COVID-19 Vaccines Induce Severe Hemolysis in Paroxysmal Noct
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According to recent research reports published in Blood ,Patients with paroxysmal nocturnal hemoglobinuria (PNH) who receive vaccination for COVID-19 may be at risk of severe hemolysis. Two mRNA-based vaccines that lead to transient expression of the SARS-CoV-2 spike protein are highly efficacious in preventing severe infection.

Reactions to these vaccines are generally mild; however, increased complement amplification could theoretically lead to more severe effects in diseases like paroxysmal nocturnal hemoglobinuria (PNH), where blood cells lack complement regulatory proteins. In the current study, researchers describe significant adverse reactions to COVID-19 vaccines in four patients with PNH.

They also present two PNH patients who received the vaccine without significant adverse effects or hemolysis. Patients were identified based on self-report of receiving the vaccine. Patients were aged 25-63 years, had PNH granulocyte clones of greater than or equal to 80%, and had not received transfusions in the past year. Reactions occurred from the day of administration to five days later and lasted one to six days.

Four of six patients reported fever. Patients 2, 3, and 4 experienced severe hemolysis with 2-4 g/dL hemoglobin decrease. Patient 1 had a presumptive thrombotic manifestation. Patients 5 and 6 received both doses of the Pfizer-BioNTech BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine without clinical or laboratory signs of hemolysis.

"Based on these observations, we sought to evaluate whether the SARS-CoV-2 spike protein directly leads to increased hemolysis. Recent data suggests the SARS-CoV-2 spike protein binds heparan sulfate on nucleated cells and amplifies the alternative pathway of complement through interference with the binding of CFH, an alternative pathway inhibitor. However, CFH primarily binds sialic acid on human erythrocytes, and mature erythrocytes express little heparan sulfate."the team opined.

"This study provides insight into the mechanism of pharmacodynamic breakthrough precipitated by COVID-19 vaccination in PNH patients on ravulizumab. Similar disease flares may be anticipated in other complement-mediated disorders. As SARS-CoV-2 leads to a severe inflammatory state, the benefits of vaccinating patients with PNH likely outweigh the risks; however, clinicians and patients should be aware of this serious adverse effect, and patients should be educated to report any symptoms postvaccination." the team concluded.