Early Use of Fibrinogen Replacement Therapy in Postpartum Hemorrhage-A Systematic Review
Transfusion medicine reviews. 2020
Fibrinogen levels drop early in postpartum hemorrhage (PPH), and low fibrinogen levels predict outcomes. There is increasing interest in replacing fibrinogen early in severe PPH and this systematic review's aim was to assess if early fibrinogen replacement therapy improves outcomes in severe PPH. We searched the following databases from inception to June 2019: CDSR and CENTRAL (The Cochrane Library), MEDLINE, Embase, CINAHL, PubMed, Transfusion Evidence Library, LILACS, Web of Science Conference Proceedings Citation Index-Science, ClinicalTrials.gov and the WHO International Clinical Trials Registry Portal. We included randomized (RCT) and well-designed controlled observational studies where fibrinogen replacement therapy was given early (within 90 minutes of bleeding) compared with standard protocol in pregnant women > 24 weeks' gestation who developed PPH, defined as estimated blood loss ≥500 mL up to 24 hours post-delivery. Two independent reviewers extracted and reviewed the data on the primary outcome of allogeneic blood transfusion at 24 hours after intervention and secondary outcomes including all-cause mortality, rate of thrombosis, and the need for surgical and non-surgical interventions. We identified 5 eligible studies: 2 completed (total of 299 women) RCTs comparing fibrinogen concentrate with placebo, and 3 ongoing RCTs. There was no completed study assessing cryoprecipitate transfusion. There was variation of: timings of intervention administration; severity of PPH; fibrinogen doses and use of tranexamic acid. There was insufficient evidence that early administration of fibrinogen in PPH reduces the need for allogeneic blood transfusion at 24 hours (risk ratio 0.83 (95% CI 0.54-1.26), P = 0.38) (2 trials, 299 participants) or improves other outcomes. Both studies were underpowered to answer our outcomes. There is a lack of evidence that early fibrinogen replacement therapy improves outcomes in PPH. Future studies are needed to address this, underpinned by data on the optimal fibrinogen dose, protocol-driven approaches versus targeted therapy, and cost-effectiveness of cryoprecipitate versus fibrinogen concentrate therapy in PPH.
Fibrinogen for the management of critical obstetric hemorrhage
The Journal of Obstetrics and Gynaecology Research. 2018;45((1):):13-21.
AIM: In cases of critical obstetric hemorrhage leading to extreme hypofibrinogenemia, fibrinogen is the marker that indicates the critical severity, and early fibrinogen supplementation centering on hemostatic resuscitation is a vital treatment to stabilize a catastrophic condition. In this review, we investigated the effect of fibrinogen level on hemostasis and what we can do to treat hypofibrinogenemia efficiently and improve patients' outcome. METHODS We reviewed numerous articles related to hypofibrinogenemia in critical obstetric hemorrhage. Especially, we performed a systematic review on target value of fibrinogen for hemostasis and effectiveness of fibrinogen concentrate. We also reviewed the articles about the methods for early normalization of fibrinogen level such as tranexamic acid, massive transfusion protocol, and point-of-care testing. RESULTS The target value of fibrinogen calculated by needs for massive transfusion was 200 mg/dL or 10 mm of A5FIBTEM . Although fibrinogen concentrate worked poorly on fibrinogen levels within the normal range, it improved the blood fibrinogen levels rapidly when it was administered to critical obstetric hemorrhage patients with serious hypofibrinogenemia. Hence, the volume of FFP transfused could be reduced along with a reduction in the frequency of pulmonary edema due to volume overload. CONCLUSION The patient group for which fibrinogen concentrate works most effectively is cases with severe hypofibrinogenemia. Further research is required in the light of evidence. The essence of the transfusion algorithm in critical obstetric hemorrhage is to approach the target value for obtaining hemostasis, ensure an accurate and prompt grasp of the severity using point-of-care testing, introduce a massive transfusion protocol and use tranexamic acid.
The role of fibrinogen and haemostatic assessment in postpartum haemorrhage
Danish Medical Journal. 2015;61((4):):pii B5055.
Pregnancy is a state of hypercoagulobility that might be an evolutionary way of protecting parturients from exsanguination following child birth. Observational studies suggest an association between a low level of fibrinogen (coagulation factor I) at the start of postpartum haemorrhage (PPH) and subsequent severity of bleeding. Fibrinogen concentrate may be prescribed to correct acquired hypofibrinogenaemia, but evidence is lacking regarding the treatment efficacy. This thesis assesses the current evidence for the use of fibrinogen concentrate and haemostatic assessment in bleeding patients with special attention to the obstetrical population. It includes five papers: In Paper I the benefits or harms of fibrinogen concentrate in bleeding patients in general was evaluated using a systematic Cochrane review methodology with metaanalysis of all published randomized controlled trials (RCTs). Six trials with high risk of bias were included (248 patients). Fibrinogen appeared to reduce the need of allogenic transfusions by 53%. However, the included trials were conducted only in an elective surgical setting with a population of mainly cardiac surgical patients. Paper II was also a systematic review based on Cochrane methodology evaluating the use of viscoelastic haemostatic assays to guide haemostatic transfusion in bleeding patients. Nine RCTs (776 patients) with high risk of bias were included primarily in elective cardiac surgical patients and none were specific for the obstetric subpopulation. Viscoelastic haemostatic assay guided transfusion algorithm reduced blood loss and the proportion of patients exposed to fresh frozen plasma (FFP) or platelets. In both studies, we were unable to make firm conclusion on our primary outcome, "all cause mortality" due to lack of adequate data. Paper III was based on two national Danish registries evaluating the predictability of postpartum blood transfusion. Prediction was found difficult. However, retained placental parts seemed to be the strongest predictor. Since this diagnosis is made very late and often in association with the onset of bleeding, tools to perform an early diagnosis is highly warranted. Paper IV includes recommendations of the European Society of Anaesthesiology regarding the use of fibrinogen concentrate in PPH, and is based on very weak (GRADE 2) evidence and low confidence in estimates of effect (GRADE C). Paper V describes the protocol for a RCT of early fibrinogen supplementation in women with severe postpartum haemorrhage. Several practical, ethical and trial management challenges need to be addressed when conducting independent clinical research involving parturients with severe bleeding, placebo-controlled and blinded administration of a drug in a multicenter set-up with enrolments during the entire day and with many personnel involved.