Human Reproduction, Vol. 16, No. 2, 395-396,
February 2001
© 2001 European Society of Human Reproduction and Embryology
Letters to the editor |
Thrombophilias and adverse pregnancy outcome
1 Placental Research Unit, Department of Pathology, Women's and Children's Hospital, North Adelaide, Australia 2 Department of Histopathology, Women's and Children's Hospital, North Adelaide, Australia 3 Obstetric Medicine, Department of Obstetrics and Gynaecology, Women's and Children's Hospital, North Adelaide, Australia
Dear Sir,
The findings of Mousa and Alfirevic (2000) cannot go unchallenged.
The crux of the paper asked whether there was a relationship between placental lesions and maternal thrombophilia. Unfortunately, there is scant regard to the precision, or otherwise, of placental histopathology. Diagnosis of placental lesions can be fraught with inter-observer and, to a lesser extent, intra-observer variance even among placental pathologists (Khong et al., 1995
; Grether et al., 1999). Clinico–pathological studies such as this are best performed when the histopathology is reviewed contemporaneously, preferably with at least two independent blinded observers (Grether et al., 1999; Beebe et al., 2000).
Infarction, massive perivillous fibrin deposition and intervillous thrombosis can be misleadingly similar. An experienced placental pathologist may be consistent in their naked eye assessment of these lesions without histological confirmation but junior pathologists and those less interested in the placenta may fail to differentiate them. Were blocks taken of abnormal as well as seemingly normal macroscopic areas? We are not aware of a definition of perivillous fibrin deposition that includes migration of trophoblastic cells into the fibrin deposits. Perivillous fibrin deposition is a common finding in placentae in the third trimester and usually of no clinical significance. Massive perivillous fibrin deposition, on the other hand, is less common but clinically important. There is a difference in the incidence of placental (or maternal) floor infarction trans-Atlantically, probably due to nosological concepts. The criteria for the depth (thickening) and extent of encasing of villi are unclear in the literature. This is one of many placental lesions that the Perinatal Interest Group of the Society for Pediatric Pathology are attempting to attain consensus opinion (Bendon et al., 2000).
We have not been provided with any details whatsoever regarding the sampling protocol of the placentae in this study. We cannot be assured that a failure to detect infarction is due to a true absence or due to inadequate sampling. As the authors discuss, minor degrees of placental infarction are insignificant and yet the authors did not attempt to separate significant from insignificant infarction. Furthermore, assessment of the maternal utero–placental vasculature, the compromise of which is the cause of placental infarction (Fox 1997), was not included in this report. A higher detection rate of histological markers of utero–placental arterial disease, e.g. maternal utero–placental vascular thrombosis, is possible if an alternative, non-conventional, histological block of the placenta is taken (Khong and Chambers, 1992).
The maternal demographic details lack information on smoking or substance abuse, which may be associated with abruption, growth restriction or stillbirth (Raymond and Mills, 1993; Salafia and Shiverick, 1999). Despite this being a high risk obstetric population, no details were given regarding possible treatment of the mothers with aspirin, heparin or folate, all of which may affect outcome and placental pathology. A well-known cause of fetal thrombotic vasculopathy is maternal diabetes mellitus (Fox, 1997) but no information is provided as to whether either of the two women, one with fetal stem thrombosis and the other with thrombotic vasculopathy, were so affected. If histological examination of the placenta was performed as a routine clinical practice, as claimed in the Materials and methods section, why was placental histology `incomplete or not performed' in some women; we would have liked to know and decide for ourselves whether the 23 women with incomplete or absent thrombophilia screening and/or placental histology may have skewed the results.
Other less serious defects in the study demonstrate a lack of understanding of the subject. No indication is given of whether the cases were a consecutive series or not; in itself, this may not be important but calibration of laboratory tests including placental histology (see above), can vary over time. For example, what are the inter- and intra-assay coefficients of variance for the coagulation assays? The authors write of low activated protein C resistance (APCR) as being abnormal; it is a high APCR or a low APCR ratio that indicates thrombophilic tendency. Pre-eclampsia/eclampsia, placental abruption, intra-uterine growth restriction (IUGR) and stillbirth are inter-related but Table V does not allow the reader to determine the frequency of the placental lesions in each of these complications in the absence of concurrence.
In summary, the article is seriously flawed and while the authors may well be correct in their conclusion and proposal, the scientific and medical community will be better served if more robust proof is forthcoming, preferably with inter-disciplinary collaboration.
Notes
1 To whom correspondence should be addressed. E-mail: yee.khong{at}adelaide.edu.au 
References
Beebe, L.A., Cowan, L.D., Hyde, S.R. et al. (2000) Methods to improve the reliability of histopathological diagnoses in the placenta. Paediatr. Perinat. Epidemiol., 14, 172–178.[Medline]
Bendon, R., Khong, Y. and Seguin, J. (2000) Perinatal section-Society for Pediatric Pathology News. http://path.upmc.edu/spp/pubs/maps0300.htm, accessed 2nd September, 2000.
Fox, H. (1997) Pathology of the Placenta. W.B.Saunders, London, UK, 488 pp.
Grether, J.K., Eaton, A., Redline, R. et al. (1999) Reliability of placental histology using archived specimens. Paediatr. Perinat. Epidemiol., 13, 489–495.[Medline]
Khong, T.Y. and Chambers, H.M. (1992) Alternative method of sampling placentas for the assessment of uteroplacental vasculature. J. Clin. Pathol., 45, 925–927.
Khong, T.Y., Staples, A., Bendon, R.W. et al. (1995) Observer reliability in assessing placental maturity by histology. J. Clin. Pathol., 48, 420–423.
Mousa, H.M. and Alfirevic, Z. (2000) Do placental lesions reflect thrombophilia state in women with adverse pregnancy outcome. Hum. Reprod., 15, 1830–1833.
Raymond, E.G. and Mills, J.L. (1993) Placental abruption. Maternal risk factors and associated fetal conditions. Acta Obstet. Gynecol. Scand., 72, 633–639.[Web of Science][Medline]
Salafia, C. and Shiverick, K. (1999) Cigarette smoking and pregnancy II: Vascular effects. Placenta, 20, 273–279.[Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||