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Clinical and Epidemiological Features of Paroxysmal Cold Hemoglobinuria: A Systematic Review.
Blood Advances 2023 January 30
Paroxysmal cold hemoglobinuria (PCH) is a rare autoimmune hemolytic anemia often overlooked as a potential etiology of hemolysis, and is challenging to diagnose due to the complicated testing methods required. We performed a systematic review of all reported cases to better assess the clinical, immunohematologic, and therapeutic characteristics of PCH. We systematically analyzed PubMed, Medline, and EMBASE to identify all cases of PCH confirmed by Donath-Landsteiner (DL) testing. Three authors independently screened articles for inclusion, and systematically extracted epidemiologic, clinical, laboratory, treatment, and outcomes data. Discrepancies were adjudicated by a fourth author. We identified 230 cases, with median presentation hemoglobin of 6.5 g/dL (IQR 4.8-9.0 g/dL) and nadir of 5.5 g/dL (IQR 4.4-7.2 g/dL). The most common direct antiglobulin test (DAT) result was the presence of complement and absence of IgG bound to red blood cells, though other findings were observed in one-third of cases. Seventy-one patients had DL antibody class and specificity reported, of which 83.1% were IgG anti-P. The use of corticosteroids is common, though we found no significant difference in the length of hospitalization for patients with and without steroid therapy. Recent reports have highlighted the use of complement inhibitors. Amongst patients with follow-up, 99% (213/216) were alive at the time of reporting. To our knowledge, this represents the largest compilation of PCH cases to date. We discovered contemporary PCH most commonly occurs in children with a preceding viral infection, corticosteroid use is frequent (but potentially ineffective), and DAT results are more disparate than traditionally reported.
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