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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
15 – 17 identified as a predictor of morbidity.
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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 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
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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 blood loss and the subsequent morbidity and transfusion rates were similar, non-inferior, with a trend to be lower after the switch to fibrinogen concentrates. No adverse events were attributed to fibrinogen supplementation. 23 Kikuchi et al observed |
the successful correction of dilutional coagulopathy in 12 patients undergoing a PPH receiving fibrinogen concentrates. 24 Makino’ s series was larger: the Japanese five-year national survey assessed 101 severe PPH patients who received 3g fibrinogen concentrate( repeated once in 17 patients). The initial plasma fibrinogen level was 0.7g / l. Final blood loss was 4562 ± 3198ml. The single dose infusion increased the plasma fibrinogen level to 1.87 ± 0.72g / l; the supplementation was not able to reach the target of 1.5g / l for the two patients who died. 25 In this PPH cases series, the dose of fibrinogen could have been too low to correct the plasma level; the timing of administration could have been too late; the transfusion and coagulation data collected were limited to |
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