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Blood Transfusion

Nadia Zaki, MD

Professor of Internal Medicine,


Hematology Unit, Faculty of
Medicine, Alex. University

BLOOD TRANSFUSION
Blood groups:

RBC antigens have varying biochemical,


phenotypic, and immunological characteristics.
Based on this, there are several clinically
important blood group system: ABO, Rh, Kell,
Kidd, and Duffy.

Naturally occurring Abs such as anti-A and/or


anti-B are present in absence of prior sensitizing
stimulus. Development of most other allo-Abs
requires prior sensitization.

Blood compatibility
Blood

components that contain >


2 ml of RBC must be compatible
with patients plasma.

Blood components
1- Whole blood

Indications:
- Acute hypovolemia with RBC loss.
- Exchange transfusion.

It is not a source of functional PLT or


granulocytes, which deteriorate in < 24 hours at
refrigerator temp.

2- Packed RBCs:
1

Unit of packed RBC increases Hb


by 1 g/dl in an average-sized adult.
In average pediatric patient,
transfusion of 8-10 ml of RBCs is
expected to increase Hb by 3 g/dl

Indications:

treatment of
symptomatic anemia.

3- Platelets
May be separated from whole blood
shortly after collection (random donor
or PLT concentrates) or collected by
apheresis (single donor or apheresis
PLT).
Indications:
- Bleeding associated with
thrombocytopenia.
- Qualitative PLT defects.
- Prophylaxis for major bleeding in
severely thrombocytopenic patients.

Platelet refractoriness
This may be:
Non-immune mediated: fever, infection,
splenomegaly, DIC, massive bleeding and
medications that enhance PLT destruction.
Immune-mediated: repeated
transfusions especially with non-leukocyte
reduced PLT and multiparity
(alloimmunization to HLA and human PLT
antigens).
Management: HLA-compatible PLT or
cross-match compatible PLT.

4- Granulocytes

Collected by apheresis, form donors who


are mobilized prior to collection with GCSF.
Indications:
- Neutropenia (ANC < 0.5 109/L)
and documented infection.
- Defective granulocyte function (in
chronic granulomatous disease).

5- Fresh-frozen plasma

* Indications:
Correction of multiple clotting factor
deficiencies in bleeding patients or prior to
invasive procedures.
DIC, liver disease, massive transfusions.
Plasma exchange (as in TTP).
Rapid removal of warfarin effect.
Congenital factor deficiencies (concentrated
or recombinant factor preparations are
preferable to decrease viral transmission).
* Should not be used for volume expansion or
protein replacement in nutritional deficiencies.

6- Cryoprecipitate
A

unit of cryoprecipitate is < 15 ml of


plasma and contains factor VIII,
fibrinogen, factor XIII and vWF activity.

Indications:

treatment of fibrinogen
deficiency, dysfibrinogenemia, factor
XIII deficiency, DIC, urgent treatment
of hemophilia A and von Willebrand
disease in the absence of F VIII
concentrate or recombinant F VIII.

7- Hematopoietic stem and


progenitor cells

Collected from the peripheral blood (PBSC)


via apheresis for reconstitution of
hematopoiesis and immune function in
patients with a variety of malignancies and
immune disorders.

PBSC increase by mobilizing the donor with


hematopoietic growth factors, most often GCSF, or in autologous transplants, a
combination of chemotherapy and HGFs.

Blood derivatives
Blood

products produced
commercially by fractionation of
plasma and include colloids such
as albumin, immune globulins,
coagulation factor concentrates
and others (e.g.; 1-antitrypsin,
antithrombin).

Rh immune globulin
Available in IM and IV forms.
Indications:
- Prevention of alloimmunization of Rh
ve recipients exposed to Rh +ve RBCs.
- Prevention of development of anti-D by
pregnant Rh ve women with Rh +ve
fetuses and subsequent hemolytic dis. of
newborn (HDN).
-Treatment of ITP in Rh +ve patients only (IV
Rh Ig).

Albumin

Indications:
- Hypovolemia: volume expansion.
- Acute liver failure: osmotic pressure,
binds excess bilirubin.
- Cardiopulmonary bypass surgery:
hemodilution.
- After extensive burns.
- Prior to exchange transfusion for HDN:
binds excess free bilirubin to decrease risk
of kernicterus.

Intravenous immune globulin (IVIG)

Indications:
Passive immunity and passive Ab
prophylaxis.
Replacement in 1ry immunodeficiencies.
Immunomodulation of some autoimmune
disorders: refractory ITP.
Treatment of certain infectious disorders:
thrombocytopenia related to HIV, pediatric
HIV infection, CMV interstitial
pneumonitis, Guillian-Barr syndrome.

Derivative and recombinant


coagulation factors

Recombinant factor VIIa (rVIIa):


- F VII deficiency (rare).
- Refractory hemophilia A or B.
- High F VIII or IX inhibitor levels in hemophilia A
or B.
- Severe bleeding refractory to other therapy.
Factor VIII concentrate: F VIII def. and vWD.
Recombinant F VIII: hemophilia A.
Factor IX complex (prothrombin complex):
concentrated F IX and variable amounts of
activated F II, VII, X and protein C; indicated in
hemophilia B, F X def. and F VII def.
Recombinant factor IX: hemophilia B.

Adverse reactions and complications


Immunologic

Nonimmunologic

Acute
FNHTR
Allergic
AHTR
TRALI
-Bacterial
contamination
-Hypocalcemia
-Circulatory
overload

Delayed
DHTR
TAGVHD
PTP
Infections
Hemosiderosis

Febrile non-hemolytic transfusion


reaction (FNHTR)

Defined by > 1C increase in temperature. It is a


diagnosis of exclusion (AHTR, TRALI and sepsis).
Presentation: fever, chills, rigors, tachycardia,
tachypnea, nausea, headache.

Mechanism: Cytokines in blood component bag


accumulated during storage and/or pyrogens
passively transferred from the donor to the recipient
in the blood component.

Management: slow the rate of transfusion, and


antipyretic (paracetamol).
Prevention: leukodepletion , removal of plasma and
premedication with antipyretics.

Mild allergic/urticarial transfusion


reactions

Relatively common, do not progress to anaphylaxis


and rarely lethal and do not necessarily recur with
subsequent transfusions.

Presentation: localized erythema, pruritus, flushing


and urticaria, usually near the IV site.

Mechanism: mediated by IgE Abs, against plasma


proteins or other allergens present in donor plasma
release of histamine and other anaphylotoxins.

Management: antihistamines.

Anaphylactic transfusion
reactions

Presentation: flushing, chills, vomiting, diarrhea,


initial hypertension followed by hypotension,
generalized edema, dyspnea, wheezing,
coughing, stridor, laryngeal edema respiratory
distress and shock. Fever is not a feature.

Mechanism: presence of anti-IgA in an IgA


deficient patient. These Abs react with IgA in the
transfused plasma.

Management: stop transfusion, adrenaline,


corticosteroids and circulatory support. .

Acute hemolytic transfusion


reaction (AHTR)

Presentation: fever, chills, flank/back pain, dyspnea, chest pain,

anxiety, flushing of face, throbbing in the head, nausea and in severe


cases hypotension, renal failure, shock and death.

Mechanism: destruction of transfused RBCs by pre-formed,

naturally occurring isohemagglutinins of the IgM class in the recipients


plasma.

Management:

- stop transfusion.
- Support of BP and renal blood flow with fluids and pressors and
induction of diuresis to maintain urine output > 100 ml/hour.
- Check the identity of the patient and units transfused. Obtain blood
samples (repeat type, cross match, DAT (should be +ve), HCT
decrease, LDH increase, bilirubin increase (within 6-10 Hs) as
indicators of hemolysis.

Transfusion-related acute lung injury


(TRALI)

A non-cardiogenic pulm edema associated with transfusion of


plasma containing blood components.

Presentation: acute respiratory insufficiency, hypotension,

Symptoms subside rapidly, chest X-ray becomes normal within 96


hours and clinical recovery occurs in 48-96 hours.

Mechanism: passive transfer of leukoagglutinis (mostly anti-

Management: discontinue transfusion-supportive therapy in

rigors, fever and a bilateral pulmonary infiltrate on chest X-ray in


absence of heart failure or increase CVP.

HLA class I or II or granulocyte Abs) in donor plasma


endothelial injury, alveolar damage and inflammatory changes
mediated by cytokines and other mediators. Most donors are
multiparous females.
ICU and attention to fluid balance. Fatality rate is 5-8%.

Delayed hemolytic transfusion


reaction (DHTR)

Occurs within days to weeks post transfusion.


Presentation: triad of fever, hyperbilirubinemia
and anemia. DAT is +ve. Hemoglobinuria is rare
because hemolysis is extravascular.
Mechanism: Anamnestic reaction in a previously
alloimmunized patient (by transfusion or
pregnancy) upon re-exposure to the offending
Ag.
Management: Close monitoring of patients Hb
for evidence of continuing hemolysis and
supportive treatment.
Prevention: future transfusion must be Ag ve
for the implicated Ab.

Transfusion-associated GVHD
(TAGVHD)

At risk patients include immunocompromized post


stem cell or organ transplant patients, congenital
immune deficiencies, and some tumors (esp.
lymphomas).

Mechanism: lymphocytes of the donor recognize


patients antigen as foreign immune response.

Prevention: -irradiation of blood components at


2500 cGY. Leukoreduction does not prevent
TAGVHD.

Post transfusion purpura (PTP)

Rare sudden profound thrombocytopenia 7-10


days after transfusion of PLT-containing blood
components, usually RBCs.

Mechanism: presence in the recipient of an Ab


(anti-HPA-1a) against the PLT specific Ag (HPA1a). The Ab results from a previous transfusion or
pregnancy.

Management: self limited, but if severe, IVIG or


plasma exchange.

Prevention: transfusion of Ag ve blood.

Bacterial contamination and


sepsis
Presentation: rigors, chills, fever, nausea, vomiting, abd.

cramps, bloody diarrhea, hemolysis, hemoglobinuria, hypotension


circulatory failure, renal failure, shock and DIC.

Mechanism: Commonly implicated bacteria in RBC:

bacteria that survive the cold storage conditions (Yersinia,


pseudomonas). PLT are stored at room temp. and thus more
susceptible to bacterial growth. Commonly implicated bacteria in
PLT: staphylococci.

Management

& Prevention:

- Broad spectrum antibiotics + treatment of shock.


- Keep blood in controlled refrigerators (at 2-6C) and never
obtain multiple units for the same patient and leave unused
units at room temp. until needed.

Circulatory overload

Symptoms are similar to TRALI but associated with increase in


CVP and cardiac failure. Pulm. edema is cardiogenic in origin

Children, elderly, those with cardiac or pulmonary function


compromise and those with plasma volume expansion are at
particular risk.

Presentation: cough, dyspnea, cyanosis, orthopnea, rales,


headache, congested neck veins, restlessness and tachycardia.

Management & Prevention:

- Stop transfusion.
- Supportive care (O2, diuresis, phlebotomy if
necessary).
- At risk patients should receive smaller amounts of blood at
slower rates (1 - 4 ml/kg/H).

Transfusion-transmitted infections
Viruses :

Hepatotropic: HAV (very rare), HBV,HCV.

Retroviruses: HIV1, and HIV2


HTLV I and HTLV II.

Herpesviruses: CMV, EBV.

Others: Parvovirus B19, West nile


virus (in North America).

Transfusion-transmitted infections
Bacteria: T.B, brucellosis, Syphilis.
Parasites : Malaria,
trypanosomiasis, leishmaniasis and
toxoplasmosis.

Prions: Protein particles believed

to be responsible for transmission of


Creutzfeldt-Jakob disease (CJD).

Hemosiderosis

Occurs in patients who receive repeated (> 20


blood transfusions).
Presentation: Bronze skin, hepatic fibrosis,
diabetes, other endocrine dysfunction and cardiac
failure.
Mechanism: accumulation of iron in the skin and
internal organs. One unit of RBCs contains 200250 mg of iron.
Management: iron studies and iron chelation or
phlebotomy when appropriate.
Prevention: consider chelation for > 20 unit RBC
burden.

Massive transfusion
The administration of blood components
over a 24-hour period in amounts that
equal or exceed the total blood volume of
the patient ( 10 units of whole blood or
20 units of packed RBC in the adult).
Dilution and/or consumption of hemostatic
constituents of blood .
Hypothermia, acidosis, and electrolyte
disturbances.
Hypocalcemia 2ry to citrate accumulation
when large volumes of blood are
administered at rapid rate.

Alternatives of allogeneic blood


transfusion
Pre-operative:

collection.

autologous blood

Intra-operative:

blood salvaged
from a sterile surgical field.

Post-operative:

from drainage.

blood recovered

Thank You

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