2. INTRODUCTION:
Blood component therapy refers to the transfusion of the
specific part of the blood which the patient needs as
opposed to routine transfusion of whole blood.
Blood components are preferred because each
component has specific optimal storage conditions and
component therapy maximises the use of blood
donations.
3. Why not Whole Blood and why components…???
This conserves blood resources, since one donated unit
can benefit several patients.
It also provides the optimal method of transfusing
patients who require large amounts of a specific blood
component.
Blood components are prepared from single donations by
conventional methods. Blood group compatibility
between the component and the patient is important.
In contrast, blood derivatives eg. Factor concentrates
are prepared from large pools of donor plasma by
fractionation and purification, they have more lenient
storage requirements and can be administered without
regard to ABO compatibility.
4. The various blood components are:
STANDARD: SPECIALISED:
1. Whole blood 1. Saline washed red cells
2. Packed red cells 2. Frozen red cells
3. Platelets (RDP,SDP) 3. Leucodepleted products
4. Fresh frozen plasma 4. Irradiated products
5. Cryoprecipitate. 5. Granulocytes
6. Lymphocytes
7. Lyophilized factor VIII conc
Antihemophilic factor
8. Activated Prothrombin
Complex Concentrates.
9. Porcine Factor VIII conc.
5. Whole Blood
SLOW CENTRIFUGATION
HIGH SPEED CENTRIFUGATION
RAPID FREEZING
THAWED
PRP PRBC
PLATELETS FFP
CRYOPRECIPITATE
PREPARATION OF BLOOD COMPONENTS
7. Pre Transfusion testing :
Donor blood is routinely tested for its ABO and Rh group
status.
After ensuring compatibility, a cross match is performed which
consists of 2 parts.:
1. Major Cross match
Patient’s serum + donor red cell suspension.
Look for agglutination or hemolysis.
2. Minor cross match
Patient’s red cell suspension + donor’s serum
Look for agglutination or hemolysis.
1
8. Also some routine biochemical and immunological
tests are performed:
Hb by CuSO4 specific gravity test.
HIV
HBsAg
HCV
Malaria.
VDRL for Syphilis.
9. Transfusion Practices unique to Newborn:
Newborns have a different type of O2 dissociation curve and a
unique response to anemia or blood loss. It responds to
anemia with poor cardiovascular responses and a much
delayed bone marrow response.
Newborn can poorly tolerate calcium, potassium and blood
lactate loads. Hence it is better to use blood which is < 5 days
old. Also old blood will have depleted stores of 2,3 –DPG
which will further shift the O2 dissociation curve to left which
is already to the left due to presence of high levels of HbF.
Blood products should be at room temperature before
transfusion as even though the quantity is small, it can cause
hypothermia and can make a newborn sick, especially a
preterm; more so during exchange transfusion.
10. The immune system of a neonate is immature and unresponsive to
antigenic stimulation in the first 4 months of life. Even when exposed
to RBC antigens, newborns do not produce alloantibodies. Almost all
the antibodies present in the newborn are derived transplacentally.
Hence standards for pre transfusion compatibility testing can be
relaxed for the first 4 months of life.
Donor is tested for ABO and Rh blood group and baby is tested for
ABO and Rh for the first time.
Mother’s blood is tested for ABO and Rh as well as for antibody
screen. If mother’s blood is not available, baby’s blood is tested for
antibody screen. If Ab screen is negative, all subsequent transfusions
can be given without cross matching provided the blood is of either O
group or is ABO identical/ compatible with both child & mother & is
Rh–ve / Rh compatible with the baby.
11. If the initial antibody screen is positive, corresponding antigen –
negative blood should be given as long as the antibody persists
in the neonatal circulation.
T cell immunity is also immature in newborns, especially
preterms . This can lead to increased chances of TA-GVHD
following use of un- irradiated blood products or use of relative
as a donor.
12. CHOICE OF ABO GROUP
RECIPIENT
BLD.GROUP
RBC PLATELET FFP
O GROUP O O/A/B/AB O
A GROUP A/O A/O A/AB
B GROUP B/O B/A/O B/AB
AB GROUP AB/A,B/O AB/A AB/A
13. WHOLE BLOOD
Whole blood should be used when a patient requires both
volume replacement and increase in oxygen carrying capacity.
INDICATIONS:
1. Acute massive blood loss > 25% of estimated blood volume
or(> 17ml/kg of blood loss).
2. Exchange transfusion in neonates.
3. Hyperleucocytosis (WBC count > 100000/cmm) e.g. in
acute leukamia.
4. Cardiac Surgery.
5. ECMO
14. INDIVIDUAL COMPONENTS:
RBCs :
RBCs are the most frequently transfused blood component, and
are given to increase the oxygen carrying capacity of the blood
to ultimately achieve a satisfactory tissue oxygenation.
Packed RBCs are obtained from whole blood by sedimentation
or by heavy spin at 5 C to achieve a hematocrit of 70 to 80 %.
The removal of plasma decreases the amount of electrolytes
and ammonia and is beneficial to patients with incipient CCF,
Renal failure or hepatic failure.
Moreover the chances of allergic or anaphylactic reactions are
minimised.
15. Special Considerations:
I. LEUCOREDUCTION:
Why leucodepletion …???
Donor lymphocytes present in most of the blood components
do not serve much purpose but can lead to major side effects.
Antibodies can develop against lymphocytes and platelets and
lead to Non Hemolytic Febrile Transfusion Reactions (NHFTR).
Activated lymphocytes can release cytokines like IL2 and TNFa
during storage which can also cause NHFTR. NHFTR is
especially a problem for patients needing recurrent
transfusions.
Lymphocytes lead to allosensitization, HLA antigen and
subsequent platelet refractoriness as well as graft rejection in
prospective candidates for bone marrow transplants.
16. Lymphocytes bear intracellular pathogens and can transmit
infections like HIV, HTLV, EBV and CMV.
Lymphocytes can lead to pulmonary toxicities like ARDS.
In surgical patients lymphocytes can lead to immune supression
and delay healing.
In immunocompromised patients , newborns especially preterm
babies and in transfusion from first degree relatives, it can lead to
transfusion associated GVHD.
The dose needed for NHFTR is >5*10^6 lymphocytes & for
TAGVHD > 10^7 cells/ kg body weight.
One pack of PRBC has 10^9 WBC, RDP has 2.5*10^8 WBC and
Granulocyte pack has 10^11 WBC.
Hence all these components must be leucodepleted before
transfusion so that they contain not more than 5*10^6 WBC.
17. The various techniques employed are:
1. Centrifugation (at 5000g for 7 mins) followed by
removal of plasma and buffy coat (~80% WBCs are removed).
2. Filtration using microaggregate , cotton wool or polyester
filters at the time of transfusion or just prior to issue
from blood bank.(>99% WBCs are removed).
3. Washing of RBCs in normal saline removes >85%
WBCs.
4. Deglycocerolyzing frozen, thawed RBCs (98% WBCs are
removed). This procedure is more expensive.
18. The benefits of leucoreduction are:
1. Decreased immunisation to antigens on leucocytes such
as human leucocyte antigen (HLA).
2. Decreased rate of febrile transfusion reactions.
3. Minimisation of possible (and controversial)
immunomodulatory effect of blood transfusion.
4. Decreased rate of CMV transmission.
19. IRRADIATION:
Blood products should be irradiated prior to transfusion.
Irradiation prevents transfusion associated graft versus host
disease (TA-GVHD) from transfused leucocytes in cellular blood
components
It is especially important for those at risk for this fatal
complication. eg. Premature infants and children with certain
immunodeficiencies.
Directed or designated donations have a small increase in rate
of infectious disease transmission.
Also if a relative donates blood components, the blood must be
irradiated since it is at increased risk for causing TA-GVHD if
the donor is a first degree relative of the patient
20. It is thus essential to irradiate all red cell and platelet
components (except FFP) for:
1. Intrauterine transfusion (IUT).
2. Exchange transfusion of red cells after IUT.
3. Top up transfusion after IUT.
4. When the donor is a first or second degree relative or a HLA
selected donor.
5. When a child has a proven or suspected immunodeficiency.
21. Anticoagulant - preservative solutions used:
Each unit contains approximately 250 ml of a concentrated
solution of RBCs .
Composition:
Hematocrit : 70%to 80%
Sodium :62mg
Citrate: 222mg
Phosphate: 46 mg
Iron: 200 to 250 mg
22. Three types of units are currently approved for use:
i. CPD – this contains 773 mg of Dextrose and has a 21 day
shelf life.
ii. CP2D – This contains 1546 mg of dextrose and has a shelf
life of 21 days.
iii CPDA1 - This contains 965 mg of dextrose and 8.2 mg of
adenine and has a shelf life of 35 days. This is the most
widely used of the anticoagulant-preservative solutions.
Additive solutions used: Most RBC units contain additive
solutions, each unit of~350 ml, an average hematocrit of 50%
to 60% and has a shelf life of 42 days. They contain Mannitol
in addition to all other constituents. Proportions of all vary an
different types
23. The changes that occur in PRBC during storage are:
The pH decreases from 7.4 to 7.55 to a pH of 6.5 to 6.6.
Potassium is released from RBCs. After 42 days of storage
plasma K levels are ~ 50mEq/L.
2,3 Diphosphoglycerate (2,3- DPG) levels drop rapidly during
the first two weeks of storage. This increases the affinity on
hemoglobin for oxygen and decreases its efficiency in
delivering oxygen to tissue.
24. INDICATIONS:
1.Chronic anemia due to any underlying diseases such as renal
failure or malignancy and Hb <5gm%.The transfusion
requirements of each patient should be based on clinical
status rather than any predetermined HCT or Hb value.
2. Thalessemia wherein the aim is to maintain the
pretransfusion Hb level between 9 – 10gm%.
3. Aplastic anemia where bone marrow transplantation is not
feasible transfusion is recommended when Hb is < 7gm%
4. Nutritional anemia when Hb drops to <5gm%. In severe
anemia when there is an overt CHF multiple small
transfusions of 3-5ml/kg over 3 hrs should be given.
25. 5. Malignancies when Hb <7gm%. Situations where
transfusions should be given in the absence of symptoms are:
(a) during radiation therapy.
(b) following an intensive cycle of chemotherapy that
causes myelosupression.
26. GUIDELINES FOR PEDIATRIC RBC
TRANSFUSIONS:
CHILDREN AND ADOLESCENTS:
Acute blood loss > 25% of circulating blood volume
Hb <8gm% in the perioperative period
Hb <13gm% and severe cardiopulmonary disease.
Hb <8gm% and symptomatic chronic anemia.
Hb <8gm% and marrow failure.
INFANTS WITHIN FIRST 4 MONTHS OF LIFE:
Hb <13gm% and severe pulmonary disease
Hb <10gm% and moderate pulmonary disease
Hb <13gm% and severe cardiac disease
Hb <10gm% and major surgery
Hb <8gm% and symptomatic anemia
27. DOSAGE AND ADMINISTRATION:
The usual dose is 5 to 15ml/kg at the rate of 5ml/kg/hr. This
may be adjusted depending on the severity of the anemia and/
or the patients ability to tolerate increases in intravascular
volume.
The higher hematocrit of CPD or CPDA RBCs (70 to80%)
results in increased viscosity which may slow the transfusion
rates. 50 to 100ml of isotonic NS may be used to dilute the
CPD RBC to decrease the viscosity.
The lower hematocrit of AS RBC unit (50 to 60%) permits
permits more rapid infusion rates.
Each 8ml/kg of RBC in children and each 3ml/ kg in infants is
expected to raise the Hb by 1gm/dl and PCV by 3%
28. PLATELETSPLATELETS
PREPARATION AND CONTENTS:
Platelets are prepared from whole blood donations or collected
by apheresis.
Each bag of 50 to 60 ml should contain at least 5* 10^10
platelets in sufficient plasma to maintain a pH of greater than 6
throughout the storage period. The anticoagulant –
preservative solution used is CPD, CP2D or CPDA.
Regardless of the technique used platelets are stored for upto 5
days at 20 to 24 c with a constant gentle agitation which
ensures a near normal post transfusion recovery and survival.
29. RDP
When a single unit of whole blood collected in triple pack plastic
collection bags, PRP is separated from packed RBCs after
centrifugation at 2000g. This PRP is then centrifuged at 5000g at
20’C for 2 mins , platelets separated, PPP transferred to other
bag for FFP and cryoprecipitate. By this technique under optimal
operating conditions 85% of platelets are removed from 1 unit of
whole blood.
SDAP
Apheresis refers to a technique of drawing peripheral blood,
separating it and selectively removing one or more components
while returning the remainder to the donor.
30. GUIDELINES FOR PEDIATRIC PLATELET
TRANSFUSIONS
CHILDREN AND ADOLESCENTS:
PLT < 50000/cmm and bleeding.
PLT < 50000/cmm and invasive procedure.
PLT < 20000/cmm & marrow failure & hemorrhagic risk factors.
PLT < 10000/cmm marrow failure without hemorrhagic risk
factors.
PLT at any count but with platelet dysfunction + Bleeding or an
invasive procedure.
INFANTS WITHIN FIRST 4 MONTHS:
PLT <100000/cmm and bleeding.
PLT <50000/cmm and invasive procedure.
PLT <20000/cmm and clinically stable.
PLT <100000/cmm and clinically unstable.
PLT at any count but with platelet dysfunction + bleeding or an
invasive procedure.
31. DOSE:
The usual dose is 10ml/ kg
OR
1 unit / 10 kg body weight.
ADMINISTRATION:
Before administration the platelet bag should be
warmed to room temperature and should be infused over 15
to 20 min or as fast as possible.
INCREMENT:
1 unit / 10 kg of RDP will increase the platelet count by
40000 – 50000/mm3.
6 units of platelet conc. of RDP = 1 SDAP unit will increase the
platelet count by 70000 to 80000/mm3.
32. FRESH FROZEN PLASMA
Plasma separated from single units of whole blood collected in
CPD or CPDA by heavy spin at 1 – 6’c if frozen within 6 hours of
collection, yields FFP.
Volume from single donation is 200 ml.
It is stored at < -30’c to preserve the activity of clotting factors.
Can be stored for up to 1 yr at this temperature.
33. CONTENTS:
This plasma contains essentially normal levels factors II, V, VIII,
IX, X and fibrinogen except factors V and VIII which often lose
their activity during several months of storage.
Factor VIII levels are 0.6–0.7 units/ml (60 to 70%). Each bag of
FFP contains 180 to 220 cc of plasma ie.~ 180-200 units of
factor VIII and IX.
It should be thawed in a water bag at 37C and administered
within 1/2 hour after thawing as the activity of factor V and VIII
is rapidly lost.
34. INDICATIONS:
1. Replacement of coagulation factors in liver disease, def of Vit K
dependant factors (II, VII, IX, X), DIC, overdoses of
anticoagulants, cardiopulmonary bypass, massive blood
transfusions;
2. Specific deficiencies of factors V, VIII, XI
3. Replacement of hemostatic factors when specific concentrate
preparations are not available eg. Hemophilia A and B,
deficiencies of VII, X, fibrinogen and prothrombin, von
Willebrand’s disease, antithrombin III deficiency ;
35. 4. In situations where certain plasma constituents are
lacking e.g. fibronectin in septicemia,C1 esterase in
hereditary angioneurotic edema, PGI2 in thrombotic
thrombocytopenic purpura.
5. FFP transfusion is the only known treatment for rare
inherited deficiency of factors V, XI,XII,XIII and Flecther and
Fitzgerald factors.
36. Dose: 10 to 20 ml/kg.
However it is useful only in management of mild bleeding. It
cannot be used to control severe bleeding where large amount
of factor is needed for the fear of overload as in IC bleed, acute
hemarthrosis and muscular hemorrhages.
Only 10 to 15 ml/kg may be given with safety in single dose.
Expected rise is of 20 to 30 % in factor VIII activity.
It should be compatible with recipients ABO type.
As FFP is harvested from single donor it holds less risk of
Hepatitis, AIDS and other plasma borne infections.
37. SIDE EFFECTS:
1. Circulatory overload.
2. Pyrogenic reactions.
3. Allergic or anaphylactoid reactions.
4. Headache or abdominal pain
5. TRALI is more likely.
6. Acute hemolytic reactions.
7. Citrate induced hypocalcemia.
8. Development of antibodies of Factor VIII inhibitors.
38. CRYOPRECIPITATE
WHOLE BLOOD
FFP
Slowly Thawed 2-4’C for
18 to 24 hrs
PRECIPITATEPLASMA
CRYOPRECIPITATE
Used for other purposes
(contains all CF except factor
VIII & fibrinogen)
Rapid centrifugation
Refrozen & stored at
temp< -30’C for 3-12
months
39. Cryoprecipitate contains:
i. Antihemophilic factor (factor VIII) 40-160 units/bag.
ii. Riestocetin or von Willebrand factor (factor viii cofactor).
iii. Factor VIII related antigen (factor VIIIR Ag).
iv. Fibrinogen 200 to 250 mg/ bag.
v. Factor XIII and trace elements of other factors.
The amount of factor VIIIc and fibrinogen in individual bags may
vary widely.
Factor IX is not present in clinically significant amounts.
40. INDICATIONS:
i. Hemophilia A.
ii. Von Willebrand’s disease.
iii. Congenital hypo and Afibrinogenemia.
iv. Cryoprecipitate shortens the abnormally long
bleeding time in platelet functional disorders,
Hermansky Pudlak syndrome, Uremia, DIC and
Liver disorders.
41. Advantages:
1. Normal factor level can be achieved without the danger of
volume overload. It contains ~ 20 times as much factor VIII
per unit volume of FFP.
2. Less expensive than factor VIII concentrate.
3. Treatment of choice in von Willebrand’s disease since it
contains factor VIII c and von Willebrand factor.
4. Cryoprecipitate causes less transfusion reactions than does
plasma as the former has only a few foreign immunogenic
proteins.
5. Less risk of hepatitis and AIDS as compared to factor VIII
concentrate as it is prepared by a single donor. However,
unlike factor VIII conc. Cryoprecipitate cannot be heat treated
to eliminate contaminating viruses.
42. DISADVANTAGES:
1. To retain factor VIII activity for more than a few weeks, it
must be kept frozen below -30’c.
2. Cryoprecipitate is extremely viscous, difficult to mix and time
consuming and laborious to administer.
3. Amount of factor VIII activity varies from bag to bag.
4. Less common side effects seen are hemolytic anemia,
paradoxical hemorrhages due to defective platelet function,
alloimmunization to IgG determinants and the induction of
circulating immune complexes. It is also causally related to
increase incidence of hypertension and renal dysfunction in
hemophiliacs.
43. GRANULOCYTES
Granulocytes concentrates can be prepared manually by
harvesting the buffy coat layer from a single unit of blood or by
leucopheresis.
This yields 0.5 to 0.6 x 10^9 granulocytes per unit of whole
blood.
1 unit prepared by apheresis = 18-20 units of buffy coat.
Granulocytes concentrates can be stored at 20-24 c for 24 hrs
The product must be ABO compatible.
The dose of Granulocytes recommended is 1-2 *10^9cells/kg
in 10-15 ml/kg of volume. It can be repeated 12-24 hourly for
4 to 6 days
44. Guidelines for transfusing neutrophils in
children:
Blood neutrophils <500 /cmm and bacterial infection
unresponsive to antibiotics.
Blood neutrophils <500 /cmm and yeast or fungal infections
progressing or appearing during treatment with antimicrobials.
Neutrophils dysfunctions with bacterial, yeast, fungal infections
unresponsive to antimicrobials.
Guidelines for transfusing neutrophils in infants
<4 months:
Blood Neutrophils <3000 /cmm and fulminant sepsis during the
first week of life.
Blood Neutrophils <1000 /cmm and fulminant sepsis after 1st
week of life.
45. FACTOR VIII CONCENTRATE
Lyophilised concentrate containing 250-1500 units of factor VIII
c in a reconstituted volume of about 25 cc arte prepared from
large pools of FFP from 2000-5000 paid donors.
Factor viii is purified by combining cryoprecipitation and
precipitation with glycine, polyetheneglycol or ethanol and
further fractionated and freeze dried.
The products are packaged in individual vials indicating the
exact number of units of factor VIII activity.
46. ADVANTAGES:
1. Factor content per unit volume is 10-40 times greater than
plasma and hence prevents volume overload.
2. They can be stored at 4’C in a home fridge and
reconstituted with sterile water warmed to body temp,
drawn into a syringe through a filter needle and then
infused into the patient.
3. Transfusion reactions are virtually eliminated with the
removal white cells and platelets.
47. DISADVANTAGES:
1. Since factor VIII concentrates are prepared from large lots
of cold plasma, they carry the major risks of transfusion
hepatitis, AIDS, toxoplasmosis and other viral infections.
2. Factor VIII concentrate are extremely expensive and are
available with difficulty only in major cities. They cost
about Rs.2-4 per unit.
3. More complete purification processes result in less yield of
factor VIII particularly after heat treatment.
48. PROTHROMBIN COMPLEX
CONCENTRATES (PCC)
Lyophilized concentrate of factors II, VII, IX and X containing
500-1000 I.U. of factor IX in 25 cc are used mainly for
treatment of factor IX deficiency.
They can also be used for other rare bleeding disorders as in
congenital or acquired deficiencies of factor II, VII and X.
It is also used for patients with antibodies for factors VIII & IX.
49. ADVANTAGES.
1. Standardization.
2. Storage at 4’C.
3. Easy reconstitution with sterile water.
4. Ease of administration with syringe.
50. DISADVANTAGES:
1. Greater chances of Hepatitis and AIDS .
2. Increased amount of thrombogenic material leading to
increased risk of thrombogenic phenomenon.
3. High risk of acute myocardial infarction and DIC.
4. Mild reactions like headache and flushing. Hence give slowly.
5. Other immediate reactions may be nausea, fever, chills,
urticaria, paresthesia, hypotension and anaphylactoid
reactions.
51. ACTIVATED PROTHROMBIN COMPLEX
CONENTRATES
This product is mainly developed to bypass factor VIII or IX
especially for persons with high levels of antibodies to these
factors.
Limitations – High costs, high risk of transmission of hepatitis
and AIDS and difficulty in lab monitoring for the effectiveness.
Trade name – AUTOPLEX, FEIBA
52. PORCINE FACTOR VIII CONCENTRATE
Factor VIII concentrate made from porcine plasma has low
cross activity towards most antibodies.
Limitations – Severe adverse effects like anaphylaxis,
thrombocytopenia and pyrogenic reactions.
To minimize these adverse effects, improved methods of
fractionations are now employed to yield concentrates of very
high purity with fewer or no side effects which can be further
minimized by administering 100 mg of hydrocortisone.
Infusion of porcine factor VIII may be followed by rise in level
of inhibiters in both human and porcine. Hence it should be
monitored after treatment.
53. INTRAVENOUS IMMUNOGLOBINS
IVIG is a purified concentrate of solution of immunoglobulin with
stabilizers such as sucrose. They can be both non diseases
specific or disease specific.
Most products contain >90% Ig G with small amounts of Ig M
and Ig A.
Non disease specific Ig are prepared from fractionation of
plasma while specific Ig are separated from plasma from donors
who possess high titres of specific antibodies.
54. The indications for use are:
1. Prevention and treatment of diseases such as hepatitis,
rubella, Varicella Zoster, Tetanus, Measles, Rabies, etc..
2. Replacement therapy in Ig deficiency syndrome.
3. Treatment of immune disorders such as Immune
thrombocytopenic purpura,
4. Prevention of sensitization in Rh negative women by
administrating Anti D globulin.
5. Prophylaxis and treatment of neonatal sepsis.
6. Kawasaki disease.
57. INFECTIOUS COMPLICATIONS:
1. VIRAL INFECTIONS: HIV 1, Hepatitis B Virus, Hepatitis C
Virus, Other Hepatitis Viruses like rarely HAV or
HGV, CMV, HTLV Type I and Parvovirus B 19.
2. BACTERIAL INFECTIONS: Some Gm –ve bacteria e.g.
Yersinia and Pseudomonas species can grow
at 1 to 6’C. Platelet concentrates stored at
room temperature are more likely to contain
skin contaminants such as Gm +ve
organisms including Coagulase negative
Staphylococci.
3. OTHER INFECTIOUS AGENTS: Parasites like those
causing Malaria, Babesiosis and Chagas disease.
Rarely West Nile Virus, Lyme’s disease and
Creutzfield Jacob disease.