Attribution of posttransplantation toxicity to methotrexate regarding genotype of methylenetetrahydrofolate reductase gene ( MTHFR ) polymorphism needs further clarification

Unfortunately, Drs Djulbegovic and Cohen erroneously assumed that nonhemorrhagic deaths were included in the death rate of 0.019. But this rate only represents fatal hemorrhages and is entirely in accordance with their original estimates obtained from pooled information from 17 case series. Here we want to address 2 other important issues: First, nonhemorrhagic deaths should also be addressed when defining to what extent ITP compromises life expectancy. This led us to suggest that the only reliable estimate of the risk to die from ITP is obtained by comparing the mortality risk of patients with ITP with mortality risks in the general population, the method applied in our study. Second, hemorrhagic and nonhemorrhagic deaths should be differentiated. In our population, deaths due to lethal infections exceeded deaths due to bleeding, necessitating a discussion about the severe adverse effects of presently available treatment options for refractory ITP. Therefore, although we did not advocate a “watchful waiting trategy,” our results underscore the fact that risks of hemorrhages and the risks of serious adverse effects must be carefully weighed when administering second-line treatment for refractory ITP.