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Transfusion and blood
component therapy
Presenter – Dr Vivekanand
Moderator- Dr Chandni Sinha
Contents
1. What is blood transfusion.
2. Whole blood / blood components
3. Indications
4. Compatibility testing
5. Emergency transfusion and massive transfusion protocol
6. Complications and management
7. Patient blood management
What is blood transfusion.
• Blood transfusion is defined as the process of receiving blood products into
one’s circulation intravenously.
• This is usually done as a life saving maneuver to replace blood cells or blood
products lost through severe bleeding , during surgery when severe blood loss
occurs or to increase the blood count in an anaemic patient.
• •Transfusions usually involve the use of two sources of blood–one’sown
(autologous transfusion) or someone else’s (allogenic transfusion).
• •Blood transfusions involves the use of whole blood ,red blood cells , white
blood cells , plasma , clotting factors and platelets.
Whole blood / blood components
Blood Components
Cellular components Plasma components Plasma derivatives
Red cell concentrate Fresh frozen plasma Albumin 5% and 25%
Leucocytes-reduced red
cells
Single donor plasma Plasma protein
fractions
Platelet concentrate Cryoprecipitate Factor VIII concentrate
Leucocytes-reduced
platelet concentrate
Cryo-poor plasma Other coagulation
factors
Platelet apheresis Immunoglobulins
Granulocyte apheresis
Whole blood
• Whole blood has a shelf life of 35 days and typically 70ml of citrate preservative
solution is added to 420 ml blood.
• Indications
• Rarely used now a days
• Infrequently used in massive trauma
• Cardiac surgeries
• Post operative bleeding unresponsive to standard replacement therapy.
• Paediatric practice, mostly for neonatal exchange transfusion or paediatric surgery
(cardiac or craniofacial).
Packed RBC’s
• Produced by removing between 150-200ml of citrated plasma from a unit of
whole blood.
• Stored under refrigeration at controlled temperatures of 1 to 6°C to maintain
the viability and to prevent the growth of bacteria.
Preservative solutions of PRBC
• CPD -21days
• Citrate is an anticoagulant,
• Phosphate serves as a buffer,
• Dextrose is a red cell energy source
• CDPA -35 days (Adenine allows RBCs to resynthesize ATP)
• SAGM – 42 days
• AS-1 (Adsol) 42 days -Adenine, glucose, sodium chloride , and mannitol.
• AS-3 (Nutricel )- Adenine, glucose, NaCl citrate and phosphate.
• AS-5 (Optisol)-, adenine, NaCl and mannitol .
PACKED RED BLOOD CELLS
• Leukoreduced
• Irradiated
• Saline washed
• CMV negative
• Antigen Negative
• Sickle negative
• Frozen thawed
Leukoreduced
• A red cell component prepared by removing a proportion of the plasma from
leucocyte depleted whole blood or by leuco-depleting plasma reduced red cells.
• Non-LR RBC contain 1-3 x 109 WBC
• LR contain < 5 x 106 WBC and retains 85% of the original cells.
• Certain complications of PRBCs are likely due to leukocytes, Eg- HLA
alloimmunization against class I antigens, febrile reactions, and CMV infections.
Leukoreduced Indications -
• Chronically transfused patients,
• Potential transplant recipients,
• Patients with transplants,
• Patients with previous febrile nonhemolytic transfusion reactions,
• CMV-seronegative at-risk patients for whom seronegative components are not
available.
Irradiated
• PRBC units are exposed to gamma irradiation (2,500 cGy) to damage donor
WBC DNA.
• Prevent a cellular immune proliferative response to the recipient’s tissues.
• Usually performed in cesium-137 blood irradiators,
Irradiated Indications:
• Units from blood relatives
• Intrauterine transfusion
• Highly immunosuppressed patients at risk for this complication(GVHD)
• Neonates/Infants undergoing exchange transfusion or ECMO
• Hodgkin’s Disease
• Cellular immune deficiency
• Solid Organ Transplants
Washed red cells (Microaggregate-free blood)
• Designed machines are used to wash the red blood cells (RBCs), which are
then suspended in sterile saline.
• Saline washing removes residual plasma (98%), and reduces the concentration
of leucocytes, platelets and cellular debris.
• Can be carried out at any time during the shelf life of a unit of blood.
• Usually have haematocrits of 70-80% and a volume of about 180ml.
Indications-
• Patients with recurrent or severe allergic or febrile reactions to red cells,
• Severely IgA-deficient patients with anti-IgA antibodies for whom red cells
from an IgA deficient donor are not available.
• Microaggregate-free blood is used to prevent reactions to leucocyte and
platelet antigens.
CMV negative RBC
• Indications-
• All neonates (up to 4 months old)
• Intrauterine Transfusions
• High risk lung transplant
• Allogeneic stem cell transplants
• DiGeorge Syndrome.
CHANGES DURING STORAGE OF BLOOD
• Blood can be stored for 42 days is a mixed blessing, the obvious advantage is the
increased availability of blood.
• During storage, RBCs metabolize glucose to lactate, hydrogen ions accumulate, and
plasma pH decreases.
• The storage temperatures of 1° to 6° C stimulate the sodium potassium pump, and
RBCs lose K+ and gain Na.
• The osmotic fragility of RBCs increases during storage, and some cells undergo lysis,
resulting in increased plasma Hb levels.
• Progressive decreases in RBC concentrations of ATP and 2,3- diphosphoglycerate
(2,3- DPG) occur during storage.
GRANULOCYTE TRANSFUSIONS
• The buffy coat contains a high concentration of white cells and platelets.
• Buffy coats that are not used to make platelet concentrates are used for
granulocyte production.
• Apheresis technique can also be employed for collecting granulocytes.
• Granulocytes are stored at 22+2ºC without agitation.
• • Each pack of Leucocytes, Buffy Coat, Irradiated
• 50ml in volume, has a haematocrit of 45%, contains 1-2 x109 white cells,
90x109 platelets and 9.5g of haemoglobin.
• A dose of ten packs for adults.
• 10 -20ml / kg for children less than 50kg (to a maximum of 10 packs).
• Children less than 30Kg should receive 10-20ml/Kg to a maximum of two
packs.
Indications
• Therapeutic granulocyte transfusions indicated -for patients with a known congenital
disorder of neutrophil function, regardless of neutrophil count .
• Severe neutropenia, defined as ANC <0.5 x 109/L1 due to congenital or acquired
bone marrow failure syndromes.
• Receiving active treatment in an attempt to achieve disease remission.
• Proven or highly probable fungal or bacterial infection that is unresponsive to
appropriate antimicrobial therapy as demonstrated by visible spreading lesions on
skin, mucosa or radiological examination.
• • In whom neutrophil recovery is expected (ANC>0.5x109/l) in the near future and /
or in whom definitive therapy of curative potential is planned.
PLATELET CONCENTRATES
• Two methods to collect this component
• – Random donor pooled platelets
• – Single donor Apheresis platelets
PLATELET CONCENTRATES
• A single unit of platelets can be isolated by centrifuging from every unit of
donated whole blood.
• As the platelet number is inadequate, four to six units are pooled together.
• These are called whole blood-derived or random donor pooled platelets
PLATELET CONCENTRATES
• Advantages
• – lower cost,
• – ease of collection and
• – processing (a separate donation procedure and pheresis equipment are not
required).
• Disadvantage
• -is recipient exposure to multiple donors in a single transfusion and logistic
issues related to bacterial testing.
Single donor Apheresis platelets
• Platelets are collected in 2-3 hr apheresis procedure.
• Platelets and some white blood cells are removed, and red blood cells and plasma are
returned to the donor.
• A typical apheresis platelet unit provides the equivalent of six or more units of platelets
from whole blood (ie, 3 to 6 x 1011 platelets).
• Advantages
• -exposure of the recipient to a single donor rather than multiple donors,
• -and the ability to match donor and recipient characteristics such as HLA type,
cytomegalovirus (CMV) status, and blood type for certain recipients.
Unit of platelets concentrates
• Volume: 150–450 ml.
• pH: between 6.4 and 7.4 throughout the shelf-life.
• Leucocyte Count= <5* 106/pool
• Platelets are stored at room temperature, because cold induces clustering of von
Willebrand factor 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.
• Platelets are stored at a core temperature of 22°C +/- 2°C with continuous
gentle agitation for up to five days in a closed system.
• Platelets are stored at room temp which enhances bacterial growth.
• For any patient who develops a fever within 6 hours after receiving platelets,
sepsis from platelets should be considered.
Indications
• Stable patients without evidence of bleeding or coagulopathy <10,000/μL
• Prophylaxis for invasive procedures such as lumbar puncture, neuraxial anesthesia,
central venous catheterization, endoscopy with biopsy, liver biopsy, or major surgery
<50,000/μL
• Stable patients with clinical evidence of bleeding or coagulopathy <50,000/μL
• Patients with DIC and signs of ongoing bleeding <50,000/μL
• Patients undergoing massive transfusion <75,000/μL
• Patients having surgery at critical sites (eye or central nervous System) <100,000/μL
Calculation of dose
• One platelet concentrate is usually given to most adult patients.
• In small children (< 20 kg), 10–15 ml ⁄ kg up to the adult dose of one platelet
concentrate is used;
• In older children, an adult dose of platelets should be used.
• One platelet concentrate usually produces an increase of approximately 7000
to 10,000 platelets/mm3 at 1 hour after transfusion to the 70-kg adult.
• Ten units of platelet concentrates are required to increase the platelet count by
100,000 cells/mm3.
FRESH FROZEN PLASMA
• Frozen plasma (FP) is prepared from whole blood by separating and freezing
the plasma (200–250 ml) within 6 h of donation.
• It may be stored for up to 1 year at –18°C or lower.
• Contains all of the coagulation factors and other proteins present in the
original unit of blood.
Usage
• On order the FFP should be thawed between 30 and 37°C with constant
agitation.
• After thawing, can be stored at 4o C (refrigerator) and can be used safely
within 24 hours;
• when kept at room temperature, must be used within 4 hours.
Different types of frozen plasmas are available:
• Fresh frozen plasma (FFP): Plasma frozen at - 18oC or colder within 6 hours
of donation.
• F24 plasma: Plasma frozen at -18oC or colder within 24 hours
• Cryosupernatant or cryo-reduced plasma (CRP):
• Solvent-detergent treated plasma
• Liquid plasma:
Plasma F24 (PF 24):
• Plasma frozen at -18oC or colder within 24 hours.
• PF24 maintains all the clotting factors at the same levels as in FFP, except that
factor VIII levels are in the range of 65 to 80 percent of normal and protein C
is decreased.
Cryosupernatant or cryo-reduced plasma (CRP):
• The plasma remaining after removing cryoprecipitate.
• This product is also referred to as "Cryo-Poor Plasma.“
• Used as plasma replacement in some patients with thrombotic
thrombocytopenic purpura.
• vitamin K deficiency or correction of major bleeding in the setting of warfarin
anticoagulation because the removal of Cryoprecipitate from plasma does not
deplete the vitamin K-dependent clotting factors.
Liquid plasma:
• Plasma not immediately frozen as FFP or F24 and stored at 1-6 oC.
• Used for preparation of plasma derivatives like albumin, factor concentrate
and immunoglobulins.
Solvent-detergent treated plasma (S/D Plasma)
• Treatment of pooled plasma prior to freezing with a solvent and a nonionic
detergent inactivates a number of lipid envelopes virsues, including HIV, hep B and
hep C.
• Non-enveloped viruses (eg, hep A, parvo B19) are not inactivated by this process,
and even prions.
• Solvent/Detergent (S/D) method is similar to that used to inactivate viruses in
immune globulin and coagulation factors.
• S/D Plasma has similar levels of most clotting factors and similar hemostatic
properties as standard FFP.
Indications
• Correction of inherited factor deiciencies when there is no specific factor concentrate
(e.g., factor V)
• When the PT or aPTT is >1.5 times the mean control
• Correction of acquired multi-factor deiciencies with clinical evidence of bleeding or in
anticipation of major surgery or an invasive procedure with PT or aPTT >1.5 times
the control
• Liver dysfunction with clinical signs of bleeding
• DIC with clinical signs of bleeding
• Reversal of vitamin K antagonists (warfarin)
Indications
• Microvascular bleeding associated with massive transfusion and estimated
blood loss > one blood volume.
• Heparin resistance secondary to anti-thrombin deficiency when AT
concentrate is not available
• Treatment of thrombotic microangiopathies (thrombotic thrombocytopenic
Purpura, HELLP syndrome, or hemolytic uremic syndrome)
• Treatment of hereditary angioedema when C1-esterase inhibitor is not
available.
Dosing of FFP
• The initial therapeutic dose of FFP averages 10 to 15 mL/kg in an attempt to
obtain at least 30% factor activity.
• Repeat dosing should follow the results of serial diagnostic coagulation tests
such as the PT and aPTT.
• The guidelines for FFP continue to recommend prophylactic transfusions in
patients at risk for bleeding.
• The burden of adverse reactions in conjunction with limited prophylactic
benefits and high frequency of inappropriate use makes FFP arguably the
riskiest blood component transfused.
FFP in trauma
• Traditional methods- fluids, RBC, FFP only abnormal coagulation results.
• Problem -dilutional coagulopathy resulting in prolonged microvascular
bleeding.
• Recent studies show improved outcomes with higher ratios of red cell units
to FFP (more than 3:2).
CRYOPRECIPITATE (Con. AHF)
• Originally it was developed as a therapy for Haemophilia A (Used for 50 yrs).
• Enriched with fibrinogen, Fac VIII, vWF, Fac XIII.
• Prepared from processing FFP
• When FFP is thawed at 40C, a precipitate is formed, this is seperated from
the supernatant plasma, and resuspended in a small volume of plasma and
then refrozen at -180C.
• Can be stored for 1 year
• On ordering the cryoprecipitate is thawed in a 370C
• water bath & issued in individual bags or a pooled product
• After thawing- must be kept in room temperature
• Expiration time- 6hr for un-pooled & 4hr for pooled
• Can be stored for 1 year
• One unit of cryoprecipitate – derived from 1 unit of whole blood/ 250ml plasma-
contains
• – Volume- 10-20ml
• – 150-250 mg Fibrinogen
• – 80-100 units of Fac VIII
• – 50-100 units of Fac XIII
• – 50-60 mg of fibronectin
• – 40-70% of vWF Concentrate
Indications-
• Prophylaxis in non bleeding perioperative or peripartum patients with
congenital fibrinogen deficiencies or von Willebrand's disease unresponsive to
1-desamino-8-D-arginine vasopressin (DDAVP).
• Bleeding patients with von Willebrand's disease
• Correction of microvascular bleeding in massively transfused patients with
fibrinogen concentrations less than 80–100 mg/dl (or when fibrinogen
concentrations cannot be measured in a timely fashion)
• As a source of fibrinogen Congenital- Hypofibrinogenaemia/ Afibrinogenaemia
• Acquired- severe coagulaopathy, DIC, massive transfusion
• Trauma
• Significant bleeding after major trauma accompanied by a plasma fibrinogen level <
100mg/dl
• Significant bleeding accompanied with signs of functional fibrinogen deficit on TEG
• Preparation of Fibrin sealant/fibrin glue used in sealing large raw surfaces.
• Fibrin glue- Cryoprecipitate, bovine or human thrombin and calcium chloride.
Dosing-
• 2-3 unit of cryoprecipitate per 10 kg body weight raises the plasma
fibrinogen concentration by approximately 100 mg/dl in the absence of
continued consumption or massive bleeding.
• Maintenance dose- I bag per 15 kg –can be given daily till the bleeding is
controlled.
• Fibrinogen required(mg) = (Desired Fb – Current Fb) * plasma volume/100.
• Bags required= Fibrinogen required mg/250mg.
• Plasma volume= blood volume * (1- Hemotocrit)
Compatibility testing
• The ABO-Rh type, crossmatch, and antibody screen are frequently referred to as
compatibility tests.
• Approximately 85% of individuals possess the D antigen and are classified as
Rh(D) positive; the remaining 15%, who lack the D antigen, are classified as
Rh(D) negative.
COMPATIBILITY TESTING
CROSSMATCHING
• Trial transfusion within a test tube in which donor RBCs are mixed with recipient serum to detect a
potential for serious transfusion reaction.
• The crossmatch can be completed in 45 to 60 minutes and is performed in three phases: an
immediate phase, an incubation phase, and an antiglobulin phase.
• Immediate phase detects ABO incompatibilities and those caused by naturally occurring antibodies
in the MN, P, and Lewis systems. This takes 1 to 5 minutes to complete.
• Incubation phase involves incubation at 37° C in albumin or low– ionic strength salt solution . This
phase primarily detects antibodies in the Rh system.
• Antiglobulin phase of the crossmatch, the indirect antiglobulin test, involves the addition of
antiglobulin sera to the incubated test tubes.
• This phase detects most incomplete antibodies in the blood group systems, including the Rh, Kell,
Kidd, and Duffy blood group systems.
ANTIBODY SCREENING
• Also carried out in three phases and is similar in length to the crossmatch.
• Trial transfusion between the recipient’s serum and commercially supplied
RBCs that are specifically selected to contain optimal numbers of RBC antigens
or antigens that will react with antibodies that are commonly implicated in
hemolytic transfusion reactions.
• The screen for unexpected antibodies is also used on donor serum and is
performed shortly after withdrawal of blood from the donor.
Emergency transfusion and massive transfusion
protocol
• In many situations, urgent need for blood occurs before completion of compatibility
testing (ABO-Rh, antibody screen, and crossmatch ,for those situations that do not
allow time for complete testing, an abbreviated format for testing can be used .
• TYPE-SPECIFIC, PARTIALLY CROSSMATCHED BLOOD-This takes 1 to 5
minutes and eliminates serious hemolytic reactions resulting from errors that may occur
in ABO typing.
• TYPE-SPECIFIC, UNCROSSMATCHED BLOOD-For those who have never been
exposed to foreign RBCs, most ABO type-specific transfusions are successful
• TYPE O RH-NEGATIVE (UNIVERSAL DONOR), UNCROSSMATCHED
BLOOD-
Emergency transfusion and massive transfusion
protocol
• Some hospitals have an emergency-release RBC pack, which is uncrossmatched
RBCs that are O negative.
• If clinicians think the situation is urgent, this blood usually can be provided in
approximately 5 minutes.
• Also available in concept in some hospitals is a massive transfusion protocol
(MTP), which includes 4 units uncrossmatched O negative RBCs, 4 units
thawed AB plasma, and 1 unit of platelet concentrates.
MASSIVE BLOOD TRANSFUSION
• Defined as:
• Replacement of 1 circulating blood volume (around 10–12 units of PRBCS) within
24 hrs
• Loss of 50% of circulating blood volume within 3 hrs
• Loss of 10% of circulating blood volume within 10 mins
• Transfusion of 10 units of blood within 6 hrs
• Transfusion of 4 units of blood within 1 hour with continuing blood loss
• Transfusion of 1 unit of blood within 5 minutes.
Preparation for Massive Blood Transfusion
• Two large gauge venous cannula (14 G)
• Triple lumen central venous catheter
• Monitors:
• Triple lumen central venous catheter used for:
• Rapid blood sampling
• Measurement of CVP.
• Foleys catheter to measure urine output
• Central and peripheral temperature should be measured
• Pulse oximetry, arterial pressure and ECG should be monitored.
Method of Administration
• Constant pressure infusion device
• For faster rates of transfusion:
• –– Increase height of fluid above patient
• –– Manual compression of bag
• –– Using syringe and three way tap to aspirate and push volume.
• Warming of Stored Blood
• Double length blood warming coil
• Counter current aluminium heat exchangers
• Plastic coils/plastics cassettes in warm water bath (37–38°􀂃C)
• Warming plates which have an upper (43 􀂃C) and lower limits (33 􀂃C) is safest.
Management of Massive Transfusion
Complications of Massive Transfusion
• Coagulopathy- Transfusion guidelines:
• –– If platelet count < 50000/μl, platelet transfusion
• –– If INR > 1.5, transfuse FFP
• –– If fibrinogen < 100 mg/dl, transfuse cryoprecipitate.
• Citrate Toxicity
• Not caused by citrate ion per se, but because citrate binds to Ca2+
• Each unit of blood contains 3 gms of citrate
• Hypocalcemia occurs only when:
• -- Rates of transfusion > 1 ml/kg/min
• -- 1 unit blood transfused in 5 min.
• –– Rate of citrate metabolism reduces by 50% when body temperature reduces from 37°􀂃C
to 31 􀂃C.
• Clinical features:
• –– Reduced myocardial function
• –– Hypotension, narrow pulse press, increased diastolic pressure and CVP
• –– Increased QTc, widened QRS and flattened T-waves.
Treatment:
• –– 1 gm calcium gluconate (10%) given IV for every 5 units blood/FPP
• –– 13.4% calcium chloride contains 0.192 mmol/ml of Ca2+
• –– 10% calcium gluconate contains only 0.22 mmol/ml of Ca2+
• –– CaCl2 is not used much even though it contains more Ca2+ as it very
irritant to veins.
Hyperkalemia
• Serum K+ is as high as 19–30 mEq/l in stored blood after 21 days
• This is because RBCs exchange K+ ions to uptake H+ ions generated by metabolism
• Precipitating factors:
• –– Large amounts of blood must be given for hyper K+ to occur
• –– Rate of blood infusion > 120 ml/min
• –– Premature infants are especially susceptible
• Transfuse only fresh (< 8 days old) plasma reduced or washed PRBCs if rapid transfusion is
required (> 10–15 ml/kg/2 hours) in premature infants
• Hypokalemia occurs 24 hrs after transfusion as the transfused cells correct their electrolyte
composition and K+ enters cells.
Hypernatremia
• Serum Na+ of whole blood and FFP > normal blood levels due to sodium
citrate
• Hypernatremia occurs when large volume of plasma is given to patients with
disordered salt and water handling: Liver disease, cardiac and renal disease
• Na+ increases to 150–160 mm/l after 3 weeks of storage of plasma.
Acid Base Abnormalities
• Causes of acidosis of bank blood:
• –– pH of storage media like CPDA is very low (5.5).
• –– Accumulation of lactic acid and pyruvate by RBC metabolism.
• –– PCO2 increases to 150–220 mm Hg as the plastic container does not provide air
escape mechanisms for CO2.
• On blood transfusion, the citrate present in stored blood is metabolized in liver
• This generates large amounts of bicarbonate which may neutralize metabolic acidosis
initially.
• Thus, initially, metabolic acidosis and hyperkalemia occur while later alkalosis and
hypokalemia occur.
Hypothermia
• • One unit of PRBCs at 40 􀂃C will reduce core temperature of 70 kg patient by 0.25 􀂃C
• • Blood warming device must be used for any transfusion requiring > 2 U blood
• • If < 30 􀂃C ventricular irritability and cardiac arrest occurs
• • Safest method is passing blood through plastic coils or plastic cassettes in warm water bath (37–38 􀂃C)
• • Harmful effects of hypothermia:
• –– Shifts ODC curve to left
• –– Reduces metabolism of citrate, lactate and other drugs
• –– Impairs hemostasis
• –– Increased postoperative infection
• –– Shivering increases O2 consumption by 400%.
Tissue Oxygenation
• Depletion of 2, 3-DPG shifts ODC curve to left
• Tissue oxygen delivery is reduced
• After transfusion, 2,3-DPG returns to normal in 12–24 hrs.
Hyperbilirubinemia
• Jaundice as significant amounts of transfused blood may not survive
• Also, liver function may be impaired, particularly in the presence of sepsis or multi
organ failure,
• Paradoxical conjugated hyper bilirubinemia occurs
• –– Increased load of bilirubin from destroyed RBCs occurs which is conjugated
• –– There may be delayed excretion which causes conjugated hyperbilirubinemia.
Multiorgan Dysfunction
• • Due to lysis of RBCs during storage causing free Hb release
• This causes oxidant mediated injury causing MODS
Microaggregates
• Platelet aggregates form during 2nd–5th day
• From 10 days onwards, larger aggregates form with:
• –– Fibrin
• –– Degenerated WBCs
• –– Platelets
• –– Size of 100–200 μm which can cause:
• -- Acute lung injury
• -- Hypoxemia
• -- DIC and tissue ischemia
• -- Complement activation.
• Use filter when > 1 L of blood is transfused.
Adverse Transfusion Events
• Classified into
-Immediate
-Delayed
Immediate
• Further divided into
• A – Immunological
1) Haemolytic transfusion reaction
2) Febrile nonhemolytic transfusion reaction
3) Allergic reactions
4) Anaphylaxis
5) TRALI
Immediate…
• B - Non Immunological
1) Bacterial contamination
2) Circulatory overload
3) Metabolic complications
4) Non immune haemolysis
Delayed
• A – Immunological
1) Delayed haemolytic tranfusion reaction
2) TAGVHD
3) Post transfusion Purpura (PTP)
4) Alloimmunization
• B - Non Immunological
1) Iron overload
2) Transfusion transmitted diseases
TRANSFUSION-RELATED
ACUTE LUNG INJURY
• Non cardiogenic form of pulmonary edema occurring after blood product
administration
• New acute lung injury occurring within 6 hrs of a completed transfusion
with ratio of PaO2/FiO2< 300 mm Hg or O2 saturation as measured by
pulse oximetry of less than 90% when the patient is breathing room air.
Risk Factors
• Associated with transfusion of all products:
• –– Whole blood
• –– PRBCs
• –– FFP, platelets, cryoprecipitate
• –– Intravenous immunoglobulin therapy (IVIg therapy)
• –– Granulocytes, stem cell preparation.
Risk Factors
• • Multiparous donors
• Underlying clinical conditions: Two hit hypothesis
• –– Trauma
• –– Surgery
• –– Sepsis
• –– Systemic Inflammatory Response Syndrome(SIRS)
• Storage of blood products causes:
• –– Accumulation of cytokines which injuries alveolar capillary membrane
• –– Depletion of nitric oxide causing pulmonary vasoconstriction
• –– Depletion of nitric oxide also causes increase in hydrostatic pressure and
TRALI
• Massive transfusion: strong association between exposure to multiple
transfusions and development of TRALI.
Pathogenesis
• Antigranulocyte Antibody Theory
• Donor blood contains antibodies against recipient WBC antigen causing cellular activation
• The activated neutrophils lodge in pulmonary capillaries.
• Granulocyte Priming Theory
• Biologically active substances (such as lipids and cytokines) are present within the transfusion
• These substances are called Biological Response Modifiers or BRM
• Examples of BRM are lysophosphatidyl choline
• These have the ability to prune the activity of granulocytes in pulmonary vasculature
Clinical Features
• Acute onset dyspnea, severe hypoxemia
• Fever, chills, rigors
• Noncardiogenic pulmonary edema, hypotension/ hypertension
• Fluid in ET tube within 1–2 hrs after transfusion but in full force within 6 hrs
• If undiluted edema fluid obtained from ETT, edema fluid protein: plasma protein ratio
> 0.6 suggests TRALI rather than TACO
• Chest X-ray shows bilateral chest infiltrates
• PO2 levels return to normal within 48–96 hrs
• Hypoxia and chest X-ray infilterates may persists for 7 days.
Treatment
• Immediately stop blood transfusion
• Mainly supportive hemodynamic and ventilatory support
• Supplemental O2 if mild manifestations
• Mechanical ventilation with low tidal volume and plateau pressures if moderate-severe
manifestations
• High FiO2, PEEP may be required (similar to ARDS)
• Diuretics have no role in TRALI can be tried if TRALI cannot be differentiated from TACO
• IV corticosteroids have been tried to reduce complement mediated granulocyte activation.
• Rapid resolution usually occurs in 96 hrs
Pharmacological Blood Sparing Strategies
• ERYTHROPOIETIN- 300 U /kg x14 days or 600 U / kg thrice a week.
• ANTIFIBRINOLYTICS, includes EACA and tranexamic acid, which are plasminogen inhibitors.
• tranexamic acid – 10 – 15 mg / kg prior to release of tourniquet
• SERINE PROTEASE INHIBITORS- aprotinin, nafamostat, and ecallantide.
• Aprotinin – 2 million loading 0.5 million units / hr -inhibits fibrinolysis and improves platelet
function.
• SYNTHETIC ANALOGUES OF THE ANTIDIURETIC HORMONE VASOPRESSIN. -
• Desmopressin (1-deamino-8-D-arginine vasopressin [DDAVP])- increases the levels of factor VIII
and von Willebrand factor
• FIBRINOGEN – ( Combination of bovine thrombin & human fibrinogen)
Patient blood management
• Transfusion trigger-
• Transfusion is rarely indicated when the haemoglobin concentration is greater than 10
gm/dl, and is almost always indicated when it is less than 6 gm/dl.
• For intermediate haemoglobin concentrations (6–10 gm/dl), justifying transfusion
Based on
• – ongoing indication of organ ischemia,
• – potential or actual ongoing bleeding (rate and magnitude),
• – the patient's intravascular volume status, and
• – the patient's risk factors for complications of inadequate oxygenation.
Monitoring for blood loss.
• A visual assessment of the surgical field should be periodically conducted to assess
the presence of excessive microvascular bleeding (i.e , coagulopathy).
• Standard methods for quantitative measurement of blood loss (e.g., suction and
sponge) should be used.
• Monitoring for inadequate perfusion and oxygenation of vital organs.
• Clinical indications of tissue hypoxia-Unstable vital signs
Laboratory and invasive monitor indices
• Mixed venous O2 saturation (SVmO2) <50%
• Central venous O2 saturation (SVcO2) <60%
• Increased O2 extraction ratio (O2ER) >50%
• Lactic acidosis (metabolic acidemia with lactate >2 mmol/L)
• Electrocardiographic (ST changes, onset of arrhythmias) or echocardiographic
indications of myocardial ischemia
• Electroencephalographic indications of cerebral hypoperfusion
• New onset oliguria (less than 0.5 mL/kg/h for >6 h)
Autologous Blood Harvesting
• A) Preoperative Autologous Blood Donation( PABD)
• B) Acute Normovoluemic Hemodilution (ANH)
PABD
• Patients visit 6 weeks in advance to donate blood
• Blood donation 1 per week
• Blood donation stops 3 weeks before surgery
• Iron therapy is integral to PABD
• No PABD 72 hrs before surgery
• Usually 2 units sufficient
Contraindications to PABD
• 1) If HB < 11 gm /dl
• 2) More than 6 units reqd
• 3) Comorbidity e.g cardiac disease
• 4) Patient having infectious disease markers
• Since maximum allowed storage interval for RBC is 6 weeks , hence PABD is
executed 6 weeks in advance.
ANH
• Removal of whole blood , replacement with acellular fluid shortly before
anticipated blood loss
• Done after Induction of Anesthesia and before start of surgery
Advantages of ANH
• 1) Reduced Absolute RBC loss
• 2) Unit with patient ; no wrong transfusion
• 3) No microbiological testing reqd
• 4) No risk of hemolytic reaction
• Caution: Should be restricted to patients with sufficiently high Hb, who can
withstand 1 lt of whole blood to be taken out and in whom low target Hb is deemed
appropriate.
Cell Salvage
• INTRAOPERATIVE / POSTOPERATIVE
-Shed surgical blood is suctioned under low pressure into a reservoir filled with saline
-Then washed & filtered & returned to patient
-Can be given upto 6 hrs at room temperature
-Cost effective if loss is > 1000 ml
• CONTRAINDICATIONS
-Malignancy
-Leakage of bowel contents in surgical field
• Thank you

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Transfusion and blood component therapy

  • 1. Transfusion and blood component therapy Presenter – Dr Vivekanand Moderator- Dr Chandni Sinha
  • 2. Contents 1. What is blood transfusion. 2. Whole blood / blood components 3. Indications 4. Compatibility testing 5. Emergency transfusion and massive transfusion protocol 6. Complications and management 7. Patient blood management
  • 3. What is blood transfusion. • Blood transfusion is defined as the process of receiving blood products into one’s circulation intravenously. • This is usually done as a life saving maneuver to replace blood cells or blood products lost through severe bleeding , during surgery when severe blood loss occurs or to increase the blood count in an anaemic patient. • •Transfusions usually involve the use of two sources of blood–one’sown (autologous transfusion) or someone else’s (allogenic transfusion). • •Blood transfusions involves the use of whole blood ,red blood cells , white blood cells , plasma , clotting factors and platelets.
  • 4. Whole blood / blood components
  • 5. Blood Components Cellular components Plasma components Plasma derivatives Red cell concentrate Fresh frozen plasma Albumin 5% and 25% Leucocytes-reduced red cells Single donor plasma Plasma protein fractions Platelet concentrate Cryoprecipitate Factor VIII concentrate Leucocytes-reduced platelet concentrate Cryo-poor plasma Other coagulation factors Platelet apheresis Immunoglobulins Granulocyte apheresis
  • 6.
  • 7. Whole blood • Whole blood has a shelf life of 35 days and typically 70ml of citrate preservative solution is added to 420 ml blood. • Indications • Rarely used now a days • Infrequently used in massive trauma • Cardiac surgeries • Post operative bleeding unresponsive to standard replacement therapy. • Paediatric practice, mostly for neonatal exchange transfusion or paediatric surgery (cardiac or craniofacial).
  • 8. Packed RBC’s • Produced by removing between 150-200ml of citrated plasma from a unit of whole blood. • Stored under refrigeration at controlled temperatures of 1 to 6°C to maintain the viability and to prevent the growth of bacteria.
  • 9. Preservative solutions of PRBC • CPD -21days • Citrate is an anticoagulant, • Phosphate serves as a buffer, • Dextrose is a red cell energy source • CDPA -35 days (Adenine allows RBCs to resynthesize ATP) • SAGM – 42 days • AS-1 (Adsol) 42 days -Adenine, glucose, sodium chloride , and mannitol. • AS-3 (Nutricel )- Adenine, glucose, NaCl citrate and phosphate. • AS-5 (Optisol)-, adenine, NaCl and mannitol .
  • 10.
  • 11.
  • 12. PACKED RED BLOOD CELLS • Leukoreduced • Irradiated • Saline washed • CMV negative • Antigen Negative • Sickle negative • Frozen thawed
  • 13. Leukoreduced • A red cell component prepared by removing a proportion of the plasma from leucocyte depleted whole blood or by leuco-depleting plasma reduced red cells. • Non-LR RBC contain 1-3 x 109 WBC • LR contain < 5 x 106 WBC and retains 85% of the original cells. • Certain complications of PRBCs are likely due to leukocytes, Eg- HLA alloimmunization against class I antigens, febrile reactions, and CMV infections.
  • 14. Leukoreduced Indications - • Chronically transfused patients, • Potential transplant recipients, • Patients with transplants, • Patients with previous febrile nonhemolytic transfusion reactions, • CMV-seronegative at-risk patients for whom seronegative components are not available.
  • 15. Irradiated • PRBC units are exposed to gamma irradiation (2,500 cGy) to damage donor WBC DNA. • Prevent a cellular immune proliferative response to the recipient’s tissues. • Usually performed in cesium-137 blood irradiators,
  • 16. Irradiated Indications: • Units from blood relatives • Intrauterine transfusion • Highly immunosuppressed patients at risk for this complication(GVHD) • Neonates/Infants undergoing exchange transfusion or ECMO • Hodgkin’s Disease • Cellular immune deficiency • Solid Organ Transplants
  • 17. Washed red cells (Microaggregate-free blood) • Designed machines are used to wash the red blood cells (RBCs), which are then suspended in sterile saline. • Saline washing removes residual plasma (98%), and reduces the concentration of leucocytes, platelets and cellular debris. • Can be carried out at any time during the shelf life of a unit of blood. • Usually have haematocrits of 70-80% and a volume of about 180ml.
  • 18. Indications- • Patients with recurrent or severe allergic or febrile reactions to red cells, • Severely IgA-deficient patients with anti-IgA antibodies for whom red cells from an IgA deficient donor are not available. • Microaggregate-free blood is used to prevent reactions to leucocyte and platelet antigens.
  • 19. CMV negative RBC • Indications- • All neonates (up to 4 months old) • Intrauterine Transfusions • High risk lung transplant • Allogeneic stem cell transplants • DiGeorge Syndrome.
  • 20. CHANGES DURING STORAGE OF BLOOD • Blood can be stored for 42 days is a mixed blessing, the obvious advantage is the increased availability of blood. • During storage, RBCs metabolize glucose to lactate, hydrogen ions accumulate, and plasma pH decreases. • The storage temperatures of 1° to 6° C stimulate the sodium potassium pump, and RBCs lose K+ and gain Na. • The osmotic fragility of RBCs increases during storage, and some cells undergo lysis, resulting in increased plasma Hb levels. • Progressive decreases in RBC concentrations of ATP and 2,3- diphosphoglycerate (2,3- DPG) occur during storage.
  • 21.
  • 22. GRANULOCYTE TRANSFUSIONS • The buffy coat contains a high concentration of white cells and platelets. • Buffy coats that are not used to make platelet concentrates are used for granulocyte production. • Apheresis technique can also be employed for collecting granulocytes. • Granulocytes are stored at 22+2ºC without agitation. • • Each pack of Leucocytes, Buffy Coat, Irradiated
  • 23. • 50ml in volume, has a haematocrit of 45%, contains 1-2 x109 white cells, 90x109 platelets and 9.5g of haemoglobin. • A dose of ten packs for adults. • 10 -20ml / kg for children less than 50kg (to a maximum of 10 packs). • Children less than 30Kg should receive 10-20ml/Kg to a maximum of two packs.
  • 24. Indications • Therapeutic granulocyte transfusions indicated -for patients with a known congenital disorder of neutrophil function, regardless of neutrophil count . • Severe neutropenia, defined as ANC <0.5 x 109/L1 due to congenital or acquired bone marrow failure syndromes. • Receiving active treatment in an attempt to achieve disease remission. • Proven or highly probable fungal or bacterial infection that is unresponsive to appropriate antimicrobial therapy as demonstrated by visible spreading lesions on skin, mucosa or radiological examination. • • In whom neutrophil recovery is expected (ANC>0.5x109/l) in the near future and / or in whom definitive therapy of curative potential is planned.
  • 25. PLATELET CONCENTRATES • Two methods to collect this component • – Random donor pooled platelets • – Single donor Apheresis platelets
  • 26. PLATELET CONCENTRATES • A single unit of platelets can be isolated by centrifuging from every unit of donated whole blood. • As the platelet number is inadequate, four to six units are pooled together. • These are called whole blood-derived or random donor pooled platelets
  • 27. PLATELET CONCENTRATES • Advantages • – lower cost, • – ease of collection and • – processing (a separate donation procedure and pheresis equipment are not required). • Disadvantage • -is recipient exposure to multiple donors in a single transfusion and logistic issues related to bacterial testing.
  • 28. Single donor Apheresis platelets • Platelets are collected in 2-3 hr apheresis procedure. • Platelets and some white blood cells are removed, and red blood cells and plasma are returned to the donor. • A typical apheresis platelet unit provides the equivalent of six or more units of platelets from whole blood (ie, 3 to 6 x 1011 platelets). • Advantages • -exposure of the recipient to a single donor rather than multiple donors, • -and the ability to match donor and recipient characteristics such as HLA type, cytomegalovirus (CMV) status, and blood type for certain recipients.
  • 29. Unit of platelets concentrates • Volume: 150–450 ml. • pH: between 6.4 and 7.4 throughout the shelf-life. • Leucocyte Count= <5* 106/pool • Platelets are stored at room temperature, because cold induces clustering of von Willebrand factor 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.
  • 30. • Platelets are stored at a core temperature of 22°C +/- 2°C with continuous gentle agitation for up to five days in a closed system. • Platelets are stored at room temp which enhances bacterial growth. • For any patient who develops a fever within 6 hours after receiving platelets, sepsis from platelets should be considered.
  • 31. Indications • Stable patients without evidence of bleeding or coagulopathy <10,000/μL • Prophylaxis for invasive procedures such as lumbar puncture, neuraxial anesthesia, central venous catheterization, endoscopy with biopsy, liver biopsy, or major surgery <50,000/μL • Stable patients with clinical evidence of bleeding or coagulopathy <50,000/μL • Patients with DIC and signs of ongoing bleeding <50,000/μL • Patients undergoing massive transfusion <75,000/μL • Patients having surgery at critical sites (eye or central nervous System) <100,000/μL
  • 32. Calculation of dose • One platelet concentrate is usually given to most adult patients. • In small children (< 20 kg), 10–15 ml ⁄ kg up to the adult dose of one platelet concentrate is used; • In older children, an adult dose of platelets should be used. • One platelet concentrate usually produces an increase of approximately 7000 to 10,000 platelets/mm3 at 1 hour after transfusion to the 70-kg adult. • Ten units of platelet concentrates are required to increase the platelet count by 100,000 cells/mm3.
  • 33. FRESH FROZEN PLASMA • Frozen plasma (FP) is prepared from whole blood by separating and freezing the plasma (200–250 ml) within 6 h of donation. • It may be stored for up to 1 year at –18°C or lower. • Contains all of the coagulation factors and other proteins present in the original unit of blood.
  • 34. Usage • On order the FFP should be thawed between 30 and 37°C with constant agitation. • After thawing, can be stored at 4o C (refrigerator) and can be used safely within 24 hours; • when kept at room temperature, must be used within 4 hours.
  • 35. Different types of frozen plasmas are available: • Fresh frozen plasma (FFP): Plasma frozen at - 18oC or colder within 6 hours of donation. • F24 plasma: Plasma frozen at -18oC or colder within 24 hours • Cryosupernatant or cryo-reduced plasma (CRP): • Solvent-detergent treated plasma • Liquid plasma:
  • 36. Plasma F24 (PF 24): • Plasma frozen at -18oC or colder within 24 hours. • PF24 maintains all the clotting factors at the same levels as in FFP, except that factor VIII levels are in the range of 65 to 80 percent of normal and protein C is decreased.
  • 37. Cryosupernatant or cryo-reduced plasma (CRP): • The plasma remaining after removing cryoprecipitate. • This product is also referred to as "Cryo-Poor Plasma.“ • Used as plasma replacement in some patients with thrombotic thrombocytopenic purpura. • vitamin K deficiency or correction of major bleeding in the setting of warfarin anticoagulation because the removal of Cryoprecipitate from plasma does not deplete the vitamin K-dependent clotting factors.
  • 38. Liquid plasma: • Plasma not immediately frozen as FFP or F24 and stored at 1-6 oC. • Used for preparation of plasma derivatives like albumin, factor concentrate and immunoglobulins.
  • 39. Solvent-detergent treated plasma (S/D Plasma) • Treatment of pooled plasma prior to freezing with a solvent and a nonionic detergent inactivates a number of lipid envelopes virsues, including HIV, hep B and hep C. • Non-enveloped viruses (eg, hep A, parvo B19) are not inactivated by this process, and even prions. • Solvent/Detergent (S/D) method is similar to that used to inactivate viruses in immune globulin and coagulation factors. • S/D Plasma has similar levels of most clotting factors and similar hemostatic properties as standard FFP.
  • 40. Indications • Correction of inherited factor deiciencies when there is no specific factor concentrate (e.g., factor V) • When the PT or aPTT is >1.5 times the mean control • Correction of acquired multi-factor deiciencies with clinical evidence of bleeding or in anticipation of major surgery or an invasive procedure with PT or aPTT >1.5 times the control • Liver dysfunction with clinical signs of bleeding • DIC with clinical signs of bleeding • Reversal of vitamin K antagonists (warfarin)
  • 41. Indications • Microvascular bleeding associated with massive transfusion and estimated blood loss > one blood volume. • Heparin resistance secondary to anti-thrombin deficiency when AT concentrate is not available • Treatment of thrombotic microangiopathies (thrombotic thrombocytopenic Purpura, HELLP syndrome, or hemolytic uremic syndrome) • Treatment of hereditary angioedema when C1-esterase inhibitor is not available.
  • 42. Dosing of FFP • The initial therapeutic dose of FFP averages 10 to 15 mL/kg in an attempt to obtain at least 30% factor activity. • Repeat dosing should follow the results of serial diagnostic coagulation tests such as the PT and aPTT. • The guidelines for FFP continue to recommend prophylactic transfusions in patients at risk for bleeding. • The burden of adverse reactions in conjunction with limited prophylactic benefits and high frequency of inappropriate use makes FFP arguably the riskiest blood component transfused.
  • 43. FFP in trauma • Traditional methods- fluids, RBC, FFP only abnormal coagulation results. • Problem -dilutional coagulopathy resulting in prolonged microvascular bleeding. • Recent studies show improved outcomes with higher ratios of red cell units to FFP (more than 3:2).
  • 44. CRYOPRECIPITATE (Con. AHF) • Originally it was developed as a therapy for Haemophilia A (Used for 50 yrs). • Enriched with fibrinogen, Fac VIII, vWF, Fac XIII. • Prepared from processing FFP • When FFP is thawed at 40C, a precipitate is formed, this is seperated from the supernatant plasma, and resuspended in a small volume of plasma and then refrozen at -180C. • Can be stored for 1 year
  • 45. • On ordering the cryoprecipitate is thawed in a 370C • water bath & issued in individual bags or a pooled product • After thawing- must be kept in room temperature • Expiration time- 6hr for un-pooled & 4hr for pooled • Can be stored for 1 year
  • 46. • One unit of cryoprecipitate – derived from 1 unit of whole blood/ 250ml plasma- contains • – Volume- 10-20ml • – 150-250 mg Fibrinogen • – 80-100 units of Fac VIII • – 50-100 units of Fac XIII • – 50-60 mg of fibronectin • – 40-70% of vWF Concentrate
  • 47. Indications- • Prophylaxis in non bleeding perioperative or peripartum patients with congenital fibrinogen deficiencies or von Willebrand's disease unresponsive to 1-desamino-8-D-arginine vasopressin (DDAVP). • Bleeding patients with von Willebrand's disease • Correction of microvascular bleeding in massively transfused patients with fibrinogen concentrations less than 80–100 mg/dl (or when fibrinogen concentrations cannot be measured in a timely fashion)
  • 48. • As a source of fibrinogen Congenital- Hypofibrinogenaemia/ Afibrinogenaemia • Acquired- severe coagulaopathy, DIC, massive transfusion • Trauma • Significant bleeding after major trauma accompanied by a plasma fibrinogen level < 100mg/dl • Significant bleeding accompanied with signs of functional fibrinogen deficit on TEG • Preparation of Fibrin sealant/fibrin glue used in sealing large raw surfaces. • Fibrin glue- Cryoprecipitate, bovine or human thrombin and calcium chloride.
  • 49. Dosing- • 2-3 unit of cryoprecipitate per 10 kg body weight raises the plasma fibrinogen concentration by approximately 100 mg/dl in the absence of continued consumption or massive bleeding. • Maintenance dose- I bag per 15 kg –can be given daily till the bleeding is controlled.
  • 50. • Fibrinogen required(mg) = (Desired Fb – Current Fb) * plasma volume/100. • Bags required= Fibrinogen required mg/250mg. • Plasma volume= blood volume * (1- Hemotocrit)
  • 51. Compatibility testing • The ABO-Rh type, crossmatch, and antibody screen are frequently referred to as compatibility tests. • Approximately 85% of individuals possess the D antigen and are classified as Rh(D) positive; the remaining 15%, who lack the D antigen, are classified as Rh(D) negative.
  • 53. CROSSMATCHING • Trial transfusion within a test tube in which donor RBCs are mixed with recipient serum to detect a potential for serious transfusion reaction. • The crossmatch can be completed in 45 to 60 minutes and is performed in three phases: an immediate phase, an incubation phase, and an antiglobulin phase. • Immediate phase detects ABO incompatibilities and those caused by naturally occurring antibodies in the MN, P, and Lewis systems. This takes 1 to 5 minutes to complete. • Incubation phase involves incubation at 37° C in albumin or low– ionic strength salt solution . This phase primarily detects antibodies in the Rh system. • Antiglobulin phase of the crossmatch, the indirect antiglobulin test, involves the addition of antiglobulin sera to the incubated test tubes. • This phase detects most incomplete antibodies in the blood group systems, including the Rh, Kell, Kidd, and Duffy blood group systems.
  • 54. ANTIBODY SCREENING • Also carried out in three phases and is similar in length to the crossmatch. • Trial transfusion between the recipient’s serum and commercially supplied RBCs that are specifically selected to contain optimal numbers of RBC antigens or antigens that will react with antibodies that are commonly implicated in hemolytic transfusion reactions. • The screen for unexpected antibodies is also used on donor serum and is performed shortly after withdrawal of blood from the donor.
  • 55.
  • 56. Emergency transfusion and massive transfusion protocol • In many situations, urgent need for blood occurs before completion of compatibility testing (ABO-Rh, antibody screen, and crossmatch ,for those situations that do not allow time for complete testing, an abbreviated format for testing can be used . • TYPE-SPECIFIC, PARTIALLY CROSSMATCHED BLOOD-This takes 1 to 5 minutes and eliminates serious hemolytic reactions resulting from errors that may occur in ABO typing. • TYPE-SPECIFIC, UNCROSSMATCHED BLOOD-For those who have never been exposed to foreign RBCs, most ABO type-specific transfusions are successful • TYPE O RH-NEGATIVE (UNIVERSAL DONOR), UNCROSSMATCHED BLOOD-
  • 57. Emergency transfusion and massive transfusion protocol • Some hospitals have an emergency-release RBC pack, which is uncrossmatched RBCs that are O negative. • If clinicians think the situation is urgent, this blood usually can be provided in approximately 5 minutes. • Also available in concept in some hospitals is a massive transfusion protocol (MTP), which includes 4 units uncrossmatched O negative RBCs, 4 units thawed AB plasma, and 1 unit of platelet concentrates.
  • 58. MASSIVE BLOOD TRANSFUSION • Defined as: • Replacement of 1 circulating blood volume (around 10–12 units of PRBCS) within 24 hrs • Loss of 50% of circulating blood volume within 3 hrs • Loss of 10% of circulating blood volume within 10 mins • Transfusion of 10 units of blood within 6 hrs • Transfusion of 4 units of blood within 1 hour with continuing blood loss • Transfusion of 1 unit of blood within 5 minutes.
  • 59. Preparation for Massive Blood Transfusion • Two large gauge venous cannula (14 G) • Triple lumen central venous catheter • Monitors: • Triple lumen central venous catheter used for: • Rapid blood sampling • Measurement of CVP. • Foleys catheter to measure urine output • Central and peripheral temperature should be measured • Pulse oximetry, arterial pressure and ECG should be monitored.
  • 60. Method of Administration • Constant pressure infusion device • For faster rates of transfusion: • –– Increase height of fluid above patient • –– Manual compression of bag • –– Using syringe and three way tap to aspirate and push volume. • Warming of Stored Blood • Double length blood warming coil • Counter current aluminium heat exchangers • Plastic coils/plastics cassettes in warm water bath (37–38°􀂃C) • Warming plates which have an upper (43 􀂃C) and lower limits (33 􀂃C) is safest.
  • 61. Management of Massive Transfusion
  • 62. Complications of Massive Transfusion • Coagulopathy- Transfusion guidelines: • –– If platelet count < 50000/μl, platelet transfusion • –– If INR > 1.5, transfuse FFP • –– If fibrinogen < 100 mg/dl, transfuse cryoprecipitate. • Citrate Toxicity • Not caused by citrate ion per se, but because citrate binds to Ca2+ • Each unit of blood contains 3 gms of citrate
  • 63. • Hypocalcemia occurs only when: • -- Rates of transfusion > 1 ml/kg/min • -- 1 unit blood transfused in 5 min. • –– Rate of citrate metabolism reduces by 50% when body temperature reduces from 37°􀂃C to 31 􀂃C. • Clinical features: • –– Reduced myocardial function • –– Hypotension, narrow pulse press, increased diastolic pressure and CVP • –– Increased QTc, widened QRS and flattened T-waves.
  • 64. Treatment: • –– 1 gm calcium gluconate (10%) given IV for every 5 units blood/FPP • –– 13.4% calcium chloride contains 0.192 mmol/ml of Ca2+ • –– 10% calcium gluconate contains only 0.22 mmol/ml of Ca2+ • –– CaCl2 is not used much even though it contains more Ca2+ as it very irritant to veins.
  • 65. Hyperkalemia • Serum K+ is as high as 19–30 mEq/l in stored blood after 21 days • This is because RBCs exchange K+ ions to uptake H+ ions generated by metabolism • Precipitating factors: • –– Large amounts of blood must be given for hyper K+ to occur • –– Rate of blood infusion > 120 ml/min • –– Premature infants are especially susceptible • Transfuse only fresh (< 8 days old) plasma reduced or washed PRBCs if rapid transfusion is required (> 10–15 ml/kg/2 hours) in premature infants • Hypokalemia occurs 24 hrs after transfusion as the transfused cells correct their electrolyte composition and K+ enters cells.
  • 66. Hypernatremia • Serum Na+ of whole blood and FFP > normal blood levels due to sodium citrate • Hypernatremia occurs when large volume of plasma is given to patients with disordered salt and water handling: Liver disease, cardiac and renal disease • Na+ increases to 150–160 mm/l after 3 weeks of storage of plasma.
  • 67. Acid Base Abnormalities • Causes of acidosis of bank blood: • –– pH of storage media like CPDA is very low (5.5). • –– Accumulation of lactic acid and pyruvate by RBC metabolism. • –– PCO2 increases to 150–220 mm Hg as the plastic container does not provide air escape mechanisms for CO2. • On blood transfusion, the citrate present in stored blood is metabolized in liver • This generates large amounts of bicarbonate which may neutralize metabolic acidosis initially. • Thus, initially, metabolic acidosis and hyperkalemia occur while later alkalosis and hypokalemia occur.
  • 68. Hypothermia • • One unit of PRBCs at 40 􀂃C will reduce core temperature of 70 kg patient by 0.25 􀂃C • • Blood warming device must be used for any transfusion requiring > 2 U blood • • If < 30 􀂃C ventricular irritability and cardiac arrest occurs • • Safest method is passing blood through plastic coils or plastic cassettes in warm water bath (37–38 􀂃C) • • Harmful effects of hypothermia: • –– Shifts ODC curve to left • –– Reduces metabolism of citrate, lactate and other drugs • –– Impairs hemostasis • –– Increased postoperative infection • –– Shivering increases O2 consumption by 400%.
  • 69. Tissue Oxygenation • Depletion of 2, 3-DPG shifts ODC curve to left • Tissue oxygen delivery is reduced • After transfusion, 2,3-DPG returns to normal in 12–24 hrs.
  • 70. Hyperbilirubinemia • Jaundice as significant amounts of transfused blood may not survive • Also, liver function may be impaired, particularly in the presence of sepsis or multi organ failure, • Paradoxical conjugated hyper bilirubinemia occurs • –– Increased load of bilirubin from destroyed RBCs occurs which is conjugated • –– There may be delayed excretion which causes conjugated hyperbilirubinemia.
  • 71. Multiorgan Dysfunction • • Due to lysis of RBCs during storage causing free Hb release • This causes oxidant mediated injury causing MODS
  • 72. Microaggregates • Platelet aggregates form during 2nd–5th day • From 10 days onwards, larger aggregates form with: • –– Fibrin • –– Degenerated WBCs • –– Platelets • –– Size of 100–200 μm which can cause: • -- Acute lung injury • -- Hypoxemia • -- DIC and tissue ischemia • -- Complement activation. • Use filter when > 1 L of blood is transfused.
  • 73. Adverse Transfusion Events • Classified into -Immediate -Delayed
  • 74. Immediate • Further divided into • A – Immunological 1) Haemolytic transfusion reaction 2) Febrile nonhemolytic transfusion reaction 3) Allergic reactions 4) Anaphylaxis 5) TRALI
  • 75. Immediate… • B - Non Immunological 1) Bacterial contamination 2) Circulatory overload 3) Metabolic complications 4) Non immune haemolysis
  • 76. Delayed • A – Immunological 1) Delayed haemolytic tranfusion reaction 2) TAGVHD 3) Post transfusion Purpura (PTP) 4) Alloimmunization • B - Non Immunological 1) Iron overload 2) Transfusion transmitted diseases
  • 77.
  • 78.
  • 79. TRANSFUSION-RELATED ACUTE LUNG INJURY • Non cardiogenic form of pulmonary edema occurring after blood product administration • New acute lung injury occurring within 6 hrs of a completed transfusion with ratio of PaO2/FiO2< 300 mm Hg or O2 saturation as measured by pulse oximetry of less than 90% when the patient is breathing room air.
  • 80. Risk Factors • Associated with transfusion of all products: • –– Whole blood • –– PRBCs • –– FFP, platelets, cryoprecipitate • –– Intravenous immunoglobulin therapy (IVIg therapy) • –– Granulocytes, stem cell preparation.
  • 81. Risk Factors • • Multiparous donors • Underlying clinical conditions: Two hit hypothesis • –– Trauma • –– Surgery • –– Sepsis • –– Systemic Inflammatory Response Syndrome(SIRS)
  • 82. • Storage of blood products causes: • –– Accumulation of cytokines which injuries alveolar capillary membrane • –– Depletion of nitric oxide causing pulmonary vasoconstriction • –– Depletion of nitric oxide also causes increase in hydrostatic pressure and TRALI • Massive transfusion: strong association between exposure to multiple transfusions and development of TRALI.
  • 83. Pathogenesis • Antigranulocyte Antibody Theory • Donor blood contains antibodies against recipient WBC antigen causing cellular activation • The activated neutrophils lodge in pulmonary capillaries. • Granulocyte Priming Theory • Biologically active substances (such as lipids and cytokines) are present within the transfusion • These substances are called Biological Response Modifiers or BRM • Examples of BRM are lysophosphatidyl choline • These have the ability to prune the activity of granulocytes in pulmonary vasculature
  • 84. Clinical Features • Acute onset dyspnea, severe hypoxemia • Fever, chills, rigors • Noncardiogenic pulmonary edema, hypotension/ hypertension • Fluid in ET tube within 1–2 hrs after transfusion but in full force within 6 hrs • If undiluted edema fluid obtained from ETT, edema fluid protein: plasma protein ratio > 0.6 suggests TRALI rather than TACO • Chest X-ray shows bilateral chest infiltrates • PO2 levels return to normal within 48–96 hrs • Hypoxia and chest X-ray infilterates may persists for 7 days.
  • 85. Treatment • Immediately stop blood transfusion • Mainly supportive hemodynamic and ventilatory support • Supplemental O2 if mild manifestations • Mechanical ventilation with low tidal volume and plateau pressures if moderate-severe manifestations • High FiO2, PEEP may be required (similar to ARDS) • Diuretics have no role in TRALI can be tried if TRALI cannot be differentiated from TACO • IV corticosteroids have been tried to reduce complement mediated granulocyte activation. • Rapid resolution usually occurs in 96 hrs
  • 86.
  • 87. Pharmacological Blood Sparing Strategies • ERYTHROPOIETIN- 300 U /kg x14 days or 600 U / kg thrice a week. • ANTIFIBRINOLYTICS, includes EACA and tranexamic acid, which are plasminogen inhibitors. • tranexamic acid – 10 – 15 mg / kg prior to release of tourniquet • SERINE PROTEASE INHIBITORS- aprotinin, nafamostat, and ecallantide. • Aprotinin – 2 million loading 0.5 million units / hr -inhibits fibrinolysis and improves platelet function. • SYNTHETIC ANALOGUES OF THE ANTIDIURETIC HORMONE VASOPRESSIN. - • Desmopressin (1-deamino-8-D-arginine vasopressin [DDAVP])- increases the levels of factor VIII and von Willebrand factor • FIBRINOGEN – ( Combination of bovine thrombin & human fibrinogen)
  • 88. Patient blood management • Transfusion trigger- • Transfusion is rarely indicated when the haemoglobin concentration is greater than 10 gm/dl, and is almost always indicated when it is less than 6 gm/dl. • For intermediate haemoglobin concentrations (6–10 gm/dl), justifying transfusion Based on • – ongoing indication of organ ischemia, • – potential or actual ongoing bleeding (rate and magnitude), • – the patient's intravascular volume status, and • – the patient's risk factors for complications of inadequate oxygenation.
  • 89.
  • 90.
  • 91. Monitoring for blood loss. • A visual assessment of the surgical field should be periodically conducted to assess the presence of excessive microvascular bleeding (i.e , coagulopathy). • Standard methods for quantitative measurement of blood loss (e.g., suction and sponge) should be used. • Monitoring for inadequate perfusion and oxygenation of vital organs. • Clinical indications of tissue hypoxia-Unstable vital signs
  • 92.
  • 93.
  • 94. Laboratory and invasive monitor indices • Mixed venous O2 saturation (SVmO2) <50% • Central venous O2 saturation (SVcO2) <60% • Increased O2 extraction ratio (O2ER) >50% • Lactic acidosis (metabolic acidemia with lactate >2 mmol/L) • Electrocardiographic (ST changes, onset of arrhythmias) or echocardiographic indications of myocardial ischemia • Electroencephalographic indications of cerebral hypoperfusion • New onset oliguria (less than 0.5 mL/kg/h for >6 h)
  • 95.
  • 96. Autologous Blood Harvesting • A) Preoperative Autologous Blood Donation( PABD) • B) Acute Normovoluemic Hemodilution (ANH)
  • 97. PABD • Patients visit 6 weeks in advance to donate blood • Blood donation 1 per week • Blood donation stops 3 weeks before surgery • Iron therapy is integral to PABD • No PABD 72 hrs before surgery • Usually 2 units sufficient
  • 98.
  • 99. Contraindications to PABD • 1) If HB < 11 gm /dl • 2) More than 6 units reqd • 3) Comorbidity e.g cardiac disease • 4) Patient having infectious disease markers • Since maximum allowed storage interval for RBC is 6 weeks , hence PABD is executed 6 weeks in advance.
  • 100.
  • 101. ANH • Removal of whole blood , replacement with acellular fluid shortly before anticipated blood loss • Done after Induction of Anesthesia and before start of surgery
  • 102.
  • 103. Advantages of ANH • 1) Reduced Absolute RBC loss • 2) Unit with patient ; no wrong transfusion • 3) No microbiological testing reqd • 4) No risk of hemolytic reaction • Caution: Should be restricted to patients with sufficiently high Hb, who can withstand 1 lt of whole blood to be taken out and in whom low target Hb is deemed appropriate.
  • 104. Cell Salvage • INTRAOPERATIVE / POSTOPERATIVE -Shed surgical blood is suctioned under low pressure into a reservoir filled with saline -Then washed & filtered & returned to patient -Can be given upto 6 hrs at room temperature -Cost effective if loss is > 1000 ml • CONTRAINDICATIONS -Malignancy -Leakage of bowel contents in surgical field
  • 105.