Fibrinogen concentrate is a safe and comparable alternative to cryoprecipitate in critical bleeding: a retrospective audit at the Royal Hospital for Women

Abstract

Fibrinogen concentrate (FC) was implemented at the Royal Hospital for Women (RHW) in 2022 alongside cryoprecipitate, the existing standard treatment, for use in critical bleeding where the FIBTEM A5 measured on rotational thromboelastometry (ROTEM) was less than 12mm. Currently, FC is an off-label, relatively expensive alternative for acquired hypofibrinogenaemia, with the only approved indication being acute bleeding in patients with congenital fibrinogen deficiency [1]. The aim of this study was to audit relevant outcomes of the new therapy (FC) with the existing therapy (cryoprecipitate) and the practice of combining FC and cryoprecipitate for the treatment of acquired hypofibrinogenaemia in critical bleeding.

Methods Data from January 2022 to June 2024 on women with critical bleeding and fibrinogen deficit (FIBTEM A5 ≤ 12mm) demonstrated on ROTEM at the RHW, were retrospectively audited. Primary data relating to transfusion rates of packed red blood cells (PRBC), fresh frozen plasma (FFP) and platelets (PLT) within the first 24 hours of bleeding and estimated blood loss (EBL) were compared between patients who received cryoprecipitate, FC or both. Secondary data included the fibrinogen dose ratio (FC dose administered divided by the dose recommended by the local transfusion algorithm), as a marker for appropriateness of FC administration, and adverse reactions associated with treatment (thromboembolism, pulmonary oedema). Initial and repeat FIBTEM A5 values were then compared for patients for whom sequential ROTEM data were available, to assess the increment in fibrinogen levels following therapy.

Results Of the 44 patients with a FIBTEM A5 ≤12mm, 23 received FC only, 13 received cryoprecipitate only, six received both and two cases received neither. The surgical categories were obstetric (36/44 = 82%), gynaecology (5/44 = 11%) and breast (3/44 = 6%). There was no evidence of any difference in transfusion rates of PRBC, FFP or PLT, nor any difference in EBL between the three groups. The fibrinogen dose ratio was greater than one in 17/19 (89%) patients. Two patients were underdosed: the first patient was no longer bleeding and the second patient’s dose was not adjusted for a higher weight. Two adverse events occurred where clinical management deviated from the algorithm: one fluid overload with a large volume of non-ROTEM 1:1:1 pack followed by FC, and one subclinical pulmonary emboli where FC was given prophylactically. For cases where a ROTEM FIBTEM A5 was repeated after therapy, administration of cryoprecipitate, FC or both resulted in a repeat FIBTEM A5 that normalised in 10/13 (77%) patients.

Discussion When used in accordance with the RHW transfusion algorithm, FC was a safe and comparable alternative to cryoprecipitate for the correction of acquired hypofibrinogenaemia, with similar overall product administration and blood loss. In most cases, the recommended minimum dose was given and the FIBTEM A5 was corrected to within the normal range, demonstrating good compliance with the transfusion algorithm. There were no complications where the algorithm was followed correctly. The advantages of FC over cryoprecipitate include: a higher and standardised concentration of fibrinogen, storage as a powder at room temperature, rapid reconstitution without logistical delays of thawing, and administration in a smaller volume. Hospitals providing obstetric services may benefit from the convenience of FC being readily available, especially if there is no on-site blood bank. Future prospective studies, adequately powered, would be especially useful if focussed on cases of very low FIBTEM A5 or where there is a greater delay to receiving cryoprecipitate.