Transfusion Support in Hematology/Oncology

 

Blood Products

 

 

Whole Blood

 

Indications:       exchange transfusion

 

Product:           reconstituted PRBCs, FFP, platelets

fresh whole blood (rarely used)

 

Dose:               double-volume exchange q 12-24 hours

 

Toxicities:         volume, citrate

red cell, white cell, plasma exposure

incomplete viral testing (if fresh)

 

Red Blood Cells

Indications:       improve oxygen carrying capacity

 

Product:           packed cells (PRBCs)

HCTs 65-80%

 

Dose:               HCT(desired - actual) x TBV

HCTPRBCs

 

Toxicities:         red cell, white cell exposure

 

Frozen Plasma F8 (<8hrs) or F24 (frozen 8-24 hrs slightly reduced V and Vlll)

 

Indications:       clotting factor replacement

 

Product:           fresh frozen plasma (FFP)

100% factor levels

 

Dose:               10 cc/kg  à 20% activity

T½ varies with factor  (eg, FVIII = 12 hour)

 

Toxicities:         plasma exposure

volume, citrate, hypernatremia

 

 


Cryoprecipitate

 

Indications:       replace fibrinogen

factor XIII deficiency

(von Willebrand's Disease)

 

Product:           300 mg fibrinogen/unit

80 IU F VIII, vWF, F XIII/unit

                                   

Dose:               0.3 u/kg à 200 mg% fibrinogen

  = 4 days

 

Toxicities:         plasma exposure

 

 

 

Normal Fibrinogen level:

 

Fibrinogen 177 – 466 mg/dL

 

Platelets

 

 

Indications:       thrombocytopenia

qualitative platelet defects

WITH bleeding risk

 

Product:           5.5 x 1010/unit

apheresis product > 5 units/bag

 

Dose:               0.1 u/kg à 50,000/mm3

 

Toxicities:         red cell, white cell, plasma exposure

refractoriness (alloimmunization)

 

 

Platelet count unit is per ul

 

For example, if 4 x1011 platelets or approximately 6 platelet concentrates are pooled or administered as 1 dose to a patient with a 2m2 body surface area, and the patient’s post transfusion platelet count minus the transfusion platelet precount is 40 000/mL (taken within 1 hour of transfusion) then the CCI = (40 000/4) x 2 = 20 000.

 

 

White Blood Cells

 

Indications:       severe infection and neutropenia

 

Parameters:      progressive infection despite antibiotics

rapid granulocyte recovery unlikely

 

Product:           1-5 x 1010 granulocytes/unit

 

Dose:               > 1 x 1010/m2 q 12-24 hours

 

Toxicities:         incomplete viral testing

volume, citrate

red cell, white cell, plasma exposure

pulmonary reactions

Donor: G-CSF or steroid, apheresis +/- starch

 

 

 

 


 

Complications of Transfusion

 

Volume intolerance

Cause:              large volume replacement, small children, ongoing needs

 

Symptoms:       fluid overload

 

Treatment:        supportive (e.g., diuretics)

 

Prevention:       concentrate products, small aliquot transfusion, exchange transfusion

 

Hyperviscosity

Cause:              Super “physiologic” hematocrit elevation

 

Symptoms:       Polycythemia, CNS, respiratory

 

Risk Groups:    Chronic hypoxemia

cyanotic heart disease

pulmonary disease

“Over” transfusion

sickle cell disease

 

Treatment:        Hydration, isovolumetric red cell removal

 

Prevention:       Minimize iron supplementation

calculate transfusion volumes

small aliquot transfusion, serial hematocrits

 

Citrate toxicity

Cause:              Hypocalcemia due to citrate anticoagulant

 

Symptoms:       irritability, pallor, diaphoresis, chills, paresthesias, abd pain, nausea, vomiting, tachycardia, hypotension tetany, death

 

Findings:           low ionized calcium

prolonged QT, QRS interval; depressed LV function

 

Risks:               Plasma rich blood products

Large volume, fast transfusion

Infants, young children

Hepatic, renal dysfunction, Shock, acidosis

 

Prevent:            Low transfusion rates

Serial ionized calcium assays

Cardiovascular monitoring

 

Treat:               Interrupt transfusion

Calcium supplementation

 

Transfusion Reactions*

* All transfusions should be immediately interrupted when a reaction is suspected.

 

Immediate hemolytic reaction

Cause:              "major" RBC antigen mismatch (usually ABO)

clerical error

 

Symptoms:       back pain, fever, shock, hemoglobinuria, oliguria, DIC

 

Treatment:        supportive (e.g., pressors, hydration, diuretics)

 

Prevention:       meticulous adherence to cross-check procedures

 

Delayed hemolytic reaction

Cause:              "minor" RBC antigen mismatch

common in sickle cell disease

 

Symptoms:       7-14 days post-transfusion

anemia, hemoglobinuria, myalgias

 

Treatment:        supportive

 

Prevention:       extended antigen-matched RBC transfusion

 

Febrile reaction

Cause:              WBC alloantigen sensitization, WBC products

bacterial contamination (rarely)

 

Symptoms:       fever, chills, myalgias

 

Treatment:        antipyretics

narcotics for rigors

antibiotics (if sepsis suspected)

 

Prevention:       leukocyte depleted (e.g., leukofiltered) blood products

? premedication with antipyretics

 

Allergic reaction

Cause:              plasma protein sensitization

 

Symptoms:       pruritus, urticaria, bronchospasm, anaphylaxis

 

Treatment:        supportive (e.g., epinephrine, antihistamines, hydration)

 

Prevention:       ? premedication with antihistamines and/or corticosteroids

plasma depleted (e.g., washed) blood products

 


Rh sensitization

 

Cause:              Rh(D) positive RBC exposure

Rh(D) negative patient

 

Symptoms:       isoimmunization with future Rh(D)+ pregnancy

 

Prevention:       anti-Rh(D) IgG (RhoGam, RhIg) with exposure

 

 

   CURRENT RISK OF TRANSFUSION-TRANSMITTED INFECTIONS

   (Courtesy of DTM, NIH)

   Agent

Risk/Unit

Serologic Test

   HBV

1:205,000

HBsAg, anti-HBc

   HCV

1:1,935,000

anti-HCV,  NAT

   HIV

1:2,135,000

anti-HIV-1/2, HIV-Ag, NAT

   HTLV-1

1:2,993,000

anti-HTLV-I

   WNV

1:1,750,000

NAT

   Syphilis

<1:108 (last case reported in 1969)

RPR (FTA)

   Bacteria

<1:50,000 platelets

BacT Alert culture bottles for platelets; red cells not tested

 

Human immunodeficiency virus infection

Cause:              HIV infected blood products

 

Symptoms:       AIDS

 

Treatment:        supportive, anti-retroviral therapy

 

Prevention:       Risk of transmission ~1:2 million with screening (anti-HIV-1/2, HIV-Ag, NAT)

 

Hepatitis C infection

Cause:              HCV infected blood products

 

Symptoms:       biochemical chronic hepatitis (50%)

chronic active hepatitis/cirrhosis (10-20%)

 

Treatment:        supportive, interferon

 

Prevention:       Risk of transmission ~1:2 million with screening (anti-HCV, NAT)

 

 


Hepatitis B infection

Cause:              HBV infected blood products

 

Symptoms:       acute hepatitis

chronic active hepatitis/cirrhosis

 

Treatment:        supportive, interferon

 

Prevention:       risk ~1/200,000 with screening (HBsAg, anti-HBc)

universal immunization

 

Cytomegalovirus infection

Cause:              Transfusion of CMV positive cellular blood products

CMV negative, immunocompromised patients

 

Symptoms:       Severe, disseminated CMV

 

Treatment:        ganciclovir

 

Prevention:       CMV negative cellular blood products

Leukodepleted red cells, platelets commonly substituted

 

Risk groups:     Very low birth weight neonates

Fetal transfusion (intrauterine, pregnancy)

Immunodeficiency syndromes (proven or potential)

Bone marrow transplantation (pre- and post-)

Solid organ transplantation (pre- and post-)

 

Transfusion-associated Graft-vs-Host Disease

Cause:              Transfusion of immunocompetent T-cells

Non-destruction of transfused T-cells by recipient

T-cell recognition of foreign host antigens

 

Symptoms:       Skin, liver, GI tract, hematopoietic toxicity

> 80% mortality despite aggressive treatment

 

Risk groups:     Potentially immunocompromised patients

 

Prevention:       Irradiation of cellular blood components- use 25Gy

 


Transfusional Iron Overload

Cause:              > 500 ml/kg PRBC transfusion load

 

Symptoms:       Liver: hepatitis

Skin: hyperpigmentation

Heart: CHF, arrhythmias

Endocrine: diabetes, hypogonadism, et al

 

Risk Groups:    Thalassemia, sickle cell disease, DBA

 

Treatment:        Iron chelation

 

Prevention:       Decrease transfusion burden

Exchange transfusion    

 

Transfusion-Related Acute Lung Injury (TRALI)

Cause:              Donor/Recipient alloreactivity, cytokines

 

Symptoms:       within 4 hours of transfusion

Respiratory distress, hypoxemia, pulmonary infiltrates

Chills, fever, hypotension

Resolution 1-4 days

 

Treatment:        Supportive (e.g., oxygen, mechanical ventilation, ? steroids)

 

Prevention:       Avoid implicated donor(s)

Donor antibody screening

 

 

Specialized blood products

 

Leukofiltration

Products:          Red cells

Platelets

 

Indications:       Reduce risk of febrile reactions

Reduce risk of platelet alloimmunization

Reduce risk of CMV transmission

 

Single Donor Platelets

Product:           Apheresis platelets

 

Indications:       Reduce donor exposure

Reduce risk of platelet alloimmunization

Reduce risk of septic reactions


CMV negative

Products:          Whole blood

Red cells*

Platelets*

White cells

 

Indication:         Prevent CMV transmission

*Leukodepleted products commonly substituted

 

Irradiation

Products:          Whole blood

Red cells

Platelets

White cells

 

Indication:         Prevent graft-vs-host disease

 

 

Concentration

Purpose:           Plasma depletion

 

Products:          Red cells

Platelets

 

Indication:         Volume overload

Antibody depletion

 

Washed

Purpose:           Plasma depletion

 

Products:          Red cells

Platelets

 

Indications:       Repeated, severe allergic reactions

Antibody depletion

 

Antigen-Matched Red Cells

Purpose:           Manage/prevent red cell alloimmunization

 

Product:           Red cells

C, c, E, e, Kell matched

Extended antigen-matched

 

Indications:       Alloantibodies, delayed hemolytic reactions

Sickle cell disease, ? chronic transfusion patients, ? African-Americans


Formulas for Pediatric Transfusion

 

Total blood volume (TBV)*

 

Newborn          100 ml/kg        

Child                80 ml/kg

Adult                65 ml/kg

*Nomograms which estimate TBV based on height and weight can also be used.

 

 

Packed red blood cell transfusion

 

volume of packed cells required (ml) = (HCTd - HCTi) x TBV

HCTPRBCs

 

Example: To raise the HCT from 20% to 35% in a child with a TBV of 1800 ml using packed cells with a HCT of 75%:

 

(.15)(1800) = 360 ml.

                                          .75

 

 

Manual partial exchange transfusion for correction of anemia*

 

exchange volume (ml) =            (Hctd - Hcti) x TBV 

HctPRBCs - (Hcti + Hctd)

             2

 

* Adapted from Neiburg, P.I., Stockman, J.A.: Rapid correction of anemia with partial exchange transfusion. Am J Dis Child 1977;131:60-1.

 

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Abbreviations:

 

HCTi:               initial hematocrit

HCTd:              desired hematocrit

HCTPRBCs:        hematocrit of packed red blood cells transfused (usually 0.7-0.8)

TBV:                total blood volume