Acitretin-contaminated blood products and pregnancy

Dear Sir,

We recently published the pregnancy outcome of nine women who were transfused with blood products inadvertently obtained from donors treated with acitretin. The study gained the attention of Professor Fletcher who extensively criticised our paper, from the title to the study design to the possibility of sending a wrong message to the readers which may lead to a misuse of retinoids.

Being a case series, it is very difficult to depict any ‘epidemiological’ conclusion with a sample size of nine cases. As such, we did not attempt to go far from what was observed. In South Korea, the standard manufacturing process of blood products results in an elimination of >99.99% of acitretin and etretinate (Park et al. 2008). We obtained blood samples to quantify acitretin and etretinate in seven of the nine cases, and found measurable levels in only one of them, i.e. 2.2 ng/ml (LLOQ: 2 ng/ml) (Han et al. 2009).

In our case series, transfusion occurred 1.3–3 years prior to pregnancy in seven cases and late in the third trimester of pregnancy in the other two. Since Sturkenboom et al. (1994) found measurable levels of etretinate in subcutaneous tissue for long periods of time, they recommended a contraception period of 2 years after cessation of acitretin therapy. Excluding the two cases who were transfused in the third trimester, four of our nine cases received blood products within this ‘critical’ window, and three of them delivered healthy babies.

In contrast to one of the comments made by Fletcher, exposure to retinoids in the third trimester would not necessarily be without any consequences. As he properly cited in his letter, intellectual deficits may occur in children exposed in utero to these teratogenic compounds.

Thus, the two cases exposed late in pregnancy, although anecdotal information, added to the negative findings from the other cases. Altogether, our case series support the low risk of transfusions with blood products inadvertently obtained from donors treated with acitretin if the manufacturing process is able to efficiently remove acitretin and etretinate.

In this context, readers are invited to examine the manufacturing process of blood products in their own settings. If a high removal efficiency of etretinate can be demonstrated, we encourage them to follow a proactive teratogen risk counselling giving a critical appraisal of all available data to transfused women, similar to that recommended elsewhere (Nava-Ocampo and Koren 2007).

The information provided in our case series (Han et al. 2009), however, is specifically related to women who were transfused with blood products inadvertently obtained from donors treated with acitretin which underwent a manufacturing process that efficiently removed acitretin and etretinate (99.99%). Our findings are not intended to be extrapolated to other types of exposures.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.