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GUIDELINES FOR RATIONAL USE OF
BLOOD
Dr. Guvera Vasireddy
Department of Pathology
Osmania Medical College
departmentofpathology,osmanamedical
college,Hyderabad
1
THEFIRSTBLOODBANKINMOSCOW
The first
academic
institution
devoted to
the science
of blood
transfusion
was
founded by
Alexander
Bogdanov
in Moscow
in 1925.
2
departmentofpathology,osmanamedical
college,Hyderabad
―WARS WERE MOTIVATED BY PROFITS, NOT
PRINCIPLES‖
departmentofpathology,osmanamedical
college,Hyderabad
3
 Henry Norman Bethune
(March 4, 1890 – November
12, 1939;) was a Canadian
physician and medical
innovator.
 Known for his service in war
time medical units during
the Spanish Civil War and
with the Communist Eighth
Route Army (Ba Lu Jun)
during the Second Sino-
Japanese War.
 He developed the first
mobile blood-transfusion
service in Spain in 1936
MAJOR MILESTONES IN BLOOD TRANSFUSION
 Soviet experience travels to America, in 1937 Bernard
Fantus, director of therapeutics at the Cook County Hospital in
Chicago, established the first hospital blood bank in the United
States.
 In 1947, the American Association of Blood Banks, now known as
the AABB, was formed.
 In 1953, the plastic blood bag was invented by the Fenwal Co.,
 By 1962, America's Blood Centres network was established with the
help of hospitals, doctors, local civic groups and community-based
blood centres.
 By 1970, blood banks were using a volunteer donating system;
approximately 5 to 6 million units of blood per year were being
collected.
4
departmentofpathology,osmanamedical
college,Hyderabad
AIDS: A NEW DEADLY DISEASE ARRIVES
 Young gay men in the United States started dying from a
mysterious disease in the late 70s and 80s.
 1981 January, Michael S. Gottlieb, MD, a young assistant
professor of medicine at the University of California at Los
Angeles School of Medicine, met Michael — the man who
would become the AIDS index case.
 1982, July 27, The term AIDS (acquired immune deficiency
syndrome) is proposed at a meeting in Washington of gay-
community leaders, federal bureaucrats and the CDC to
replace GRID (gay-related immune deficiency) as evidence
showed it was not gay specific.
5
departmentofpathology,osmanamedical
college,Hyderabad
THE DEADLY VIRUS GETS A NAME
 1983, January, Françoise Barré-Sinoussi, at the Pasteur
Institute in Paris, isolates a retrovirus that kills T-cells from
the lymph system of a gay AIDS patient.
 1984, March 4 edition of the MMWR, CDC notes that most
cases of AIDS have been reported among homosexual men
with multiple sexual partners, injection drug
users, Haitians, and hemophiliacs.
 The report suggests that AIDS may be caused by an
infectious agent that is transmitted sexually or through
exposure to blood or blood products and issues
recommendations for preventing transmission.
 This retrovirus would be called by several names, including
LAV and HTLV-III before being named HIV in 1986. 6
departmentofpathology,osmanamedical
college,Hyderabad
departmentofpathology,osmanamedical
college,Hyderabad
7
SCREENING FOR HIV MADE MANDATORY
o 1985, March 2, FDA approves the first AIDS antibody
screening tests for use on all donated blood and
plasma intended for transfusion and product
manufacture.
o In addition to HIV several other pathogens have been
made part of routine screening programs in blood
banks world wide.
8
departmentofpathology,osmanamedical
college,Hyderabad
WHY DO WE NEED TO BE WARY OF TRANSFUSING
BLOOD AND BLOOD PRODUCTS?
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departmentofpathology,osmanamedical
college,Hyderabad
BLOOD TRANSFUSION RISKS
 Despite rigorous screening blood components
continue to pose a small risk of transmission of
pathogens, including viruses, bacteria, and
parasites.
 Currently unrecognized pathogens may also
emerge in time.
 Some studies have suggested that allogeneic blood
may have an immunomodulatory effect.
10
departmentofpathology,osmanamedical
college,Hyderabad
INFECTIOUS DISEASE RISKS
Primary Risks
 Bacteria
 Hepatitis B virus
 Hepatitis C virus
 HIV-1
 HIV-2
 Malaria (primarily
Plasmodium malariae
and P. falciparum)
 Syphilis (Treponema
pallidum)
Additional Risks in
Immunocompromised
Recipients
 Cytomegalovirus
 Parvovirus B19
 Epstein-Barr virus
 Babesiosis (Babesia
microti)
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departmentofpathology,osmanamedical
college,Hyderabad
RARE RISKS
 Chagas disease
(Trypanosoma cruzi)
 West Nile virus
 Hepatitis A
 Variant Creutzfeldt-
Jakob disease
 Human T-cell
lymphotropic viruses
 Leishmaniasis (visceral
Leishmania tropica and
possibly L. donovani)
 Human anaplasmosis
(formerly human
granulocytic
anaplasmosis and
human granulocytic
ehrlichiosis)
 Dengue fever
12
departmentofpathology,osmanamedical
college,Hyderabad
THEORETICAL, BUT UNREPORTED RISKS
 Creutzfeldt-Jakob disease
 Human ehrlichiosis (formerly human monocytic
ehrlichiosis)
 Lyme disease (Borrelia burgdorferi)
 Toxoplasmosis (Toxoplasma gondii)
13
departmentofpathology,osmanamedical
college,Hyderabad
ESTIMATED RESIDUAL RISKS OF SOME
TRANSFUSION-TRANSMISSIBLE VIRUSES
Virus Recent Risk Estimate Ranges
HIV-1 1/1,467,000 units
HCV 1/1,149,000 units
HBV 1/280,000 – 1/357,000 units
HTLV 1/1,208,000 units
14
departmentofpathology,osmanamedical
college,Hyderabad
NON-INFECTIOUS COMPLICATIONS OF
TRANSFUSION
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departmentofpathology,osmanamedical
college,Hyderabad
IMMUNOLOGIC COMPLICATIONS, IMMEDIATE
 Hemolytic transfusion reaction
 Immune-mediated platelet destruction.
 Febrile nonhemolytic reaction.
 Allergic reactions as mild or self-limiting urticaria or
wheezing.
 Anaphylactoid/anaphylactic reactions.
 Transfusion-related acute lung injury (TRALI).
16
departmentofpathology,osmanamedical
college,Hyderabad
IMMUNOLOGIC COMPLICATIONS, DELAYED
 Delayed hemolytic reactions occur in previously red-cell-
alloimmunized patients in whom antigens on transfused red
cells provoke anamnestic production of antibody.
 Alloimmunization to antigens of red cells, white cells,
platelets, or plasma proteins may occur unpredictably after
transfusion.
 Post transfusion purpura (PTP) is characterized by the
development of dramatic, sudden, and self limited
thrombocytopenia.
 Transfusion-associated graft-vs.-host disease (TA-GVHD). 17
departmentofpathology,osmanamedical
college,Hyderabad
METABOLIC AND PHYSIOLOGIC COMPLICATIONS
 Citrate ―toxicity‖ reflects a depression of ionized calcium
caused by the large quantities of citrate anticoagulant.
 Because citrate is promptly metabolized by the liver, this
complication is rare.
 Acidosis or alkalosis and hyper- or hypokalemia
 Transfusion Associated Circulatory Overload can accompany
transfusion of any component at a rate more rapid than the
recipient‘s cardiac output can accommodate.
 Iron overload is a long-term complication of repeated RBC
transfusions
18
departmentofpathology,osmanamedical
college,Hyderabad
HOW TO PREVENT TRANSFUSION RELATED
INFECTIONS AND ADVERSE REACTIONS?
19
departmentofpathology,osmanamedical
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HAEMOVIGILANCE
 "Haemovigilance is required to identify and prevent
occurrence or recurrence of transfusion related
unwanted events, to increase the safety, efficacy and
efficiency of blood transfusion, covering all activities of
the transfusion chain from donor to recipient."
otherwise
 '… A set of surveillance procedures covering the whole
transfusion chain (from the collection of blood and its
components to the follow-up of recipients), intended to
collect and assess information on unexpected or
undesirable effects resulting from the therapeutic use of
labile blood products, and to prevent their occurrence or
recurrence …' 20
departmentofpathology,osmanamedical
college,Hyderabad
TRANSFUSON RELATED ISSUES IN
SURGICAL PATIENTS
21
departmentofpathology,osmanamedical
college,Hyderabad
ENSURE APPROPRIATENESS OF BLOOD
TRANSFUSION
 Risk should be outweighed by the potential
benefits.
 Alternative strategies to reduce the use of
allogeneic blood should be considered.
 Patients should be informed that transfusion is part
of the planned intervention
 The patient‘s consent should be obtained for the
planned transfusion and recorded in the patient‘s
medical chart. 22
departmentofpathology,osmanamedical
college,Hyderabad
23
departmentofpathology,osmanamedical
college,Hyderabad
REDUCE EXPOSURE TO ALLOGENEIC TRANSFUSION
 Autologous transfusion
 Surgical, anaesthetic and pharmacological
approaches to reduce blood loss.
 Strategies for management of transfusion
requirements in surgical patients:
1. Pre-operative
2. Intra-operative
3. Post-operative
24
departmentofpathology,osmanamedical
college,Hyderabad
PRE-OPERATIVE MANAGEMENT
 Treatment of Pre-existing Anaemia
 Predeposit Autologous Donation
 Avoidance of Drugs that Increase Surgical Blood
loss.
25
departmentofpathology,osmanamedical
college,Hyderabad
PATIENTS ANTICOAGULATED WITH WARFARIN 1
ELECTIVE SURGERY
 Stop warfarin 3 days pre-operatively and monitor INR
daily
 Give heparin by infusion or subcutaneously, if required.
 Stop heparin 6 hours pre-operatively.
 Check INR and APTT ratio immediately prior to surgery.
 Commence surgery if INR and APTT ratio are < 2.0.
 Restart warfarin as soon as possible post-operatively.
 Restart heparin at the same time and continue until INR
is in the therapeutic range.
26
departmentofpathology,osmanamedical
college,Hyderabad
PATIENTS ANTICOAGULATED WITH
WARFARIN 2
 EMERGENCY SURGERY
 Give vitamin K, 0.5-2.0 mg by slow IV infusion.
 Give fresh frozen plasma, 15 ml/kg. This dose may
need to be repeated to bring coagulation factors to
an acceptable range.
 Check INR immediately prior to surgery.
 Commence surgery if INR and APTT ratio are < 2.0.
27
departmentofpathology,osmanamedical
college,Hyderabad
PATIENTS ANTICOAGULATED WITH HEPARIN
ELECTIVE SURGERY
 Stop heparin 6 hours pre-operatively.
 Commence surgery if INR and APTT ratio are < 2.0.
 Check APTT ratio immediately prior to surgery.
 Restart heparin as soon as appropriate post-operatively.
EMERGENCY SURGERY
 Consider reversal with IV protamine sulphate. 1 mg of
protamine neutralizes 100 iu heparin.
PATIENTS RECEIVING LOW-DOSE HEPARIN
 It is rarely necessary to stop low-dose heparin injections,
used in the prevention of deep vein thrombosis and
pulmonary embolism, prior to surgery.
28
departmentofpathology,osmanamedical
college,Hyderabad
INTRA-OPERATIVE MANAGEMENT
 Management of Blood Loss
 Management of Volume Replacement
 Reduction of Oxygen Demand
 Intra-operative Blood Salvage (IBS)
 Antifibrinolytic Agents
29
departmentofpathology,osmanamedical
college,Hyderabad
POST-OPERATIVE MANAGEMENT
 Post-operative Blood Salvage (PBS)
 Management of Volume Replacement & On-going
Blood Loss
 Post-operative patients in ICU/HDU require close
monitoring of haemodynamic
status, oxygenation, pain relief, biochemical and
haematological indices and on going blood loss.
 Red Cell Transfusion 30
departmentofpathology,osmanamedical
college,Hyderabad
THRESHOLDS FOR SPECIFIC SITUATIONS
 Hb <7-10g/dL during surgery associated with major
blood loss or if evidence of impaired oxygen
transport
 Hb <8g/dL; patients on a chronic transfusion
regimen or during marrow suppressive therapy (for
symptom control and appropriate growth)
 Hb <10g/dL; only for very select populations (eg.
neonates)
31
departmentofpathology,osmanamedical
college,Hyderabad
RECOMMENDATIONS BY AAAB
32
departmentofpathology,osmanamedical
college,Hyderabad
departmentofpathology,osmanamedical
college,Hyderabad
33
 In hospitalized, hemodynamically stable patients, at what
hemoglobin concentration should a decision to transfuse RBCs
be considered?
 The AABB recommends adhering to a restrictive transfusion
strategy.
 In adult and pediatric intensive care unit patients, transfusion
should be considered at hemoglobin concentrations of 7 g/dL or
less.
 In postoperative surgical patients, transfusion should be
considered at a hemoglobin concentration of 8 g/dL or less or for
symptoms
 Quality of evidence: high; strength of recommendation: strong.
 In hospitalized, hemodynamically stable patients with
preexisting cardiovascular disease, at what hemoglobin
concentration should a decision to transfuse RBCs be
considered?
 The AABB suggests adhering to a restrictive transfusion
strategy. Transfusion should be considered at a
hemoglobin concentration of 8 g/dL or less or for
symptoms.
 Quality of evidence: moderate; strength of
recommendation: weak.
34
departmentofpathology,osmanamedical
college,Hyderabad
 In hospitalized, hemodynamically stable patients with
the acute coronary syndrome, at what hemoglobin
concentration should an RBC transfusion be
considered?
 The AABB cannot recommend for or against a liberal or
restrictive RBC transfusion threshold.
 Further research is needed to determine the optimal
threshold.
 Quality of evidence: very low; strength of
recommendation: uncertain.
35
departmentofpathology,osmanamedical
college,Hyderabad
 In hospitalized, hemodynamically stable patients, should
transfusion be guided by symptoms rather than
hemoglobin concentration?
 The AABB suggests that transfusion decisions be
influenced by symptoms as well as hemoglobin
concentration.
 Quality of evidence: low; strength of recommendation:
weak.
36
departmentofpathology,osmanamedical
college,Hyderabad
departmentofpathology,osmanamedical
college,Hyderabad
37
BLOOD MANAGEMENT –
GETTING THE RIGHT BLOOD TO THE
RIGHT PATIENT AT THE RIGHT TIME
38
departmentofpathology,osmanamedical
college,Hyderabad
HOSPITAL TRANSFUSION COMMITTEE
 Every hospital should establish a hospital
transfusion committee to monitor clinical blood use
and investigate any acute and delayed transfusion
reactions.
 Committee should include medical and surgical
departments along with blood bank director.
 The committee should ensure that National
guidelines on the clinical use of blood are followed.
 If no national guidelines exist, each hospital should
develop local guidelines
39
departmentofpathology,osmanamedical
college,Hyderabad
COMMITTEE SHOULD ENSURE THAT THE
FOLLOWING ARE IN PLACE
1. A blood request form.
2. A blood ordering schedule for common surgical
procedures.
3. Guidelines on clinical and laboratory indications
for the use of blood, blood products and simple
alternatives to transfusion
4. Medical devices to minimize the need for
transfusion.
5. Standard operating procedures for each stage in
the clinical transfusion process.
6. The training of all staff involved in the transfusion
process to follow standard operating procedures. 40
departmentofpathology,osmanamedical
college,Hyderabad
STANDARD OPERATING PROCEDURES FOR
TRANSFUSION PROCESS
1. Ordering blood and blood products for elective/planned
surgery
2. Ordering blood and blood products in an emergency
3. Completing the blood request form
4. Taking and labelling the pre-transfusion blood sample
5. Collecting blood and blood products from the blood bank
6. Storing and transporting blood and blood products, including
storage in the clinical area
7. Administering blood and blood products, including the final
patient identity check
8. Recording transfusions in patient records
9. Monitoring the patient before, during and after transfusion
10. Managing, investigating and recording transfusion reactions.
41
departmentofpathology,osmanamedical
college,Hyderabad
42
departmentofpathology,osmanamedical
college,Hyderabad
ESTABLISHING MAXIMUM SURGICAL BLOOD
ORDERING SCHEDULE
 A table of surgical procedures which lists the
number of units of blood routinely requested, and
cross-matched for them pre-operatively.
 The schedule is based on retrospective analysis of
actual blood usage associated with the individual
surgical procedure.
 However when antibody screen is positive,
compatible blood must be made available in all
cases before surgery.
43
departmentofpathology,osmanamedical
college,Hyderabad
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departmentofpathology,osmanamedical
college,Hyderabad
DEVELOPING MSBOS
 Data on blood request for all procedures for 6 months is
analysed.
 For each procedure, indicate the number of units cross-
matched and the number of units transfused.
 Calculate the percentage of blood usage:
 In procedures where blood usage is less than 30%, GSH are
performed.
 Other procedures are allotted based on the average number
of blood transfused.
45
departmentofpathology,osmanamedical
college,Hyderabad
IMPLEMENTATION OF MSBOS
 MSBOS should be explained to all doctors in the
hospitals and the best way is through the Transfusion
Committee.
 When all heads of department have agreed on a
schedule, it should be circulated and implemented.
 Regular monitoring is necessary to detect any problems
and for ‗fine tuning‘ of the schedule if necessary.
 Confidence in the operation of MSBOS and compliance
by users depend on the laboratory being able to provide
compatible blood whenever it is required, including
urgent requests.
46
departmentofpathology,osmanamedical
college,Hyderabad
PROTOCOL FOR GSH GROUP
1. Serum saved for cross-matching must be accurately labelled
and readily accessible.
2. Procedures must be clearly defined to enable blood
transfusion staff to provide compatible blood safely should an
emergency occur during a GSH operation.
3. Communication between the operating theatre and the blood
transfusion laboratory must be clearly defined.
4. Transporting blood between the laboratory and the operating
theatre must have an established priority.
5. For GSH category, the serum is kept for 48 hours. 47
departmentofpathology,osmanamedical
college,Hyderabad
PROCEDURE FOR EMERGENCIES
 Blood samples from all patients must have a full ABO
and RhD grouping and antibody screening done.
 If required urgently, blood of the same ABO and RhD
can be given after an appropriate ‗quick blood
method‘.
 After been issued, the laboratory would continue to
do a full cross-match.
 If any incompatibility is detected, the patient‘s doctor
must be informed immediately.
48
departmentofpathology,osmanamedical
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RECOMMENDATIONS IN RH D NEGATIVE PATIENTS
 All Rh D negative patients must receive D negative
whole blood or packed red cells except in certain
situations.
 All blood banks should have a few RhD negative units in
their stock based on their requirement.
 Blood banks to keep a list of their RhD negative donors
who can be contacted in an emergency.
 When D negative blood is not available, the treating
clinicians may decide to allow RhD positive blood to be
given instead. 49
departmentofpathology,osmanamedical
college,Hyderabad
INSTRUCTIONS FOR USE
 All blood and blood components must be stored under
appropriate conditions as described in the AABB Standards.
 The intended recipient and the blood container must be
properly identified before the transfusion is started.
 Aseptic technique must be employed during preparation and
administration.
 All blood components must be transfused through a filter
designed to remove clots and aggregates (generally a
standard 170- to 260-micron filter).
 Blood and blood components should be mixed thoroughly
before use.
50
departmentofpathology,osmanamedical
college,Hyderabad
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departmentofpathology,osmanamedical
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PRECAUTIONS DURING TRANSFUSION
 No medications should be added to or infused
through the same tubing with blood.
 Lactated Ringer‘s, Injection (USP) or other
solutions containing calcium should never be
added.
 Blood components should be warmed if clinically
indicated.
 Unless otherwise indicated by the patient‘s clinical
condition, the rate of infusion should initially be
slow.
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departmentofpathology,osmanamedical
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SPECIAL SITUATIONS
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MANAGEMENT OF ANEMIA IN CANCER PATIENTS
 Cancer-related anemia adversely affects quality of life
and is associated with reduced overall survival.
 Thecorrection of anemia in cancer patients has the
potential to improve treatment efficacy and increase
survival.
 Treatment of anemia in cancer patients using
erythropoiesis-stimulating agents (ESAs) significantly
increases hemoglobin levels.
 Decreases transfusion requirements and improves quality
of life, predominantly by reducing fatigue.
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departmentofpathology,osmanamedical
college,Hyderabad
GRADING OF ANEMIA ACCORDING TO THE
NATIONAL CANCER INSTITUTE
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departmentofpathology,osmanamedical
college,Hyderabad
ERYTHROPOIESIS-STIMULATING AGENTS
 ESAs are capable of increasing hemoglobin levels in
most anemic patients with cancer.
 ESAs increase the risk of thromboembolic events.
 During chemotherapy, ESA treatment should be initiated
when hemoglobin values are lower than 10 g/dl.
 ESAs should not be used in patients with cancer who are
not receiving chemotherapy.
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departmentofpathology,osmanamedical
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IRON
 Chemotherapy is associated with abnormal iron
metabolism.
 Another mechanism contributing to iron deficiency in cancer
patients is the low bioavailability of orally administered iron.
 The use of intravenous iron (and not oral iron) during
treatment with ESAs may improve hemoglobin levels even
in the absence of depleted iron stores (or absolute iron
deficiency).
 Recommendations for the optimal supplementation with
ESA treatment in cancer-related anemia need to be
established. 57
departmentofpathology,osmanamedical
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BLOOD TRANSFUSION
 Blood transfusion is capable of immediately correcting
the signs or symptoms resulting from anemia.
 There is wide variation in the levels of hemoglobin that
are used to justify blood transfusions among the various
studies and among different types of cancers.
 There are several acute hazards related to blood
transfusion, and long-term side effects have not been
properly studied.
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departmentofpathology,osmanamedical
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SHELF LIFE OF IRRADIATED RED CELLS
 Irradiation of blood products is undertaken using a
dedicated blood irradiator with a long half-life gamma
emitting source.
 Irradiation of red blood cells and whole blood results in
reduced post transfusion red cell recovery and
increases the rate of efflux of intracellular potassium.
 Packs irradiated within 14 days of collection expire 28
days after collection.
 Packs irradiated more than 14 days after collection
expire either 5 days after irradiation OR at original expiry
of pack, whichever comes first.
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departmentofpathology,osmanamedical
college,Hyderabad
SHELF LIFE OF IRRADIATED COMPONENTS
 In patients where hyperkalaemia is a concern, red cells
should be transfused within 24 hours of irradiation.
 Irradiation of platelets has not been shown to cause any
clinically significant change in platelet function.
 Platelets may be irradiated at any stage during their 5
day storage life.
 Granulocytes should be transfused as soon as possible
after collection and irradiation.
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departmentofpathology,osmanamedical
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IRRADIATED BLOOD COMPONENTS IN INFANTS
 Irradiation of cellular blood components with a minimum
of 2,500 rad (25 Gy) is recommended for the following:
 infants < 1500 g birth weight
 infants with known or suspected congenital
immunodeficiency syndromes involving T-cells, eg:
DiGeorge syndrome
 infants receiving granulocyte transfusions
 infants receiving directed donor blood components from
blood relatives
 infants undergoing immunosuppressive therapy or
chemotherapy
 Infants receiving exchange transfusions
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departmentofpathology,osmanamedical
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CYTOMEGALOVIRUS (CMV)
 Blood components from CMV-seropositive donors
may contain residual leucocytes which are
potentially infectious to seronegative infants.
 CMV-seronegative or leucoreduced cellular
components (RBCs, platelets, granulocytes) should
be provided for infants who weigh <1,200 g at birth
or who are immunocompromised,
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departmentofpathology,osmanamedical
college,Hyderabad
ALTERNATIVES TO TRANSFUSION
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departmentofpathology,osmanamedical
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AUTOLOGOUS BLOOD COLLECTION AND
TRANSFUSION
 Preoperative collection.
 Frozen autologous blood
 Perioperative acute haemodilution.
 Intraoperative blood salvage.
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departmentofpathology,osmanamedical
college,Hyderabad
PLASMA EXPANDERS
 Crystalloid Solutions (Plasmalyte®)
 Gelatin Solutions (Gelofusin®)
 Dextran Solutions (Dextran 40, Dextran 70)
 Hydroxyethyl Starch (HES; HESPAN®;
PENTASPAN®:)
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departmentofpathology,osmanamedical
college,Hyderabad
OXYGEN CARRYING COMPOUNDS
 Although artificial blood in the form of perfluoro compounds and modified
haemoglobin solutions have been under investigation for many years
there is no indication that these compounds will be widely available for
routine use in the near future.
 Products based on polymerised haemoglobin Hemopure® (Biopure
Corporation), a bovine-derived product which despite safety concerns is
currently approved for human use in South Africa;
 PolyHeme® (Northfield Laboratories), which uses human
haemoglobin, has been taken to phase III clinical trials in the US,
 Second-generation products Hemospan® (Sangart) uses
humanhaemoglobin conjugated with polyethylene glycol (PEG) and is
currently in a phase II trial in the US and entering phase III trials in
Europe.
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departmentofpathology,osmanamedical
college,Hyderabad
HAEMOPOIETIC GROWTH FACTORS
 Recombinant Human Erythropoietin (rEPO; Epoetin
beta, EPRE X™, Recormon®)
 Granulocyte Stimulating Factor (G-CSF; Neupogen®)
 Thrombopoietin (TPO)
 Recombinant Coagulation Factors
 on-transfusion Therapy using Desmopressin (DDAVP;
Minirin®;Octostim®)
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departmentofpathology,osmanamedical
college,Hyderabad

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Guidelines for rational use of blood

  • 1. GUIDELINES FOR RATIONAL USE OF BLOOD Dr. Guvera Vasireddy Department of Pathology Osmania Medical College departmentofpathology,osmanamedical college,Hyderabad 1
  • 2. THEFIRSTBLOODBANKINMOSCOW The first academic institution devoted to the science of blood transfusion was founded by Alexander Bogdanov in Moscow in 1925. 2 departmentofpathology,osmanamedical college,Hyderabad
  • 3. ―WARS WERE MOTIVATED BY PROFITS, NOT PRINCIPLES‖ departmentofpathology,osmanamedical college,Hyderabad 3  Henry Norman Bethune (March 4, 1890 – November 12, 1939;) was a Canadian physician and medical innovator.  Known for his service in war time medical units during the Spanish Civil War and with the Communist Eighth Route Army (Ba Lu Jun) during the Second Sino- Japanese War.  He developed the first mobile blood-transfusion service in Spain in 1936
  • 4. MAJOR MILESTONES IN BLOOD TRANSFUSION  Soviet experience travels to America, in 1937 Bernard Fantus, director of therapeutics at the Cook County Hospital in Chicago, established the first hospital blood bank in the United States.  In 1947, the American Association of Blood Banks, now known as the AABB, was formed.  In 1953, the plastic blood bag was invented by the Fenwal Co.,  By 1962, America's Blood Centres network was established with the help of hospitals, doctors, local civic groups and community-based blood centres.  By 1970, blood banks were using a volunteer donating system; approximately 5 to 6 million units of blood per year were being collected. 4 departmentofpathology,osmanamedical college,Hyderabad
  • 5. AIDS: A NEW DEADLY DISEASE ARRIVES  Young gay men in the United States started dying from a mysterious disease in the late 70s and 80s.  1981 January, Michael S. Gottlieb, MD, a young assistant professor of medicine at the University of California at Los Angeles School of Medicine, met Michael — the man who would become the AIDS index case.  1982, July 27, The term AIDS (acquired immune deficiency syndrome) is proposed at a meeting in Washington of gay- community leaders, federal bureaucrats and the CDC to replace GRID (gay-related immune deficiency) as evidence showed it was not gay specific. 5 departmentofpathology,osmanamedical college,Hyderabad
  • 6. THE DEADLY VIRUS GETS A NAME  1983, January, Françoise Barré-Sinoussi, at the Pasteur Institute in Paris, isolates a retrovirus that kills T-cells from the lymph system of a gay AIDS patient.  1984, March 4 edition of the MMWR, CDC notes that most cases of AIDS have been reported among homosexual men with multiple sexual partners, injection drug users, Haitians, and hemophiliacs.  The report suggests that AIDS may be caused by an infectious agent that is transmitted sexually or through exposure to blood or blood products and issues recommendations for preventing transmission.  This retrovirus would be called by several names, including LAV and HTLV-III before being named HIV in 1986. 6 departmentofpathology,osmanamedical college,Hyderabad
  • 8. SCREENING FOR HIV MADE MANDATORY o 1985, March 2, FDA approves the first AIDS antibody screening tests for use on all donated blood and plasma intended for transfusion and product manufacture. o In addition to HIV several other pathogens have been made part of routine screening programs in blood banks world wide. 8 departmentofpathology,osmanamedical college,Hyderabad
  • 9. WHY DO WE NEED TO BE WARY OF TRANSFUSING BLOOD AND BLOOD PRODUCTS? 9 departmentofpathology,osmanamedical college,Hyderabad
  • 10. BLOOD TRANSFUSION RISKS  Despite rigorous screening blood components continue to pose a small risk of transmission of pathogens, including viruses, bacteria, and parasites.  Currently unrecognized pathogens may also emerge in time.  Some studies have suggested that allogeneic blood may have an immunomodulatory effect. 10 departmentofpathology,osmanamedical college,Hyderabad
  • 11. INFECTIOUS DISEASE RISKS Primary Risks  Bacteria  Hepatitis B virus  Hepatitis C virus  HIV-1  HIV-2  Malaria (primarily Plasmodium malariae and P. falciparum)  Syphilis (Treponema pallidum) Additional Risks in Immunocompromised Recipients  Cytomegalovirus  Parvovirus B19  Epstein-Barr virus  Babesiosis (Babesia microti) 11 departmentofpathology,osmanamedical college,Hyderabad
  • 12. RARE RISKS  Chagas disease (Trypanosoma cruzi)  West Nile virus  Hepatitis A  Variant Creutzfeldt- Jakob disease  Human T-cell lymphotropic viruses  Leishmaniasis (visceral Leishmania tropica and possibly L. donovani)  Human anaplasmosis (formerly human granulocytic anaplasmosis and human granulocytic ehrlichiosis)  Dengue fever 12 departmentofpathology,osmanamedical college,Hyderabad
  • 13. THEORETICAL, BUT UNREPORTED RISKS  Creutzfeldt-Jakob disease  Human ehrlichiosis (formerly human monocytic ehrlichiosis)  Lyme disease (Borrelia burgdorferi)  Toxoplasmosis (Toxoplasma gondii) 13 departmentofpathology,osmanamedical college,Hyderabad
  • 14. ESTIMATED RESIDUAL RISKS OF SOME TRANSFUSION-TRANSMISSIBLE VIRUSES Virus Recent Risk Estimate Ranges HIV-1 1/1,467,000 units HCV 1/1,149,000 units HBV 1/280,000 – 1/357,000 units HTLV 1/1,208,000 units 14 departmentofpathology,osmanamedical college,Hyderabad
  • 16. IMMUNOLOGIC COMPLICATIONS, IMMEDIATE  Hemolytic transfusion reaction  Immune-mediated platelet destruction.  Febrile nonhemolytic reaction.  Allergic reactions as mild or self-limiting urticaria or wheezing.  Anaphylactoid/anaphylactic reactions.  Transfusion-related acute lung injury (TRALI). 16 departmentofpathology,osmanamedical college,Hyderabad
  • 17. IMMUNOLOGIC COMPLICATIONS, DELAYED  Delayed hemolytic reactions occur in previously red-cell- alloimmunized patients in whom antigens on transfused red cells provoke anamnestic production of antibody.  Alloimmunization to antigens of red cells, white cells, platelets, or plasma proteins may occur unpredictably after transfusion.  Post transfusion purpura (PTP) is characterized by the development of dramatic, sudden, and self limited thrombocytopenia.  Transfusion-associated graft-vs.-host disease (TA-GVHD). 17 departmentofpathology,osmanamedical college,Hyderabad
  • 18. METABOLIC AND PHYSIOLOGIC COMPLICATIONS  Citrate ―toxicity‖ reflects a depression of ionized calcium caused by the large quantities of citrate anticoagulant.  Because citrate is promptly metabolized by the liver, this complication is rare.  Acidosis or alkalosis and hyper- or hypokalemia  Transfusion Associated Circulatory Overload can accompany transfusion of any component at a rate more rapid than the recipient‘s cardiac output can accommodate.  Iron overload is a long-term complication of repeated RBC transfusions 18 departmentofpathology,osmanamedical college,Hyderabad
  • 19. HOW TO PREVENT TRANSFUSION RELATED INFECTIONS AND ADVERSE REACTIONS? 19 departmentofpathology,osmanamedical college,Hyderabad
  • 20. HAEMOVIGILANCE  "Haemovigilance is required to identify and prevent occurrence or recurrence of transfusion related unwanted events, to increase the safety, efficacy and efficiency of blood transfusion, covering all activities of the transfusion chain from donor to recipient." otherwise  '… A set of surveillance procedures covering the whole transfusion chain (from the collection of blood and its components to the follow-up of recipients), intended to collect and assess information on unexpected or undesirable effects resulting from the therapeutic use of labile blood products, and to prevent their occurrence or recurrence …' 20 departmentofpathology,osmanamedical college,Hyderabad
  • 21. TRANSFUSON RELATED ISSUES IN SURGICAL PATIENTS 21 departmentofpathology,osmanamedical college,Hyderabad
  • 22. ENSURE APPROPRIATENESS OF BLOOD TRANSFUSION  Risk should be outweighed by the potential benefits.  Alternative strategies to reduce the use of allogeneic blood should be considered.  Patients should be informed that transfusion is part of the planned intervention  The patient‘s consent should be obtained for the planned transfusion and recorded in the patient‘s medical chart. 22 departmentofpathology,osmanamedical college,Hyderabad
  • 24. REDUCE EXPOSURE TO ALLOGENEIC TRANSFUSION  Autologous transfusion  Surgical, anaesthetic and pharmacological approaches to reduce blood loss.  Strategies for management of transfusion requirements in surgical patients: 1. Pre-operative 2. Intra-operative 3. Post-operative 24 departmentofpathology,osmanamedical college,Hyderabad
  • 25. PRE-OPERATIVE MANAGEMENT  Treatment of Pre-existing Anaemia  Predeposit Autologous Donation  Avoidance of Drugs that Increase Surgical Blood loss. 25 departmentofpathology,osmanamedical college,Hyderabad
  • 26. PATIENTS ANTICOAGULATED WITH WARFARIN 1 ELECTIVE SURGERY  Stop warfarin 3 days pre-operatively and monitor INR daily  Give heparin by infusion or subcutaneously, if required.  Stop heparin 6 hours pre-operatively.  Check INR and APTT ratio immediately prior to surgery.  Commence surgery if INR and APTT ratio are < 2.0.  Restart warfarin as soon as possible post-operatively.  Restart heparin at the same time and continue until INR is in the therapeutic range. 26 departmentofpathology,osmanamedical college,Hyderabad
  • 27. PATIENTS ANTICOAGULATED WITH WARFARIN 2  EMERGENCY SURGERY  Give vitamin K, 0.5-2.0 mg by slow IV infusion.  Give fresh frozen plasma, 15 ml/kg. This dose may need to be repeated to bring coagulation factors to an acceptable range.  Check INR immediately prior to surgery.  Commence surgery if INR and APTT ratio are < 2.0. 27 departmentofpathology,osmanamedical college,Hyderabad
  • 28. PATIENTS ANTICOAGULATED WITH HEPARIN ELECTIVE SURGERY  Stop heparin 6 hours pre-operatively.  Commence surgery if INR and APTT ratio are < 2.0.  Check APTT ratio immediately prior to surgery.  Restart heparin as soon as appropriate post-operatively. EMERGENCY SURGERY  Consider reversal with IV protamine sulphate. 1 mg of protamine neutralizes 100 iu heparin. PATIENTS RECEIVING LOW-DOSE HEPARIN  It is rarely necessary to stop low-dose heparin injections, used in the prevention of deep vein thrombosis and pulmonary embolism, prior to surgery. 28 departmentofpathology,osmanamedical college,Hyderabad
  • 29. INTRA-OPERATIVE MANAGEMENT  Management of Blood Loss  Management of Volume Replacement  Reduction of Oxygen Demand  Intra-operative Blood Salvage (IBS)  Antifibrinolytic Agents 29 departmentofpathology,osmanamedical college,Hyderabad
  • 30. POST-OPERATIVE MANAGEMENT  Post-operative Blood Salvage (PBS)  Management of Volume Replacement & On-going Blood Loss  Post-operative patients in ICU/HDU require close monitoring of haemodynamic status, oxygenation, pain relief, biochemical and haematological indices and on going blood loss.  Red Cell Transfusion 30 departmentofpathology,osmanamedical college,Hyderabad
  • 31. THRESHOLDS FOR SPECIFIC SITUATIONS  Hb <7-10g/dL during surgery associated with major blood loss or if evidence of impaired oxygen transport  Hb <8g/dL; patients on a chronic transfusion regimen or during marrow suppressive therapy (for symptom control and appropriate growth)  Hb <10g/dL; only for very select populations (eg. neonates) 31 departmentofpathology,osmanamedical college,Hyderabad
  • 33. departmentofpathology,osmanamedical college,Hyderabad 33  In hospitalized, hemodynamically stable patients, at what hemoglobin concentration should a decision to transfuse RBCs be considered?  The AABB recommends adhering to a restrictive transfusion strategy.  In adult and pediatric intensive care unit patients, transfusion should be considered at hemoglobin concentrations of 7 g/dL or less.  In postoperative surgical patients, transfusion should be considered at a hemoglobin concentration of 8 g/dL or less or for symptoms  Quality of evidence: high; strength of recommendation: strong.
  • 34.  In hospitalized, hemodynamically stable patients with preexisting cardiovascular disease, at what hemoglobin concentration should a decision to transfuse RBCs be considered?  The AABB suggests adhering to a restrictive transfusion strategy. Transfusion should be considered at a hemoglobin concentration of 8 g/dL or less or for symptoms.  Quality of evidence: moderate; strength of recommendation: weak. 34 departmentofpathology,osmanamedical college,Hyderabad
  • 35.  In hospitalized, hemodynamically stable patients with the acute coronary syndrome, at what hemoglobin concentration should an RBC transfusion be considered?  The AABB cannot recommend for or against a liberal or restrictive RBC transfusion threshold.  Further research is needed to determine the optimal threshold.  Quality of evidence: very low; strength of recommendation: uncertain. 35 departmentofpathology,osmanamedical college,Hyderabad
  • 36.  In hospitalized, hemodynamically stable patients, should transfusion be guided by symptoms rather than hemoglobin concentration?  The AABB suggests that transfusion decisions be influenced by symptoms as well as hemoglobin concentration.  Quality of evidence: low; strength of recommendation: weak. 36 departmentofpathology,osmanamedical college,Hyderabad
  • 38. BLOOD MANAGEMENT – GETTING THE RIGHT BLOOD TO THE RIGHT PATIENT AT THE RIGHT TIME 38 departmentofpathology,osmanamedical college,Hyderabad
  • 39. HOSPITAL TRANSFUSION COMMITTEE  Every hospital should establish a hospital transfusion committee to monitor clinical blood use and investigate any acute and delayed transfusion reactions.  Committee should include medical and surgical departments along with blood bank director.  The committee should ensure that National guidelines on the clinical use of blood are followed.  If no national guidelines exist, each hospital should develop local guidelines 39 departmentofpathology,osmanamedical college,Hyderabad
  • 40. COMMITTEE SHOULD ENSURE THAT THE FOLLOWING ARE IN PLACE 1. A blood request form. 2. A blood ordering schedule for common surgical procedures. 3. Guidelines on clinical and laboratory indications for the use of blood, blood products and simple alternatives to transfusion 4. Medical devices to minimize the need for transfusion. 5. Standard operating procedures for each stage in the clinical transfusion process. 6. The training of all staff involved in the transfusion process to follow standard operating procedures. 40 departmentofpathology,osmanamedical college,Hyderabad
  • 41. STANDARD OPERATING PROCEDURES FOR TRANSFUSION PROCESS 1. Ordering blood and blood products for elective/planned surgery 2. Ordering blood and blood products in an emergency 3. Completing the blood request form 4. Taking and labelling the pre-transfusion blood sample 5. Collecting blood and blood products from the blood bank 6. Storing and transporting blood and blood products, including storage in the clinical area 7. Administering blood and blood products, including the final patient identity check 8. Recording transfusions in patient records 9. Monitoring the patient before, during and after transfusion 10. Managing, investigating and recording transfusion reactions. 41 departmentofpathology,osmanamedical college,Hyderabad
  • 43. ESTABLISHING MAXIMUM SURGICAL BLOOD ORDERING SCHEDULE  A table of surgical procedures which lists the number of units of blood routinely requested, and cross-matched for them pre-operatively.  The schedule is based on retrospective analysis of actual blood usage associated with the individual surgical procedure.  However when antibody screen is positive, compatible blood must be made available in all cases before surgery. 43 departmentofpathology,osmanamedical college,Hyderabad
  • 45. DEVELOPING MSBOS  Data on blood request for all procedures for 6 months is analysed.  For each procedure, indicate the number of units cross- matched and the number of units transfused.  Calculate the percentage of blood usage:  In procedures where blood usage is less than 30%, GSH are performed.  Other procedures are allotted based on the average number of blood transfused. 45 departmentofpathology,osmanamedical college,Hyderabad
  • 46. IMPLEMENTATION OF MSBOS  MSBOS should be explained to all doctors in the hospitals and the best way is through the Transfusion Committee.  When all heads of department have agreed on a schedule, it should be circulated and implemented.  Regular monitoring is necessary to detect any problems and for ‗fine tuning‘ of the schedule if necessary.  Confidence in the operation of MSBOS and compliance by users depend on the laboratory being able to provide compatible blood whenever it is required, including urgent requests. 46 departmentofpathology,osmanamedical college,Hyderabad
  • 47. PROTOCOL FOR GSH GROUP 1. Serum saved for cross-matching must be accurately labelled and readily accessible. 2. Procedures must be clearly defined to enable blood transfusion staff to provide compatible blood safely should an emergency occur during a GSH operation. 3. Communication between the operating theatre and the blood transfusion laboratory must be clearly defined. 4. Transporting blood between the laboratory and the operating theatre must have an established priority. 5. For GSH category, the serum is kept for 48 hours. 47 departmentofpathology,osmanamedical college,Hyderabad
  • 48. PROCEDURE FOR EMERGENCIES  Blood samples from all patients must have a full ABO and RhD grouping and antibody screening done.  If required urgently, blood of the same ABO and RhD can be given after an appropriate ‗quick blood method‘.  After been issued, the laboratory would continue to do a full cross-match.  If any incompatibility is detected, the patient‘s doctor must be informed immediately. 48 departmentofpathology,osmanamedical college,Hyderabad
  • 49. RECOMMENDATIONS IN RH D NEGATIVE PATIENTS  All Rh D negative patients must receive D negative whole blood or packed red cells except in certain situations.  All blood banks should have a few RhD negative units in their stock based on their requirement.  Blood banks to keep a list of their RhD negative donors who can be contacted in an emergency.  When D negative blood is not available, the treating clinicians may decide to allow RhD positive blood to be given instead. 49 departmentofpathology,osmanamedical college,Hyderabad
  • 50. INSTRUCTIONS FOR USE  All blood and blood components must be stored under appropriate conditions as described in the AABB Standards.  The intended recipient and the blood container must be properly identified before the transfusion is started.  Aseptic technique must be employed during preparation and administration.  All blood components must be transfused through a filter designed to remove clots and aggregates (generally a standard 170- to 260-micron filter).  Blood and blood components should be mixed thoroughly before use. 50 departmentofpathology,osmanamedical college,Hyderabad
  • 52. PRECAUTIONS DURING TRANSFUSION  No medications should be added to or infused through the same tubing with blood.  Lactated Ringer‘s, Injection (USP) or other solutions containing calcium should never be added.  Blood components should be warmed if clinically indicated.  Unless otherwise indicated by the patient‘s clinical condition, the rate of infusion should initially be slow. 52 departmentofpathology,osmanamedical college,Hyderabad
  • 54. MANAGEMENT OF ANEMIA IN CANCER PATIENTS  Cancer-related anemia adversely affects quality of life and is associated with reduced overall survival.  Thecorrection of anemia in cancer patients has the potential to improve treatment efficacy and increase survival.  Treatment of anemia in cancer patients using erythropoiesis-stimulating agents (ESAs) significantly increases hemoglobin levels.  Decreases transfusion requirements and improves quality of life, predominantly by reducing fatigue. 54 departmentofpathology,osmanamedical college,Hyderabad
  • 55. GRADING OF ANEMIA ACCORDING TO THE NATIONAL CANCER INSTITUTE 55 departmentofpathology,osmanamedical college,Hyderabad
  • 56. ERYTHROPOIESIS-STIMULATING AGENTS  ESAs are capable of increasing hemoglobin levels in most anemic patients with cancer.  ESAs increase the risk of thromboembolic events.  During chemotherapy, ESA treatment should be initiated when hemoglobin values are lower than 10 g/dl.  ESAs should not be used in patients with cancer who are not receiving chemotherapy. 56 departmentofpathology,osmanamedical college,Hyderabad
  • 57. IRON  Chemotherapy is associated with abnormal iron metabolism.  Another mechanism contributing to iron deficiency in cancer patients is the low bioavailability of orally administered iron.  The use of intravenous iron (and not oral iron) during treatment with ESAs may improve hemoglobin levels even in the absence of depleted iron stores (or absolute iron deficiency).  Recommendations for the optimal supplementation with ESA treatment in cancer-related anemia need to be established. 57 departmentofpathology,osmanamedical college,Hyderabad
  • 58. BLOOD TRANSFUSION  Blood transfusion is capable of immediately correcting the signs or symptoms resulting from anemia.  There is wide variation in the levels of hemoglobin that are used to justify blood transfusions among the various studies and among different types of cancers.  There are several acute hazards related to blood transfusion, and long-term side effects have not been properly studied. 58 departmentofpathology,osmanamedical college,Hyderabad
  • 59. SHELF LIFE OF IRRADIATED RED CELLS  Irradiation of blood products is undertaken using a dedicated blood irradiator with a long half-life gamma emitting source.  Irradiation of red blood cells and whole blood results in reduced post transfusion red cell recovery and increases the rate of efflux of intracellular potassium.  Packs irradiated within 14 days of collection expire 28 days after collection.  Packs irradiated more than 14 days after collection expire either 5 days after irradiation OR at original expiry of pack, whichever comes first. 59 departmentofpathology,osmanamedical college,Hyderabad
  • 60. SHELF LIFE OF IRRADIATED COMPONENTS  In patients where hyperkalaemia is a concern, red cells should be transfused within 24 hours of irradiation.  Irradiation of platelets has not been shown to cause any clinically significant change in platelet function.  Platelets may be irradiated at any stage during their 5 day storage life.  Granulocytes should be transfused as soon as possible after collection and irradiation. 60 departmentofpathology,osmanamedical college,Hyderabad
  • 61. IRRADIATED BLOOD COMPONENTS IN INFANTS  Irradiation of cellular blood components with a minimum of 2,500 rad (25 Gy) is recommended for the following:  infants < 1500 g birth weight  infants with known or suspected congenital immunodeficiency syndromes involving T-cells, eg: DiGeorge syndrome  infants receiving granulocyte transfusions  infants receiving directed donor blood components from blood relatives  infants undergoing immunosuppressive therapy or chemotherapy  Infants receiving exchange transfusions 61 departmentofpathology,osmanamedical college,Hyderabad
  • 63. CYTOMEGALOVIRUS (CMV)  Blood components from CMV-seropositive donors may contain residual leucocytes which are potentially infectious to seronegative infants.  CMV-seronegative or leucoreduced cellular components (RBCs, platelets, granulocytes) should be provided for infants who weigh <1,200 g at birth or who are immunocompromised, 63 departmentofpathology,osmanamedical college,Hyderabad
  • 65. AUTOLOGOUS BLOOD COLLECTION AND TRANSFUSION  Preoperative collection.  Frozen autologous blood  Perioperative acute haemodilution.  Intraoperative blood salvage. 65 departmentofpathology,osmanamedical college,Hyderabad
  • 66. PLASMA EXPANDERS  Crystalloid Solutions (Plasmalyte®)  Gelatin Solutions (Gelofusin®)  Dextran Solutions (Dextran 40, Dextran 70)  Hydroxyethyl Starch (HES; HESPAN®; PENTASPAN®:) 66 departmentofpathology,osmanamedical college,Hyderabad
  • 67. OXYGEN CARRYING COMPOUNDS  Although artificial blood in the form of perfluoro compounds and modified haemoglobin solutions have been under investigation for many years there is no indication that these compounds will be widely available for routine use in the near future.  Products based on polymerised haemoglobin Hemopure® (Biopure Corporation), a bovine-derived product which despite safety concerns is currently approved for human use in South Africa;  PolyHeme® (Northfield Laboratories), which uses human haemoglobin, has been taken to phase III clinical trials in the US,  Second-generation products Hemospan® (Sangart) uses humanhaemoglobin conjugated with polyethylene glycol (PEG) and is currently in a phase II trial in the US and entering phase III trials in Europe. 67 departmentofpathology,osmanamedical college,Hyderabad
  • 68. HAEMOPOIETIC GROWTH FACTORS  Recombinant Human Erythropoietin (rEPO; Epoetin beta, EPRE X™, Recormon®)  Granulocyte Stimulating Factor (G-CSF; Neupogen®)  Thrombopoietin (TPO)  Recombinant Coagulation Factors  on-transfusion Therapy using Desmopressin (DDAVP; Minirin®;Octostim®) 68 departmentofpathology,osmanamedical college,Hyderabad