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BLOOD COMPONENT THERAPY Dr. Gagan pal singh SR, Cardiac Anaesthesia Max Devki Devi Heart & Vascular Institute, New Delhi


HISTORY 1628- Sir William Harvey described venous circulation 1665- Richard Lower performed first animal to animal blood transfusions in a dog in london 1667- Jean-Baptiste Denis in France reported successful transfusions of lamb’s blood to humans

History : 

History 1818 - James Blundell, a British obstetrician, performed the first successful transfusion of human Blood for the treatment of postpartum hemorrhage. Considered to be Father of Autotransfusion He also devised various instruments for performing Blood transfusions.

Further Developments : 

Further Developments 1901 –Karl Landsteiner, an Austrian physician, documented the first three human blood groups A, B and O. 1902 - A fourth main Blood type, AB was found by A. Decastrello and A. Sturli. 1914 - Long-term anticoagulants, among them sodium citrate, were developed, allowing longer preservation of Blood. 1926 - The British Red Cross instituted the first human Blood transfusion service in the world.

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1940 - Freeze dried plasma was developed. 1940 - Edwin Cohn developed a cold ethanol fractionation proces. Albumin, Gamma globulin and Fibrinogen were isolated and became available for clinical use. 1950 - Glycerol cryoprotectant for freezing red blood cells. 1950 - Carl Walter and W. P. Murphy introduced the plastic bag for blood collection.

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1954 – The blood product Cryoprecipitate was developed for people suffering from hemophilia. 1960 - A. Solomon and J. L. Fahey reported the first therapeutic plasmapheresis procedure. 1972 - Apheresis was used to extract one cellular component. 1979 - A new anticoagulant preservative, CPDA-1, which extends the shelf life of whole Blood and red Blood cells to 35 days is introduced.


AVAILABLE PRODUCTS Whole Blood Packed Red Cells Red Cell Aliquots Irradiated Red Cells Leukoreduced Red Cells Frozen Deglycerolized Red Cells Platelet Concentrate Random Donor Platelets Single Donor Platelets


PRODUCTS…. Plasma Fresh Frozen Plasma Single Donor Plasma Solvent Detergent Plasma IgA Deficient Fresh Frozen Plasma Cryoprecipitate Granulocyte concentrates Plasma derivatives CMV-negative blood products

Whole Blood : 

Whole Blood 450 ml of blood 63 ml of anticoagulant solution. Hct-36-44% No components have been removed. Store at 1-6 oC Shelf life- Citrate-Phophate-Dextrose (CPD) - 21 days CPDA-1 (adenine) - 35 days AS-1, AS-3, AS-5 – 42 days Administer through standard blood filter (150-280 micron) Infuse within 4 hours of issue

Whole Blood : 

Whole Blood Drawbacks: After storage for >24 hours, platelets and WBC are non-functional Factor V and VIII (labile factors) decrease with storage Fluid overload Indications: Acute blood loss > 25% TBV

Packed Red Cells : 

Packed Red Cells Made by spinning whole blood and expressing off the supernatant 200 mL red blood cell volume. Hct ~70%. Do not provide viable platelets or coagulation factors. One unit ↑Hb by 1 g/dl or ↑Hct 3%. Must be ABO & Rh compatible Stored at 1-6 oC Shelf-life: 21 days (CPD) 35 days (CPDA-1) 42 days AS-1

ASA Guidelines forTransfusion of Packed Red Cells in Adults : 

ASA Guidelines forTransfusion of Packed Red Cells in Adults Transfusion for patients on cardiopulmonary bypass with hemoglobin level ≤6.0 g/dL is indicated. Hemoglobin level ≤7.0 g/dL in patients >65 years and patients with chronic cardiovascular or respiratory diseases justifies transfusion. For stable patients with hemoglobin level between 7 and 10 g/dL, the benefit of transfusion is unclear. Transfusion is recommended for patients with acute blood loss more than 1,500 mL or 30% of blood volume. Evidence of rapid blood loss without immediate control warrants blood transfusion. *Ann Thorac Surg 2007;83:S27–86

Red cell aliquots : 

Red cell aliquots For babies 10-25 mL units. 5 mL/kg will raise Hb by ~1 gm/dL.

Irradiated Red Cells : 

Irradiated Red Cells Gamma-radiated to kill the lymphocytes. The lack of T-cells prevents graft-vs-host disease. Use for Severely immunocompromised patients Lymphoma patients Stem-cell / marrow transplants Intrauterine transfusion Units from close “blood relatives” Neonates undergoing exchange transfusion or ECMO Hodgkin’s Disease

Leukoreduced red cells : 

Leukoreduced red cells 99.9% of white cells filtered out by freezing-thawing-washing technique. Reduces febrile reactions Reduces HLA alloimmunization Effective in reducing CMV & CJD transmission Cellular immune function preservation Does NOT prevent GVHD

Frozen Deglycerolized Red Cells : 

Frozen Deglycerolized Red Cells RBCs are glycerolized and frozen < -65 oC for as long as 10 years Good only for 24 hours after thawing Deglycerolization washes away plasma and WBC Reduces FNHTR, allergic reactions and CMV risk Advantages Blood of rare types can be stored for long periods Reduce risk of transfusion hepatitis Safer in massive blood transfusion Prompt tissue oxygenation Does not prevent GVHD

Platelet concentrate ( Random Donor Platelets) : 

Platelet concentrate ( Random Donor Platelets) Differential centrifugation from freshly drawn blood units Volume- 60ml Store at 20-24 oC with constant & gentle agitation Use within 5 days Bacterial contamination a problem 1unit raise the platelet count by 5k-10k/microliter. ABO matched platelets preferable

Single-donor platelets : 

Single-donor platelets Obtained by plateletpheresis technique. 6 - 8 times as many platelets as in a random-donor unit. Larger volumes and HLA-compatibility results in an increase of 30k-60k. Leukoreduced because of apheresis collection  ABO matched platelets preferable Rh negative receive Rh negative platelets

ASA Recommendations : 

ASA Recommendations Prophylactic platelet transfusion is ineffective and rarely indicated when thrombocytopenia is due to increased platelet destruction (e.g., ITP) Prophylactic platelet transfusion in surgical patients rarely indicated when the platelet count is >100 x 109 /l usually indicated when the count is <50 x 109 /l. with intermediate platelet counts (50-100 x 109 /l) - based on the risk of bleeding

ASA Recommendations…. : 

ASA Recommendations…. Surgical and obstetric patients with microvascular bleeding usually require transfusion if the platelet count is <50 x 109 /l rarely require therapy if it is >100 x 109 /l With intermediate platelet counts (50-100 x 109 /l)-based on the patient's risk for more significant bleeding Vaginal deliveries or operative procedures ordinarily associated with insignificant blood loss may be undertaken in patients with platelet counts less than 50 x 109 /l Platelet transfusion may be indicated despite an apparently adequate platelet count if there is known platelet dysfunction and microvascular bleeding.

Fresh Frozen Plasma : 

Fresh Frozen Plasma Prepared from blood within 8 hrs of donation Rich in the clotting factors V & VIII, proteins C and S, complement, and immunoglobulins. Good for 24 hours post thaw Then it can be stored for 5 days as liquid plasma (labile factors V and VIII decreased) Shelf life: 1 year

Indications for FFP Transfusion : 

Indications for FFP Transfusion Urgent reversal of warfarin therapy Correction of known coagulation factor deficiencies for which specific concentrates are unavailable Correction of microvascular bleeding in the presence of elevated (> 1.5 times normal) PT or PTT Correction of microvascular bleeding secondary to coagulation factor deficiency in patients transfused with more than one blood volume and when PT and PTT cannot be obtained in a timely fashion

FFP : 

FFP Dose 10-15 ml/kg of FFP For warfarin reversal, 5-8 ml/kg of FFP FFP is contraindicated for augmentation of plasma volume or albumin concentration.

Single Donor Plasma : 

Single Donor Plasma Prepared from stored blood Poor in coagulation factors Cannot be used to correct coagulation factor deficiencies Effective as volume expander

Solvent- Detergent Plasma : 

Solvent- Detergent Plasma Plasma from multiple donors is pooled Added a mixture of solvent (tri-n-butyl phosphate) & detergent (Triton X-100) Inactivate lipid enveloped infectious agents Disadvantages: Risk of contamination of nonenveloped agents Expensive

Other Types : 

Other Types Donor Retested Single Donor Plasma IgA Deficient Fresh Frozen Plasma

Cryoprecipitate : 

Cryoprecipitate Plasma concentrate, rich in fibrinogen, factor VIII, vWF, factor XIII & fibronectin Volume- 15ml/unit 1 unit contains100 clotting units of Factor VIII and 250 mg of fibrinogen Stored frozen at <-18 oC Infuse within 6 hrs of thawing Adult dose is 10 units or 1U/10kg

Indications : 

Indications Fibrinogen <40 mg/dl Fibrinogen <100 mg/dl with bleeding or surgery DIC in obstetric patient Abnormal fibrinogen Factor XIII deficiency vwD with bleeding or surgery

Granulocyte Concentrate : 

Granulocyte Concentrate Obtained by apheresis from family members for administration to cancer patients. Contain 1.0 x 1010 granulocytes Pre-treatement with recombinant G-CSF and dexamethasone can yield 4-8 x 1010 granulocytes Stored at 24 oC Infuse within 24 hours of collection

Criteria : 

Criteria ANC <500 Fever Documented infection (bacterial or fungal) for 24-48 hours Unresponsive to appropriate antibiotics Reasonable hope of marrow recovery

Plasma Derivatives : 

Plasma Derivatives Factor VIII Concentrate Factor IX Concentrate AT-III Concentrate Factor XIII concentrate Albumin IV Immunoglobulin Rh Immunoglobulin

Albumin : 

Albumin Prepared from large pool of plasma reconstituted in isotonic electrolyte solution 96% albumin and 4% globulin and other proteins Heat treated to prevent viral transmission Available as 5% or 25% solutions T1/2=16 hours Used for Hypovolemia or hypoproteinemia Can be given without regard to ABO blood type & cross match

IV Immunoglobulins : 

IV Immunoglobulins Cold ethanol fractionation of pools of human plasma 90% of protein is IgG Trace IgA and IgM T1/2 = 18 to 32 days Used in primary immunodeficiencies, ITP, Neuropathies, GBS, etc Headache, fatigue, chills, backache, lightheadedness, fever, flushing, nausea, anaphylaxis. Risk of infectious transmission

Rh Immunogloblin : 

Rh Immunogloblin Pooled human plasma-derived anti-D IgG IM or IV preparations Available in 50μg and 300μg doses Used for protection of Rh-negative patients who are exposed to D antigen during pregnancy. One full dose can protect against 15 ml of Rh positive red blood cells

Recombinant Products : 

Recombinant Products Recombinant Factor VII (Novoseven) Recombinant Factor VIII (Recombinate) Recombinant Factor IX (BeneFIX)

CMV- Negative Blood Products : 

CMV- Negative Blood Products For Pregnant women Newborns Immunocompromised.

Complications : 


Tissue hypoxia : 

Tissue hypoxia Depletion of 2-3-diphosphoglycerate, adenosine triphosphate, and nitrite reductase activity Leftward shift of O2 - dissociation Curve Reduces erythrocyte deformability Oxygen supply-demand mismatch, Capillary sludging, and tissue hypoxia.

Coagulopathy : 

Coagulopathy Dilutional thrombocytopenia Low levels of factor V & VIII DIC Like Syndrome

Transfusion Reactions : 

Transfusion Reactions

Hemolytic Transfusion Reaction : 

Hemolytic Transfusion Reaction ABO incompatability Transfusion services error 10 ml of blood can cause intravascular hemolysis Mortality is 20-60%

Hemolytic Transfusion Reaction : 

Hemolytic Transfusion Reaction Signs & Symptoms Fever, chills, chest & flank pain, nausea ↓ Anaesthesia Haemoglobinuria, Bleeding, hypotension

Management : 

Management STOP THE TRANSFUSION Maintain urine output @75-100ml/hr Generous IV fluids Mannitol Furosemide Alkalinize the urine Prevent hypotension Assay urine & plasma Hb concentrations Determine platelet count, PTT & serum fibrinogen level Return unused blood to blood bank for repeat crossmatch Send patient’s blood & urine sample to Blood bank

Delayed Hemolytic Transfusion Reaction : 

Delayed Hemolytic Transfusion Reaction Extravascular immune reaction Incidence- 1/ 5-10,000 Hemolysis occur 2-21 days after transfusion Occur in recipients sensitized to RBC antigens by previous blood transfusions or pregnancy Fever, anaemia, jaundice

Non hemolytic transfusion reaction : 

Non hemolytic transfusion reaction Febrile reactions Infections Leucocytes Allergic reactions Foreign protein in transfused blood

Clinical features : 

Clinical features Febrile reactions Fever, Chills, Headache, Myalgia, Nonproductive cough occurring shortly after blood transfusion. Hypotension, chest pain less common Pulmonary infiltrates on X-ray. Direct globulin test differentiates from hemolytic reaction.

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Allergic reactions Urticaria, itching, facial swelling, fever Severe anaphylaxis with dyspnoea, hypotension, laryngeal edema and shock can occur → seen in IgA deficient individuals. No need to stop transfusion in case of mild allergic reactions. Antihistaminics given for symptomatic relief.

Infections : 

Infections Hepatitis HIV HTLV CMV West Nile virus Yersinia enterocolitica Malaria Syphilis Chagas disease Sars Creutzfeldt jakob

Graft Vs Host disease : 

Graft Vs Host disease Donor lymphocytes initiate immune reaction against host tissue Manifest as rash, leucopenia, thrombocytopenia Usually fatal Can be prevented by irradiation of blood products.

Transfusion related acute lung injury : 

Transfusion related acute lung injury Second leading cause of transfusion mortality. Under diagnosed and under reported. Non cardiogenic pulmonary edema due to immune reactivity of leucocyte antibodies. Symptoms appear 1-2 hours after transfusion and peak in 6 hours. Fever, dyspnoea, hypoxia, pulmonary edema. All blood components especially FFP Treatment- Stop the transfusion supportive measures

Immunomodulation : 

Immunomodulation Non specific immunosuppression like cytokine production natural killer cell activity, monocyte function cell mediated cytotoxicity suppresor cell number and function

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Thank You

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