BLOOD COMPONENT THERAPY : BLOOD COMPONENT THERAPY Dr. Gagan pal singh
SR, Cardiac Anaesthesia
Max Devki Devi Heart & Vascular Institute, New Delhi HISTORY : 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. Slide 5: 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. Slide 6: 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 : AVAILABLE PRODUCTS Whole Blood
Packed Red Cells
Red Cell Aliquots
Irradiated Red Cells
Leukoreduced Red Cells
Frozen Deglycerolized Red Cells
Random Donor Platelets
Single Donor Platelets PRODUCTS…. : PRODUCTS…. Plasma
Fresh Frozen Plasma
Single Donor Plasma
Solvent Detergent Plasma
IgA Deficient Fresh Frozen Plasma
CMV-negative blood products Whole Blood : Whole Blood 450 ml of blood
63 ml of anticoagulant solution.
No components have been removed.
Store at 1-6 oC
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
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.
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
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.
Severely immunocompromised patients
Stem-cell / marrow transplants
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
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
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
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
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
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
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
Factor XIII concentrate
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
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
Immunocompromised. Complications : 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
Haemoglobinuria, Bleeding, hypotension Management : Management STOP THE TRANSFUSION
Maintain urine output @75-100ml/hr
Generous IV fluids
Alkalinize the urine
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
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. Slide 47: 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
West Nile virus
Creutzfeldt jakob Graft Vs Host disease : Graft Vs Host disease Donor lymphocytes initiate immune reaction against host tissue
Manifest as rash, leucopenia, thrombocytopenia
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
natural killer cell activity,
cell mediated cytotoxicity
suppresor cell number and function Slide 52: Thank You