Haematology and Transfusion
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1 Haematology and Transfusion Wolfram Engelhardt Offenburg, Germany James Blundell 1828
2 Diameter 6-8 µm Erythrocytes Women: Men: 4-5 x 10 6 /µl 5-6 x 10 6 /µl live days contain no nucleus contain haemoglobin and carry O 2 to tissues 2 x 10 6 / s are produced in marrow of long bones (healthy adults) production is stimulated by erythropoetin (Erythropoiesis) normally 1% reticulocytes are removed from circulation in the reticuloendothelial system in the spleen, liver and bone marrow
3 Thrombocytes Diameter: 1,5-3 µm /µL (= x 10 9 /L) activation of megakaryocytes by thrombopoietin live for 5-10 days contain no nucleus Platelets aggregate using fibrinogen and von Willebrand factor as a connecting agent The most abundant platelet aggregation receptor is glycoprotein IIb/IIIa
4 Plasma Coagulation factors Factor Level Half-life available µm h concentrate Fibrinogen Prothrombin Factor V Factor VII Factor VIII Factor IX Factor X Factor XI Factor XIII von Willebrand-F Bolliger D et al.
5 Karl Landsteiner * 14. Juni 1868 near Vienna, 26. Juni 1943 in New York
6 AB0-compatible transfusion of Red blood cells Plasma (FFP)
7 Serologic compatibility testing AB0 / Rh typing Patient erythrocytes against test sera Anti-A, Anti-B Patient plasma against test erythrocytes A1, A2, B, 0 Antibody-screening Patient plasma against test erythrocytes detects all relevant antibodies against frequent antigens (Kell, Duffy, Kidd,...) Crossmatching Patient plasma against unit erythrocytes detects antibodies against this unit
8 Erythrocytes / Red Blood Cells (RBCs) 1 unit of RBCs increases haemoglobin concentration by 1g/dL in an average weight adult in Europe only leucocyte-depleted RBCs improve quality strongly reduce risk of immunization against human leucocyte antigens (HLA) almost eliminate transmission of intracellular viruses (CMV) storage at +4 ± 2 C up to 42 days
9 Irradiation of blood components renders T lymphocytes incapable of proliferation approved method to prevent transfusion-associated graft-versus-host disease Indications selected immunocompromised recipients recipients of cellular components from a blood relative recipients who have undergone marrow transplantation recipients of cellular components whose donor is selected for HLA compatibility fetal or neonatal recipients of intrauterine transfusions
10 Thrombocytes / Platelet concentrates contain plasma and small amounts of erythrocytes and leucocytes => AB0-identical transfusion Platelet concentrate produced from a unit of whole blood contains 7,5 x platelets on average and should increase the platelet count by 5 10 x 10 9 /L in a 70 kg recipient Pooled platelet concentrates from 4 6 donors Thrombocytapheresis platelet concentrates generally contain 3 6 x platelets are stored for up to 5 days in gas-permeable plastic bags at 22 ± 2 C with continuous agitation
11 Fresh Frozen Plasma (FFP) FFP is transfused AB0-identical, AB plasma to patients with other groups only in emergency. Serological compatibility testing is not necessary. Plasma contains all clotting factors with considerable variability between donors. 1 ml/kg body weight increases factor and inhibitor levels or prothrombin time by 1%; less in cases of increased turnover In adults: ANY DOSE BELOW 800ml IS USELESS! stored at -30 C up to 1 year Risks: Hypervolaemia Transfusion-related acute lung injury (anti-hla antibodies)
12 Serious Hazards of Transfusion (SHOT) United Kingdom Transfusion-related acute lung injury FFP + Platelets Erythrocytes Male-only plasma was initiated in 2003
13 Anaemia Women: Hb < 12 g/dl 7,4 mmol/l pregnant: Hb < 11 g/dl 6,8 mmol/l Men: Hb < 13 g/dl 8.1 mmol/l under-recognized under-diagnosed under-treated World Health Organization
14 % operative patients aged 65 years or older < , , , , , , , ,9 Haematocrit % 30-day-mortality Cardiac event rates in 30 days 42-44, , , ,9 >54
15 The American College of Surgeons n= Mortality National Surgical Quality Improvement Program Morbidity Bernard AC et al. Units of Packed Red Blood Cells transfused
16 n=922 A = Anaemia Tx = Transfusion Engoren M et al.
17 Anaemia MCV mean corpuscular volume: MCH mean corpuscular haemoglobin: fl pg microcytic normocytic macrocytic < 80 fl fl > 96 fl hypochromic normochromic hyperchromic iron deficiency acute blood loss deficiency of anaemia of chronic disease vitamin B12 Globin synthesis aplastic anaemia folic acid defect thalassaemia
18 Laboratory diagnostics in anaemia Anaemia of chronic disease Iron deficiency Serum iron Ferritin normal / Transferrin / normal Transferrin saturation Ferritin Transferrin
19 Goodnough LT Management of preoperative anemia
20 AABB, American Red Cross, America s Blood Centers, Armed Services Blood Program Contraindications Red-cell containing components should not be used to treat anemias that can be corrected with specific hematinic medications such as iron, vitamin B 12, folic acid, or erythropoietin. Revised December
21 Infectious Risks of Blood Transfusion Donors are tested for Hepatitis B virus Human immunodeficiency virus Hepatitis C virus Human T-cell lymphotropic virus West Nile Virus Bacteria (in platelets only) Trypanosoma cruzi Cytomegalovirus Syphilis Donors are not routinely tested for Hepatitis A virus Parvovirus B19 Dengue fever virus Babesia Plasmodium (Malaria) Leishmania Brucella New variant Creutzfeldt- Jakob disease
22 McIntyre L et al.
23 Causes of transfusion-related deaths in the USA TRALI transfusion-related acute lung injury HTR haemolytic transfusion reaction TACO transfusion-associated cardiac overload TAS transfusion-associated sepsis GVHD graft-versus host disease
24 Adverse effects of RBC transfusion contrasted with other risks Risk is depicted on a logarithmic scale. Carson JL et al.
25 RBC Transfusions are associated with mortality postoperative infections myocardial infarction stroke renal failure cancer progression non-hodgkin-lymphoma immunomodulation
26 Mortality in severe anaemia 30 day mortality n=293 n=300 Jehovah s witness patients, retrospective cohort studies Carson JL et al. Transfusion 2002; 42:812-8 Shander A et al. Transfusion 2014; e-pub ahead of print
27
28 2,6 ± 4,1 RBC units / patient Transfusion when haemoglobin < 7 g/dl Survival % 5,6 ± 5,3 RBC units / patient haemoglobin < 10 g/dl n=838 Days
29 Transfusion threshold: liberal group: Haemoglobin <10 g/dl restrictive group: Haemoglobin < 8 g/dl or symptoms of anaemia 47 hospitals in USA and Canada age y (mean 81,6) 82 % hypertension 40% coronary artery disease 25% diabetes mellitus
30 Group liberal restrictive n haemoglobin before transfusion (g/dl) 9,2 ± 0,5 7,9 ± 0,6 units red cells % transfusion 96,7% 41,0% death or inability to walk after 60 d 35,2% 34,7% death after 60 d 7,6% 6,6% myocardial infarction, unstable angina or in-hospital death 4,3% 5,2% p<0,05
31 Transfusion when haemoglobin < 7 g/dl haemoglobin < 9 g/dl Days
32
33 restrictive transfusion strategy (7-8 g/dl) in hospitalized, stable patients (strong recommendation; high-quality evidence) restrictive strategy in hospitalized patients with preexisting cardiovascular disease (with symptoms or hemoglobin <8 g/dl) (weak recommendation; moderate-quality evidence) uncertain recommendation in hospitalized, hemodynamically stable patients with the acute coronary syndrome (very low-quality of evidence) Carson JL et al.
34 Physiologic transfusion triggers Cardiopulmonary symptoms tachycardia hypotension unexplained decrease in blood pressure dyspnoe ECG changes typical of ischemia new ST-depression or elevation or new rhythm disorder Echocardiography: New regional myocardial contractility disorder Indices of an insufficient oxygen delivery decrease mixed venous po 2 < 32mmHg ScvO2 < 60% lactate acidosis Gesamtdokument-englisch_ pdf
35
36
37 Intra- and postoperative iv iron combined with low-dose human erythropoetin in iron-deficient patients EPO bilateral total knee arthroplasty 200mg iron sucrose IE EPO sc intraoperatively and up to 2x postop. if Hb 7-8 g/dl transfusion rate: 20 vs. 54%, p<0,01 2 x 54 patients control RBCs transfusion when Hb< 7 g/dl Na H-S et al Transfusion 2011; 51:118-24
38 27 year old female, 46kg, thoracolumbar scoliosis surgery Araújo Azi LM et al.
39 Definitions of massive transfusion
40 Management of bleeding following major trauma: an updated European guideline We recommend a target haemoglobin of 7 9 g/dl no different threshold in severe traumatic brain injury initial administration of plasma (FFP or pathogen-inactivated plasma) or fibrinogen (1C) in patients with massive bleeding treatment with fibrinogen concentrate or cryoprecipitate if bleeding is accompanied by thrombelastometric signs of fibrinogen deficit or fibrinogen level less than 1.5 g/l that platelets be administered to maintain a platelet count above 50 x 10 9 /L Grade 1C 1B 1C 1C 1C Spahn DR et al.
41 Early infusion of 15 ml/kg FFP should be used to prevent haemostatic failure. Established coagulopathy will require more than 15 ml/kg FFP to correct. The most effective way to achieve fibrinogen replacement rapidly is by giving fibrinogen concentrate or cryoprecititate if fibrinogen is anavailable.
42 1:1:1 red cell : FFP : platelet regimens, as used by the military, are reserved for the most severely traumatized patients. Group-specific blood can be issued without an antibody screen because patients will have minimal circulating antibodies.
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