Comparative analysis of hyperfibrinolysis with activated coagulation between amniotic fluid embolism and severe placental abruption

Abstract

Amniotic fluid embolism (AFE) and placental abruption (PA) are typical obstetric diseases associated with disseminated intravascular coagulation (DIC). AFE is more likely to be complicated with enhanced fibrinolysis than PA. AFE may have an additional mechanism activating fibrinolytic cascade. We aimed to compare the coagulation/fibrinolysis factors among AFE, PA, and peripartum controls. We assessed AFE cases registered in the Japanese AFE Registry, and PA cases complicated with DIC (severe PA) and peripartum controls recruited at our hospital. The following factors in plasma were compared: prothrombin fragment 1 + 2 (PF1 + 2), plasmin α2-plasmin inhibitor complex (PIC), tissue factor (TF), tissue plasminogen activator (tPA), annexin A2 (AnnA2), total thrombin activatable fibrinolysis inhibitor (TAFI) including its activated form (TAFIa), and plasminogen activator inhibitor-type 1 (PAI-1). PF1 + 2 and PIC were markedly increased in both AFE (n = 27) and severe PA (n = 12) compared to controls (n = 23), without significant difference between those disease groups; however, PIC in AFE showed a tendency to elevate relative to PF1 + 2, compared with severe PA. AFE had significantly increased tPA and decreased total TAFI levels compared with severe PA and controls, which might be associated with further plasmin production in AFE and underlie its specific fibrinolytic activation pathway.

Figure 1

(a) Prothrombin fragment 1 + 2 (PF1 + 2) and (b) Plasmin α2-plasmin inhibitor complex (PIC) among groups of control, amniotic fluid embolism (AFE), and severe placental abruption (sPA). Both PF1 + 2 and PIC levels in AFE and sPA groups were significantly increased compared to the control; however, there were no significant differences between the AFE and sPA groups. Filled circles show fatal cases in the AFE group in this and all the following figures.

Figure 2

Correlation between PF1 + 2 and PIC in the (a) AFE and (b) sPA groups. There was no significant correlation between PF1 + 2 and PIC in the AFE group, whereas a positive correlation was found in the sPA group. We found a larger increase in plasma levels of PIC compared to those of PF1 + 2 in AFE patients in comparison with sPA patients.

Figure 3

Coagulation and fibrinolysis factors of interest in the control, AFE, and sPA groups. We evaluated (a) tissue factor (TF), (b) tissue plasminogen activator (tPA), (c) annexin A2 (AnnA2), (d) total thrombin activatable fibrinolysis inhibitor (total TAFI, which included TAFI and TAFIa), and (e) plasminogen activator inhibitor-type 1 (PAI-1). The AFE group had significantly increased plasma levels of tPA and decreased total TAFI. AnnA2 levels were significantly higher in sPA than AFE patients; however, there were two fatal cases with the high levels of AnnA2 in the AFE group.

Figure 4

(a) Fibrin degradation products (FDP) and (b) D-dimer classified with Clauss fibrinogen levels in AFE and sPA groups. White circles and squares represent the AFE and sPA patients, respectively. Filled circles show fatal cases in the AFE group.