Fibrinogen replacement therapy in acquired perioperative bleeding

1.Introduction10
2.Pathophysiology of Fibrinogen12
2.1.Hereditary Fibrinogen Disorders12
2.1.1.Type I Fibrinogen Deficiency12
2.1.2.Type II Fibrinogen Deficiency13
2.1.3.Laboratory Testing and Treatments13
2.2.Genetic Polymorphisms and Altered Fibrin Structure13
2.3.Hyperfibrinogenaemia14
2.4.Disseminated Intravascular Coagulation14
2.5.Fibrinogen Disorders in Major Trauma14
2.6.Fibrinogen Disorders in Cardiovascular Surgery16
2.7.Fibrinogen Disorders in Liver Transplantation17
2.8.Fibrinogen Disorders in Obstetric Haemorrhage18
2.9.Summary and Perspectives18
2.10.References19
3.Fibrinogen in Cardiac Surgery24
3.1.Mechanisms of Fibrinogen Consumption during Cardiac Surgery24
3.2.The Association between Bleeding and Fibrinogen Levels25
3.3.Fibrinogen Supplementation in Cardiac Surgery27
3.4.Paediatric Setting30
3.5.Conclusion30
3.6.References31
4.Fibrinogen and Other Factor Concentrates in Trauma Bleeding33
4.1.Mechanism of Bleeding in Trauma – Setting the Scene33
4.2.Monitoring – or Why are Viscoelastic Tests Important34
4.3.Fibrinogen Concentrate – How and Why35
4.4.Timing for Fibrinogen – Sequence of Actions38
4.5.Is there an Indication for Prothrombin Complex Concentrate (PCC) in Trauma?38
4.6.PCC, New Oral Anticoagulant Agents (NOACs) and Trauma39
4.7.One Patient – More Than One Concentrated Factor: Both Fibrinogen and PCC40
4.8.Conclusion41
4.9.References41
5.Fibrinogen and Peri-Partum Haemorrhage45
5.1.Hypofibrinogenaemia is a Risk Marker of PPH Severity46
5.2.The Way to Correct Fibrinogen Plasma Level47
5.3.When Should Hypofibrinogenaemia Be Corrected?50
5.4.Which Fibrinogen Concentrate Dose Target to Stop Bleeding?51
5.5.Is Concomitant Inhibition of Fibrinolysis Indicated?51
5.6.When do We Need Drugs to Boost Thrombin Generation?52
5.7.Factor XIII in PPH Induced Coagulopathy52
5.8.Balanced Benefit Risk Regarding Side Effects and Economic Balance54
5.9.Who Should Correct Hypofibrinogenaemia?54
5.10.Conclusion54
5.11.References54
6.Fibrinogen and Other Concentrates in Paediatric Patients57
6.1.Fibrinogen Physiologic and Pathological Role in Haemostasis57
6.2.Fibrinogen Supplementation Modalities58
6.3.Fibrinogen Concentrate58
6.4.Prothrombin Complex Concentrate59
6.5.Factor XIII Concentrate60
6.6.Recombinant Activated Factor VII60
6.7.Antifibrinolytics60
6.8.References61
7.Fibrinogen Replacement: Plasma, Cryoprecipitate, Concentrate64
7.1.Available Sources for Fibrinogen Supplementation64
7.2.Use and Comparison of Plasma and Fibrinogen Concentrate65
7.3.Further Research, Experimental Studies and Outlook of Fibrinogen Supplementation66
7.4.Conclusion66
7.5.References66
8.Factor Concentrates (Fibrinogen, PCC, FXIII) versus Cryoprecipitate70
8.1.Cryoprecipitate70
8.2.Prothrombin Complex Concentrates72
8.3.Factor XIII73
8.4.Fibrinogen Concentrate73
8.5.Conclusion74
8.6.References74
9.Factor Concentrates (Fibrinogen, PCC, FXIII) versus FFP in Patient Blood
Management77
9.1.Fresh Frozen Plasma77
9.2.Fibrinogen80
9.3.Prothrombin Complex Concentrate82
9.4.FXIII83
9.5.Conclusion85
9.6.References85
10.Fibrinogen in the ESA Guidelines91
10.1.An Introduction to the GRADE System91
10.2.Fibrinogen Recommendations of the ESA Guideline 201794
10.3.Randomized Controlled Trials Evaluating Fibrinogen Concentrate94
10.4.Bias Assessment of Randomized Controlled Trials94
10.5.Bias related to observational, non-randomized studies99
10.6.Conclusion101
10.7.References101
Index103