Blood Transfusion in Children

Ma. Ysabel Lesaca-Medina, MD

Pre Lecture QUIZ

#1
Rate of transfusion of pRBC
a. b. c. d. 1 unit in 4 hours 1 unit in 6 hours 3-5 ml/kg/hour 5-10 ml/kg/hour

#2
A reasonable approach to refractory platelet transfusion is a. use crossmatched platelet b. double platelet dose c. administer IVIg one hour prior d. use expiring platelet units

#3
Rate of transfusion of 15 ml/kg FFP
a. 4 hours b. 3 hours c. 2 hours d. 1 hour

#4
What is the purpose of irradiating blood products?
a. decrease risk of Transfusion associated GVHD b. decrease chance for alloimmunization c. decrease risk of bacterial contamination d. decrease allergic reactions

#5
Which of the ff blood products will you transfuse in a patient with congenital hypofibrinogenemia? a.FFP b.Cryoprecipitate c.Platelets d.Whole blood

#6
Patient develops fever (38.5 c) one hour after starting transfusion. You stop transfusion and administer antipyretics. What will you do once px is afebrile? a. resume transfusion of same unit b. rule out acute hemolytic transfusion rxn (AHTR) and administer another unit of blood c. rule out AHTR and resume transfusion of same unit d. once afebrile for 24 hours, administer another unit of blood

OBJECTIVES

OBJECTIVES
Know description , indications and dosing of commonly used blood products
FWB,WB, prbc, platelets, FFP, cryoprecipitate

Understand use of special processes that blood products undergo

Leukoreduction, Irradiation, Washing

OBJECTIVES
Understand the management of common acquired coagulopathies Understand the mechanism, presentation and management of common transfusion related complications

A. Red cell products

Fresh Whole blood Whole Blood Packed red cells

1. Fresh Whole blood

Indications
Cardiac surgery Exchange transfusion in newborns Massive transfusion Fresh whole blood ( < 3 to 5 to
7 days old) For infants who undergo CARDIAC SURGERY and cardiopulmonary bypass * For EXCHANGE TRANSFUSION

Fresh Whole Blood

Justification for fresh blood
Greater O2 capacity bec has max level of 2,3DPG Minimal waste products, e.g. K

Fresh whole blood

Significant
in premature infants
if rapid transfusion or large volume (Exchange
Transfusion)

Impaired cardiac or pulmonary fxn, e.g.

on ECMO

2. Whole Blood
Indications
For concomitant rbc and volume deficits Not routinely available
Standard of care for active bleeding: prbc, plasma, cryoprecipitate or platelets as needed Reconstituted whole blood: prbc + FFP ( or 5% albumin or saline)

2. Whole Blood
Dose
10 ml/kg
Rate: 2.5- 5 ml/kg hour

Note
Platelets, granulocytes, labile factors V and VIII : not reliable

3. Packed red cells

Indications: symptomatic anemia

Packed red cells

Dose:
10-15 ml/kg (round off to nearest RBC unit approximately 300 ml/unit) Will increase blood Hb by 20 40 g/L

Rate:
3-5 ml/kg/hour
10 ml/kg - - - transfuse in 2-4 hours 15 ml/kg --- transfuse in 3-5 hours

PRBC transfusion Indications

transfusion trigger
Difficult to assign; depends on:
Clinical setting Physiologic status of patient
Physiologic response to anemia in children different from adults < 6 g/dL symptoms appear (chronic anemia)

RBC transfusion guidelines for infants < 4 mos Hct

< 20
< 30

Transfuse if
With symptoms of anemia and low retic count
- Needing < 35% O2, CPAP, or Ventilation, BUT

- w/ apnea, bradycardia, tachycardia or tachypnea - w/ low weight gain

(<10g/day x 4 days while receiving >/=100 kcal/kg/day)

< 35 < 45

Needing

> 35% O2, CPAP, or Ventilation

Infant on ECMO or with cyanotic CHD

RBC transfusion for > 4 mos

Hb < 7 RBC transfusion recommended, since most such children become symptomatic (malaise, irritability,
lattitude)

7-10

>10

Decision depends on clinical situation No transfusion required

RBC transfusion guidelines for children and adolescents Hb

No specific Hb < 100 < 80

Transfuse if
>/=25% acute blood loss
(blood volume = 65 ml/kg body weight)

Acute or chronic anemia and severe CP distress Symptomatic chronic anemia Bone Marrow failure Perioperative, critical care

Special Processing

1. LEUKOREDUCTION
WBCs removed by high efficient filters - reduce
WBCs by > 99.9%

Use: It decreases
1. febrile nonhemolytic transfusion reactions 2. incidence of HLA alloimmunization 3. transmission of infectious agents (CMV, EBV, TLV-1) --transmitted by cellular components of the blood

4. transfusion associated immunomodulation (TRIM)

2. GAMMA-IRRADIATION
WHAT IS TA-GVHD ?
is caused by viable, reproducing competent donor lymphocytes that are transfused into a PATIENT who either
does not recognize these cells as foreign or does not have the capacity to destroy them Engrafted lymphocytes immunologic attack against recipient tissues, including hematopoietic cells, pancytopenia bleeding and infectious cxs

Begins 8 to 10 days ff transfusion Almost inevitably FATAL !

2. GAMMA-IRRADIATION
The only acceptable method to prevent TA-GVHD 2500 cGy inactivates lymphocytes Radiation is not sufficient to kill viruses
Does not kill CMV and does not eliminate need for either leukoreduction or CMV seronegative blood product

Components requiring irradiation

Prbc and platelets FFP (questionable) (cryo no need)

2. GAMMA-IRRADIATION
Produces some damage to rbcs leak intracell fluid ( inc K)
Shortens expiration date of rbcs either on
original expiration date or 28 days from irradiation, which ever is shorter

Platelets are not damaged

2. GAMMA IRRADIATION
GVHD does not occur after most transfusions
Why? donor lymphocytes are destroyed by recipients immune system before mounting a response against the host

But the PROTECTIVE RESPONSE DOESNT HAPPEN IN 2

SETTINGS Immunocompetent With partial HLA match Cells not recognized as foreign Severe Immunocompromise Cells unable to mount a reponse Setting
HSCT, Hodgkins, , solid tumors with ablative chemo, IU transfusions, neonatal exchange transfusions, cellular immunodeficiencies, severe immunosuppression

GVHD presentation
Fever, anorexia, nausea, vomiting, diarrhea Skin : variably severe May begin as erythematous maculopapular eruption erythroderma with bullae and desquamation GI bleeding ( bloody diarrhea usually) Hepatic dysfunction with hyperbil ( Direct) Do skin biopsy , liver biopsy, BM biopsy

GVHD diagnosis
Skin biopsy vacuolization of epid basal cell layer, dermal epithelial layer separation and formation of bullae Liver bx eosinophil infiltration and degeneration of small bile ducts Bone marrow- empty marrow, with fibrosis and lymphocytic infiltration (= aplastic )

3. WASHING RBC (& plt)

Purpose
Reduce recurrence of severe allergic or anaphylactic transfusion rxns Dec incidence of hyperK+ ( in large vol transfusions ) Intraoperative Red cell salvage Decrease T activation
Bacterial infection exposes rbc T cryptantigen binds IgM anti T ( in plasma) agglutination and hemolysis

B. PLATELETS

Platelets
Normal (all) = 150-450k/uL When platelet < 10k significant risk of ICH Approximately 7k/uL/day required to maintain endothelial integrity integrity (Hanson and Slichter 1985)

Platelet Transfusion INDICATIONS - neonates

< 100k Non-bleeding sick preterm

<50 k

Non-bleeding stable preterm

< 30k <50k (if stable) <100k (if sick)

Nonbleeding term Before invasive procedure Active bleeding

Platelet Transfusion INDICATIONS-children

<10k Without other risk factors for bleeding > With active bleeding > Planned procedure DIC Hemorrhage w/coagulation problem Bleeding with qualitative platelet defect Cardiovascular bypass surgery with excessive bleeding <50 k

<100k

Any count

Platelet Transfusion INDICATIONS

Factors that inc bleeding risk and warrant increase platelet threshold FEVER ACTIVE BLEEDING SURGERY CLOTTING ABN

Platelet Transfusion DOSE

DOSE (raise by 50K)
1 unit per 10 kg 4 units /m2 BSA 10-15 ml/kg ( neonates) 10 ml/kg (for apheresis unit; 1 unit = 300 ml)

RATE:
20 30 ml/kg/hr ( 1unit ~ 100 ml)
E.g. 10 kg 1 unit Transfuse in 20 - 30 minutes

Platelet transfusion
Should be ABO and Rh matched when possible
To attain best response from the platelet transfusion and decrease the potential for RBC hemolysis If mismatched, may contribute to an eventual platelet refractory state

Refractoriness to platelet transfusion

Non immune factors
Splenomegaly Infection Fever Bleeding DIC

Refractoriness to platelet transfusion

Drugs ( amphotericin, vancomycin, ciprofloxacin, heparin) Patient factors (male sex, inc wt, inc ht, previous pregnancies, previous transfusions)

Refractoriness to platelet transfusion

Immune factors
Antibodies (HLA, platelet specific, erythrocyte)
ABO incompatible platelets repeated transfusions could inc titres of recipients anti-A and Anti-B
fall in post transfusion platelet count increments by 30%

Alloimmunization
Platelets express HLA-A, HLA-B and human platelet antigens (HPA)

Strong association bet HLA antibodies and platelet refractoriness Chronically transfused patients develop Abs to HLA class 1 antigens

Refractoriness to platelet transfusion

Approach
Transfuse ABO compatible Use fresh HLA-matched crossmatched

FFP

FFP contents
Proteins albumin, complement, enzymes, transport molecules, Ig, coagulation factors Colloids Nutrients Crystalloids Hormones Vitamins

FFP contents-coagulation factors

Fibrinogen VWF 2-3 mg/ml 5-10 ug/ml

Factor VIII Factor II,VII,IX,X Factor XIII

100 u/ml 1 u/ml each 60 ug/ml

FFP
Indications for transfusion Treatment of coagulation factor deficiencies
Specific factor concentrates not available Immediate hemostasis critical

FFP
Specific indications
Acquired coagulation deficits
ESLD Massive transfusion DIC

Rapid reversal of warfarin Plasma infusion or exchange for TTP Congenital coagulation defect ( except when specific factor tx available)

FFP transfusion
Dose: 10 to 20 ml/kg
Basis:
FFP contains 1 u/ml of all factors Plasma volume 40 ml/kg
Infusion of 20 ml/kg provides about 50% of normal levels = adequate for hemostasis

To maintain short half-life factors, dosing necessary q6-8

hours

Rate: over 1 hour

(not to exceed 1 ml/kg/min)-risk of hypocalcemia

Cryoprecipitate

Cryoprecipitate
FFP (300 ml) Fibrinogen VWF Factor VIII II,VII,IX,X Factor XIII Fibronectin 2-3 mg/ml 5-10 ug/ml 100 ng/ml 1 u/ml each 60 ug/ml 0 Cryoppt (15-18 ml) 180-250 u/unit 100-150 u/unit 80-150 u /unit 0 + +

Cryoprecipitate
Indications
VWD, Factor VIII deficiency
(if pharmaceutical form not available)

Low fibrinogen
Congenital Acquired (e.g. DIC)

Cryoprecipitate for fibrinogen replacement

Contains 180 250 mg fibrinogen/unit 1 Unit = 15 -18 ml DOSE
5-10 ml/kg OR 1 unit / 5-10 kg Will raise fibrinogen by 60 100 mg/dL

Type specific

Transfusion IN acquired coagulopathies

Vitamin K deficiency
Coagulopathy w/o bleeding
Vitamin K is sufficient
IV
only in high risk setting or if other routes are not feasible High risk of anaphylaxis

Oral
Correction w/in 6-8 hours

Sub Q
Safe and effective Correction in 2-6 hrs

Vitamin K deficiency
If with bleeding
Vitamin K plus
FFP 10 20 ml/kg Intermediate purity FIX (prothrombin complex concentrate, Factors II, IX, X)

Repeat coags to ensure correction is complete

Vitamin K DOSE
Asymptomatic with mild deficiency
Bleeding Life threatening bleed
1-5 mg, SQ (depending on BW)
2-10 mg, SQ 5-20 mg, IV

DIC
FFP 10 15 mg/kg
unless coagulopathy is mild (coags < 1.5 x control and child is not bleeding

Cryoprecipitate 5-10 ml/kg

If fibrinogen falls to < 0.8 1 g/L

Platelet concentrate
For significant thrombocytopenia

Monitor DIC to guide blood product therapy Primary aim: correct underlying cause

Liver Disease
Accompanied by profound coagulation derangements, including hypo-fibrinogenemia Support with cyroprecipitate, FFP until liver recovers Liver biopsy safe if INR < 1.4 or less than 4 secs off normal range (APTT not relevant for decision making)
Response to FFP is unpredictable repeat coagulation tests immediately ff infusion

ADVERSE EFFECTS of TRANSFUSION

Question

What is the most risk-free transfusion?

Answer

The one that never happens.

So

Consider whether each and every transfusion is truly indicated!

Types of complications from transfusion

Transfusion reactions Metabolic Complications Infectious complications Others
Cardiac overload Alloimmunization T-antigen activation Dilutional coaguloapthy Iron overload

Transfusion reactions
1. 2. 3. 4. Acute hemolytic Febrile non-hemolytic Allergic Delayed Hemolytic

Acute Hemolytic Transfusion Reaction (AHTR)

Incidence Pathophysiology 1:38,000 1:70,000 ABO-Incompatible unit antibodies bind -> intravascular hemolysis hemoglobinemia & hemoglobinuria (immune complexes complement activation, coagulation cascade, neuroendocrine and systemic inflammatory responses) Fever, chills ; pain (lower back, flanks, chest, along infusion vein), hypotension, bleeding/DIC; renal failure

Diagnosis

Acute Hemolytic Transfusion Reaction (AHTR)

Lab Evaluation Clerical check of unit DAT on posttransfusion spec visual inspection of plasma Additional testing: - repeat typing - Repeat crossmatch - repeat Ag screen STOP TRANSFUSION! 1. Supportive tx of hypotension: IV colloid
or pNSS, / + low dose dopamine

Management

2. Furo to maintain urine flow 3. FFP, platelet, cryoppt for DIC Prevention 1. Proper patient identification ( typing and crossmatch)

Febrile Non-Hemolytic Transfusion reaction (FNHTR)

Temp inc (>1 C), assctd w/ transfusion Not attributable to other causes During or w/in 4 hrs of transfusion Need to rule out
AHTR septic transfusion reactions

Febrile Non-hemolytic trasnfusion reaction (FNHTR)

Incidence Pathophysiology 0.5-2% of transfusions - More freq with platelets

Prior alloimmunization of recipient(previous transfusion or pregnancy) Activation of donor leukocytes (by preformed Abs of recipient) Pyrogenic cytokines ( from donor leukocytes or passive transfer of cytokines ) ant hypothalamus releases PGE2

Clinical Evaluation

Discontinue transfusion First rule out AHTR

FNHTR
Lab Evaluation Management As in AHTR Proper patient identification ( typing and crossmatch)
1. Premedicate with acetaminophen (30-60 mins prior) 2. Leukoreduction 3. Washed blood ( if recurrent)

Prevention

Allergic Transfusion Reaction

Spans a wide continuum
Mild cutaneous to severe systemic reactions to Anaphylaxis

Treatment
Guided by severity of respiratory and cardiovascular symptoms

Allergic transfusion Reactions

Incidence Pathophysiology 1-3% IgE or IgE independent mechanisms mast cell activation Mast cell release of: 1. histamine urticaria, pruritus, bronchospasm, abd discomfort, hypotension 2. Leukotrienes (LKD4 and PG) bronchospasm, urticaria and inc vasc permeab

Implicated antigens: IgA, Cr, haptoglobin, chemicals (leach from tubings), drugs (penicillin)
Clinical Evaluation Stop transfusion -Most are mild ( not apparent until several hours after transfusion ) -Anaphylaxis (immediate and severe)

Allergic transfusion Reactions

Symptoms 1. 2. 3. 4. Systemic predominate in more serious reactions Respiratory dyspnea, cough, hoarseness, stridor, wheezing, chest tightness, pain GI nausea, cramps, vomiting, diarrhea Cardiac tachycardia, arrhythmia, dardiac arrest

> (-) fever > (+)Urticaria

-

Points to Allergy

Often isolated; some Recurrent Pxs with hx of atopy more likely to develop urticaria Do not increase in severity if they recur

Allergic Transfusion reaction

Lab Evaluation
1. 2. 3. Systemic allergic reactions as in
AHTR

Urticaria only just record in

patients record

Anaphylaxis test for IgA

deficiency

Management

1.

2.

Mild cutaneous only stop transfusion; antihistamine resume Other than urticaria- stop and investigate; do not resume

Allergic Transfusion Reaction

Prevention
1. Premedicate with antihistamine ( at least 30 mins prior) 2. Steroids premeds if antihistamines fail 3. Washed blood if premeds fail 4. Volume reduced

NOTE !
1. Routine use of premedications excessive and unnecessary

2. Antihistamines as prophylaxis for FNHTRs not indicated

Delayed Hemolytic transfusion reaction

Incidence Pathophysiology 0.2 2.6% Red cell allo-immunization Ab mediated extravascular hemolysis - Exposure to foreign rbc Ag IgM Abs produced allotype switch to IgG diminish to undetectable levels rexposure secondary or anamnestic immune response (rapid production of IgGs) IgGs attach to foreign rbc macrophages recognize targeted cells phagocytosis

phagocytosis

Delayed Hemolytic Transfusion

Clinical evaluation
- Unexpected anemia or a less than expected posttransfusion increment - Variable onset: most within the first 2 weeks - Symptoms of extravascular hemolysis: fever/chills; jaundice, malaise and back pain

Lab evaluation - Dec Hb/Hct

Spherocytes and reticulocytosis In IB, LDH Positive DAT in a mixed field pattern Antibody screen

Delayed Hemolytic Transfusion reaction

Management 1. Additional transfusion may be needed
Try to select blood lacking Ag corresponding to newly discovered Ab

2. Adequate hydration and monitor renal function

Thank your for your attention!