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I. Introduction Transfusion Medicine

Proper selection and utilization of blood components

Removal of blood/ blood components

For tx and prevention of dse

Indications for transfusion: 1. Replacement of oxygen- carrying capacity

(eg: anemic px) 2. Replacement of hemostatic components

(eg: coagulation factors/ platelets) 3. Replacement of circulating volume (eg:

active bleeding)

II. Blood Preservatives

To prolong the corresponding shelf-life of stored blood

Preservative Shelf-life

ACD: Acid Citrate Dextrose 21

CPD: Citrate Phosphate Dextrose

21

CPDA-1: CPD + Adenine 35

RBC Additives (Adsol) High concentration of Dextrose Adenine Mannitol (+/-) Saline

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Adenine- enhances ATP production

Dextrose- provides energy

Mannitol- RBC stabilizing agent

III. Biochemical Changes in Stored Blood

pH ATP 2,3- DPG Sodium

Potassium Hemoglobin

IV. Blood Components

Blood products which are made directly from a unit of blood using different methods of physical separation

Component Therapy

Using only specific portions of the blood

Advantages: More specific Effects and danger of circulatory

overload are less (transfusion of whole blood)

The available blood supply is more effectively used. One unit of blood can be used by several patients.

Whole blood

Packed RBC Plasma

Platelets WBC Cryoprecipitate

Fresh Frozen Plasma

(Thawing)

SY 2

011-2

012 Subject: Pathology (CP)

Topic: Blood Transfusion Lecturer: Dr. Joan Pascual Date of Lecture: September 01, 2011

Transcriptionist: 케이트 ^-^

Pages: 14

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Triple bag set up (packed RBC, plasma and its components)

Single bag set up (1 unit)

Double bag set up (packed RBC and plasma)

Plasma Extractor- separate plasma from packed red cells

V. Blood Preparations A. Products Containing RBC

BLOOD COMPONENT Whole Blood (Stored/

Fresh)

Packed RBC

pRBC Washed pRBC Leukocyte-Poor RBC Frozen (Deglycerolized)

RBC Irradiated RBC

CHARACTERISTICS - RBC, plasma, WBC, platelets

- Fresh blood with ¾ of the plasma taken out

- Produced by centrifugation of whole blood

- contains pRBC with reduced plasma volume (20-25% or original unit), WBC, Platelets

- pRBC that has undergone several saline washings to remove up to 99% of WBC

- Contains RBC, minimal platelets, no plasma

- pRBC with 80-90% of WBC removed by several methods, such as: sedimentation, centrifugation, microaggregate blood filtration

- pRBC frozen to prolong storage life

- contains only RBC & 5% of WBC, no plasma or platelets

* Preparation: Addition of glycerol

prevents crystallization of intracellular water at low temperature

Thawed & washed before use (up to 20% of RBCs are lost during thawing)

- red cells exposed to gamma radiation

- radiation is done to destroy donor lymphocytes & prevent GVHD (Graft vs. Host Disease) in immunocompromised patients

VOLUME - 520mL (with preservatives)

- 400-450mL (real blood component)

260mL 250mL --- 250mL ---

SHELF-LIFE 1-35days 24H (after washing) - 10 years at -65ºC or colder

- 24 hours at 1-6ºC after washing

---

STORAGE 1-6

0C

--- ---

EFFECT 1 unit raises Hgb by 1g/dL and Hct by 0.3% ----------

INDICATIONS Active bleeding with >25% bld loss

- Anemia due to destruction or poor production of RBC

- Chronic anemia - Anemia in patients with

CHF

- PNH (Paroxysmal Nocturnal Hemoglobinemia) complement is removed

- Repeated febrile non-hemolytic transfusion

- Repeated febrile non-hemolytic reactions due to leukoagglutinins (agglutinins present in WBC)

- Same as Washed pRBC - Autologous transfusions

- Recipients of autologous or allogenic bone marrow grafts

- Severe congenital immunodeficiency syndromes involving T-lymphocytes

- Donation to

Whole blood

Packed RBC

Centrifuge: Hard Spin

Plasma

- Debilitated patients - Neonates & infants

reactions due to leukocyte antibodies & other plasma proteins

- Emergency transfusion of Group O RBCs to patients of other ABO groups

- Prevention of anaphylactic reactions in IgA-deficient patients

immunocompetent first-degree relatives of immunocompromised patients

ADVANTAGES - Provides both red cells and volume replacement

- Reduces the exposure to multiple donors

- Less risk for volume overload

- Contains less anticoagulant, ammonia, & electrolyte

- Contains less antibodies & plasma proteins

- Reduces risk of febrile reactions due to WBC & platelets

- Washing reduces formation of microaggregates

- The product is almost devoid of plasma

- Eliminates anticoagulants & unwanted metabolites

--- - Allows storage of rare blood types

- Enables blood bank to maintain a large inventory of blood type

- Eliminates 95% of WBC, platelets & plasma proteins

- Prevents febrile reactions & immunization

---

DISADVANTAGES - Indiscriminate use can availability of components to multiple patients

- May cause hypovolemia & CHF in patients who are not actively bleeding

- Does not contain any functioning platelets (because platelets are nonviable after 48 hours)

- Factors V & VII are decreased

- Increase in potassium is dangerous to patients with renal disease

- Citrate accumulation leading to hypercalcemia, which can lead to development of MI (because citrate binds to Ca)

- Slower infusion rate - Preparation is time-consuming & labor-intensive

--- - Costly & tedious - Significant time is lost

during thawing - Once thawed, cells must

be used within 24 hours

---

Soft spin

B. Platelets

PLATELET COMPONENT Platelet Concentrate Platelet Immunologic Refractory State

QUALITY CONTROL - Contains at least 5.5 x 1010

platelets in 75% of PC units tested - Pxs receiving repeated platelet transfusions - Pxs develop HLA-Ab against transfused platelets,

hence, platelets from HLA-matched donors should be used

* HLA- Human Leukocyte Antigen

VOLUME - 50mL donor plasma and 10M WBC

PREPARATION - Must be separated from freshly collected blood within 8H (inactivated within 48H)

SHELF-LIFE 5days

STORAGE 20-240C with gentle agitation (using a platelet rotator)

EFFECTS - Adults: 4,000/mm3/unit

- Children: 7,000/mm3/unit

INDICATIONS - Prophylactically correct thrombocytopenia to prevent catastrophic haemorrhage - Bleeding pxs in surgery/ trauma with platelets <75,000 - Bleeding pxs with qualitative platelet d/os

NOT EFFECTIVE - Conditions causing rapid platelet destruction: DIC, ITP, Gram (-) Septic Shock

C. Plasma, Plasma Components and Derivatives

PLASMA – non-cellular, straw-colored fluid portion of anti-coagulated whole blood when the WB is allowed to settle or is centrifuged COMPOSITION OF PLASMA:

Water

Electrolytes

Proteins: Albumin, Globulins, Coagulation Factors Others: (Not discussed in the table)

Fibrinogen

Plasma protein fraction (PPF)

Albumin

Immune serum globulins

PLASMA COMPONENT Stored Plasma Fresh Frozen Plasma (FFP) Cryoprecipitate Coagulation Factor Concentrates

CHARACTERISTICS --- - plasma from fresh whole blood immediately separated and frozen

- contains plasma proteins, all coagulation factors, complement, 90% water, 6-8% protein, carbohydrates, lipids

- material that does not become totally liquid when FFP is thawed

- contains 80 units of: Factor VIII, Von Willebrand Factor, Factor XIII, Fibrinogen, Fibronectin, Other plasma proteins

- prepared from a pool of donor blood and lyophilized

VOLUME --- 200-260 ml 10-15mL ---

Hard spin

Whole blood

Packed RBC Platelet-rich Plasma

Plasma

Platelet concentrate

PREPARATION - Prepared from 1 unit of WB using a plasma extractor

--- - FFP thawed slolwly at 1-60C (not 30-

370C as when preparing it for

transfusion) - Centrifuge - Remove liquid plasma leaving 15mL of

plasma and the remaining product is refrozen and stored at -18

0C or below

---

SHELF- LIFE 40 days (or less) from the date of WB collection

- 1 year at -18ºC or colder - After thawing, store at 1º-6–C and use within

24 hours

- 1 year at -18ºC or colder - Use within 6 hours after thawing - Should not be refrozen once thawed

---

STORAGE 1-6ºC ---

INDICATIONS - Blood volume expansion - Coagulation defects

- Bleeding due to liver disease, DIC, or massive transfusion (where hemorrhage is secondary to factor deficiency)

- In single or multiple coagulation deficiencies, either prophylactically or as treatment of bleeding

- Replacement of factor deficiency when specific component therapy is not available or appropriate (factors II, V, VII, IX, X or XI)

- factor VIII deficiency - von Willebrand disease - Factor XIII deficiency - Hypofibrogenemia - Replacement of fibronectin lost in

burns & traumatic shock

1. Factor VIII Concentrate - Haemophilia A

2. Factor IX Concentrate - Haemophilia B - Hemophilia A pxs with Factor VIII

inhibitors - Factor II, VII, X deficiency if FFP

cannot be used

ADVANTAGES --- --- - Preferable to FFP in correction of bleeding disorders because of smaller volume

---

DISADVANTAGES --- - Should not be used as a plasma expander or source of protein nutrition or immunoglobulins

- Should be ABO compatible with recipient’s RBC (crossmatching not required)

- Cannot be used for bleeding disorders other than those specified

---

Fresh frozen plasma (FFP)

Whole blood

Packed RBC Plasma Fresh Frozen Plasma

Centrifuge

Freeze at -180C

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VI. Blood Collection A. Donor Registration

Name Date of birth Address

Date of donation Consent form

B. Donor Selection

1. Donor criteria Medical hx PE

Basic qualification

2. Deferral- act of putting off to a future time

TYPE Permanent Temporary

DESCRIPTION Can NEVER donate NOT ALLOWED to donate at a PARTICULAR TIME

CAUSES - Drug abuse - Chronic alcoholism (potential for liver dse) - Prolonged bleeding - Unexplained wt loss (>5kg x 6mos) - High risk sexual bvr (continuing exposure to

hepatitis, HIV/AIDS, STD) - High risk occupation (prostitutes) - STD - Severe lung dse - Severe liver dse (hepatitis, jaundice of unknown

origin) - Cardiac dses - CA

- Past exposure to HIV, AIDS or Hepatitis - Diagnosed/ treated malaria - Alcohol intake - Vaccination (depends on vaccine administered) - Medications (eg: aspirin) - <16y/o; >65y/o - Athletes with PR <50bpm - Hyper/hypotension - Hazardous occupation (eg: construction) - Skin lesions at venepuncture site - Past exposure to unhygienic skin piercing (eg:

tattoo can donate if tattoo is already >1year; for safety: REJECT)

- Pregnancy - Major operation - Previous donation - Blood transfusion - Fever

3. Basic qualifications Good health, 16-55y/o Wt: 50kgs (450mL donation); 40kgs

(250mL donation) Afebrile (during the time of

examination)

PR: 50-11bpm, regular rhythm BP: 90-160mmHg (systolic); 60-

100mmHg (diastolic) Hgb: 12.5g/dL

C. Blood Screening Tests

1. ABO Typing 2. Rh Typing 3. VDRL (Syphilis)- Venereal Dse Research

Laboratory Test

4. Malarial Smear 5. HBsAg- surface Ag of Hepatitis B Virus 6. HCV- Hepatitis C Virus 7. HIV- Human Immunodeficiency Virus

D. Phlebotomy

405-495mL of bld is withdrawn in 7-10min Bld is collected in a bag containing 63mL CPDA-1/ CPD preservatives 30mL drawn into pilot tube Stored at 1-6

0C except in platelet preparation

Donor rxn: o Vaso-vagal rxns: bradycardia, dizziness, diaphoresis, pallor, nausea, vomiting o Hyperventilation: may lead to respiratory alkalosis and convulsions o Hematoma o Hypotension (d/t hypovolemia): tachycardia, hypotension, loss of consciousness

Precautions: o Check phlebotomy site o Allow patient to remain reclining in bed for next 24H o Increase fluid intake for the next 4 hours

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o May resume normal activities after 30 minutes if donor is feeling well, except for persons working with heavy machinery or at heights.

o Blood volume rapidly returns to normal with adequate fluid intake, complete blood volume restoration should take less than 12 hours

VII. Blood Transfusion – infusion of bld components

A. Safety Checks Prior to Transfusion

Proper identification

Check data in donor bag (ABO, Rh Type, expiratioin date)

Check bld in donor bag (appearance)

Check IV line for transfusion (0.9% NSS)

Check transfusion devices (eg: filters)

B. During Transfusion

Monitor VS q15min (before, during, after transfusion)

Check speed of transfusion (60gtts/min; 1unit x 3-4H)

Check for s/sxs that might be confused with a transfusion rxn

VIII. Special Types of Transfusions and Related Procedures

TYPE OF TRANSFUSION

Hemapheresis Autologous Transfusion Massive Transfusion Neonatal Hemotherapy Exchange Transfusion Emergency

Transfusion

DESCRIPTION - a procedure in which whole blood is removed from a person, anticoagulated, and separated into components

- unwanted portions are returned to the donor

- makes use of: Cell/ plasma separators, plasmapheresis machine

- Transfusion of blood & blood products derived from the recipient’s own blood

- Infusion of blood equivalent to patient blood volume (8-10 units) within 24 hours or replacement of ½ of the patient’s blood volume at any one time

- blood transfusion in neonates (from birth to 4 months)

- small amounts of blood are removed from the baby & replaced with donor blood, until 1 or 2 total blood volume exchange is completed

- If the patient cannot receive blood of his own ABO Group, then an alternative ABO Group is used

USES - To obtain blood components needed for transfusion

- To remove pathologic elements, cells, & dissolved plasma factors circulating in the blood

- Rare blood types - For patients who reacts

adversely to homologous blood

- For patients who refuse homologous blood due to religious beliefs (e.g. Jehovah’s Witnesses)

- To avoid harmful effects of infection, hemolytic reactions, & non-hemolytic reactions

--- - to replace blood lost during blood examinations in infants (bld <7days old should be used to maximize 2,3-DPG levels)

- Hemolytic Disease of the Newborn

- To remove unbound IgG antibody, excess bilirubin, & uncoated RBC

- To correct anemia & replace fetal RBC with adult RBC (which is better capable of releasing oxygen to the tissues)

- Sepsis - Diffuse Intravascular

Coagulopathy (DIC) - Polycytemia - Respiratory Distress Syndrome - Hyperammonemia - Toxin removal

---

ADVANTAGES - Components can be obtained in large quantities and more frequently from a single donor

- Prevents transfusion-transmitted diseases

- Eliminates alloimmunization to cellular elements & plasma proteins

- Eliminates GVHD (Graft Versus Host Disease)

--- --- --- ---

TYPES 1. PLATELET PHERESIS – for extracting platelets

2. GRANULOCYTOPHERESIS – for extracting granulocytes

3. PLASMA PHERESIS – for extracting plasma

1. PRE-SURGICAL / PRE-DEPOSIT PHLEBOTOMY - patient is bled as often as

every 72 hours prior to surgery

- iron supplements are given

--- --- --- ---

4. THERAPEUTIC PLASMA PHERESIS – plasma exchange. (Ix: polycythemia vera)

2. INTRA-OPERATIVE SALVAGE - blood is aspirated from

operative site, filtered & washed, & transfused to the patient within 6H

- use: For massive bleeding, when blood is not readily available

- Disadvantage: blood may be contaminated

3. NORMOVOLEMIC HEMODILUTION - Bld is collected

intraoperatively into bld collection bags and replaced by saline

- Collected bld is returned at or near the end of the procedure (<8H after collection)

- Bld is recycled

OTHERS --- --- ADVERSE CONDITIONS: 1. Circulatory overload 2. Complications related to physical

/ biochemical changes in stored blood: - Bleeding due to deterioration

of platelets, Factor V, & Factor VII in stored WB

- Decreased 2,3-DPG in stored blood (shifts oxygen dissociation curve to the left; Hgb doesn’t readily release oxygen to the tissues freely)

- Increased Ammonium & Potassium (dangerous to patients with renal & liver dses)

- Citrate toxicity & hypocalcemia - Hypothermia – may lead to

ventricular fibrillation

--- DONOR BLOOD REQTS: 1. Must be negative for the RBC

antigen to which the mother has the corresponding antibody

2. Must be ABO- and Rh- compatible with the infant’s blood group

3. Must be crossmatched with the mother’s serum - if the mother’s specimen is

not available, Type O blood must be used

- Rh(+) blood may be given to Rh(+) infants whenever the mother lacks anti-D

4. Must be < 7 days old

Rh (-) BLOOD SHOULD BE RESERVED FOR: - Rh (-) females of

child-bearing age

- Rh (-) patients, because Rh(-) blood is rare

- For those who have exhibited anti-Rh antibodies

SELECTION OF ABO GROUP COMPATIBLE FOR EXCHANGE TRANSFUSION

MOTHER’S GROUP INFANT’S GROUP DONOR GROUP

O, A, B O O

O or B A O

A or AB A A or O

O or A B O

B or AB B B or O

A AB A or O

B AB B or O

AB AB AB, A, B, O

EMERGENCY TRANSFUSION ABO GROUPS

PATIENT’S GROUP 1ST

CHOICE 2ND

CHOICE

A O None

B O None

AB A & B O

O No alternative

Rh TYPE

PATIENT’S TYPE Rh (-) Rh (+)

Rh (-) Yes Emergency only

Rh (+) Yes Yes

IX. Transfusion Reactions

the adverse symptoms produced by an erythrocyte incompatibility between a patient & a unit of donor blood

Causes of fatal rxns: Misidentification of patients Mislabeling of blood samples Error in laboratory reports

Mistakes in blood typing Inaccurate antibody screening or in crossmatching

Types of Transfusion Reactions

ACUTE - Occurs within

minutes to 24H of the transfusion

A. HEMOLYTIC ACUTE HEMOLYTIC TRANSFUSION REACTIONS (AHTR) - ABO/ Rh incompatibility - Mechanism: infusion of incompatible red cells in the presence of existing Abs initiates Ag-Ab rxn with activation of complement, plasminogen, kinin and

coagulation system lead to DIC - AHTR Ag-Ab results in:

o Neuroendocrine response (bradykinins) hypotension sympathetic NS o Complement activation hemolysis o Intrinsic pathway activation DIC

- Tx and prevention: o Give IV fluids to maintain intravascular volume o Monitor and maintain urine output >100mL/h using diuretics in addition to fluids o Treat hyperkalemia, and if present, bleeding caused by DIC o Prevention relies on error elimination

Intravascular hemolysis - Caused by rapid complement activation by IgM - S/Sxs:

o fever with/without chills o pain at transfusion site o low back pain o hypotension o facial flushing o DIC

Extravascular hemolysis - caused by IgG Abs that coat RBC removal by macrophages of the RES - lab findings:

o increased LDH o spherocytes on PBS o increased unconjugated bilirubin

o Shortness of breath o Acute renal failure

- Lab findings: o Hemoglobinemia o Decreased serum haptoglobulin o Increased LDH o hemoglobinuria

B. NON-HEMOLYTIC

FEBRILE NON-HEMOLYTIC TRANSFUSION REACTIONS (FNHTR) - >/1

0C increase in T

0 (take VS

before/ during transfusion) - Most commonly associated with

platelet transfusions - Abs in the recipient that react

with donor leukocytes cytokine release and pyogenic soluble factors

- s/sxs: o fever o chills o n/v o uneasiness/ discomfort

typically developing during/ within 1-2H of transfusion

- tx and prevention: o antipyretics o leukocyte-reduced RBCs and

platelets (for recurrent FNHTR)

BACTERIAL CONTAMINATION - most commonly

associated with transfusion of platelets (because they are stored at 20-24

0C x 5days) or

RBCs - storage makes the bld

more prone to contamination

- sources of contamination: skin, bld bag, phlebotomist’s bacteria

- s/sxs: (similar with sepsis) o fever, chills o hypotension o n/v o SOB o Voluminous bloody

diarrhea o Shock, renal failure,

DIC - Tx and prevention: o Broad spectrum

antibiotic therapy o Adhere to proper

procedures for collecting, storing, and handling bld products

o Inspect all components before transfusing (clots, hemolyzed, discoloured)

ALLERGIC REACTIONS - Caused by substances in the donor

bld to which the recipient is allergic (recipient Abs against donor Ags)

- Activation of recipient mast cells/ basophils (histamine)

- s/sxs: o mild allergic rxn:

pruritus and localized urticarial (hives) during or shortly after the transfusion

o severe allergic or anaphylactic rxns: (rapid and dramatic in onset – within 1H of starting transfusion) generalized urticarial angioedema respiratory distress

(bronchospasm/ laryngeal edema)

GI sxs (n/v, cramps, diarrhea) Profound hypotension

- Prevention: o If possible, determine the

allergen and use bld products lacking the allergen

o Pre-medicate before transfusion if allogenic plasma must be transfused which is not allergen free

o Predeposit autologous bld/ components before elective surgery

o Provide washed allogenic cellular components

TRANSFUSION RELATED ACUTE LUNG INJURY (TRALI) - Caused by donor Abs to

recipient leukocyte Ags complement activation and clustering of granulocytes in the recipient’s lung microvasculature endothelial damage and capillary leakage

- s/sxs: (similar to ARDS) o severe bilateral

pulmonary edema, hypoxia, fever, tachycardia, hypotension, cyanosis

o typically develops 1-6H post transfusion of plasma-containing bld compoents (because plasma contains leukocyte Ag)

TRANSFUSION RELATED CIRCULATORY OVERLOAD (TRACO) - d/t rapid transfusion

of large volume of bld - may also occur when

small amt of bld is transfused to pxs with abnormal cardiac fxn

- s/sxs: o SOB o Tachycardia o Hypertension o Headache o Edema

- Tx and prevention: o Give diuretics and

O2 o Adm future

transfusions very slowly

DELAYED - Develop

within days to months or even years after the transfusion

A. HEMOLYTIC DELAYED HEMOLYTIC TRANSFUSION REACTIONS (DHTR) - Typically caused by IgG Abs against RBC Ags that developed in response to a previous transfusion/ pregnancy - Anamnestic response causes abs to quickly increase in titer and coat RBCs - Removal of Ab- coated RBCs by macrophages of the RED extravascular hemolysis - s/sxs: (often mild, may even be asymptomatic)

o fever (most common) o pain o post-transfusion jaundice and hyperbilirubinemia o anemia (with spherocytes in PBS) o +/- renal failure o Sudden drop in Hgb with no evidence of haemorrhage/ hemodilution

- Anemia, fever, recent tranasfusion suggestive of DHTR

B. NON- HEMOLYTIC

INFECTIOUS DISEASE TRANSMISSION - Mos after receiving bld - Hepatitis B,C - HIV - Malaria - CMV - Syphilis

TRANSFUSION ASSOCIATED GRAFT-VERSUS-HOST DISEASE (TA-GVHD) - d/t bld transfused to immunocompromised/suppressed recipient - immunocompetent T lymphocytes transfused to an immunodeficient recipient

recognize host Ags as foreign - usually seen in pxs who received transplant - s/sxs: (develops 1-2wks after transfusion)

o lymphocytic infiltrates in intestine, skin, liver o rash (trunk to extremities) o diarrhea, n/v o fever o elevated liver fxn test o pancytopenia of the bone marrow

Factors that influence whether a transfusion reaction will be acute/ delayed:

Number of incompatible red cells infused

Ab class/ subclass

Achievement of optimal temperature for binding

Intravascular Hemolysis Extravascular Hemolysis

RBC

Iron

Globin chain

Heme

Hgb: binds haptoglobin (plasma protein)

Binds transferrin

Binds hemopexin

RBC

Heme

Bilirubin (excreted through bile duct)

Iron, ferritin, hemosiderin, globin chains

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Investigation of Transfusion Reactions 1. Stop transfusion STAT! 2. Check ID (px and donor bld) 3. Obtain bld samples (px and donor) 4. Check for hemolysis (visual and chemical) 5. Do direct Coombs Test 6. Repeat ABO-Rh typing

7. Others: a. Serum haptoglobin/ bilirubin b. Haptoglobin binding capacity c. Urinalysis (to check for hemoglobinuria) d. Culture and gram-stain of donor bld

--------------------------------------------- ------------------END OF TRANSCRIPTION ---------------------------------------------------------------

~ please read your books for more info……. ^_^v

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