Correlations between clinical and placental histopathological and immunohistochemical features in women with and without hereditary thrombophilia

Vol. 60 No. 1, 2019


Janina Georgiana Nacea, Ionela Rotaru, Mihaela Niculescu, Radu Stanescu, Nicolae Cernea, Ana-Maria Patrascu, Loredana Elena Stoica, Stefania Tudorache

Aim: The primary objective of this study was to correlate hereditary thrombophilia (high- or low-risk) with specific placental histopathological (HP) and/or immunohistochemical (IHC) changes, for confirming/ruling out a possible linkage between these two biological parameters. Patients, Materials and Methods: We present a 3-year prospective study conducted between 2016 and 2019 that enrolled 90 women registered in two Clinics of Obstetrics and Gynecology in Craiova, Romania, with personal thrombotic and/or pathological obstetrical history. The HP and IHC analysis of the placenta was performed using monoclonal anti-cluster of differentiation 34 (CD34) antibody, anti-hypoxia-inducible factor-1 alpha (HIF-1alpha) and anti-endothelial nitric oxide synthase (eNOS) antibody. Results: There was a high incidence of all thrombophilia (TPh) mutations in Caucasian women with thrombotic and obstetrical complications. Among them, both HP and IHC examination revealed significant changes. These were more severe in the placentas of patients with homozygous Factor V Leiden (FVL) gene mutation and double heterozygous FVL/PII gene mutation. Multiple placental infarctions with massive fibrinoid necrosis and an increase in syncytial knots are common findings. In the same group, we found by means of IHC examination - intense positive HIF-1alpha and eNOS immunoexpression, and low positive CD34 expression, especially in fibrinoid necrosis and thrombosis areas. We found no correlation between clinical, HP and IHC changes in patients with low-risk TPh or without TPh. Conclusions: Among patients with obstetric and thrombotic complications, there is a high prevalence of TPh. It appears that hypercoagulability reported in high-risk thrombophilia (HR-TPh) has major effects on placental tissue (fibrinoid necrosis, multiple thromboses, hypoxia and oxidative stress). Significant placental changes were found predominantly in women with HR-TPh. Strategies for TPh screening based on HP/IHC pattern would be, most probably, more cost-effective compared with the extended TPh testing offered in large populations. This way, a smaller number of patients will be tested and in this group a higher proportion of patients will be found as having HR-TPh mutations.

Corresponding author: Ionela Rotaru, Lecturer, MD, PhD; e-mail:

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