Präsentation zum Thema: "Patient Blood Management-"— Präsentation transkript:
1 Patient Blood Management- das moderne perioperative TransfusionskonzeptABCPrä-Intra-Post-operativProf. Dr. med. Thomas Frietsch,MBA Gesundheitsökonomie(EBS)IAKH e.V.Präsentiert am im BwZK Koblenzmit freundl. Genehmigung bei einigen Anteilen von A. Hofmann
2 Conflict of interests CLS Behring Essex Pharma Janssen Cilag Novo NordiskInterdisziplinäre Arbeitsgemeinschaft für Klinische Hämotherapie IAKHArbeitskreis Bluttransfusion der DGAI und BDASektion Hämotherapie und Hämostaseologie der DIVI2
3 Learning Objectives:Was sind die Risiken & Gefahren der Bluttransfusion ?Welches sind die Bestandteile des ITM /PBM ?Kenntnis der Anämieprävalenz in der inneren Medizin und der ChirurgieAnämietherapie mit Epo und EisenKenntnis der realen Kosten der FremdbluttransfusionKenntnis der potenziellen klinischen und ökonomischen Vorteile von ITM /PBMHomework: Entwickeln Sie klinische Patientenpfade für das Blutmanagement in Ihrer Klinik3
4 Risiken & Komplikationen Transfusion-related immunomodulation (TRIM)Systemic inflammatory response syndrome (SIRS)Transfusion-related acute lung injury (TRALI)Übertragung von Erregern (viral u. bakteriell)Nosokomiale Infektionsrate ↑Mortalität ↑AdministrationsfehlerAkute und verzögerte TransfusionsreaktionenLagerungsschaden: “The Cold Storage Lesion”Freies HämoglobinHigh on the list of complications today is transfusion-related immune modulation (TRIM). Blood is a foreign object and when it is transfused to the recipient, not only are the cells active but the plasma itself contains a large number of proteins, which may be foreign to the recipient.Data from trauma patients shows that patients who receive allogeneic blood after trauma have an increase in the systemic inflammatory response syndrome (SIRS), and those patients are at high risk of developing complications secondary to SIRS.Patients who receive transfusions can also developed what is called transfusion-related lung injury (TRALI), which is also immune mediated. It is thought to be due to the HLA type 1 and 2 antigens, as well as from lipid-based particles from the blood of the donor.These complications are associated with increased risk for morbidity and mortality, and are now considered greater risks than administrative errors, which were once considered the greatest risk of mortality after transfusion.The risk of viral and bacterial infection exists but is extremely low. However, nosocomial infection is a very common complication, probably second to that of TRIM.Administrative error—the wrong unit of blood to the wrong patient—occurs between 1 and 12,000 to 1 in 14,000 units in the US and about 1 in 28,000 units in the UK. Why there is a difference between the US and the UK is unclear. Administrative error results in mortality in about 1 in 600,000 units.The so-called “cold storage lesion” is another complication. Blood is stored at 4 °C up to 42 days. During that time, 23DPG is completely removed from the red cells as well as ATP, which is lost. This does not allow the red cells that are stored to have the same configuration as the native red cells. The transfused cells are spherocytes and rigid, and cannot get through the microcirculation, which may actually block the entry of native cells into the microcirculation. The cold storage also increases the senescence of these cells so that they die quicker than native cells do, releasing free hemoglobin. Free hemoglobin can cause vasoconstriction compounding the problem of oxygen delivery.
5 Serious Hazards of Transfusion (SHOT) DTR (28)4.6%TRALI (23)3.8%TTI (3)0.5%PTP (2) 0.3%ATR (68)11.2%IBCT (485)79.6%The SHOT study is being conducted in the UK and Ireland. Because those countries handle blood in the same fashion as is handled in the US, the data can be extrapolated for use in the US.Incorrect blood component transfused comprises almost 80% of all the reported severe complications associated with transfusions. This is therefore a major concern. However, as already mentioned, the immune modulatory events are currently probably more of a concern in terms of mortality.N=609ATR = acute transfusion reaction; DTR = delayed transfusion reaction; IBCT = incorrect blood component transfused; PTP = posttransfusion purpura; TRALI = transfusion related acute lung injury; TTI = transfusion transmitted infection. Serious Hazards of Transfusion Annual Report Available at:: Accessed April 24, 2007.
7 Verwechslungen “Fehltransfusion” geschätzt 1:14,000 RBC units in the US11:28,000 RBC units in the UK2~ 10% – Ettikettierfehler (1:1 000 Proben)~ 25% – LaborfehlerRest – KlinikLetalität übersteigt HIV-assoz. Transmissionsrisiko um das 4- to 8-fold↑This slide again shows that mistransfusion occurs in approximately 1 in 14,000 units transfused in the US and in approximately 1 in 28,000 units transfused in the UK. Approximately 10% of these are due to labeling errors and about 25% are due to laboratory errors. The lion’s share of the complications and errors are associated with the clinical setting—that is on the floor with physicians and nurses.Fatality from administrative errors exceeds fatality from HIV by about 4- to 8-fold. So again, this is much more of a concern than the risk of viral transmission, but less of a concern than that of transfusion-related immune modulation.Williamson LM, et al. BMJ. 1999;319:16-19.Sazama K. Transfusion. 1990;30:
8 Transfusion-related Acute Lung Injury (TRALI) Incidence estimates vary1Difficulty in ruling out left atrial hypertension (eg, transfusion-associated circulatory overload [TACO], congestive heart failure) as causeCharacteristics of acute lung injury indistinguishable from TRALILack of agreement on case definitionLack of awareness, underreporting/underdiagnosis of TRALILeading cause of transfusion-related mortality1 (1:200,000 cases2)Proposed mechanismsPassively transfused donor HLA class I/II or neutrophil antigens3Mixture of predisposition and infusion of blood-related lipid-derived mediators4,5Incidence estimates for TRALI vary for a number of reasons, as shown on the slide.TRALI is now considered the leading cause of transfusion-related mortality, as reflected by transfusion-related fatality data reported to the FDA. Assuming that there are 3.2 million transfusion recipients annually and that there is not underreporting of TRALI fatalities to the FDA, this leads to an estimate that TRALI contributes to mortality in 1:200,000 transfusion recipients.Several mechanisms for TRALI have been proposed. One mechanism cites the interaction between passively transfused donor HLA class I/II or neutrophil antibodies and reciprocal recipient antigens. An alternative mechanism is the infusion of biologically active lipids that accumulate in blood components during storage.Kleinman S. Transfusion. 2006;46:Holness L. Available at: Accessed May 22, 2007.Popovsky MA, Moore SB. Transfusion. 1985;25:Silliman CC, et al. Vox Sang. 1992;63:Silliman CC, et al. Transfusion. 1997;37:
9 Blood Components Associated With TRALI Significant # reportedWhole bloodRBCFFPApheresis plateletsWhole-blood–derived plateletIsolated #WBCIVIGCryoprecipitateStem cellsBlood components associated with TRALI are listed in this slide.FFP = fresh frozen plasma; IVIG = IV immune globulin; RBC = red blood cells; WBC = white blood cells.Shander A, Popvsky MA. Chest. 2005;128:
10 Übertragung Infektionen Simian foamy virus (SFV)HHV-8West Nile virusChagasnCJDMalariaSARSInfluenzaThe simian population is hunted, butchered, and sold on the open market as animal protein in sub-Sahara Africa. All of these animals are infected with simian foamy virus. In addition, the meat handlers and their family members are also infected with the virus. Just as was initially the case with HIV, simian foamy virus does not at this point cause disease in these animals or in the meat handlers; however, there is concern that at some point, just as was the case with HIV, the virus is going to mutate or change in behavior.Human herpes virus 8 and West Nile virus have also been demonstrated to be transmitted by blood.One of the current concerns of the FDA is the appearance of trypanosoma cruzi, which is responsible for Chagas disease, in the blood supply in the United States. It used to only be endemic in Central and South America. We now know that trypanosoma cruzi is in the blood supply in the United States, and there is now a test to help identify donors who have trypanosoma cruzi, and to eliminate them from the donor pool. Chagas disease causes blindness and attacks the heart. To date, there is no cure for Chagas disease.nCJD, malaria, SARS, in addition to other infections that are not listed, can all be transmitted through transfusion. The potential risk of an epidemic exists any time a new organism enters the blood pool, dependent on the type and behavior of the organism.
11 Bakterielle Infektionen Risiko der bakteriellen SepsisFFP 1: TEEK 1:25,000 TEThrombos 1:3000 TEBacterial detection performed early will miss late infection (platelets)Pathogen inactivation, is that the answer?Blajchman MA, et. al. Transfus Med Rev. 2005;19:
12 of Transfused Blood Component Risk of Transmission per Unit Decline in Risks of Transfusion-Transmitted HIV, HBV, HCV, and Bacterial InfectionsDashed lines represent estimates.10-210-310-410-510-610-719841987199019931996199920022005of Transfused Blood ComponentRisk of Transmission per UnitBacteria in plateletsHBVHCVHIVThis graph shows the decline in the risks associated with both HIV and hepatitis C viruses, which is due to the judicious work of the blood industry in both detecting and eliminating donors who can potentially effect the population.We have been somewhat successful with hepatitis B, but not to the extent that we have been with hepatitis C and HIV, partially due to the testing that is done but also due to the behavior of the virus. Of the patients who do contract hepatitis B from transfusion, 95% of them have no sequelae thereafter.Revised HIV Non-A, non-B HCV p24 HCV and HIV West Nile Bacterial donor antibody hepatitis antibody antigen nucleic acid virus nucleic screeningdeferral screening surrogate screening testing testing acid testing of platelets criteria testingAdapted with permission from Blajchman MA, Vamvakas EC. N Engl J Med. 2006;355: and Busch MP, et al. JAMA. 2003;289:
13 Acute Transfusion Reactions Anaphylaxis1:10,000–1: transfusions (platelets)IgA-mediated, IgA-deficient recipientFatal – up to 5%Transfusion-associated circulatory overload (TACO) – 1:3000 for all productsOther immune- and antibody-mediated reactionsAcute transfusion reactions are listed here.
14 Spender-LeukozytenPersistenz bei Unfallpatienten bis zu 1.5 J nach Fremdbluttransfusion2 x 109 WBCs in einem undepletierten EK1 x 108 WBCs – spezielles Zentrifugenprogramm, buffy- coat scharf abgetrennt1-5 x 106 WBCs – Leukozytenfilter, depletiertThe amount of white cells that accompany the red cells in the bag of red cell concentrate—about 109 white cells. Those white cells carry DNA in them, and they may persist as a lineage within the recipient for years. One case report on a patient who received a single unit of blood after postpartum hemorrhage found that white donor cells were detected 10 years later. This persistence of donor white cells in the recipient circulation is called microchimerism.To reduce the exposure of the recipient to white cells, the blood can be either buffy coated or centrifuged, removing about 10-fold of the white cells. With the new leukocyte filters, white blood cells can now be reduced to 1-5 x 105. Although this reduces the amount of white blood cells substantially, it does not eliminate them, and therefore does not eliminate the risk of donor leukocytes.Lee TH, et al. Blood. 1999;93:
15 The Cold Storage Lesion Storage EffectsConsequencesReduced to absent 2,3-diphosphoglycerateIncreased oxygen affinity and decreased oxygen unloading by hemoglobinReduced to absent ATPErythrocyte shape changesIncreased osmotic fragilityDecreased deformabilityMicrovesiculation and loss of lipid membraneDecreased erythrocyte viabilityLipid peroxidationCellular injury and early cell death – free HbLoss of NOVasoconstriction and poor unloadingDue to the cold storage lesion effect there is reduced benefit in allogeneic blood due to the fact that the blood is stored at 4 °C for up to 42 days. During that time, there is reduced to absent 2,3-diphosphoglycerate (2,3-DPG), which is responsible for the unloading of oxygen in the periphery. Under those circumstances, this blood, which is devoid of 2,3-DPG, can carry oxygen very well, so it becomes like a sponge and may actually compete with the tissues for oxygen until it replenishes the 2,3-DPG, which may take hours to a full day.The reduction of ATP can change the shape of the erythrocytes, making them more fragile, as well as decreasing their ability to deform. Microvesiculation and lipid peroxidation can also contribute to this.The loss of nitric oxide, because of the free hemoglobin binding of nitric oxide, causes vasoconstriction. When the cells are devoid of ATP, they become fragile. They die quicker and free large amounts of free hemoglobin into the circulation.Free hemoglobin has an 8,000 times greater affinity for nitric oxide than it does for oxygen. So favorably, it attaches itself to nitric oxide. Nitric oxide being the most potent vasodilator produced by the endothelial cells, causes vasoconstriction when it is being completely absorbed by hemoglobin.So, for those cells that are poorly deformed, if vasoconstriction occurs, they cannot get to the periphery to unload oxygen.Offner PJ, et al. Arch Surg. 2002;137: Brown M, Whalen PK. Crit Care Nurse. 2000;20(suppl):1-14.Zallen G, et al. Shock. 2000;13:29-33.
16 Transfusion-related Immunomodulation (TRIM) Allogeneic blood transfusionInfuses recipient with potentially immunomodulatory substances: foreign cells, cell-associated + soluble antigens, biological response modifiersHuman studies (controversial and hotly debated) suggest ABT (vs no transfusion/autologous transfusion):‘Positive’ effects: ↑ renal allograft survival; ↓ risk of recurrent abortion; ↓ recurrence of Crohn’s diseaseNegative effects: ↑ recurrence rate of resected malignancies; ↑ post-op bacterial infections; ↑ mortalityTRIM effect thought to be due to leukocytesAnimal dataStrong signal in human dataHuman studies, which are controversial, suggest that allogeneic blood transfusion versus no transfusion or autologous transfusion improved renal allograft survival. This is old data. It also has been shown to reduce the risk of recurrent abortion and reduced the risk of Crohn’s disease—all due to the reduction of the receipient’s immune modulation. Today there drugs are available to do that and they are much better than the use of blood.Studies have also shown that patients undergoing colon resection or any type of cancer resection who receive allogeneic blood have a higher incidence of recurrence of malignancy compared with patients who do not receive blood. In addition, there is an increased incidence of bacterial and nosocomial infection and mortality in patients who are transfused versus those that are not.Evidence suggests that the transfusion-related immunomodulation (TRIM) effect is believed to be due to leukocytes. Limited human data suggest that lipid depletion reduces febrile effects of transfusion and may actually improve mortality and morbidity.
17 Effect of Blood Transfusion on Long-term Survival After Cardiac Surgery 1.00No XFNn=5460.95Patients at Risk1-y2-y3-y4-y5-yTx:528518502349188No Tx:539519408254Survival0.90XFNn=5460.85Engoren et al conducted a retrospective study that included 1915 patients who underwent first-time isolated coronary artery bypass operations. Patients with transfusions were compared with those who had not been transfused. Long-term survival data were obtained from the United States Social Security Death Index.Transfused patients were older, smaller, and more likely to be female, and had more comorbidity. Transfused patients also had twice the 5-year mortality (15% vs 7%) of nontransfused patients. After correction for comorbidities and other factors, transfusion was still associated with a 70% increase in mortality.1224364860Months after CABGKaplan-Meier estimates of survival based on equal propensity scores of any transfusion (XFN) versus no transfusion (No XFN).CABG = coronary artery bypass grafting.Figure reproduced with permission from Engoren MC, et al. Ann Thorac Surg. 2002;74:
18 Nosocomial Infections in the ICU Overall18P<.005Transfused patients15.4Nontransfused patients1612Percentage of Patients85.92.94To determine whether critically ill patients who receive allogeneic packed red blood cell transfusions are at increased risk of developing nosocomial infections during hospitalization, Taylor et al conducted a retrospective database study utilizing Project IMPACT. Nosocomial infection rates were compared among 3 groups: the entire cohort (N=1717), the transfusion group (n=416), and the nontransfusion group (n=1301).The average number of units transfused per patient was 4.0. The nosocomial infection rate for the entire cohort was 5.9%. The nosocomial infection rates for the transfusion group and the nontransfusion group was 15.4% and 2.9%, respectively (P<.005). Transfusion of packed red blood cells was related to the occurrence of nosocomial infection, and there was a dose-response pattern (the more units of packed red blood cells transfused, the greater the chance of nosocomial infection; P<.0001). The transfusion group was 6 times more likely to develop nosocomial infection compared with the nontransfusion group.N=1717n=416n=1301Reproduced with permission from Taylor RW, et al. Crit Care Med. 2002;30:
19 Transfusions Correlate With Infections in a Dose-Dependent Manner 1.20-15 Units of PRBC1.0Y = e0.1187xR2 =0.8Incidence of Infection0.60.40.2The tradition has been that if you are going to transfuse a patient, you should give 2 units versus 1 unit. However, these data and many other data show that each transfused unit of blood carries its own additive risk. Therefore, nonexsanguinating patients should be transfused 1 unit at a time, and should be re-evaluated between each unit.As you can see, even with the first unit, the incidence of infection does not start out at zero. And then every time you add a unit, the incidence of infection becomes additive. So, the data dispel that dictum that 2 units should be given when 1 is being considered.0.0246810121416TransfusionsReproduced with permission from Claridge JA, et al. Am Surg. 2002;68:
20 Association Between Allogeneic Blood Transfusion and Mortality Odds ratio: d mortality in OHS studies (all European)2-40.1110100Meta-analysis, RCTs: WBC-containing transfusions and mortality1No association detected across clinical settingsAssociation may exist in open heart surgery (OHS)2-4van deWatering et alBilgin et alWallis et alA meta-analysis of randomized controlled trials investigating WBC-containing transfusions and mortality detected no association across clinical settings. However, an association may exist in open heart surgery (OHS).Netherlands, N=914: CABG +/- valves and valves; infections, LOS: no significant differenceNetherlands, N=496: valves +/- CABG; infections: significant with S-RBCsBritain, N=509: CABG +/- valve and valves; infections: with S-RBCs in hospital but postdischarge: no differenceSummaryORFigure adapted with permission from Vamvakas EC.1Vamvakas EC. Transfusion. 2003;43:Van de Watering LM, et al. Circulation. 1998;97:Bilgin YM, et al. Circulation. 2004;109:Wallis JP, et al. Transfusion. 2002;42:
21 Die 3 Elemente des Patient Blood Management Optimierung des Hämoglobinspiegels durch Diagnose und Therapie in allen klinischen SituationenIndividuelles perioperatives AnämiemanagementAlternative TransfusionsmethodenBlood management can be broken down into 3 pillars, which consist of optimizing hemoglobin levels, understanding anemia and harnessing the physiology of it, and having a consistent approach.Medical Society for Blood ManagementSociety of Advancement in Blood Management
22 Patient Blood Management Patienten-zentrierteOptimierung derErythrozytenmasseAngemesseneTransfusions-StrategienBlutsparendeMaßnahmenAccording to a conservative estimate, 30% of blood and blood products in the United States are given to patients that actually do not need them and have no impact in terms of improving patient outcomes, and that may actually be detrimental.Blood management encompasses the full spectrum of techniques designed to avoid allogeneic blood transfusion—appropriate transfusion medicine (allogeneic blood transfusion is periodically necessary); blood conservation, which should be recognized as a valued and valid approach for all patients, medical or surgical; and the approach must be patient-centered—that is, it should result in improved patient outcomes, and that the needs of different patients with different requirements be addressed in a rational way and in a manner that will lead to positive outcomes.
23 Die 3 Säulen des IAKH – ITM Interdisziplinäres Transfusionsmanagement A: Präoperative Strategien: Anämie, Algorithmen, AllianzenB: Individuelles intraoperatives Anämiemanagement im AkutkrankenhausC: Postoperatives TransfusionsmanagementBlood management can be broken down into 3 pillars, which consist of optimizing hemoglobin levels, understanding anemia and harnessing the physiology of it, and having a consistent approach.23
24 Säule A: Präoperative Strategien Optimierung der Erythrozytenmasse in der perioperativen Medizin bei zu erwartendem TransfusionsbedarfAdäquate Bedarfsplanung (Bereitsstellung und Berechnung des Patientenblutvolumens)Anämievermeidung, -diagnostik und -therapieAutologe BlutspendeAufdeckung von Blutungsneigungen und hämorrgaischen DiathesenAlgorithmen und Patientenpfade zur Diagnostik und TherapieAllianzen- und Netzwerkbildung zu Niedergelassenen, Akutkrankenhaus und Rehabilitationszentrum unter Einbezug der KostenträgerA
25 Säule B: Intrahospitale Strategien Berücksichtigung und konsequente Einhaltung von evidenzbasierten, restriktiven TransfusionstriggernBlutarme Chirurgische TechnikChirurgische Technik mit sorgfältiger BlutstillungMinimal invasive und endoskopische TechnikenUltraschall/Laser/ElektrokautertechnikSaugdisziplin/Wiegen der TücherBedarfsgerechte HämotherapieMaschineller AutotransfusionHomologen TransfusionskonzeptenProphylaktischer Einsatz von AntifibrinolytikaPoint of Care-GerinnungsmonitoringMinimierung des Blutverlusts durchSchnelle Diagnostikzielgerechte KomponententherapieB25
26 3 Säulen-Strategie in der Chirurgie PräoperativGesenkter TransfusionstriggerGesteigerte ErythrozytenmasseIntraoperativSorgfältige BlutstillungSpezielle OperationstechnikANHMATPostoperativeReduzierte LaborkontrollenStrategies to reduce surgical patients’ exposure to allogeneic blood can be broken down into those that are appropriate during the preoperative, intraoperative, and postoperative periods.Adapted from Goodnough LT, et al. Transfusion. 2003;43:
27 Säule C: Postoperative Strategien Toleranz der chirurgisch bedingten Anämie Berücksichtigung und konsequente Einhaltung von evidenzbasierten, restriktiven TransfusionstriggernVermeidung unnötiger BlutverlusteEinsatz von Mikrolaborgefäßen, restriktive DiagnostikEinsatz von POCT-GerinnungsdiagnostikRechtzeitige Revisionschirurgie bei anhaltenden DrainagenverlustenMAT-Einsatz, wo möglichFrühmobilisation und enge Kooperation von Akutkrankenhaus und RehabilitationszentrumC27
28 Potenzieller Nutzen des Interdisziplinären Transfusionsmanagements Beseitigt die Symptome und Effekte der AnämieReduziert die FremdblutexpositionVerbessert das Patienten-”Outcome”Reduziert Versorgungsengpässe mit Blut durch verringerten VerbrauchReduziert die Trägerkosten für BlutprodukteBereitet die Klinik für den Wettbewerb (Blutverbrauchvergleiche der Krankenkassen)There are many potential benefits of blood management, which are listed here.Interdisziplinarität involviert alle Beteiligten → Akzeptanz ↑Größerer Methodenreichtum →Effekt ↑++
29 ITM- A 1: Prähospitale Optimierung der Erythrozytenmasse: Adäquate Bedarfsplanung 1.1 Schätzung / Berechnung der Erythrozytenmasse EM:EM = [Hb](g/l) x Blutvolumen BV (l)BV = KG (kg) x 0,07 (Männer) oder 0,065 (Frauen)1.2 Statistischer Blutverlust des geplanten Eingriffs in Krankenhaus x- Abteilung y von Team z1.3 Real zu planender Blutbedarf unter Berücksichtigung der individuellen Risiken
30 ITM- A 2: Vermeidung einer prähospitalen Anämie Inzidenz bei 25-30% → Transfusionsbedarf ↑Diagnose- (Labor : Hb, MCV/MCH, Fe, Ferritin)Therapie:KausalFeEPO und Fe
31 WHO Definition of Anemia vs Hb Distribution in the General Population Anemia in Men:Hb <13 g/dLHb distribution in women: 13.3 0.9 g/dL3000Hb distribution in men: 15.2 0.9 g/dL2500Anemia in Women:Hb <12 g/dL2000N=40,000 (NHANES III, )Frequency15001000Superimposing the World Health Organization (WHO) anemia definition over graphs of the distribution of Hb levels by gender is revealing: anemia under this definition comprises Hb levels that are significantly lower than mean Hb levels in the population.Although there is no definitive agreement on the definition of anemia, one of the most commonly used definitions is the one used by the WHO. The WHO defines anemia as Hb <13 g/dL in men and <12 g/dL in premenopausal, nonpregnant women.5001010.51111.51212.51313.51414.51515.51616.51717.518Hb Level (g/dL)World Health Organization. Geneva, Switzerland; 2001.Dallman PR, et al. In: Iron Nutrition in Health and Disease. London, UK:John Libbey & Co; 1996:65-74.
32 Präoperative Anämie : Ursache & Prävalenz J.Tomeczkowski, C. von Heymann 2011 unpublishedPräoperative Anämie : Ursache & PrävalenzUrsache der AnämieReferenznKollektivAlterDef.PrävalenzEisen-ACDandere[Mean][Hb in g/dl]mangel(EPO-M.)Guralnik et al.2 069ohne75M13,0;F12,011%20%32%34%Ezekowitz et al.12 065Herzinsuff77k.A.17%21%58%Saleh et al.1 142THA/TKA68M13,0;F11,523%164%213%Bisbe et al.715M+F 13,019%30%344%26%Myers et al.225THA64M12,5;F11,515%60%44%Basora et al.2187139%30%k.A.7Theusinger et al.9321%8Goodnough et al.290605721%933%1070%11
33 Prevalence of Anemia in Critically Ill Patients Hb <10 g/dL Vincent et al, 2002(N=3534)Hb <12 g/dL Vincent et al, 2002Hb 11 g/dL von Ahsen et al, 1999(N=96)2040608010029%63%77%These data, which are from intensive care units in Europe, show the prevalence of anemia in the critical care population. Approximately 30% of patients have a hemoglobin level <10 g/dL. When the hemoglobin level used is ≤11 g/dL, the prevalence reaches 77%. Therefore, the prevalence of anemia varies widely, partly because of the issue of definition, and partly because studies vary in regard to which hemoglobin levels are used—initial, nadir, or discharge values.Percentage of Critically Ill Patients With AnemiaVincent JL, et al. JAMA. 2002;288: von Ahsen N, et al. Crit Care Med. 1999;27:
34 Prevalence of Anemia at Admission Among Various Patient Groups Patient type Prevalence (%) ReferenceRheumatoid arthritis33-60Wilson, 20041Surgery5-75.8Shander, 20042Cancer30-90Knight, 20043HIV1.3-95Belperio, 20044Again, the data show tremendous variability for the prevalence of anemia among various patient groups.Wilson A, et al. Am J Med. 2004;116(suppl 7A):50S-57S.Shander A, et al. Am J Med. 2004;116(suppl 7A):58S-69S.Knight K, et al. Am J Med. 2004;116(suppl 7A):11S-26S.Belperio PS, et al. Am J Med. 2004;116(suppl 7A):27S-43S.
35 Preoperative evaluation Alter und Anämie3025201510565,788 patients ( )Preoperative evaluationWHO anemia definitionMen Women%Using the WHO definition for anemia, Kulier et al conducted a large study that included patients over a 20-year period; they evaluated the incidence of preoperative anemia. This graph clearly shows an increase in the incidence of anemia with advanced age, which may reflect underlying disease.20-3031-4041-5051-6061-7071-8081-90>90YearsReproduced with permission from Kulier A, Gombotz H. Anaesthesist. 2001;50:73-86.
36 Anemia: A Potent Multiplier of Mortality No HF, No CKD, No Anemia1Anemia Only1.9CKD Only2.05HF Only2.86CKD, Anemia3.37HF, Anemia3.78HF, CKD4.86HF, CKD, AnemiaThe top bar depicts patients without heart failure, chronic kidney disease, or anemia; they have a relative risk of 2-year mortality of 1. However, when you start adding each one of the diseases independently, the risk of mortality increases to 2 to 3 times that of normal. And when you add anemia to any one of the other 2 diseases, the risk of mortality increases even higher. When all 3 are present—heart failure, chronic kidney disease and anemia—the risk of mortality increases to 6 times the normal level.Therefore, it appears that anemia is a potential multiplier of mortality. However, it is still not clear whether anemia is in itself a potent additive to mortality or whether anemia is merely a signal of the 2 other diseases being more severe.6.071234567Relative Risk of 2-Year MortalityN = 1.1 million (5% Medicare sample, )Herzog CA, et al. Presented at: 6th Annual Scientific Meeting of the Heart Failure Society of America; September 22-25, 2002; Boca Raton, Florida. Abstract 226.
37 NATA Leitlinie Hb-Bestimmung 28 Tage vor elektivem Eingriff- Grad 1C Präop. Ziel Hb- Niveau oberhalb WHO-Grenzen- Grad 2CLabordiagnose der Anämie- Grad 1ABehandlung von nutritiven Ursachen Grad 1CEpo-Therapie, wenn nicht nutritiv oder korrigiert Grad 2AGrad 1- empfohlenGrad 2- vorgeschlagenA-B-C Evidenzlevel von hoch bis niedrig
39 Effects of Anemia Treatment Partial correction of anemia to Hb g/dL in patients with CKD may:Reduce morbidity,hospitalization,and mortality1-3Improve QOL,6,7 exercise capacity,8 cognitive function,2 and sexual function3Improve LV structure and function4,5The evidence suggests that the partial correction of anemia (Hb g/dL) can reduce morbidity, hospitalization, and mortality in patients with chronic renal disease. Data also suggest that LV structure and function is improved, and that quality of life and exercise capacity is also improved. The data, however, are less robust for improved cognitive and sexual function.1. Xia H, et al. J Am Soc Nephrol. 1999;10:2. Bedani PL, et al. Nephron. 2001;89:3. Wu SC, et al. Scand J Urol Nephrol. 2001;35:4. Hayashi T, et al. Am J Kidney DIs. 2000;35:5. Portoles J, et al. Am J Kidney Dis. 1997;29:6. Revicki DA, et al. Am J Kidney Dis. 1995;25:7. Furuland H, et al. Nephrol Dial Transplant. 2003;18:8. Clyne N, et al. Nephron. 1992;60:
40 Chronic Anemia: Lower the Transfusion Trigger Point? Hb 7.0 g/dL-9.0 g/dL sufficient in critically ill patientsHébert PC, et al. N Engl J Med. 1999;340:Much lower Hb tolerated (>5.0 g/dL) in nonstressed normal patientsWeiskopf RB, et al. Anesthesiology. 2000;92:Patients with CAD may require Hb levels in slightly higher ranges (8.0 g/dL-9.0 g/dL) and avoid tachycardia-blockersEuvolemiaMinimum, safe (optimal) Hb/Hct unknownTrigger can be lowered to avoid transfusionsOne frequently asked question is “What is the lowest possible tolerated hemoglobin level?”Hébert et al conducted a randomized, controlled trial that included over 800 critically ill patients with euvolemia after initial treatment who had hemoglobin concentrations of <9.0 g/dL within 72 hours after admission to the ICU. They were randomly assigned to a restrictive strategy of transfusion, in which red cells were transfused if the hemoglobin concentration dropped below 7.0 g/dL and hemoglobin concentrations were maintained at 7.0 to 9.0 g/dL, and to a liberal strategy, in which transfusions were given when the hemoglobin cencentration fell below 10.0 g/dL and hemoglobin concentrations were maintained at 10.0 to 12.0 g/dL. Overall, 30-day mortality was similar in the 2 groups. However, the rates were significantly lower with the restrictive transfusion strategy among patients who were less acutely ill and among patients who were <55 years of age, but not among patients with clinically significant cardiac disease.Weiskopf et al showed that nonstressed normal volunteers were able to tolerate hemoglobin levels between 5.0 to 6.0 g/dL; however they did experience subtle, reversible increases in reaction time and impaired immediate and delayed memory.Without any definitive data, there is a prevailing belief that patients who have active coronary artery disease may require higher hemoglobin concentrations compared to the other groups. However, anemia is well tolerated, even in the patients with coronary artery disease, provided that they are euvolemic and nontachycardic.Because patients vary in the way they react to low hemoglobin levels, a single recommended concentration value is not appropriate. However, the optimal hemoglobin range versus the minimal hemoglobin level is still unknown. But we do know that the reserve is significant and that the trigger for transfusion of allogeneic blood can be lowered.
41 Compensatory Mechanisms of Anemia Hb = g/dL tolerable (blood loss controlled + good cardiac function) Cardiac output Coronary flow Blood viscosity O2 consumption O2 extractionThis slide shows the compensatory mechanisms associated with anemia. When the hemoglobin concentration falls to 6.0 to 7.0 g/dL (or to 7.0 to 8.0 g/dL in some people) cardiac output increases to compensate for the reduction of oxygen delivery, and coronary flow improves. The lowering of blood viscosity probably has the greatest impact—a patient needs to be euvolemic to gain the benefit of reduced hemoglobin and improved flow. Oxygen consumption is reduced because the tolerance to exercise is reduced and total body oxygen extraction is actually increased.Corwin HL, Hébert PC. Physiology of anemia and red blood cell transfusion. In: Spiess BD, Spence RK, Shander A, eds. Perioperative Transfusion Medicine. 2nd ed. Philadelphia: Lippincott Williams & Wilkins; 2006:chap 6.
42 Funktionaler Eisenmangel Ungleichgewicht zwischen Angebot ans KM und VerbrauchRetikulozytenzahl und HCC (Hypochromie) reduziertNiedriges TransferrinWhen patients receive erythropoietin, they also need to receive the substrate. If they do not receive the substrate, iron is depleted very quickly. The iron stores in the bone marrow and other tissues are very tightly regulated and there is no stimulation to release of the iron store. To overcome this, the patient needs to receive a supplement with small amounts of iron, either orally or intravenously, so that the red cells that are being produced have enough iron to be incorporated, producing normal functioning and normal sized red cells.Scigalla P, et al. Contrib Nephrol. 1990;82: Mcdougall IC, et al. Br Med J. 1989;29: Thomas C, Thomas L. Clin Chem. 2002;48: Mittman N, et al. Am J Kidney Dis. 1997;30:
43 Andere nutritiv bedingte Anämien EisenFolsäureVitamin B12ErythropoetintherapieWhen treating patients with epoetin, it is important to provide simultaneous treatment with iron, folic acid, and vitamin B12. Epoetin increases the production of red cells, but does not increase the release of iron or the availability of folic acid or vitamin B12.
44 Distribution of Iron in Tissue Dietary ironDuodenum(average, 1-2 mgper day)UtilizationUtilizationPlasma transferrin(3 mg)Bone marrow(300 mg)Muscle(myoglobin)(300 mg)Circulatingerythrocytes(hemoglobin)(1800 mg)StorageironAbsorption of iron is about 1 to 2 mg per day, and the iron loss is equivalent to that. Most of the iron is stored in the liver―about 1 gram is stored in the liver and about .3 grams is stored in muscle.The plasma transferrin, which is a protein that transfers iron from the different locations is very important because it contains the majority of the iron in the body in liquid form.Bone marrow contains about .3 grams and about 1.8 grams of iron is contained in the red cells. If you add bone marrow production and the endothelial cells, you end up with approximately 1.5 grams of iron.In addition to the 1 to 2 mg of iron that is replenished a day, the same amount is also absorbed from dietary intake.Sloughed mucosal cellsDesquamationMenstruationOther blood loss(average, 1-2 mg per day)Iron lossLiverparenchyma(1000 mg)Reticulo-endothelialmacrophages(600 mg)Adapted with permission from Andrews NC. N Engl J Med. 1999;341:
45 Gründe für den Eisenmangel Inadequate iron absorptionIncreased blood lossGastrointestinal blood loss (eg, epistaxis, varices, gastritis, ulcer, tumor, IBD)Genitourinary blood loss (menorrhagia, cancer, chronic infection)Pulmonary blood loss (pulmonary hemosiderosis, infection)Other blood loss (trauma, excessive phlebotomy, large vascular malformations)This slide lists the causes of iron deficiency.Andrews NC. N Engl J Med. 1999;341:
46 Efficacy of IV Iron Therapy Quickly replenishes depleted iron storesRaises serum ferritinCorrects iron-deficient erythropoiesisRaises transferrin saturation (TSAT) and Hb reticulocyte content (CHr)Increases Hb, or decreases epoetin dose for same HbMaintains iron-sufficient erythropoiesisReplenishing iron stores assures adequate iron supply in patients prone to blood loss (eg, hemodialysis-related)Intravenous iron quickly replenishes depleted iron stores and raises the amount of iron in serum ferritin and corrects iron-deficient erythropoiesis, measured by the serum iron over the total iron binding capacity, which is transferrin saturation (TSAT). It also increases hemoglobin and may actually attenuate the amount of epoetin that is required, especially in the presence of iron deficiency anemia or slight iron deficiency.Again, replenishing iron stores ensures adequate iron supply in patients prone to blood loss, such as those patients on hemodialysis where iron is constantly being repleted through the blood system. As was mentioned already, the RBCs and the reticuloendothelial macrophages contain a significant amount of iron. If those are lost in the dialysis machine, these patients lose large amounts of iron.
47 Current Status of Intravenous Iron Therapy BeneficialNo BenefitInvestigationalAnemia of renal failure, with or without erythropoietin therapyAutologous blood donation in patients with or without iron deficiencyBlood loss, iron deficiency, and erythropoietin therapyPatients with ongoing blood lossAnemia of chronic disease and erythropoietin therapyJehovah’s Witness patients with iron deficiency and/or blood lossPerisurgical anemia, with or without erythropoietin therapyThis slide shows instances for which intravenous iron is beneficial, offers no benefit, and instances for which the benefit remains unclear.Absolute iron deficiency is defined as ferritin <200 μg/L and/or iron saturation <20%, or relative iron deficiency (ferritin <400 μg/L in dialysis patients receiving erythropoietin therapy, or the presence of >10% hypochromic erythrocytes and/or reticulocytes).
48 FDA-Approved Indications for IV Iron Therapy Iron dextran injection, USP1,2Patients with documented iron deficiency in whom oral administration is unsatisfactory or impossibleBlack box warning regarding risk of fatal anaphylactic-type reactionsSodium ferric gluconate complex in sucrose injection3Iron deficiency anemia in patients undergoing chronic hemodialysis who are receiving supplemental epoetin therapyIron sucrose injection, USP4Iron deficiency anemia in:Nondialysis dependent-chronic kidney disease (NDD-CKD) patients receiving or not receiving an erythropoietinHemodialysis dependent-chronic kidney disease (HDD-CKD) patients receiving an erythropoietinPentoneal dialysis dependent-chronic kidney disease (PDD-CKD) patients receiving an erythropoietinThe FDA-approved indications for IV iron therapy are listed on this slide.Dexferrum® (iron dextran injection, USP) full prescribing information. Shirley, NY: American Regent Laboratories, Inc.INFeD® (iron dextran injection, USP) full prescribing information. Morristown, NJ: Watson Pharma, Inc.Ferrelecit® (sodium ferric gluconate complex in sucrose injection) full prescribing information. Corona, Calif: Watson Pharma, Inc.Venofer® (iron sucrose injection, USP) full prescribing information. Shirley, NY: American Regent Laboratories, Inc.
49 Dosierung des intravenösen Eisens Eisendextran (Dexferrum®, INFeD®)Natriumeisenglukonatkomplex in Sucrose (Ferrlecit®)10 mL (125 mg of elemental iron) verdünnt in 100 mL 0.9% NaCl langsam über 1 h oder langsam unverdünnt i.v. (Rate max mg/min)Eisensucrose (Venofer®)HDD-CKD: 100 mg unverdünnt langsam i.v. über 2-5 min oder als Infusion in 100 mL 0.9% NaCl über 15 min (Gesamtdosis 1000 mg)NDD-CKD: Gesamtdosis von 1000 mg über 14 d als eine 200 mg IV Injektion über 2-5 minThis slide includes the dosing regimens for available intravenous iron agents.Dexferrum® (iron dextran injection, USP) full prescribing information. Shirley, NY: American Regent Laboratories, Inc.INFeD® (iron dextran injection, USP) full prescribing information. Morristown, NJ: Watson Pharma, Inc.Ferrelecit® (sodium ferric gluconate complex in sucrose injection) full prescribing information. Corona, Calif: Watson Pharma, Inc.Venofer® (iron sucrose injection, USP) full prescribing information. Shirley, NY: American Regent Laboratories, Inc.
50 Preoperative Iron Supplementation in Colorectal Cancer Patients Kohorte von 569 Patienten32 Pat. Hb ≤10 g/dL -2 Wochen präoperative Eisentherapie (200 mg)84 Pat. Hb ≤10 g/dL ohne EisentherapieResults: Anstieg Hb um 2 g/dLTransfusionsrate: 9% der Verumgruppe vs 27%Okuyama et al conducted a study to investigate whether giving an iron preparation to anemic patients before colorectal cancer surgery improves their anemia and reduces the need for intraoperative blood transfusion.Among 569 patients who underwent colorectal cancer surgery, they studied 32 anemic patients who received iron supplementation for at least 2 weeks preoperatively and 84 anemic patients who did not. Anemia was defined as a hemoglobin (Hb) level at first presentation of ≤10.0 g/dL. Hemoglobin and hematocrit (Ht) levels were measured at first presentation, then immediately before and after surgery. They also calculated intraoperative blood loss and compared intraoperative transfusion rates.Hb and Ht values were similar in both groups at first presentation, but significantly different immediately before surgery (P<.0001). There were no significant differences in intraoperative blood loss between the groups, but significantly fewer patients in the iron supplementation group needed an intraoperative blood transfusion (9.4% vs 27.4%; P<.05).Okuyama M, et al. Surg Today. 2005;35:36-40.
51 Erythropoietin Regulates Red Blood Cell Production Renal interstitial peritubular cells detect low blood oxygen levelsEPO stimulates the proliferation and differentiation of erythroid progenitors into reticulocytes and prevents apoptosisErythropoietin (EPO) secreted into the bloodEPOMore reticulocytes enter circulating bloodIncreased oxygen delivery to tissuesThis slide illustrates the life cycle of erythropoietin in response to a reduced oxygen level or even hypoxia, which is detected by the interstitial peritubular cells in the kidney. A signal is sent out and erythropoietin, which is produced in the kidney in adults, and then stimulates the bone marrow.The bone marrow, in response to erythropoietin, proliferates and differentiates the erythroid progenitors into reticulocytes and prevents apoptosis. More reticulocytes enter the circulating blood, and the reticulocytes differentiate into erythrocytes, increasing the erythron size, resulting in increased oxygen delivery to the tissues.Reticulocytes differentiate into erythrocytes, increasing the erythron sizeDessypris E. In: Lee G, et al, eds. Wintrobe’s Clinical Hematology. Vol 1. Baltimore, Md: Lippincott, Williams & Wilkins; 1998:Bunn H. In: Isselbacher K, et al, eds. Harrison’s Principles and Practice of Internal Medicine. 13th ed. New York, NY: McGraw-Hill; 1994:
52 Erythropoietic Agents: Exogenous Erythropoietin FormulationsEpoetin alfa (global)Epoetin beta, epoetin delta, epoetin omega (non-US, international)Darbepoetin alfa (novel erythropoiesis-stimulating protein with longer terminal half-life than epoetin alfa)Hematologic effects identical to endogenous erythropoietinApoptotic agents – neuro-/cardioprotectionThe FDA-approved formulations of erythropoietin available in the United States are epoetin-alpha and darbepoetin-alpha; epoetin beta, epoetin delta, and epoetin omega are not currently available in the United States.The hematologic effects of these exogenous formulations are identical to endogenous erythropoietin. These agents also provide neuro- and cardiac protection.
53 Erythropoietin: Dosierung Chronisches Nierenversagen: IV or SC injection 3 x weekly*Zidovudine-treated HIV-infected patients: IV or SC injection 3 x weeklyCancer patients on chemotherapy: SC 3 x weekly or weeklySurgery patients:300 U/kg/d SC for 10 days before surgery, on the day of surgery, and for 4 days after surgery; or600 U/kg SC once weekly (21, 14, and 7 days before surgery) plus a fourth dose on the day of surgeryAll patients should receive adequate iron supplementationThis slide reviews the appropriate dosing regimens for epoetin alfa and darbepoetin alfa.*IV route is recommended for patients on dialysis..
54 Standard in Studien (Ferritin > 100 μg/l und/oder TSAT > 20%) -4 Monate-3 Monate-2 Monate-1 MonatOPERYPO IE s.c.EPO s.c.EPO s.c.EPO s.c.EPO s.c.200 mg Fe-II-Substitution pro TagEisen per os+Fe p.o./i.v.Standard bei Eisenmangel (Ferritin < 100 μg/l und/oder TSAT < 20%)-4 Monate-3 Monate-2 Monate-1 MonatOPERYPO IE s.c.EPO s.c.EPO s.c.EPO s.c.EPO s.c.i.v.entsprechend Eisenmangel p.o. 200 mg Fe-II-Substitution pro Tag+Fe i.v.+Fe i.v.+Fe i.v.+Fe i.v.oderEisen per os+Fe p.o./i.v.
55 präoperativer Hb-Wert 10-12 g/dl Ziel 15g/dl Stratifiziert nach Hb-Wert und dosisadaptiert (Ferritin > 100 μg/l und/oder TSAT > 20%)präoperativer Hb-Wert g/dlZiel 15g/dlOP-4 Monate-3 Monate-2 Monate-1 MonatERYPONach Fach-Information600 I.E./kg KG zum Bsp.:68kg KG = I.E. (40K)85kg KG= 40K + 10K102kg KG=40K + 20K119kg KG=40K + 30K136kg KG=40K + 40KEPO s.c.EPO s.c.EPO s.c.EPO s.c.Eisen per os+Fe p.o./i.v.präoperativer Hb-Wert g/dlZiel 15g/dl-4 Monate-3 Monate-2 Monate-1 MonatOPEPO s.c.EPO s.c.EPO s.c.Eisen per os+Fe p.o./i.v.FERRITINi.v.entsprechend Eisenmangel p.o. 200 mg Fe-II-Substitution pro Tagpräoperativer Hb-Wert 13 g/dlZiel 15g/dl-4 Monate-3 Monate-2 Monate-1 MonatOPEPO s.c.EPO s.c.Eisen per os+Fe p.o./i.v.
56 New Safety Information Black Box Warnung der FDA:risk for death and serious cardiovascular events when administered to achieve a target Hb >12 g/dL in cancer, renal failure, and surgical patients1-4Venöse Thromboembolien und TumorprogressRevised product labeling for Aranesp, Epogen, and Procrit includes a new boxed warning about using the lowest dose possible to avoid the need for blood transfusion because of the increased risk for death and serious cardiovascular events when administered to achieve a target hemoglobin (Hb) >12 g/dL in cancer, renal failure, and surgical patients.It had been previously thought that achieving a target Hb >12 g/dL improves patient quality of life, but the recent data does not show that to be the case.US Food and Drug Administration Center for Drug Evaluation and Research. Information for Healthcare Professionals. Erythropoiesis stimulating agents (ESA) [Aranesp (darbepoetin), Epogen (epoetin alfa), and Procrit (epoetin alfa). FDA alert 11/16/2006, updated 2/16/2007 and 3/09/2007. Available at: Accessed April 30, 2007.Aranesp® (darbepoetin alfa) prescribing information. Thousand Oaks, Calif: Amgen Inc.; 3/2007.Epogen® (epoetin alfa) prescribing information. Thousand Oaks, Calif: Amgen Inc.; 3/2007.Procrit® (epoetin alfa) prescribing information. Raritan, NJ: Ortho Biotech Products, LP; March 2007.
57 New Safety Information (cont.) In patients receiving ESAs preoperatively for reduction of allogeneic RBC transfusions, a higher incidence of DVT was documented in patients not receiving prophylactic anticoagulationAntithrombotic prophylaxis should be strongly considered for such patientsThe remainder of the black box warning is detailed on this slide.US Food and Drug Administration Center for Drug Evaluation and Research. Information for Healthcare Professionals. Erythropoiesis stimulating agents (ESA) [Aranesp (darbepoetin), Epogen (epoetin alfa), and Procrit (epoetin alfa). FDA alert 11/16/2006, updated 2/16/2007 and 3/09/2007. Available at: Accessed April 30, 2007.Aranesp® (darbepoetin alfa) prescribing information. Thousand Oaks, Calif: Amgen Inc.; 3/2007.Epogen® (epoetin alfa) prescribing information. Thousand Oaks, Calif: Amgen Inc.; 3/2007.Procrit® (epoetin alfa) prescribing information. Raritan, NJ: Ortho Biotech Products, LP; March 2007.
58 Strategies for Primary and Secondary Prevention of Venous Thromboembolism Pharmacologic1,2LMWH (eg, enoxaparin, dalteparin)Unfractionated heparin (UFH)Oral anticoagulants (eg, warfarin)Antiplatelet (eg, aspirin)Pentasaccharide (eg, fondaparinux)Direct thrombin inhibitors (eg, bivalirudin, argatroban)Mechanical1Intermittent pneumatic compressionGraduated compression elastic stockingsStrategies to prevent DVT and PE should include both nonpharmacologic approaches, such as the use of intermittent pneumatic compression and graduated compression elastic stockings, and pharmacologic approaches. For prevention and treatment of VTE, low-molecular-weight heparin (LMWH) is presently the standard of care. Current recommendations for thromboprophylaxis in general surgery, orthopedic surgery, trauma, abdominal surgery, spinal cord surgery, and medical conditions include a combination of LMWH (or, in some cases, unfractionated heparin) and warfarin, used in combination with nonpharmacologic approaches. However, limitations to these approaches include a narrow therapeutic window, lack of oral bioavailability, and variable dose response. This has led to the development of newer agents. One of the new anticoagulants, fondaparinux, has been found more effective than enoxaparin in the prevention of VTE in hip fracture surgery. The direct thrombin inhibitors hirudin, bivalirudin, argatroban, and the investigational agent ximelagatran are not approved for use in VTE prophylaxis or treatment; however, they are being studied in this capacity and may prove effective.1. Geerts WH, et al. Chest. 2004:126(3 suppl):338S-400S. 2. Nutescu E, Racine E. Am J Health-Syst Pharm. 2002;59:S7-S14.
59 Conditions for Which CMS Proposed ESA Treatment “Not Reasonable and Necessary” Tumoranämie bedingt durch Folsäuremangel, Eisenmangel, Hämolyse, chron. Blutverlust , Vit. B12 Mangel, KM-FibroseAnämie bei akuter und chronischer myeloischer Leukämie (CML, AML), or erythroipetischen TumorenTumoranämie nicht auf Chemotherapie zurückzuführenBestrahlungsinduzierte ChemotherapieProphylaktische TherapieEpo-Resistenz durch AK-BildungKombination von Tumoranämie und schlecht eingestellten HTNCMS proposed that ESA treatment is not reasonable and necessary for the following conditions:Any anemia in cancer or cancer treatment patients due to folate deficiency, B deficiency, iron deficiency, hemolysis, bleeding, or bone marrow fibrosisAnemia of myelodysplasiaAnemia of myeloid cancersAnemia associated with the treatment of myeloid cancers or erythroid cancersAnemia of cancer not related to cancer treatmentAnemia associated with radiotherapyProphylactic use to prevent chemotherapy-induced anemiaProphylactic use to reduce tumor hypoxiaPatients with erythropoietin-type resistance due to neutralizing antibodiesPatients with treatment regimens including anti-angiogenic drugs such as bevacizumabPatients with treatment regimens including monoclonal/polyclonal antibodies directed against the epidermal growth factor receptorAnemia due to cancer treatment in patients with uncontrolled hypertensionPatients with thrombotic episodes related to malignancyCenters for Medicare & Medicaid Services (CMS). Decision Memo for Erythropoiesis Stimulating Agents (ESAs) for non-renal disease indications (CAG-00383N). Available at: Accessed September 20, 2007.
60 CMS’s EPO- Therapie-Richtlinien bei MalignompatientenAnämie <10 g/dL (or HCT <30%)Start Dosis: 150/U/kg 3 x wkHb-Kontrolle alle 14 TageDosisverringerung um 25% wennAnstieg Hb >1 g/dL (HCT >3%) in 2 wkDosiserhöhung um 25% wennnach 4 Wochen immer noch <10 g/dL (or HCT <30%)Und gleichzeitigen Anstieg Hb 1 g/dL (HCT 3%)Centers for Medicare & Medicaid Services (CMS). Decision Memo for Erythropoiesis Stimulating Agents (ESAs) for non-renal disease indications (CAG-00383N). Available at: Accessed September 20,
61 Efficacy of Erythropoietin in Treating Patients Undergoing Major Elective Orthopedic Surgery 60N=200rHuEPO300 U/kg SC50N=208N=316Placebo40Transfusions, %302010In 3 trials that evaluated the efficacy of erythropoietin in patients undergoing major elective orthopedic surgery, erythropoietin significantly reduced the number of patients who underwent transfusions.COPES1*Faris et al2de Andrade et al3* Primary outcome event = any transfusion or Hb concentration <8 g/dL.Canadian Orthopedic Perioperative Erythropoietin Study Group. Lancet. 1993;341:Faris PM, et al. J Bone Joint Surg Am. 1996;78A(suppl):62-72.de Andrade JR, et al. Am J Orthop. 1996;25:
62 Efficacy of Erythropoietin in Treating Critically Ill Patients RHuEPO (n=80)Placebo (n=80)Total units transfused*166305% Transfused or died days 8-424555Hct change (baseline to final)†4.8 (95% CI, 3.8, 5.9)1.4 (95% CI, 0.3, 2.8)Final Hct‡35.1 ± 5.631.6 ± 4.1Reticulocyte % change(baseline to final)†2.5 (95% CI, 1.9, 3.0)0.8 (95% CI, 0.3, 1.3)In a study by Corwin et al, critically ill ICU patients were randomized to receive rHuEPO 300 units/kg (n=80) or placebo (n=80). rHuEPO was given for a minimum of 2 weeks or until ICU discharge up to a total of 6 weeks postrandomization.The cumulative number of units of RBCs transfused was significantly less in the rHuEPO group than in the placebo group. The rHuEPO was transfused with a total of 166 units of RBCs versus 305 units of RBCs tranfused in the placebo group. The final hematocrit concentration of the rHuEPO patients was significantly greater than the final hematocrit concentration of placebo patients. A total of 45% of patients in the rHuEPO group received a blood transfusion between days 8 and 42 or died before study day 42 compared with 55% of patients in the placebo group. There were no significant differences between the 2 groups either in mortality or in the frequency of adverse events.The administration of rHuEPO to critically ill patients is effective in raising their hematocrit concentrations and in reducing the total number of units of RBCs they require.*P<.002; †P<.001; ‡P<.01.Adapted with permission from Corwin HL, et al. Crit Care Med. 1999;27:
63 Strategies for Reducing Blood Loss During Surgery Careful surgical dissection and hemostasisUse of controlled hypotensive anesthesia1Maintenance of normothermia1Blood cell salvage1Tolerance of normovolemic anemia1Elevating the surgical site2The strategies for reducing blood loss during surgery are outlined in this slide.Gil O, et al. Ann Thorac Surg. 1995;60:Park CK. Anesth Analg. 2000;91:
64 Kosteneffekte PBM/ITM KH-PerspektiveVorstationäre EPO-Kosten (Präparat und Verabreichung)Präparatekosten Epo und EisenPerioperative Kosten Blut- management Entnahme EigenblutAufbewahrung EigenblutMAT: Material und Personalletzte 1-2 EPO-u. Fe-InjektionenTransfusionen: PräparateTransfusionen: Vorbereitung, Verabreichung, Logistik (in KH)Effekte Infektionen und RevisionenHöhere Fallkosten bei gleicher DRG durch Antibiose (ca € bei 3-6%)Ungeplante RevisionEffekte Verweildauer erhöhte Pflegekosten
65 Anwender-Kosten der Fremdbluttransfusion Fixkosten und variable KostenBasha et al. Transfusions And Their Costs: Managing PatientsNeeds And Hospitals Economics. Int J Emer Int Care Med 2009
66 Fremdbluttransfusion Reale Kosten 1 jährlichesTransfusionsvolumenin den USA D (gemäß PEI) €:29 Mio TE(14.2 Mio EK, 5.5 Mio FFP (2005-6)) 4,8 Mio TE (2009) 2,5 MrdKomplikationen / Risiko/ verursachte Kosten> 125 Todesfälle durch Transfusion ? (1/6 USA = 21)> 64 TRALI 1: : (2006/7)9 AB0 Inkompatibilität1: (FDA) < 1: (IAKH)1Solheim BG. Indications for use and cost-effectiveness of pathogen reduced AB0-universal plasma.Curr Opin Hematol 2008; 15:612-72Chaiwat O, et al. Early Packed Red Blood Cell Transfusion and ARDS after Trauma. Anesthesiology 2009; 110:
67 Fremdbluttransfusion Komplikationsrisiko und -kostenUSA D €Letale Sepsis 1: : (UK Erlangen) 1000/Tag2ARDS 0,6 Mrd US$/14 Tage ? 700/Tag2Intensivmedizin/beatmete Pat.: Kosten Verweildauer 6.3 Tage (CI ) ? 6 300 Mortalität 21% (OR 1.21, CI 1.00 – 1.48) ? Infektionen US$/Infektion Kosten US $ (CI )2Zilberberg MD et al. Transfusion-attributable Acute Respiratory Distress Syndrome, Hospital: Materials and MethodsTransfusionsmedizin Transfusionsmedizin Alter Med 2008, 10/13Zilberberg MD et al. Anemia, transfusions and hospital outcomes among critically ill. CritiCare 2008; 12: R60 (n=4400, retrospekiv, Beatmung > 96h)
68 Korrekte Berechnung der kompletten Kosten der Fremdbluttransfusion Kosten autologer Techniken hängen in erster Linie von Infektionsrisiko abMittleres Infektionsrisiko von 3,7%Mittlere Kosten einer Infektion US$RR > 2.4autolog dominant ( RR 3.7, $/QUALY)2,4 > RR > 1.1 autolog noch dom < $/QALY1,1 > RR > 0 cost effectiveness up to 3,400,000 $/QALY
69 Wahrscheinlichkeit des Auftretens bestimmt Mehrkosten Linzer Transfusionsgespräche Workshop STrategie/Ökonomie
70 Angebot von Kleingruppenarbeit Überdenken Sie die kritischen Elemente des Transfusionsmanagements in ihrer Klinik und denken Sie über Modifikationen nach (10 min)Wo erwarten Sie Widerstand bei der Umsetzung in Ihrer Klinik (10 min)Entwickeln Sie einen Plan zur Umsetzung (10 min)
71 Wiesbaden Transfusionsgespräche der IAKH e.V. 18/19.Nov. 2011 18./19. März 2011Wiesbaden Transfusionsgespräche der IAKH e.V. 18/19.Nov. 2011Arbeitskreis der DIVI Hämotherapiein Zusammenarbeit mit derInterdisziplinären Arbeitsgemeinschaft für Klinische Hämotherapie (IAKH)Sektion Klinische Hämotherapie der DIVIFehlerregister der IAKHFehlermelden unter
73 Welche Kosten müssen Sie wissen? Fixkosten:Geräte/Investitionskosten (Abschreibungs- und altersabh.)BlutgruppenautomatGefrier- und KühlschränkeRäume, Strom, Licht etc. (verzichtbar)PersonalLaborpersonal für Blutgruppe und VerträglichkeitsprobeArzt für BedSide und AdministrationHol und Bringe DienstVariable Kosten:Erwerbskosten aller Blutprodukte von Blutbank, aller Gerinnungspräparate von ApothekeLaborkosten- Verträglichkeitsproben, Blutgruppenautomat