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Journal ArticleDOI

A critical evaluation of cryoprecipitate for replacement of fibrinogen

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)

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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For Peer Review
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
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TL;DR: The fibrinogen level at PPH diagnosis is a marker of the risk of aggravation and should serve as an alert to clinicians.
Abstract: Background The aim of the study was to determine whether the fibrinogen level at diagnosis of postpartum haemorrhage (PPH) is associated with the severity of bleeding. Methods This is a secondary analysis of a population-based study in 106 French maternity units identifying cases of PPH prospectively. PPH was defined by a blood loss exceeding 500 ml during the 24 h after delivery or a peripartum haemoglobin decrease of more than 20 g litre−1. This analysis includes 738 women with PPH after vaginal delivery. Fibrinogen levels were compared in patients whose PPH worsened and became severe and those whose PPH remained non-severe. Severe PPH was defined as haemorrhage by occurrence of one of the following events: peripartum haemoglobin decrease ≥40 g litre−1, transfusion of concentrated red cells, arterial embolization or emergency surgery, admission to intensive care, or death. Results The mean fibrinogen concentration at diagnosis was 4.2 g litre−1 [standard deviation (sd)=1.2 g litre−1] among the patients without worsening and 3.4 g litre−1 (sd=0.9 g litre−1) (P Conclusions The fibrinogen level at PPH diagnosis is a marker of the risk of aggravation and should serve as an alert to clinicians.

226 citations

Journal ArticleDOI
TL;DR: Perioperatively, fibrinogen concentrate was generally associated with improved outcome measures, although more high-quality, prospective studies are required before any definitive conclusions can be drawn, and suggests it can be detrimental.
Abstract: Haemostatic therapy in surgical and/or massive trauma patients typically involves transfusion of fresh frozen plasma (FFP). Purified human fibrinogen concentrate may offer an alternative to FFP in some instances. In this systematic review, we investigated the current evidence for the use of FFP and fibrinogen concentrate in the perioperative or massive trauma setting. Studies reporting the outcome (blood loss, transfusion requirement, length of stay, survival and plasma fibrinogen level) of FFP or fibrinogen concentrate administration to patients in a perioperative or massive trauma setting were identified in electronic databases (1995 to 2010). Studies were included regardless of type, patient age, sample size or duration of patient follow-up. Studies of patients with congenital clotting factor deficiencies or other haematological disorders were excluded. Studies were assessed for eligibility, and data were extracted and tabulated. Ninety-one eligible studies (70 FFP and 21 fibrinogen concentrate) reported outcomes of interest. Few were high-quality prospective studies. Evidence for the efficacy of FFP was inconsistent across all assessed outcomes. Overall, FFP showed a positive effect for 28% of outcomes and a negative effect for 22% of outcomes. There was limited evidence that FFP reduced mortality: 50% of outcomes associated FFP with reduced mortality (typically trauma and/or massive bleeding), and 20% were associated with increased mortality (typically surgical and/or nonmassive bleeding). Five studies reported the outcome of fibrinogen concentrate versus a comparator. The evidence was consistently positive (70% of all outcomes), with no negative effects reported (0% of all outcomes). Fibrinogen concentrate was compared directly with FFP in three high-quality studies and was found to be superior for > 50% of outcomes in terms of reducing blood loss, allogeneic transfusion requirements, length of intensive care unit and hospital stay and increasing plasma fibrinogen levels. We found no fibrinogen concentrate comparator studies in patients with haemorrhage due to massive trauma, although efficacy across all assessed outcomes was reported in a number of noncomparator trauma studies. The weight of evidence does not appear to support the clinical effectiveness of FFP for surgical and/or massive trauma patients and suggests it can be detrimental. Perioperatively, fibrinogen concentrate was generally associated with improved outcome measures, although more high-quality, prospective studies are required before any definitive conclusions can be drawn.

210 citations


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  • ...However, despite growing evidence based on both preclinical and clinical studies to support its efficacy and safety [17-20], fibrinogen concentrate is not yet a standard component of many transfusion protocols....

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TL;DR: The concept of early, individualized and goal-directed therapy is explored in this review and the AUVA Trauma Hospital algorithm for managing trauma-induced coagulopathy is presented.
Abstract: Severe trauma-related bleeding is associated with high mortality. Standard coagulation tests provide limited information on the underlying coagulation disorder. Whole-blood viscoelastic tests such as rotational thromboelastometry or thrombelastography offer a more comprehensive insight into the coagulation process in trauma. The results are available within minutes and they provide information about the initiation of coagulation, the speed of clot formation, and the quality and stability of the clot. Viscoelastic tests have the potential to guide coagulation therapy according to the actual needs of each patient, reducing the risks of over- or under-transfusion. The concept of early, individualized and goal-directed therapy is explored in this review and the AUVA Trauma Hospital algorithm for managing trauma-induced coagulopathy is presented.

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

  • ...Cryoprecipitate, another source of fibrinogen, is still available in the US and the UK, but it has been withdrawn from some European countries in response to significant safety concerns [72]....

    [...]

Journal ArticleDOI
TL;DR: Emerging evidence suggests that viscoelastic monitoring, using thrombelastography- or thromboelastometry-based tests, may be useful for rapid assessment and for guiding haemostatic therapy during PPH, but further studies are needed to define the ranges of reference values that should be considered ‘normal’ in this setting.
Abstract: Postpartum haemorrhage (PPH) is a major risk factor for maternal morbidity and mortality. PPH has numerous causative factors, which makes its occurrence and severity difficult to predict. Underlying haemostatic imbalances such as consumptive and dilutional coagulopathies may develop during PPH, and can exacerbate bleeding and lead to progression to severe PPH. Monitoring coagulation status in patients with PPH may be crucial for effective haemostatic management, goal-directed therapy, and improved outcomes. However, current PPH management guidelines do not account for the altered baseline coagulation status observed in pregnant patients, and the appropriate transfusion triggers to use in PPH are unknown, due to a lack of high-quality studies specific to this area. In this review, we consider the evidence for the use of standard laboratory-based coagulation tests and point-of-care viscoelastic coagulation monitoring in PPH. Many laboratory-based tests are unsuitable for emergency use due to their long turnaround times, so have limited value for the management of PPH. Emerging evidence suggests that viscoelastic monitoring, using thrombelastography- or thromboelastometry-based tests, may be useful for rapid assessment and for guiding haemostatic therapy during PPH. However, further studies are needed to define the ranges of reference values that should be considered ‘normal’ in this setting. Improving awareness of the correct application and interpretation of viscoelastic coagulation monitoring techniques may be critical in realizing their emergency diagnostic potential.

183 citations

References
More filters
Journal ArticleDOI
TL;DR: Fresh‐frozen plasma (FFP), cryoprecipitate and cryosupernatant plasma are very limited and should not be used to reverse warfarin anticoagulation in the absence of severe bleeding, and PRP may be used as an alternative to FFP.
Abstract: The indications for transfusing fresh-frozen plasma (FFP), cryoprecipitate and cryosupernatant plasma are very limited. When transfused they can have unpredictable adverse effects. The risks of transmitting infection are similar to those of other blood components unless a pathogen-reduced plasma (PRP) is used. Of particular concern are allergic reactions and anaphylaxis, transfusion-related acute lung injury, and haemolysis from transfused antibodies to blood group antigens, especially A and B. FFP is not indicated in disseminated intravascular coagulation without bleeding, is only recommended as a plasma exchange medium for thrombotic thrombocytopenic purpura (for which cryosupernatant is a possible alternative), should never be used to reverse warfarin anticoagulation in the absence of severe bleeding, and has only a very limited place in prophylaxis prior to liver biopsy. When used for surgical or traumatic bleeding, FFP and cryoprecipitate doses should be guided by coagulation studies, which may include near-patient testing. FFP is not indicated to reverse vitamin K deficiency for neonates or patients in intensive care units. PRP may be used as an alternative to FFP. In the UK, PRP from countries with a low bovine spongiform encephalopathy incidence is recommended by the Departments of Health for children born after 1 January 1996. Arrangements for limited supplies of single donor PRP of non-UK origin are expected to be completed in 2004. Batched pooled commercially prepared PRP from donors in the USA (Octaplas) is licensed and available in the UK. FFP must be thawed using a technique that avoids risk of bacterial contamination. Plastic packs containing any of these plasma products are brittle in the frozen state and must be handled with care.

786 citations

Journal ArticleDOI
TL;DR: Point-of-care coagulation monitoring using TEG resulted in fewer transfusions in the postoperative period, and this data support the use of TEG in an algorithm to guide transfusion therapy in complex cardiac surgery.
Abstract: Transfusion therapy after cardiac surgery is empirically guided, partly due to a lack of specific point-of-care hemostasis monitors. In a randomized, blinded, prospective trial, we studied cardiac surgical patients at moderate to high risk of transfusion. Patients were randomly assigned to either a thromboelastography (TEG)-guided transfusion algorithm (n 5 53) or routine transfusion therapy (n 5 52) for intervention after cardiopulmonary bypass. Coagulation tests, TEG variables, mediastinal tube drainage, and transfusions were compared at multiple time points. There were no demographic or hemostatic test result differences between groups, and all patients were given prophylactic antifibrinolytic therapy. Intraoperative transfusion rates did not differ, but there were significantly fewer postoperative and total transfusions in the TEG group. The proportion of patients receiving freshfrozen plasma (FFP) was 4 of 53 in the TEG group compared with 16 of 52 in the control group (P , 0.002). Patients receiving platelets were 7 of 53 in the TEG group compared with 15 of 52 in the control group (P , 0.05). Patients in the TEG group also received less volume of FFP (36 6 142 vs 217 6 463 mL; P , 0.04). Mediastinal tube drainage was not statistically different 6, 12, or 24 h postoperatively. Point-of-care coagulation monitoring using TEG resulted in fewer transfusions in the postoperative period. We conclude that the reduction in transfusions may have been due to improved hemostasis in these patients who had earlier and specific identification of the hemostasis abnormality and thus received more appropriate intraoperative transfusion therapy. These data support the use of TEG in an algorithm to guide transfusion therapy in complex cardiac surgery. Implications: Transfusion of allogeneic blood products is common during complex cardiac surgical procedures. In a prospective, randomized trial, we compared a transfusion algorithm using point-of-care coagulation testing with routine laboratory testing, and found the algorithm to be effective in reducing transfusion requirements. (Anesth Analg 1999;88:312‐9)

763 citations

Journal ArticleDOI
TL;DR: It is concluded that deficiency of fibrinogen develops earlier than any other hemostatic abnormality when plasma-poor RCCs are used for the replacement of major blood loss.
Abstract: The purpose of this study was to assess the change of platelet and fibrinogen concentrations and the change of activities of prothrombin and factors V and VII when major surgical blood loss was replaced with plasma-poor red cell concentrates (RCCs) and colloid plasma substitutes. Sixty patients were studied. The average blood loss was 65% +/- 41% of the calculated blood volume (CBV). Blood loss was monitored carefully and replaced without delay to ensure stable blood volume. Blood samples were obtained at the induction of anesthesia and at the end of the recovery room period, or before the patient was given fresh frozen plasma. In addition, a platelet count was determined after each 20% blood loss. The results were converted to relative values, and simple linear regression with logarithmic transformation was applied. The initial platelet concentration was 257 +/- 89 x 10(3)/mm3 and the extrapolation of the regression line intercepted the critical level of 50 x 10(3)/mm3 at 230% (confidence interval 169%-294%) blood loss. The initial fibrinogen concentration was 3.7 +/- 1.1 g/L and the hemostatically significant level of 1.0 g/L was already reached at 142% (117%-169%) blood loss (r2 = 0.90). Activities of prothrombin and coagulation factors V and VII reached their critical levels at 201% (160%-244%), 229% (167%-300%), and 236% (198%-277%) blood loss, respectively. We conclude that deficiency of fibrinogen develops earlier than any other hemostatic abnormality when plasma-poor RCCs are used for the replacement of major blood loss.

632 citations


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

  • ...However, in the modern era of intravenous fluids and red cell concentrates, fibrinogen deficiency was the first defect observed (Hiippala et al, 1995)....

    [...]

Journal ArticleDOI
TL;DR: Findings indicate that a simple fibrinogen measurement can anticipate the risk of severe bleeding in PPH.

617 citations


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

  • ...Thus, the threshold level for treatment may be substantially higher than the ‘historical’ 1 g/l, particularly in patients suffering from postpartum bleeding [4 g/l; (Charbit et al, 2007)] or excessive blood loss during cardiac surgery [3Æ8 g/l; (Karlsson et al, 2008)]....

    [...]

  • ...In postpartum bleeding, low levels of fibrinogen are associated with severe bleeding, with a positive predictive value of 100% (Charbit et al, 2007)....

    [...]

  • ...In a study of postpartum haemorrhage (PPH), fibrinogen concentrations less than 2 g/l had a 100% positive predictive value for severe PPH (Charbit et al, 2007)....

    [...]

Journal ArticleDOI
TL;DR: In patients with combat-related trauma requiring massive transfusion, the transfusion of an increased fibrinogen: RBC ratio was independently associated with improved survival to hospital discharge, primarily by decreasing death from hemorrhage.
Abstract: Background: To treat the coagulopathy of trauma, some have suggested early and aggressive use of cryoprecipitate as a source of fibrinogen. Our objective was to determine whether increased ratios of fibrinogen to red blood cells (RBCs) decreased mortality in combat casualties requiring massive transfusion. Methods: We performed a retrospective chart review of 252 patients at a U.S. Army combat support hospital who received a massive transfusion (≥10 units of RBCs in 24 hours). The typical amount of fibrinogen within each blood product was used to calculate the fibrinogen-to-RBC (F:R) ratio transfused for each patient. Two groups of patients who received either a low (<0.2 g fibrinogen/RBC Unit) or high (≥0.2 g fibrinogen/RBC Unit) F:R ratio were identified. Mortality rates and the cause of death were compared between these groups, and logistic regression was used to determine if the F:R ratio was independently associated with survival. Results: Two-hundred and fifty-two patients who received a massive transfusion with a mean (SD) ISS of 21 (±10) and an overall mortality of 75 of 252 (30%) were included. The mean (SD) F:R ratios transfused for the low and high groups were 0.1 grams/Unit (±0.06), and 0.48 grams/Unit (±0.2), respectively (p < 0.001). Mortality was 27 of 52 (52%) and 48 of 200 (24%) in the low and high F:R ratio groups respectively (p < 0.001). Additional variables associated with survival were admission temperature, systolic blood pressure, hemoglobin, International Normalized Ratio (INR), base deficit, platelet concentration and Combined Injury Severity Score (ISS). Upon logistic regression, the F:R ratio was independently associated with mortality (odds ratio 0.37, 95% confidence interval 0.171-0.812, p = 0.013). The incidence of death from hemorrhage was higher in the low F:R group, 23/27 (85%), compared to the high F:R group, 21/48 (44%) (p < 0.001). Conclusions: In patients with combat-related trauma requiring massive transfusion, the transfusion of an increased fibrinogen: RBC ratio was independently associated with improved survival to hospital discharge, primarily by decreasing death from hemorrhage. Prospective studies are needed to evaluate the best source of fibrinogen and the optimal empiric ratio of fibrinogen to RBCs in patients requiring massive transfusion.

402 citations


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

  • ...Cryoprecipitate contains a higher concentration of fibrinogen than FFP, typically around 15 g/l (Stinger et al, 2008)....

    [...]

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