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Clinical and Experimental Obstetrics & Gynecology  2020, Vol. 47 Issue (2): 159-165    DOI: 10.31083/j.ceog.2020.02.5176
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Amniotic fluid embolism: the pathophysiology, diagnostic clue, and blood biomarkers indicator for disease prediction
R. Suvannasarn1, T. Tongsong1, P. Jatavan1, *()
1Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Chiang Mai University, Chiang Mai, Thailand
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Abstract  Objective: This article aims to review and provide more understanding of current knowledge of amniotic fluid embolism regarding pathophysiology, diagnostic criteria, risk factors, indicating biomarkers, treatment strategies and outcomes of some case reports. Study design: A systematic literature review was performed using the PubMed database, restricted to articles published in English from 1992 to 2018. Original research, case reports, guideline recommendations, and review articles were reviewed in this study. Summary: Amniotic fluid embolism (AFE) is a rare catastrophic obstetric condition defined by clinical manifestations of pregnancy with sudden onset of cardiopulmonary arrest, consumptive coagulopathy or neurological deficits without other explainable illnesses. The incidence varies from 1.7-14.8 cases per 100,000 worldwide. The current understanding of AFE pathophysiology includes fetal components obstructing maternal microvessels with subsequent anaphylactoid reaction. Maternal pulmonary vasospasm and hematologic activation occur later, followed by heart failure and sudden cardiovascular collapse. Some of the possible risk factors for AFE include; 1) Maternal risk: age over 35 years, hypertensive disorder and diabetes mellitus; 2) Fetal risk: polyhydramnios, multiparity, non-vertex at delivery, fetal distress and fetal macrosomia; 3) Obstetric risks: amniocentesis, artificial amniotic fluid injection, oxytocin infusion, and placental abruption. Some of the useful biomarkers have been proposed including zinc coproporphyrin-1, squamous cell carcinoma antigen, carcinoembryonic antigen, cancer antigen 125, Siatyl Tn, monoclonal antibody TKH-2, C3, C4, tryptase, insulin-like growth factor binding protein-1, C1 esterase inhibitor. Management of AFE requires immediate basic life support and advanced cardiac life support. Adequate oxygenation, ventilation, coagulopathy correction, and appropriate vasopressors are recommended. However, the outcome prediction of AFE remains challenging.
Key words:  Amniotic fluid embolism      Pathophysiology      Biomarker      Diagnosis      Cases     
Published:  15 April 2020     
Fund: Chiang Mai University Fund
*Corresponding Author(s):  P. Jatavan     E-mail:  kod.thanata@gmail.com

Cite this article: 

R. Suvannasarn, T. Tongsong, P. Jatavan. Amniotic fluid embolism: the pathophysiology, diagnostic clue, and blood biomarkers indicator for disease prediction. Clinical and Experimental Obstetrics & Gynecology, 2020, 47(2): 159-165.

URL: 

https://ceog.imrpress.com/EN/10.31083/j.ceog.2020.02.5176     OR     https://ceog.imrpress.com/EN/Y2020/V47/I2/159

Figure 1.  — Diagnostic criteria of AFE in different countries.

Figure 2.  — Mechanism of AFE.

Table 1  — Risk factors for AFE.
Maternal Risk Fetal Risk Obstetric Risk
- Age over 35 years - Polyhydramnios - Amniocentesis
- Hypertensive disorder - Multiparity - Artificial amniotic fluid injection
- Pre-eclampsia or eclampsia - Non-vertex at delivery - Oxytocin infusion
- Diabetes - Male fetus - Cesarean section
- Fetal distress - Forceps or vacuum-assisted delivery
- Fetal macrosomia - Uterine rupture or laceration
- Intrauterine death - Placenta previa
- Placental abruption
- Cervical laceration
Table 2  — Biomarkers and tests proposed for AFE diagnosis.
Author, Year Marker Abnormal finding AFE cases Non-AFE cases Sensitivity Specificity
Kanayama N, 1992 [20] Zinc Coproporphyrin-1 Serum level > 35 nmol/L 4 50 100% 98%
Sarandakou A, 1992 [31] CEA Serum level, Umbilical 0 56 - -
cord blood, Amniotic

CA-125
fluid level > 5 ng/ml
Serum level, Umbilical

0

56

-

-
cord blood, Amniotic

Squamous cell car-
fluid level > 35 U/ml
Serum level, Umbilical

0

56

-

-
cinoma antigen cord blood, Amniotic

Kobayashi H, 1993 [19]

Siatyl Tn
fluid level > 2.5 ng/ml
Serum level > 50 U/mL

4

32

100%

96%
Kobayashi H, 1997 [29] Monoclonal anti- Positive staining 4 4 100% 100%
body TKH-2
Benson M, 2001 [14] C3 Serum level < 70
mg/dL
6 22 87.50% 100%
C4 Serum level < 16
mg/dL
6 22 100% 100%
Tryptase Serum level > 2 SD 9 22 0% -
Sialyl Tn 22 77.80% -
Iwai K, 2011 [21] Sialyl-Tn Serum level > 47 U/ml 127 74 25.80% 97.30%
Zinc
coproporphyrin-1
Serum level > 1.6
pmol/ml
127 74 45.90% 73%
Legrand M, 2012 [23] Insulin-like growth
factor binding
Serum level > 104.5
nmol/L
25 94 92% 97.80%
protein-1
Tanura N, 2014 [25] C1 Esterase in- Serum activity level 106 88 - -
hibitor 25%
Koike N, 2017 [22] Squamous cell carcinoma antigen Serum level > 7.15 ng/mL 20 74 60.00% 89.20%
Table 3  — Cases reports of AFE and outcomes.
Author, Year Age GA (week) Route of delivery Onset Cardiac arrest Outcome Remark
MahshidN, 2009 [34] 27 35 Cesarean section Following placental delivery Yes Dead
Lee JH, 2010 [35] 33 40+6 Cesarean section 5 minutes after spinal block Yes Dead
Hosoya Y, 2013 [36] 40 36 Cesarean section - Yes Resolved
Campanharo FF 2015 [27] 33 Cesarean section Rapidly after anesthetic block No Resolved Maternal underlying of systemic lupus erythematous
Mita K, 2017 [37] 29 37 Cesarean section After placental delivery Yes Resolved Complicated with pheochromocytoma crisis
Drukker L, 2017 [15]
36 24 - Rapidly after amnio-centesis No Resolved Maternal underlying of portal hypertension, portal vein thrombosis, esophageal varices, factor V Leiden homozygosity, hypothyroidism
Tincres F, 2017 [38] 35 39 Cesarean section 4 hours after epidural analgesia Yes Resolved Successfully treated by veno-arterial extracorporeal membrane oxygenation
Lynch W, 2017 [39] 28 41 Vaginal delivery with vacuum extraction After labor epidural catheter was placed Yes Resolved Lipid emulsion infusion was applied for rescue
Chen W, 2018 [40] 28 39 Vaginal delivery with forceps extraction 20 minutes after artificial rupture of membrane Yes Dead Complicated with maternal hepatic rupture
Maack KH, 2018 [41] 40 40+2 Cesarean section Immediately after spontaneous rupture of membrane Yes Resolved Complicated with maternal right heart mass
Seong GM, 2018 [10] 32 39+1 Vaginal delivery After entirely opened cervix Yes Resolved Successfully treated by veno-arterial extracorporeal membrane oxygenation
[1] Oi H., Naruse K., Noguchi T., Sado T., Kimura S., Kanayama N., et al.: “Fatal factors of clinical manifestations and laboratory testing in patients with amniotic fluid embolism”. Gynecol. Obstet. Invest., 2010, 70, 138.
doi: 10.1159/000313302 pmid: 20424471
[2] Clark S.L., Romero R., Dildy G.A., Callaghan W.M., Smiley R.M., Bracey A.W., et al.: “Proposed diagnostic criteria for the case definition of amniotic fluid embolism in research studies”. Am. J. Obstet. Gynecol., 2016, 215, 408.
doi: 10.1016/j.ajog.2016.06.037 pmid: 27372270
[3] Kanayama N., Tamura N.: “Amniotic fluid embolism: pathophysiology and new strategies for management”. J. Obstet. Gynaecol. Res., 2014, 40, 1507.
doi: 10.1111/jog.12428 pmid: 24888909
[4] Kobayashi H., Akasaka J., Naruse K., Sado T., Tsunemi T., Niiro E., et al.: “Comparison of the Different Definition Criteria for the Diagnosis of Amniotic Fluid Embolism”. J. Clin. Diagn. Res., 2017, 11, QC18.
doi: 10.7860/JCDR/2017/26746.10283 pmid: 28892982
[5] Ito F., Akasaka J., Koike N., Uekuri C., Shigemitsu A., Kobayashi H.: “Incidence, diagnosis and pathophysiology of amniotic fluid embolism”. J. Obstet. Gynaecol., 2014, 34, 580.
doi: 10.3109/01443615.2014.919996
[6] Abenhaim H.A., Azoulay L., Kramer M.S., Leduc L.: “Incidence and risk factors of amniotic fluid embolisms: a population-based study on 3 million births in the United States”. Am. J. Obstet. Gynecol., 2008, 199, 49.e1.
[7] Kramer M.S., Rouleau J., Baskett T.F., Joseph K.S., System MHSGotCPS.: “Amniotic-fluid embolism and medical induction of labour: a retrospective, population-based cohort study”. Lancet, 2006, 368, 1444.
doi: 10.1016/S0140-6736(06)69607-4 pmid: 17055946
[8] Fitzpatrick K.E., Tuffnell D., Kurinczuk J.J., Knight M.: “Incidence, risk factors, management and outcomes of amnioticfluid embolism: a population-based cohort and nested case-control study”. BJOG, 2016, 123, 100.
doi: 10.1111/1471-0528.13300 pmid: 25683758
[9] Knight M., Berg C., Brocklehurst P., Kramer M., Lewis G., Oats J., et al.: “Amniotic fluid embolism incidence, risk factors and outcomes: a review and recommendations”. BMC Pregnancy Childbirth, 2012, 12, 7.
doi: 10.1186/1471-2393-12-7 pmid: 22325370
[10] Seong G.M., Kim S.W., Kang H.S., Kang H.W.: “Successful extracorporeal cardiopulmonary resuscitation in a postpartum patient with amniotic fluid embolism”. J. Thorac. Dis., 2018, 10, E189.
doi: 10.21037/jtd.2018.03.06 pmid: 29707371
[11] Farhana M., Tamura N., Mukai M., Ikuma K., Koumura Y., Furuta N., et al.: “Histological characteristics of the myometrium in the postpartum hemorrhage of unknown etiology: a possible involvement of local immune reactions”. J. Reprod. Immunol., 2015, 110, 74.
doi: 10.1016/j.jri.2015.04.004 pmid: 26048052
[12] Society for Maternal-Fetal Medicine(SMFM), Pacheco L.D., Saade G., Hankins G.D., Clark S.L.: “Amniotic fluid embolism: diagnosis and management”. Am. J. Obstet. Gynecol., 2016, 215, B16.
doi: 10.1016/j.ajog.2016.03.012 pmid: 26987420
[13] Busardò F.P., Frati P., Zaami S., Fineschi V. : “Amniotic fluid embolism pathophysiology suggests the new diagnostic armamentarium: β-tryptase and complement fractions C3-C4 are the indispens-able working tools”. Int. J. Mol. Sci., 2015, 16, 6557.
doi: 10.3390/ijms16036557 pmid: 25807263
[14] Benson M.D., Kobayashi H., Silver R.K., Oi H., Greenberger P.A., Terao T.: “Immunologic studies in presumed amniotic fluid embolism”. Obstet. Gynecol., 2001, 97, 510.
doi: 10.1016/s0029-7844(00)01213-8 pmid: 11275019
[15] Drukker L., Sela H.Y., Ioscovich A., Samueloff A., Grisaru- Granovsky S.: “Amniotic Fluid Embolism: A Rare Complication of Second-Trimester Amniocentesis”. Fetal Diagn. Ther., 2017, 42, 77.
doi: 10.1159/000446983 pmid: 27287307
[16] Sultan P., Seligman K., Carvalho B.: “Amniotic fluid embolism: update and review”. Curr. Opin. Anaesthesiol., 2016, 29, 288.
doi: 10.1097/ACO.0000000000000328 pmid: 27153475
[17] Oi H., Naruse K., Koike N., Tsunemi T., Shigetomi H., Kanayama N., et al.: “Predictor of mortality in patients with amniotic fluid embolism”. J. Obstet. Gynaecol. Res., 2014, 40, 941.
doi: 10.1111/jog.12278 pmid: 24320844
[18] Indraccolo U., Battistoni C., Mastrantonio I., Di Iorio R., Greco P., Indraccolo S.R.: “Risk factors for fatality in amniotic fluid embolism: a systematic review and analysis of a data pool”. J. Matern. Fetal Neonatal Med., 2018, 31, 661.
doi: 10.1080/14767058.2017.1293034 pmid: 28282766
[19] Kobayashi H., Ohi H., Terao T.: “A simple, noninvasive, sensitive method for diagnosis of amniotic fluid embolism by monoclonal antibody TKH-2 that recognizes NeuAc alpha 2-6GalNAc”. Am. J. Obstet. Gynecol., 1993, 168, 848.
doi: 10.1016/s0002-9378(12)90832-7 pmid: 8456891
[20] Kanayama N., Yamazaki T., Naruse H., Sumimoto K., Horiuchi K., Terao T.: “Determining zinc coproporphyrin in maternal plasma—a new method for diagnosing amniotic fluid embolism”. Clin. Chem., 1992, 38, 526.
pmid: 1568317
[21] Iwai Ho K., Tsunemi T., Naruse K., Noguchi T., Sado T., Kobayashi H., et al.: “Sialyl Tn and Zinc coproporphyrin1 as potential serum markers of amniotic fluid embolism”. Adv. Obstet. Gynecol., 2011, 63, 483.
[22] Koike N., Oi H., Naruse K., Kanayama N., Kobayashi H.: “Squamous cell carcinoma antigen as a novel candidate marker for amniotic fluid embolism”. J. Obstet. Gynaecol. Res., 2017, 43, 1815.
doi: 10.1111/jog.13453 pmid: 28892217
[23] Legrand M., Rossignol M., Dreux S., Luton D., Ventré C., Barranger E., et al.: “Diagnostic accuracy of insulin-like growth factor binding protein-1 for amniotic fluid embolism”. Crit. Care Med., 2012, 40, 2059.
doi: 10.1097/CCM.0b013e31824e6737 pmid: 22584758
[24] Wernet A., Luton D., Muller F., Ducarme G.: “Use of insulin-like growth factor binding protein-1 for retrospective diagnosis of amniotic fluid embolism in first trimester”. Arch. Gynecol. Obstet., 2014, 289, 461.
doi: 10.1007/s00404-013-2970-1 pmid: 23872982
[25] Tamura N., Kimura S., Farhana M., Uchida T., Suzuki K., Sugihara K., et al.: “C1 esterase inhibitor activity in amniotic fluid embolism”. Crit. Care Med., 2014, 42, 1392.
doi: 10.1097/CCM.0000000000000217 pmid: 24561565
[26] Benson M.D.: “Current concepts of immunology and diagnosis in amniotic fluid embolism”. Clin. Dev. Immunol., 2012, 2012, 946576.
doi: 10.1155/2012/946576 pmid: 21969840
[27] Campanharo F.F., Santana E.F., Araujo Júnior E., Sarmento S.G., Fernandes F.C., Sun S.Y. et al.: “Amniotic embolism with complement activation in a lupic pregnant woman”. J. Obstet. Gynaecol., 2015, 35, 416.
doi: 10.3109/01443615.2014.969206 pmid: 25356886
[28] Hiroshi Kobayashi„ Toshiyuki Sado, Taketoshi Noguchi, Shozo Yoshida„ Hiroshi Shigetomi, AOaHO. "Search for Amniotic Fluid-Specific Markers: Novel Biomarker Candidates for Amniotic Fluid Embolism". Open Womens Health J., 2011, 5, 7.
[29] Kobayashi H., Ooi H., Hayakawa H., Arai T., Matsuda Y., Gotoh K., et al.: “Histological diagnosis of amniotic fluid embolism by monoclonal antibody TKH-2 that recognizes NeuAc alpha 2-6GalNAc epitope”. Hum. Pathol., 1997, 28, 428.
doi: 10.1016/s0046-8177(97)90031-9 pmid: 9104942
[30] Nakagami H., Kajihara T., Kamei Y., Ishihara O., Kayano H., Sasaki A., et al.: “Amniotic components in the uterine vasculature and their role in amniotic fluid embolism”. J. Obstet. Gynaecol. Res., 2015, 41, 870.
doi: 10.1111/jog.12650 pmid: 25510819
[31] Sarandakou A., Kontoravdis A., Kontogeorgi Z., Rizos D., Phocas I.: “Expression of CEA, CA-125 and SCC antigen by biological fluids associated with pregnancy”. Eur. J. Obstet. Gynecol. Reprod. Biol., 1992, 44, 215.
doi: 10.1016/0028-2243(92)90102-5 pmid: 1607061
[32] Tanaka H., Katsuragi S., Osato K., Hasegawa J., Nakata M., Murakoshi T., et al.: “Value of fibrinogen in cases of maternal death related to amniotic fluid embolism”. J. Matern. Fetal Neonatal Med., 2017, 30, 2940.
doi: 10.1080/14767058.2016.1269166 pmid: 27921446
[33] Conde-Agudelo A., Romero R.: “Amniotic fluid embolism: an evidence-based review”. Am. J. Obstet. Gynecol., 2009, 201, 445.e1.
doi: 10.1016/j.ajog.2009.04.052
[34] Mahshid N., Ahmad S., Nahid M., Afshin F.: ‘Sudden cardiac arrest during cesarean section — a possible case of amniotic fluid embolism”. Middle East J. Anaesthesiol., 2009, 20, 315.
[35] Lee J.H., Yang H.J., Kim J.H., Lee S.Y., Gill H.J., Kim B.K., et al.: “Amniotic fluid embolism that took place during an emergent Cesarean section -A case report”. Korean J. Anesthesiol., 2010, 59, S158.
[36] Hosoya Y., Watanabe M., Terashima M., Amiya E., Nakao T., Hasegawa A., et al.: “Cardiac magnetic resonance imaging in a patient with amniotic fluid embolism associated with severe cardiopulmonary complications”. Int. Heart J., 2013, 54, 119.
[37] Mita K., Tsugita K., Yasuda Y., Matsuki Y., Obata Y., Kamisawa S., et al.: “A successfully treated case of cardiac arrest after Caesarean section complicated by pheochromocytoma crisis and amniotic fluid embolism”. J. Anesth., 2017, 31, 140.
doi: 10.1007/s00540-016-2281-3 pmid: 27832332
[38] Tincrès F., Conil J.M., Crognier L., Rouget A., Georges B., Ruiz S. : “Veno-arterial extracorporeal membrane oxygenation in a case of amniotic fluid embolism with coexisting hemorrhagic shock: lessons learned”. Int. J. Obstet. Anesth., 2018, 33, 99.
doi: 10.1016/j.ijoa.2017.10.002 pmid: 29203288
[39] Lynch W., McAllister R.K., Lay J.F., Culp W.C.: “Lipid Emulsion Rescue of Amniotic Fluid Embolism-Induced Cardiac Arrest: A Case Report”. Case Rep., 2017, 8(3), 64-66.
[40] Chen W., Qi J., Shang Y., Ren L., Guo Y.: “Amniotic fluid embolism and spontaneous hepatic rupture during uncomplicated pregnancy: a case report and literature review”. J. Matern. Fetal Neonatal Med., 2018, 1.
[41] Maack K.H., Munk K., Dahl K., Jørgensen H.H., Christiansen A., Helmig R.B.: “Right heart masses demonstrated by echocardiography in a patient with amniotic fluid embolism during labour”. Acta Anaesthesiol. Scand., 2018, 62, 134.
doi: 10.1111/aas.13006 pmid: 28983905
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