Pillar 2: minimising bleeding and blood loss.
On the role of iron therapy for reducing allogeneic blood transfusion in orthopaedic surgery.
Muñoz M, García-Erce JA, Cuenca J, Bisbe E, Naveira E; AWGE (Spanish Anaemia Working Group).
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Guidelines. Blood transfusion and the anaesthetist: management of massive haemorrhage.
Thomas D, Wee M, Clyburn P, Walker I, Brohi K, Collins P, Doughty H, Isaac J, Mahoney PM, Shewry L.
1. Hospitals must have a major haemorrhage protocol in
place and this should include clinical, laboratory and
2. Immediate control of obvious bleeding is of paramount
importance (pressure, tourniquet, haemostatic
3. The major haemorrhage protocol must be mobilised
immediately when a massive haemorrhage situation is
4. A fibrinogen < 1 g.l)1 or a prothrombin time (PT) and activated partial thromboplastin time (aPTT) of > 1.5 times normal represents established haemostatic
failure and is predictive of microvascular bleeding.
Early infusion of fresh frozen plasma (FFP;
15 ml.kg)1) should be used to prevent this occurring
if a senior clinician anticipates a massive haemorrhage.
5. Established coagulopathy will require more than
15 ml.kg)1 of FFP to correct. The most effective way
to achieve fibrinogen replacement rapidly is by giving
fibrinogen concentrate or cryoprecipitate if fibrinogen
6. 1:1:1 red cell:FFP:platelet regimens, as used by the
military, are reserved for the most severely traumatised
7. A minimum target platelet count of 75 · 109.l)1 is
appropriate in this clinical situation.
8. Group-specific blood can be issued without performing
an antibody screen because patients will have
minimal circulating antibodies. O negative blood
should only be used if blood is needed immediately.
9. In hospitals where the need to treat massive
haemorrhage is frequent, the use of locally developed
shock packs may be helpful.
10. Standard venous thromboprophylaxis should be
commenced as soon as possible after haemostasis has
been secured as patients develop a prothrombotic
state following massive haemorrhage.
Pathophysiology and Treatment of Coagulopathy in Massive Hemorrhage and Hemodilution
Daniel Bolliger, M.D.,* Klaus Go¨ rlinger, M.D.,† Kenichi A. Tanaka, M.D., M.Sc.‡
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Fluid resuscitation after massive hemorrhage in major surgery and trauma may result in extensive hemodilution and
coagulopathy, which is of a multifactorial nature. Although
coagulopathy is often perceived as hemorrhagic, extensive
hemodilution affects procoagulants as well as anticoagulant, profibrinolytic, and antifibrinolytic elements, leading to a complex coagulation disorder. Reduced thrombin activation is partially compensated by lower inhibitory activities of antithrombin and other protease inhibitors, whereas plasma fibrinogen is rapidly decreased proportional to the extent of hemodilution. Adequate fibrinogen levels are essential in managing dilutional coagulopathy. After extensive hemodilution,
fibrin clots are more prone to fibrinolysis because
major antifibrinolytic proteins are decreased.
Fresh frozen plasma, platelet concentrate, and cryoprecipitate are considered the mainstay hemostatic therapies. Purified factor concentrates of plasma origin and from recombinantsynthesis are increasingly used for a rapid restoration of targeted factors. Future clinical studies are necessary to establish the specific indication, dosing, and safety of novel hemostatic interventions.
IN patients with trauma and those who undergo major
surgery, multiple breaches of vascular integrity result in
bleeding, and in some cases, exsanguination. Fluid (volume)
replacement with crystalloids or colloids is usually the initial measure to stabilize systemic circulation by compensating for hypovolemia. When the blood loss is considered major (hemoglobin concentration below 6–10 g/dl),1 erythrocyte(RBC) concentrates are transfused to sustain hemoglobin levels (i.e., oxygen-carrying capacity). The transfusion of ten or more erythrocyte units (i.e., replacement of one blood volume) within 24 h is generally considered as massive transfusion in adults.2 Other arbitrary definitions include six or more erythrocyte units within 12 h and over 50 units of
blood product use within 24 h, including erythrocytes, platelet concentrates, and fresh frozen plasma (FFP).3,4 There are differences in the initial pathophysiology of coagulopathy between trauma and major surgery, which can be attributed in part to the mechanism of vascular injury, extent of hemorrhage, type of fluid resuscitation, and prophylactic use of antifibrinolytic therapy.5–8 However, hemostatic defects based on conventional laboratory data are often indistinguishable between trauma and major surgery after massive transfusion. Unlike congenital bleeding disorders that are due mostly to a single factor deficiency (e.g., hemophilia, afibrinogenemia), coagulopathy encountered in trauma and major surgery is of a multifactorial nature. All elements incoagulation, including procoagulant, anticoagulant, fibrinolytic,
and antifibrinolytic proteins, exhibit various degrees of
deficiency. Although this topic has been reviewed recently by others,5,8,9 the mechanism of coagulopathy related to massive transfusion and hemodilution is not fully understood. In this review, we focus on the effects of hemodilution on thrombin generation, fibrin polymerization, and fibrinolysis, using experimental results as well as existing clinical data to shed light on the mechanisms of dilutional coagulopathy. In
addition, we discuss various therapeutic approaches and their clinical implications.
Blood transfusion as a quality indicator in cardiac surgery.
Management of major blood loss: An update
associated with coagulopathy secondary to tissue injury,
hypoperfusion, dilution and consumption of clotting factors
and platelets. Concepts of damage control surgery
have evolved, prioritizing the early control of the cause of bleeding by non-definitive means, while haemostatic control resuscitation seeks early control of coagulopathy.
Haemostatic resuscitation provides transfusions with
plasma and platelets in addition to red blood cells
(RBCs) in an immediate and sustained manner as part of
the transfusion protocol for massively bleeding patients.
Transfusion of RBCs, plasma and platelets in a similar
proportion as in whole blood prevents both hypovolaemia
and coagulopathy. Although an early and effective reversal
of coagulopathy is documented, the most effective means
of preventing coagulopathy of massive transfusion
remains debated and randomized controlled studies are
lacking. Results from recent before-and-after studies
in massively bleeding patients indicate that trauma
exsanguination protocols involving the early administration
of plasma and platelets are associated with improved
survival. Furthermore, viscoelastic whole blood assays,
such as thrombelastography (TEG)/rotation thromboelastometry(ROTEM), appear advantageous for identifying coagulopathy in patients with severe haemorrhage, as opposed to conventional coagulation assays. In our view,patients with uncontrolled bleeding, regardless of its cause, should be treated with goal-directed haemostatic control resuscitation involving the early administration of plasma and platelets and based on the results of the TEG/ROTEM analysis. The aim of the goal-directed therapy should be to maintain a normal haemostatic competence until surgical haemostasis is achieved, as this appears to be associated with reduced mortality.
Clinical impact of blood storage lesions
The safety and efficacy of intravenous ferric carboxymaltose in anaemic patients undergoing haemodialysis: a multi-centre, open-label, clinical study.
Clinical practice guideline: red blood cell transfusion in adult trauma and critical care.
Can intravenous iron therapy meet the unmet needs created by the new restrictions on erythropoietic stimulating agents?
Intravenous iron in inflammatory bowel disease.
Iron metabolism, iron deficiency, thrombocytosis, and the cardiorenal anemia syndrome.
Hierro intravenoso/Intravenous iron
Parenteral iron is a useful and safe therapeutic measure to treat anaemia, and is a proven clinical alternative to blood transfusion. This review article summarises the main characteristics of the different formulations of parenteral iron, their advantages, indications, dosages and adverse effects. Moreover, we analyse some of the most important published articles on parenteral iron therapy in General Surgery and other surgical specialties, as well as providing information about new formulations that will soon be available
Anemia after bariatric surgery: more than just iron deficiency
Regulation of iron homeostasis in anemia of chronic disease and iron deficiency anemia: diagnostic and therapeutic implications
Randomized, Double-Blind, Placebo-Controlled Trial of Effects of Enteral Iron Supplementation on Anemia and Risk of Infection during Surgical Critical Illness
Results of a national survey on transfusion habit in Intensive Care Units
Unexplained anemia in the elderly
Anemia of aging: the role of chronic inflammation and cancer
Nutritional anemias and the elderly
Epidemiology of anemia in older adults
Anemia and cerebral outcomes: many questions, fewer answers
Increased mortality, morbidity, and cost associated with red blood cell transfusion after cardiac surgery
Efficacy of red blood cell transfusion in the critically ill: a systematic review of the literature
Serum transferrin receptor
Cell-Free Hemoglobin-Based Blood Substitutes and Risk of Myocardial Infarction and Death: A Meta-analysis
Complement split products and proinflammatory cytokines in intraoperatively salvaged unwashed blood during hip replacement: comparison between heparin-coated and non-heparin-coated autotransfusion systems
Efficacy and safety of intravenous iron therapy as an alternative/adjunct to allogeneic blood transfusion
Anemia management: intravenous iron can enable a reduction in blood transfusions – a benefit for patients and hematology wards
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Chronic iron deficiency is a common cause of symptomatic anemia, but despite this it is often overlooked or not optimally managed. Frequently, this is because the diagnosis is not confirmed and the response to treatment may be inadequate because of poor compliance, malabsorbtion or recurrent blood loss. Oral iron is blamed for many treatment-limiting gastrointestinal symptoms, and if patients are admitted to hospital with symptoms they are frequently transfused. Intravenous iron can be used to deliver a predictable dose of iron over a short time with many safety, time and economic advantages compared with blood transfusion. Unlike blood transfusion, it is easy to replace physiological storage iron or even to anticipate future blood loss. Preparations of intravenous iron are available which enable even severely anemic patients to be fully treated in two hospital visits. The speed of response to intravenous iron is fast, with rises in hemoglobin levels exceeding 2 g/dL per week in severely
iron-deficient subjects. In patients with recurrent blood loss and a satisfactory response, multiple ongoing treatments with intravenous iron are feasible.
Clinical experience with intravenous iron
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Recently there has been an enormous tumult over the use of the erythropoiesis-stimulating agents (ESAs) epoetin alfa and beta and darbepoetin alfa. Recommendations ranging from stopping their use in certain tumor types to withholding therapy until hemoglobin levels reach 9 g/dL or less have been proposed. These recommendations result from inconclusive and imbalanced trials favoring the placebo groups but which nonetheless raise significant concerns about the potential of ESAs to upregulate erythropoietin receptors on tumor cells. Therefore, there has never been a greater need to ensure that appropriate administration of intravenous iron is given with ESAs. In several published and soon-to-be-published trials comparing adjuvant therapy with intravenous and oral iron, without exception intravenous iron improved hemoglobin and hematopoietic responses, shortened times to maximal response, decreased exposure to ESAs and provided huge cost savings. Furthermore, these benefits were independent of patients’ pretreatment iron parameters, such as serum ferritin, transferrin saturation and the presence or absence of bone marrow hemosiderin. Nonetheless, resistance to intravenous iron usage in oncology abounds. This resistance is due to misinformation and misinterpretation of the incidence and clinical nature of serious adverse events. Now that there are three safe intravenous iron preparations, a new paradigm incorporating intravenous iron to ESA therapy in oncology needs to be examined
Intravenous iron as a transfusion alternative
Anemia en la insuficiencia cardiaca: fisiopatología, patogenia, tratamiento e incógnitas
Rev Esp Cardiol
Carlos Caramelo, Soledad Justo y Paloma Gil
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Aunque la anemia ha pasado a ocupar un plano relevante
en la concepción patogénica actual de la insuficiencia
cardiaca (IC), se trata aún de una entidad rodeada
de incógnitas. La prevalencia de anemia y su
importancia clínica en la población con IC son muy elevadas.
Sin embargo, no se han establecido aún con certeza
suficiente los objetivos de tratamiento de la anemia en la
población con IC. El presente trabajo revisa aspectos clínicos
y fisiopatológicos de esta forma particular de anemia,
con especial atención a los mecanismos celulares y
moleculares de regulación, y sus implicaciones en el tratamiento.
Estimating the cost of blood: past, present, and future directions
Aprotinin; friend or foe? A review of recent medical literature
Anaemia during critical illness.
The role of intravenous iron in cancer-related anemia.
Recombinant factor VIIa and the surgical patient.
Curr Opin Crit Care.
Scarpelini S, Rizoli S.
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PURPOSE OF REVIEW: Bleeding remains a challenge in surgery. A unique drug, recombinant factor VIIa, causes clotting exclusively at bleeding sites. Recombinant factor VIIa has recently been introduced to surgery where current evidence, consisting mostly of case reports, suggest remarkable safety and efficacy. The first randomized controlled trials are only now being published with less remarkable results. This manuscript summarizes the current evidence. RECENT FINDINGS: In trauma, a single randomized control trial suggests recombinant factor VIIa reduces bleeding and transfusion in blunt trauma, particularly in coagulopathic patients. In cardiac surgery, one randomized control trial, open-label studies and case reports suggest benefit in refractory bleeding. For liver surgery, randomized control trials do not support use in liver transplant or gastrointestinal bleeding. In neurosurgery, one randomized control trial demonstrated improved outcome in intracerebral hemorrhage. In urology, one randomized control trial demonstrated significant reduction in perioperative bleeding. For orthopedics, a single randomized control trial showed no benefit in pelvic/acetabular surgery. In obstetrics/gynecology, limited evidence suggests benefit in massive bleedings. SUMMARY: Current evidence does not yet support recombinant factor VIIa as standard of care in surgery. However, the evidence indicates that recombinant factor VIIa should be used in intracerebral hemorrhage and massive perioperative or traumatic bleeding refractory to conventional therapies. For now, the bedside decision to use recombinant factor VIIa remains a matter of surgical judgment
The effects of colloid solutions on hemostasis
Can J Anaesth.
.Van der Linden P, Ickx BE.
Department of Anesthesiology, CHU Brugmann – HUDERF, 4 Place Van Gehuchten, B-1020 Brussels, Belgium.
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PURPOSE: Colloid solutions are widely used to prevent or to correct hypovolemia in surgical patients. Although more efficacious than crystalloids, they are more expensive and can be associated with adverse effects, in particular when they interfere with the hemostatic system. METHODS: This narrative review focuses on the effects of albumin and synthetic colloids on the biological markers of coagulation and their clinical consequences. RESULTS: All colloidal plasma substitutes interfere with the physiological mechanisms of hemostasis either through a non-specific effect correlated to the degree of hemodilution or through specific actions of these macromolecules on platelet function, coagulation proteins, and the fibrinolytic system. Albumin has the least effect, while high molecular weight (Mw) dextrans and hydroxyethyl starches (HES) have the most significant effects. Gelatins and medium Mw HES with a low molar substitution ratio have moderate and, probably, comparable effects. The use of dextrans and high in vivo Mw HES may be associated with increased bleeding, while gelatins and low in vivo Mw HES are unlikely to have such an effect. CONCLUSIONS: In most cases, the clinical consequences of the biological effects of colloids on hemostasis are limited, provided that safety considerations are observed (maximum daily dosage, duration of treatment, patient’s hemostatic status, clinical conditions). The implications may be different in patients with hemostatic disorders, either inherited or related to preoperative antiplatelet or anticoagulant treatment. In these patients, crystalloids, gelatins or even albumin solutions should be preferred when hemodilution exceeds 30% of the circulating blood volume.
Recombinant human erythropoietins and cancer patients: updated meta-analysis of 57 studies including 9353 patients.
Pharmacological approaches to reducing blood loss and transfusions in the surgical patient
Service d’Anesthesie-Reanimation Chirurgicale, France
Massive transfusion practices around the globe and a suggestion for a common massive transfusion protocol.
Malone DL, Hess JR, Fingerhut A.
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BACKGROUND: Massive transfusion, the administration of 10 to more than 100 units of red blood cells (RBC) in less than 24 hours, can be a life saving therapy in the treatment of severe injury. The rapid administration of large numbers of RBC, along with sufficient plasma and platelets to treat or prevent coagulopathy, is frequently a disorderly process. Patient care and collaborative research might be aided with a common protocol. METHODS: The authors polled trauma organizations and trauma centers to find examples of massive transfusion protocols. The goals and ease of use of these protocols were evaluated. RESULTS: Massive transfusion protocols exist at a relatively small number of large and well-organized trauma centers. Most of these protocols are designed to treat pre-existing and/or ongoing coagulopathy. CONCLUSIONS: The evidence would suggest that prevention of coagulopathy is superior to its treatment. Simple ratios such as 1:1:1 RBC:plasma:platelets have the benefit of ease of use and the relatively higher plasma and platelet doses appear to be associated with improved outcome. Such a standard protocol can foster multicenter research on resuscitation and hemorrhage control. The fixed volume ratios might allow the number and rate of administered units of RBC to be used as surrogates for blood loss and primary treatment effect.
Lineage-specific hematopoietic growth factors.
Cost and utilization of blood transfusion associated with spinal surgeries in the United States.
Eur Spine J
Blanchette CM, Wang PF, Joshi AV, Asmussen M, Saunders W, Kruse P.
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Premier Inc., Pharmaceutical Research Services, Charlotte, NC, USA.
The purpose of this study was to examine factors associated with the utilization and cost of blood transfusion during and post-spinal fusion surgery. A retrospective, observational study of 42,029 inpatients undergoing spinal fusion surgery in United States hospitals participating in the Perspective(TM) Comparative Database for inpatient use was conducted. Descriptive analysis, logistic regression, and ordinary least squares (OLS) regression were used to describe the factors associated with the use and cost of allogeneic blood transfusion (ABT). Hospitalization costs were $18,690 (SD=14,159) per patient, erythropoietin costs were $85.25 (SD=3,691.66) per patient, and topical sealant costs were $414.34 (SD=1,020.06) per patient. Sub-analysis of ABT restricted to users revealed ABT costs ranged from $312.24 (SD=543.35) per patient with whole blood to $2,520 (SD=3,033.49) per patient with fresh frozen plasma. Patients that received hypotensive anesthesia (OR,1.61; 95% CI, 1.47-1.77), a volume expander (OR,1.95; 95% CI, 1.75-2.18), autologous blood (OR, 2.04; 95% CI, 1.71-2.42), or an erythropoietic agent (OR=1.64; 95% CI, 1.27-2.12) had a higher risk of ABT. Patients that received cell salvage had a lower risk of transfusion (OR=0.40; 95% CI, 0.32-0.50). Most blood avoidance techniques have low utilization or do not reduce the burden of transfusion associated with spinal fusion.
Detection, Evaluation, and Management of Anemia in the Elective Surgical Patient
The prevalence of anemia in elective surgical patients may be as frequent as 75% in certain populations. A national audit demonstrated that 35% of patients scheduled for joint replacement therapy have a hemoglobin <13 g/dL on preadmission testing. Standard practice currently consists of preadmission testing 3 to 7 days before an elective operative procedure, precluding the opportunity to effectively evaluate and manage a patient with unexpected anemia. Therefore, a standardized approach for the detection, evaluation, and management of anemia in the preoperative surgical setting was identified as an unmet medical need. To address this knowledge gap, we convened a panel of physicians to develop a clinical care pathway for anemia management in this setting. Elective surgery patients should receive a hemoglobin (Hgb) determination a minimum of 30 days before the scheduled surgical procedure. Because the identification and evaluation of anemia in this setting will assist in expedited diagnosis and treatment of underlying comorbidities and will improve patient outcomes, unexplained anemia (Hgb <12 g/dL for females and <13 g/dL for males) should cause elective surgery to be deferred until an evaluation can be performed.
Grupos sanguíneos y enfermedad
Guía sobre la transfusión de componentes sanguíneos
Anemia of Chronic Disease
Fisiopathology of iron metabolism: diagnostic and therapeutic implications
Blood management in total joint arthroplasty.
Preoperative erythropoietin in spine surgery.
Diagnosis and management of iron-deficiency anaemia
Iron-Deficiency Anemia: Reexamining the Nature and Magnitude of the Public Health Problem
Stephen J. Oppenheimer
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Curr Opin Crit Care
. 2008 Apr;14(2):156-62. Links
Optimal hemoglobin concentration in patients with subarachnoid hemorrhage, acute ischemic stroke and traumatic brain injury.Leal-Noval SR, Múñoz-Gómez M, Murillo-Cabezas F.
Neurocritical Care Division, Hospital Universitario Virgen del Rocío, Seville, Spain. email@example.com
PURPOSE OF REVIEW: The review outlines recent clinical and experimental studies regarding the effects of red blood-cell transfusion on clinical outcome in neurocritical patients, including patients with subarachnoid hemorrhage, acute ischemic stroke and traumatic brain injury. Optimal hemoglobin transfusion trigger and the role of other transfusion indicators for neurocritical patients are discussed. RECENT FINDINGS: Acute anemia (hemoglobin levels near 7 g/dl) is well tolerated by healthy subjects, but extreme anemia might negatively affect clinical outcome of neurocritical patients. Conversely, high hemoglobin levels, attained by means other than red blood-cell transfusion, improve clinical outcome, whereas red blood-cell transfusion is associated with poorer clinical outcome (mortality, length of stay and disability) in patients presenting subarachnoid hemorrhage, acute ischemic stroke and traumatic brain injury. Studies defining the optimal hemoglobin concentration in neurocritical patients are lacking, but a restrictive transfusion policy seems to be safe and is often recommended. In the near future, signals coming from the brain, such as brain tissue oxygen tension and regional cerebral oxygen saturation, might potentially be developed into transfusion triggers. SUMMARY: Both severe anemia and red blood-cell transfusion may negatively influence clinical outcome in neurocritical patients. Acceptance of low hemoglobin concentrations may be justified by avoiding negative transfusion effects. No evidence-based transfusion trigger in neurocritical patients can be recommended.