The cause of hemolytic crises in this disease is unknown (mainly due to intravascular haemolysis). There is rapid and massive destruction of red blood cells with the production of hemoglobinemia (hemoglobin in the blood, but outside the red blood cells), hemoglobinuria (hemoglobin in urine), intense jaundice, anuria (passing less than 50 milliliters of urine in a day), and finally death in the majority of cases.
The most probable explanation for blackwater fever is an autoimmune reaction apparently caused by the interaction of the malaria parasite and the use of quinine. Blackwater fever is caused by heavy parasitization of red blood cells with Plasmodium falciparum. There has been at least one case, however, attributed to Plasmodium vivax.
Blackwater fever is a serious complication of malaria, but cerebral malaria has a higher mortality rate. Blackwater fever is much less common today than it was before 1950. It may be that quinine plays a role in triggering the condition, and this drug is no longer commonly used for malaria prophylaxis. Quinine remains important for treatment of malaria except when the parasite is resistant to chloroquine, a problem that has been on the rise since 1990.