Fibrinogen may aid in the early differentiation between amniotic fluid embolism and postpartum haemorrhage: a retrospective chart review.

This study aimed to determine whether blood loss and fibrinogen can differentiate amniotic fluid embolism (AFE) from postpartum haemorrhage (PPH). This retrospective case-control study included nine patients with clinical AFE ("AFE group") and 78 patients with PPH managed at our tertiary care perinatal centre between January 2014 and March 2016. Patients meeting the Japanese diagnostic criteria for AFE were stratified into cardiopulmonary collapse-type AFE and disseminated intravascular coagulation (DIC)-type AFE groups. The relationship between blood loss and fibrinogen at onset was examined to compare DIC severity. Vital signs at onset were not significantly different. The AFE group had significantly less blood loss at onset (1506 mL vs 1843 mL, P = 0.0163), significantly more blood loss 2 h post-onset (3304 mL vs 1996 mL, P < 0.0001) and more severe coagulopathy and fibrinolysis. The blood loss/fibrinogen (B/F) ratio at onset was significantly higher in the DIC-type AFE group (23.15 ± 8.07 vs 6.28 ± 3.35 mL dL/mg, P < 0.0001). AFE was complicated by catastrophic DIC irrespective of blood loss at onset. Fibrinogen exhibited the strongest correlation among test findings at onset. The B/F ratio may help differentiate PPH from DIC-type AFE and diagnose clinical AFE, facilitating optimal replacement of coagulation factors during the early stages.

Amniotic fluid embolism pathophysiology suggests the new diagnostic armamentarium: ß-tryptase and complement fractions C3-C4 are the indispensable working tools.

Amniotic fluid embolism (AFE) is an uncommon obstetric condition involving pregnant women during labor or in the initial stages after delivery. Its incidence is estimated to be around 5.5 cases per 100,000 deliveries. Therefore, this paper investigated the pathophysiological mechanism, which underlies AFE, in order to evaluate the role of immune response in the development of this still enigmatic clinical entity. The following databases (from 1956 to September 2014) Medline, Cochrane Central, Scopus, Web of Science and Science Direct were used, searching the following key words: AFE, pathophysiology, immune/inflammatory response, complement and anaphylaxis. The main key word "AFE" was searched singularly and associated individually to each of the other keywords. Of the 146 sources found, only 19 were considered appropriate for the purpose of this paper. The clinical course is characterized by a rapid onset of symptoms, which include: acute hypotension and/or cardiac arrest, acute hypoxia (with dyspnoea, cyanosis and/or respiratory arrest), coagulopathies (disseminated intravascular coagulation and/or severe hemorrhage), coma and seizures. The pathology still determines a significant morbidity and mortality and potential permanent neurological sequelae for surviving patients. At this moment, numerous aspects involving the pathophysiology and clinical development are still not understood and several hypotheses have been formulated, in particular the possible role of anaphylaxis and complement. Moreover, the detection of serum tryptase and complement components and the evaluation of fetal antigens can explain several aspects of immune response.

Challenges in managing amniotic fluid embolism: an up-to-date perspective on diagnostic testing with focus on novel biomarkers and avenues for future research.

Amniotic fluid embolism (AFE) continues to pose a formidable clinical challenge with its high rate of morbidity and mortality. A novel biomarker that acts as an early warning system for the clinician would be a welcomed addition to our medical armamentarium. Here we review the state of diagnosing AFE with our current methods of evaluation and testing along with recently discovered potential biomarkers that may be clinically efficacious. Additionally we explore the future of proteomics, lipidomics, and transcriptomics as tools to identify potential novel signaling pathways and biomarkers.

C1 esterase inhibitor activity in amniotic fluid embolism.

OBJECTIVES: Amniotic fluid embolism exhibits activation of the complement system and the kallikrein-kinin and coagulofibrinolytic systems. C1 esterase inhibitor is a major inhibitor of C1 esterase and can inhibit plasma kallikrein and also factors XIIa and XIa. Its activity has been shown to be significantly lower in pregnancy and labor than in the nonpregnant state. The purpose of this study was to determine C1 esterase inhibitor activity levels in amniotic fluid embolism. DESIGN: Retrospective study. SETTING: A single university-based center. PATIENTS: One hundred six cases with amniotic fluid embolism in a total of 194 singleton pregnant women between January 2010 and December 2011. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred six cases of amniotic fluid embolism had applied to the Japan amniotic fluid embolism registration center in Hamamatsu University School of Medicine between January 2010 and December 2011. In amniotic fluid embolism cases, 85 cases were nonfatal and 21 cases were fatal. Eighty-eight women who delivered without amniotic fluid embolism were regarded as a control. C1 esterase inhibitor activity levels were significantly lower in amniotic fluid embolism patients (30.0% ± 1.8%) than in control women (62.0% ± 2.0%) (p < 0.0001). C1 esterase inhibitor activity levels in fatal amniotic fluid embolism cases (22.5% ± 3.4%) were significantly lower than those in nonfatal amniotic fluid embolism cases (32.0% ± 2.1%) (p < 0.05). CONCLUSIONS: These results demonstrated that low C1 esterase inhibitor activity levels were closely associated with the pathogenesis of amniotic fluid embolism suggesting that C1 esterase inhibitor activity levels have potential as a prognosis factor of amniotic fluid embolism.

[Activity and role of tryptase after entrance of amniotic fluid into blood in rats].

OBJECTIVE: To investigate the activity and role of tryptase after entrance of amniotic fluid into blood in rats. METHODS: Thirty female Wistar rats (20 day pregnancy) were divided into the control group (10, injected with normal saline), amniotic group (10, injected with amniotic fluid), meconium group (10, injected with 1% meconium). After injection, pulmonary tissue was taken out. Tryptase activity was measured by special substrate. The histology of pulmonary tissue was determined by immunohistochemistry (HE). RESULTS: (1) Dropsy, hemorrhage, and infiltration of neutrophil (PMN), macrophage, leukomonocyte were observed in two experimental groups, but no such changes were found in control group. (2) After injection, tryptase activity in meconium group 176.4 +/- 8.6 and amniotic fluid group 165.4 +/- 7.4 was significantly higher than preexperimental groups 146.8 +/- 8.9 and 147.8 +/- 9.5, respectively (t = 7.58 and t = 4.64, P < 0.01); tryptase activity in control group was 145.3 +/- 10.6 before injection and 146.9 +/- 9.4 after injection, respectively, there was no difference (t = 0.37, P > 0.05). After injection, tryptase activity in meconium and amniotic fluid groups was significantly increased than that in control group (F = 30.66, P < 0.05). CONCLUSION: The activity of tryptase was significantly increased after entrance of amniotic fluid into blood in rats. Degranulation of mast cells to release tryptase may be the important cause of the pathophysiologic change after entrance of amniotic fluid into blood. These results suggest a role for mast cell activation in the mechanism of amniotic fluid embolism. This method is sensitive and effective for diagnosis of amniotic fluid embolism in clinic.

Nitrotyrosine immunostaining correlates with increased extracellular matrix: evidence of postplacental hypoxia.

Nitrotyrosine residues (NT), an index of oxidative stress arising from peroxynitrite formation and action, are found in placental vasculature of pregnancies complicated by pre-eclampsia (PE) or pregestational insulin-dependent diabetes mellitus (IDDM). This study correlates conventional placental pathology with NT immunostaining in 20 cases of perinatal mortality (13 stillbirths and seven cases of neonatal mortality) associated with PE, IDDM, amniotic fluid infection syndrome (AFIS), or from fetal/neonatal demise not related to these conditions (congenital anomalies) (n = five/group). Patients with PE have more decidual arteriolopathy and Tenney-Parker change, while patients with IDDM and ascending infection have more villous cytotrophoblastic hyperplasia. Archival paraffin-embedded placental sections were immunostained for NT for correlation with clinical features and H&E histological findings. The intensity of immunostaining for NT varied from absent (n = 7) to 1+ (n = 5) or 2+ (n = 8). All eight placentae with 2+ staining showed increased villous extracellular matrix (ECM), compared to none of five with 1+ staining and two of seven with no staining (chi2 = 14.3, P = 0.001). There was no statistically significant difference in the percentage of stem villi with luminal vascular abnormalities (5.7 vs 10 vs 35.7 per cent, F = 2.3, P = 0.1). Our data show that increased production of reactive oxygen species by placental tissue may be associated with increased extracellular matrix, itself produced by fibroblasts under the influence of oxygen. NT immunostaining may therefore help differentiate those cases of perinatal morbidity/mortality associated with post-placental hypoxia provided that the secondary impact of intrauterine fetal death can be excluded by future studies.

Expression of endothelin-1 in amniotic fluid embolism and possible pathophysiological mechanism.

Since endothelin is a potent vasoconstrictor and bronchoconstrictor, endothelin-1 expression in the lung was investigated using immunohistological techniques in two cases of amniotic fluid embolism. Intense expression of endothelin-1 was observed in amniotic squames while weaker staining was seen in alveolar epithelium, bronchiolar epithelium and intraalveolar macrophages and focally in vascular endothelium. Endothelin-1 may play a role in the early and transient haemodynamic alteration of pulmonary hypertension in amniotic fluid embolism.

[Clinico-laboratory and pathomorphologic study of intravascular blood coagulation syndrome in experimental amniotic embolism]. / Kliniko-laboratornye i patomorfologicheskie issledovaniia DVS- sindroma pri émbolii okoloplodnymi vodami v éksperimente.

The time-course of hemocoagulative and morphological changes affected by intravenous administration of amniotic fluids was examined in experiments on Chinchilla rabbits weighing 2.0-2.5 kg. Laboratory studies revealed profound phasic changes in hemocoagulation (hyper- and hypocoagulation) which were typical of the DIC syndrome. At the same time, pronounced hemocirculatory abnormalities were pathomorphologically detected chiefly in the lung; there were also highly moderate phenomena of platelet aggregation and thrombus formation. These findings suggest that the contribution made by the demands of coagulative factors is not so significant in the pathogenesis of microcirculatory abnormalities in amniotic embolism as it is generally accepted today. The paper provides evidence for expediency of performing special investigations to elucidate the real role which the DIC syndrome plays in the pathogenesis of microcirculatory abnormalities in other diseases.