Blood is LIFEBlood is also a Poison Blood Transfusion: Basics and Recent Developments Speaker: Prof. Dr. Manzur Morshed MRCP (UK) Clinical Hematology FCPS, BASICS Blood Products Whole Blood Red cell preparations Platelet products Plasma products leukocyte concentrates . BLOOD COMPONENTS …… RBC products Packed RBCs Leukocyte-poor (Leuco-reduced) red cells Washed RBCs Irradiated RBCs. Platelet products Random-donor platelets Single-donor platelets HLA-matched platelets Leukocyte (granulocyte) concentrates . IX) Albumin Immune globulins .BLOOD COMPONENTS contd. Plasma products Fresh-frozen plasma (FFP) Cryoprecipitate Factor concentrates (VIII.. not whole blood Fresh blood ??? .When transfusion therapy is contemplated: Component.g. Packed RBC. e. the donation needs to be processed and tested.ucsfhealth.Fresh Blood Can Blood be transfused immediately after donation? No. This takes three working days from the date of donation http://www.org/education/donating_blood/ . Packed RBC. e.g. Is extended phenotyping necessary? .T & S.Who is the donor? . not whole blood Fresh blood ??? Ensure safety of blood product .When transfusion therapy is contemplated: Component. k.RBC typing & screening Is extended phenotyping necessary? Extended Phenotype: Patients requiring long-term transfusion therapy (ie. . Here. Thalassemia) often produces an unexpected antibody to one or more red cell antigens (such as K. Jka. Fyb). extended phenotypes help identify the safest product for transfusion. Jkb. Fya. Leucofiltration . e.g.Who is the donor? . Is extended phenotyping necessary? .When transfusion therapy is contemplated: Component.Is product modification necessary? . Packed RBC.Irradiated RBCs and platelets . not whole blood Fresh blood ??? Ensure safety of blood product .T & S.Role of RBC washing . Blood Product Modifications: Washing. Leukofiltration and Irradiation RBCs/Platelets can be washed “to remove antibodies. excess of electrolytes. which may be harmful for some transfusion recipients”. cytokines and occasionally. Patients with Thalassemia Patients with a history of severe allergic reactions to blood components Neonates undergoing exchange/massive transfusion . All transplant or potential transplant patients. e. infants. for persons who may be candidate for marrow transplantation.Prevention of HLA alloimmunization. Leukofiltration and Irradiation Leukocyte-poor red cells .to avoid febrile reactions due to white cell products . All neonates. All chemotherapy patients.g. .Blood Product Modifications: Washing. children & multiparous (≥3 pregnancies) women requiring tx. . Indications: Patients who had 2 mild/moderate or 1 severe febrile reaction.to minimize transmission of viral disease such as HIV or CMV. . transfusion from relatives. Leukofiltration and Irradiation Performed to prevent transfusion-associated graftversus-host-disease (TA-GVHD) Indications: Congenital immune deficiencies.Blood Product Modifications: Washing. HLA-matched platelets. Hodgkin Lymphoma (current or history of). Hematologic malignancies receiving aggressive chemotherapy. BMT recipients. .there may be an indication… . Exchange transfusion in infants for hemolytic disease of newborn In our country….Indications of transfusion Whole blood FWB is unlikely to become an FDA approved therapy Acute hemorrhage with hypovolemia (impending shock): In trauma setting. anemia in malignancy/ after chemo. when cardiac function is compromised . anemia of inflammation) Anemia in elderly patients with angina or congestive heart disease Peri-operative. MDS.or radiotherapy .aplastic anemia. mylofibrosis Anemia of chronic disease (ACD.Indications of transfusion Packed RBCs Thalassemias and other hemoglobinopathies Hypoproliferative anemia . 2 x109/L who failed to response to appropriate antibiotics within 48h of therapy.Indications of transfusion Granulocyte transfusions Patients with documented sepsis (especially Gram negative) with granulocyte count <0. . unless matched Prophylactic: <10.000 Single donor 200-400 ml Equivalent to pool of 6 units random donor No significant benefit over random donor. >50 for procedures.Indications of transfusion Platelet transfusions Stored at room temp Random donor 50-70 ml per unit 6 units should increase plt by 30.000 (<20 if febrile). >80-100 for major surgery Indications and contraindications . Red Cell Transfusion Factors to consider include: The severity of anemia: is it symptomatic? Cause of anemia Patient’s age Presence of underlying cardiac or pulmonary disease or any other co-morbidity . Blood Transfus.Transfusion decisions are often taken – based on limited and frequently low quality evidence an often exaggerated anxiety towards any level of anemia. 11(2): 193–202. . Ref: A new perspective on best transfusion practices Shander et al. Apr 2013. Transfusion Trigger in anemic patients: common mistakes Incidental finding of low Hb and propose transfusion Begin transfusion without trying to identify the cause . A case scenario___ . . dilutional metabolic. pul microembolism) Increased short term mortality .Adverse effects of transfusion Immunologic Infections Volume overload (TACO) Hemosiderosis Rare (hypothermia. severe (anaphylaxis) 3. Post-transfusion purpura 7. Graft-versus-host disease (TA-GVHD) 6.minor (urticaria) .Immunologic effects of transfusion 1. Allergic .delayed 4. Transfusion-related acute lung injury (TRALI) 5. Immune modulation . Febrile transfusion reactions 2. Hemolytic transfusion reactions .immediate . Pre-storage leucodepletion has reduced this risk to in <1% of txs. Paracetamol and antihistamine (avil) . . Slow restart after exclusion of serious differentials.Febrile non-haemolytic transfusion reactions (FNHTR) Cause: Cytokines or donor HLA/ other antigens on granulocytes or platelets reacting to recipient antibodies (as a result of previous tx/ pregnancies). Washed red cells if the patient has recurrent allergic reactions to tx. Antihistamines may be given Restart tx at a slow rate & complete within 4 hours. . Rarely due to donor medication.Minor allergic reactions Cause: Hypersensitivity to allergens or plasma proteins in the transfused unit. adrenaline and steroids as required. Use IgA-deficient or washed RBCs. To prevent recurrence: Consider pre-medication with steroids and antihistamine. if patient is IgA deficient & has anti-IgA . antihistamines. Avoid plasma. Oxygen.Severe allergic reactions (anaphylaxis) IgE antibody interacts with a plasma protein in donated blood. . Hemolytic Transfusion Reaction Recipient’s immune system attacks the RBCs of donor. Acute: ABO mismatch Mortality related to amount of blood transfused. Kidd. Occurs several days to a week after transfusion . Kell. organ failure Delayed: Often directed against Rh. Duffy. infection HLA antibodies in donor plasma leading to destruction of host granulocytes and activation of the complement system leading to lung injury .results in fluid accumulating in the lungs. Hypoxemia. bilateral infiltrates and hypotension (form of ARDS ) developing within 6 hours after transfusion. Major differential includes CHF/volume overload. fever. Treatment is supportive. May include ventilatory support Recovery is usually rapid and complete .TRALI: 3rd most common cause of transfusionrelated death. Host Disease (Ta-GVHD) When donor lymphocytes attack the recipient tissues Develops 4 . Biopsy: satellite dyskeratosis. vomiting.Transfusion Related Graft vs. abnormal LFTs and electrolyte abnormalities. profuse diarrhea. Circulating lymphocytes have a different HLA phenotype from host cells.mainly patients with Hodgkin's disease and leukemia.30 days after transfusion. Also occurs in normal blood recipient when the donor is homozygous for an HLA haplotype and recipient is heterozygous for that haplotype (related donor) Lab: pancytopenia. Fever and a maculopapular rash progressing to erythroderma and toxic epidermal necrolysis. and cough. TGVH is prevented by irradiating blood products . In immunosuppressed recipients . abdominal pain. Other symptoms include anorexia. . . Alloimmunisation to antigens (HPA-1a. GIT. HPA-1b and HLA antigens) have been implicated. the platelet count is expected to rise in 4 days. With IVIG.10 days after transfusion. Multiparous female patients are more affected than males.Post-transfusion purpura (PTP) A reaction where a patient develops sudden & self-limiting thrombocytopenia (<10 x 109/L in 80% of cases). typically 7 . urinary tract bleeding or even Intracranial haemorrhage can occur Patients usually have a history of sensitisation by either pregnancy or transfusion. Immune Modulation ? . parasitic or bacterial infections Circulatory overload can cause heart failure Iron overload (hemosiderosis) .Non-immunological effects of transfusion Viral. malaria.anti-HCV. C.HBsAg. Anti-HBc. NAT. B.VDRL and . . HTLV .HIV ab1 & 2. . CMV. other) CMV EBV HIV Malaria Syphilis Different bacteria Other organisms Infections Safe blood transfusion law. EBV. DNA. approved by the Bangladesh Parliament in 2002 makes it mandatory for all transfusion service centres to screen all donations for 5 transmissible diseases through testing for .Non-immunological effects of transfusion: Hepatitis (A. . RECENT CONCEPTS . . Transfusion situations Surgical: peri-operative Critical Care and Sepsis Coronary disease GI bleeding Other general . the indications for transfusion in the perioperative setting have not been definitively evaluated. Despite the common use of RBC transfusions in surgical patients. .Transfusion in surgical setting • • In the USA. 60 – 70 % of all RBC units are transfused in surgical setting. When the concentration of Hb is < 8-10 gm/100 cc blood.Peri-operative TransfusionIndications: in old days • “This condition. it is wise to give blood transfusion” Adams RC. Anesthesia in cases of poor surgical risk: some suggestions for decreasing the risk. 74:1011–1015 . Lundy JS. Surg Gynecol Obstet 1942. owing to the lowered oxygen carrying capacity of the blood interferes with the adequate transportation of oxygen to the tissues. Peri-operative TransfusionIndications: in recent days NIH Consensus Conference (1988) on Peri-operative RBC Transfusions suggested – Decision to transfuse is based on patient’s clinical condition rather than a given level of Hb blood transfusion of patients with chronic stable anemia is probably unjustifiable if Hb is above 7g per 100ml . . . . 2011 Dec 29.365(26):2453-62.The FOCUS study: Liberal or restrictive transfusion in high-risk patients after hip surgery Carson JL et al N Engl J Med. a liberal transfusion strategy (transfuse RBC to keep the Hb > 10g/dL) or . Outcome: Death or an inability to walk across a room on 60-day follow up. . 2011 Dec 29.a restrictive transfusion strategy (symptoms of anemia or at physician discretion only if hb is < 8 g/dL).365(26):2453-62. 2016 patients ≥ 50 years age history or risk factors for CVD Hb <10g/dL following surgery for hip fracture Intervention: Random assignment to .The FOCUS study: Liberal or restrictive transfusion in high-risk patients after hip surgery Carson JL et al N Engl J Med. did not reduce death rate or inability to walk or reduce in-hospital morbidity in elderly patients at high cardiovascular risk. 2011 Dec 29. 652 units) Liberal tx strategy.866 vs.365(26):2453-62 Tx were 3 times higher in liberal group compared to restrictive group (1. . Observations: This study demonstrates that limiting blood tx in this high-risk patient group is not associated with less favorable outcomes than a liberal tx policy. as compared to restrictive strategy. Rates of other complications similar.The FOCUS study: Liberal or restrictive transfusion in high-risk patients after hip surgery Carson JL et al N Engl J Med. 365(26):2453-62. . 2011 Dec 29. (2) less mixed up transfusions. As the authors found no differences between 2 groups. they put forward the advantages of restrictive transfusion regimes as – (1) less viral infections due to less blood transfusion (hepatitis B/C).The FOCUS study: Liberal or restrictive transfusion in high-risk patients after hip surgery Carson JL et al N Engl J Med. (3) less bacterial infections due to contaminated blood products and (4) less influence on the immune system of the blood recipient and (5) lower costs. Transfusion in Critical Care and Sepsis TRICC trial 1999 ABC trial 2002 Surviving sepsis campaign 2013 TRISS trial 2014 . A MULTICENTER, RANDOMIZED, CONTROLLED CLINICAL TRIAL OF TRANSFUSION REQUIREMENTS IN CRITICAL CARE (TRICC): INVESTIGATORS FOR THE CANADIAN CRITICAL CARE TRIAL GROUP; N Engl J Med 1999;340:409-17 838 critically ill patients were randomly assigned within 72 hours after admission to ICU – 418 patients to a restrictive strategy of tx, in which red cells were transfused if Hb dropped <7g/dl & Hb was maintained at 7 to 9g/dl and 420 patients to a liberal strategy, in which tx was given when Hb fell <10g/dl & Hb was maintained at 10 to 12g/dl. TRICC Trial of 838 patients Hebert, NEJM, 1999 A MULTICENTER, RANDOMIZED, CONTROLLED CLINICAL TRIAL OF TRANSFUSION REQUIREMENTS IN CRITICAL CARE (TRICC): INVESTIGATORS FOR THE CANADIAN CRITICAL CARE TRIAL GROUP; N Engl J Med 1999;340:409-17 30-day mortality: Subgroup analyses demonstrated that a restrictive transfusion strategy was associated with significantly lower mortality in patients with APACHE II score ≤20 and age <55 years. . 0% vs 14.1% (no tx).9%. Both ICU and overall mortality were significantly higher in patients who had vs had not received a tx ICU mortality rates: 18. 2002. P<. For similar degrees of organ dysfunction. P<. The mean pretransfusion Hb was 8.288:1499–1507 3534 patients from 146 W. Vincent JL et al JAMA.5% (tx) vs 10. Overall mortality rates: 29. patients who had a transfusion had a higher mortality rate.001. European ICUs.3 g/dl. This effect again was clear with more than 2 RBC units transfused .ABC trial in Europe Anemia and blood transfusion in critically ill patients.001. Followed up for 28 days or until hospital discharge/ death.4 ± 1. . After that. 2012 R. .Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock. Intensive Care Medicine. pp 165-228 Surviving Sepsis Campaign recommendations regarding blood transfusion in patients with septic shock: Transfusion to maintain a hct of > 30% in the presence of hypoperfusion in the first 6 hours. severe hypoxemia. Issue 2. February 2013. P. or ischemic CAD. aiming at levels between 7g & 9g/dl in patients who do not have myocardial ischemia. Dellinger et al. Volume 39. hemorrhage. the transfusion threshold should be a Hb of <7g/dl. or in the numbers of days alive & out of the hospital between the groups. RESULTS: No differences in mortality at 90 days. with older age. . Similar results were observed in subgroups of patients with chronic cardiovascular disease. 371:1381-1391. or with greater disease severity.& 496 in higher-threshold group) patients with septic shock . 2014 998 ICU (502 in lower. October 9. randomized TRISS trial N Engl J Med 2014.Multicenter. {≤7 g /dl (lower threshold) or ≤9 g /dl (higher threshold)}. in the numbers of patients with ischemic events or in the use of life support. Transfusion in coronary disease . 1001/jama.13.292(13):1555-1562. doi:10. 2004.1555 .292.Relationship of Blood Transfusion and Clinical Outcomes in Patients With Acute Coronary Syndromes JAMA. .1001/jama... doi:10. 2004.1555 Conclusions Blood transfusion in the setting of acute coronary syndromes is associated with higher mortality. . and this relationship persists after adjustment for other predictive factors and timing of events. .292. We suggest caution regarding the routine use of blood transfusion to maintain arbitrary hematocrit levels in stable patients with ischemic heart disease.Relationship of Blood Transfusion and Clinical Outcomes in Patients With Acute Coronary Syndromes JAMA.13.292(13):1555-1562. 956 patients undergoing CABG and valve surgery at 3 European University Hospitals. Interact Cardiovasc Thorac Surg. 2014. Mariscalco G et al.Red blood cell transfusion is a determinant of neurological complications after cardiac surgery. Nov 2. The prognostic impact of RBC transfusion on postoperative stroke and TIA was investigated. . CONCLUSIONS: Transfusion of more than 2 units of RBCs after cardiac surgery is associated with a significantly increased risk of postoperative stroke and TIA. 14. Randomization was stratified according to the presence or absence of liver cirrhosis. a restrictive strategy significantly improved outcomes in patients with acute upper GI bleeding. CONCLUSIONS: As compared with a liberal transfusion strategy. N Engl J Med 2013. 368:11-21 January 3.Transfusion Strategies for Acute Upper GI Bleeding Càndid Villanueva et al. . 2013 921 patients with severe acute upper GI bleeding: 461 assigned to a restrictive strategy (tx if Hb <7 g/dl) 460 to a liberal strategy (tx when the Hb fell <9 g/dl). Restrictive transfusion strategies were associated with a statistically significant reduction in the rates of infection. Carless PA et al. .Transfusion thresholds and other strategies for guiding allogeneic red blood cell transfusion.(10):CD002042 • • 17 trials involving a total of 3746 patients. Restrictive transfusion strategies reduced the risk of receiving a RBC transfusion by a relative 37%. the data may constitute a stronger basis for avoiding transfusion. The existing evidence supports the use of restrictive transfusion triggers in patients. 2010 Oct 6. Cochrane Database Syst Rev. In countries with inadequate screening of donor blood. Take home message 1. Cause of anemia should be identified before deciding to transfuse a patient . 5. infection screening extended phenotyping Leucofiltration Blood product irradiation Whole blood transfusion should be avoided if possible Blood from near relatives should be avoided Increased mortality is a real concern after transfusion of blood products. We should be aware of the limitations in transfusion facilities in our hospitals that compromise the quality of blood products 2. 4. 3. William Osler Thank you .... One of the first duties of the physician is to educate the masses not to take medicine.Last word….