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Journal Article•DOI•

A critical evaluation of cryoprecipitate for replacement of fibrinogen

Benny Sørensen1, David Bevan1•
King's College London1
01 Jun 2010-British Journal of Haematology (Br J Haematol)-Vol. 149, Iss: 6, pp 834-843
TL;DR: Wider availability and use of fibrinogen concentrate may improve the management of perioperative bleeding and further benefits may accrue from more rapid and accurate techniques for monitoring fibr inogen levels.
Abstract: Maintaining the plasma fibrinogen concentration is important to limit excessive perioperative blood loss. This article considers the evidence for this statement, and questions the justification for using cryoprecipitate rather than virus-inactivated fibrinogen concentrate to support plasma fibrinogen levels. Haemophilia was historically treated with cryoprecipitate, but specific coagulation factor concentrates are now preferred. In contrast, primary fractions of allogeneic donor blood, including cryoprecipitate, are still commonly used to treat perioperative bleeding. When compared with cryoprecipitate and fresh-frozen plasma (FFP), freeze-dried fibrinogen concentrate offers standardized fibrinogen content, faster reconstitution and improved efficacy. Pasteurization and purification processes employed in the preparation of fibrinogen concentrate reduce the risk of pathogen transmission and immune-mediated complications, in comparison with cryoprecipitate and FFP. When all costs associated with administration are taken into consideration, the cost of fibrinogen concentrate is not substantially different to that of cryoprecipitate. In conclusion, wider availability and use of fibrinogen concentrate may improve the management of perioperative bleeding. Further benefits may accrue from more rapid and accurate techniques for monitoring fibrinogen levels. Clinical studies are needed to evaluate methods of measuring fibrinogen and assessing fibrin polymerization, and to define critical haemostatic plasma fibrinogen concentrations in different perioperative situations.

Summary (2 min read)

Jump to: [Introduction] – [Perioperative bleeding] – [Current sources of fibrinogen] – [Efficacy] – [Safety] – [Cost and availability] and [Conclusions]

Introduction

  • In patients without pre-existing haemostatic disorders, coagulation defects that occur during surgery and/or massive haemorrhage are caused by loss, consumption and dilution of coagulation factors, collectively referred to as ‘dilutional coagulopathy’.
  • Some types of surgery disturb haemostasis in other ways: during cardiopulmonary bypass (CPB), interactions with the extracorporeal circuit activates the coagulation and fibrinolytic systems, resulting in platelet dysfunction, which is exacerbated by parallel induction of an inflammatory enzymatic cascade (Dietrich 2000).
  • Fibrinogen plays an important role in the coagulation process and clot stabilisation via its cleavage by thrombin to form fibrin polymers capable of binding factor XIII (Velik-Salchner, et al 2007), with consequent crosslinkage to form a robust fibrin network.
  • Alternatively, pasteurised human fibrinogen concentrates are available.
  • As initially stated almost a decade ago (Bevan 1999), the use of cryoprecipitate in the treatment of perioperative bleeding represents a double standard since it is contraindicated for the treatment of haemophilia, in preference for recombinant and pathogen-reduced plasma-fractionated products when available, on safety grounds.

Perioperative bleeding

  • Initially, whole blood was used in the management of perioperative bleeding, but this evolved to the use of blood components including red blood cells, FFP, cryoprecipitate and platelets.
  • Other ongoing developments include haemoglobin- or perfluorocarbon-based artificial oxygen carriers (Henkel-Honke and Oleck 2007).
  • During the era of whole-blood transfusion, thrombocytopenia was the first haemostatic abnormality observed during blood loss.
  • A further indication of the importance of fibrinogen comes from the observation that patients with high fibrinogen levels experience fewer bleeding complications than those with low levels (Blome, et al 2005, Fries, et al 2005, Pothula, et al 2004, Ucar, et al 2007a).
  • Based on this work, some current guidelines recommend transfusing fibrinogen concentrate in massive bleeding.

Current sources of fibrinogen

  • Today’s therapeutic options for supplementing plasma fibrinogen are FFP, cryoprecipitate and fibrinogen concentrate.
  • Other potential complications associated with the use of FFP include volume overload and transfusion-related acute lung injury (Stanworth 2007).
  • In afibrinogenaemia, homozygous or double heterozygous inheritance of lesions in the FGA, FGB or FGG genes encoding the paired Aα, Bβ and γ chains that form the hexameric fibrinogen molecule result in profound quantitative deficiency of fibrinogen (plasma concentration <0.1 g/L).
  • In terms of safety, cryoprecipitate retains, to a degree, the statistically low risk of pathogen transmission entailed by its single-donor origin.
  • For all these reasons, appropriately treated fibrinogen concentrate, if available, offers clear advantages over cryoprecipitate as therapy for inherited deficiencies and disorders of fibrinogen.

Efficacy

  • This is even more the case for cryoprecipitate (Danes, et al 2008), with no published studies specifically addressing the efficacy of cryoprecipitate in the management of perioperative bleeding.
  • In an observational study of 69 patients suffering from various forms of acquired severe hypofibrinogenaemia, most (62%) had consumptive hypofibrinogenaemia (Danes, et al 2008).
  • Furthermore, there was an association between plasma fibrinogen concentrations after treatment and 7-day patient survival.
  • This may reflect differences between the two study populations including underlying clinical conditions and proportion of paediatric patients.
  • There are no published studies comparing the efficacy of fibrinogen concentrate with cryoprecipitate.

Safety

  • In the past, nearly all patients with haemophilia who received factor VIII concentrates were exposed to transfusion-transmitted viruses, due to factor VIII being unable to withstand heating at 60°C during the standard pasteurisation process.
  • By 2002, four transplant-associated cases and 23 transfusion-transmitted symptomatic cases of WNV had been identified.
  • The use of methylene blue for viral inactivation of plasma was first described in 1991.
  • The authors proposed compensation for low fibrinogen content as the most plausible explanation for this increase.
  • Cryoprecipitate is not subject to the same postmarketing surveillance as fibrinogen concentrate, but has been associated with thrombotic events (Nizzi, et al 2002).

Cost and availability

  • Fibrinogen concentrate is often perceived as much more expensive than cryoprecipitate.
  • The true cost of cryoprecipitate may not be seen by operating theatre staff.

Conclusions

  • There is evidence that effective fibrinogen supplementation in patients with perioperative bleeding can: reduce blood loss, lower the requirement for transfusion of other blood components such as FFP and platelet concentrates, restore coagulation, and improve survival.
  • Where cryoprecipitate is still used, replacement with fibrinogen concentrate would offer improvements in efficacy and safety, bringing the standard of treatment for surgical patients in line with that offered to haemophilia patients.
  • Additional improvements to perioperative bleeding management may be attained by the introduction of more rapid and reliable tests for monitoring fibrinogen levels, and by clarification of the level of fibrinogen at which therapy should be initiated.
  • In congenital fibrinogen deficiencies, the argument for using current pathogenreduced fibrinogen concentrates as replacement therapy, in preference to cryoprecipitate, is very strong, although the current unlicensed status of this product in the UK is a significant impediment.

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A critical evaluation of cryoprecipitate for replacement
of brinogen
Benny Sørensen, David Bevan
To cite this version:
Benny Sørensen, David Bevan. A critical evaluation of cryoprecipitate for replacement of brinogen.
British Journal of Haematology, Wiley, 2010, 149 (6), pp.834. �10.1111/j.1365-2141.2010.08208.x�.
�hal-00552594�
For Peer Review
A critical evaluation of cryoprecipitate for replacement of
fibrinogen
Journal:
British Journal of Haematology
Manuscript ID:
BJH-2009-02003.R1
Manuscript Type:
Annotations
Date Submitted by the
Author:
25-Mar-2010
Complete List of Authors:
Sørensen, Benny; Center for Haemophilia and Thrombosis,
Department of Clinical Biochemistry
Bevan, David; Haemostasis Research Unit, Centre for Haemostasis
and Trombosis, Guy's and St Thomas NHS Trust Foundation &
King's College London School of Medicine
Key Words:
COAGULATION FACTORS, fibriogen, congentical fibrinogen
deficiency, cryprecipitate, mangement of perioperative bleeding
British Journal of Haematology
For Peer Review
Sørensen & Bevan Cryoprecipitate versus Fibrinogen concentrate
Page 1
A critical evaluation of cryoprecipitate for
replacement of fibrinogen
Benny Sørensen and David Bevan
Haemostasis Research Unit, Centre for Haemostasis and Thrombosis, Guy’s and St. Thomas’ NHS
Foundation & King’s College London School of Medicine, London, UK
Key words: Cryoprecipitate, fibrinogen concentrate, congenital fibrinogen deficiency,
acquired fibrinogen deficiency, perioperative bleeding
Word count: 4441 (excluding abstract, references, tables and figures)
Running short title: Cryoprecipitate versus Fibrinogen concentrate
Conflict of interest statements: Dr Benny Sørensen has participated in advisory
boards and/or received speaker honorariums from Novo Nordisk, Baxter, CSL
Behring, Bayer, Pentapharm, Biovitrum. Dr David Bevan has performed a CME
accredited talk on cryoprecipitate with unrestricted sponsorship provided by CSL
Behring. The Haemostasis Research Unit receives unrestricted research support from
Novo Nordisk, Grifols, CSL Behring, LFB, Baxter, Bayer, Octapharma.
Correspondence:
Benny Sørensen, E-mail: benny.sorensen@kcl.ac.uk
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Sørensen & Bevan Cryoprecipitate versus Fibrinogen concentrate
Page 2
Summary
Maintaining the plasma fibrinogen concentration is important to limit excessive
perioperative blood loss. In this review, we consider the evidence for this statement,
and question the justification for using cryoprecipitate rather than virus-inactivated
fibrinogen concentrate to support plasma fibrinogen levels. Haemophilia was
historically treated with cryoprecipitate, but specific coagulation factor concentrates
are now preferred. In contrast, primary fractions of allogeneic donor blood, including
cryoprecipitate, are still commonly used to treat perioperative bleeding.
When compared with cryoprecipitate and fresh-frozen plasma (FFP), freeze-dried
fibrinogen concentrate offers standardised fibrinogen content, faster reconstitution
and improved efficacy. Pasteurisation and purification processes employed in the
preparation of fibrinogen concentrate reduce the risk of pathogen transmission and
immune-mediated complications, in comparison with cryoprecipitate and FFP. When
all costs associated with administration are taken into consideration, the cost of
fibrinogen concentrate is not substantially different to that of cryoprecipitate.
In conclusion, wider availability and use of fibrinogen concentrate may improve the
management of perioperative bleeding. Further benefits may accrue from more rapid
and accurate techniques for monitoring fibrinogen levels. Clinical studies are needed
to evaluate methods of measuring fibrinogen and assessing fibrin polymerisation,
and to define critical haemostatic plasma fibrinogen concentrations in different
perioperative situations.
Word count: 197
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Sørensen & Bevan Cryoprecipitate versus Fibrinogen concentrate
Page 3
Introduction
In patients without pre-existing haemostatic disorders, coagulation defects that occur
during surgery and/or massive haemorrhage are caused by loss, consumption and
dilution of coagulation factors, collectively referred to as ‘dilutional coagulopathy’.
Some types of surgery disturb haemostasis in other ways: during cardiopulmonary
bypass (CPB), interactions with the extracorporeal circuit activates the coagulation
and fibrinolytic systems, resulting in platelet dysfunction, which is exacerbated by
parallel induction of an inflammatory enzymatic cascade (Dietrich 2000). In liver
surgery, portal hypertension results in splenic platelet sequestration and
thrombocytopenia (Gorlinger 2006).
Current responses to severe perioperative bleeding include transfusion of allogeneic
blood products such as red blood cell concentrates, fresh frozen plasma (FFP),
platelets, and, in a few countries, cryoprecipitate. Transfusion of fibrinogen
concentrate is not yet a standard component of such protocols in either the UK or the
USA. In the past 5 years, several studies, which are reviewed below, have revealed
the importance of supplementing fibrinogen levels in correcting coagulopathy
associated with surgery. Fibrinogen plays an important role in the coagulation
process and clot stabilisation via its cleavage by thrombin to form fibrin polymers
capable of binding factor XIII (Velik-Salchner, et al 2007), with consequent cross-
linkage to form a robust fibrin network. In addition, it induces platelet activation and
aggregation by binding to the platelet fibrinogen receptor, the α
2
β
3
integrin
GPIIb/IIIa.
Cryoprecipitate is a good source of fibrinogen prepared by controlled thawing of
frozen plasma to precipitate high molecular weight proteins. These include factor
VIII, von Willebrand factor (vWF), and fibrinogen. The precipitated proteins are
separated by centrifugation, resuspended in a small volume of plasma (typically 10–
20 mL) and stored frozen at -20°C (Poon 1993). In those countries that still use
cryoprecipitate, the current rationale is solely to provide fibrinogen. Although
cryoprecipitate is prepared as single units, these are pooled prior to administration –
a typical adult dose is 10 units (Stanworth 2007). Alternatively, pasteurised human
fibrinogen concentrates are available. In Europe, fibrinogen concentrate is well
established for treatment of congenital fibrinogen deficiency, and is increasingly
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Citations
More filters
Journal Article•DOI•
Management of severe perioperative bleeding Guidelines from the European Society of Anaesthesiology

[...]

Sibylle A. Kozek-Langenecker, Arash Afshari1, Pierre Albaladejo2, Cesar Aldecoa Alvarez Santullano3, Edoardo De Robertis4, Daniela Filipescu, Dietmar Fries5, Thorsten Haas, Georgina Imberger, Matthias Jacob6, Marcus D. Lancé7, Juan V. Llau8, Susan Mallett, Jens Meier, Niels Rahe-Meyer, Charles Marc Samama, Andrew Smith9, Cristina Solomon10, Philippe Van der Linden, Anne Wikkelsø1, Patrick Wouters, Piet Wyffels •
University of Copenhagen1, Centre Hospitalier Universitaire de Grenoble2, University of Valladolid3, University of Naples Federico II4, Innsbruck Medical University5, Ludwig Maximilian University of Munich6, Maastricht University7, University of Valencia8, Royal Lancaster Infirmary9, University of Salzburg10
01 Jun 2013-European Journal of Anaesthesiology
TL;DR: These guidelines are intended to provide an overview of current knowledge on the subject with an assessment of the quality of the evidence in order to allow anaesthetists throughout Europe to integrate this knowledge into daily patient care wherever possible.
Abstract: The aims of severe perioperative bleeding management are three-fold. First, preoperative identification by anamesis and laboratory testing of those patients for whom the perioperative bleeding risk may be increased. Second, implementation of strategies for correcting preoperative anaemia and stabilisation of the macro- and microcirculations in order to optimise the patient’s tolerance to bleeding. Third, targeted procoagulant interventions to reduce the amount of bleeding, morbidity, mortality and costs. The purpose of these guidelines is to provide an overview of current knowledge on the subject with an assessment of the quality of the evidence in order to allow anaesthetists throughout Europe to integrate this knowledge into daily patient care wherever possible. The Guidelines Committee of the European Society of Anaesthesiology (ESA) formed a task force with members of scientific subcommittees and individual expert members of the ESA. Electronic databases were searched without language restrictions from the year 2000 until 2012. These searches produced 20 664 abstracts. Relevant systematic reviews with meta-analyses, randomised controlled trials, cohort studies, case-control studies and cross-sectional surveys were selected. At the suggestion of the ESA Guideline Committee, the Scottish Intercollegiate Guidelines Network (SIGN) grading system was initially used to assess the level of evidence and to grade recommendations. During the process of guideline development, the official position of the ESA changed to favour the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. This report includes general recommendations as well as specific recommendations in various fields of surgical interventions. The final draft guideline was posted on the ESA website for four weeks and the link was sent to all ESA members. Comments were collated and the guidelines amended as appropriate. When the final draft was complete, the Guidelines Committee and ESA Board ratified the guidelines.

883 citations

Journal Article•DOI•
First-line Therapy with Coagulation Factor Concentrates Combined with Point-of-Care Coagulation Testing Is Associated with Decreased Allogeneic Blood Transfusion in Cardiovascular Surgery A Retrospective, Single-center Cohort Study

[...]

Klaus Görlinger, Daniel Dirkmann, Alexander A. Hanke, Markus Kamler, Eva Kottenberg, Matthias Thielmann, Heinz Jakob1, Jürgen Peters1 •
University of Duisburg-Essen1
01 Dec 2011-Anesthesiology
TL;DR: First-line administration of coagulation factor concentrates combined with point-of-care testing was associated with decreased incidence of blood transfusion and thrombotic/thromboembolic events.
Abstract: INTRODUCTION Blood transfusion is associated with increased morbidity and mortality. We developed and implemented an algorithm for coagulation management in cardiovascular surgery based on first-line administration of coagulation factor concentrates combined with point-of-care thromboelastometry/impedance aggregometry. METHODS In a retrospective cohort study including 3,865 patients, we analyzed the incidence of intraoperative allogeneic blood transfusions (primary endpoints) before and after algorithm implementation. RESULTS Following algorithm implementation, the incidence of any allogeneic blood transfusion (52.5 vs. 42.2%; P < 0.0001), packed red blood cells (49.7 vs. 40.4%; P < 0.0001), and fresh frozen plasma (19.4 vs. 1.1%; P < 0.0001) decreased, whereas platelet transfusion increased (10.1 vs. 13.0%; P = 0.0041). Yearly transfusion of packed red blood cells (3,276 vs. 2,959 units; P < 0.0001) and fresh frozen plasma (1986 vs. 102 units; P < 0.0001) decreased, as did the median number of packed red blood cells and fresh frozen plasma per patient. The incidence of fibrinogen concentrate (3.73 vs. 10.01%; P < 0.0001) and prothrombin complex concentrate administration (4.42 vs. 8.9%; P < 0.0001) increased, as did their amount administered per year (179 vs. 702 g; P = 0.0008 and 162 × 10³ U vs. 388 × 10³ U; P = 0.0184, respectively). Despite a switch from aprotinin to tranexamic acid, an increase in use of dual antiplatelet therapy (2.7 vs. 13.7%; P < 0.0001), patients' age, proportion of females, emergency cases, and more complex surgery, the incidence of massive transfusion [(≥10 units packed red blood cells), (2.5 vs. 1.26%; P = 0.0057)] and unplanned reexploration (4.19 vs. 2.24%; P = 0.0007) decreased. Composite thrombotic/thromboembolic events (3.19 vs. 1.77%; P = 0.0115) decreased, but in-hospital mortality did not change (5.24 vs. 5.22%; P = 0.98). CONCLUSIONS First-line administration of coagulation factor concentrates combined with point-of-care testing was associated with decreased incidence of blood transfusion and thrombotic/thromboembolic events.

382 citations

Journal Article•DOI•
Fibrinogen and hemostasis: a primary hemostatic target for the management of acquired bleeding.

[...]

Jerrold H. Levy1, Fania Szlam, Kenichi A. Tanaka, Roman M. Sniecienski•
Emory University1
01 Feb 2012-Anesthesia & Analgesia
TL;DR: The prospective study of fibrinogen supplementation in acquired bleeding is needed to accurately assess the range of clinical settings in which this management strategy is appropriate, the most effective method of supplementation and a comprehensive safety profile of fibinogen concentrate used for such an approach.
Abstract: Fibrinogen plays several key roles in the maintenance of hemostasis. Its cleavage by thrombin and subsequent polymerization to form fibrin strands provides the structural network required for effective clot formation. During cases of acute blood loss, attempts to maintain circulating volume and tissue perfusion often involve the infusion of crystalloids, colloids, and red blood cells. Intravascular volume resuscitation, although vital, frequently results in dilution of the remaining clotting factors and onset of dilutional coagulopathy. In such cases, fibrinogen is the first coagulation factor to decrease to critically low levels. There currently is a lack of awareness among physicians regarding the significance of fibrinogen during acute bleeding and, at many centers, fibrinogen is not monitored routinely during treatment. We reviewed current studies that demonstrate the importance of considering fibrinogen replacement during the treatment of acquired bleeding across clinical settings. If depleted, the supplementation of fibrinogen is key for the rescue and maintenance of hemostatic function; however, the threshold at which such intervention should be triggered is currently poorly defined. Although traditionally performed via administration of fresh frozen plasma or cryoprecipitate, the use of lyophilized fibrinogen (concentrate) is becoming more prevalent in some countries. Recent reports relating to the efficacy of fibrinogen concentrate suggest that it is a viable alternative to traditional hemostatic approaches, which should be considered. The prospective study of fibrinogen supplementation in acquired bleeding is needed to accurately assess the range of clinical settings in which this management strategy is appropriate, the most effective method of supplementation and a comprehensive safety profile of fibrinogen concentrate used for such an approach.

258 citations

Cites background from "A critical evaluation of cryoprecip..."

  • ...Cryoprecipitate is unsuitable for viral inactivation processes in its native form,(40) though plasma derivatives that have been pretreated with methylene blue or SD can be used for its production.(39) Unfortunately, such pretreatment processes can reduce the concentration of functional fibrinogen present....

    [...]

  • ...Although fibrinogen concentrate is manufactured using human plasma from a large pool of donors, the production processes involved remove antibodies and antigens, largely mitigating the risk of immunological and allergic reactions resulting from its administration.(39) It should be noted that although this risk is much reduced, as with all blood products, fibrinogen concentrate administration will always have the theoretical potential for transmission of new emerging infectious agents....

    [...]

  • ...However, the existing risk of immunological reactions and the transmission of infectious agents has led to its withdrawal in several European countries.(39) Cryoprecipitate is unsuitable for viral inactivation processes in its native form,(40) though plasma derivatives that have been pretreated with methylene blue or SD can be used for its production....

    [...]

  • ...Predicting the increase in plasma fibrinogen concentrations that will result after cryoprecipitate administration is troublesome, because of the wide variation in fibrinogen concentration between units.(39)...

    [...]

  • ...Unfortunately, such pretreatment processes can reduce the concentration of functional fibrinogen present.(39,40) As with FFP, cryoprecipitate requires blood type matching and thawing before infusion, delaying administration in time-critical situations....

    [...]

Journal Article•DOI•
Fibrinogen as a therapeutic target for bleeding: a review of critical levels and replacement therapy.

[...]

Jerrold H. Levy1, Ian J. Welsby1, Lawrence T. Goodnough2•
Duke University1, Stanford University2
01 May 2014-Transfusion
TL;DR: Results show that fibrinogen concentrate is associated with a reduction or even total avoidance of allogeneic blood product transfusion, and represents an important option for the treatment of coagulopathic bleeding; further studies are needed to determine precise dosing strategies and thresholds for fibr inogen supplementation.

253 citations

Journal Article•DOI•
Effects of fibrinogen concentrate as first-line therapy during major aortic replacement surgery: a randomized, placebo-controlled trial.

[...]

Niels Rahe-Meyer, Cristina Solomon1, Alexander A. Hanke1, Dirk S. Schmidt2, Dietrich Knoerzer2, Gerald Hochleitner2, Benny Sørensen3, Christian Hagl1, Maximilian Pichlmaier1 •
Hannover Medical School1, CSL Behring2, Guy's and St Thomas' NHS Foundation Trust3
01 Jan 2013-Anesthesiology
TL;DR: Hemostatic therapy with fibrinogen concentrate in patients undergoing aortic surgery significantly reduced the transfusion of allogeneic blood products.
Abstract: BACKGROUND Fibrinogen is suggested to play an important role in managing major bleeding. However, clinical evidence regarding the effect of fibrinogen concentrate (derived from human plasma) on transfusion is limited. The authors assessed whether fibrinogen concentrate can reduce blood transfusion when given as intraoperative, targeted, first-line hemostatic therapy in bleeding patients undergoing aortic replacement surgery. METHODS In this single-center, prospective, placebo-controlled, double-blind study, patients aged 18 yr or older undergoing elective thoracic or thoracoabdominal aortic replacement surgery involving cardiopulmonary bypass were randomized to fibrinogen concentrate or placebo, administered intraoperatively. Study medication was given if patients had clinically relevant coagulopathic bleeding immediately after removal from cardiopulmonary bypass and completion of surgical hemostasis. Dosing was individualized using the fibrin-based thromboelastometry test. If bleeding continued, a standardized transfusion protocol was followed. RESULTS Twenty-nine patients in the fibrinogen concentrate group and 32 patients in the placebo group were eligible for the efficacy analysis. During the first 24 h after the administration of study medication, patients in the fibrinogen concentrate group received fewer allogeneic blood components than did patients in the placebo group (median, 2 vs. 13 U; P < 0.001; primary endpoint). Total avoidance of transfusion was achieved in 13 (45%) of 29 patients in the fibrinogen concentrate group, whereas 32 (100%) of 32 patients in the placebo group received transfusion (P < 0.001). There was no observed safety concern with using fibrinogen concentrate during aortic surgery. CONCLUSIONS Hemostatic therapy with fibrinogen concentrate in patients undergoing aortic surgery significantly reduced the transfusion of allogeneic blood products. Larger multicenter studies are necessary to confirm the role of fibrinogen concentrate in the management of perioperative bleeding in patients with life-threatening coagulopathy.

253 citations

Additional excerpts

  • ...Diabetes mellitus, n (%) 2 (7) 1 (3) Hypertension, n (%) 21 (72) 25 (78) Hyperlipidemia, n (%) 7 (24) 7 (22) Previous myocardial infarction, n (%) 9 (31) 6 (19) Previous heart operation, n (%) 5 (17) 2 (6) Smoking, n (%) 8 (28) 8 (25) Preoperative data FIBTEM MCF, mean ± SD, mm 18 ± 6....

    [...]

References
More filters
Journal Article•DOI•
Efficacy and tolerability of human fibrinogen concentrate administration to patients with acquired fibrinogen deficiency and active or in high-risk severe bleeding.

[...]

A. Farriols Danés, L. Gallur Cuenca, S. Rodriguez Bueno, L. Mendarte Barrenechea, J. Bruno Montoro Ronsano 
01 Apr 2008-Vox Sanguinis
TL;DR: Plasma‐derived fibrinogen concentrates are indicated for reversing the haemorrhagic diathesis found in congenital and acquired deficiencies.
Abstract: Background and Objectives Fibrinogen deficiency is a cause for massive haemorrhage whose management in emergency situations is the subject of debate. Plasma-derived fibrinogen concentrates are indicated for reversing the haemorrhagic diathesis found in congenital and acquired deficiencies. Materials and Methods We report on the results of an observational study that evaluated the effects of fibrinogen concentrates in patients suffering from various forms of acquired severe hypofibrinogenaemia with life-threatening consumptive thrombo-haemorrhagic disorders (surgery, trauma and digestive haemorrhage), or underlying disease states that limit fibrinogen synthesis (hepatic dysfunction, haematological malignancies). Results Sixty-nine patients were identified and included, in whom most of the processes (62%) corresponded to consumptive hypofibrinogenaemia. After a median dose of 4 g, a mean absolute increase of 1·09 g/l in plasma fibrinogen was measured and coagulation parameters were significantly improved (P < 0·001). Mortality rates of 32·3% and 44·2% were reported after 24 h and 72 h, respectively. Conclusion We conclude that the administration of fibrinogen concentrates in unresponsive, life-threatening haemorrhage with acquired hypofibrinogenaemia improves laboratory measures of coagulation, and may also be life saving. Although observational in nature, our data indicate a direct relationship between plasma fibrinogen levels and survival in acquired fibrinogen deficiency. Further studies are warranted to ascertain a clear relationship between fibrinogen levels and survival.

132 citations

"A critical evaluation of cryoprecip..." refers background in this paper

  • ...The risk of viral transmission is similar to that with FFP, the fibrinogen concentration is variable, and blood group matching is needed (Danes et al, 2008)....

    [...]

  • ...Although scientific evidence regarding the clinical efficacy of fibrinogen concentrate is limited, this is even more the case for cryoprecipitate (Danes et al, 2008), with no published studies specifically addressing the efficacy of cryoprecipitate in the management of perioperative bleeding....

    [...]

  • ...…Aygoren-Pursun et al, 2007), and data on its use in patients with acquired deficiencies in a variety of surgical settings is beginning to emerge (Heindl et al, 2005; Danes et al, 2008; Fenger-Eriksen et al, 2008, 2009b; Haas et al, 2008; Weinkove & Rangarajan, 2008; Rahe-Meyer et al, 2009a,b)....

    [...]

  • ...%) had consumptive hypofibrinogenaemia (Danes et al, 2008)....

    [...]

  • ...There is a clear consensus that treatment with FFP is inappropriate in cases of severe fibrinogen deficiency as it contains insufficient concentrations of fibrinogen (Chowdhury et al, 2004; Danes et al, 2008)....

    [...]

Journal Article•DOI•
Coagulation management during liver transplantation

[...]

K. Goerlinger
01 Aug 2006-Hamostaseologie
TL;DR: An algorithm is summarised in an algorithm for ROTEM-based perioperative coagulation management for liver transplantation and it is shown that therapy with an antifibrinolytic drug only was necessary in 40% of the patients.
Abstract: In the course of liver transplantation many patients develop coagulation and bleeding disorders. On the other hand, some patients suffer thromboembolic events in the perioperative period with sometimes fatal outcome. For this reason, in 1999 we changed our coagulation management for liver transplantation and abolished the routine prophylaxis with antifibrinolytic drugs. In this context we implemented the ROTEM® system (Pentapharm GmbH, Munich) in our perioperative point-of-care coagulation management. From 2000 to 2005, we analysed more than 18.000 ROTEM® measurements in the context of 642 liver transplantations. Prophylactic administration of antifibrinolytic drugs was only done in patients with fulminant liver failure or if MCF in ExTEM ≤35 mm at the beginning of surgery. In the other patients hyperfibrinolysis could be detected in 60% during the operation. However, therapy with an antifibrinolytic drug was only necessary in 40% of the patients. Our experience with ROTEM® analysis was summarised in an algorithm for ROTEM® based perioperative coagulation management for liver transplantation.

130 citations

"A critical evaluation of cryoprecip..." refers background in this paper

  • ...In liver surgery, portal hypertension results in splenic platelet sequestration and thrombocytopenia (Gorlinger, 2006)....

    [...]

Journal Article•DOI•
Fibrinogen in craniosynostosis surgery.

[...]

Thorsten Haas1, Dietmar Fries, Corinna Velik-Salchner, Elgar Oswald, Petra Innerhofer •
Innsbruck Medical University1
01 Mar 2008-Anesthesia & Analgesia
TL;DR: Administration of fibrinogen concentrate effectively improves fibr inogen polymerization and total clot strength, which were the main underlying problems of dilutional coagulopathy in children undergoing craniosynostosis surgery.
Abstract: BACKGROUND:During craniosynostosis repair, massive blood loss, consumption and dilution of clotting factors often result in coagulopathy, for which cryoprecipitate, fresh frozen plasma (FFP), and platelets are recommended for treatment. However, cryoprecipitate is not available in most European coun

129 citations

"A critical evaluation of cryoprecip..." refers background in this paper

  • ...Cryoprecipitate is not available in most European countries (Haas et al, 2008) but is still used in the US and the UK whereas fibrinogen concentrate is far more widely available than cryoprecipitate in Central Europe....

    [...]

  • ...…Aygoren-Pursun et al, 2007), and data on its use in patients with acquired deficiencies in a variety of surgical settings is beginning to emerge (Heindl et al, 2005; Danes et al, 2008; Fenger-Eriksen et al, 2008, 2009b; Haas et al, 2008; Weinkove & Rangarajan, 2008; Rahe-Meyer et al, 2009a,b)....

    [...]

  • ...Several authors consider a threshold of 1 g/l to be too low when blood loss is continuing (Haas et al, 2008)....

    [...]

Journal Article•DOI•
Reduced quality of clot formation with gelatin-based plasma substitutes

[...]

S.N. Mardel, F M Saunders, H Allen, G. Menezes, C.M. Edwards, L. Ollerenshaw, D. Baddeley, A Kennedy, R M Ibbotson 
01 Feb 1998-BJA: British Journal of Anaesthesia
TL;DR: Reduction in clot quality with gelatin-based colloids has not been noted previously and further work is needed to ascertain if this occurs in vivo as these solutions are used frequently in patients who require full haemostatic competence.
Abstract: We have studied, over a wide range of dilutions using techniques of clot weight, thrombelastography and scanning electron microscopy, the physical properties of a blood clot formed in vitro when fresh blood was diluted with gelatin-based colloid solutions compared with crystalloid controls. The colloid solutions tested (3.5% polygeline (Haemaccel) and 4% succinylated gelatin (Gelofusine)) produced clots that had reduced median weight (P

129 citations

"A critical evaluation of cryoprecip..." refers methods in this paper

  • ...The Clauss method for measuring fibrinogen may give falsely high fibrinogen levels if colloids have been used for volume replacement because they impair fibrin polymerization (Hiippala, 1995; Mardel et al, 1998; Fries et al, 2002; Innerhofer et al, 2002; Mittermayr et al, 2007)....

    [...]

Journal Article•DOI•
Transfusion-related acute lung injury (TRALI) - under-diagnosed and under-reported

[...]

Wallis Jp
01 May 2003-BJA: British Journal of Anaesthesia

128 citations

"A critical evaluation of cryoprecip..." refers background in this paper

  • ...Although it is under-diagnosed (Wallis, 2003), not least because the same clinical features are seen in acute lung injury resulting from other causes such as sepsis, trauma and shock, TRALI is a common cause of transfusionrelated death....

    [...]

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