How to use lupus anticoagulants in neonates born to mothers with antiphospholipid syndrome
.Dear Sir, We read with great interest the accurate paper by Sen et al. regarding the indications for testing lupus anticoagulants (LA) in pediatric patients1. We believe that two further considerations might provide a complete overview on this issue. First, it has to be underlined the important contribution given by Boffa MC concerning either the laboratory methods for the detection of LA2 or the association between antiphospholipid syndrome (APS) and obstetrical complications in women3. Second, in the article by Sen et al. the authors do not take into consideration infants born to mothers with APS. To date, it is still unclear how neonates born to mothers with APS should be evaluated and which is the true clinical relevance of neonatal antiphospholipid antibodies (APL). Concerning the indications to LA testing, the authors suggested two main indications: the presence of thrombosis and/or of unexplained prolonged aPTT. We agree with the authors concerning the first indication, i.e. APL testing in all infants with thrombosis even in neonates born to mothers with negative APL4. Concerning the second indication, it should be specified that the activated partial thromboplastin time (aPTT) in neonates is intrinsically longer than in adults and changes according to postnatal age5. Boffa et al. suggested that APL should be sistematically tested at birth in neonates born to mothers with APS6 since unpredictable transplacental passage occurs in about 30% of cases. The low rate and the unpredictable entity of APL crossing through the placenta could depend on the absorption of antibodies by trophoblast cells and by their binding to heparin, administered to mothers with APS during pregnancy. Interesting data have been recently provided by the European registry of babies born to mothers with APS7. First, maternal APL crossing over the placental barrier was confirmed. Second, the kind of neonatal APL correlated with the same mother's isotype before 6 months of life and mostly disappeared thereafter. Third, 10% of children showed persistent APL at 24 months of life. Fourth, de-novo production of antibodies was reported; in particular, de-novo anti-beta2 glycoprotein-I antibodies synthesis occurred in 16% and LA in 4% of cases. It was suggested that prolonged APS exposure could represent an immunological trigger, as well as vaccinations or infections, for de-novo synthesis of APL. Nevertheless, the exact clinical relevance of neonatal APL positivity is still poorly understood. Although only few case reports of thrombosis have been described among children born to mothers with APS6, this increased prothrombotic risk should not be underestimated. In addition, the European registry of babies born to mothers with primary APS reported four cases of neurodevelopmental anomalies during the 5-year follow-up7. According to the current knowledge on this topic, APL screening should be performed at birth only in case of thrombosis, and after 6 months of life in asymptomatic neonates to investigate the eventual persistence of APL. In this case, a long lasting follow-up is required to verify the true clinical significance of persisting APL.
References 1. Sen ES, Beresford MW, Avcin T, Ramanan AV. How to use lupus anticoagulants. Arch Dis Child Educ Pract Ed. 2012 Oct 6. 2. Lambert M, Ferrard-Sasson G, Dubucquoi S, Hachulla Eet al. Diluted Russell viper- venom time improves identification of antiphospholipid syndrome in a lupus anticoagulant-positive patient population. Thromb Haemost 2009;101(3):577- 81. 3. Soulier JP, Boffa MC: Avortements a repetition, thromboses et anticoagulant circulant anti-thromboplastine: trois observations. Nouv Presse Med 1980;9:859. 4 De Carolis MP, Salvi S, Bersani I, De Carolis S. Isolated cerebral sinovenous thrombosis: a rare case of neonatal antiphospholipid syndrome. Indian Pediatr. 2012 May;49(5):411-2. 5. Andrew M, Paes B, Milner R, et al. Development of the human coagulation system in the full-term infant. Blood 1987;70(1):165-72. 6. Boffa MC, Lachassinne E. Infant perinatal thrombosis and antiphospholipid antibodies: a review. Lupus 2007;16(8):634-41. Review. 7. Mekinian A, Lachassinne E, Nicaise- Roland P, et al. European registry of babies born to mothers with antiphospholipid syndrome. Ann Rheum Dis. 2012 May 15.
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