Therapy for antiphospholipid miscarriages: Throwing the baby out with the bathwater?

Problem: The association of low molecular weight heparin (LMWH) with low-dose aspirin (LDASA) provides the therapeutic cornerstone of obstetric anti-phospholipid syndrome (APS). This combo approach is not effective in all patients, and few women still experience recurrences. Method of Study: In an elegant in vitro study, Chiombori Quao and colleagues demonstrated that anti-phospholipid antibodies (aPL) affect the functionality of endometrial endothelial cells interfering with angiogenesis. LMWH and LDASA, in combination or alone, did not display any protective activity but exacerbated aPL-mediated effects. Results: The above data were advocated as a demonstration of the inefficacy of LMWH and LDASA in obstetric APS. Given the lack of thrombotic lesions in APS placentae, this treatment is mainly empirical. However, clinical practice clearly shows that LMWH and LDASA are effective in most patients. Non-responsive women represent a peculiar subgroup, with a high-risk aPL profile. All experimental models, including in vitro models of obstetric APS, display limitations that should be considered before translating data to patients. In particular, the use of a monoclonal antibody specific for Domain (D) 5 does not fit with the evidence that anti-D1, but not anti-D4,5, are associated with both vascular and obstetric APS manifestations. Conclusion: The association of LMWH and LDASA is the most effective therapeutic option for pregnant aPL-positive women. The lack of a clear demonstration of the pharmacological action of LMWH/LDASA should urge to further invtrestigate the pathophysiology of aPL-associated miscarriages.