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.