Paroxysmal cold hemoglobinuria successfully treated with complement inhibition

Abstract

Key Points This is the first-ever demonstration of successful treatment of paroxysmal cold hemoglobinuria using the complement inhibitor eculizumab.

Adult paroxysmal cold hemoglobinuria following mRNA COVID‐19 vaccination

“…Although immune‐suppressive therapies including corticosteroid, rituximab, intravenous immunoglobulin (IVIG), and azathioprine have been used for severe or chronic hemolysis due to PCH, the true efficacy of these agents are unclear. Eculizumab, a humanized anti‐C5 monoclonal antibody which blocks the complement pathway at the C5 stage, has been looked upon as a promising treatment method for PCH [ 14 ]. In the presented case, hemolysis promptly improved with warming alone and no recurrence has been seen, and thus additional therapies were not necessary.…”

Enterovirus 71-Induced Autoimmune Hemolytic Anemia in a Boy

“…Currently, monoclonal antibodies targeting specific effector cells or molecules responsible for AIHA are being developed 32 and successful treatment with these monoclonal antibodies have been increasingly reported. 33 - 36 For example, complement can be responsible for opsonization of red blood cells leading to phagocytosis of these cells, complement inhibition with eculizumab was reported to be effective in treatment of PCH in one case report. 35 Although PCH was the most likely diagnosis in this patient and corticosteroid efficacy in PCH is uncertain, 37 this patient received prednisone upon AIHA diagnosis because the type of AIHA could not be determined initially and the patient had very low hemoglobin level and anemic symptom.…”

“… 33 - 36 For example, complement can be responsible for opsonization of red blood cells leading to phagocytosis of these cells, complement inhibition with eculizumab was reported to be effective in treatment of PCH in one case report. 35 Although PCH was the most likely diagnosis in this patient and corticosteroid efficacy in PCH is uncertain, 37 this patient received prednisone upon AIHA diagnosis because the type of AIHA could not be determined initially and the patient had very low hemoglobin level and anemic symptom. Steroid could be considered in cases with severe PCH.…”

The choice of new treatments in autoimmune hemolytic anemia: how to pick from the basket?

“…The term biphasic implies that the antigen-antibody reaction and fixation of the early complement components occur at temperatures below 37°C, whereas further complement activation takes place after rewarming to central body temperature ( 18 , 95 ). Today, most cases of this rare condition occur as an acute, transient hemolytic anemia following a viral or other febrile infection in children ( 18 , 96 ). The chronic paroxysmal (adult) form of PCH has become extremely rare and can occur in tertiary syphilis, hematologic malignancies, or without any identifiable cause.…”