Haematology and Transfusion dr.w.engelhardt@gmail.com Wolfram Engelhardt Offenburg, Germany James Blundell 1828
Diameter 6-8 µm Erythrocytes Women: Men: 4-5 x 10 6 /µl 5-6 x 10 6 /µl live 100-120 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
Thrombocytes Diameter: 1,5-3 µm 150 000-400 000/µL (= 150-400 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
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 D et al.
Karl Landsteiner * 14. Juni 1868 near Vienna, 26. Juni 1943 in New York
AB0-compatible transfusion of Red blood cells Plasma (FFP)
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
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 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
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 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)
Serious Hazards of Transfusion (SHOT) United Kingdom Transfusion-related acute lung injury FFP + Platelets Erythrocytes Male-only plasma was initiated in 2003
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 20 15 10 5 0 310 311 operative patients aged 65 years or older <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 Haematocrit % 30-day-mortality Cardiac event rates in 30 days 42-44,9 45-47,9 48-50,9 51-53,9 >54
The American College of Surgeons n=125 223 Mortality National Surgical Quality Improvement Program Morbidity 2005-2006 Bernard AC et al. Units of Packed Red Blood Cells transfused
n=922 A = Anaemia Tx = Transfusion Engoren M et al.
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
Laboratory diagnostics in anaemia Anaemia of chronic disease Iron deficiency Serum iron Ferritin normal / Transferrin / normal Transferrin saturation Ferritin Transferrin
Goodnough LT Management of preoperative anemia
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 2009 http://www.aabb.org/resources/bct/documents/coi0809r.pdf
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
McIntyre L et al.
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
Adverse effects of RBC transfusion contrasted with other risks Risk is depicted on a logarithmic scale. Carson JL et al.
RBC Transfusions are associated with mortality postoperative infections myocardial infarction stroke renal failure cancer progression non-hodgkin-lymphoma immunomodulation
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
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
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 51-103 y (mean 81,6) 82 % hypertension 40% coronary artery disease 25% diabetes mellitus
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 Days
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.
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
http://www.sabm.org/
Intra- and postoperative iv iron combined with low-dose human erythropoetin in iron-deficient patients EPO bilateral total knee arthroplasty 200mg iron sucrose + 3000 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
27 year old female, 46kg, thoracolumbar scoliosis surgery Araújo Azi LM et al.
Definitions of massive transfusion
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.
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.
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.