Extravascular hemolysis is produced when the recipient's antibodies opsonize the donor's red blood cells, leading to their sequestration and phagocytosis by phagocyte immune cells such as macrophages.

Extravascular hemolysis does not involve the release of RBC constituents directly into the circulation, but rather occurs within the confines of the reticuloendothelial system and rarely involves complement. If no detectable hemolysis is identified, the process is termed a DSTR.

DHTRs are characterized clinically by an unexpected drop in hemoglobin or less than expected post transfusion increment in hemoglobin following transfusion. Symptoms of extravascular hemolysis may include fever, chills, jaundice, back pain and uncommonly renal failure.

In DHTRs the haemolysis is mainly extravascular, so although haemoglobinuria may occur in rare cases, acute renal failure and DIC are not normally seen. Occur in approximately 1:2,500 of transfusions, but found more frequently in patients who have received frequent blood transfusions.

DHTRs are the most common presentation of transfusion-associated immune hemolysis. DHTRs often involve the Rh system. Patients present with a fever, a falling hematocrit, and the development of a positive DAT with an eluate demonstrating a new RBC alloantibody.