Pediatric Transfusion Management

Pediatric Transfusion Management

Synonyms

Blood administration, transfusion, blood product handling

Related Conditions

Pediatric: trauma, surgery (general, orthopedic, neurosurgery, plastics, urologic, oropharyngeal, cardiovascular), extracorporeal membraneous oxygenation (ECMO), therapeutic apheresis (leukopheresis, erythrocytapheresis, plasma exchange), sepsis, renal failure (dialysis dependent), oncology, sickle cell disease/hemoglobinopathies, stem cell transplantation, respiratory failure/pneumonia

1. Description of the problem

Core Transfusion Medicine Concepts

What every clinician needs to know about red blood cell antigens (ABO) and the plasma they come in (anti-A IgM, anti-B IgM, and anti-A, B IgG):

The ABO antigens (oligosaccharides) of the ABO blood group (Type A, B, AB, and O) are the most clinically significant antigens in all of transfusion practice.

For example, if you are blood type A there is A antigen on your red blood cells and tissues. In the next 3 months to 1 year of age anti-B will begin to form in the plasma due to exposure of the gut to different microbes that on the outer surface look similar to the B antigen. The predominant isohemagglutinin will be anti-B IgM.

The universal donor of red blood cells is Group O blood type. There aren’t any antigens on the red cell surface of those cells so they can go into any recipients plasma. The recipient can have anti-A or anti-B of any type and those antibodies will not have a target to cause hemolysis. However, the same cannot be said for the plasma of an O donor. The O plasma has anti-A and anti-B and anti-A, B IgM and IgG antibodies.

Different individuals have different titers of these antibodies and they are hemolytic antibodies. This means if a red blood cell with an A antigen or a B antigen or both A and B antigens mixes with the O plasma an acute hemolytic transfusion reaction can occur potentially killing the patient.

The universal donor of plasma is therefore AB plasma since AB donors have A and B antigens on the surface of their red blood cells but no isohemagglutinins in their plasma. This explains why O red blood cells can be given in an emergency because no cross matching of the RBCs with the donor plasma/serum is necessary because O red blood cells are compatible with all blood types. AB plasma is given in an emergency because it does not have isohemagglutinins and won’t cause a hemolytic transfusion reaction in the recipient no matter what their ABO blood type may be.

Figure 1 is the best way to conceptually think about all blood types. It also give the rule of “4”s so you can remember the rarest and most common ABO types. This is just an approximation of all blood donors. 44 % are type A, 4+4=8% are type B, and 4% are type AB, and finally 44% are O blood type.

Figure 1.

The RBC surfaces are self explanatory with the distinct antigens.

The plasmas of each blood type, recipient or donor, are what most people forget about and are the most critical. A mis-match of RBCs or plasma (such as with platelet transfusion and plasma transfusions) can be just as hemolytic and cause mortality in the patient.

• Anti-A and anti–B can generally be detected in serum after the first few months of life.

• Antibody production reaches the adult level at 5-10 years of age.

• IgM is the major class of antibody produced in group A and group B people; small amounts of IgG are also present.

• IgG is the dominant class of antibody in group O people (anti-A,B), and is responsible for ABO hemolytic disease of the newborn – hyperbilirubinemia – and can lead to a manual exchange transfusion in the PICU with readmission.

• Both classes agglutinate RBCs best at room temperature or below, and activate complement at 37°C.

What Blood Products are Available in their Hospital's Blood Bank?

Possibilities include but are not limited to:

Whole blood, packed red blood cells (pRBCs), platelets in two types (apheresis platelets (AP) and whole blood derived platelets (WBDP) , frozen plasma (fresh frozen plasma (FFP) and frozen plasma (F24)), liquid plasma, cryoprecipitate, cryo-poor plasma, granulocytes, albumin.

What is in Each Blood Product?

Figure 2

Figure 2.

1. Whole Blood

Factors V and VIII decrease to 5-30% by day 21

Cytokines accumulate and contribute to WBC-related complications

2. pRBCs

Anti-coagulant preservative solutions (pRBC storage solutions)

Citrate, phosphate, dextrose (CPD, CP2D, CPDA-1)

• Shelf-life 21 days, volume 250 ml

• Shelf-life 35 days usually yield Hct~70%, volume 250 ml

Adsol (AS-1, AS-3, AS-5)

• Additive solution licensed in US (1980s) contains mannitol, phosphate buffer, adenine, NaCl and dextrose

• Increases red cell shelf life to 42 days

• Preserves metabolism of red cells with slower K+ leak

• Addition of 100 ml AS dilutes RBC so Hct~ 50 – 60%

• Volume usually 350 ml

• 10 ml/kg of CPDA-1 unit raises Hgb 2 gm/dL and AS raises Hgb 1.5 g/dL

Liquid pRBCs

• Shelf-life/volume depends upon anticoagulant preservative solution

• After whole blood donation unit is spun down and pRBCs go to bottom of unit

• Platelet-rich plasma is removed (supernatant) and additive solution is added to pRBCs if necessary

Cryopreserved pRBCs

• Glycerol is a cryoprotectant, allows for long-term frozen storage of rare pRBCs (e.g. frozen, 40% glycerol, store @ -65°C stored for 10 years)

• Glycerol washed away after thawing

• ~90% leukoreduced

• Platelets and CMV destroyed

• Must be transfused within 24 hrs

• Indicated for anemic patients with rare blood types or multiple alloantibodies

RBC unit storage lesions (pathophysiologic changes during storage on shelf in blood bank)

During liquid preservation of pRBCs the following metabolic changes occur:

• extracellular potassium rises

• extracellular free Hgb rises

• intracellular 2,3 DPG falls returns to normal levels 24 hours after transfusion

• intracellular pH falls

Sequelae of RBC storage lesion

Cardiac arrhythmia and neonatal deaths have occurred subsequent to transfusion of stored (35 day old) RBC prompting recommendation to use younger RBC for transfusions of neonates < 5 days old.

Events above occurred with transfusion of large volume pRBC > 20 ml/kg, stored in CPDA-1.

K+ leak is slower with AS stored RBCs thus, many think that transfusion of > 5 days old is safe for neonates, as long as the volumes are 10 -20 ml/kg aliquots.

3. Platelets

Figure 3. Plasma exchange device-centrifugation process

Figure 3.

Figure 4. Centrifugation device for blood separation

Figure 4.

1 units of SDP = 6-8 units of RDPs

1 RDP unit = 50-60 ml

1 SDP unit = 300-600 ml

AP platelets are leukoreduced when they come out of the machine whereas WBDP need to go through a filter after collection and separation from whole blood to then be leukoreduced prior to storage. Figure 5. WBDP composition/separation

Figure 5.

Made from a whole blood donation. Once blood is collected a hard spin is performed and RBCs go to bottom of unit. Platelet-rich-plasma(PRP) is on top and then removed. Then PRP is spun and platelets go to bottom and plasma is left at top. Plasma is removed and approximately 50ml of plasma and platelets are left at bottom of unit which comprises the platelet concentrate (PC). This unit is not leukoreduced and needs to be filtered with a leukoreduction filter prior to storage.

4. Frozen Plasma

Figure 6. Frozen plasma

Figure 6.

• Production:

  FFP: frozen within 8 hrs of collection at <-18°C from CPD, CP2D or CPDA-1 whole blood or frozen within 6 hrs from ACD plasma

  F24 plasma: frozen within 8–24 hrs after collection

• Viral testing only, no viral inactivation

• Volume: 150–300 ml per unit

• Contents: contains all factors:

  1 IU/ml of clotting factors (labile and nonlabile)

• Thaw:

  FFP thaw @ 30-37°C; store @ 1-6°C for 24 hrs

  F24 Thaw @ 30-37°C; store @ 1-6° for 5 days

• Expiration:

  FFP: 12 MOS @ -18°C for 7 yrs @ -65°C

  F24 : 12 mos. @ -18°C

5. Liquid Plasma

Production: Cold insoluble portion of plasma that remain after FFP has been allowed to thaw at 1-6°C. Separated from plasma and refrozen.

• PLASMA REMOVED FROM WHOLE BLOOD UP TO 5 DAYS AFTER EXPIRATION DATE, BUT NEVER FROZEN

• Expire: 5 days post original expiration date @1-6°C

• Elevated potassium and ammonia and low factor VIII (vs. FFP)

• Sent to manufacturer for fractionation

• Derived from donor plasma

  Prepared by cold alcohol fractionation

• Pasteurized by heating to 60° C for 10 hours

  destroys viruses

• 5% or 25% solution

  (5% is oncotically and osmotically equivalent to plasma)

Indications

• Hypovolemia with hypoproteinemia

  Thermal injury, nephrotic syndrome, shock

Contraindications

• Long-term therapy for chronic or nutritional hypoalbuminemia

6. Cryoprecipitate

Production from cold insoluble portion of plasma that remain after FFP has been allowed to thaw at 1-6°C. Separated from plasma and refrozen.

• Viral testing – no viral inactivation process

• Volume: 10-20 mL (may need diluent if amount of plasma is less than 15 mL)

• Contents: 80-100 units factor VIII; 150-250 mg fibrinogen;

  80 units of von Willebrand Factor (40-70% of the original amount in the unit)

  40-60 units of factor XIII (20-30% of the original amount) 30-60 mg fibronectin

• Thaw: 37°C waterbath; store 6 hrs room temperature

• Pool: 4 hours @ 20-24°C

• Preparation Time: 10-20 minutes

Figure 7

Figure 7.

7. Cryo-poor Plasma

• Cryoprecipitated antihemophilic factor (AHF) precipitates out when FFP is thawed between 1-6°C

• The 10-15 ml of cryo. is removed and the FFP is refrozen within 1 hour

• Expires: 12 mos @ -18°C (24 hr thawed)

• Thaw @ 37°C; store @ 1-6°C

• Use: TTP patients (lacks the high molecular weight multimers of vWF and contains the metalloprotease enzyme)

8. Granulocytes

• Collected by apheresis techniques from volunteer donors.

• Transfuse within 6-10 hours of collection, without leukoreduction filter for optimal beneficial effect.

• WBCs should be stored at room temperature with as little agitation as possible.

• Donor WBC mobilization can be stimulated with dexamethasone alone or with dexamethasone plus G-CSF.

• Dex + G-CSF donor stimulation can yield neutrophil collection ranges between 3 to 10 x 1010 neutrophils.

• Ideal WBC product dose is 1 x 109 neutrophils/kg or 15 ml/kg.

• WBC transfusions with low or high neutrophil counts have not consistently been demonstrated to increase the survival rates of neutropenic septic neonates or children.

9. Albumin

• Derived from donor plasma

  Prepared by cold alcohol fractionation

• Pasteurized by heating to 60° C for 10 hours

  destroys viruses

• 5% or 25% solution

  (5% is oncotically and osmotically equivalent to plasma)

Indications

• Hypovolemia with hypoproteinemia

  Thermal injury, nephrotic syndrome, shock

Contraindications

• Long-term therapy for chronic or nutritional hypoalbuminemia.

How are Each of the Blood Products Stored?

Which Blood Products Require Testing Prior to Use?

Erythrocytes

Routine pre-transfusion testing required. ABO is the only system that the reciprocal antibodies are present in the sera/plasma of most individuals with no previous exposure

Platelets

Testing of patient’s ABO type is necessary, but no crossmatching is done unless patient is in an immune refractory state. For children, goal is to transfuse ABO type specific or compatible platelets due to their small plasma volume.

Frozen Plasma/Cryo

ABO type is necessary, no crossmatching performed. Goal to transfuse ABO type specific or compatible plasma.

Granulocytes

ABO typing and crossmatch must be done on all granulocyte transfusions due to the contaminating red blood cells in the product.

Blood Product Dosing and Expected Post-transfusion Outcome for respective laboratory monitoring parameter

Knowing the patient’s weight is absolutely critical as it is with all pediatric dosing of medications etc.

pRBCs

5,10,15, sometimes 20 ml/kg per dose: expect 1-2 gm/dL rise in hemoglobin level post transfusion if no bleeding

Platelet concentrate

10 ml/kg

• If give 0.1-0.2 units/kg it will raise post-tx platelet count by 50-100,000/microliter in patients with hypoproliferative thrombocytopenia induced by chemotherapy

Platelet pheresis

10-15 ml/kg

Frozen plasma

10 ml/kg will raise factor levels approximately 15-20%

Cryoprecipitate

1-2 units (each approximately 5-15 ml in volume total)/ 10 kg rise in fibrinogen of 60-100 mg/dL.

2. Emergency Management

Clinical features for transfusion indications below:

anemia, thrombocytopenia, coagulopathy, prolong neutropenia, hyperleukocytosis

Indications for transfusion

Note: These are usually rules of thumb not hard and fast. The indications are usually established by local practice the medical executive team of each hospital. One should go to the transfusion committee at their respective hospitals to obtain a copy of the transfusion indications use for each blood product. The Joint Commission requires that these are established at each hospital and monitored by the organization.

A. Packed Red Blood Cell Transfusion

• Improved oxygen carrying capacity to maintain adequate hemoglobin and relieve symptomatic anemia (i.e. congestive heart failure)

• Maintain adequate pre-operative hemoglobin > 8 g/dL

• Chronic transfusion, every 2-4 weeks for different complications in certain diseases such as sickle cell anemia, beta-thalassemia major, severe hereditary spherocytosis, myelodysplasia, etc.

Autologous Packed Red Blood Cells

Useful in older children for orthopedic surgery, scoliosis repair, marrow-donor harvest

Directed Donors

Test requirements impossible for emergent transfusion, relative should not be used as blood donor for potential stem cell transplant due to potential for transplant rejection, recognize that first time donors can exhibit higher rates of infectious disease markers (i.e. HIV, HCV, HBV) than repeat volunteer donors.

B. Platelet Transfusion

With Thrombocytopenia

• Platelet count 5-10,000/μl with failure of platelet production

• Platelet count < 30,000/μl in neonates with failure of platelet production

• Platelet count < 50,000/μl in stable premature infant with:

  Active bleeding

  Before intensive procedure with failure of platelet production

• Platelet count < 100,000/μl in sick premature infant with:

  Active bleeding

  Before an invasive procedure in patient with DIC

Without Thrombocytopenia

• Active bleeding with qualitative platelet defect

• Unexplained excessive bleeding in patient undergoing cardiopulmonary bypass

• Patient undergoing ECMO with:

  Platelet count < 100,000/μl

  Higher platelet count and bleeding.

C. Frozen Plasma Products

INDICATIONS: FFP and F24

1. Congenital or acquired coagulation factor deficiency with active bleeding or prior to an invasive procedure when the specific concentrates are not available

2. Massive blood transfusion with coagulopathy

3. Multiple acquired coagulation defects (i.e. liver disease or DIC)

4. Deficiency of ATIII, protein C, or protein S when a concentrate is not available

5. Plasma exchange for TTP

6. Rapid reversal of warfarin effect

NON-INDICATIONS: FFP and F24

1. Volume expansion

2. Nutrients

3. Immunodeficiency (use fractionated IgG)

4. Wound healing

5. Reconstitution of RBCs (except for neonatal RBC exchange)

Cryoprecipitate

INDICATIONS

1. Congenital or acquired hypofibrinogenemia

2. Factor XIII deficiency (1 unit/10-15 kg q 2 weeks)

3. Topical hemostatic or adhesive agent (fibrin glue) combined with thrombin

4. Wound or bone healing (fibronectin)

5. Uremic bleeding unresponsive to dialysis or DDAVP

6. Hemophilia A and vWD; only when virus-inactivated concentrates are unavailable

NON-INDICATIONS

1. Deficiency of Factors II, V, VII, X or XI

2. Hemophilia A (Factor VIII deficiency)

3. Hemophilia B (Factor IX deficiency)

4. vWD responsive to DDAVP

5. Sole treatment of DIC

6. Don’t use for any deficiency in which a viral-inactivated concentrate is available or in which the factor is not present in cryoprecipitate.

D. Granulocytes

1. Neonates and children with neutropenia or granulocyte dysfunction with bacterial sepsis and lack of responsiveness to standard antimicrobial therapy (neutrophil + band count < 3 x 109/L)

2. Bacterial sepsis, no response to antibiotics, (neutrophil + band count < 5 x 109/L)

3. Neutropenic neonates or children with fungal disease not responsive to standard therapy.

E. Therapeutic Pheresis

Therapeutic Plasma Exchange (TPE)