Blood Transfusion

Introduction

• In the past “Benign intervention”

• Present “outcome to be avoided”

• Why?

Components

Indications

Complications & management

ComponentsWhole blood

Fresh frozen plasma

Fresh plasma

Cryoprecipitate Cryosupernatant

Cellular components

Red cellsPlatelets

Factor VIIIFibrinogen

AlbuminImmunoglobulin

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, and syphilis,CMV

• Other potential agents• Simian foamy virus

(SFV)• HHV-8• West Nile virus• Chagas• nCJD• Malaria

• Other potential agents• SARS• Influenza• Bartonella spp., • Borrelia spp.,• Brucella spp.,• Leishmania spp.,• Parvovirus spp.,• rickettsia,• 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

Offner PJ, et al. Arch Surg. 2002;137:711-717.Brown M, Whalen PK. Crit Care Nurse. 2000;20(suppl):1-14. Zallen G, et al. Shock. 2000;13:29-33.

Storage Effects ConsequencesReduced to absent 2,3-diphosphoglycerate

Increased oxygen affinity and decreased oxygen unloading by hemoglobin

Reduced to absent ATP

Erythrocyte shape changes

Increased osmotic fragility

Decreased deformability

Microvesiculation and loss of lipid membrane

Decreased erythrocyte viability

Lipid peroxidation Cellular injury and early cell death – free Hb

Loss of NO Vasoconstriction and poor unloading

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.”

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