To the Editor: 

We read with interest the educational case scenario of amniotic fluid embolism (AFE) by Dean et al.  1The authors propose a flow chart for clinical management of AFE. However, we believe that the authors' diagram may depict an oversimplified approach for acquired coagulopathy during the course of AFE.

Although coagulopathic bleeding is not absolutely necessary for the diagnosis of AFE, it is still a prominent feature and one of the most challenging complications for which appropriate early intervention is crucial. The event of AFE introduces both procoagulant and anticoagulant factors into the maternal bloodstream, and ensuing imbalance of coagulation can evolve into disseminated intravascular coagulation. Alternatively, coagulopathy can result from the dilution of procoagulant factors after aggressive fluid resuscitation. The exact mechanism of bleeding during AFE remains unclear and is likely multifactorial, but hypofibrinogenemia is frequently reported.2,3Delayed fibrinogen replacement can impair hemostasis and increase morbidity and mortality from inadequate clot formation, ongoing hemorrhage, acidosis, and hypothermia.

Cryoprecipitate is mentioned in the case scenario, although the use of fibrinogen-rich products, such as cryoprecipitate or fibrinogen concentrate, is not mentioned in the flow chart or emphasized in the discussion section. The flow chart proposed by Dean et al.  suggests considering hysterectomy, recombinant factor VIIa, or uterine artery embolization for persistent uterine hemorrhage, and discontinuation of resuscitation if these efforts do not achieve hemostasis. Early fibrinogen replacement should be emphasized, and the use of recombinant factor VIIa discouraged except for cases of hemorrhage refractory to massive component transfusion. We urge caution on the use of recombinant factor VIIa when AFE is suspected, as a recent analysis of such cases revealed that the use of recombinant factor VIIa was associated with significantly increased major organ thrombosis and death.3 

The Food and Drug Administration approved fibrinogen concentrate (RiaSTAP) for treatment of congenital hypofibrinogenemia in 2009, and its successful use has been reported in the management of disseminated intravascular coagulation related to both AFE2,3and postpartum hemorrhage.4In contrast to cryoprecipitate, which takes 30–60 min to thaw before use, fibrinogen concentrate can be reconstituted and administered rapidly. Stocked at room temperature in lyophilized form, fibrinogen concentrate is a viable option even in remote locations. Moreover, it requires much less volume infused to restore adequate fibrinogen for clot integrity than cryoprecipitate or fresh frozen plasma.5 

Although there may be no flow chart that perfectly captures every potential decision point, we believe that careful coagulopathy control plays a major role in survival after AFE, and deserves more emphasis. We suggest expansion of the flow chart with greater attention on coagulopathy management. Clearly defined transfusion guidelines can be integrated with institution-specific transfusion protocols, and along with staff education, may improve AFE-related hemorrhage management.6Amendments to the existing flow chart may have major implications, because AFE is the second leading cause of maternal death in developed countries and near-miss morbidity is often a modifiable precursor.7 


Dean LS, Rogers RP 3rd, Harley RA, Hood DD: Case scenario: Amniotic fluid embolism. ANESTHESIOLOGY 2012; 116:186–92
Annecke T, Geisenberger T, Kürzl R, Penning R, Heindl B: Algorithm-based coagulation management of catastrophic amniotic fluid embolism. Blood Coagul Fibrinolysis 2010; 21:95–100
Leighton BL, Wall MH, Lockhart EM, Phillips LE, Zatta AJ: Use of recombinant factor VIIa in patients with amniotic fluid embolism: A systematic review of case reports. ANESTHESIOLOGY 2011; 115:1201–8
Bell SF, Rayment R, Collins PW, Collis RE: The use of fibrinogen concentrate to correct hypofibrinogenaemia rapidly during obstetric haemorrhage. Int J Obstet Anesth 2010; 19:218–23
British Committee for Standards in Haematology, Stainsby D, MacLennan S, Thomas D, Isaac J, Hamilton PJ: Guidelines on the management of massive blood loss. Br J Haematol 2006; 135:634–41
Rizvi F, Mackey R, Barrett T, McKenna P, Geary M: Successful reduction of massive postpartum haemorrhage by use of guidelines and staff education. BJOG 2004; 111:495–8
Geller SE, Rosenberg D, Cox SM, Brown ML, Simonson L, Driscoll CA, Kilpatrick SJ: The continuum of maternal morbidity and mortality: Factors associated with severity. Am J Obstet Gynecol 2004; 191:939–44