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The occurrence of thrombotic microangiopathy (TMA) in pregnancy is an unfortunate emergency condition. Proper diagnosis is mandatory which requires the consideration of two overlapping diagnoses: severe preeclampsia/haemolysis, elevated liver enzymes, and low platelet syndrome (SPE/HELLP) and thrombotic thrombocytopenic purpura (TTP). The long turn-around times of ADAMTS13 testing precludes the timely distinction between the two conditions. We aimed at evaluating schistocyte counts and immature platelet fraction (IPF%), as both increase in TMAs, to discriminate between TTP and SPE/HELLP of pregnancy. IPF% was measured using Sysmex XE-2100 automated hematology analyzer, and schistocyte counts were estimated microscopically as per the International Council for Standardization in Hematology-Schistocyte Working Group guidelines. The study included 30 pregnant patients with SPE/HELLP, 13 pregnant patients with TTP, and 30 women with normal pregnancy. The discrimination between the two patient categories was based on clinical judgment and TTP cases were identified using the PLASMIC score. TTP patients had higher values of IPF% than SPE/HELLP [19.5% (16.9–27.1) vs 13% (9.5–23.25); p < 0.001]; similar results were revealed regarding schistocyte counts [6.5% (3.9–8.6) vs 2.1% (1.6–3.5); p < 0.001]. IPF% and schistocyte counts were able to discriminate between TMA patients and normal pregnant women, and between and SPE/HELLP and TTP patients. Moreover, the discriminatory function of each was improved when the two parameters were used in combination. IPF% analysis should be used in conjunction with manual schistocyte counting in TMA cases to distinguish TTP pregnant patients from patients having SPE/HELLP. [ABSTRACT FROM AUTHOR]

This study was a comprehensive analysis of placental phenotypes in hypertensive conditions of pregnancy, including recently described placental hypoxic lesions and lesions of shallow placentation. To this end, consecutive placentas from > 21 weeks pregnancies that were signed out by the author at 4 tertiary care centers on 3 continents were included. Twenty-four clinical and 50 placental phenotypes were studied in 6 groups and statistically compared: 91 cases of gestational hypertension, 187 cases of mild preeclampsia, 211 cases of severe preeclampsia, 84 cases of HELLP or eclampsia, 127 cases of chronic hypertension, and 55 cases of preeclampsia superimposed on chronic hypertension. Twenty percent of the placental and clinical phenotypes were statistically significantly different between the groups. Gestational hypertension and chronic hypertension distinguished themselves by having the highest perinatal mortality, lowest cesarean section rates, highest acute chorioamnionitis, and highest fetal vascular ectasia but conspicuously fewer differences in hypoxic and thrombotic lesions. The preeclamptic groups showed the highest rates of decidual arteriolopathy (both hypertrophic and atherosis), uterine pattern of chronic placental injury, villous infarctions, and clusters of maternal floor multinucleate trophoblasts. Based on placental pathology, severe preeclampsia may be more of a placental disease and mild preeclampsia more of a maternal disease; however, the significant overlap among the groups does not make the difference absolute, and the occurrence of decidual arteriolopathy in gestational hypertension and chronic hypertension may indicate that the conditions could be regarded as "occult preeclampsia." [ABSTRACT FROM AUTHOR]

The mother's immune system has to adapt to pregnancy accepting the semi-allograft fetus and preventing harmful effects to the developing child. Aberrations in feto-maternal immune adaptation may result in disease of the mother, such as liver injury. Five pregnancy-associated liver disorders have been described so far, however, little is known concerning immune alterations promoting the respective disease. These liver disorders are pre-eclampsia, hemolysis, elevated liver enzymes, low platelet count (HELLP), acute fatty liver, hyperemesis gravidarum, and intrahepatic cholestasis of pregnancy. On the other hand, pre-existing autoimmune liver injury of the mother can be affected by pregnancy. This review intends to summarize current knowledge linking feto-maternal immunology and liver inflammation with a special emphasis on novel potential biomarkers. [ABSTRACT FROM AUTHOR]

Gastrokines (GKNs) were originally described as stomach-specific tumor suppressor genes. Recently, we identified GKN1 in extravillous trophoblasts (EVT) of human placenta. GKN1 treatment reduced the migration of the trophoblast cell line JEG-3. GKN2 is known to inhibit the proliferation, migration and invasion of gastric cancer cells and may interact with GKN1. Recently, GKN2 was detected in the placental yolk sac of mice. We therefore aimed to further characterize placental GKN2 expression. By immunohistochemistry, healthy first-trimester placenta showed ubiquitous staining for GKN2 at its early gestational stage. At later gestational stages, a more differentiated expression pattern in EVT and villous cytotrophoblasts became evident. In healthy third-trimester placenta, only EVT retained strong GKN2 immunoreactivity. In contrast, HELLP placentas showed a tendency of increased levels of GKN2 expression with a more prominent GKN2 staining in their syncytiotrophoblast. Choriocarcinoma cell lines did not express GKN2. Besides its trophoblastic expression, we found human GKN2 in fibrotic villi, in amniotic membrane and umbilical cord. GKN2 co-localized with smooth muscle actin in villous myofibroblasts and with HLA-G and GKN1 in EVT. In the rodent placenta, GKN2 was specifically located in the spongiotrophoblast layer. Thus, the gestational age-dependent and compartment-specific expression pattern of GKN2 points to a role for placental development. The syncytial expression of GKN2 in HELLP placentas might represent a reduced state of functional differentiation of the syncytiotrophoblast. Moreover, the specific GKN2 expression in the rodent spongiotrophoblast layer (equivalent to human EVT) might suggest an important role in EVT physiology. [ABSTRACT FROM AUTHOR]

The association between antiphospholipid antibodies (aPL) and clinical problems goes beyond what is stated in the antiphospholipid syndrome (APS) classification criteria, namely thrombosis and pregnancy morbidity, and thrombocytopenia is the most common non-criteria hematologic manifestation of aPL with a frequency ranging from 20 to 50 %. Thrombocytopenia is rarely severe, and hemorrhage is far less common than thrombosis. However, when anticoagulation is considered, it may constitute a clinical problem with increased bleeding risk. Furthermore, thrombocytopenia represents a risk factor for thrombosis in aPL-positive patients. Therefore, it is important to understand the pathogenesis and the clinical associations of thrombocytopenia to build the right medical approach in aPL-positive patients. In this paper, we review the literature on aPL/APS-associated thrombocytopenia and briefly discuss the other conditions that can result in thrombocytopenia as they have commonalities with APS and their recognition is important to establish the most appropriate treatment strategy. [ABSTRACT FROM AUTHOR]

Preeclampsia can cause myriad organ dysfunction, including cranial nerve palsies that pose diagnostic and management dilemmas. We present an unusual case of third nerve palsy, (presenting as diplopia, ptosis) with hypertension, hyperreflexia, proteinuria, easy bruising in a parturient at 34 + 6/52 weeks of twins gestation. She was treated as for severe preeclampsia and HELLP syndrome; intravenous magnesium sulphate and labetalol commenced and emergent cesarean delivery performed under general anesthesia due to concerns of low platelets and for airway protection should her glascow coma scale (GCS) deteriorate. Postoperatively, stroke, aneurysm and intra-cerebral causes of third nerve palsy were excluded, with subsequent recovery of symptoms upon blood pressure normalization. The eye signs are postulated to be due to two preeclamptic mechanisms involving disordered cerebral autoregulation: (1) hyperperfusion and breakdown of the blood-brain barrier that occurs with rising hypertension, causing fluid/blood product extravasation into brain parenchyma, or (2) focal reactive vasoconstriction and local hypoperfusion, contributed to by endothelial dysfunction. [ABSTRACT FROM AUTHOR]

Background: HELLP syndrome is associated with high morbidity and mortality which is attributed most commonly to intracranial hemorrhage (ICH) and/or stroke. The presence of other complications further worsens the prognosis. Methods: We present a rare case of HELLP syndrome which presented with ICH and further complicated by seizures, disseminated intravascular coagulation, and acute renal failure. Results: Aggressive surgical and medical management of her ICH, HELLP syndrome and associated complications resulted in good functional recovery. Hypothermia seems to be a good adjunctive in treatment. Conclusion: ICH associated with HELLP syndrome when managed aggressively can have meaningful neurological recovery. [ABSTRACT FROM AUTHOR]

Lewis antigens belong to the blood group of antigens and mediate cellular adhesion through interaction with selectins. Invasive trophoblasts use an array of adhesion molecules to facilitate cell–cell and cell–extracellular matrix interactions. Here, we examined immunohistochemically the expression of Sialyl Lewis a (sLea), Sialyl Lewis x (sLex) and Lewis y (Ley) in term placentas obtained from cases of normal, intrauterine growth retardation (IUGR), preeclamptic (PE) and hemolysis, elevated liver enzymes and low platelets syndrome (HELLP) pregnancies. We report the expression of sLex in third trimester extravillous trophoblasts (EVT). sLex was significantly decreased in IUGR and moderately decreased in PE compared to normal placentas. sLex was additionally found in syncytiotrophoblast, without however any significant differences in staining intensity between normal and pathological cases. sLea was restricted to amnion epithelium. Finally, Ley was expressed in cytotrophoblasts and villous endothelial cells. Ley expression was significantly upregulated in IUGR and HELLP, whereas there was a trend toward increase in PE compared to normal placentas. The present study suggests that downregulation of sLex in EVT might be associated with IUGR and PE. Furthermore, Ley, which was recently described as a potent angiogenic factor, is upregulated in placental villi in conditions associated with placental malperfusion. [ABSTRACT FROM AUTHOR]

During human pregnancy the placenta produces a variety of proteins for the establishment of the fetoplacental unit, including inhibins and activins. Inhibins are dimeric glycoproteins, composed of an α-subunit and one of two possible β-subunits (βA or βB). Aims of the present study were (a) the determination of the frequency and tissue distribution patterns of the inhibin/activin subunits in human placental tissue of normal pregnancies and pregnancies complicated with preeclampsia and HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) and (b) the assessment of a combined expression of inhibin-α- and both β-subunits (βA- and βB-subunits) using double immunofluorescence technique. A significant lower expression of the inhibin-α subunit in preeclamptic and HELLP placental tissue compared to normal pregnancies was observed, while the inhibin-α immunostaining was significantly upregulated in syncytotrophoblast. Additionally, we demonstrated a significant down-regulation of inhibin-βB subunit in extravillous trophoblast cells between normal and preeclamptic compared to HELLP placental tissue, while inhibin-βA-subunit was significantly higher in preeclamptic syncytotrophoblast cells. A colocalization of inhibin-α and the beta-subunits could be demonstrated, suggesting a production and secretion of intact inhibin A and inhibin B. Therefore, inhibin A and activin A might be useful markers in preeclampsia. Valuable parameters in HELLP syndrome could be inhibin A, rather than inhibin B, and activin B. Furthermore, the lower βB-subunit production in extravillous trophoblast cells demonstrates that this subunit might have an important role in the pathogenesis of HELLP syndrome. Additionally, the higher production of the βA-subunit in syncytotrophoblast cells suggest a higher production of activin A rather than inhibin A in preeclampsia that might be utilized as a marker of placental function. [ABSTRACT FROM AUTHOR]

Objective:Despite emerging data on the in vitro modulatory effects of trophoblast-associated human leukocyte antigen G (HLA-G), its in vivo function needs to be determined. Immunohistochemical studies show a decrease in protein expression of trophoblast HLA-G in preeclampsia. Such a decrease in protein might be the consequence of a shift in HLA-G mRNA spliceform pattems. In an exploratory pilot study we determined trophoblast HLA-G mRNA spliceform distribution in preeclampsia.Methods:Placental samples were collected immediately after cesarean delivery from pregnancies complicated by preeclampsia or the syndrome hemolysis, elevated liver enzymes, and low platelet count (HELLP) and uncomplicated normotensive pregnancies as controls. HLA-G mRNA spliceform distribution was analyzed using a semiquantitative reverse transcriptase polymerase chain reaction procedure.Results:Analysis of HLA-G spliceform distribution showed a significant increase in frequency of the G5 form encoding for a soluble HLA-G molecule in preeclampsia. This increase in G5 form was not found in pregnancies complicated by HELLP.Conclusion:The increased frequency in the expression of the HLA-G G5 spliceform may play a role in the pathophysiology of preeclampsia, in particular through a recently suggested effect of this soluble HLA-G molecule on remodeling of the spiral arteries. [ABSTRACT FROM PUBLISHER]

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Pregnancy is considered to be a hypercoagulable state per se with an increased risk for cerebrovascular events, however cerebellar infarction has been rarely described in pregnant women. A nulliparous pre-eclamptic woman at 25 weeks’ gestation was submitted to an echocardiographic exam that showed an impaired cardiac structure and function. After 2 h, the patient underwent caesarean section for diagnosis of haemolysis, elevated liver enzymes, low platelet (HELLP) syndrome. Afterwards her platelet count raised, and eight days later she developed nystagmus, ataxia, dysmetria and motor deficit in the right limbs and sensory impairment in the right side of the face and in the left limbs. Cerebral magnetic resonance imaging (MRI) demonstrated a right cerebellar and median posterior bulbar infarction. Colour-coded sonography of cerebral vessels showed an occlusion of the right vertebral artery. Coagulation pattern analysis evidenced double heterozygosis of the methylenetetrahydrofolate reductase (MTHFR) gene and single mutation of the prothrombin gene. This case report gives evidence of the importance of considering the different risk factors involved in stroke occurrence during pregnancy. [ABSTRACT FROM AUTHOR]

Purpose of Review: The purpose of this review is to discuss current and new knowledge regarding liver disease in pregnancy and pregnancy post-liver transplantation. Recent Findings: Severe liver disease associated with pregnancy is rare. Liver biopsy is rarely needed for diagnosis but is safe in selected cases. Intrahepatic cholestasis of pregnancy (ICP) with serum bile acids level > 40 μmol/L is associated with adverse fetal outcomes. Ursodeoxycholic acid should be initiated at diagnosis. Portal hypertension can worsen during pregnancy and screening endoscopy should be performed in the 2nd trimester. Maternal hepatitis B antiviral therapy can be considered in the 3rd trimester if HVB DNA > 200,000 IU/ml. Tacrolimus is the optimal immunosuppressive therapy during pregnancy post-transplantation. Preconception renal function predicts pregnancy outcome. Overall, the outcome of pregnancy post-transplantation is good but there is an increased risk of preterm delivery, low birth weight, hypertension, and pre-eclampsia. Summary: Liver disease of pregnancy can be divided into diseases unique to pregnancy, exacerbated by pregnancy or coexisting with pregnancy. Overall, the outcome of pregnancy post-liver transplantation is good. [ABSTRACT FROM AUTHOR]