Introduction to Transfusion Medicine •Blood component • •1 – 10 donors •↑ risk of infection transmission • •Blood establishments (within ČR) •Red Blood Cells, Platelets, Plasma, Granulocytes •Blood derivative • •pooled plasma (thousands donors) •↓ risk of infection transmission – Pathogen Reduction Technology •Plasma fractionation centers (abroad) •Solvent/detergent-treated plasma, Coagulation factor concentrates, Immunoglobulins, Albumin… • Blood components may be obtained: •whole blood donation –→ centrifugation –→ separation into its constituent elements – •apheresis –only the desired component is collected, while the remaining blood is returned to the donor – usually further processing not needed • N:\TOKB\Prezentace\FOTOGRAFIE TTO\4021,4022 dárci krve, ambulance\Foto dárci\16486928_1239581472744219_4584060492298899305_o.jpg BLOOD COMPONENTS Whole Blood •source material for component preparation •not used for transfusion (usually) –storage conditions and shelf life are specific for each component type –patients should receive only the component required to correct their specific deficiency •whole blood may be indicated in limited clinical settings Red blood cells •Shelf life: 42-49 days •Storage temperature: 2-6°C •ABO/Rh(D) compatibility between donor and recipient necessary, pre-transfusion testing Decision to transfuse …is complex: •Cause of anaemia •Severity of anaemia •In case of haemorrhage: the rate and amount •Ability to compensate for the blood loss •Presence of comorbidities affecting compensatory mechanisms Indication •The aim of red blood cell transfusion is to provide oxygen delivery to organs and tissues when there is evident hypoxia caused by severe anaemia. • ØHaemoglobin > 100 g/l: no indication ØHaemoglobin 70-100 g/l: individual evaluation ØHaemoglobin < 60 - 70 g/l: indication almost sure • 1 TU of RBCs is expected to raise haemoglobin by 10 g/l Platelets •Shelf life: 4 to 5 days –7 days in case of sterility control or use of PRT •Storage conditions: at 20-24°C with continuous agitation •ABO/Rh(D) compatibility recommended •no pre-transfusion testing • • P1050638 Indications •Thrombocytopenia or thrombocytopathy –Therapeutic: active platelet-related bleeding •platelet count trigger for transfusion is not strict: evaluate bleeding severity, cause, suspected dynamics –Prophylactic: as prevention of bleeding •< 10 x 109/l to prevent spontaneous bleeding •< 50 x 109/l in case of invasive and major surgical procedures, cardiac or intracranial surgery 80-100 x 109/l • 1 TD increases platelet count by 20-40 x 109/l Plasma •Storage: 36 months at -25°C • 3 months at -18°C •balanced amount of coagulation factors and coagulation inhibitors (and other plasma proteins) •ABO compatibility necessary •RhD not relevant •no pre-transfusion testing C:\Dokumenty 2003 - 2008\Publikační činnost\2010\Penka - GRADA - ZL\VERZE - POSLEDNÍ - CD\10_Obrázek_733_8_Sklad_plazmy.TIF Indications •use of plasma (FFP) less frequent - replaced: –coagulation factor concentrates –pooled plasma solvent detergent treated (OctaplasLG) •massive bleeding •DIC with active bleeding •TTP (plasma exchange) •Vitamin K deficiency associated bleeding (+ vit K) Dosage: 10 – 15 ml/kg Granulocytes (rare use) •Shelf life: short – administrated as soon as possible •Storage temperature: 20-24°C •ABO/Rh(D) compatibility between donor and recipient necessary, pre-transfusion testing •Indication: severe inf. + neutropenia •Irradiation always BLOOD COMPONENT ADJUSTMENT Leucocyte depletion •without indication limitation (safer) •leucocytes < 1x 106 •prevention/reduction –↓ adverse transfusion reactions –↓ alloimunisation –↓ haemotherapy-associated immunosuppression –↓ pathogen transmission (EBV, CMV) - alternative of CMV negative blood component • • – • C:\Users\uživatel\Desktop\drive-download-20190112T213000Z-001\IMG_20190128_143534.jpg C:\Users\uživatel\Desktop\drive-download-20190112T213000Z-001\IMG_20190115_101732.jpg Irradiation •prevention of TA-GvHD •γ rays of 25-50 Gy inactivate T lymfocytes •indications: –immature or altered immune system –transfusions from relatives / of HLA-matched blood components •doesn´t replace leucodepletion neither destroys pathogens Washing •indications: –repeated severe allergic reactions due to plasma proteins –selective IgA deficiency •shortened shelf life •anaphylactic reaction prevention •performed by additive solution or saline •goal: total protein < 0,5 g / TU – • Smaller amount needed? - blood component may be divided •Red blood cells – according to childs weight •Platelets – standard pediatric dose = 1/2 of adult TD •Plasma – production of pediatric dose possible, usually not cost effective – • IMMUNOHAEMATOLOGY (JUST BASICS..) Pre-transfusion testing •compulsory serological tests done before erytrocyte blood component administration •valid for 3 days •100% safety not guaranteed • Pre-transfusion testing comprises: • •blood group testing: ABO and RhD •screening for red cell antibodies (non-ABO) •compatibility test – • ABO_blood_type ABO and RhD testing of recipient •ABO •ABO antigens (aglutinogens) –monoclonal anti-A and anti-B diagnostic serum •ABO antibodies (aglutinins) – reverse grouping –diagnostic A1 and B erytrocytes •RhD •using 2 different diagnostic anti-D (IgM) sera • Diamed karty Screening for red cell allo-antibodies Antibody identification Compatibility testing •recipient serum x donor erytrocytes Emergency red cells •insufficient time for pre-transfusion testing •blood sampling for additional testing •O negative or patient´s blood group if known •adverse transfusion reaction risk due to possibility of pre-existing antibodies! PRINCIPLES OF HAEMOTHERAPY General principles of haemotherapy •Transfusion when indicated! •Consistent compliance with guidelines •effective haemotherapy and restrictive transfusion strategy – always consider possible alternatives to transfusion •procedures to increase safety of haemotherapy •Patient education about benefits and risks of transfusion Alternatives to transfusion Patient blood management •Optimization of patient´s endogenous red cell mass: –screening and treating for anaemia - iron substitution, erytropoetin –autotransfusion •↓ blood loss and optimization of coagulation –medication correction (with bleeding risk) –surgical techniques –haemostatic agents (tranexamic acid, tissue adhesives) –controlled intraoperative hypotension –reduction of diagnostic blood sampling –coagulation factor concentrates •↑ tolerance of anaemia • Transfusion administration •within 6 hours •monitored (patient blood pressure, pulse, temperature before and after; adverse reactions) •Bed side test •administration through transfusion set (filter), separately •rest of the blood component should be left for 24 hours HAEMOTHERAPY COMPLICATIONS Mandatory testing of blood donations •Infection markers serologically –HBV (HBsAg) –HCV (anti-HCV) –HIV (dual tests) –Syphilis (antibodies against T.P.) •Imunohaematology –Blood group testing (ABO and RhD typing) –Antierytrocyte antibody screening Most complications are due to: • • • • solution: •leucocyte depletion •irradiation • – – – solution: •selection of clinical plasma donors (without history of immunisation) •using of additive solutions for blood component preparation •washing •coagulation factor concentrates •Solvent/detergent-treated pooled plasma (OctaplasLG) • > > Leucocytes Plasma Complications of transfusion - classification •etiology •time-to-onset •severity Etiology •Infection transmission •Cardiovascular and metabolic complications –circulatory overload, hypothermia, hyperkalemia, hypocalcemia, transfusion haemosiderosis, hypotension, hypertension •Immune-mediated complications –Transfusion-related immunomodulation – associated with dose of transfused leucocytes and storage time of blood component –Allo-imunisation –Immune-mediated transfusion reactions •acute and a delayed haemolytic reaction, FNHTR, allergic reaction, anaphylactic, TRALI, TA-GvHD, posttransfusion purpura • Transfusion complications according to time of their development •Acute –< 24 h after transfusion –e.g. acute haemolytic reaction, FNHTR, TRALI, allergic, cardiovascular and metabolic complications •Delayed –> 24h after transfusion, days to weeks –e.g. delayed haemolytic reaction, Ta-GvHD, infection, allo-imunisation, transfusion haemosiderosis (iron overload) Transfusion complications according to severity •Nonserious –mild clinical course –usually fade away soon after the transfusion is stopped –symptoms are mild and reversible •Serious –severe symptoms, may be life-threatening –require vital signs monitoring Frequent cause of transfusion complications is administrative error! •sample change •error in identification data •error in blood group testing •change of blood component •not respecting standard procedures • Acute haemolytic reactions •Cause: •Immune: incompatible transfusion – mostly administrative error! •Non-immune: temperature, mechanical, bacterial contamination •Symptoms: •chills/fever, dyspnoea, back pain or chest pain, tachycardia, hypotension, shock, anxiety, vomiting •Diagnosis: •↑ bilirubin, ↑ LDH, ↓ haptoglobin, haemoglobinemia, haemoglobinuria •blood group verification of patient and blood component, DAT (positive), compatibility test (positive) •Treatment/management: •stop the transfusion, vital signs monitoring •intensive care may be needed to prevent shock, kidney failure (maintain urine output, haemodialysis), DIC Delayed haemolytic reaction •Cause: •Immunisation in the past (prior transfusion, pregnancy) •Symptoms: •fever, icterus, development of anaemia in 5 to 14 days – extravascular haemolysis, kidney failure not so often •Diagnosis: •anaemia, ↑ bilirubin, ↑ LDH, ↓ haptoglobin, haemoglobinuria, positive DAT, identification of anti-erytrocyte allo-antibodies •Treatment/management: •supportive •transfusion of compatible RBCs lacking the antigen against which is the patient immunised •Prevention: •respecting standard/safe procedures (documentation) Febrile non-haemolytic transfusion reaction •one of more fequent transfusion complications •Cause: •cytokines released from leucocytes during storage •HLA antibodies •Symptoms: •fever, chills, shivering during or shortly after transfusion (usually occurs in 30-60 minutes from beginning of transfusion) •Diagnosis: •temperature rise ≥ 1˚C from baseline •FNHTR is a diagnosis of exclusion! Symptoms of FNHTR also occur in other more serious reactions – acute hemolysis, bacterial contamination, TRALI •Treatment/management: •antipyretics •Prevention: •leucocyte depletion (occurence in countries with widespread leucocyte depletion has significantly decreased). Transfusion-associated sepsis •Cause: •bacterial contamination of blood component •highest risk have platelets stored in room temperature •Symptoms: •fever, chills, vomiting, diarrhoea, tachycardia, hypotension, shock •Diagnosis: •blood culture (patient), sterility testing (blood component) •bacterial contamination should be excluded in all serious reactions with fever and hypotension •Treatment: •antibiotics, symptomatic/supportive •Prevention: •visual control of the blood component •respecting of the storage conditions Allergic and anaphylactic •Cause: •most often after blood components with plasma content •antibodies against plasmatic proteins in blood components •anaphylaxis – selective IgA deficiency patients with anti-IgA antibodies •Symptoms: •urticaria, itching, vomiting, diarrhoea, hypotension, shock, dyspnoea •Diagnosis: •patient´s IgA level should be examined if severe allergic transfusion reaction repeates •Treatment: •symptomatic, antihistamines •Prevention: •washing of cellular blood components (for patients with severe reactions), premedication with steroids and/or antihistamines TRALI Transfusion Related Acute Lung Injury •Cause: •anti-HLA or anti-HNA antibodies (prior immunisation) - activating neutrophiles → sequestration in lung microcirculations - endothelium damage - capillary leakage - ARDS •Symptoms: •fever, hypotension, respiratory failure with bilateral pulmonary infiltrates, without symptoms of circulatory overload •onset ˂ 6 hours from transfusion •Diagnosis: •oxygen saturation, chest X-ray, anti-HLA / anti-HNA antibodies •Treatment: •oxygen, ventilation •leucodepleted blood components •Prevention: restriction on female-donor plasma TRALI •Before transfusion • •After transfusion • TACO Transfusion Associated Circulatory Overload •Cause: •after high volume transfusions – acute hypervolemia •Symptoms: •dyspnoea, cough, acute pulmonary oedema, tachycardia, cyanosis •onset < 12 hours after transfusion •Diagnosis: •development of acute dyspnoea, low oxygen saturation •chest X-ray of cardiac decompensation •Treatment: •oxygen therapy, diuretics •Prevention: •transfusion rate should be 2-4ml/kg/hour, 1ml/kg/hour in high risk patient TA – GvHD (Transfusion-associated Graft versus Host disease) •Cause: •donor lymphocyte proliferation in immunocopromised or HLA similar recipient •rare, but usually fatal •Symptoms: •fever, erythema, vomiting, diarrhoea, lymphadenopathy, hepatopathy, pancytopenia •onset 4 – 30 days after transfusion •Diagnosis: •biopsy consistent with GvHD •evidence of donor and recipient lymphocyte chimerism •Prevention: •irradiation, not administering transfusion from relatives Hypothermia •body temperature drop to 32 – 34˚C •usually after massive transfusions (rather than single unit transfusion) •Prevention: preheating of blood components Hyperkalemia •abnormal increase of blood potassium level after transfusion • •fast RBCs administration (> 60 ml/min.) •longer storage time / irradiation of RBCs • •could be serious - cardiac arrest •fastest diagnosis - ekg Hypotension •blood pressure drop ≥ 30 mmHg within 4 h •other causes should be excluded Hypertension •blood pressure raise ≥ 30 mmHg within 4 h with exclusion of other causes • Post-transfusion purpura •Cause: •specific anti-platelet antibodies (e.g. anti-HPA 1a) •Symptoms: •severe thrombocytopenia, bleeding •serious transfusion complication •Diagnosis: •identification of anti-platelet antibodies •Treatment: •IVIG Post-transfusion hemosiderosis •iron overload caused by multiple transfusions (transfusion-dependent patients) •hemosiderin = large aggregates of ferritin → tissue dammage (liver cirrhosis, cardiomyopathy, endocrinopathy,…) •1 TU contains approx 230 mg of iron Material for investigation of transfusion complications: •pre-transfusion blood sample •post-transfusion blood sample •rest of the blood component (5-10 ml) • •transfusion reaction reporting form • Take home message •follow guidelines •respect indications – restrictive transfusion politics – consider bloodless alternatives •use procedures to increase haemotherapy safety •interdisciplinary cooperation transf Thank you for your attention.