Early cryoprecipitate transfusion versus standard care in severe postpartum haemorrhage: a pilot cluster‐randomised trial

Abstract

There is a lack of evidence evaluating cryoprecipitate transfusion in severe postpartum haemorrhage. We performed a pilot cluster-randomised controlled trial to evaluate the feasibility of a trial on early cryoprecipitate delivery in severe postpartum haemorrhage. Pregnant women (>24 weeks gestation), actively bleeding within 24 h of delivery and who required at least one unit of red blood cells were eligible. Women declining transfusion in advance or with inherited clotting deficiencies were not eligible. Four UK hospitals were randomly allocated to deliver either the intervention (administration of two pools of cryoprecipitate within 90 min of first red blood cell unit requested plus standard care), or the control group treatment (standard care, where cryoprecipitate is administered later or not at all). The primary outcome was the proportion of women who received early cryoprecipitate (intervention) vs. standard care (control). Secondary outcomes included consent rates, acceptability of the intervention, safety outcomes and preliminary clinical outcome data to inform a definitive trial. Between March 2019 and January 2020, 199 participants were recruited; 19 refused consent, leaving 180 for analysis (110 in the intervention and 70 in the control group). Adherence to assigned treatment was 32% (95%CI 23-41%) in the intervention group vs. 81% (95%CI 70-90%) in the control group. The proportion of women receiving cryoprecipitate at any time-point was higher in the intervention (60%) vs. control (31%) groups; the former had fewer red blood cell transfusions at 24 h (mean difference À0.6 units, 95%CI À1.2 to 0); overall surgical procedures (odds ratio 0.6, 95%CI 0.3-1.1); and intensive care admissions (odds ratio 0.4, 95%CI 0.1-1.1). There was no increase in serious adverse or thrombotic events in the intervention group. Staff interviews showed that lack of awareness and uncertainty about study responsibilities contributed to lower adherence in the intervention group. We conclude that a full-scale trial may be feasible, provided that protocol revisions are put in place to establish clear lines of communication for ordering early cryoprecipitate in order to improve adherence. Preliminary clinical outcomes associated with cryoprecipitate administration are encouraging and merit further investigation.

Deferred consent in emergency obstetric research: findings from qualitative interviews with women and recruiters in theACROBATpilot trial for severe postpartum haemorrhage

“…The rate of refusal to consent was low (9.5%). Anonymised routine data in the absence of consent was collected in 25.1% of cases, because participants were not given study documentation prior to hospital discharge or could not be contacted postdischarge 17…”

“…The study protocol (including patient-facing documentation) and findings in relation to the feasibility of intervention delivery and main study outcomes are published separately. 17 18 Advance consent for participation was waived with Research Ethics Committee approval (Ref: 18/LO/2062). Women in both intervention and control sites were approached by the research team postnatally for written, informed consent to collect their routine, deidentified, clinical data.…”

“…The intervention group received earlier administration of cryoprecipitate (within 90 min of the first request of red blood cells for transfusion) compared with standard care, where cryoprecipitate is given later, or not at all in the haemorrhage management. The study protocol (including patient-facing documentation) and findings in relation to the feasibility of intervention delivery and main study outcomes are published separately 17 18. Advance consent for participation was waived with Research Ethics Committee approval (Ref: 18/LO/2062).…”

Comparison of Bacterial Risk in Cryo AHF and Pathogen Reduced Cryoprecipitated Fibrinogen Complex

“…Replenishing these components is important for forming stable clots and hemostasis. Recent studies have demonstrated the benefits of early replenishment of fibrinogen, namely faster bleeding control resulting in improved outcomes, among pediatric [ 5 ], trauma [ 6 ], and post-partum hemorrhage [ 7 ] patients, making a strong argument to address these deficiencies earlier. The positive impact such care has on patient blood management and overall blood utilization [ 8 ], at a time when blood supplies are strained, furthers the need for early administration of fibrinogen and key clotting factors.…”

“…Several challenges present when institutions attempt to implement earlier cryo AHF administration, largely associated with the product’s limited post-thaw shelf life of 4–6 h, resulting in an inability to prepare the product in advance of requirement without meaningful logistical challenges and wastage [ 6 , 15 , 16 ] that govern the timing of product availability. Two recent studies—Curry et al and Green et al—focused on the feasibility of transfusing cryo AHF into actively bleeding patients within 90 min and experienced several obstacles in achieving the target [ 6 , 7 ].…”