Fibrinogen Replacement Therapy for Traumatic Coagulopathy: Does the Fibrinogen Source Matter?

Fibrinogen is the first coagulation protein to reach critically low levels during traumatic haemorrhage. There have been no differential effects on clinical outcomes between the two main sources of fibrinogen replacement: cryoprecipitate and fibrinogen concentrate (Fg-C). However, the constituents of these sources are very different. The aim of this study was to determine whether these give rise to any differences in clot stability that may occur during trauma haemorrhage. Fibrinogen deficient plasma (FDP) was spiked with fibrinogen from cryoprecipitate or Fg-C. A panel of coagulation factors, rotational thromboelastography (ROTEM), thrombin generation (TG), clot lysis and confocal microscopy were performed to measure clot strength and stability. Increasing concentrations of fibrinogen from Fg-C or cryoprecipitate added to FDP strongly correlated with Clauss fibrinogen, demonstrating good recovery of fibrinogen (r2 = 0.99). A marked increase in Factor VIII, XIII and α2-antiplasmin was observed in cryoprecipitate (p < 0.05). Increasing concentrations of fibrinogen from both sources were strongly correlated with ROTEM parameters (r2 = 0.78–0.98). Cryoprecipitate therapy improved TG potential, increased fibrinolytic resistance and formed more homogeneous fibrin clots, compared to Fg-C. In summary, our data indicate that cryoprecipitate may be a superior source of fibrinogen to successfully control bleeding in trauma coagulopathy. However, these different products require evaluation in a clinical setting.

Management of Major Obstetric Haemorrhage using ROTEM Point-of-Care Haemostasis Analysers Can Reduce Blood Product usage Without Increasing Fibrinogen Replacement Therapy

Major obstetric haemorrhage (MOH) is a leading cause of maternal death and morbidity, with the majority of deaths occurring within four hours of delivery. Therefore, prompt identification of women at risk of MOH is crucial for the rapid assessment and management of blood loss to urgently restore haemodynamic stability. Furthermore, as the rate of blood loss during MOH can increase rapidly in the time when laboratory results are awaited, the management of MOH could benefit from point-of-care coagulation testing by the ROTEM analyser which has a quicker turnaround time compared to standard laboratory coagulation tests. A number of studies indicate that ROTEM-based management of MOH has resulted in a significant reduction in massive transfusions and decreased transfusion of concentrated red cells (CRC) and fresh frozen plasma (FFP) due to a reduction in total blood loss. Several reports which have linked MOH to the depletion of fibrinogen reserves indicate that the reduction in CRC and FFP transfusions is largely due to an increase in early fibrinogen replacement therapy which corrects hypofibrinogenemia. This short report discusses preliminary findings on the impact of ROTEM point-of-care haemostasis analyser on the transfusion of various blood products to obstetric women experiencing MOH at the Royal Gwent Hospital in South wales. The number of blood products transfused following decisions based on the ROTEM analyser measurements (ROTEM group) was compared to historical transfusion data before the ROTEM analyser became available (Pre-ROTEM group). Blood product transfusion in the Pre-ROTEM group was guided by measurements of standard laboratory coagulation tests in conjunction with the established major haemorrhage protocols at the time. The findings indicate that the ROTEM analyser was effective in managing MOH at point-of-care and led to a reduction in the transfusion of CRC, FFP and platelets. However, contrary to published studies, the reduction in blood product usage was not accompanied by an increase in fibrinogen replacement transfusion therapy, suggesting that the ROTEM’s FIBTEM assay accurately quantified fibrinogen levels based on fibrin-clot firmness to enable an early diagnosis of hypofibrinogenemia. Early establishment of the absence of hypofibrinogenemia helped to prevent unnecessary transfusion of fibrinogen concentrate in this study. These findings support the adoption of routine use of ROTEM analysers at point-of-care on labour wards to manage MOH and reduce fibrinogen replacement therapy. The ease of use and rapidity of ROTEM tests could enable departure from globally directed correction of coagulopathy during MOH to a more focussed and precise target transfusion therapy, which will ultimately reduce blood product wastage (including fibrinogen concentrate) whilst minimising transfusion-associated side effects such as alloimmunisation, circulatory overload and dilutional coagulopathy.

Postpartum hemorrhage: a continuing challenge

Obstetric hemorrhage remains a leading cause of maternal morbidity and mortality worldwide. Many postpartum hemorrhages (PPHs) do not have identifiable risk factors; maternity units should therefore have obstetric hemorrhageprotocols in place for all parturients as every pregnancy has the potential to be complicated by hemorrhage. This review will examine the epidemiology of PPH as well as current recommendations for key elements in obstetric hemorrhage protocols. Recent advances in hematologic management of PPH will be also be reviewed, including: (1) recognition of hypofibrinogenemia as a risk factor for severe PPH, (2) use of antifibrinolytic therapy, and (3) strategies for fibrinogen replacement therapy.

How I use fibrinogen replacement therapy in acquired bleeding

Fibrinogen is a critical protein for hemostasis and clot formation. However, transfusion guidelines have variable recommendations for maintaining fibrinogen levels in bleeding patients. An increasing number of studies support the practice of fibrinogen replacement therapy for acquired coagulopathies, and additional studies are underway. Fibrinogen therapy can be administered with cryoprecipitate or fibrinogen concentrates, and clinical practice varies according to their availability and licensing status. Fibrinogen concentrate therapy has been studied in animal models and clinical trials and supports the critical role of fibrinogen repletion in bleeding patients. Point-of-care testing will have an important role in guiding fibrinogen replacement for hemostatic therapy in clinical settings such as cardiovascular surgery, postpartum hemorrhage, and trauma. Fibrinogen therapy is an important component of a multimodal strategy for the treatment of coagulopathic bleeding.