Prediction of thrombosis risk in patients with paroxysmal nocturnal hemoglobinuria
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic disease with thrombosis as a major complication. The mechanism of thrombosis and related risk factors in PNH patients are still not well characterized. We retrospectively enrolled 99 patients with newly diagnosed PNH at our institute from 2011 to 2016. According to binary logistic regression model analysis, we first identified four baseline clinical risk factors which may be associated with incidence of thrombosis in the PNH cohort, including PNH clone sizes (fluorescent aerolysin of neutrophil) ≤ 80 (OR 1.056, 95%CI 1.016–1.097, P = 0.005), hemoglobin ≤ 75 g/L (OR 4.202, 95%CI 0.984–17.954, P = 0.053), platelet > 100 × 109/L (OR 6.547, 95%CI 1.490–28.767, P = 0.013) and rs495828 = G (OR 5.243, 95%CI 1.314–20.916, P = 0.019). These independent risk factors were combined together to develop a risk model to evaluate thrombosis risk (AUC = 0.756, 95%CI 0.607–0.905, P < 0.001). Our risk model revealed a higher cumulative incidence of thrombosis and an earlier thrombosis events in PNH patients with high risk (risk score ≥ 23) compared with those with low risk (risk score < 23, P < 0.001 and P = 0.043, respectively). Although with some limitations, we set up a prediction model for thrombosis risk in patients with PNH for the first time, but it needed to be verified in a prospective study with larger patients and longer follow-up time in the future.
KeywordsParoxysmal nocturnal hemoglobinuria (PNH) Thrombosis Risk score Prediction model
Y.H. and B.H. designed the study and wrote the manuscript. Y.H. analyzed clinical and experimental data. X.L. helped analyzed the risk model. C.Y. and M.C. helped to design the study. Z.L. and W.Z. collected the samples, performed genotyping, and helped to analyze the data. H.L. and F.C. helped to perform genotyping. All authors reviewed the manuscript finally. Y.H., M.C., and B.H. approved the final submission of the manuscript.
This study was supported by grants from the Chinese Academy of Medical Sciences (CAMS) innovation fund for medical sciences (2016-I2M-3-004), The National Key Research and Development Program of China (2016YFC0901500), and Beijing Natural Science Foundation (7192168).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Research involving human participants
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was approved by the PUMCH Ethics Committee.
Informed consent was obtained before study start from all individuals included in the study.
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