Blood Transfusion Teoman SOYSAL Prof MD Blood Donation

Blood Transfusion Teoman SOYSAL Prof. MD

Blood Donation Healty adult donors • 450 ml +/- 10% per whole blood donation • Male: 5/year, Female : 4/year • > 8 weeks between two donations

Apheresis: Platelets Plasma White cells (or subsets) Red cells The procedure can be done for treatment or transfusion purposes.

Blood Preservation • Whole blood or red cells 1 -Liquid phase storage : 1 -6º C • 63 ml anticoagulant-preservation liquid/unit duration of preservation – ACD: 3 weeks – CPD-A 1: 35 days – RBC concentrate with SAG-Mannitol : 7 weeks 2 - Frozen storage of red cells • -80 to - 196 º C , with glycerol etc: Years

Blood Preservation • Effects of storage – Red cells: ATP, 2 -3 DPG, osmotic fragility and oxygen affinity – Plasma : Hb, K, NH 3 : p. H: – Platelets: Lost in 2 days – Coagulation factors: Eg: • FV: adequate levels for about 5 days • FVIII: Below 80% of original level after 1 -2 days • FXI: Less than 20% of original level after 7 days

Blood Preservation • Platelets: – liquid phase : 1 - 5 days, room temp. , avoid light exposure kept on special agitator • Plasma : Use fresh or freeze – frozen at -18 º C within 8 hrs of collection

Blood components & products • Cell containing components – Red cells: • Whole blood( fresh or not) • Red cells: packed red blood cells washed red blood cells frozen red blood cells leukocyte – reduced red blood cells – Platelets: Random donor platelets Apheresis platelets ( single donor platelets) – Granulocytes or mononuclear cells – Peripheral blood progenitor cells

Blood components & products • Plasma and products – Plasma : fresh / fresh-frozen plasma – Cryopresipitate – Coagulation factor concentrates – Immunglobulin preperations – Albumin – others

Deciding blood transfusion; • Severity of symptoms • Cause of anemia • Rapidity of anemia or symptoms • Co-morbidities and the age of the patient • Can we treat the anemia without transfusion? And • Is there enough time to wait for the response of such a treatment ?

This is not a guide to be used in every patient • Hemoglobin >10 g/d. L : Tx rarely needed • Hemoglobin < 6 -7 g/d. L: Tx mostly necessary • Hemoglobin : 6 -10 g/d. L: Dependable

Important: • Symptoms related to anemia may differ from one patient to another for a given Hb level; • The trigger for red cell transfusion may differ from one patient to another!!!!!

Indications for transfusion of blood or its components • Whole blood: Acute massive bleeding 1 unit increases Hb: 1 g/dl, Hct: 3% • Fresh whole blood: – Massively bleeding patient/shock – Exchange transfusion, open heart surg, severe renal or hepatic failure, • Red blood cells: – (To increase the oxygen carrying capacity in case of symptomatic anemia not treatable by other means or due to urgency of symptoms) – Symptomatic anemia (May be due to different causes), post-bleeding hypovolemia – 1 unit increases Hb: 1 g/dl, Hct: 3%

Indications for transfusion of blood or its components • White cells reduced RBC’s: < 5 x 106 WBC’s per unit White cell filters (before storage or before transfusion) • An indication for RBC transfusion + – To prevent reactions caused by WBC antibodies • Febrile non-hemolytic transfusion reactions – To prevent alloimmunization – To prevent CMV transmission

Indications for transfusion of blood or its components Washed RBC’s: • An indication for RBC transfusion + – Any need to prevent the recipient allo-immunisation to WBC’s , plasma antigens or any contraindication to infuse complement • PNH • Ig. A deficiency • Prevention of anaphylaxis • Washed units must be transfused no later than 24 hours Frozen RBC’s: • An indication for RBC transfusion + – Autologous transfusion: rare blood groups, – Catastrophy etc Washed before infusion !!

Indications for transfusion of blood or its components Blood Irradiation To prevent transfusion related GVHD in; • Congenital immune deficient states • Bone marrow or stem cell transplantation • Some cases of hematologic malignancies – Hodgkin’s disease – Purin analogue or anti-CD 52 treatment • Intra-uterin transfusion • New borne exchange transfusion • Transfusions between relatives – first or second degree • HLA matched platelets

Some of the indications for platelet transfusions • Decreased platelet production because of bone marrow failure or infiltration : bleeding or risk of bleeding – – – • • Leukemia MDS Myelofibrosis Malignant tm infiltration Myelosupression Aplastic anemia Functional platelet disease and bleeding or risk of bleeding Dilutional thrombocytopenia (after massive transfusion) Cardiac by-pass surgery Increased platelet destruction or consumption – – DIC Drug induced sepsis ITP

Indications for transfusion of blood or its components • Platelets: Thrombocytopenia due to decreased platelet production Platelet count/mm 3 Bleeding /surgery > 50. 000, < 50. 000 10. 000 -20. 000 No Yes No Indication for plt transfusion No Yes No (if there is bleeding/fever/DIC/plt dysfunction) Yes < 10. 000 Yes or No Yes

Some special conditions about platelet transfusion Disease status may change Practical issues the transfusion effectiveness: • ABO matched platelets have a longer in-vivo life span after transfusion • Use Rh- platelets for Rhrecipients (to prevent Rh immunisations) or use anti. Rh(D) Ig if Rh+ component used in such recipients • • DIC Hypersplenism Sepsis Allo-immunisation Cotraindicated in Thrombotic Thrombocytopenic Purpura: Used only in high risk bleeding Not effective/useful in Immune Thrombocytopenic Purpura: Used only in high risk bleeding

Types of platelet concentrates • Random donor plt concentrate (single unit) – 5, 5 x 1010 plts – 5. 000 -6. 000/mm 3 plt increase after transfusion • Pooled plt concentrate (eg: 6 random units) • Apheresis plts – >3 x 1011 plts – 30. 000 -50. 000/mm 3 increase after transfusion • WBC reduction of platelets is indicated in the same situations like red cells.

Indications for transfusion of blood or its components/products • Fresh frozen plasma ( contains all coag. Factors) – Congenital or acquired coag. Factor deficiency (bleeding or surgery) – Oral anticoagulant overdose – Plasma exchange (eg: TTP) – After massive transfusion – 10 -20 ml/kg : to increase deficient factor level about 20 -30% from baseline

Indications for transfusion of blood or its components/products • Cryoprecipitate – Includes FVIII, v. WF, FXIII, fibrinogen and fibronectin – 80 -120 units of FVIII, ≥ 150 mg fibrinogen and 20 -30 % of FXIII that is in one unit of plasma – Can be used for the purpose of replacing the deficient state of these factors in case of bleeding or surgery

Practical Issues • • • Is there a need for transfusion? Which product should be used? Number of units? Re-check the blood types of the patient and donör and be sure about the cross match Read label, ID, inspect the product Is irradiaton necesssary? Temperature? Filters? Flow rate ? (start 5 ml/min-15 minutes , the rest 200 -500 ml/hr) Drugs ?

Transfusion Reactions • Immunologic reactions • Non-immune reactions or • Acute reactions • Late reactions

Hemolytic reactions • Reasons: Mismatched transfusion Transfusion of hemolysed blood » During storage or warming etc • May be acute or late

Acute hemolytic reaction • Frequency up to 1/25. 000 • 1/600. 000 Tx mortal • 40% symptomatic • ABO mismatch • Ig. M antibodies (anti-A or anti-B) , complement binding and intravascular hemolysis • Early onset ( first 50 -100 ml’s), seldom after 1 -2 hrs – pain at the infusion site, flushing, chest or back pain, dyspnea, vomiting, fever-chills, hypotension and tachicardia, bleeding, hemoglobinuria • Complications: Acute Renal Failure, shock, DIC

Acute hemolytic reaction • Stop transfusion, • Take measures to keep normal BP and urine output: hydration/diuretics, • Re-check groups, re-cross, take blood cultures, • Follow signs of hemolytic anemia, antiglobulin tests, renal function and DIC tests, • Treat accordingly (eg: dialysis/ICU etc)

Delayed hemolytic reaction • 1/2500 -1/6000 • Onset: 3 -21 days after transfusion • Reason: Rh, Kidd etc mismatches – Previous alloimmunization and anamnestic response • Coombs + ( do not confuse with OIHA) • Jaundice or absence of the expected increase in red cell values. • Frequently undetected • Treatment : none

Febrile reactions • 0, 5 - 3% of all transfusions • Cause: Antibodies against white cell/plt/plasma antigens • Fever-chills, increased pulse rate during or after transfusion • Antipyretics/antihistamines • Stop transfusion if there is doupt about hemolysis • Prophylaxis: White cell reduction

Allergic reactions • Cause: Antibodies against donor plasma • • proteins Pruritus, urticaria, edema, anaphylaxis, broncho spasm Ig. A deficient patients are under the greatest risk Treat according to the type of reaction For Ig. A deficient patients: use washed or frozen red cells instead of regular red cells or whole blood.

Pulmonary hypersensitivity reaction/TRALI • 1/5000 frequency • Cause : Leukocyte incompatibility and agglutination of white cells inside the pulmonary vascular area leading to complement activation and endothelial damage- pulmonary edema. • Fever-chills, tachycardia, chest pain, hemoptysis, BP fall within 4 hrs of transfusion • Respiratory support may be necessary

Transfusion Related Graft- versus Host Disease • Cause: Immune deficient recipient transfused with viable lymphocytes which are engrafted and start allo-reaction against mismatched HLA and other antigens of the recipient. • High fatality with skin, liver and gut symptoms, pancytopenia and infections • Prophylaxis: Blood irradiation • Treatment: immunosupressive drugs • Mortality high

Circulatory overload • Old aged or premature/ new borne or patients with cardiopulmonary compromise are under risk. • Clinics: Acute heart failure • Treatment: As acute myocardial failure • Prophylaxis: Slow infusion rate, low volume of transfusion

Bacterial Contamination • Bacterial contamination may cause a reaction with symptoms resembling Acute Hemolytic Reaction without LAB findings of hemolysis. • May be fatal: – Mortality: Plt constr: 1/17. 000 – 1/65. 000 Red cells: <1/700. 000 • Stop transfusion, take cultures, treat with IV fluids and antibiotics , take support measures and follow against shock, renal failure, DIC

Air embolism • May cause acute respiratory and circulatory failure • Clump the tubing • Change the posture of the patient: – Left side / Trandelenburg (left side , headdown, legs upside) – Swan -Ganz catheter

• Patients with bone marrow failure , transfused chronically are under the risk of transfusion hemosiderosis. • Massive transfusion may cause: – Citrate toxicity: Hypocalcemia – Hyperkalemia – Bleeding ( due to thrombocytopenia and /or factor deficiency)

Transfusion transmitted pathogens • • • Hepatitis ( C, B, A , D etc ) HIV HTLV CMV E-Barr HHV Creutzfeldt-Jakob or variant CJD (therotical) Parvovirus • • Malaria Lyme ? (not enough evidence) Chagas Babesiosis Sy Toxoplasmosis West Nil virus