Haematology and Transfusion Prof Dr Wolfram Engelhardt Anaesthesiology and Intensive Care Medicine Offenburg Hospital, Germany dr.w.engelhardt@gmail.com
James Blundell 1828 Lancet 1828; 11:321
Erythrocytes Women: Men: 4-5 x 10 6 /µl 5-6 x 10 6 /µl live 100-120 days contain no nucleus Diameter 6-8 µm 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
Thrombocytes 150 000-400 000/µL (= 150-400 x 10 9 /L) Diameter: 1,5-3 µm 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
Plasma Coagulation factors Factor Level Half-life available µm h concentrate Fibrinogen 7.6 72-120 + Prothrombin 1.4 72 + Factor V 0.03 36 -- Factor VII 0.01 3-6 + Factor VIII 0.00003 12 + Factor IX 0.09 24 + Factor X 0.17 40 + Factor XI 0.03 80 + Factor XIII 0.03 120-200 + von Willebrand-F. 0.03 10-24 + Bolliger Anesthesiology 2010; 113:1205
Thrombelastometry assesses kinetics of clot formation stability or lysis of the formed clot Bolliger Anesthesiology 2010; 113:1205
AB0-compatible transfusion of Red blood cells Plasma (FFP)
Serologic compatibility testing AB0 / Rh typing Patient erythrocytes against test sera Anti-A, Anti-B, Anti-D 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
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
Irradiation of blood components renders T lymphocytes incapable of proliferation approved method to prevent transfusion-associated graft-versus-host disease selected immunocompromised recipients recipients of cellular components from a blood relative recipients who have undergone allogenic stem cell or marrow transplantation recipients of cellular components whose donor is selected for HLA compatibility Indications fetal or neonatal recipients of intrauterine transfusions
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 10 10 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 10 11 platelets are stored for up to 5 days in gas-permeable plastic bags at 22 ± 2 C with continuous agitation
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 stored at -30 C up to 1 year In adults: ANY DOSE BELOW 800ml IS USELESS! Risks: Hypervolaemia Transfusion-related acute lung injury (anti-hla antibodies)
Serious Hazards of Transfusion (SHOT) Transfusion-related acute lung injury FFP + Platelets Erythrocytes United Kingdom: Male-only plasma was initiated in 2003
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
Risks associated with RBC and platelet transfusion McIntyre L
RBC Transfusions are associated with mortality postoperative infections myocardial infarction stroke renal failure cancer progression non-hodgkin-lymphoma immunomodulation
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
% 40 35 30 25 n= 310 311 30-day-mortality Cardiac event rates in 30 days 20 15 10 5 0 <18 18-20,9 21-23,9 24-26,9 27-29,9 30-32,9 33-35,9 36-38,9 39-41,9 42-44,9 45-47,9 48-50,9 51-53,9 >54 Haematocrit %
Musallam
The American College of Surgeons National Surgical Quality Improvement Program n=125 223 Mortality Morbidity Units of Packed RBCs Bernard J Am Coll Surg 2009; 208:931
n=922 A = Anaemia Tx = Transfusion Engoren Ann Thorac Surg 2014; 97:514
Anaemia MCV mean corpuscular volume: MCH mean corpuscular haemoglobin: 80 96 fl 28 33 pg microcytic normocytic macrocytic < 80 fl 80 96 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
Microcytic Anemia DeLoughery N Engl J Med 2014; 371:1324
Laboratory diagnostics in anaemia Anaemia of Iron deficiency chronic disease Serum iron Ferritin normal / Transferrin / normal Transferrin saturation Ferritin Transferrin
Management of preoperative anaemia Goodnough Anesthesiology 2013; 118:223
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 November 2013 http://www.aabb.org/tm/coi/documents/ coi1113.pdf
Intravenous iron combined with low-dose human erythropoetin in iron-deficient patients bilateral total knee arthroplasty RBCs transfusion when Hb< 7 g/dl transfusion rate: 20 vs. 54%, p<0,01 EPO control 200mg iron sucrose + 3000 IU EPO sc intraoperatively and up to 2x postopoperatively if Hb 7-8 g/dl 2 x 54 patients Na H-S Transfusion 2011; 51:118-24
Survival % 2,6 ± 4,1 RBC units / patient Transfusion when haemoglobin < 7 g/dl haemoglobin < 10 g/dl 5,6 ± 5,3 RBC units / patient
Group liberal restrictive n 1007 1009 haemoglobin before transfusion (g/dl) 9,2 ± 0,5 7,9 ± 0,6 units red cells 1866 652 % 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
Transfusion when haemoglobin < 7 g/dl haemoglobin < 9 g/dl
leukocyte depleted RBC when haemoglobin < 7 g/dl haemoglobin < 9 g/dl
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 http://www.bundesaerztekammer.de/downloads/ Querschnittsleitlinie_Gesamtdokument-englisch_ 07032011.pdf
n=5334 n=2027 Hollis RH
Mortality in severe anaemia 30 day mortality n=293 n=300 Jehovah s witness patients, retrospective cohort studies Carson JL Transfusion 2002; 42:812-8 Shander A Transfusion 2014; 54:2688-95
27 year old female, 46kg, thoracolumbar scoliosis surgery Araújo Azi LM
Br J Anaesth 2012; 109:55-68
Management of bleeding following major trauma: an updated European guideline We recommend Grade a target haemoglobin of 7 9 g/dl 1C no different threshold in severe traumatic brain injury FFP or pathogen-inactivated plasma in a plasma-rbc ratio of 1:2 1B or fibrinogen concentrate and RBC according to Hb level fibrinogen concentrate or cryoprecipitate if bleeding is accompanied by viscoelastic signs of fibrinogen deficit or fibrinogen level less than 1.5-2.0 g/l; initial dose 3-4 g tranexamic acid as early as possible; loading 1g, infusion 1g/8h platelets to maintain a platelet count above 50 x 10 9 /L above 100 x 10 9 /L in traumatic brain injury or ongoing bleeding 1C 1C 1A 1C 2C
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. Anaesthesia 2010;65:1153-61