blood and blood components in medicine.pptx

components of blood, blood transfusion reactions and its management

1. BLOOD AND BLOOD COMPONENTS Dr G.VENKATA RAMANA MBBS DNB FAMILY MEDICINE

2. BLOOD COMPOSITION Blood flows throughout the body in the vascular system, and consists of: 1 . Formed elements R ed cells , which transport oxygen from the lungs to the tissues W hite cells , which defend against infection P latelets , which interact with blood vessels and clotting factors to maintain vascular integrity and prevent bleeding 2 . Plasma C ontains proteins with many functions, including antibodies and coagulation factors

3. BLOOD AND BLOOD COMPONENTS Whole blood Packed RBCs Platelets Fresh-frozen plasma (FFP) Cryoprecipitate Plasma derivatives Coagulation factors : Concentrates of factors VIII and IX Immunoglobulins : Intravenous immunoglobulin G ( IVIgG ), Anti-Rhesus D immunoglobulin Human albumin : 5% solution, 20% solution

4. BLOOD COMPONENTS COLLECTION The procedure consists of initial centrifugation at low speed to separate whole blood into two parts: Packed RBCs and platelet-rich plasma (PRP ) Subsequently, PRP is centrifuged at high speed to yield two parts: Random donor platelets and FFP Cryoprecipitates are obtained by thawing of FFP followed by centrifugation Apheresis is the technique of direct collection of large excess of platelets from a single donor

5. Whole Blood Before centrifugation After centrifugation

6. Composition of blood bag ANTI- COAGULANTS FULL FORM SHELF LIFE ACD ACID CITRATE DEXTROSE 21 DAYS CPD CITRATE PHOSPHATE DEXTROSE 21 DAYS CPD A CITRATE PHOSPHATE DEXTROSE + ADENOSINE 35 DAYS SAGM SODIUM ADENINE GLUCOSE MANNITOL (Longest shelf life) 42 days

7. Functions of the components of blood bag COMPONENT FUCNTION CITRATE Anti-coagulant by chelating calcium PHOSPHATE Acts as buffer & helps in maintaining pH DEXTROSE Provides nutrition ADENINE Provides substrate for ATP synthesis (increased shelf life)

8. Whole blood Shelf life  35 days Average unit of blood 350+49 or 450ml+63ml anticoagulant Both red cell and plasma component can be prepared Indication Acute hypovolemic coagulopathy requiring massive transfusion Rarely used now a days

9. Packed RBCs Types Leukoreduced Irradiated Saline washed

10. Leuko reduced RBC Prepared by removing a proportion of the plasma from leucocyte depleted whole blood Chances of a febrile reaction can be reduced Indications Chronically transfused patients Potential and transplant recipients Patients with previous febrile non hemolytic transfusion reactions

11. Irradiatied RBC   RBC units can be irradiated prior to transfusion by subjecting them to 2500 cGy of irradiation, targeted to the central portion of the component, with a minimum dose of 1500 cGy delivered to any part of the component Irradiation sources include gamma rays from either a cesium-137 or cobalt-60 blood irradiator or x-rays using a standalone machine Viable donor lymphocytes can attack recipient cells in individuals who are unable to mount an immune response against them, causing transfusion-associated graft-versus-host disease ( ta-GVHD) Ta-GVHD can target all hematopoietic cells as well as other tissues, leading to bone marrow aplasia and other complications that are ultimately fatal Irradiation is used to prevent ta-GVHD in at-risk individuals

12. Indications Recipients of intrauterine or neonatal exchange transfusion; premature neonates Individuals with congenital cell-mediated immunodeficiency states Individuals treated with specific types of potent immunosuppressive therapies (purine analogs, antithymocyte globulin [ATG], certain monoclonal antibodies); this may include those being treated for non-Hodgkin lymphoma (NHL) or other hematologic malignancies Recipients of hematopoietic stem cell transplant (autologous or allogeneic) Individuals with Hodgkin lymphoma (any stage of disease) Individuals at risk for partial HLA matching with the donor due to directed donations, HLA-matched products, or genetically homogeneous populations

13. Washed red cells Units of RBCs can be washed to reduce or eliminate complications associated with the small amount of residual plasma in the unit I ndications Severe or recurrent allergic reactions ( eg , hives) associated with red cell transfusion IgA deficiency with circulating anti-IgA antibodies that react with IgA in the donor plasma, when an IgA-deficient donor is not available. Frozen deglycerolized red cells may be the component of choice for these individuals Individuals at risk for hyperkalemia Washing is done in an automated system using 0.9 percent sodium chloride immediately before infusion The shelf-life of washed blood is four hours at 20 to 24°C or 24 hours if stored at 1 to 6°C Frozen deglycerolized RBC units also undergo extensive washing and can be used for the same indications

14. Platelets Collection methods Apheresis (single donor) platelets Whole blood derived (WBD) pooled platelets Means of collection and content of a unit  A unit of whole blood derived (WBD) platelets contains approximately 7 x 10 10  platelets, and four to six of these units are typically pooled for transfusion Apheresis platelets are collected from a single donor and contain approximately 3 to 4 x 10 11  platelets (the equivalent of a pool of four to six WBD units)

15. Apheresis (single donor) platelets   Collected from volunteer donors in a one to two-hour apheresis procedure Platelets are selectively removed along with some white blood cells (WBCs) and plasma, and most red blood cells (RBCs) and plasma are returned to the donor Some systems will also remove the majority of WBCs, resulting in a leukodepleted product Advantages E xposure of the recipient to a single donor rather than multiple donors A bility to match donor and recipient characteristics such as human leukocyte antigen (HLA) type, cytomegalovirus (CMV) status, and blood type

16. Whole blood derived (WBD) pooled platelets A single unit of platelets can be isolated from a whole blood donation by centrifuging the blood within the closed collection system to separate the platelets from the red blood cells (RBCs ) Two manufacturing methods are used The platelet rich plasma (RPR) method It involves the centrifugation of the whole blood first under a sufficient g-force to pellet the RBCs (the "soft spin") but leaves most of the platelets in suspension in the RPR The PRP is then centrifuged again in a second container at a higher g-force to pellet the platelets (the "hard spin ") The supernatant platelet-poor plasma is removed The platelets are then resuspended in the residual plasma and stored

17. The buffy coat method In this method, whole blood is first subjected to a hard spin to allow plasma to be expressed off the top and the sedimented RBCs to be expressed off the bottom, leaving behind the platelet-containing buffy coat Several buffy coat units can then be pooled together with plasma or platelet additive solution, and the pool is subjected to a soft spin to sediment the residual RBCs The pooled platelet concentrate is then expressed off the RBCs and store Advantages of WBD platelets Lower cost and ease of collection and processing Disadvantage of WBD platelets Recipient exposure to multiple donors in a single transfusion and the increased work of bacterial testing In addition, it is more labor intensive and time consuming to perform the required bacterial testing

18. INDICATIONS FOR PLATELET TRANSFUSION Actively bleeding patients with thrombocytopenia Preparation for an invasive procedure  if the thrombocytopenia is severe Neurosurgery or ocular surgery – <100,000/ microL Most other major surgery – <50,000/ microL Endoscopic procedures – <50,000/ microL for therapeutic procedures; 20,000/ microL for low risk diagnostic procedures Bronchoscopy with bronchoalveolar lavage (BAL) – <20,000 to 30,000/ microL Central line placement – <20,000/ microL Lumbar puncture <10,000 to 20,000/ microL in patients with hematologic malignancies <40,000 to 50,000 in patients without hematologic malignancies Neuraxial analgesia/anesthesia – <80,000/ microL Bone marrow aspiration/biopsy – <20,000/ microL

19. Prevention of spontaneous bleeding   Afebrile patients with platelet counts <10,000/ microL due to bone marrow suppression For patients with fever, infection, or inflammation,transfuse at a platelet count ≤15,000 to 20,000/ microL due to the increased risk of bleeding Patients with acute promyelocytic leukemia (APL) have a coexisting coagulopathy, transfuse at a platelet count ≤30,000 to 50,000/ microL

20. Storage Room temperature, because cold induces clustering of von Willebrand factor (WVF) receptors on the platelet surface and morphological changes of the platelets, leading to enhanced clearance by hepatic macrophages and reduced platelet survival in the recipient S helf life 5 days Dose Adults one WBD unit per 10 kg of body weight, which translates to four to six units of WBD platelets or one apheresis unit P ediatric dose is 5 to 10 mL/kg

21. Infusion rate For an average-sized adult, six units of WBD platelets or one unit of apheresis platelets are transfused over approximately 20 to 30 minutes Patients at risk for transfusion-associated circulatory overload (TACO) can be transfused at a slower rate as long as the transfusion is completed within four hours of issuance from the blood bank Complications of platelet transfusion Both WBD and apheresis platelets contain some WBCs that were collected along with the platelets These WBCs can cause febrile nonhemolytic transfusion reactions (FNHTR), alloimmunization , transmission of CMV, or transfusion-associated graft-versus-host disease (TA-GVHD) in some patients

22. Complications Platelet products are suspended either in plasma or in platelet additive solution, which reduces the plasma volume by approximately one-third Because of their plasma content, transfused platelets can cause adverse reactions including transfusion-related acute lung injury (TRALI) and anaphylaxis Platelets concentrates also contain a small number of RBCs that express Rh antigens on their surface (platelets do not express Rh antigens ) Avoid giving platelets from RhD -positive donors to RhD -negative females of childbearing potential because of the potential risk of RhD alloimmunization and subsequent hemolytic disease of the fetus and newborn (HDFN)

23. Fresh Frozen Plasma (FFP) P repared from single units of whole blood or from plasma collected by apheresis techniques. F rozen at -18 to -30°C within eight hours of collection and, when appropriately stored, is usable for one year from the date of collection Volume of approximately 200 to 250 mL J umbo units - 600 mL C ontains all of the coagulation factors and other proteins present in the original unit of blood, slightly diluted by the citrate-containing anticoagulant solution used to collect the blood

24. Indications Massive transfusion Severe liver disease or DIC Rare clotting factor deficiencies Therapeutic plasma exchange inTTP Warfarin overdose if not corrected by vitamin k and/or PCC ,depending on the clinical setting DOSE AND INFUSION RATE   10 to 15 mL/kg ( ie , approximately three to five units) in most adults Healthy individual – 2 to 3 mL/kg/hour Individual with volume overload or heart failure – 1 mL/kg/hour Individual undergoing plasma exchange – 60 mL/minute

25. ABO MATCHING Due to the normal presence of A and/or B alloantibodies in patients with blood types A, B, and O, donor plasma must be either ABO- identical  or ABO- compatible  with the recipient A patient with type A blood can accept plasma from donors who are type A (identical) or type AB (compatible). A patient with type B blood can accept plasma from donors who are type B (identical) or type AB (compatible). A patient with type O blood can accept plasma from donors who are type O (identical) or types A, B, or AB (compatible). A patient with type AB blood can only accept plasma from donors who are type AB (identical )

26. RISKS Febrile and allergic reactions Volume overload (TACO ) Transfusion-related acute lung injury (TRALI)  Anaphylactic reactions  Infection

27. Cryoprecipitate &Fibrinogen concentrate Composition   Cryoprecipitate is manufactured using already frozen Fresh Frozen Plasma (FFP) or Plasma Frozen Within 24 Hours After Phlebotomy (PF24), thawing, and concentrating the proteins that precipitate It contains fibrinogen (factor I), factor VIII, fibronectin , factor XIII, and von Willebrand factor ( VWF) Pathogen-inactivated (PI) Cryoprecipitate is made from PI plasma Fibrinogen concentrate  is purified from pooled human plasma using several purification steps and heat treatment

28. Indications Congenital fibrinogen disorders Cardiac surgery Postpartum hemorrhage Trauma and massive transfusion  DIC L iver disease Kidney disease Contraindications   Cryoprecipitate and fibrinogen concentrate  have no role in treating bleeding due to thrombocytopenia, platelet dysfunction, or anticoagulation Cryoprecipitate is generally not used for conditions for which a purified or recombinant factor concentrate is available

29. Dose of cryoprecipitate For most adults , between 5 and 10 units ABO compatible Infusion rate 2 to 5 mL per minute Adverse effects Transfusion - transmitted infection Volume overload Hemolytic transfusion reactions Thromboembolic events Allergic reactions

30. BLOOD DONATION Blood donations are obtained by either venesection of a unit of whole blood or collection of a specific component, such as platelets, by apheresis During apheresis, the donor’s blood is drawn via a closed system into a machine that separates the components by centrifugation and collects the desired fraction into a bag, returning the rest of the blood to the donor

31. Screening of blood Donated blood should be screened for: HIV Hepatitis B Hepatitis C Malaria Syphilis Testing for Trypanosoma cruzi in South America and the United States Tests for West Nile virus in United States and UK Platelet concentrates may be tested for bacterial contamination Hepatitis C: Most common transfusion transmitted infection Malaria can be transmitted by all blood products

32. BLOOD DONATION

33. Blood products Start transfusion Complete transfusion Whole blood With in 30minutes of removing from refrigerator ≤ 4 hours PRBC With in 30minutes of removing from refrigerator ≤ 4 hours Platelet concentrate Immediately With in 30 minutes FFP As soon as possible With in 30 minutes Cryoprecipitate As soon as possible With in 30 minutes

34. Blood Transfusion Reactions

35. Acute hemolytic transfusion reaction Typical time course : During transfusion or within 24 hours of transfusion completion Mechanism: ABO incompatibility (Type 2 Hypersensitivity ) Pre existing high affinity IgM antibodies rapidly induce competent mediated lysis , intra vascular hemolysis, and hemoglobinuria Clinical findings Fever,chills,chest pain,back pain tachypnea,tachycardia , hypotension, DIC , acute renal failure Laboratory findings Hemoglobinemia , hemoglobinuria , positive direct antiglobulin (Coombs) test (may be negative if all cells have hemolyzed ), findings of DIC (prolonged PT, prolonged aPTT , low fibrinogen, thrombocytopenia)

36. Implicated products RBCs, plasma (much less common), rarely platelets Incompatible blood product (typically ABO incompatible due to clerical error) Treatment Supportive Vigorous hydration with isotonic saline and diuretics to maintain urine output In patients with DIC and severe bleeding, PC, plasma, and cryoprecipitate or fibrinogen may be required

37. Febrile non-hemolytic transfusion reaction Typical time course: During transfusion or within 4 hours of transfusion completion Mechanism : Interaction between donor leukocytes and recipient antibodies leads to interleukin-1 release from donor leucocytes  PGE2 production  fever Causes : P roinflammatory cytokines in the BC or by recipient Abs directed against donor cell Ags present in the BC Clinical findings : Fever Laboratory findings : None Implicated products : All blood products, but plasma is much rare Prevention : Prestorage l eukocyte reduction

38. Allergic transfusion reaction Typical time course During transfusion or within 4 hours of transfusion completion Mechanism: Allergic reactions are related to plasma proteins found in transfused components Reciepient IgE against donor components causing mast cell activation Clinical findings Rash , pruritus, urticaria , and localized edema Laboratory findings : None  Implicated products : All blood products Treatment : A ntihistamines, steroids

39. Anaphylactic transfusion reaction Typical time course During transfusion or within 4 hours of transfusion completion Clinical findings Hypotension, angioedema, wheezing, respiratory distress Laboratory findings Hypoxemia, IgA deficiency, anti-IgA Implicated products RBCs, platelets, plasma products Treatment Adrenaline 0.01mg/kg ,0.5mg IM in to the mid-outer thigh Additional treatment with steroids, antihistamine drugs, and bronchodilators may also be required

40. Transfusion-related acute lung injury (TRALI) Typical time course During transfusion or within 6 hours of transfusion completion Recipient factors associated with an increased risk of TRALI include smoking, chronic alcohol use, shock, liver surgery (transplantation), cancer surgery, mechanical ventilation, and positive fluid balance Pathophysiology Transfusion of antibodies and or/ other non immunologic mediators to a susceptible patient HLA class I,HLA class II and HNA 5,7 antibodies These antibodies activate the leucocytes,which bind to the endothelium in the lungs,causing endothelial injury and edema

41. Transfusion-related acute lung injury (TRALI) Clinical findings Respiratory distress, hypotension Laboratory findings Abnormal chest radiography, hypoxemia, transient leukopenia, anti-neutrophil or anti-HLA antibodies (if tested) Implicated products RBCs, platelets, plasma products Treatment Supportive Oxygen Mechanical Ventilation if required

42. Transfusion-associated circulatory overload ( TACO) Typical time course During transfusion or within 12 hours of transfusion completion Risk factors O lder age, renal failure , preexisting fluid overload, cardiac dysfunction, administration of a large volume of BCs, and an excessive rate of transfusion in relation to the patient’s hemodynamic tolerance Pathophysiology Too much fluid is added to the system too quickly for the transfusion recipient Clinical findings Respiratory distress, rales

43. Transfusion-associated circulatory overload (TACO) Laboratory findings Abnormal chest radiography, hypoxemia, increased BNP or NT- proBNP Implicated products RBCs, platelets, plasma products, and other fluids Treatment Stoppage of transfusion,Oxygen , Diuretics (furosemide) Prevention Identifying at-risk patients, close monitoring, a slow transfusion rate (1 RBCC over 3–4 h), and use of diuretics in hemodynamically stable patients with a history of TACO

44. Sepsis/bacterial infection Typical time course During transfusion or within 72 hours of transfusion completion Clinical findings Fever, chills, hypotension, DIC Laboratory findings Bacteremia, leukocytosis, findings of DIC Implicated products Platelets most commonly implicated, but can be any product Product may show bacterial contamination Treatment Broad spectrum antibiotics after sending cultures Prevention Pathogen reduction of platelets and plasma, and perhaps soon of RBCs as well, offers an additional means of reducing transfusion infection risks

45. Delayed Hemolytic Transfusion Reaction Onset A fter 24hrs ( usually 2 weeks) Mechanism Recipients have prior exposure to RBC antigens After the transfusion, anamnestic response results in antibody production Typically caused by I gG antibodies to foreign protein antigens and are associated with laboratory features of hemolysis Presentation Mild fever, hemolytic anemia, Coomb’s test-positive Management Supportive care

46. Post transfusion Purpura Rare reaction (~1/105 BCs) Thrombocytopenia-related bleeding disorder developing 5–12 days after PC (and more rarely RBCC) transfusion, predominantly in women Platelet-specific alloAbs are found in the recipient, most frequently anti-HPA-1a in HPA-1a-negative alloimmunized individuals The delayed thrombocytopenia is due to a secondary increased production of alloAbs The mechanisms for the destruction of the patient’s own platelets remain unclear

47. Post transfusion Purpura Management Supportive Polyvalent immunoglobulin Steroids Plasma exchange Additional platelet transfusions may worsen the thrombocytopenia or be associated with poor increments Prevention Use of washed BCs or BCs from HPA-compatible donors

48. Graft-Versus-Host Disease Extremely rare adverse reaction Mediated by engrafted donor T lymphocytes in a recipient unable to reject such allogenic lymphocytes (as in severely immunosuppressed patients or patients homozygous for an HLA haplotype shared with the donor) Such donor T lymphocytes interact with host HLA Ags and mount an immune response, which is manifested clinically by the development, of cytopenia , fever, a characteristic skin rash, diarrhea, and liver function abnormalities 5–10 days after transfusion H ighly resistant to treatment with immunosuppressive therapies as well as ablative therapy followed by allogeneic bone marrow transplantation and is fatal in >90% of cases. Prevention in at-risk patients I rradiation of cellular BCs (minimum of 25 Gy ) or treating BCs with pathogen reduction technology that will deplete all living cells in the component

49. Iron overload Each unit of RBCs contains 200–250 mg of iron In frequently transfused recipients, iron accumulation that is left untreated will affect endocrine, hepatic, and cardiac function Death may occur from cardiac failure or arrhythmia Iron overload can be assessed by means of serum ferritin measurements, magnetic resonance imaging , and liver biopsy Prevention and treatment Careful monitoring and iron chelation

50. MASSIVE BLOOD TRANSFUSION Transfusion of ≥10 units of whole blood (WB) or packed red blood cells ( pRBCs ) in 24 hours ≥ 3 units of pRBCs in one hour ≥ 4 blood components in 30 minutes Indications :Trauma , cardiac surgery, obstetric bleeding, and liver disease Monitoring   : Attention must be paid to hemoglobin, platelet count, hemostasis, and metabolic status This includes complete blood count (CBC) with platelet count after each 5 units, along with coagulation testing Standard tests of coagulation include the prothrombin time (PT), activated partial thromboplastin time ( aPTT ), and fibrinogen concentration Ionized calcium and other metabolic parameters should be monitored and treated systematically

51. Complications of massive blood transfusion Hemostatic   Plasma (2 to 8 units) is transfused if the PT or aPTT exceed 1.5 times the control value due to dilutional coagulopathy Platelets (1 apheresis unit or 6 units of WB-derived platelets) are transfused if the platelet count decreases to <50,000/ microL Cryoprecipitate or  fibrinogen concentrate  can be used for fibrinogen <100 mg/ dL (<200 for obstetric bleeding ) Hypothermia   Rapid transfusion of BCs still at 4°C can result in hypothermia and cardiac dysrhythmias Use of an inline warmer will prevent this complication

52. Complications of massive blood transfusion Metabolic   Hypocalcemia can be caused by citrate toxicity S ymptomatic hypocalcemia is treated with intravenous  calcium chloride  or  calcium gluconate (2 to 5 mL of a 10 percent calcium chloride solution per unit of WB or pRBCs plus plasma; maximum 10 mL ) RBC leakage during storage, longer storage, and irradiation increase the concentration of potassium in the unit Neonates and patients with renal failure or other comorbidities (e.g., hyperglycemia or hypocalcemia ) are at risk of hyperkalemia and resulting acute cardiac toxicity Treatment includes insulin, glucose, calcium gluconate , and furosemide

53. Prevention I ncludes the use of washed or plasma-reduced RBCCs or a storage age of <7–10 days and the avoidance of RBCCs stored for >24 h after irradiation For individuals treated with blood component resuscitation, a ratio of 1:1:1 (plasma to platelets to pRBCs ) to prevent complications of massive transfusion

54. ALTERNATIVES AND PERSPECTIVES Erythropoietin S timulates erythrocyte production in patients with anemia from chronic renal failure and other conditions, thus avoiding or reducing the need for transfusion Thrombopoietin receptor agonists Reduce platelet transfusion needs resulting from chemotherapy-induced thrombopenia Gene therapy In patients with sickle cell or major thalassemia offer the potential of dramatically reducing their transfusion needs Stem cell–derived blood cells such as RBCs or platelets may in the future become a suitable alternative to rare blood donors

55. Blood substitutes