.03) and lower mean platelet count (48,500 vs. 129,000 × 1000/microL, P<0.01), as well as a greater fall in hematocrit over the first 3 hospital days (7 vs. 1%, P<0.003) than the remaining 6 patients. No significant differences were found between the 4 patients with and the 6 patients without the splenial lesions with respect to mean age, days of fever before admission, parasite count on admission, parasite count after 24 hours of hospitalization (near the time of the initial MRI examination), and parasite or fever clearance time. After effective antimalarial treatment with artemisinin combination therapy, repeat studies 4 weeks later found resolution of the hematological differences between the groups and no residua of the splenial lesions. We conclude that reversible white matter injury was initially present in at least some nonimmune patients with acute uncomplicated falciparum malaria and resolved after early treatment with potent antimalarial drugs. P. falciparum modifies the surface of infected erythrocytes so that the parasitized red blood cells sequester by adhering to endothelial cells lining the microvasculature of vital organs, especially within the brain. The blood supply to the splenium of the corpus callosum may make this area particularly vulnerable to sequestration of parasitized red blood cells and microvascular obstruction. In addition, platelet-mediated autoagglutination has been reported with falciparum malaria in Thailand. In our patients, increased sequestration and destruction of both red blood cells and platelets in platelet-mediated autoagglutinates may have contributed to the severity of the hemolysis and thrombocytopenia as well as to the microvascular obstruction underlying the lesions in the splenium of the corpus callousum. Episodes of uncomplicated falciparum malaria may be an unrecognized source of neurological disease and disability in affected populations, both in southeast Asia and globally.