HELLP Syndrome (Postplacental Hypoxia)

To our best knowledge, data on the placental histology in the case of HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome have never been published. We, too, have analyzed only very few cases of acute HELLP syndrome, resulting in C-section between 28 and 32 weeks of pregnancy. These cases showed a surprising structural homogeneity. All of them were characterized by features of postplacental hypoxia, similar to those described above for IUGR with ARED, combined with early-onset preeclampsia: Mature intermediate villi and terminal villi were extremely long, thin, filiform, and largely unbranched. Terminal villous side branches are largely missing. Consequently, intervillous space is abnormally wide (Fig. 15.18A, B). The terminal capillary loops, resulting from nonbranching angiogenesis are long, slender, and usually unbranched (Fig. 15.18D). Their geometry explains the abnormally high umbilical Doppler resistance indices. As in postplacental hypoxia, villous cytotrophoblast is barely undetectable. Accordingly, in spite of ample immunore-activities for proliferation marker MIB-1 in the villous stroma, proliferating cytotrophoblast is missing. The thickness of villous syncytiotrophoblast is dramatically decreased. Signs of apoptotic knotting and respective TUNEL reactivity are largely missing, whereas disintegration of the apical plasmalemma, accumulation of trophoblastic debris in the intervillous space, as wells as fresh intervillous blood clot and perivillous fibrinoid are universally visible.

Because most placentas in HELLP syndrome are delivered at the beginning of the third trimester, local areas with obvious synchronous villous immaturity are found (Fig. 15.18C). These are in striking contrast to the otherwise prematurely differentiated villi.

These preliminary findings support the view that HELLP syndrome is a hypertensive disorder of the late second trimester and therefore shows features similar to those of early-onset preeclampsia combined with IUGR with ARED (see above). As already indicated above, our findings are based on only a few cases. Two findings from the literature suggest, however, that the general structural features described above may be representative:

•  Our findings of numerical reduction of villous cytotro-phoblast and increased syncytiotrophoblast necrosis suggest a decreased rate of syncytial fusion. This is in agreement with the data by Knerr et al. (2002), who showed that syncytin expression in these placentas is reduced (cf. Chapter 6).

•  Prevalence of nonbranching angiogenesis in the placental villi, as described above, is supported by the findings by Zhou et al. (2002), who found reduced VEGF but normal placental growth factor (PlGF) expression, by cytotrophoblast from HELPP placentas, both in situ and in vivo. This is a combination of angiogenetic

Figure 15.18. Placenta from a patient with severe HELLP syndrome showing typical features of postplacental hypoxia, 30th week of gestation. A: Paraffin survey picture. Note the long, poorly branched bundles of mostly filiform terminal villi with an extremely wide intervillous space. x25. B: In higher magnification the unusually small diameter of the majority of terminal

Villi becomes evident. x50 C: The center of a villous tree of the same case still shows synchronous immaturity, which reflects the stage of pregnancy. x50. D: QBend10 staining of the same case reveals few, mostly undilated, poorly branched capillaries (brown). This feature is highly characteristic for postplacental hypoxia. x140.

Growth factors that are thought to be responsible for J the development of excessive nonbranching angiogenesis in placental villi (for review see Charnock-Jones et al., 2004 and Kaufmann et al., 2004).

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