Perioperative anemia management in colorectal cancer patients: a pragmatic approach.

Editorial: World J Gastroentero
Fecha: 01/02/2014
Muñoz M, Gómez-Ramírez S, Martín-Montañez E, Auerbach M.

Anemia, usually due to iron deficiency, is highly prevalent among patients with colorectal cancer. Inflammatory cytokines lead to iron restricted erythropoiesis further decreasing iron availability and impairing iron utilization. Preoperative anemia predicts for decreased survival. Allogeneic blood transfusion is widely used to correct anemia and is associated with poorer surgical outcomes, increased post-operative nosocomial infections, longer hospital stays, increased rates of cancer recurrence and perioperative venous thromboembolism. Infections are more likely to occur in those with low preoperative serum ferritin level compared to those with normal levels. A multidisciplinary, multimodal, individualized strategy, collectively termed Patient Blood Management, minimizes or eliminates allogeneic blood transfusion. This includes restrictive transfusion policy, thromboprophylaxis and anemia management to improve outcomes. Normalization of preoperative hemoglobin levels is a World Health Organization recommendation. Iron repletion should be routinely ordered when indicated. Oral iron is poorly tolerated with low adherence based on published evidence. Intravenous iron is safe and effective but is frequently avoided due to misinformation and misinterpretation concerning the incidence and clinical nature of minor infusion reactions. Serious adverse events with intravenous iron are extremely rare. Newer formulations allow complete replacement dosing in 15-60 min markedly facilitating care. Erythropoiesis stimulating agents may improve response rates. A multidisciplinary, multimodal, individualized strategy, collectively termed Patient Blood Management used to minimize or eliminate allogeneic blood transfusion is indicated to improve outcomes

Pillar 2: minimising bleeding and blood loss.

Editorial: Best Pract Res Clin
Fecha: 01/03/2013
Bisbe E1, Moltó L.

One of the main factors that contributes to the need for transfusion in the surgical patient is excessive blood loss. Pillar 2 of patient blood management (PBM) includes all the strategies to reduce bleeding and preserve the patient’s own blood, designed with an aim to reducing or avoiding transfusion. Some of these strategies, such as identifying and planning the management of patients at high risk of bleeding, can be implemented as early as at the preoperative assessment visit. During the intra-operative period, local haemostasis is the most important factor in the control of bleeding; in this context, therefore, surgical technique and meticulous haemostasis are fundamental measures. However, there are also additional anaesthetic techniques that can help reduce blood loss and transfusion requirements, such as the use of pharmacological or haemostatic agents. After surgery, PBM continues in the postoperative recovery unit or on the ward with the monitoring and management of postoperative bleeding. The blood lost via drains can be filtered, washed and reinfused, if needed

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.

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1. Hospitals must have a major haemorrhage protocol in
place and this should include clinical, laboratory and
logistic responses.
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 should be used to prevent this occurring
if a senior clinician anticipates a massive haemorrhage.
5. Established coagulopathy will require more than
15 of FFP to correct. The most effective way
to achieve fibrinogen replacement rapidly is by giving
fibrinogen concentrate or cryoprecipitate if fibrinogen
is unavailable.
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.

Management of major blood loss: An update

Editorial: Acta Anaesthesiol Sc
Fecha: 01/10/2010

Haemorrhage remains a major cause of potentially preventable deaths. Trauma and massive transfusion are
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

Editorial: Am J Hematol
Fecha: 01/02/2010
Zubair AC

Recent reports suggest that transfusion of old red blood cell (RBC) units (>2 weeks) was associated with increased risks of postoperative complications and higher mortality rate caught public attention (Yap et al., Ann Thorac Surg 2008; 86:554-559 and Koch et al., 2008; 358:1229-1239). This rekindled the decades old discussion regarding the impact of RBC aging and storage lesions in patient care. The objectives of this review are to provide readers with an overview of the process of banking RBC that may have an impact on its quality, the reported clinical impact of storage lesions, the consequences of transfusing new RBC units only to the nation’s blood supply and potential solutions that may improve the feasibility of blood banks to issue new blood units only.

The safety and efficacy of intravenous ferric carboxymaltose in anaemic patients undergoing haemodialysis: a multi-centre, open-label, clinical study.

Editorial: Nephrol Dial Transpl
Fecha: 01/02/2010
Covic A, Mircescu G.

BACKGROUND: Patients with chronic kidney disease (CKD) often present with iron depletion and iron deficiency anaemia (IDA) because of frequent blood (and iron) loss. Therapy consists of repletion of iron stores and intravenous (i.v.) iron has become the standard care in this setting. However, older i.v. iron preparations have their limitations. This study primarily investigated the safety, and also the efficacy, of ferric carboxymaltose (FCM), a next-generation i.v. iron formulation, given as a bolus-push injection in patients with CKD undergoing maintenance haemodialysis (HD). METHODS: Patients (aged 18-65 years) with IDA undergoing HD received 100-200 mg of iron as FCM via an i.v. bolus-push injection into the HD venous line, two to three times weekly for /=1.0 g/dl increase in haemoglobin (Hb) from baseline at any time during the study. Enrolled patients (safety population) receiving >/=1 dose of study medication were included in the efficacy analyses [intent-to-treat (ITT) population]. RESULTS: Of 163 patients enrolled, 150 (92%) completed the study. The mean +/- SD total cumulative dose of iron as FCM administered was 2133.3 +/- 57.7 mg. In total, 193 AEs were reported in 89 out of 163 (54.6%) patients. Almost three-quarters of patients (73.6%) received erythropoiesis-stimulating agents (ESAs), but the dose remained stable during the study. Serious AEs occurred in 12 out of 163 (7.4%) patients and two patients died; none of these was considered by the investigator to be related to the study medication. Only five out of 163 (3.1%) patients discontinued study medication due to an AE. Overall, 100 out of 162 (61.7%; ITT population) patients were treatment responders, and mean Hb levels increased from 9.1 +/- 1.30 g/dl at baseline to 10.3 +/- 1.63 g/dl at follow-up. CONCLUSIONS: FCM is well-tolerated and effective in the correction of Hb levels and iron stores in patients with IDA undergoing HD. As changes in anaemia treatment other than i.v. FCM (e.g. increased ESA doses) were not permitted during the study, the clinically relevant increase in Hb in the majority of patients can be solely attributed to efficient iron utilization. The incidence of AEs was as expected for this population

Clinical practice guideline: red blood cell transfusion in adult trauma and critical care.

Editorial: J Trauma
Fecha: 01/12/2009
Napolitano LM, Kurek S, Luchette FA, Anderson GL, Bard MR, Bromberg W, Chiu WC, Cipolle MD, Clancy KD, Diebel L, Hoff WS, Hughes KM, Munshi I, Nayduch D, Sandhu R, Yelon JA, Corwin HL, Barie PS, Tisherman SA, Hebert PC; EAST Practice Management Workgroup; American College of Critical Care Medicine (ACCM) Taskforce of the Society of Critical Care Medicine (SCCM).

Can intravenous iron therapy meet the unmet needs created by the new restrictions on erythropoietic stimulating agents?

Editorial: Transfusion
Fecha: 01/11/2009
Shander A, Spence RK, Auerbach M.

In 2008, after reports of an association between erythropoietic stimulating agent (ESA) therapy and the potential for either thrombotic cardiovascular events or more rapid tumor progression in some cancers, the Food and Drug Administration changed the product labeling for ESAs, adding a black box warning as well as more restrictive indications, especially in oncology patients. In addition the Centers for Medicare and Medicaid Services has placed significant restrictions on payments for ESA therapy. These new limitations on ESA have led to increased use of transfusions in anemic cancer patients. This increase in allogeneic transfusions potentially will place an additional burden on the US blood supply. Although allogeneic blood transfusion is one answer to ESA restrictions, the use of intravenous iron therapy (IV iron) is another possible alternative. We will discuss the use of IV iron as primary therapy for anemia, the use of combination IV iron and ESA therapy to improve efficiency and decrease costs, and evidence that IV iron with and without ESA therapy can reduce allogeneic blood transfusions in surgical patients. We will also review the available IV iron agents and their comparative safety profiles.

Intravenous iron in inflammatory bowel disease.

Editorial: World J Gastroentero
Fecha: 01/10/2009
Muñoz M, Gómez-Ramírez S, García-Erce JA.

The prevalence of anemia across studies on patients with inflammatory bowel disease (IBD) is high (30%). Both iron deficiency (ID) and anemia of chronic disease contribute most to the development of anemia in IBD. The prevalence of ID is even higher (45%). Anemia and ID negatively impact the patient’s quality of life. Therefore, together with an adequate control of disease activity, iron replacement therapy should start as soon as anemia or ID is detected to attain a normal hemoglobin (Hb) and iron status. Many patients will respond to oral iron, but compliance may be poor, whereas intravenous (i.v.) compounds are safe, provide a faster Hb increase and iron store repletion, and presents a lower rate of treatment discontinuation. Absolute indications for i.v. iron treatment should include severe anemia, intolerance or inappropriate response to oral iron, severe intestinal disease activity, or use of an erythropoietic stimulating agent. Four different products are principally used in clinical practice, which differ in their pharmacokinetic properties and safety profiles: iron gluconate and iron sucrose (lower single doses), and iron dextran and ferric carboxymaltose (higher single doses). After the initial resolution of anemia and the repletion of iron stores, the patient’s hematological and iron parameters should be carefully and periodically monitored, and maintenance iron treatment should be provided as required. New i.v. preparations that allow for giving 1000-1500 mg in a single session, thus facilitating patient management, provide an excellent tool to prevent or treat anemia and ID in this patient population, which in turn avoids allogeneic blood transfusion and improves their quality of life.

Iron metabolism, iron deficiency, thrombocytosis, and the cardiorenal anemia syndrome.

Editorial: Oncologist
Fecha: 01/10/2009
Besarab A, Hörl WH, Silverberg D.

In treating moderate to severe anemia of chronic kidney disease (CKD), oral iron is effective only in a minority of nondialysis patients. Intravenous iron is more effective and can raise levels of hemoglobin even without the use of erythropoiesis-stimulating agents (ESAs). Unfortunately, the current assays of iron status that are presently widely available are not especially helpful in predicting response. In patients on dialysis, i.v. iron is effective over a wide range of serum ferritin from <100 ng/ml to 800 ng/ml. None of the three available randomized controlled trials comparing oral with i.v. iron showed evidence of nephrotoxicity caused by i.v. iron. Iron deficiency is a risk factor for thrombocytosis and should, wherever possible, be avoided. Optimal coadministration of iron may reduce the risk for ESA-driven cardiovascular events. Increased total body iron stores (imperfectly reflected by serum ferritin levels in CKD) do not appear to be related to such events or hospitalization in CKD; it is unclear what other risk factors and mechanisms need to be considered. In the appreciable proportion of patients with both renal and cardiac dysfunction, management is further complicated by a vicious circle (which can be characterized as cardiorenal anemia syndrome) in which CKD, heart failure, and anemia exacerbate each other. In such patients, correction of anemia appears to improve cardiac function and quality of life without a greater risk for adverse events.

Hierro intravenoso/Intravenous iron

Editorial: Cir Esp
Fecha: 01/07/2009
Madrazo González Z, García Barrasa A, Rodríguez Lorenzo L, Rafecas Renau A.

El hierro intravenoso representa una medida terapéutica eficaz y segura para corregir la anemia, y constituye una alternativa respecto a la transfusión sanguínea clínicamente demostrada. El presente artículo de revisión resume las principales características de los distintos preparados de hierro parenteral, sus ventajas, indicaciones, dosificación y efectos adversos. Asimismo, se analizan algunos de los principales estudios publicados sobre ferroterapia parenteral en Cirugía General y especialidades quirúrgicas afines, y se avanzan algunos datos sobre las nuevas formulaciones próximamente disponibles

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

Editorial: Nutr Clin Pract
Fecha: 01/04/2009
von Drygalski A, Andris DA.

Bariatric surgery for morbid obesity is rapidly gaining popularity. Restrictive and/or malabsorptive surgical interventions result in dramatic weight loss with significantly decreased obesity-related morbidity and mortality. Anemia, which may affect as many as two-thirds of these patients, is of concern and generally thought to be caused by iron deficiency. Although iron deficiency in this population may be frequent given pouch hypoacidity, defunctionalized small bowel, and red meat intolerance, it may not account for all anemias seen. First, there is increasing evidence that obesity creates a state of chronic inflammation. Both iron deficiency anemia and anemia of chronic inflammation present with low serum iron levels. Most studies reporting anemia after bariatric surgery lack serum ferritin determinations so that the relative contribution of inflammation to anemia cannot be assessed. Second, a significant number of anemias after bariatric surgery remain unexplained and may be attributable to less frequently seen micronutrient deficiencies such as copper, fatsoluble vitamins A and E, or an imbalance in zinc intake. Third, although deficiencies of folate and vitamin B(12) are infrequent, study observation periods may be too short to detect anemia attributable to vitamin B(12) deficiency because vitamin B(12) storage depletion takes many years. This review is intended to increase awareness of the mechanisms of anemia above and beyond iron deficiency in the bariatric patient and provide healthcare providers with tools for a more thoughtful approach to anemia in this patient population

Regulation of iron homeostasis in anemia of chronic disease and iron deficiency anemia: diagnostic and therapeutic implications

Editorial: Blood
Fecha: 01/03/2009
Theurl I, Aigner E, Theurl M, Nairz M, Seifert M, Schroll A, Sonnweber T, Eberwein L, Witcher DR, Murphy AT, Wroblewski VJ, Wurz E, Datz C, Weiss G.

The anemia of chronic disease (ACD) is characterized by macrophage iron retention induced by cytokines and the master regulator hepcidin. Hepcidin controls cellular iron efflux upon binding to the iron export protein ferroportin. Many patients, however, present with both, ACD and iron deficiency anemia (ACD/IDA), the later due to chronic blood loss. We used a rat model of ACD due to chronic arthritis and mimicked ACD/IDA by additional phlebotomy in order to define differing iron regulatory pathways. Iron retention during inflammation occurs in macrophages and the spleen, but not in the liver. In rats and humans suffering from ACD, serum hepcidin concentrations are elevated, which is paralleled by reduced duodenal and macrophage expression of ferroportin. Individuals suffering from ACD/IDA have significantly lower hepcidin levels than ACD subjects, and ACD/IDA individuals, in contrast to ACD subjects, were able to absorb dietary iron from the gut and to mobilize iron from macrophages. Circulating hepcidin levels affect iron traffic in ACD and ACD/ IDA and are more responsive to the erythropoietic demands for iron than to inflammation. Hepcidin determination may aid to differentiate between ACD and ACD/IDA and in selecting appropriate therapy for these patients

Randomized, Double-Blind, Placebo-Controlled Trial of Effects of Enteral Iron Supplementation on Anemia and Risk of Infection during Surgical Critical Illness

Editorial: Surg Infect
Fecha: 01/02/2009
Pieracci FM, Henderson P, Rodney JR, Holena DN, Genisca A, Ip I, Benkert S, Hydo LJ, Eachempati SR, Shou J, Barie PS.

Abstract Background: Critical illness is characterized by hypoferremia, iron-deficient erythropoiesis (IDE), and anemia. The relative risks and benefits of iron supplementation in this setting are unknown. Methods: Anemic, critically ill surgical patients with an expected intensive care unit length of stay (ULOS) >/= 5 days were randomized to either enteral iron supplementation (ferrous sulfate 325 mg three times daily) or placebo until hospital discharge. Outcomes included hematocrit, iron markers (i.e., serum concentrations of iron, ferritin, and erythrocyte zinc protoporphyrin [eZPP]), red blood cell (RBC) transfusion, transfusion rate (mL RBC/study day), nosocomial infection, antibiotic days, study length of stay (LOS), ULOS, and death. Iron-deficient erythropoiesis was defined as an elevated eZPP concentration. Results: Two hundred patients were randomized; 97 received iron, and 103 received placebo. Socio-demographics, baseline acuity, hematocrit, and iron markers were similar in the two groups. No differences were observed between the iron and placebo groups with respect to either hematocrit or iron markers following up to 28 days. However, patients treated with iron were significantly less likely to receive an RBC transfusion (29.9% vs. 44.7%, respectively; p = 0.03) and had a significantly lower transfusion rate (22.0 mL/day vs. 29.9 mL/day; p = 0.03). Subgroup analysis revealed that these differences were observed in patients with baseline IDE only. Iron and placebo groups did not differ with respect to incidence of infection (46.8% vs. 48.9%; p = 0.98), antibiotic days (14 vs. 16; p = 0.45), LOS (14 vs. 16 days; p = 0.24), ULOS (12 vs. 14 days; p = 0.69), or mortality rate (9.4% vs. 9.9%; p = 0.62). Conclusions: Enteral iron supplementation of anemic, critically ill surgical patients does not increase the risk of infection and may benefit those with baseline IDE by decreasing the risk of RBC transfusion. A trial comparing enteral and parenteral iron supplementation in this setting is warranted ( number, NCT00450177).

Results of a national survey on transfusion habit in Intensive Care Units

Editorial: Med Intensiva
Fecha: 01/01/2009
Quintana Díaz M, Sánchez Casado M, Leal Noval SR, García de Lorenzo Y Mateos A; Grupo de Trabajo de Hemoderivados y Alternativas Transfusionales.

INTRODUCTION: Blood derivatives are clinical products that are currently used, for which their lack of availability, clinical relevance and presence of associated side effect that make it necessary to known and evaluate their utility rigorously are characteristic. OBJECTIVE: To analyze knowledge of attitudes, knowledge and behavior on transfusional policy in the different Spanish Intensive Care Units (ICU). DESIGN: A mail-based survey (electronic and conventional) in the ICUs. DURATION: The study was planned in 2005 and conducted during the year 2006. SETTING: Spanish ICUs. PATIENTS AND METHOD: A 27-question questionnaire. RESULTS: Most are middle-sized ICUs (10-20 beds), with predominantly medical activities. The staff member, alone or with the resident, generally decides the transfusion based on his/her experience, although with a tendency to follow the scientific guidelines. Generally, there is no transfusional committee. When red blood packs are transfused, generally between 2 to 4 units are used. The hemoglobin value is orientative, although the decision is clear if < 7 g/dl (10 g/dl if there is heart disease). Drug alternatives to transfusion are not generally used due to lack of evidence and price. In 50% of cases, the association between transfusion and increase in mortality is considered to be certain. CONCLUSIONS: Strong consideration must be made about transfusion and its over use should be avoided. For this purpose, educational guidelines and consensus meetings are necessary to establish recommendations on the use of blood products and their pharmacological alternatives.

Unexplained anemia in the elderly

Editorial: Semin Hematol
Fecha: 01/10/2008
Makipour S, Kanapuru B, Ershler WB.

Among the elderly, anemia occurs with increasing frequency with each advancing decade. Unlike when anemia occurs in younger adults, the cause of anemia in the elderly is oftentimes not readily apparent or attributable to a single cause. However, this commonly observed form of anemia in the elderly (termed unexplained anemia [UA]) can generally be dissected to its root causes, which include renal insufficiency, inflammation, testosterone deficiency, and stem cell proliferative decline. Myelodysplasia (MDS) occurs commonly in this age group but can and should, for both diagnostic and therapeutic considerations, be distinguished from UA.

Anemia of aging: the role of chronic inflammation and cancer

Editorial: Semin Hematol
Fecha: 01/10/2008
Ferrucci L, Balducci L.

Aging is associated with increased incidence and prevalence of anemia, leading to a number of adverse health outcomes. These include death, functional dependence, increased risk of therapeutic complications, falls, and dementia. In approximately 30% of cases, anemia in older individuals is due to either relative or absolute erythropoietin (EPO) deficiency. Absolute EPO deficiency may be primary or secondary to declining renal function. Relative EPO deficiency is due to an age-related pro-inflammatory status that reduces the sensitivity of erythropoietic precursors to EPO. Despite this condition of EPO deficiency, the management of anemia of aging with erythropoiesis-stimulating agents (ESAs) is controversial, unless the anemia is due to renal insufficiency. The main concern related to this treatment arises from eight studies of ESAs in cancer, suggesting that ESAs may reduce patient survival in addition to increasing the risk of deep vein thrombosis. The results of these studies contrast with a host of other trials showing the safety of ESAs. The discrepancy may be explained in part by the fact that, in the trials suggesting a detrimental effect of ESAs, the goal was to obtain hemoglobin (Hb) levels higher than 12 g/dL. Because of this concern, correction of anemia in elderly individuals with relative EPO insufficiency should not be attempted outside clinical trials.

Nutritional anemias and the elderly

Editorial: Semin Hematol
Fecha: 01/10/2008
Carmel R.

Nutritional anemias are important because they are easily reversed and because their underlying causes, most often unrelated to dietary intake, require individualized assessment. Iron-deficiency anemia (IDA) usually results from iron losses accompanying chronic bleeding, including loss to intestinal parasites, or from gastric disorders or malabsorption in the elderly. Cobalamin-deficiency anemia, the only nutritional anemia with predilection for the elderly, nearly always stems from failure of intrinsic factor (IF)-related absorption. Folate-deficiency anemia, the only nutritional anemia usually caused by poor intake, has nearly disappeared in countries that fortify food with folic acid. Copper-deficiency anemia, which usually results from malabsorptive disorders or from medical or nutritional interventions that provide inadequate copper or excess zinc, is uncommon but increasingly recognized. The prevalences of nutritional anemias, which are not always distinguished from non-anemic deficiency, are uncertain. The mean corpuscular volume (MCV) provides an essential diagnostic tool leading to judicious matching of relevant biochemical changes with relevant anemia. Nutritional anemias usually feature abnormal MCV, whereas the predominant anemias in the aged, especially the anemias of chronic disease/chronic inflammation (ACD/ACI), of renal failure, and of unknown causes, are typically normocytic.

Epidemiology of anemia in older adults

Editorial: Semin Hematol
Fecha: 01/10/2008
Patel KV

Anemia is a common, multifactorial condition among older adults. The World Health Organization (WHO) definition of anemia (hemoglobin concentration <12 g/dL in women and <13 g/dL in men) is most often used in epidemiologic studies of older adults. More than 10% of community-dwelling adults age 65 years and older has WHO-defined anemia. After age 50 years, prevalence of anemia increases with advancing age and exceeds 20% in those 85 years and older. In nursing homes, anemia is present in 48% to 63% of residents. Incidence of anemia in older adults is not well characterized. Among older adults with anemia, approximately one third have evidence of iron, folate, and/or vitamin B(12) deficiency, another third have renal insufficiency and/or chronic inflammation, and the remaining third have anemia that is unexplained. Several studies demonstrate that anemia is associated with poorer survival in older adults. This review details the distribution and consequences of anemia in older adults and identifies future epidemiologic research needs.

Anemia and cerebral outcomes: many questions, fewer answers

Editorial: Anesth Analg
Fecha: 01/10/2008
Hare GM, Tsui AK, McLaren AT, Ragoonanan TE, Yu J, Mazer CD.

A number of clinical studies have associated acute anemia with cerebral injury in perioperative patients. Evidence of such injury has been observed near the currently accepted transfusion threshold (hemoglobin [Hb] concentration, 7-8 g/dL), and well above the threshold for cerebral tissue hypoxia (Hb 3-4 g/dL). However, hypoxic and nonhypoxic mechanisms of anemia-induced cerebral injury have not been clearly elucidated. In addition, protective mechanisms which may minimize cerebral injury during acute anemia have not been well defined. Vasodilatory mechanisms, including nitric oxide (NO), may help to maintain cerebral oxygen delivery during anemia as all three NO synthase (NOS) isoforms (neuronal, endothelial, and inducible NOS) have been shown to be up-regulated in different experimental models of acute hemodilutional anemia. Recent experimental evidence has also demonstrated an increase in an important transcription factor, hypoxia inducible factor (HIF)-1alpha, in the cerebral cortex of anemic rodents at clinically relevant Hb concentrations (Hb 6-7 g/dL). This suggests that cerebral oxygen homeostasis may be in jeopardy during acute anemia. Under hypoxic conditions, cytoplasmic HIF-1alpha degradation is inhibited, thereby allowing it to accumulate, dimerize, and translocate into the nucleus to promote transcription of a number of hypoxic molecules. Many of these molecules, including erythropoietin, vascular endothelial growth factor, and inducible NOS have also been shown to be up-regulated in the anemic brain. In addition, HIF-1alpha transcription can be increased by nonhypoxic mediators including cytokines and vascular hormones. Furthermore, NOS-derived NO may also stabilize HIF-1alpha in the absence of tissue hypoxia. Thus, during anemia, HIF-1alpha has the potential to regulate cerebral cellular responses under both hypoxic and normoxic conditions. Experimental studies have demonstrated that HIF-1alpha may have either neuroprotective or neurotoxic capacity depending on the cell type in which it is up-regulated. In the current review, we characterize these cellular processes to promote a clearer understanding of anemia-induced cerebral injury and protection. Potential mechanisms of anemia-induced injury include cerebral emboli, tissue hypoxia, inflammation, reactive oxygen species generation, and excitotoxicity. Potential mechanisms of cerebral protection include NOS/NO-dependent optimization of cerebral oxygen delivery and cytoprotective mechanisms including HIF-1alpha, erythropoietin, and vascular endothelial growth factor. The overall balance of these activated cellular mechanisms may dictate whether or not their up-regulation leads to cytoprotection or cellular injury during anemia. A clearer understanding of these mechanisms may help us target therapies that will minimize anemia-induced cerebral injury in perioperative patients.

Increased mortality, morbidity, and cost associated with red blood cell transfusion after cardiac surgery

Editorial: Curr Opin Anaesthesi
Fecha: 01/10/2008
Reeves BC, Murphy GJ.

PURPOSE OF REVIEW: Literature since 2006 was reviewed to identify the harms and costs of red blood cell (RBC) transfusion. RECENT FINDINGS: Several studies, on people having various cardiac surgery operations, found strong associations of RBC transfusion with mortality and postoperative morbidity. The effect on mortality was strongest close to the time of operation but extended to 5 years. Morbidity outcomes included serious wound and systemic infections, renal failure, prolonged ventilation, low cardiac index, myocardial infarction, and stroke. RBC transfusion was also strongly associated with increased intensive care and ward postoperative stay, and hence increased cost of admission; available studies did not consider all resources used and the associated costs. SUMMARY: The harms of RBC transfusion have potentially serious and long-term consequences for patients and are costly for health services. This evidence should shift clinicians’ equipoise towards more restrictive transfusion practice. The immediate aim should be to avoid transfusing small numbers of RBC units for general malaise attributed to anaemia, a practice which appears to occur in about 50% of transfused patients. Randomized trials comparing restrictive and liberal transfusion triggers are urgently needed to compare directly the balance of benefits and harms from RBC transfusion

Efficacy of red blood cell transfusion in the critically ill: a systematic review of the literature

Editorial: Crit Care Med
Fecha: 01/09/2008
Marik PE, Corwin HL.

BACKGROUND: Red blood cell (RBC) transfusions are common in intensive care unit, trauma, and surgical patients. However, the hematocrit that should be maintained in any particular patient because the risks of further transfusion of RBC outweigh the benefits remains unclear. OBJECTIVE: A systematic review of the literature to determine the association between red blood cell transfusion, and morbidity and mortality in high-risk hospitalized patients. DATA SOURCES: MEDLINE, Embase, Cochrane Register of Controlled Trials, and citation review of relevant primary and review articles. STUDY SELECTION: Cohort studies that assessed the independent effect of RBC transfusion on patient outcomes. From 571 articles screened, 45 met inclusion criteria and were included for data extraction. DATA EXTRACTION: Forty-five studies including 272,596 were identified (the outcomes from one study were reported in four separate publications). The outcome measures were mortality, infections, multiorgan dysfunction syndrome, and acute respiratory distress syndrome. The overall risks vs. benefits of RBC transfusion on patient outcome in each study was classified as (i) risks outweigh benefits, (ii) neutral risk, and (iii) benefits outweigh risks. The odds ratio and 95% confidence interval for each outcome measure was recorded if available. The pooled odds ratios were determined using meta-analytic techniques. DATA SYNTHESIS: Forty-five observational studies with a median of 687 patients/study (range, 63-78,974) were analyzed. In 42 of the 45 studies the risks of RBC transfusion outweighed the benefits; the risk was neutral in two studies with the benefits outweighing the risks in a subgroup of a single study (elderly patients with an acute myocardial infarction and a hematocrit <30%). Seventeen of 18 studies, demonstrated that RBC transfusions were an independent predictor of death; the pooled odds ratio (12 studies) was 1.7 (95% confidence interval, 1.4-1.9). Twenty-two studies examined the association between RBC transfusion and nosocomial infection; in all these studies blood transfusion was an independent risk factor for infection. The pooled odds ratio (nine studies) for developing an infectious complication was 1.8 (95% confidence interval, 1.5-2.2). RBC transfusions similarly increased the risk of developing multi-organ dysfunction syndrome (three studies) and acute respiratory distress syndrome (six studies). The pooled odds ratio for developing acute respiratory distress syndrome was 2.5 (95% confidence interval, 1.6-3.3). CONCLUSIONS: Despite the inherent limitations in the analysis of cohort studies, our analysis suggests that in adult, intensive care unit, trauma, and surgical patients, RBC transfusions are associated with increased morbidity and mortality and therefore, current transfusion practices may require reevaluation. The risks and benefits of RBC transfusion should be assessed in every patient before transfusion.

Serum transferrin receptor

Editorial: Am. J. Hematol
Fecha: 01/09/2008
Skikne BS

Transferrin receptors (TfRs) are the conventional pathway by which cells acquire iron for physiological requirements. Under iron-deficient conditions there is an increased concentration of surface TfR, especially on bone marrow erythroid precursors, as a mechanism to sequester needed iron. TfRs are also present in the circulation, and the circulating serum TfR (sTfR) level reflects total body TfR concentration. Under normal conditions erythroid precursors are the main source of sTfR. Disorders of the bone marrow with reduced erythroid precursors are associated with low sTfR levels. The sTfR concentration begins to rise early in iron deficiency with the onset of iron-deficient erythropoiesis, and continues to rise as iron-deficient erythropoiesis progressively worsens, prior to the development of anemia. The sTfR level does not increase in anemia of chronic inflammation, but is increased when anemia of chronic inflammation is combined with iron deficiency. The sTfR level is also increased in patients with expanded erythropoiesis, including hemolytic anemias, myelodysplastic syndromes, and use of erythropoietic stimulating agents. The ratio of sTfR/ferritin can be used to quantify the entire spectrum of iron status from positive iron stores through negative iron balance, and is particularly useful in evaluating iron status in population studies. The sTfR/log ferritin ratio is valuable for distinguishing anemia of chronic inflammation from iron deficiency anemia, whether the latter occurs alone or in combination with anemia of chronic inflammation. ., 2008. (c) 2008 Wiley-Liss, Inc

Cell-Free Hemoglobin-Based Blood Substitutes and Risk of Myocardial Infarction and Death: A Meta-analysis

Editorial: JAMA
Fecha: 01/04/2008
Natanson C, Kern SJ, Lurie P, Banks SM, Wolfe SM

CONTEXT: Hemoglobin-based blood substitutes (HBBSs) are infusible oxygen-carrying liquids that have long shelf lives, have no need for refrigeration or cross-matching, and are ideal for treating hemorrhagic shock in remote settings. Some trials of HBBSs during the last decade have reported increased risks without clinical benefit. OBJECTIVE: To assess the safety of HBBSs in surgical, stroke, and trauma patients. DATA SOURCES: PubMed, EMBASE, and Cochrane Library searches for articles using hemoglobin and blood substitutes from 1980 through March 25, 2008; reviews of Food and Drug Administration (FDA) advisory committee meeting materials; and Internet searches for company press releases. STUDY SELECTION: Randomized controlled trials including patients aged 19 years and older receiving HBBSs therapeutically. The database searches yielded 70 trials of which 13 met these criteria; in addition, data from 2 other trials were reported in 2 press releases, and additional data were included in 1 relevant FDA review. DATA EXTRACTION: Data on death and myocardial infarction (MI) as outcome variables. RESULTS: Sixteen trials involving 5 different products and 3711 patients in varied patient populations were identified. A test for heterogeneity of the results of these trials was not significant for either mortality or MI (for both, I(2) = 0%, P >/= .60), and data were combined using a fixed-effects model. Overall, there was a statistically significant increase in the risk of death (164 deaths in the HBBS-treated groups and 123 deaths in the control groups; relative risk [RR], 1.30; 95% confidence interval [CI], 1.05-1.61) and risk of MI (59 MIs in the HBBS-treated groups and 16 MIs in the control groups; RR, 2.71; 95% CI, 1.67-4.40) with these HBBSs. Subgroup analysis of these trials indicated the increased risk was not restricted to a particular HBBS or clinical indication. CONCLUSION: Based on the available data, use of HBBSs is associated with a significantly increased risk of death and MI.Published online April 28, 2008 (doi:10.1001/jama.299.19.jrv80007).

Complement split products and proinflammatory cytokines in intraoperatively salvaged unwashed blood during hip replacement: comparison between heparin-coated and non-heparin-coated autotransfusion systems

Editorial: Vox Sang
Fecha: 01/04/2008
Kvarnström A, Schmidt A, Tylman M, Jacobsson M, Bengtsson A.

Background and Objectives The aim of the present study was to investigate the quality of shed blood collected in a new intraoperative autotransfusion system (Sangvia(R), AstraTech, Sweden) and to study whether heparin-coated surfaces in the device reduce the production of inflammatory mediators. Material and Methods The study was randomized and prospective. Twelve total hip arthroplasty patients whose blood was collected with a device having a heparin-coated surface and 12 patients whose blood was collected with a device having a non-heparin-coated surface were included. Venous blood was drawn from the patients preoperatively. Intraoperatively 200 ml salvaged blood was collected and samples were also withdrawn; samples were obtained from the blood bag. Results Compared to venous blood, elevated concentrations of interleukin 6 (IL-6), IL-8, C3a and polymorphonuclear elastase were found in collected blood. No significant differences in inflammatory mediators were found between the heparin-coated and the non-heparin-coated groups. The median haemoglobin concentration in the salvaged blood was 74 g/l in both groups. Plasma haemoglobin and potassium concentrations were also elevated. There were no significant differences between the groups. Conclusion The present study indicates that the blood salvaged intraoperatively contains elevated levels of complement split product and proinflammatory cytokines and that heparin-coated surfaces of the salvage device do not significantly influence the formation of inflammatory mediators

Efficacy and safety of intravenous iron therapy as an alternative/adjunct to allogeneic blood transfusion

Editorial: Vox Sang
Fecha: 01/01/2008
Muñoz M, Breymann C, García-Erce JA, Gómez-Ramírez S, Comin J, Bisbe E.

Anaemia is a common condition among patients admitted to hospital medicosurgical departments, as well as in critically ill patients. Anaemia is more frequently due to absolute iron deficiency (e.g. chronic blood loss) or functional iron deficiency (e.g. chronic inflammatory states), with other causes being less frequent. In addition, preoperative anaemia is one of the major predictive factors for perioperative blood transfusion. In surgical patients, postoperative anaemia is mainly caused by perioperative blood loss, and it might be aggravated by inflammation-induced inhibition of erythropoietin and functional iron deficiency (a condition that cannot be corrected by the administration of oral iron). All these mechanisms may be involved in the anaemia of the critically ill. Intravenous iron administration seems to be safe, as very few severe side-effects were observed, and may result in hastened recovery from anaemia and lower transfusion requirements. However, it is noteworthy that many of the recommendations given for intravenous iron treatment are not supported by a high level of evidence and this must be borne in mind when making decisions regarding its application to a particular patient. Nonetheless, this also indicates the need for further large, randomized controlled trials on the safety and efficacy of intravenous iron for the treatment of anaemia in different clinical settings

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

Editorial: TATM
Fecha: 01/09/2007

Intravenous iron has been used extensively in nephrology for decades. However, the rare but serious reactions associated with high-molecular-weight iron dextran administration have resulted in largely unjustified fears over its use, thus limiting its application in other indications. In Europe, and more recently in the USA, the availability of several iron formulations that are safe and effective – iron sucrose, ferric gluconate and low-molecular-weight iron dextran – has extended the use of intravenous iron to a number of medical settings. Although oral iron continues to be widely used in the correction of iron-deficiency anemia, it cannot cover the needs of all patients. It is slow-acting and not always well absorbed or well tolerated because of gastrointestinal disturbances. It takes weeks for oral iron to raise the hemoglobin level and months to replenish iron stores. Intravenous iron given to anemic iron-deficient patients can raise the hemoglobin level in a few days and can replenish iron stores in a few weeks. Furthermore, it has been shown to correct the anemia of chronic disease when used in combination with exogenous erythropoietin. With some preparations, the total iron deficit can be corrected with one infusion, making the treatment more cost-effective by eliminating repeat visits. Intravenous iron has contributed to decreasing the need for transfusions and to reducing the doses of erythropoiesis-stimulating agents necessary to correct anemia in nephrology, in obstetrics and gynecology, in patients with cancer undergoing chemotherapy, and in surgery and orthopedics. The safety and ease of administration of the new iron preparations continues to expand the application of intravenous iron to new areas

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

Editorial: Best Pract Res Clin
Fecha: 01/06/2007
Shander A, Hofmann A, Gombotz H, Theusinger OM, Spahn DR.

Understanding the costs associated with blood products requires sophisticated knowledge about transfusion medicine and is attracting the attention of clinical and administrative healthcare sectors worldwide. To improve outcomes, blood usage must be optimized and expenditures controlled so that resources may be channeled toward other diagnostic, therapeutic, and technological initiatives. Estimating blood costs, however, is a complex undertaking, surpassing simple supply versus demand economics. Shrinking donor availability and application of a precautionary principle to minimize transfusion risks are factors that continue to drive the cost of blood products upward. Recognizing that historical accounting attempts to determine blood costs have varied in scope, perspective, and methodology, new approaches have been initiated to identify all potential cost elements related to blood and blood product administration. Activities are also under way to tie these elements together in a comprehensive and practical model that will be applicable to all single-donor blood products without regard to practice type (e.g., academic, private, multi- or single-center clinic). These initiatives, their rationale, importance, and future directions are described

Aprotinin; friend or foe? A review of recent medical literature

Editorial: Eur J Anaesthesiol
Fecha: 01/01/2007
Royston D, van Haaften N, De Vooght P.

Recent articles published in peer review journals have questioned the safety of using aprotinin in patients having heart surgery. Also, evidence has been published to suggest an increase in renal events in patients given aprotinin when compared to those where tranexamic acid was used. The present review will focus principally on the first of these articles in relation to previously published data and experience.

The role of intravenous iron in cancer-related anemia.

Editorial: Oncology
Fecha: 01/09/2006
Henry DH.

Patients with cancer may have an absolute or functional iron deficiency as a result of their disease or its treatment. These conditions can lead to an insufficient supply of iron for incorporation into erythrocytes during supportive care with erythropoiesis-stimulating proteins for chemotherapy. The use of supplemental iron therapy is well established in patients with chronic kidney disease and anemia, but less well studied in the oncology/hematology setting. Furthermore, the use of oral iron formulations in patients with cancer and anemia is limited by poor absorption in the duodenum, arduous dosing requirements (three times a day), and a high likelihood of gastrointestinal side effects. Two recent studies have shown that intravenous (i.v.) iron (iron dextran or ferric gluconate) increases the hematopoietic response rates in cancer patients who were receiving chemotherapy and treated with epoetin alfa (Procrit) for anemia. The effects on hemoglobin levels and measures of iron metabolism were notably greater with i.v. iron formulations than with oral iron formulations. The results from several ongoing trials of i.v. iron in patients treated with epoetin alfa or darbepoetin alfa (Aranesp) for chemotherapy-induced anemia should lead to a greater understanding of the role of i.v. iron supplementation in improving the hematopoietic responses in these patients

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.

Editorial: J Natl Cancer Inst
Fecha: 01/06/2006
Bohlius J, Wilson J, Seidenfeld J, Piper M, Schwarzer G, Sandercock J, Trelle S, Weingart O, Bayliss S, Djulbegovic B, Bennett CL, Langensiepen S, Hyde C, Engert A.

This is an updated systematic review of 57 trials and 9353 cancer patients from articles, abstracts, and reports published between January 1, 1985, and April 30, 2005, on the effects of epoetin alfa and beta (i.e., epoetin) and darbepoetin alfa (i.e., darbepoetin). We included randomized controlled trials comparing epoetin or darbepoetin plus red blood cell transfusion with red blood cell transfusion alone for prophylaxis or treatment of anemia in cancer patients with or without concurrent antineoplastic therapy. The Cochrane Library, MEDLINE, EMBASE, and conference proceedings were searched. Effect estimates and 95% confidence intervals (CIs) were calculated with fixed-effects models. Treatment with epoetin or darbepoetin statistically significantly reduced the risk for red blood cell transfusions (relative risk [RR] = 0.64, 95% CI = 0.60 to 0.68; 42 trials and 6510 patients) and improved hematologic response (RR = 3.43, 95% CI = 3.07 to 3.84; 22 trials and 4307 patients). Treatment with epoetin or darbepoetin increased the risk of thrombo-embolic events (RR = 1.67, 95% CI = 1.35 to 2.06; 35 trials and 6769 patients). Uncertainties remain as to whether and how epoetin or darbepoetin affects overall survival (hazard ratio = 1.08, 95% CI = 0.99 to 1.18; 42 trials and 8167 patients). Caution is advised when using epoetin or darbepoetin in combination with thrombogenic chemotherapeutic agents or for cancer patients who are at high risk for thrombo-embolic events

Pharmacological approaches to reducing blood loss and transfusions in the surgical patient

Editorial: Can J Anaesth
Fecha: 01/06/2006
Ozier Y, Schlumberger S.
Service d’Anesthesie-Reanimation Chirurgicale, France

PURPOSE: To review the efficacy, effectiveness and safety of hemostatic drugs to reduce surgical blood loss. METHODS: Analysis of randomized controlled trials and meta-analyses exploring the efficacy of desmopressin, aprotinin, lysine analogues and recombinant activated factor VII (rFVIIa) on clinically important endpoints. MAIN FINDINGS: Although potentially useful in surgical patients with mild hemophilia or type I von Willebrand’s disease, desmopressin has no proven benefit in patients without previous hemostatic defects. Aprotinin has been studied extensively in cardiopulmonary bypass surgery, with evidence of a blood sparing effect. Additional benefits are suggested. The drug is less consistently effective in liver transplantation and major orthopedic surgery. Although rare, hypersensitivity reactions to aprotinin may occur, especially on re-exposure. Tranexamic acid can reduce blood transfusion in cardiac surgery, liver transplantation and total knee arthroplasty surgery with a satisfactory safety profile. Epsilon aminocaproic acid has not been investigated adequately, despite its widespread use. While rFVIIa may be beneficial in controlling massive coagulopathic bleeding in trauma and surgical patients, there is currently no evidence to support its prophylactic use in elective surgical patients. CONCLUSION: Aprotinin and tranexamic acid are valuable pharmacologic options for reducing surgical bleeding. The expected benefit of these drugs is highly dependent on the actual blood usage for a given procedure at the institutional level. More studies using clinically significant endpoints are necessary to assess the relative efficacy and optimal dosing of these drugs

Massive transfusion practices around the globe and a suggestion for a common massive transfusion protocol.

j trauma
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.

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

Editorial: Anesth Analg
Fecha: 01/11/2005
Lawrence T. Goodnough, Aryeh Shander, Jerry L. Spivak, Jonathan H. Waters, Arnold J. Friedman, Jeffrey L. Carson, E. Michael Keating, Thomas Maddox and Richard Spence

Department of Pathology, Stanford University Medical Center, 300 Pasteur Drive H-1402, Stanford, CA 94305-5626, USA.

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.

Curr Opin Crit Care

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. 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.

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.

The effect of acute autologous blood transfusion on coagulation dysfunction after cardiopulmonary bypass

Editorial: Eur J Anaesthesiol
Fecha: 00/00/0000
Zisman E, Eden A, Shenderey A, Meyer G, Balagula M, Ammar R, Pizov R.

OBJECTIVE: To evaluate the influence of acute autologous blood transfusion on postcardiopulmonary bypass coagulation disturbances evaluated by thromboelastography (TEG) as a point-of-care test. METHODS: This prospective randomized controlled study included consecutive patients who underwent elective cardiac surgery with cardiopulmonary bypass. The patients in group A underwent acute autologous blood transfusion with acute normovolemic haemodilution and those in group H received homologous blood, if needed, and served as controls. RESULTS: A total of 62 patients, from 68 enrolled, completed the study: 27 in group A and 35 in group H. Both groups had similar prolongation of prothrombin time and partial thromboplastin time, decreased platelets count and changes in postoperative thromboelastographic variables. There were no differences between them for postoperative bleeding, blood transfusions or haemoglobin values. There was significant prolongation of the R value of TEG (without heparinase) in both groups at 4 h after surgery compared with the immediate postoperative values: from 11.3 +/- 4.2 to 12.3 +/- 5.5 mm, P < 0.05 for group A and from 9.9 +/- 3.7 to 12.5 +/- 5.4 mm, P < 0.01 for group H. The R values of TEG with and without heparinase differed significantly (P < 0.05) at 4 h postoperatively. CONCLUSION: Autologous blood transfusion of 15% estimated blood volume did not affect postcardiopulmonary bypass coagulopathy, nor did it decrease blood loss or homologous blood and its products transfusion in the early postoperative period. TEG is a valuable measure for detecting coagulation dysfunction with a potential role in the postoperative management of cardiac patients

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