Death from amniotic fluid embolism

H., Zagelidou1, R., Leontari2, Z., Roupa3, K., Papadopoulou4, G., Stauropoulos5

1.

MD, PhD, Forensic Pathologist, Ministry of Justice, Forensic Department of Larissa, Greece.

2. MD, PhD, Forensic Pathologist, Ministry of Justice, Forensic Department of Larissa, Greece. 3. MD, PhD, Health Visiting Department, Technological Institute of Athens, Greece. 4. MD, Paediatrician, Greece. 5. MD, PhD, Kytarologist, Greece.

Abstract: The amniotic fluid embolism syndrome (AFES) constitutes a rare complication of pregnancy and delivery in which amniotic fluid, fetal cells, hair or other debris enter the maternal circulation, causing cardiopersiratory collapse. Disseminated intravascular coagulation (DIC), is a common feature of this syndrome. We present two cases of amniotic fluid embolism in pregnant women, with fatal outcome. One of them

died with late symptoms of disseminated intravascular coagulation. The amniotic fluid embolism syndrome and the importance of the autopsy exploration are discussed, particularly in cases with legal implications. Key words: Death, amniotic fluid embolism (AFE), disseminated intravascular contamination (DIC).

INTRODUCTION

eath during pregnancy and the postpartum period, although uncommon, presents a serious forensic problem, mainly because of the difficulty in understanding the causes and mechanism of death 1. Amniotic fluid embolism is a rare but very serious cardiorespiratory complication of delivery. This entity is considered one of the most common causes of the syndrome of disseminated intravascular coagulation, the latter often being the only presenting clinical sign 1, 2 . We discuss two cases of pregnant women who died after normal delivery, because of amniotic fluid embolism. One of them presented with clinical symptoms of DIC syndrome. The importance of autopsy performing in such cases in finding the cause and mechanism of death is discussed, particularly when they result in legal proceedings for the obstetricians involved.

Case 1: During 1995, a 19-year old pregnant woman, first para, had a normal delivery, of a male baby of BW: 2300gr after a normal pregnancy, in a district private hospital. Shortly after the delivery of the placenta and the end of the whole procedure, the woman presented vaginal haemorrhage, breathlessness and dyspnoea. Hysterectomy was decided, during which the patient died, four hours after the delivery. Autopsy findings: It was the body of a pregnant woman, 19-year old, of normal body structure, with postmortem phenomena compatible with the time of death. There were no external injuries on the body, but petechiae were found on the limbs. After the opening of the body cavities, the most important autopsy findings were brain oedema, pulmonary oedema and pulmonary congestion. The uterus was empty and the wall thickness was 5 cm.

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The histopathological examination that followed showed microscopy findings of a pregnant uterus. Lung parenchyma showed congestion, dilatation of the capillary vessels of the alveoli and oedema in the alveoli. Emboli were found in the vessels of lung circulation, consisted of epithelial cells of fetal origin and masses of neutrophils. The hepatic parenchyma showed congestion and dilatation of the periportal regions with polymorphonuclear cells. Case 2: During 1994, a 22-year old pregnant woman, para four, was transferred to a district hospital with fever, pruritus and erythema of body and limbs. She had underwent a normal delivery, after a normal pregnancy at a district private hospital, which lasted ten minutes and started 12 hours after the rupture of the membranes. The patient presented with fever, pruritus and skin rash. She was initially transferred to a district hospital, where she was treated with antipyretics, antihistaminic drugs and antibiotics and then to a Regional hospital, with the diagnosis of sepsis - disseminated intravascular coagulation, seven days after the delivery. On admission the patient was well orientated and clinical examination showed: blood pressure 100/60 mmHg, 90 beats per minute, body temperature of 39, normal heart sounds, normal breath sounds, soft abdomen, non palpable liver and spleen. Neurological examination was normal. On gynaecological examination (clinical and ultrasound), uterus was found below umbilicus, with normal findings. Radiological and cardiologic evaluation was normal. There was a diffuse petechial rash on the trunk and limbs. Blood tests showed reduced haemoatocrit, leucocytosis with many polymorphs, thrombocytopenia, abnormal PTT, decreased blood glucose, increased SGOT and SGPT, bilirubin, LDH, urea, creatinine and CPK. Having been diagnosed with disseminated intravascular coagulation syndrome, the patient was treated with administration of fluids, plasma and triple antibiotic therapy. Pharyngeal culture and urine culture were negative. She deteriorated clinically and finally died, twenty hours after the admission. Autopsy findings: It was the body of a pregnant woman, 22-year old, of normal body structure, with postmortem phenomena compatible with the time of death. No external body injuries were found. Petechiae were found on the trunk and limbs. After the opening of the body cavities, the most important autopsy findings were brain oedema, pulmonary microhaemorrhagic petechiae, pulmonary oedema and pulmonary congestion.

The histopathological examination showed oedema in the lung alveoli and emboli in the vessels of lung consisted of squamous cells of fetal origin, hair, lanugo and mucin. The myocardium showed thrombosis of small vessels and haemorrhagic elements. Sections of the uterus showed sites of necrosis. Sections of the adrenals showed sites of necrosis of the adrenal cortex, with haemorrhagic elements.

Discussion Death during pregnancy and postpartum period belongs to that category of death that conforms to the criteria of forensic investigation 3 . Amniotic fluid embolism is a rare obstetric emergency in which amniotic fluid, fetal cells, hair, or other debris enter the maternal circulation, causing cardiorespiratory collapse 4. It was recognized as a distinct entity in 1941, according to the classical clinical and anatomic description by Steiner and Luschbaugh. The incidence varies between 1:8000 and 1:80000 deliveries and it presents acutely in healthy, pregnant women who usually have many children, during normal delivery, caesarian section or after the delivery of the baby. It rarely presents some hours after the delivery, after abortion or amniocentesis 2, 3, 4, 5, 6. A case is reported five weeks after delivery 7 . The mortality rate is as high as 85% and accounts for 10% of all maternal deaths. Most women who survive have permanent neurologic impairment. Neonatal survival is 70% 4, 8. The cases we present are two normal deliveries, the first was a first para woman who died four hours after the delivery, and the second was a fourth para woman who died seven days after the delivery, while the syndrome clinically presented three days after the labor. The entry criteria for inclusion of a case in the National Registry for Amniotic Fluid Embolism in the States include 9: (a) Acute hypotension or cardiac arrest. (b) Acute hypoxia, defined as dyspnea, cyanosis, or respiratory arrest. (c) Coangulopathy, defined as laboratory evidence of intra vascular consumption or fibrinolysis or severe clinical hemorrhage in the absence of other explanations. (d) Onset of the above during labor, cesarean section, or dilation and evacuation or within 30 minutes postpartum. (e) Absence of any other significant confounding condition or potential explanation for the signs and symptoms observed. Risk factors include: advanced maternal age, multiparity, meconium, celvical laceration, intrauterine fetal death, very strong frequent or uterine tetanic constractions, uterine tetany, sudden fetal expulsion, uterine rupture, chorioamnionitis,
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macrosomia (dabetic mother), male fetal sex, maternal history of allergy or atopy (41%), polyhydramnios, placenta acreta. No colleration was seen with prolonged labour and late references exclude the advanced maternal age. Whether oxytocin use presisposes is controversial 4. One of our cases was a fourth para woman. Both our cases had male babies. The mechanism of entry of amniotic fluid in mothers circulation is related to the rupture of membranes of the fetus and possibly of the cervical veins, because of the high pressure that develops. The changes in maternal circulation that follow the obstruction of the small vessels in the lungs, are connected to the vasoactive properties of prostaglandins and fatty acids of the amniotic fluid 2, 3, 6, 10 . Cotton has proposed a biphasic model for the clinical presentation 11. Amniotic fluid and fetal cells enter the maternal circulation, triggering a 2-phase process. The phase I refers to the first hour (50%) and characterizes with usually sudden onset, cardiovascular collapse, fetal distress, tachycardia, hypotension, pulmonary edema, cyanosis, breathlessness, tachypnoea, anxiety, shivering, sweating and convulsions due to release of amniotic fluid, pulmonary artery spasm, hypoxia and left ventricular and pulmonary capillary injury. Phase II usually begins 30 minutes to 4 hours later and characterizes with bleeding, thrombolysis, LV failure and ARDS. The first of our cases presented with breathlessness, dyspnoea and bleeding after the delivery, while the latter developed the clinical signs of disseminated intravascular coagulation syndrome. The syndrome presents with the clinical signs of DIC in 50-100% of the cases 2, 3, 6, 12 . The coagulopathy observed is attributed to the procoagulant characteristics of amniotic fluid. It has been shown to release platelet factor III, has factor X activating factor properties, causes platelet aggregation, and activates complement. More recently, functionally active tissue factor has been found in increasing quantities during gestation, which may be involved 8. The similar hemodynamic derangements seen with AFES, anaphylactic and septic shock have led investigators to postulate a substance in amniotic fluid resulting in the release of primary and secondary endogenous mediators (ie arachidonic acid metabolites), which might also be responsible for the associated coagulopathy in AFE 9. Differential diagnosis includes cardiovascular, obstetrical, respiratory and other conditions 13 . Treatment is basically supportive and includes maintenance of respiratory and cardiac function, as well as management of the disorders of mechanism of coagulation fibrinolysis. The fetus is continuously monitored and emergency cesarean delivery if performed in arrested mothers who are unresponsive to resuscitation 4. Further inpatient care refers to admission of the patient into the ICU or transfer to a

level 3 hospital. There are some more aggressive, invasive methods of management of the syndrome that require cardiorespiratory bypass and thrombectomy of the pulmonary artery 14. Forensic investigation must be thorough and should include the proper evaluation of the uterus body, for the possibility of wall tears. The emboli that defined with various histopathological methods, consist mainly of epithelial cells of the fetus skin, lanugo, vernix, white cells and bile acids of meconium 2, 3, 4, 6, 13 . However, in late years, the detection of fetal squamae in central venous or pulmonary blood, once considered pathognomonic for AFE, is neither sensitive nor specific 11. The monoclonal antibody TKAH-2 may prove more useful in the rapid diagnosis of AFE 15 . In cases where fetus blood group is different from mothers, it can be proven very useful to use immunohistochemical method for finding fetus ABO antigens in maternal tissues 16. Emboli can also be found in the arterioles of myocardium, kidneys and adrenal glands. Nevertheless, this is not always the case, as can be proven in the second of our cases in which there were microscopic signs of DIC in the organs, while in both cases, emboli of amniotic fluid were found in the lungs. The prevention of fatal hemodynamic collapse in experimental AFE with inhibitors of leukotriene synthesis would support an anaphylactoid mechanism for AFE, and has prompted Clark to suggest the term anaplylactoid syndrome of pregnancy be used 9 and measurment of tryptase, released during anaphylactic reactions, seems a reasonable suggestion 17 . This entity must be considered in cases of death during pregnancy, delivery or after labor. In both our cases the obstetricians were accused by district attorney and finally found not guilty. Scientific evidence shows that AFES is an unpredictable, catastrophic event and there is no causal relationship between a medical action on a pregnant woman and lethal amniotic fluid embolism. Medical pitfalls: Failure to respond emergently is a pitfall. Failure to perform perimortem cesarean delivery in a timely fashion is a pitfall. Failure to consider the diagnosis during legal abortion is a pitfall 4. References 1. Knigtht. B. Forensic Pathology, 1991, Edward Arnold A division of Hodder & Stoughton, London Melbourne Auckland, pp 394-400. 2. Price T, Baker V, Cefalo C. Amniotic fluid embolism. Three Case Reports with a Review of the Literature. Obset Gynecol Surv 1985, 40 (7): 462-475. 3. Hanzlick R, Parrish RG, Comps D. Standard Language in Death Investigation Laws. Journal of Forensic Science 1994, 39(3): 637-643.

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4. Moore LE. Amniotic Fluid Embolism. eMedical Journal 2002, 3(3). Available at URL: [Link] 5. Steiner PE, Lushbauch CC. Maternal Pulmonary Embolism by Amniotic Fluid as a Cause of Obstetric Shock and Unexpected Deaths in Obstetrics. JAMA 1986, 255(16): 2187- 2203. 6. Dodgson J, Marin J, Boswell J, Goodau HB, Smith R. Probable amniotic fluid embolism precipitated by amniocentesis and treated by exchange transfusion. Br Med J 1987, 294: 1322-1323. 7. Attwood HD, Delprado WJ. Amniotic fluid embolism: fatal case confirmed at autopsy five weeks after delivery. Pathology 1998, 29(4): 3812. 8. Green BT, Umana E. Amniotic fluid embolism. Southern Medical Journal 2000, 93(7): 721-23. 9. Clark SL, Hankins GDV, Dudley DA, Dildy GA, Porter TF. Amniotic fluid embolism: Analysis of the national registry. Am J Obstet Gynecol 1995, 172: 1158-69. 10. Pieruzzi G, Flori M, Danesino P. An Experimental Study of Amniotic Fluid Embolism. Forensic Science 1976, 7: 214-215. 11. Clark SL. Amniotic fluid embolism. In Critical Care Obstetrics. Eds Clark SL et al, 2nd ed., 1991: pp 393-410. 12. Lurie S, Feinstein M, Mamet Y. Disseminated intravascular coagulopathy in pregnancy: thorough comprehension of etiology and

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Corresponding author: Zagelidou Helen, MD, PhD, Forensic Pathologist, Ministry of Justice, Forensic Department of Larissa, Tsakalof 1, 41221 Larissa, Greece. Tel / fax: 2410 251010

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