Extremely high maternal alkaline phosphatase serum concentration with syncytiotrophoblastic origin

Abstract

An extremely high alkaline phosphatase (AP) concentration (3609 IU/litre) was found in a 20 year old primigravida at 37 week's gestation, prompting an examination of its histological and cellular origin. Immunohistochemistry and western blots using antibodies against AP, Ki-67, phosphoprotein kinase B (Akt), phospho-p44/42 mitogen activated protein kinase/extracellular signal regulated kinase 1/2 (MAPK/Erk1/2), phospho-glycogen synthase kinase-3b (GSK-3b), phospho-stress activated protein kinase/c-Jun Nterminal kinase, total-Akt, total-GSK-3b, and phospho-p38-MAPK were carried out on index and control placental samples of the same gestational age. Compared with controls, staining of the index placenta showed minimal AP labelling of the brush border and remarkable positivity of the intervillous space. Cytotrophoblastic proliferation was 8-10% in the index placenta compared with 1-2% in controls. The index placenta also had raised concentrations of protein kinases with important roles in cell differentiation. The proliferation and differentiation rates of the cytotrophoblasts were found to be five times higher in index samples than in controls. It is hypothesised that loss of syncytial membranes in immature villi led to increased AP concentrations in the maternal circulation and decreased AP staining of the placenta. Loss of the syncytium might also stimulate increased proliferation of villous cytotrophoblasts, which would then fuse and maintain the syncytium.A lkaline phosphatase (AP) is known to be produced by the liver, bones, small intestine, and kidneys, and different AP isoforms are also expressed by the placenta during pregnancy.1 The average amount of AP in one human term placenta amounts to 40 mg. 2 The placental isoforms are known as heat stable AP, because they are heat resistant at 60˚C, a property that is the main criterion for distinguishing them from the other isoenzymes. 3 In early pregnancy, the tissue non-specific AP isoenzyme is mainly expressed in the placenta, and reaches a peak value around 10 weeks of pregnancy. At the end of the second trimester, most of the AP activity comprises term placental AP isoenzymes 1 (90% of which are the P1 type, 10% the P2 type) produced by the syncytiotrophoblasts, and these isoenzymes appear in maternal serum between the 15th and 26th weeks of pregnancy.4 Their plasma concentrations increase exponentially during gestation-they are present at concentrations three times greater than those seen in nonpregnant women-and have a long half life (seven days) postpartum.

Histochemistry of placental alkaline phosphatase in preeclampsia

“…Dempsey et al [15] reported PALP activity in connective tissue stroma of preeclamptic placentae. However the findings in the present study differ from previous workers like Sammak et al, Boronkai et al and Francis et al [17,20,21] who observed decreased alkaline phosphatase activity in preeclamptic placentae as compared to control placentae.…”

Diagnostic Utility of Heat Stable Alkaline Phosphatase in Hypertensive Disorders of Pregnancy

“…In normal pregnant women it rises to a level 2-3 times higher than that of non pregnant women and do possess a long half life (seven days postpartum) [13].…”

Extremely High Isolated Maternal Alkaline Phosphatase Serum Concentration -2 Case Reports

“…Close monitoring of fetal and maternal conditions, histopathological examination of the placenta, and follow-up of declining ALP concentrations postnatally must be performed. 2 One hypothesis we can derived from this report is that mild chronic infection of the placenta may be responsible for the markedly raised ALP level in pregnancy, however more research is needed to confirm this relationship. As this condition may have high risk of recurrence in subsequent pregnancies, women should be managed in consultant led clinic Figure 1.…”

“…The mechanism responsible for the markedly elevated serum ALP due to placental origin still remains unknown. 2 Review of the literature suggests a probable correlation between significantly raised ALP levels and several perinatal complications such as low birth weight, pre-eclampsia and preterm delivery. 4,5 One study proposed that high level of ALP may cause damage to the chorionic cells as a result of placental insultthe same way in which myocardial enzymes are released into the systemic circulation from a damaged myocardial tissue.…”

“…Marked elevation of serum ALP may be caused by liver or bone pathology such as malignancy, extra hepatic biliary obstruction, and intrahepatic cholestasis. 2 We report 2 cases of markedly elevated placental isoenzymes of ALP in the third trimester in otherwise uncomplicated pregnancies. In both cases, serum ALP returned to normal level after delivery.…”