Anemia And Clinical Outcomes - Harvard University
Anesthesiology Clin N Am23 (2005) 315 – 325Anemia and Clinical OutcomesMercy Kuriyan, MD, MHAa, Jeffrey L. Carson, MDb,*aTransfusion Medicine, Department of Pathology,University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School,125 Patterson Street, Professional Building, 4th floor, New Brunswick, NJ 08903, USAbDivision of General Internal Medicine, Department of Medicine,University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School,125 Patterson Street, Professional Building, 4th floor, New Brunswick, NJ 08903, USAThe anesthesiologist and the surgeon, followed by the oncologist, areamong the largest consumers of blood products,. Typically, between 60% and70% of all red blood cell units are transfused in the surgical setting [1] In theauthors’ facility, a tertiary care university medical center, the consumption ofblood products by service is shown in Table 1. Surgical patients used 42% ofthe RBC and 40% of all the other blood components used in the hospital over a1-year period. Of the total RBC used, 36% of red blood cells were used duringsurgery, and 64% were used during the postoperative time period.Pathophysiology of anemiaPatients in the perioperative setting are at a risk of anemia primarily fromblood loss during surgery. In anemia, even at hemoglobin levels well below10 g/dL the o2 carrying capacity is decreased, but tissue oxygenation is preserved. Anemia causes hemodynamic alterations. The combined effect of hypovolemia and anemia often occur as a result of blood loss. Acute anemia thus maycause tissue hypoxia or anoxia through diminished cardiac output, resulting instagnant hypoxia, and decreased o2-carrying capacity (anemic hypoxia) (Table 2)This article was supported in part by National Heart Lung and Blood Institute Grant 1R01 HL73958-01.* Corresponding author.E-mail address: carson@umdnj.edu (J.L. Carson).0889-8537/05/ – see front matter D 2005 Elsevier Inc. All rights gy.theclinics.com
316kuriyan&carsonTable 1Red blood cell (rbc) and other blood component (bc) use by servicesServiceRBCs used(in units)Total RBCsused (%)BC used(units)Total BCused (%)OPEN HEARTGENERAL SURGERYTRAUMAORTHOPEDICSOTHER SURGERYKIDNEY 8705276836029.36.43.94.90.30Total all art transplantOutpatientOther servicesOther (service not nd total1776413548Blood use for 12 months of 2003 in a Tertiary Care University Medical Center.For surgeries for the year, 36% of the RBC was used in the OR, and 64% of the RBC was used postoperatively. For all other products used, 35% was used in the OR, and 65% was used postoperatively.[2]. The body preserves o2 delivery to vital organs by compensatory increases inmyocardial contractility and heart rate as well as by increased arterial and venousvascular tone mediated through increased sympathetic discharge. Variable increases in resting heart rate and diastolic blood pressure occur with losses rangingfrom 5% to 15% in blood volume. Larger losses cause progressive increases inheart rate and decreases in arterial blood pressure and evidence of organ hypoperfusion. The increased sympathetic tone diverts a decreasing global blood flow(cardiac output) away from the splanchnic, skeletal, and cutaneous circulationtoward the coronary and cerebral circulation. Hypovolemic shock is seen whenvital organ systems such as the kidneys, the central nervous system, and the heartare affected. The cardiovascular and systemic response to acute blood loss hasbeen categorized according to degrees of blood loss [3]. Many of these responsesare modified by the rapidity of blood loss and patient characteristics such as age,comorbid illnesses, pre-existing volume status, hemoglobin values, and the useof medications that have cardiac or peripheral vascular effects such as b blockersor antihypertensives.Well-controlled laboratory studies show an inverse relationship between hemoglobin and hematocrit levels and cardiac output, especially in chronic anemia
anemia and clinical outcomes317Table 2Equations relevant to tissue hypoxiaDefinitionsEquationsDo2 is o2 deliveryCo is total blood flow or cardiac outputCao2 is arterial o2 contentArterial o2 content may be approximatedfrom the portion bound to haemoglobinOne gram of hemoglobin binds 1.39 ml ofoxygen when fully saturatedThe small amount of dissolved plasma o2 isdirectly proportional to the partial pressureand may be calculated by multiplying Po2by a constant (k 0.00301 ml/ml/mm Hg),termed the solubility coefficientSubstitute Cao2 from equation 2 into 1Co cardiac output in L/min%Sat hemoglobin o2 saturation in %[Hb] hemoglobin concentration in g/dLDo2 Co Cao2Cao2 (ml/L) %Sat 1.39 (ml/g) [Hb] (g/dL)Do2 Co (%Sat 1.39 [Hb])Equations show that tissue hypoxia may be caused by decreased o2 delivery caused by decreases ineither hemoglobin concentration (anemic hypoxia), cardiac output (stagnant hypoxia), or hemoglobinsaturation (hypoxic hypoxia).Data from reference [29].and the level of anemia at which cardiac output begins to rise, ranging from 7 to12 g/dL of hemoglobin [4]. Similar clinical observations have been made in theperioperative setting [5]. The clinical studies are limited by confounding factorsarising from major comorbid illnesses such as cardiac disease, a lack of appropriate control patients, and significant weaknesses in study design.Interaction between pathophysiologic processes and anemiaHeart, lung, and cerebrovascular diseases potentially limit adaptive responsesand have been proposed to increase the risk of adverse consequences fromanemia. Age, severity of illness, and therapeutic interventions may also affectadaptive mechanisms.The heart may be particularly prone to adverse consequences followinganemia. This is because the myocardium consumes 60% to 75% (extraction ratio)of all o2 delivered by the coronary circulation.[6–8]. Such a high extraction ratiois unique to the coronary circulation. As a result, o2 delivery to the myocardiumcan only increase substantially by increasing blood flow [9]. Most of left ventricular perfusion is restricted to the diastolic period, and any shortening of itsduration (eg, tachycardia) constrains blood flow. Laboratory studies investigatingthe effects of normovolemic anemia on the coronary circulation [9–11] showminimal consequences from anemia, with hemoglobin levels in the range of7 g/dL if the coronary circulation is normal [12–14]. Electrocardiograph changes
318kuriyan&carsonconsistent with ischemia are seen at hemoglobin levels below 5 g/dL, whereaslactate production, depressed ventricular function, and deaths have been observedat hemoglobin levels of 3 g/dL or lower. Some animals survive with hemoglobinlevels as low as 1 to 2 g/dL [15]. However, animal studies suggest a decreasedability to tolerate anemia in the presence of cardiac disease and ST-segmentchanges, or locally depressed cardiac function occurred at hemoglobin levels inthe range of 7 to 10 g/dL [16,17].The inverse relationship between cardiac output and hemoglobin levels led tothe evaluation of the effects of hematocrit on cardiac performance in a caninemodel. This model established that optimal o2 transport occurred betweenhematocrit values of 40 to 60% [18]. Other investigators determined the maximum o2 delivery to be in the lower end of the range, at a hematocrit value of40% to 45%(13–15 g/dL) [7,10]. However, one of the most widely quoted studiesaddressing this topic found peak o2 transport to occur at hematocrit values of30% (hemoglobin, 10 g/dL) [19].Human dataHuman data are inconsistent. ECG monitoring in patients with coronary arterydisease undergoing normovolemic hemodilution have not shown an increasein cardiac complications or silent ischemia [20]. A retrospective analysis [21]involving 224 patients undergoing coronary artery bypass graft surgery failed todemonstrate any significant association between the level of hemoglobin andcoronary sinus lactate levels (an indicator of myocardial ischemia). In two smallcohort studies [22], moderate anemia was poorly tolerated in perioperative patients with cardiovascular disease, confirming observations made in the laboratory. Anemia may also result in significant increases in morbidity and mortalityin patients with other cardiac pathologies, including heart failure and valvularheart disease, presumably because of the greater burden of the adaptive increasein cardiac output.During normovolemic anemia, in laboratory [10] and human [23] studies,cerebral blood flow increased from 50% to 500% of baseline values as hemoglobin values decreased. Increased cerebral blood flow occurs because of overallincreases in cardiac output, which is preferentially diverted to the cerebral circulation. Also, as o2 delivery begins to decrease, cerebral tissues are able toincrease the amount of o2 extracted from blood. The laboratory studies suggestthat moderate degrees of anemia alone should rarely result in or worsen cerebralischemia. As a therapy in acute ischemic stroke, none of the randomized clinicaltrials found that hemodilution produced significant overall improvement inclinical outcomes. Because of the large variety of variables that may affectclinical outcomes, the negative findings may not fully rule out the possibility thathemodilution may offer some therapeutic benefits. Thus, the currently availableevidence indicates that cerebrovascular disease does not appear to predisposepatients to significant morbidity from anemia.
anemia and clinical outcomes319Studies in patients who decline blood transfusion for religious reasons provide critical insights into the effects of anemia in humans. The largest study [22]was performed in 1958 adult surgical patients who refused transfusion forreligious reasons. Mortality rates were greatest in patients with the lowest preoperative hemoglobin levels. The risk of death was markedly greater in patientswith underlying cardiovascular disease and preoperative hemoglobin levels of10 g/dL or less, whereas in patients without underlying cardiovascular disease,the differences in the mortality rates above and below 10 g/dL were not as great.These results, as well as animal and physiologic data, suggest that anemia is nottolerated as well in the presence of cardiovascular disease.In a series of studies, the effect of anemia was evaluated in normal volunteerswho underwent isovolemic reduction of hemoglobin levels to 5 g/dL. Transientand asymptomatic electrocardiogram changes were found in five of 87 volunteersincluded in two studies.[24,25]. These changes occurred when the hemoglobinlevel was between 5 and 7 g/dL and in patients with faster heart rates [26].Changes in critical oxygen delivery were not measured. Subtle but reversiblechanges in cognition were identified in nine volunteers younger than age 35 athemoglobin levels between 5 and 7 g/dL [27]. Self-rated fatigue was found ineight volunteers when the hemoglobin level fell to 7 g/dL and increased as thehemoglobin level dropped to 5 g/dL [28]. These studies suggest that importantclinical effects can be measured in young, normal humans with hemoglobinlevels between 5 and 7 g/dL. It is uncertain how these results apply to olderpatients with comorbid factors who are also under stress from surgery or acuteillness. However, it is possible that the changes measured in these young normalvolunteers would occur at higher hemoglobin levels in older patients.Efficacy of transfusionSix observational studies investigating the importance of anemia or transfusion practices in various settings have been performed [29]. There are threelarge cohort studies performed in the intensive care unit [30], coronary arterybypass surgery [31], and hip fracture [32]. Each of these studies came to adifferent conclusion. The first study [29] evaluated 4470 critically ill patientsadmitted to six Canadian tertiary level intensive care units. The need for transfusion was associated with a worse outcome. The outcomes were better forintensive care unit patients who had been transfused, especially those withcardiovascular disease. In the second study [30], 2202 patients undergoingcoronary artery bypass graft surgery were divided into three groups corresponding to their hematocrit levels on entry to the intensive care unit, high ( 34%),medium (25%–33%), and low ( 24%). Patients in the high group were morethan twice as likely to have a myocardial infarction then the low group patients.In the largest study of 8787 consecutive hip fracture patients who underwentsurgical repair, 30- and 90-day mortality was not increased or decreased byperioperative transfusion. Three smaller studies evaluated the relationship be-
320kuriyan&carsontween anemia and adverse outcomes in vascular patients [33–35]. More ischemicevents were seen in anemic patients in all three of these studies. The validity ofthese studies is uncertain because the decision to transfuse a patient is oftencorrelated with the illness burden of the patient. It is possible that comorbiditywas not adequately adjusted for in these studies. Only randomized clinical trialscan overcome this limitation.There have been 10 randomized clinical trials with a total of 1780 trial participants contrasting the effects of different transfusion thresholds [36–45]. Theclinical settings varied, although each trial randomized patients to be transfusedon the basis of a ‘‘conservative’’ or more ‘‘liberal’’ strategy. Conservative triggers(specified hemoglobin concentrations that had to be attained) ranged from 7 to9 g/dl, with two further trials specifying hematocrit values of 25% or 30%. Thealternative liberal transfusion strategies specified triggers varying from 100% ofnormal red cell volume, 2 U of blood (immediately in one trial, postoperativelyin another), irrespective of clinical state, transfusion sufficient to maintainhemoglobin levels at or above 10g/dL in three trials and above 9 g/dL in another.Two trials specified the liberal triggers as transfusion to maintain hematocritlevels of 32% and 40% or above. There is an overlap between the liberal andconservative transfusion groups in these trials. One trial (involving patients inintensive care) contributed 47% of the patients and 82% of the recorded deaths.Of the 10 trials, only three trials included more than 100 patients, and only oneof these evaluated a transfusion strategy, which included patient assessment forsymptoms. In one of these trials, 428 patients undergoing first time, electivecoronary artery bypass surgery were randomized to arms with transfusion triggersof 9 g/dL versus 8 g/dL [37]. The difference among perioperative hemoglobinlevels was small, and the mean reduction in hemoglobin levels during the admission was equal among the groups. The event rates were very low, and therewere no differences in any outcome. The second trial included 127 patientsundergoing knee arthroplasty. Patients were randomized to receive autologousblood transfusion immediately after surgery (the first unit in the recovery roomand the second unit on returning to the ward) versus receiving autologous bloodonly if the hemoglobin level fell below 9 g/dL [44]. The mean postoperativehemoglobin levels were approximately 0.7 g/dL different, although only 25% ofrestrictive group received a transfusion. There were no differences in outcomes.In a third trial (a pilot study), 84 hip fracture patients undergoing surgical repairwere randomized to a 10 g/dL threshold or to transfusion for symptoms (transfusion was permitted if the hemoglobin level was 8 g/dL) [39]. The meanprerandomization hemoglobin level was 9.1g/dL, the lowest mean hemoglobinlevel after randomization in the symptomatic group was 8.8g/dL, and the highestmean hemoglobin level in the threshold group was 11.1g/dL. There were nodifferences in outcomes (including functional recovery, mortality and morbidity),although at 60 days after surgery, there were five deaths in the symptomaticgroup and two deaths in the 10 g/dL group. In all of these trials, the number ofpatients was too small to evaluate the effect of lower transfusion triggers onclinically important outcomes such as mortality, morbidity, and functional status.
anemia and clinical outcomes321The Transfusion Requirement in Critical Care trial (pilot and main trial)[41,42] is the only adequately powered study to evaluate clinically importantoutcomes. In the main study, the investigators randomized 838 volumeresuscitated intensive care unit patients to a restrictive strategy in which patientsreceived allogeneic red blood cell transfusions at hemoglobin levels of 7 g/dL(and were maintained between 7 and 9 g/dL) or to a liberal strategy of receivingred blood cells at 10 g/dL (and were maintained between 10 and 12 g/dL).Average hemoglobin levels (8.5 versus 10.7 g/dL) and red blood cell unitstransfused (2.6 versus 5.6) were significantly lower in the restrictive comparedwith the liberal group. The 30-day mortality was slightly lower in the restrictivetransfusion group (18.7% versus 23.3%), although the finding was not statistically significant (P 0.11). Some of the important findings from this trial aresummarized in Table 3.A meta-analysis has been performed that combined data from five or moretrials for six outcomes: probability of red cell transfusion, volume of red cellstransfused, hematocrit levels, cardiac events, mortality at 30 days, and overalllength of hospital stay (Fig. 1) [46,47]. The pooled data indicated that, onaverage, a restrictive transfusion trigger reduced the probability of red cell transfusion by a proportional 42% (an average saving of 0.93 units of red cells pertransfused patient) and resulted in hematocrit levels 5.6% lower on averagethan in patients who received more liberal transfusions. The effect on length ofhospital stay and the rates of cardiac events were not increased significantly bythe use of restrictive transfusion triggers. Restrictive transfusion triggers wereTable 3Selected important findings from the Transfusion Requirement in Critical Care trialOutcome30-day mortalitySubgroupsAPACHE score b20 (N 424)Age b55 (N 344)Cardiovascular diseasea (N 357)Ischemic heart disease (N 257)bOther OutcomesMyocardial infarctionPulmonary edemaARDSRestrictive(N 418) (%)Liberal(N 420) (%)P 0.380.75.37.72.910.711.40.020.010.06Abbreviations: APACHE, Acute Physiology and Chronic Health Evaluation; ARDS, acute respiratorydistress syndrome.aCardiovascular disease is defined as all diagnoses related to ischemic heart disease (myocardialinfarct, angina, congestive heart failure, and cardiogenic shock), rhythm disturbances, cardiac arrest,other forms of shock, uncontrolled hypertension, and cardiac and vascular surgical procedures such asabdominal aortic aneurysm repair and peripheral vascular surgical procedures.bIschemic heart disease defined as myocardial infarct, angina, congestive heart failure, andcardiogenic shock.Data from references [41,53].
322StudykuriyanRestrictiven/NBLAIR 19860 / 26BRACEY 19993 / 2154 / 50BUSH 1997CARSON 1998(a)1 / 42HEBERT 19958 / 3378 / 418HEBERT 1999LOTKE 19990 / 62Liberaln/N&carsonRR(95%CI Random)2 / 246 / 2224 / 491 / 429 / 3698 / 4200 / 65120 / 85894 / 846Total(95%CI)Chi-square 1.66 (df 6) P: 0.95 Z -1.79 P: 0.10.1 .21Favours RestrictiveWeight%RR(95%CI ,1.02]5 10Favours LiberalFig. 1. Meta-analysis from randomized clinical trials evaluating the effect of restrictive versus liberaltransfusion triggers on mortality. CI, confidence interval; RR, relative risk. (Data from references[36–39,41,42,44,46].)also not associated with an increase in mortality. The Transfusion Requirement inCritical Care trial in patients in the intensive care unit contributed 83% of theinformation in the meta-analysis of mortality data.Functional recovery is another potentially important benefit of higher hematocrit levels. There is only one small pilot study evaluating the effect of red bloodcell transfusion on functional ability in anemic patients [39]. This study was toosmall to detect clinically important differences. Most of the other published datarelating anemia to function were generated from clinical trials evaluating recombinant human erythropoietin in end-stage renal failure and patients undergoingcancer chemotherapy. These limited data suggest that increasing the hemoglobinlevel in significantly anemic patients (hemoglobin 10 g/dL) may increaseexercise tolerance [48]. The studies with negative findings evaluated the effect ofincreasing hemoglobin beyond the 10 g/dL threshold [49].Transfusion thresholdThe optimal threshold at which to transfuse is uncertain in most clinicalsituations. The authors’ opinion is that in asymptomatic patients without cardiovascular disease, a transfusion trigger of 7 g/dL should be used. Pendingadditional clinical trials [39] in patients with cardiovascular disease, we suggestusing a higher transfusion threshold such as 9 to 10 g/dL. Wu et al [50] performeda retrospective study of blood transfusion patterns in 78,974 elderly patients whowere hospitalized with acute myocardial infarction. They concluded that if thehematocrit level on admission is 30% or lower, blood transfusion would beassociated with a lower short-term mortality rate. Patients with symptoms fromanemia should be transfused as needed. No set of guidelines will apply to every
anemia and clinical outcomes323patient. In the end, careful clinical assessment with thoughtful consideration ofrisks and benefits should guide the transfusion decision.The quest to define a minimum threshold hemoglobin concentration at whichpatients achieve significant (net) benefit from the transfusion of red cells is drivenby patient safety concerns, with a desire to minimize exposure to infectiousagents such as transfusion-transmissible viruses. As the viral risk is lowered,however, more attention is focused on red cell supply issues and the potential thatred cell demand may outpace the supply of units. The blood supply of NorthAmerica and Western Europe is now safer than ever; however, the need for bloodand blood components at times is greater than their availability [51]. However,the greatest risk of blood transfusion results from giving the wrong unit of bloodto the wrong patient [52]. The goal of blood transfusion should be to optimizethe outcome of the anemic patient. Further research is urgently needed to providethe evidence required for clinicians to make wise choices for their patients.References[1] Goodnough LT, Brecher ME, Kanter MH, et al. Transfusion medicine: first of two parts:blood transfusion. N Engl J Med 1999;340:438 – 47.[2] Finch CA, Lenfant C. Oxygen transport in man. N Engl J Med 1972;286:407 – 15.[3] Alexander RH, Ali J, Aprahamian C, et al. Advanced trauma life support: program forphysicians. Chicago7 American College of Surgeons; 1993.[4] Brannon ES, Merrill AJ, Warren VJ, et al. The cardiac output in patients with chronic anemiaas measured by the technique of right atrial catheterization. J Clin Invest 1945;24:332 – 6.[5] Laks H, Pilon RN, Klovekorn WP, et al. Acute hemodilution: its effect on hemodynamicsand oxygen transport in anesthetized man. Ann Surg 1974;180:103 – 9.[6] Brazier J, Cooper N, Maloney Jr JV, et al. The adequacy of myocardial oxygen delivery inacute normovolemic anemia. Surgery 1974;75:508 – 16.[7] Fan F-C, Chen RYZ, Schuessler GB, et al. Effects of hematocrit variations on regionalhemodynamics and oxygen transport in the dog. Am J Physiol 1980;238:H545 – 52.[8] Murray JF, Rapaport E. Coronary blood flow and myocardial metabolism in acute experimentalanaemia. Cardiovasc Res 1972;6:360 – 7.[9] Jan K-M, Chien S. Effect of hematocrit variations on coronary hemodynamics and oxygenutilization. Am J Physiol 1977;233:H106 – 13.[10] Jan K-M, Heldman J, Chien S. Coronary hemodynamics and oxygen utilization after hematocritvariations in hemorrhage. Am J Physiol 1980;239:H326 – 32.[11] Most AS, Ruocco NA, Gewirtz H. Effect of a reduction in blood viscosity on maximal myocardial oxygen delivery distal to a moderate coronary stenosis. Circulation 1986;74:1085 – 92.[12] Crystal GJ, Salem MR. Myocardial oxygen consumption and segmental shortening duringselective coronary hemodilution in dogs. Anesth Analg 1988;67:500 – 8.[13] Habler OP, Kleen MS, Podtschaske AH, et al. The effect of acute normovolemic hemodilution(ANH) on myocardial contractilty in anesthetized dogs. Anesth Analg 1996;83:451 – 8.[14] Spahn DR, Smith LR, Veronee CD, et al. Acute isovolemic hemodilution and blood transfusion.Effects on regional function and metabolism in myocardium with compromised coronaryblood flow. J Thorac Cardiovasc Surg 1993;105:694 – 704.[15] Wilkerson DK, Rosen AL, Sehgal LR, et al. Limits of cardiac compensation in anemic baboons.Surgery 1988;103:665 – 70.[16] Anderson HT, Kessinger JM, McFarland Jr WJ, et al. Response of the hypertrophied heart toacute anemia and coronary stenosis. Surgery 1978;84:8 – 15.
324kuriyan&carson[17] Hagl S, Heimisch W, Meisner H, et al. The effect of hemodilution on regional myocardialfunction in the presence of coronary stenosis. Basic Res Cardiol 1977;72:344 – 64.[18] Richardson TQ, Guyton AC. Effects of polycythemia and anemia on cardiac output and othercirculatory factors. Am J Physiol 1959;197:1167 – 70.[19] Messmer K, Lewis DH, Sunder-Plassmann L, et al. Acute normovolemic hemodilution. EurSurg Res 1972;4:55 – 70.[20] Spahn DR, Schmid ER, Seifert B, et al. Hemodilution tolerance in patients with coronaryartery disease who are receiving chronic b-adrenergic blocker therapy. Anesth Analg 1996;82:687 – 94.[21] Doak GJ, Hall RI. Does hemoglobin concentration affect perioperative myocardial lactate flux inpatients undergoing coronary artery bypass surgery? Anesth Analg 1995;80:910 – 6.[22] Carson JL, Duff A, Poses RM, et al. Effect of anaemia and cardiovascular disease on surgicalmortality and morbidity. Lancet 1996;348:1055 – 60.[23] Korosue K, Heros RC. Mechanism of cerebral blood flow augmentation by hemodilutionin rabbits. Stroke 1992;23:1487 – 93.[24] Leung JM, Weiskopf RB, Feiner J, et al. Electrocardiographic ST-segment changes duringacute, severe isovolemic hemodilution in humans. Anesthesiology 2000;93:1004 – 10.[25] Weiskopf RB, Viele MK, Feiner J, et al. Human cardiovascular and metabolic response toacute, severe isovolemic anemia. JAMA 1998;279:217 – 21.[26] Leung JM, Weiskopf RB, Feiner J, et al. Electrocardiographic ST-segment changes duringacute, severe isovolemic hemodilution in humans. Anesthesiology 2000;93:1004 – 10.[27] Weiskopf RB, Kramer JH, Viele M, et al. Acute severe isovolemic anemia impairs cognitivefunction and memory in humans. Anesthesiology 2000;92:1646 – 52.[28] Toy P, Feiner J, Viele MK, et al. Fatigue during acute isovolemic anemia in healthy, restinghumans. Transfusion 2000;40:457 – 60.[29] Carson JL, Hebert PC. Anemia and red blood cell transfusion. In: Simon TL, Dzik WH,Snyder EL, et al, editors. Rossi’s principles of transfusion medicine. 3rd edition. Philadelphia7Lippincott Williams & Wilkins; 2002. p. 149 – 64.[30] Hebert PC, Wells G, Tweeddale M, et al, for the Transfusion Requirements in Critical Care(TRICC) Investigators and the Canadian Critical Care Trials Group. Does transfusion practiceaffect mortality in critically ill patients? Am J Respir Crit Care Med 1997;155:1618 – 23.[31] Spiess BD, Ley C, Body SC, et al, for The Institutions of the Multicenter Study of PerioperativeIschemia (McSPI) Research Group. Hematocrit value on intensive care unit entry influencesthe frequency of Q-wave myocardial infarction after coronary artery bypass grafting. J ThoracCardiovasc Surg 1998;116:460 – 7.[32] Carson JL, Duff A, Berlin JA, et al. Perioperative blood transfusion and postoperative mortality. JAMA 1998;279:199 – 205.[33] Hogue CW, Goodnough LT, Monk TG. Perioperative myocardial ischemic episodes arerelated to hematocrit level in patients undergoing radical prostatectomy. Transfusion 1998;38:924 – 31.[34] Nelson AH, Fleisher LA, Rosenbaum SH. Relationship between postoperative anemia andcardiac morbidity in high-risk vascular patients in the intensive care unit. Crit Care Med1993;21:860 – 6.[35] Paone G, Silverman NA. The paradox of on-bypass transfusion thresholds in blood conservation.Circulation 1997;96:205 – 8.[36] Blair SD, Janvrin SB, McCollum CN, et al. Effect of early blood transfusion on gastrointestinalhaemorrhage. Br J Surg 1986;73:783 – 5.[37] Bracey AW, Radovancevic R, Riggs SA, et al. Lowering the hemoglobin threshold for transfusion in coronary artery bypass procedures: effect on patient outcome. Transfusion 1999;39:1070 – 7.[38] Bush RL, Pevec WC, Holcroft JW. A Prospective, randomized trial limiting perioperative redblood cell transfusions in vascular patients. Am J Surg 1997;174:143 – 8.[39] Carson JL, Terrin ML, Barton FB, et al. A pilot randomized trial comparing symptomatic
anemia and clinical 0][51][52][53]325vs. hemoglobin-level-driven red blood cell transfusions following hip fracture. Transfusion1998;38:522 – 9.Fortune JB, Feustel PJ, Saifi J, et al. Influence of hematocrit on cardiopulmonary functionafter acute hemorrhage. J Trauma 1987;27:243 – 9.Hebert PC, Wells G, Blajchman MA, et al, for the Transfusion Requirements in Critical CareInvestigators, Canadian Critical Care Trials Group. A multicenter, randomized, controlledclinical trial of transfusion requirements in cri
2 carrying capacity is decreased, but tissue oxygenation is pre-served. Anemia causes hemodynamic alterations. The combined effect of hypo-volemia and anemia often occur as a result of blood loss. Acute anemia thus may cause tissue hypoxia or anoxia through diminished cardiac output, resulting in stagnant hypoxia, and decreased o
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2 Your Guide to Anemia. Anemia. What Is Anemia? Anemia is a blood disorder. Blood is a vital liquid that lows through your veins and arteries. Your body contains about 5 to 6 quarts of blood, which are constantly being pumped throughout your body by your heart. Blood carries oxygen
Cooley's Anemia) - Blackfan-Diamond Anemia - Pure Red Cell Aplasia - Sickle Cell Disease Other Disorders of Blood Cell Proliferation Anemias Anemias are deficiencies or malformations of red cells. - severe Aplastic Anemia - Congenital Dyserythropoietic Anemia - Fanconi Anemia (Note: the first cord blood transplant in 1988 was for this disease)
Diagnosis and Management of Anemia in the Elderly 2 Geriatric Anemia Best Practices Anemia is not normal at any age A treatable cause can often be determined, that may improve quality of life (QOL) Mean cell volume (MCV) is a free and helpful measure in narrowing differential diagnosis
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Life science graduate education at Harvard is comprised of 14 Ph.D. programs of study across four Harvard faculties—Harvard Faculty of Arts and Sciences, Harvard T. H. Chan School of Public Health, Harvard Medical School, and Harvard School of Dental Medicine. These 14 programs make up the Harvard Integrated Life Sciences (HILS).
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Genes Sequence of bases in a DNA molecule Carries information necessary for producing a functional product, usually a protein molecule or RNA Average gene is 3000 bases long 31 . 32 . Genes Instruction set for producing one particular molecule, usually a protein Examples fibroin, the chief component of silk triacylglyceride lipase (enzyme that breaks down dietary fat) 33 .
