blood component therapy

BLOOD TRANSFUSION AND

COMPONENT THERAPYDr.Indubala Maurya Assistant professor

Department of Anaesthesia & critical care MGMCRI

Lecture Part 1 ( blood products and its uses ) Part 2 ( Complication of blood transfusion )

What Is The Need For Transfusion

INADEQUATE O2 CARRYING CAPACITY - Anemia - Blood loss

INADEQUATE COAGULATION PROTEINS -To provide adequate homeostasis

General Rules For Transfusion

Should not be the first choice Should have a policy regarding typing,

cross matching for those surgeries where it is not required

Autologous transfusion should be promoted

Whole Blood Transfusion or

Component Therapy

Can give individual component for specific illness Patient does not require all the components This policy can benefit more than one individual

One Unit Of Whole Blood One unit of RBC’S One unit of Platelets One unit of Cryoprecipitate One unit of Plasma (minus above 2 )

1 unit of whole blood = 450 ml blood 63 ml anticoagulant preservative

Blood ComponentsCellular components Plasma components Plasma derivativesRed 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

COMPATIBILITY TESTING

Changes In RBC’s During Storage

Decrease in ATP (can be improved with glucose, phosphate & adenine)

Decrease in 2,3 DPG Hyperkalaemia , Acidosis in storage RBC lysis & decrease in Hb (6 weeks storage- RBC recovery 85%) Membrane damage making it difficult to penetrate microcirculation

( can be improved with Mannitol / Citrate) Decrease in viability ( shelf life of stored RBC’s is 35 – 42 days)

Anticoagulants

AIM – To increase the RBC life, safety & overall effectiveness

1. CPDA (35 Days)2. SAGM- Saline ,Adenine , Glucose, Mannitol3. AS-1, AS-3 ,AS -5 ( Additive solution) (42 Days)4. Extended storage preservative solution containing - Dextrose - NaCl - Citric acid - Sodium citrate - Adenine and Mannitol

Status Of Heparin

Though an anticoagulant ,but maintains viability only upto 24 – 48 hrs

MAIN USE - ECMO - Exchange transfusion

LIGHT SPIN at 2000 rpm for 3 minutes at 22º

RESULT - Packed RBC - PRP

WHY LIGHT SPIN?

To avoid damage to Platelets Process required to be done within 6 hrs of whole blood collection Packed RBC’s are suspended in a hematocrit of 70% (CPDA-1) or 60 % ( AS -1 or AS- 3,5)

HEAVY SPIN at 5000 rpm ,5 minutes & 4ºC

RESULT- PPP

Heavy spin → Damage to platelets

Volume → 200 – 400 ml per whole blood transfusion bag

Platelet Poor Plasma (PPP)

FRESH PLASMA Prepared & infused within 6 hrs of preparation

FRESH FROZEN PLASMA Fresh plasma stored at -20ºC in a freezer

Is stable for 1 year

Both forms of PPP have all the Coagulation factors &

proteins

High spin at 4 ºC to PPP

RESULT - Cryoprecipitate - Cryosupernant

Cryoprecipitate Concentrated source of Von- Willebrand factor, fibrinogen, Factor VIII

and fibronectin Stable for 1 year

Cryosupernant Remaining plasma after removal of cryoprecipitate

Fresh Whole Blood

Packed Red Cells

Light spin, 22oC

Platelet Rich Plasma

Platelet Concentrate Fresh Plasma

Store at 22oC Freeze(FFP)

Heavy spin, 4oC

Thaw at 4oC & heavy spin

Fresh Frozen Plasma

Cryoprecipitate

-Refrozen within 1 hr

-Store at < - 18oC

Cryoremoved Plasma

Freeze -80oC immediately

Stored at < -18oC

VOLUME

WHOLE BLOOD → PPP → CRYOPRECIPITATE 450ml 250ml 10-20 ml

Packed RBC’s

Most frequently required and used Benefit – Will increase amount of O2 delivery to tissues 1 unit PRBCs = 200 ml RBCs

100 ml additive solution

30 ml plasma Storage - 1ºC to 6 ºC Normally, 20 days viability in CPDA solution Post transfusion viability - 75 %

Indications

Broadly Anaemia Haemorrhage

Other Indications Critically ill patients of sepsis and trauma Acutely bleeding patients - Rapid loss of > 15 % if preexisting Hb is < 10 gm / dl

Indications contd….

Perioperative period - < 8 gm / dl without significant Heart, Lung, Vascular, Renal or Neural disease - < 10 gm / dl with significant underlying diseases

Patients of chronic Anemia - Hb < 8 gm / dl with evidence of CHF, Angina or Hypovolemia

Patients of marrow failure - Hb < 10 gm / dl with Leukemia, Lymphoma , Aplastic anemia

Clinical Indications Of PRBCs Transfusion

SBP < 90 mm Hg Fall in SBP > 40 mm Hg within 4 hrs DBP < 40 mm Hg within 4 hrs Fall in DBP > 40 mm Hg within 4 hrs Heart rate > 100 bpm SpO2 < 90 mm Hg & PaO2 < 70 mm Hg

Leucocyte Reduced Blood Components

WHY REQUIRED? Average unit of RBC’S contain 1 – 2 million WBC’s Average unit of platelets contain 50 million WBC’s Febrile and inflammatory reactions largely due to WBC’s

METHODS FOR REDUCTION Washing of RBC’s( Average life 24 hrs ) Leucocytes reduction filters

Fresh Frozen Plasma (FFP)

Primary source of coagulation factors Most common blood component to be used irrationally in today’s

practice 1 unit of FFP = 200 – 250 ml plasma Expiry date 365 days Use – Thaw at 37 ºC for about 20 – 30 mins Once thawed , can be again stored for upto 24 hrs at 1- 6 ºC

SHOULD BE ABO COMPATIBLE OR IDENTICAL

CROSS MATCHING NOT REQUIRED

Indications

Congenital coagulation factor deficiencies except VII ,VIII, IX or Von Willebrand disease

Acquired coagulation problems like liver disease, Vit. K deficiency

In massive blood transfusion to provide clotting factors Treatment of TTP Dose = 10 – 20 ml / kg 1 unit of FFP = ↑ in factor levels by 3 -5 %

Cryoprecipitate

1 bag of cryoprecipitate = 250 mg of fibrinogen

15 – 20 ml plasma

Von Willebrand factor (IX)

80 – 130 units of factor VIII

Fibronectin

Factor XIII 20 -30 % Expiry date= 365 days Once thawed , use in 4 hrs

Indications

Congenital / Acquired Hypofibrinogenemia

Congenital / Acquired Factor VIII deficiency

Secondary choice in Uraemia

Platelets

CERTAIN FACTS Aphretic platelets collected from a single donor contains platelets

equivalent to 6 - 8 whole blood derived platelet concentrates Storage – 20 – 24 ºC ( Never refrigerate) Expiry – 5 - 7 days Use Platelet filters and not routine blood filters

Indications

Blood platelet count < 50,000 /μl and evidence of significant active bleeding

Thrombocytopenia DIC Dengue Platelet count <10,000 /μlt without evidence of bleeding Bone marrow failure Functional platelet defect & bleeding Dose – 1 unit = ↑ 5000 – 10000 platelets in patient 5 -6 unit = 1 aphretic unit

NO CROSS MATCHING REQUIRED

Transfusion Triggers

The RBC , transfusion triggers is a term used to describe, the set of circumstances under which transfusion is reasonable and for which no further justification is needed.

WHY the word TRIGGER ?

Transfusion Triggers contd…Two type of Physiological Triggers

1) Invasive Triggers

2) Non invasive Triggers

Invasive Triggers1. Mixed venous O2 (PVO2) The rate of a fall is more important

2. Mixed venous O2 saturation ( SVO2) Declines rapidly when haematocrit falls below 20 %

3. Oxygen uptake VO2 In sepsis and low perfusion not a true indicator as DO2 is normal but due to low pressure VO2 is reduced. Will transfusion benefit here?

4. Oxygen extraction ratio O2 ER If it is > 50% , decompensation is imminent . Usually happens at H’crit of 10%

Non invasive Triggers

DO remember1. Minimum Hb reqd to have adequate DO2 for

isolated tissue is 3-5 gm/dl.2. In healthy people, acute normovoluemic

hemodilution can be safely tolerated upto 5 gm /dl.

3. Transfusion is reqd usually at Hb < 7 gm/dl.4. Transfusion is unjustified at Hb >10 gm /dl.5. Duration of Anemia.

ASA Guidelines for Blood Component Therapy

RBC’s-Rarely for Hb>10 g/dl Usually for Hb<6g/dl Decision based on risk for complications related to inadequate oxygenation

Platelets-Rarely for PLT>100,000 Usually for PLT<50,000 For PLT between 50,000 and 100,000 decision based on assessment of risk

FFP-Microvascular bleeding present and PT or PTT is 1.5 times normal .Condemns use for volume replacement

Cryoprecipitate- Consider for fibrinogen levels < 80 mg/dL orwhen levels can not be rapidly obtained

Maximum Surgical Blood Ordering Schedule (MSBOS)

List of procedures performed in a hospital together with recommended quantity of RBC units to cross match , based upon the utilization data specific to that hospital

CROSS MATCH : TRANSFUSION ( C:T) ratio Should not exceed 2 :1

GROUP AND SAVE Procedure where transfusion is not reqd

Blood Sparing Strategies

Transfusion is either

Autologous or Homologous ( Allogenic )

Sparing Strategies in Preoperative Period

Diagnosing and effective treatment of preexisting ailments like Iron deficiency anemia, bleeding disorders.

Review of Anticoagulant therapy

Adoption of MSBOS

Utilizing Cell salvage.

Sparing Strategies in Intraoperative Period

Careful positing to reduce venous congestion To maintain Normothermia If possible controlled Hypotension Appropriate use of Diathermy , laser Utilizing cell salvage Following Transfusion Triggers

Autologous Blood Harvesting

A) Predeposit 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 /dl2) More than 6 units reqd3) 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 loss2) Unit with patient ; no wrong transfusion3) No microbiological testing reqd4) 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

Pharmacological Blood Sparing Strategies

ERYTHROPOIETIN- 300 U /kg x14 days

or 600 U / kg thrice a week

APROTININ ( Serine protease inhibitor) – 2 million loading

0.5 million units / hr

High risk of Anaphylaxis to reexposure

TRANEXAMIC ACID – 10 – 15 mg / kg prior to release of tourniquet

DESMOPRESSIN – Mainly for Haemophilia, Von Willebrand disease

FIBRINOGEN – ( Combination of bovine thrombin & human fibrinogen)

Adverse Transfusion Events

Classified into

Immediate

Delayed

Immediate Further divided into A – Immunological1) Haemolytic transfusion reaction

2) Febrile nonhemolytic transfusion reaction

3) Allergic reactions

4) Anaphylaxis

5) TRALI

ImmediateB - Non Immunological1) Bacterial contamination

2) Circulatory overload

3) Metabolic complications

4) Non immune haemolysis

DelayedA – Immunological1) Delayed haemolytic tranfusion reaction2) TAGVHD3) Post transfusion Purpura (PTP)4) Alloimmunization

B - Non Immunological1) Iron overload2) Transfusion transmitted diseases

Acute Haemolytic Transfusion Reactions

1) Intravascular Haemolysis

2) Extravascular Haemolysis

3) DIC

4) Renal failure

Intravascular Haemolysis (IVH)

Mediated by classical pathway of Complement system

Signs Sudden drop in B.P

Haemoglobinuria

Haemoglobinaemia

No rise in haematocrit

Extravascular Haemolysis (EVH)

Antibody mediated or Complement mediated cell destruction in RE system

Generally life threateningSigns Falling Haematocrit Increased unconjugated bilirubin Abnormal peripheral smear a ) Polychromasis b) Spherocytes May lead to I/V heamolysis

Extravascular Haemolysis (EVH)CAUSE Exposure to patient through previous - Pregnancy - Transplant - Transfusion Generation of antibodies in response to incompatible Antigens

Febrile Nonhemolytic Transfusion Reaction

Most common Adverse effects Increase in temperature of > 10c over base line during

transfusionCause1) Formation of Antibodies in recipients against donor WBCs

and Platelets2) Release of bioactive substances like Interleukins,

Cytokines in the blood

Transfusion Related Acute Lung Injury ( TRALI)

Rapid onset of respiratory distress, noncardiogenic pulmonary edema and hypoxia occuring during or soon after transfusion

CAUSEDue to the presence of A) Anti HLA antibody in the plasma of donor B) Antigranulocyte antibody in the plasma of donor

leads to complement activation and increased pulmonary vascular permeability

Agent - Any plasma containing blood product

TRALIDefinitionNew acute lung injury occurring during or within 6 hours post transfusion with a clear temporal relationship to the transfusionNorth American European Consensus Conference Criteria Acute Hypoxemia PaO2/ fiO2 ≤ 300 mm Hg B/L infilterates in the absence of circulatory overload Edema fluid to plasma protein ratio > 0.6

Limitations

1) Not possible to differentiate between ALI and TRALI2) No specific lab tests3) Limit of 6 hrs may exclude cases developing later

TreatmentOn the lines of ARDS

Anaphylactic Reactions

More commonly observed in Patients of hereditary IgA deficiencyPatients having IgG antibodies to infused

allergens

RemedySaline washed RBCs for future transfusions

Immediate Immunological Reactions

CLINICAL PRESENTATION Chills with fever, nausea, chest tightness Pain at I/V site, abdomen, joints Tachycardia, tachypnea Hypotension, diffuse bleeding Shock, renal failure

CLINICAL PRESENTATION UNDER ANAESTEHSIA Hypotension Dark urine Generalized ooze

Immediate Immunological Reactions

Lab Diagnosis Send blood back for repeat typing and cross

match

Rising serum bilirubin

Urine for heamoglobinuria

Chest X ray if TRALI is suspected

Immediate Immunological Reactions

Management Oxygen by face mask/ Intubation (TRALI) Catheterization Continuous vital monitoring Furosemide (if BP normal) Epinepherine/ corticoids if anaphylaxis suspected Maintain urine output between 30-100ml/hr

Aquired Diseases

Incidence getting less due to effective screening HIV 1 & 2 Hepatitis B & C Syphilis CMV Lyme Malaria Filaria

TA GVHD

Due to transfused immunocompetent lymphocytes against immunocompromised host

Rapid course Average mortality- 90 % Treatment – Gamma irradiated blood products by

exposing WBC’s to 1500 rad to 5000 rad Not much effect on RBC’s Platelet survival decreases by 30 % at higher doses

Metabolic Complications Clinically significant depletion of coagulation

proteins & platelets occur in stored blood leading on to

- Hypothermia - Hyperkalaemia - Hypocalcemia - DIC 8 – 10 units of red cells infused in a patient may

lead to fall in the level of coagulation proteins to 25 % of normal

Delayed Hemolytic Transfusion Reactions

Occuring > than 24 hrs post transfusion Previous transfusion primes the patientSigns & Symptoms Within 4 – 14 days of transfusion Progressive unexplained fall in hemoglobin Low grade fever Unconjugated hyperbilirubinemiaTreatment Self limiting till clearing of all RBC’s

Post Transfusion Purpura More in females 5 – 9 days post transfusion Due to platelet specific alloantibodiesTreatment High dose IV IgG( 2 gm/ kg over 5 days) Platelet transfusion though not effective may be

required for bleeding Steroids ? Plasma exchange?

Massive Blood Transfusion(MBT)

Replacement of one blood mass in a period of 24 hrs Transfusion of 4 or more red cell concenterates with

in 1 hr Replacement of 50% of total blood volume with in 3

hrs Rate of infusion > 1 unit in 10 minutesIndication Hypovolemic shock secondary to blood loss

Complications Of MBTPhysical Hypothermia Hemodilution Metabolic - Hyperkalemia –Plasma K+ levels in the stored blood increased by 1 mEq/ l /day - Citrate toxicity(3 gm / unit) - Acidosis - Alkalosis( 1 ml citrate = 3 mEq HCO3)

Complications Of MBT

Physiological Left shift of ODC

Decrease of labile coagulation factors

Dilutional Thromocytopenia

Citrate Toxicity

May lead to Hypocalcaemia

Look for total calcium : ionized calcium ratio (Normal 2:1)

If low give 10 – 20 ml 10 % calcium gluconate

Thank you