Introduction
Severe postpartum haemorrhage (PPH) remains the leading cause of maternal morbidity and mortality worldwide1,2. In cases requiring blood transfusions, providing adequate blood supply at the earliest time possible is essential. At least 26% of PPH-related deaths result from a lack of blood transfusion3. Blood transfusions are crucial in patients who develop severe PPH. However, access to blood markedly differs between low- and high-income countries.
Regarding initial transfusion therapy for severe PPH, packed red blood cells (RBCs), platelets, and coagulation factors are commonly used. Every obstetric facility should have a plan of comprehensive emergency management for PPH, including protocols for accessing packed RBCs4. However, blood transfusion services are highly resource intensive and require voluntary donations, donor screening, including blood-type antigen and cross-matching test, and a temperature-controlled distribution system. Thus, preparing adequate blood transfusion resources at small obstetric facilities is challenging. The spread of epidemics, including the coronavirus disease, further limits the available blood supply for transfusions worldwide5,6.
To support the blood donation and transfusion system, haemoglobin (Hb) based oxygen carriers (HBOCs) were developed as blood substitutes for RBC transfusion7. Cell-free type HBOCs exert some side effects of bared Hbs, including vasoconstriction, hypertension, and higher frequency of infarction8. These results emphasise the significance of mimicking the cellar structure of RBCs to avoid the side effects. Therefore, many studies have attempted encapsulation of Hbs using liposomes to improve their biocompatibility, storage stability, and oxygen-carrying capacity. Accordingly, haemoglobin vesicles (HbVs) as RBC substitutes were developed9,10, and the safety of HbV has been diversified previously11-15. HbVs could be useful as a resuscitative fluid for haemorrhagic shock8,16-19. Furthermore, HbVs could be stored for at least 1 year; do not need screening, including blood-type antigen or cross-matching test; and have no risk of blood contamination8,18,19.
Severe PPH is a type of haemorrhagic shock, and its resuscitative treatment is basically like that for haemorrhagic shock20. However, few studies have assessed the efficacy of HBOCs, particularly HbVs, for severe PPH. Moreover, animal models of severe PPH are limited. Yu et al. created an uncontrolled haemorrhagic shock model in pregnant rabbits21, but it was not PPH model because this haemorrhage occurred before delivery and did not satisfy the criteria for clinical PPH. This study aimed to investigate the resuscitative efficacy of HbVs for severe PPH resulting to lethal haemorrhagic shock. Towards this goal, we established a severe PPH model using pregnant rabbits based on the actual clinical treatment after delivery.