Early treatment with Fibrinogen γ-chain peptide-coated, ADP-encapsulated Liposomes (H12-(ADP)-liposomes) ameliorates post-partum hemorrhage with coagulopathy caused by amniotic fluid embolism in rabbits

© 2023 The Authors..

BACKGROUND: Amniotic fluid embolism is an unpredictable and sometimes lethal complication of childbirth. Fibrinogen γ-chain peptide-coated, ADP-encapsulated Liposomes (H12-(ADP)-liposomes), which were developed as a platelet substitute, may be useful to control postpartum hemorrhage with consumptive coagulopathy.

OBJECTIVE: This study aimed to establish a hemodynamically stable amniotic fluid embolism animal model and evaluate the efficacy of H12-ADP-liposome infusion in the initial management of postpartum hemorrhage complicated with amniotic fluid embolism-involved coagulopathy.

STUDY DESIGN: Pregnant New Zealand white rabbits (28th day of pregnancy or normal gestation period of 29-35 days) underwent cesarean delivery, followed by intravenous administration of amniotic fluid (a total of 3.0 mL administered in 4 doses over 9 minutes). Thereafter, uncontrolled postpartum hemorrhage was induced by transecting the right midartery and concomitant vein in the myometrium. After initial bleeding for 5 minutes, rabbits received isovolemic fluid resuscitation through the femoral vein with an equivalent volume of blood loss every 5 minutes for 60 minutes. The transfusion regimens included platelet-rich plasma, platelet-poor plasma, and a bolus administration of H12-ADP-liposomes followed by platelet-poor plasma transfusion (8 rabbits per group). Moreover, 60 minutes after initiation of bleeding, rabbits received surgical hemostasis by ligation of bleeding vessels, except in cases with spontaneous hemostasis.

RESULTS: The administration of amniotic fluid caused thrombocytopenia (56±3 × 103/μL) and prolonged both clotting time (before administration: 130.0±3.0 to 171.0±5.0 seconds) and prothrombin time (4.5±0.1 to 4.7±0.1 seconds). After the initial 5-minute bleeding in the rabbits, the mean arterial pressure fell to 43±2 mm Hg. Platelet-poor plasma transfusion alone further prolonged clotting time and prothrombin time at 60 minutes (192.0±10.0 and 5.2±0.1 seconds, respectively) with decreasing mean arterial pressure to <40 mm Hg. By contrast, the administration of H12-ADP-liposomes followed by platelet-poor plasma transfusion reduced the prolonged clotting time (153.0±5.0 seconds) and prothrombin time (4.9±0.1 seconds) similar to platelet-rich plasma transfusion (154.0±11.0 and 4.9±0.1 seconds, respectively) at 60 minutes. These rabbits maintained a mean arterial pressure of >45 mm Hg throughout the experiment. H12-ADP-liposome infusion and platelet-poor plasma transfusion and platelet-rich plasma transfusion yielded spontaneous hemostasis in 4 of 8 rabbits, whereas platelet-poor plasma transfusion did not stop bleeding in any of the rabbits. The total blood loss was 59±17 mL in the H12-ADP-liposomes and platelet-poor plasma group, which was half of that in the platelet-poor plasma group (124±10 mL).

CONCLUSION: H12-ADP-liposome infusion may be effective in the initial management of postpartum hemorrhage complicated with amniotic fluid embolism, resulting in mitigation of consumptive coagulopathy.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:3

Enthalten in:

AJOG global reports - 3(2023), 4 vom: 19. Nov., Seite 100280

Sprache:

Englisch

Beteiligte Personen:

Kaneko, Koki [VerfasserIn]
Hagisawa, Kohsuke [VerfasserIn]
Kinoshita, Manabu [VerfasserIn]
Ohtsuka, Yuka [VerfasserIn]
Sasa, Ruka [VerfasserIn]
Hotta, Morihiro [VerfasserIn]
Saitoh, Daizoh [VerfasserIn]
Sato, Kimiya [VerfasserIn]
Takeoka, Shinji [VerfasserIn]
Terui, Katsuo [VerfasserIn]

Links:

Volltext

Themen:

Amniotic fluid embolism
Artificial platelet substitute
Disseminated intravascular coagulation
Journal Article
Postpartum hemorrhage

Anmerkungen:

Date Revised 05.12.2023

published: Electronic-eCollection

Citation Status PubMed-not-MEDLINE

doi:

10.1016/j.xagr.2023.100280

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM365375004