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

Int J Mol Sci. 2021 Feb 22;22(4):2185. doi: 10.3390/ijms22042185.

Abstract

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.

Keywords: cryoprecipitate; factor XIII; fibrinogen; trauma coagulopathy; α2-antiplasmin.

MeSH terms

  • Blood Coagulation Disorders / etiology
  • Blood Coagulation Disorders / therapy*
  • Coagulants / administration & dosage
  • Coagulants / therapeutic use*
  • Dose-Response Relationship, Drug
  • Factor VIII / therapeutic use
  • Fibrinogen / administration & dosage
  • Fibrinogen / therapeutic use*
  • Fibrinolysis
  • Hemorrhage / complications*
  • Hemorrhage / therapy
  • Humans
  • Microscopy, Confocal
  • Thrombelastography
  • Thrombin / metabolism
  • Thrombosis / chemically induced

Substances

  • Coagulants
  • cryoprecipitate coagulum
  • Factor VIII
  • Fibrinogen
  • Thrombin