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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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