New paper – Coagulation factor XII, XI, and VIII activity levels and secondary events after first ischemic stroke

Another paper focussed on coagulation. After our paper on FVIII and cognitive function, a paper on the genetic determinants of FXI and FXII, and various papers on intrinsic coagulation protein in the etiology of first stroke and myocardial infarction (for example here, here and here), it was time to make the next step: risk of secondary events.

But studying causal effects in patient groups comes with its own difficulties such as the critical timing of the blood draw to avoid acute phase reactants showing up as causal factors, as well as a phenomenon of index event bias. JLR, who took lead in this project, made it all work, and the team indeed found out that increased FXI and FVIII was related to higher cardiovascular risk in the patients included in the PROSCIS-B study. Even though the figure only shows unadjusted results, they kinda get the whole idea of just looking at this Kaplan-Meier.

Figure 2 from the paper.

Does this mean that we should be measuring or even targeting FXI and FVIII immediately in all stroke patients? No, not really, at least not yet. The HRs are modest (HR of ~2) and therefore not likely to lead to enormous improvement of stroke prediction models – perhaps we can expect a modest contribution in the future, but only in combinations with some other biomarkers which are measured in a simple and reliable way. Targeting FXI and FVIII for treatment is an interesting option, but we are nowhere near a final stage. These proteins (esp. FVIII) is critical in proper hemostasis, and therefore messing with FVIII could lead to some serious side-effects. This is less of a problem for FXI, but still, some more works needs to be done, including the identification of the groups of patients that that will have the highest benefit.

The paper, again with the wonderful JLR in the lead, used to be a preprint at medRxiv, was published in the JTH, is open access, and can be found on my Publons profile and Mendeley profile.