Hemoglobinuria due to massive intravascular hemolysis can occur in
falciparum malaria. It is usually seen in non-immune or semi-immune individuals. Immune
individuals who have lost their immunity due to stay in a non-malarious area may also
develop the complication if they happen to get malaria on their return to malarious area.
The intravascular hemolysis can be due to
non-immune destruction of parasitized red cells in case of high parasitemia or due to
immune mediated destruction of parasitized as well as non-parasitized red cells. The
changes in the red cell antigen structure brought about by the parasitic invasion
stimulate the production of antibodies against the red cell. This triggers the immune
mediated red cell lysis. Sensitivity to quinine may play a role in some patients who have
been treated with quinine earlier, but now it seems to be rare. Patients with deficiency
of glucose 6-phosphate dehydrogenase enzyme may develop hemolysis
when treated with oxidant drugs like primaquine.
The hemolysis can occur so rapidly that
the hemoglobin may drop significantly within a few hours and it may recur periodically at
intervals of hours or days. Patient presents with head ache, nausea, vomiting and severe
pain in the loins and prostration. Fever up to 39.40C with a rigor is also
seen. Urine is dark red to almost black. Patient may have tender hepatosplenomegaly. The
urine becomes darker and the output slowly drops. Renal failure and peripheral circulatory
failure are the usual causes of death in these patients.
The increased release of hemoglobin into
the circulation results in hemoglobinuria and the urine appears dark brown or black
('Black water fever'). Due to hemoglobinemia, the hemoglobin estimation may be unreliable.
Similarly the parasite count may not represent the actual parasite load. There is
methemoglobinuria and heavy albuminuria. Renal function gets affected and the urea and
creatinine levels rise. There is increase in the levels of unconjugated and conjugated
bilirubin as well. Hepatic failure can occur in severely ill patients and is of grave
Treatment: Treatment is directed
towards anemia and renal failure.
Transfusion of whole blood or packed
cells should be started if the hemoglobin level is less than 5g%.
Renal failure can be treated
conservatively by careful fluid-electrolyte management and use of diuretics like
furoscemide. Dialysis must be considered in patients who do not respond to conservative
In cases with hemolysis following
primaquine therapy, Glucose 6 phosphate dehydrogenase assay should be
done and the drug should be stopped.
See Bruneel F, Gachot B, Wolff M, Régnier B, Danis M.
Resurgence of Blackwater Fever in Long-Term European Expatriates in Africa: Report of 21 Cases and Review.
Clinical Infectious Diseases 2001;32:1133–1140. Full text available at