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Indian J Pediatr (2010) 77:1424 1428 DOI 10.1007/s12098-010-0194-y

SYMPOSIUM ON PICU PROTOCOLS OF AIIMS

SYMPOSIUM ON PICU PROTOCOLS OF AIIMS

Transfusion of Blood and Components in Critically Ill Children

Preena Uppal & Rakesh Lodha & Sushil K. Kabra

Received: 11 August 2010 /Accepted: 19 August 2010 / Published online: 22 September 2010 # Dr. K C Chaudhuri Foundation 2010

Abstract The physicians prescribing transfusions must have a thorough understanding of the various blood products, their indications and contraindications, and requirements for modification of the blood products to prevent probable adverse effects. Decision to give an RBC transfusion should not be based solely on Hb concentration, it should take in account high severity of illness; active bleeding; emergency surgery; etc. Using restrictive transfu- sion strategy of transfusion RBCs can decrease transfusion requirements without increasing adverse outcomes. In most circumstances, platelets should be maintained greater than 10×10 9 /L. Platelet counts greater than 20×10 9 /L are indicated for invasive procedures and greater than 50× 10 9 /L for major surgeries or invasive procedures with risk of bleeding. Whenever possible, ABO-compatible platelets should be administered. Fresh frozen plasma should be transfused in multiple coagulation factor deficiencies, DIC with bleeding, replacement of rare single congenital factor deficiencies when specific concentrates are not available (e.g., protein C or factor II, V, X, XI, or XIII deficiency). During transfusion child should be monitored carefully.

Keywords Blood component therapy . Fresh frozen plasma . Platelets . Red blood cells . Critically ill children

Blood component therapy is vital to the treatment of sick children in an ICU. Nearly 50% of children admitted to PICU receive blood transfusions [1]. Developments in transfusion medicine have resulted in component prepara-

P. Uppal : R. Lodha (*) : S. K. Kabra Department of Pediatrics, All India Institute of Medical Sciences, New Delhi 110029, India e-mail: rakesh_lodha@hotmail.com

tion of red blood cells (RBCs), platelets, and plasma which are superior to whole blood used in the past [2]. The hazards of blood transfusion are being increasingly recog- nized [3]. Advances in donor selection, infectious disease testing, use of leukoreduction filters, and gamma irradiation aim to reduce the risk of transfusion related complications. Pediatric patients are more likely than adults to be long term survivors, thus in determining the benefits vs risks of transfusion, greater consideration must be given to long term complications. The pediatric transfusion practices are usually divided into two time periods, birth to 4 months and children >4 months of age. In this article discussion is limited to transfusion in children over 4 months of age. The guidelines for children less than 4 months of age are similar to those of neonates [4].

Transfusion of Red Blood Cells

Red blood cells are prepared by the removal of about 200 mL of plasma from a unit of whole blood, which is about 350 mL. RBCs collected in citrate-phosphate- dextrose-adenine (CPDA)-1 have a shelf life of 35 days [5]. The concept of permissive anemia has become more popular because the safety of RBC transfusion has been questioned, at least in part due to the increased awareness among the general public regarding the risk of contracting viral diseases, especially human immunodeficiency virus (HIV) and hepatitis [6]. However, the ideal hemoglobin level for erythrocyte transfusion in critically sick children is not established. RBC transfusions are usually given to critically ill children when their Hb concentrations are considered to be too low. However, the decision to give an RBC transfusion should not be based solely on Hb concentration.

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According to a survey, pediatric intensivists decisions to transfuse were not based solely on Hb but also on many other determinants: low SaO 2 , low CaO 2 , or low cardiac

output (poor DO 2 ); high blood lactate level, low central venous (ScVO 2 ) or mixed venous saturation of O 2 (SVO 2 ), poor VO 2 ; high severity of illness, as measured, for example, by the pediatric risk of mortality (PRISM) score; active bleeding; emergency surgery [7]. In this survey, the overall baseline hemoglobin transfusion threshold that would have prompted intensivists to transfuse a patient ranged from 7 to 13 g/dL (70 130 g/L) [6]. There is evidence that using restrictive transfusion strategy of transfusion RBCs at a hemoglobin threshold of

7 g/dL can decrease transfusion requirements without

increasing adverse outcomes [8]. However, this study excluded children who were hemodynamically unstable, had acute blood loss or had cardiovascular problems. Indications of transfusion of RBCs are given in Table 1 [6, 9, 10]. A higher threshold may be indicated for patients with cardiovascular disease or children with severe hypox- emia, hemodynamic instability, active blood loss or cyanotic heart disease. There is a trend for downward revision of these guidelines.

Choice of Blood Group

The choices are based on the principle that the recipient plasma must not contain the antibodies corresponding to donor A and/or B antigens [11, 12]. Ideally, the same blood group RBC which is compatible with the recipient plasma should be transfused. In pediatric patients, a volume of packed red cells of

10 mL/kg (with a hematocrit of 70 75%) can be anticipated

to raise the Hb concentration by 2.5 g/dL. In very severe anemia Hb <4 g/dL, RBC transfusion should be given slowly or in small quantities to avoid cardiac failure from circulatory overload. Transfusions containing leukocytes might result in organ dysfunction through stimulation of the inflammatory cascade by the transfused leukocytes [13]. Universal leukocyte reduction may decrease the proinflam- matory effects of transfusions. In pre-storage leukocyte- reduced red-cell units, red cells are first filtered to remove

Table 1 Indications for RBC transfusion in children

leukocytes and are then stored in the usual manner. If this facility is not available, then it is desirable to use in-line leukocyte filters.

Transfusion of Platelet Concentrates

Platelet concentrates (PC) are usually prepared from whole blood via centrifugation or may be collected by apheresis technique. Each PC usually contains approxi- mately 7.5×10 10 platelets, but must contain at least 5.5× 10 10 platelets in 50 70 mL of plasma. Apheresis platelets (often called single-donor platelets (SDP)) are collected from a donor by selectively removing platelets in a volume of approximately 200 400 mL of plasma, where- as the rest of the blood components are returned to the donor during the cytapheresis procedure. This technique allows collection of platelets with a minimum of 3×10 11 platelets per 250-mL bag. This limits the amount of donor exposure per platelet transfusion because this technique collects the equivalent of a pool of six to eight random donor platelets. Whenever possible, ABO-compatible platelets should be administered, because of reports of intravascular hemolysis after transfusion of ABO-incompatible platelets. Platelets can be stored for up to 5 days at 20 24°C on a constant agitator which prevents agglutination of platelets which will otherwise make the platelets inactive [14]. Most guidelines recommend that for prophylaxis, plate- let counts should be maintained greater than 10×10 9 /L. Platelet counts greater than 20×10 9 /L are indicated for invasive procedures and greater than 50×10 9 /L for major surgeries or invasive procedures with significant bleeding risk. For central nervous system bleeding or planned central nervous system surgery, the platelet count should be maintained greater than 100×10 9 /L [1, 14, 15].

Transfusion of Plasma Products

Plasma is prepared from a whole blood by centrifugation or by apheresis techniques.

a) Hemoglobin (Hb) 4 g/dL or less (Hematocrit 12%) irrespective of the clinical condition,

b) Hb 46 g/dL (Hematocrit 13%18%) with features of hypoxia, acidosis causing dyspnea or impaired consciousness,

c) Hct <30%, requiring CPAP or mechanical ventilation >0.35 FiO 2

d) Hyperparasitemia in malaria (>20%) and

e) Features of cardiac decompensation due to anemia

Transfusion for acute blood loss If the patient is not stabilized after 2 boluses of 20 mL/kg of isotonic crystalloid and the suspected blood loss is >30%.

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Immediately following collection from normal donor, plasma contains approximately 1 unit/mL each of coagula- tion factors. Plasma frozen at 18°C within 8 h of collection is called fresh frozen plasma (FFP). FFP should be thawed at 37°C in the water-bath for 20 min in the blood bank. If thawed at 4°C, cryoprecipitate will form. Indications for transfusion of FFP are given in Table 2 [1619]. FFP should be ABO compatible with recipient RBCs; however, Rh type does not need to be considered nor does a crossmatch need to be done before administering. FFP is often misused as a volume expander. It should not be used for intravascular volume expansion, correction/ prevention of protein malnutrition, and when specific factor concentrates are available; alternative products that have undergone viral inactivation through complex manufactur- ing processes are preferable. Cryoprecipitate is the precipitate formed when FFP is

thawed at 4°C. The precipitate is then refrozen withi n 1 h in 10 15 mL of donor plasma and stored at 18°C or less for

a period of up to 1 yr. Cryoprecipitate contains 80 100

units of Factor VIII, 100 250 mg of fibrinogen, 40 60 mg

of fibronectin and 40 70% of the von Willebrand factor and

30% of the factor XIII present in the original unit of plasma. It is indicated in deficiency of its constituents [17]. Compatibility testing of cryoprecipitate units is not required. The number of units of cryoprecipitate is usually based on the amount necessary to obtain a hemostatic level of fibrinogen, i.e. a fibrinogen level >0.8 1.0 g/L. This can usually be accomplished by the transfusion of 2 unit/10 kg body weight.

Precautions During Blood/Blood Component Transfusion

It is important that the decision to transfuse blood or blood

products is taken carefully. While sending the requisition check for the transfusion history and blood group of the patient and calculation of the total volume/units is required. Before transfusion, product check, blood group, total volume etc. should be done carefully. Baseline condition and vital parameters should be recorded careful-

Table 2 Indications for transfusion of Fresh Frozen Plasma (FFP)

ly and should be monitored every 5 10 min for half an hr and subsequently every 30 60 min, till transfusion is over.

Reactions Following Transfusion of Blood Components and Their Management

There are many benefits to transfusion therapy; however, there are risks that may incur acutely or in the long term. Although most acute reactions in pediatric patients are immune related, non-immune-related complications, such as bacterial contamination, transfusion-associated circulato- ry overload (TACO), and thermal/mechanical hemolysis, should always be considered. The acute reactions vary from mild hypersensitivity, allergic reactions and urticaria to moderately severe febrile non-hemolytic transfusion reac- tion to life threatening reactions like acute intravascular hemolysis, sepsis, fluid overload, anaphylactic reaction and Transfusion Related Acute Lung Injury (TRALI). There may be Delayed Hemolytic Transfusion Reaction, transfu- sion transmitted infections and iron overload. Acute haemolytic reactions may present with hypoten- sion, tachypnea, tachycardia, fever, chills, hemoglobinuria, chest pain, flank pain, and discomfort at the infusion site. Monitoring the patient s vital signs before and during the transfusion is important to identify reactions promptly. When an adverse reaction is suspected, it is imperative to stop the transfusion immediately, maintain intravenous access, verify that the correct unit was transfused to the patient, treat the patients symptoms, and notify the blood bank for further investigation. The laboratory evaluation for hemolysis includes the measurement of serum hapto- globin, lactate dehydrogenase and indirect bilirubin levels [19, 20]. The most frequent reaction associated with the transfu- sion of cellular blood components is Febrile Non Hemolytic transfusion Reaction. However, fever is a common symp- tom of transfusion reactions and serious transfusion reactions, such as acute hemolysis, sepsis, or transfusion- related acute lung injury (TRALI) need to be ruled out [21]. There are serious hazards of transfusions which include immunological reactions and transfusion-transmitted infec-

Multiple coagulation factor deficiencies (e.g., liver failure, vitamin K deficiency from malabsorbtion or biliary disease)

DIC with bleeding

Reversal of warfarin emergently when vitamin K is deemed untimely

Dilution coagulopathy from massive transfusion

Replacement of rare single congenital factor deficiencies when specific concentrates are not available (e.g., protein C or factor II, V, X, XI, or XIII deficiency)

Replacement of C1 esterase inhibitor in patients who have hereditary angioedema

Thrombotic thrombocytopenic purpura for exchange transfusion

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Table 3 Adverse effects of use of blood and blood products

Category

Signs

Symptoms

Cause(s)

Treatment

1. Mild

Urticaria, rash

Pruritus

Hypersensitivity reaction

-Slow the infusion

 

-Antihistaminic (Chlorpheniramine maleate 0.1 mg/kg)

-If no improvement in 30 min, treat as category 2

2. Moderately

Flushing

Anxiety

Hypersensitivity reaction

-Stop infusion and replace IV set

severe

Urticaria

Itching

-Notify blood bank

Rigors

Palpitation

-Sample from the bag and patient for repeat cross matching

Fever

Mild dyspnea

Restlessness

Headache

-Antihistaminic, Antipyretic

Tachycardia

-Steroid(IV) and bronchodilator if needed

 

-If improvement, restart infusion slowly -If no improvement in 15 min treat as category 3

3. Life

Rigor

Anxiety

Hemolysis

-Stop infusion

threatening

Fever

Chest pain

Bacterial contamination

-Change IV set

Restlessness

Pain at IV site

Anaphylaxis

-Normal saline 20 ml/kg and repeat if needed

Hypotension

Respiratory distress

Transfusion associated

-Inotropes if needed

Tachycardia

Backache

lung injury

-Elevate the legs

Hemoglobin uria

Headache

Septic shock

-O 2 and airway opening -Adrenaline (I:1000) 0.01 mg/kg IV/SC -Steroid(IV) and bronchodilator (if needed)

(red urine)

Dyspnea

Fluid overload

DIC (bleeding)

 

-Notify blood bank -Sample from the bag and patient for repeat cross matching -Urine sample for hemolysis

-If bleeding (DIC), give platelets, cryoprecipitates, FFP or factor concentrates -If oliguria

Check fluid balance

Frusemide (1 mg/kg)

Dialysis if needed

If bacteremia send blood c/s and antibiotics

Other delayed complications

Signs and Symptoms

Treatment

1. Delayed hemolytic

reaction

2. Post transfusion

purpura

510 days later transfusion Fever

Anemia

Jaundice

510 days after transfusion

Increased bleeding tendency

No treatment; if hypotensiontreat as acute intravascular hemolysis

High dose steroid

IVIG (Intravenous immunoglobulins)

 

Thrombocytopenia

Plasma exchange

3. Graft Vs host disease

1012 days after transfusion fever

Supportive care

Rash and desquamation, Diarrhea, Hepatitis Pancytopenia

4. Iron overload

Cardiac and liver

Iron chelating agents

failure in transfusion

Desferioxamine (subcutaneous infusion)

dependent patients

Deferiprone (oral)

tions. Infants and children are at particular risk in a number of situations, like failure to apply wristbands for identifica- tion of children too young or sick to state their identity. For these reasons, attention to the correct identification of the patient and product at all stages of the transfusion process is

essential. Monitoring during transfusion is equally neces- sary in pediatric patients as in adults and perhaps more so in younger children who may be less able to communicate discomfort or anxiety [22]. Table 3 provides the manage- ment of various transfusion reactions.

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