Platelet sequestration and consumption in the placental intervillous space contribute to lower platelet counts during pregnancy
Authors: Jessica A. Reese, Jennifer D. Peck, Zhongxin Yu, Teresa A. Scordino, David R. Deschamps, Jennifer J. McIntosh, Deirdra R. Terrell, Sara K. Vesely, James N. George
Journal: American Journal of Hematology (2018)

To the editor: Platelet counts of all women with an uncomplicated pregnancy gradually decrease at approximately the same rate throughout their pregnancy.1 Dilution of platelets by plasma volume expansion is an apparent cause for lower platelet counts, but multiple additional physiologic changes during pregnancy may also contribute to the lower platelet counts. Blood circulation through the placenta is similar to blood circulation through the spleen. In the spleen, some blood flows directly from arterioles to venules, without intervening capillaries, whereas other blood is shunted into the low pressure pools in the sinusoids. Plasma preferentially flows directly to the venules, described as “plasma skimming”, while the blood cells are sequestered in the sinusoids.2 Platelet counts in splenic blood are 7-fold greater than platelet counts in peripheral blood.3 In normal adults, one-third of all circulating platelets are transiently sequestered within the splenic sinusoids. Increased spleen size results in greater splenic sequestration of platelets and lower peripheral blood platelet counts.3 In the placenta some blood also flows directly from arterioles to venules, without intervening capillaries, while other blood is shunted into the low pressure pools in the intervillous spaces. These similar patterns of circulation suggest that there may be increased sequestration of blood cells in the placental intervillous spaces, similar to the splenic sinusoids. Although platelets sequestered within splenic sinusoids return to the circulation,3 platelets sequestered within the intervillous spaces may be consumed by incorporation into the perivillous fibrinoid. Perivillous fibrinoid is present in all term placentas. It is a product of coagulation that fills gaps in the syncytiotrophoblast cells lining the surface of mature villi and maintains the integrity of the villous surface.4, 5 Platelet counts of women with twin pregnancies are lower than platelet counts of women with singleton pregnancies at each trimester and at delivery.1 Women with twin pregnancies have larger placentas, or may have 2 placentas. This suggests that larger placentas in women with twin pregnancies may contribute to their greater platelet count decrease. Based on these observations, we postulated that blood cells are sequestered within the intervillous spaces of the placenta and that platelets are then consumed by incorporation into perivillous fibrinoid. To test this hypothesis, we compared blood cell counts in maternal peripheral blood to blood obtained from the placental intervillous space. We collected placentas from 40 women with uncomplicated singleton pregnancies who had a scheduled cesarean delivery for routine indications at the Oklahoma University Medical Center. The mother's complete blood count (CBC) from the day of delivery was recorded. At delivery, placentas were immediately immersed in a solution of 4.5 mmol ethylenediaminetetraacetic acid (EDTA) in 0.85% sodium chloride to prevent blood coagulation within the intervillous space. Maternal placental blood was collected from the intervillous space6 and placental tissue samples for microscopy were also collected at the same time. Contamination of maternal blood with fetal blood was determined by the percent of fetal red blood cells in each sample. Then a CBC was performed on the placental blood sample with the lowest percentage of fetal blood. A stained smear of the placental blood was examined for platelet clumping; if clumping occurred, the sample was not used. To correct for dilution of placental blood by the EDTA solution, we used the ratio of hemoglobin concentration in the peripheral blood to placental blood to adjust the placental white blood cell and platelet counts. To determine if contamination of maternal blood from the intervillous space by fetal blood influenced the blood counts, we separately analyzed blood counts on the 20 women with placental blood samples that had fetal blood contamination less than the median value. This study was approved by the University of Oklahoma Institutional Review Board (approval #4156). The median time between delivery and placental blood sample collection was 18 minutes (range, 13-82 minutes). The placental weight (median 501 g, range 364-938) was more than 2-fold the weight of a normal adult spleen (150-200 g). The median total white blood cell count, neutrophil count, and lymphocyte count, corrected for dilution by the EDTA solution, were all higher in placental blood than in the peripheral venous blood. These differences were significant when the placental blood of the 20 women with less fetal blood contamination was analyzed (Table 1). The median corrected platelet count in placental blood of all 40 women was lower than the platelet count in peripheral venous blood. The median corrected platelet count in placental blood of the 20 women with less fetal blood contamination was also lower than the platelet count in peripheral venous blood; however, the difference was not significant, possibly due to the smaller sample size and the variation among the platelet counts. Microscopic examination of all 40 placentas documented that they were normal. None of the placentas had excessive subchorionic or perivillous fibrinoid, intervillous or subchorionic thrombi, or inflammatory infiltrates. Immunohistochemical stains using a rabbit monoclonal antibody to the platelet membrane glycoprotein IIIa (CD61) identified platelets within the perivillous fibrinoid (Figure 1). These images suggest that platelets are consumed in the process of blood coagulation and fibrinoid generation to seal the gaps in the syncytiotrophoblastic surface of the terminal villi. The higher white blood cell counts in placental blood compared to peripheral venous blood are consistent with the sequestration of blood cells within the intervillous space, similar to the sequestration of blood cells in splenic sinusoids.3 The lower or equivalent platelet counts in placental blood compared to peripheral venous blood and the immunohistochemistry identification of platelets within the perivillous fibrinoid are consistent with the hypothesis that platelets are not only sequestered within the placental intervillous space but also consumed by incorporation into the perivillous fibrinoid, which maintains integrity of the syncytiotrophoblast surface. These data support the hypothesis that the sequestration and consumption of maternal platelets within the placental intervillous space contribute to lower platelet counts during pregnancy. This project was supported in part by 1K01HL135466-01 from the National Heart, Lung and Blood Institute (Terrell). This study was approved by the University of Oklahoma Health Sciences Center Institutional Review Board (approval #4156). Nothing to report.