We thank Bianca et al1 for their interesting comments and hereditary haemorrhagic telangiectasia (HHT) case reports. Within our structured 2009 EJHG review,2 we did not have space to discuss in detail all of the implications of the cited studies, including, of relevance here, our large thrombosis3 and pregnancy4 HHT data series (EJHG references 9 and 48).
Concern regarding thrombophilic risk in HHT patients in relation to pharmacological treatment was one of the main conclusions of our cited (EJHG reference 9) series of 309 HHT-affected individuals.3 When reviewing this manuscript, we stated that the disease spectrum in HHT now encompasses a prothrombotic state, and in Table 2, recommended ensuring that the patient is not prothrombotic before giving oestrogen–progesterone treatment or antifibrinolytic systemic treatment.2 This referred to the complex clinical management issues regarding blood loss limitation in HHT, when therapeutic manipulation of coagulation and fibrinolytic pathways may be used. As we stated in the final paragraphs, ‘routine measurement of FVIII, FV Leiden, and other thrombophilic markers in HHT patient assessments may assist individualised risk-benefit considerations’.3 We thank Dr Bianca and colleagues for allowing these important considerations to be highlighted again.
Dr Bianca and colleagues also speculate on a possible association between genetic thrombophilias and vascular gestation abnormalities, stating ‘To our knowledge there are no data on the incidence of pregnancy complications, like fetal loss or venous thrombosis, in HHT patients’. These data are in fact available, and were presented in our cited (EJHG reference 58) series of 484 HHT pregnancies published in BJOG.4 As stated in that manuscript's introduction,4 there was no evidence for increased fetal loss in HHT pregnancies in the two separate studies that analysed the outcomes, first in 40 women with HHT compared with 80 matched controls,5 and second, in 161 HHT pregnancies.6 Pregnancy-related thromboembolic events would be expected in a proportion of women, in keeping with general gestational pathophysiology, and we are aware of an unreported HHT maternal death in pregnancy that occurred because of pulmonary embolism. However, the most frequent life-threatening risks of pregnancy in the series of 484 HHT-affected women were related to haemorrhage from pulmonary and cerebral arteriovenous malformations.4 The overall maternal death rate was 1.0% (95% confidence interval 0.13–1.9%).4
Dr Bianca and colleagues suggest that to prevent vascular and pregnancy complications in patients with HHT and proven thrombophilia, ‘more appropriate pharmacological treatment’ should be considered. In our experience, even in the setting of HHT and known Factor V Leiden and/or PT20210A heterozygosity, such prophylactic considerations are highly challenging for patients and clinicians, and are not to be undertaken lightly.
References
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Shovlin CL, Sulaiman NL, Govani FS, Jackson JE, Begbie ME : Elevated factor VIII in hereditary haemorrhagic telangiectasia (HHT): association with venous thromboembolism. Thromb Haemost 2007; 98: 1031–1039.
Shovlin CL, Sodhi V, McCarthy A, Lasjaunias P, Jackson JE, Sheppard MN : Estimates of maternal risks of pregnancy for women with hereditary haemorrhagic telangiectasia (Osler-Weber-Rendu syndrome): suggested approach for obstetric services. BJOG 2008; 115: 1108–1115.
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Shovlin, C., Govani, F. Reply to Bianca et al. Eur J Hum Genet 18, 405–406 (2010). https://doi.org/10.1038/ejhg.2009.205
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DOI: https://doi.org/10.1038/ejhg.2009.205