Amniotic Fluid Embolism and the Possible Protective Effects of Heterozygous Factor V Leiden: A Case Report
Brandon Regional Hospital
amniotic fluid embolism, labor and delivery, factor V, perinatology
Female Urogenital Diseases and Pregnancy Complications | Obstetrics and Gynecology
Background: Amniotic fluid embolism (AFE) is a rare and commonly fatal obstetric emergency theorized to trigger an inflammatory reaction much like the systemic inflammatory response syndrome (SIRS) of sepsis, leading to vascular constriction and coagulation. This often results in acute respiratory distress syndrome (ARDS), cardiopulmonary arrest, disseminated intravascular coagulation (DIC), and death. With similar theorized mechanisms, we suspect factors that may modify mortality in sepsis may also modify mortality in AFE. Specifically, we ask if alterations in the coagulation cascade of heterozygous Factor V Leiden mutation (FVL+/-) can decrease mortality as seen in studies with severe sepsis. The following case describes the labor course of a patient with FVL+/- complicated by a postpartum AFE that did not progress to DIC.
Case Report: Patient is a 31-year-old G2P0 with a history of FVL+/- who presented for a scheduled induction of labor at 40 weeks and 5 days gestational age. Her pregnancy was otherwise uncomplicated. Emergency cesarean section was required due to an umbilical cord prolapse. Approximately 30 minutes following surgery, the patient developed sudden onset of shortness of breath, tachypnea, confusion, cyanosis, hypotension, brady-cardia, and hypoxemia with an oxygen saturation of 21% despite supplemental oxygen. She lost palpable pulses, and CPR was initiated as intubation was performed. Return of spontaneous circulation was achieved following CPR and administration of a single dose of epinephrine. She was transferred to the ICU, where she was started on Levophed for refractory hypotension. Chest X-ray showed severe airway disease, and chest CTA further demonstrated airspace opacities in both lungs. No evidence of venous thrombosis was noted. Additional lab findings showed 170 a fibrinogen level of 399 mg/dL and a normal coagulation panel and platelet range. Shortly after the cardiopulmonary arrest, there was a high concern for AFE based on the clinical scenario and imaging findings. While prognosis was initially guarded, the patient's condition drastically improved overnight. She was successfully extubated on postoperative day one following significant improvement in vitals, imaging, and was started on prophylactic Lovenox. She was transferred to the postpartum unit on postoperative day 2 with an uneventful remainder of her hospitalization until discharge on postoperative day five.
Discussion: We present the above case as an atypical presentation of AFE. While criteria set by the Society for Maternal-Fetal Medicine (SMFM) and Amniotic Fluid Embolism Foundation for AFE diagnosis includes the development of DIC, DIC is not always present in the setting of sepsis or AFE. Studies have shown that a FVL+/- carrier status in severe sepsis has been associated with improved survival in humans and mice. With AFE theorized to have mechanisms similar to the SIRS response of sepsis, we suspect factors that attenuate mortality in sepsis, such as DIC, may also have a similar result in AFE. We explored whether alterations in the coagulation cascade, as seen in FVL+/-, can alter the progression to DIC. We believe the mechanisms involved in FVL+/-, including resistance to cleavage by activated Protein C (APC), and increased thrombin formation help decrease mortality in patients with AFE, similar to what has been seen with sepsis in FVL+/- mouse studies. Although one may argue that increased circulation of thrombin can lead to multi-organ microvascular thrombosis and death, thrombin is an essential activator of APC. With increased levels of APC present and its potential to decrease morbidity and mortality by pathways preventing progression to DIC, recombinant APC is being investigated in sepsis. The (PROWESS) study demonstrated that administration of recombinant human activated protein C (drotrecogin alfa) resulted in lower mortality (24.7%) in the treatment group versus placebo group (30.8%). While further investigation, such as the PROWESS-SHOCK clinical trial, failed to yield similar results or demonstrate statistically significant improvement in mortality rates in adults with severe sepsis; other studies suggest that APC may mitigate coagulopathy and inflammatory effects in more select populations of sepsis patients, specifically phenotypes of sepsis associated coagulopathy.
Conclusion: While AFE is a very rare condition with limited risk factors and high morbidity and mortality, we believe certain protective factors may be present in populations, 171 including FVL+/-. Whether FVL+/- is an evolutionary advantage given the high prevalence in the population versus an unfavorable inheritance remains controversial. It seems the largest protection of FVL+/- lies behind its mechanism to decrease mortality in severe sepsis and possibly DIC development, which may be protective for patients with suspected AFE. To our knowledge, there are no published cases describing the effects of FVL+/- on AFE prognosis. We believe that additional studies may be extremely beneficial to improve the morbidity and mortality of this rare, but deadly, disease. Additionally, we believe further research on the realm of FVL+/- carriers in sepsis can help improve survival rates among pregnant sepsis patients as well.
Publisher or Conference
The Central Association of Obstetricians and Gynecologists
Amniotic Fluid Embolism and the Possible Protective Effects of Heterozygous Factor V Leiden: A Case Report. Poster presented at: The Central Association of Obstetricians and Gynecologists; November 7, 2020; Virtual Meeting.
Female Urogenital Diseases and Pregnancy Complications Commons, Obstetrics and Gynecology Commons