Blood Transfusion
Introduction
• In the past “Benign intervention”
• Present “outcome to be avoided”
• Why?
Components
Indications
Complications & management
Components
Whole
blood
Cellular components Fresh plasma
Fresh frozen plasma
Cryoprecipitate Cryosupernatant
Red cells Albumin
Factor VIII
Platelets Immunoglobulin
Fibrinogen
etc
Packed red blood cells
• Also called
• Packed cells
• RBC’s
• Description of Components:
• Concentrated erythrocytes
• Citrate anticoagulant
• Preservative solution/s
• Hct ranges from about 50-65% (e.g., AS-1, AS-3, AS-5) to
about 65-80% (e.g., CPDA-1, CPD, CP2D).
• 50 mL of donor plasma (range 20 mL to 150 mL),
• 42.5-80 g of hemoglobin or 128-240 mL of pure red cells,
• hemoglobin level of the donor,
• starting whole blood collection volume,
• Collection methodology or further processing.
• leukoreduced
Dosing and response
• One unit of compatible RBCs increases the
hemoglobin level in an average sized adult by
approximately 1g/dL or Hct by 3%.
• Dose
• Packed cells (mls)
= wt (kg) x Hb rise required(g/dL) x 4
• Half life of approximately 30 days
Packed red blood cells
• Indications
• Symptomatic deficit of oxygen-carrying capacity
• Exchange transfusion
• Hemolytic disease of new born
• Acute chest syndrome in sickle cell crisis
• Contraindications
• Anemias that can be corrected with specific
medications such as iron, vitamin B12, folic acid, or
erythropoietin
• Coagulation deficiency
• Volume expansion
• To improve oncotic pressure, wound healing and
sense of well being
Indications
• Clinical signs & symptoms
• Exertional dyspnea,
• Chest pain,
• Lethargy,
• Hypotension,
• Pallor,
• Tachycardia,
• Impaired consciousness
• Unreliable esp
• in children
• Anaesthetised patints
Indications
• Physiologic transfusion triggers
• Mixed Venous O2(PvO 2)
• Mixed Venous O2 SaturationSvO2
• O2 ConsumptionVO2
• Oxygen Extraction Ratio—O2ER
• Disadvantage
• Requires invasive monitoring
• May be unreliable in certain clinical situations
ASA Task Force
Recommendations (perioperative)
• Transfusion is rarely indicated when the hemoglobin
level is above 10 g/dL
• Almost always indicated in patients when the
hemoglobin level is below 6 g/dL;
• For hemoglobin level 6-10 g/dL
• Ongoing indication of organ ischemia,
• The rate and magnitude of any potential or actual bleeding,
• The patient’s intravascular volume status
• Risk of complications due to inadequate oxygenation.
Critical care
• Effects of hypovolemia should be
differentiated from that of anemia
• In healthy adults
• Upto 40% loss( approximately 2L in males)
• DO2 is maintained with Hb as low as 6-7 gms
Platelets
Platelets
• Single donor platelets >3.0 x 1011per
bag(250ml) (derived by apheresis)
• Random derived platelets >5.5 x 1010 per
bag(50ml)
• 4-10 RDPs are pooled for one adult transfusion
• Stored up to five days at 20-24°C (room
temperature).
• Continually agitated to prevent clumping.
Storage is limited to five days due to the risk
of bacterial contamination
Platelet Incubator
Stored with constant
agitation
Dosage And Response
• 4-10 RDPs or 1SDP in adults
• 1unit RDP/10 Kg
• 7-10,000/ mm3 for each RDPgiven, or 30-60,000/
mm3 for each SDP given.
• Rate @3ml/kg/hr over 2-3 hours.
• Response adversely affected by
• the presence of fever, sepsis,
• splenomegaly,
• severe bleeding,
• consumptive coagulopathy,
• HLA alloimmunization
• certain drugs (e.g.,amphotericin B).
Transfusion of Platelets:
Indications and Contraindications
• Indications
• Bleeding due to critically decreased circulating platelet
count or functionally abnormal platelets
• Prevention of bleeding from marrow hypoplasia (platelet
count <10,000/μL)
• Selected cases of postoperative bleeding (platelet count
<50,000/μL)
• Contraindications
• Plasma coagulation deficits
• Some conditions with rapid platelet destruction (eg,
ITP, TTP) unless life-threatening hemorrhage
Guidelines- Perioperative
• Cardiothoracic surgery:
• Routine prophylactic transfusions are not required
in the absence of bleeding.
• When coagulation parameters are not significantly
abnormal, counts <100,000/mm3 accompanied by
major unexpected microvascular bleeding
Guidelines- Perioperative
• Other surgical procedures:
• Intraoperative platelet counts as a guide
• Microvascular bleeding in dilutional thrombocytopenia may
require empiric transfusion before counts are available.
• Prophylactic preoperative transfusion
• Is rarely required for counts >100,000/mm3,
• Is usually required for counts <50,000/mm3 and is guided by risk
factors for intermediate counts.
• Procedures with insignificant blood loss or vaginal deliveries can be
performed at counts 50,000/mm3 without prophylactic transfusion.
• Neurologic or ophthalmologic procedures require a platelet
count near 100,000/mm3.
• Transfusion may be required with apparently adequate
counts when known or suspected platelet dysfunction
results in microvascular bleeding.
Guidelines- Perioperative
• Specific procedures:
• In the absence of other coagulopathy, major invasive
procedures require platelet counts of at least 40,000 to
50,000/mm3 (including CVP placement, paracentesis/
thoracentesis, respiratory tract / GI biopsies, closed Liver
biopsy, lumbar puncture, sinus aspiration & dental
extraction).
• A threshold of 80,000/mm3 has been proposed for spinal
epidural anesthesia.
• Fiberoptic bronchoscopy without biopsy by an experienced
operator may be safely performed in the presence of a
platelet count <20,000/mm3.
• GI endoscopy without biopsy may be safely performed
• at platelet counts <20,000/mm3.
Guidelines- Perioperative
• Platelet Function Defects: Transfusion is
• Indicated in critical bleeding or before major
surgery regardless of the platelet count.
• Not indicated
• When defect extrinsic to the platelet (e.g.,uremia,
certain types of von Willebrand Disease,
hyperglobulinemia)
• Antiplatelet Agents:Thienopyridine platelet ADP
receptor inhibitors and direct glycoprotein IIb/IIIa
inhibitors impair platelet function in absence of
thrombocytopenia
• But high dose therapeutic transfusion may be required
for life threatening hemorrhage in patients on these
drugs.
Guidelines :Critical Care
• Massive transfusion:
• A transfusion target of >50,000/mm3 in acutely bleeding
patients and >100,000/mm3 for those with polytrauma or
CNS injury.
• The platelet count may fall below 50,000/mm3 when >1.5–2
blood volumes have been replaced with red cells.
• In the presence of microvascular bleeding, transfusion may
be appropriate when counts are known or suspected to be
<100,000/mm3.
• Disseminated/local Intravascular coagulation
(DIC/LIC) and/or sepsis
• Microvascular bleeding is treated in children and adults with
platelet counts <50,000/mm3
• Neonates<100,000/mm3.
FRESH FROZEN PLASMA
Fresh Frozen Plasma
• Separated from whole blood and frozen within 8 hours of
collection. It can be obtained from a whole blood donation
(approx. 250 ml) or by apheresis (approx. 500 ml).
• Frozen Plasma must be thawed, usually in a water bath,
and infused immediately or stored at 1-6oC for up to 24
hours.
• Contains a normal concentration of fibrinogen and the
labile coagulation factors VIII and V.
• Fresh frozen plasma contains the clotting factors that are
necessary for hemostasis.
• Plasma also has volume expansion and oncotic
properties.
Frozen Plasma 24
• The plasma is separated after cold centrifugation and
processed to the frozen state within 24 hours of
collection
• Frozen plasma contains stable coagulation factors
such as Factor IX and fibrinogen in concentrations
similar to FFP, but reduced amounts of Factor V and
VIII.
• The indications and side effects are the same as for
FFP, except that FP should not be used to treat
coagulation factor deficiencies of Factor V and Factor
VIII.
Dosing
• Multiple coagulation factor defeciency
• 10-20 ml/kg
• Isolated coagulation factor deficiencies for which no
concentrated preparation is available (e.g., factor V, or
XI)
• The half-life of the specific factor,
• The pretransfusion level of the factor,
• The desired post transfusion level
• Duration of raised levels required.
• TTP
• initially requires exchange of 1 – 1.5 plasma volume daily
• Twice daily single plasma volume exchanges in refractory
patients.
Indications
• Active bleeding or risk of bleeding due to deficiency of
multiple coagulation factors,
• Severe bleeding due to warfarin therapy, or urgent
reversal of warfarin effect
• Massive transfusion with coagulopathic bleeding.
• Bleeding or prophylaxis of bleeding for a known single
coagulation factor deficiency for which no concentrate is
available.
• Thrombotic thrombocytopenic purpura.
• Rare specific plasma protein deficiencies, such as C1-
inhibitor.
Contra-indications
• Increasing blood volume or albumin
concentration
• Coagulopathy that can be corrected with
administration of vitamin K.
• Normalizing abnormal coagulation screen
results, in the absence of bleeding.
Cryoprecipitate
Cryoprecipitate
CRYOPRECIPITATE
• Cryoprecipitate is prepared by thawing fresh
frozen plasma at a temperature between 1°C and
6°C. After centrifugation, the supernatant plasma
is removed and the insoluble cryoprecipitate is
refrozen.
• On average, each unit of cryoprecipitate contains
80 IU or more Factor VIII (FVIII:C) and at least
150 mg of fibrinogen in 5-15 mL of plasma.
• Cryoprecipitate provides a source of coagulation
factors. Factor VIII, Factor XIII and von
Willebrand Factor.
• Fibrinogen and fibronectin are present.
CRYOPRECIPITATE
• Acellular blood component.
• Compatibility testing inluding Rh type is
unnecessary.
• CMV testing and leukoreduction are not required.
• Frozen cryoprecipitate is thawed in a protective
plastic overwrap in a waterbath at 30-37oC up to 15
minutes.
• Kept at room temp & transfused as soon as possible
after thawing or within 6 hours if it is a closed single
unit or has been pooled prior to freezing.
• It should be transfused within 4 hours if it is an open
system or units have been pooled after thawing.
Dosing
• Fibrinogen required (mg) =
• (desired F(mg/dL) - initial F (mg/dL)) X plasma
volume (mL) /100
• Bags of cryo required = mg fibrinogen required
250 mg
• A typical dose for the treatment of
hypofibrinogenemia is one cryoprecipitate unit
per 7 - 10 kg of body weight.
Indications and Contra-
indications
• Indications
• Bleeding associated with fibrinogen deficiencies (<100mg/dl) and
Factor XIII deficiency esp if FFP cannot be given due to volume
overload
• Indicated in hemophilia A or von Willebrand’s disease (vWD)
when appropriate Factor VIII concentrates or Factor VIII
concentrates containing FVIII:vWF are not available.
• Fibrin Sealant
• Uremic bleeding
• Contraindications
• Do not transfuse cryoprecipitate unless laboratory studies confirm
deficiency of a specific clotting protein for which this component
is indicated (e.g. fibrinogen).
Clotting factors
• Factor VIII
• Dose
• Loading Dose 50 u/kg
• Infusion 3u/kg/hr
• Factor IX
• Dose
• Loading dose100u/kg
• Infusion 3u/kg/hr
• Activated Factor VIIa (NovosevenTM)
• Factor XIII (13) FibrogamminTM
• ProthrombinexTM
Complications
• Immunologic Complications, Immediate
• Hemolytic transfusion reaction,
• Immune-mediated platelet destruction,
• Febrile nonhemolytic reaction
• Allergic reactions
• Anaphylactoid reactions
• Transfusion-related acute lung injury (TRALI)
Hemolytic transfusion reaction
• Pathogenesis –
• Immunologic destruction of transfused red cells, due to
antigen antibody reaction.
• Mistransfusion of ABO-incompatible blood, resulting from
identification errors
• Incompatibility unidentified during pretransfusion testing
• Symptoms and signs
• an increase in temperature and pulse rate;
• chills,
• dyspnea, chest or back pain,
• Abnormal bleeding, or shock.
• Instability of blood pressure
• In anesthetized patients,
• Hypotension
• Evidence of disseminated intravascular coagulopathy (DIC)
Hemolytic transfusion reaction
• Laboratory findings
• hemoglobinemia and/or hemoglobinuria,
• elevation of serum bilirubin;
• in less catastrophic acute hemolytic reactions, a
positive direct antiglobulin test (DAT)
• Treatment
• transfusion must be stopped
• measures to maintain or correct arterial blood
pressure; correct coagulopathy,
• promote and maintain urine flow.
• Febrile nonhemolytic reaction
• Symptoms
• Fever Shortly after transfusion
• No tests available for diagnosis
• Treatment
• Antipyretics.
• Patients who experience repeated,severe febrile reactions may
benefit from receiving leukocyte reduced components.
• Allergic reactions
• urticaria,
• wheezing or angioedematous reactions.
• Treatment
• antihistamines
• corticosteroids
• epinephrine.
Anaphylactoid reactions
• Rare but dangerous
• IgA-deficient patients who have IgA antibodies of the IgE class.
• Symptoms
• characterized by autonomic dysregulation
• severe dyspnea,
• pulmonary and/or laryngeal edema,
• bronchospasm and/or laryngospasm,
• Immediate treatment
• Corticosteroids
• epinephrine.
Transfusion-related acute lung
injury (TRALI)
• Pathogenesis
• Passively transfused donor HLA class I/II or neutrophil
antigens
• Mixture of predisposition and infusion of blood-related
lipid-derived mediators
• acutely increased permeability of the pulmonary
microcirculation causes massive leakage of fluids and
protein into the alveolar spaces and interstitium,
• usually within 6 hours of transfusion.
• Treatment consists of aggressive respiratory support.
Immunologic Complications,
Delayed
• Delayed hemolytic reaction
• Alloimunization
• Posttransfusion purpura (PTP)
• Graft-vs-host disease (GVHD)
Delayed hemolytic reaction
• Occurs in previously red-cell-alloimmunized patients
• the usual time frame is 2 to 14 days after transfusion.
• Signs may include
• unexplained fever,
• development of a positive DAT,
• unexplained decrease in hemoglobin/hematocrit.
• Hemoglobinemia and hemoglobinuria are uncommon,
• Elevation of lactic dehydrogenase (LDH) or bilirubin may
be noted.
• Treatment- Benign course- no treatment
Alloimmunization
• Antigens of red cells, white cells, platelets, or
plasma proteins
• Primary immunization does not become
apparent until days or weeks asymptomatic
• Subsequent transfusions causes accelerated
removal of components and systemic reactions
Post Transfusion puroura
• a rare syndrome characterized by the development of
dramatic, sudden, and self-limiting thrombocytopenia,
typically 7-10 days after a blood transfusion,
• history of sensitization by either pregnancy or
transfusion.
• autologous and allogeneic platelets are destroyed.
• Treatment In a bleeding patient, high dose Immune
Globulin Intravenous (IGIV) may promptly correct the
thrombocytopenia.
Graft-vs-host disease (GVHD)
• is a rare but extremely dangerous condition
• Pathogenesis
• occurs when viable T lymphocytes in the transfused
component engraft in the recipient and react against tissue
antigens in the recipient.
• GVHD can occur if the host does not recognize as foreign
and reject the transfused cells, and can follow transfusionof
any component that contains even very small numbers of
viable T lymphocytes.
• Severely immunocompromised recipients are at greatest
risk conditions)
Graft-vs-host Disease (GVHD)
• Can occur immunologically normal recipients
heterozygous for a tissue antigen haplotype for which
the donor is homozygous. This is most likely to occur
when the transfused component is from a blood
relative or has been selected for HLA compatibility.
• GVHD remains a risk with leukocyte-reduced
components because they contain sufficient residual
T lymphocytes.
• Irradiation of the component renders T lymphocytes
incapable of proliferation and is presently the only
approved means to prevent GVHD.
Nonimmunologic Complications
• Transmission of infectious disease
• Bacterial contamination
• Circulatory overload,
• Hypothermia
• Metabolic complications
Transmission of infectious disease
• HIV, HTLV, hepatitis, • Other potential agents
and syphilis,CMV • SARS
• Other potential agents • Influenza
• Simian foamy virus • Bartonella spp.,
(SFV) • Borrelia spp.,
• HHV-8 • Brucella spp.,
• West Nile virus • Leishmania spp.,
• Chagas • Parvovirus spp.,
• nCJD • rickettsia,
• Malaria • Toxoplasma spp.,
Bacterial contamination
• Risk of bacterial sepsis in red cells and
platelet 1:3000 units transfused
• Sepsis develops in 1:25,000 units of platelets
and 1:250,000 units of RBCs transfused
• Symptoms and signs
• Onset of high fever (=2 C or =3.5 F rise in
temperature),
• severe chills,
• hypotension, or circulatory collapse during or
immediately after transfusion
Bacterial contamination
• Both gram-positive and gram-negative organisms
• Treatment
• Prompt recognition of a possible septic reaction
• immediate discontinuation of the transfusion
• aggressive therapy with broad-spectrum antimicrobials
• vasopressor agents, if necessary.
• Investigations
• Prompt sampling of the patient’s blood for cultures at several
different temperatures,
• E xamination of material from the blood container by Gram’s stain,
and cultures of specimens from the container and the administration
set.
Circulatory Overload
• Excessive volume at excessive rapid rate
• In patients with chronic severe anaemia
• Transfusion of small volumes in at risk
patients
• Treatment
• Treat for pulmonary edema
• Hypothermia
• Metabolic complications
• Citrate toxicity
• Severe liver disease
• Inadequqte hepatic blood flow
• Acidosis
• Alkalosis
• Hyperkalemia
• Hypokalemia
Miscellaneous complications
• Iron overload
• Non immunologic hemolysis
• Stored donor blood: “The Cold Storage
Lesion”
• Free hemoglobin Increased nosocomial
infection
• SIRS
The Cold Storage Lesion
Storage Effects Consequences
Reduced to absent 2,3- Increased oxygen affinity and
diphosphoglycerate decreased oxygen unloading by
hemoglobin
Reduced to absent Erythrocyte shape changes
ATP Increased osmotic fragility
Decreased deformability
Microvesiculation and Decreased erythrocyte viability
loss of lipid membrane
Lipid peroxidation Cellular injury and early cell death –
free Hb
Offner PJ, et al. Arch Surg. 2002;137:711-717.
LossM, of
Brown NOPK. Crit Care Nurse. 2000;20(suppl):1-14.
Whalen Vasoconstriction and poor unloading
Zallen G, et al. Shock. 2000;13:29-33.
SUMMARY
“Because of the Risks Associated With
Transfusion, Physicians Should Remain
Familiar With Currently Recognized
Alternatives to Transfusion. Autologous
Transfusion Techniques (Such As
Perioperative Collection and Preoperative
Donation) Should Be Considered, When
Indicated, to Reduce the Need for
allogeneic Transfusion With Its Attendant
Risks of Disease Transmission and
Immune Reactions.”
THANK YOU