HHE Sponsored supplement: Managing perioperative bleed - Page 16

was the sole independent predictive factor for poor outcome. 4 A plasma fibrinogen level under a 2g/l threshold showed a predictive value for progression toward severe bleeding of 100% (CI 95% 79–100). This level was higher than the ‘historical’ threshold of <1g/l, which indicated in the general population the need to initiate replacement therapy, or the 1.5g/dl threshold identified by Grottke et al in an experimental animal setting. 9 This higher threshold could be explained by a higher than normal plasma fibrinogen level during pregnancy and the post-partum period. 10 An analysis by Cortet et al of 738 women with PPH clearly confirmed the importance of fibrinogen levels. 11 The mean plasma fibrinogen concentration at diagnosis was 4.2g/l (SD= 1.2g/l) among patients without worsening, and 3.4g/l (SD=0.9g/l; p<0.001) in the group developing severe PPH. The plasma fibrinogen level was again associated with PPH severity, independently of other factors, with an adjusted odds ratio of 1.90 (1.16–3.09) for fibrinogen levels between 2 and 3g/l, and 11.99 (2.56–56.06) for fibrinogen levels <2g/l. de Lloyd et al identified fibrinogen <1.5g as a marker of severity in patients admitted to the ICU. 12 Gayat et al identified fibrinogen decrease as a major component of a score to predict the need for invasive procedures. 13 Moreover, a plasma fibrinogen level has been implicated as an independent factor of intrauterine balloon. 14 With a high level of evidence, an early fibrinogen decrease and a FIBTEM 5 minutes amplitude were identified as a predictor of morbidity. 15–17 Correcting plasma fibrinogen levels Two serases are able to digest fibrinogen: thrombin (inhibitor: antithrombin) and plasmin (inhibitor: antiplasmin) and there are several ways to supplement its decrease. 18,19 Tranexamic 16 HHE 2018 | hospitalhealthcare.com acid is an antifibrinolytic drug blocking the ternary (tissue plasmin activator–plasminogen– fibrin) complex link. After a first positive high-dose trial, 20 use of tranexamic acid became more popular due to the results of a large international placebo-controlled, randomised controlled trial (RCT) – the WOMAN trial – which demonstrated a reduction in mortality due to bleeding. However in the WOMAN trial, mortality rate was as high as 2.3% because recruitment was mostly conducted in developing countries and neither mortality nor hysterectomy rate were reduced in the treatment group. 21 As an antifibrinolytic drug, tranexamic acid inhibits plasmin peak and fibrinolysis with no influence on fibrinogen. 5 Hence, fibrinogen supplementation is a specific part of the treatment of coagulopathy. To supplement fibrinogen plasma concentration, three blood products (plasma, cryoprecipitate or fibrinogen concentrates) are available. 18,22 Due to their concentration ratios, the volumes needed to increase plasma levels by 1g are 2400ml, 400ml and 100ml, for fresh frozen plasma, cryoprecipitate and fibrinogen concentrate, respectively. 22 Fibrinogen supplementation in PPH The role of fibrinogen supplementation in the management of PPH has been studied. 23–27 Efficacy of fibrinogen concentrate supplementation in PPH is demonstrated in case reports in various clinical settings. Ahmed et al retrospectively compared two periods of fibrinogen replacement using cryoprecipitate (n=14) or fibrinogen concentrate (n=20) in 77 cases of massive obstetric haemorrhages out of 21,614 deliveries. Clinicians used a mean dose of 2.21 ± 0.35 pools of cryoprecipitate or 4 ± 0.8g fibrinogen concentrates. The mean estimated