Blood is LIFE

Blood is also a Poison

Blood Transfusion:
Basics and Recent
Developments

Speaker:

Prof. Dr. Manzur Morshed

MRCP (UK)

Clinical Hematology

FCPS,

BASICS

Blood Products
Whole Blood
Red cell preparations

Platelet products

Plasma
products

leukocyte concentrates

BLOOD COMPONENTS

RBC products

Packed RBCs
Leukocyte-poor (Leuco-reduced) red cells
Washed RBCs
Irradiated RBCs.

Platelet products

Random-donor platelets
Single-donor platelets

HLA-matched platelets

Leukocyte (granulocyte) concentrates

BLOOD COMPONENTS contd..

Plasma

products

Fresh-frozen

plasma (FFP)
Cryoprecipitate
Factor concentrates (VIII, IX)
Albumin
Immune globulins

When transfusion therapy is contemplated:

Component. e.g. Packed RBC; not whole blood

Fresh blood ???

Fresh Blood
Can Blood be transfused immediately after
donation?

No, the donation needs to be processed and

tested. This takes three working days from
the date of donation
http://www.ucsfhealth.org/education/donating_blood/

When transfusion therapy is contemplated:

Component. e.g. Packed RBC; not whole blood

Fresh blood ???
Ensure safety of blood product
- Who is the donor?
- T & S.
Is extended phenotyping necessary?

RBC typing & screening

Is extended phenotyping necessary?
Extended Phenotype: Patients

requiring long-term transfusion

therapy (ie. Thalassemia) often
produces an unexpected antibody
to one or more red cell antigens
(such as K, k, Jka, Jkb, Fya, Fyb).
Here, extended phenotypes help

identify the safest product for

transfusion.

When transfusion therapy is contemplated:

Component. e.g. Packed RBC; not whole blood

Fresh blood ???
Ensure safety of blood product
- Who is the donor?
- T & S.
Is extended phenotyping necessary?
- Is product modification necessary?
- Role of RBC washing
- Leucofiltration
- Irradiated RBCs and platelets

Blood Product Modifications:

Washing, Leukofiltration and Irradiation

RBCs/Platelets can be washed to remove antibodies,

cytokines and occasionally, excess of electrolytes, which
may be harmful for some transfusion recipients.

Patients with Thalassemia

Patients with a history of severe allergic reactions to

blood components

Neonates undergoing exchange/massive transfusion

Blood Product Modifications:

Washing, Leukofiltration and Irradiation

Leukocyte-poor red cells

- to avoid febrile reactions due to white cell products
- to minimize transmission of viral disease such as HIV or CMV.

- Prevention of HLA alloimmunization; e.g. for persons who may

be candidate for marrow transplantation.
Indications:
Patients who had 2 mild/moderate or 1 severe febrile reaction.
All chemotherapy patients.
All transplant or potential transplant patients.
All neonates, infants, children & multiparous (3 pregnancies)
women requiring tx.

Blood Product Modifications:

Washing, Leukofiltration and Irradiation
Performed to prevent transfusion-associated graftversus-host-disease (TA-GVHD)
Indications:
Congenital immune deficiencies, transfusion from
relatives, Hodgkin Lymphoma (current or history
of), BMT recipients.
Hematologic malignancies receiving aggressive
chemotherapy, HLA-matched platelets.

Indications of transfusion
Whole blood

FWB is unlikely to become an FDA approved

therapy

Acute hemorrhage with hypovolemia

(impending shock): In trauma setting;

Exchange transfusion in infants for hemolytic

disease of newborn

In our country..there may be an indication

Indications of transfusion
Packed RBCs

Thalassemias and other hemoglobinopathies

Hypoproliferative anemia
- anemia in malignancy/ after chemo- or radiotherapy

- aplastic anemia, MDS, mylofibrosis

Anemia of chronic disease (ACD, anemia of
inflammation)
Anemia in elderly patients with angina or congestive
heart disease
Peri-operative, when cardiac function is compromised

Indications of transfusion
Granulocyte transfusions

Patients with documented sepsis (especially Gram

negative) with granulocyte count <0.2 x109/L who
failed to response to appropriate antibiotics within
48h of therapy.

Indications of transfusion
Platelet transfusions

Stored at room temp

Random donor

50-70 ml per unit

6 units should increase plt by 30,000

Single donor

200-400 ml
Equivalent to pool of 6 units random donor
No significant benefit over random donor, unless matched

Prophylactic: <10,000 (<20 if febrile). >50 for procedures, >80-100 for major
surgery

Indications and contraindications

Red Cell Transfusion

Factors to consider include:

The

severity of anemia: is it
symptomatic?
Cause of anemia
Patients age
Presence of underlying cardiac
or pulmonary disease or any
other co-morbidity

Transfusion decisions are often taken

based on limited and frequently low quality

evidence
an often exaggerated anxiety towards any level
of anemia.

Ref: A new perspective on best transfusion practices

Shander et al; Blood Transfus. Apr 2013; 11(2): 193202.

Transfusion Trigger in anemic patients:

common mistakes

Incidental finding of low Hb and propose

transfusion
Begin transfusion without trying to identify the
cause

A case scenario___

Adverse effects of transfusion

Immunologic
Infections
Volume overload (TACO)
Hemosiderosis
Rare (hypothermia, dilutional metabolic, pul
microembolism)
Increased short term mortality

Immunologic effects of transfusion

1. Febrile transfusion reactions
2. Allergic
- minor (urticaria)
- severe (anaphylaxis)
3. Hemolytic transfusion reactions
- immediate
- delayed
4. Transfusion-related acute lung injury (TRALI)
5. Graft-versus-host disease (TA-GVHD)
6. Post-transfusion purpura
7. Immune modulation

Febrile non-haemolytic transfusion reactions (FNHTR)

Cause: Cytokines or donor HLA/ other antigens on

granulocytes or platelets reacting to recipient
antibodies (as a result of previous tx/ pregnancies).
Paracetamol and antihistamine (avil) .
Slow restart after exclusion of serious differentials.
Pre-storage leucodepletion has reduced this risk to in
<1% of txs.

Minor allergic reactions

Cause: Hypersensitivity to allergens or plasma

proteins in the transfused unit. Rarely due to donor
medication.

Antihistamines may be given

Restart tx at a slow rate & complete within 4 hours.

Washed red cells if the patient has recurrent allergic

reactions to tx.

Severe allergic reactions

(anaphylaxis)

IgE antibody interacts with a plasma protein in donated

blood.

Oxygen, antihistamines, adrenaline and steroids as

required.

To prevent recurrence: Consider pre-medication with

steroids and antihistamine. Avoid plasma.

Use IgA-deficient or washed RBCs, if patient is IgA

deficient & has anti-IgA .

Hemolytic Transfusion Reaction

Recipients immune system attacks the RBCs of
donor.
Acute: ABO mismatch
Mortality related to amount of blood transfused,
organ failure
Delayed: Often directed against Rh, Kidd, Duffy,
Kell.
Occurs several days to a week after transfusion

TRALI: 3rd most common cause of transfusionrelated death.

Hypoxemia, fever, bilateral infiltrates and hypotension (form of

ARDS ) developing within 6 hours after transfusion.

Major differential includes CHF/volume overload, infection

HLA antibodies in donor plasma leading to destruction of host

granulocytes and activation of the complement system leading
to lung injury - results in fluid accumulating in the lungs.

Treatment is supportive; May include ventilatory support

Recovery is usually rapid and complete

Transfusion Related Graft vs. Host Disease

(Ta-GVHD)
When donor lymphocytes attack the recipient tissues
Develops 4 - 30 days after transfusion. Fever and a maculopapular rash
progressing to erythroderma and toxic epidermal necrolysis. Other
symptoms include anorexia, vomiting, abdominal pain, profuse
diarrhea, and cough.
In immunosuppressed recipients - mainly patients with Hodgkin's disease
and leukemia. Also occurs in normal blood recipient when the donor is
homozygous for an HLA haplotype and recipient is heterozygous for that
haplotype (related donor)
Lab: pancytopenia, abnormal LFTs and electrolyte abnormalities. Biopsy:
satellite dyskeratosis.
Circulating lymphocytes have a different HLA phenotype from host cells.
TGVH is prevented by irradiating blood products

Post-transfusion purpura (PTP)

A reaction where a patient develops sudden & self-limiting

thrombocytopenia (<10 x 109/L in 80% of cases), typically 7 - 10
days after transfusion.
GIT, urinary tract bleeding or even Intracranial haemorrhage can
occur
Patients usually have a history of sensitisation by either pregnancy
or transfusion. Multiparous female patients are more affected than
males.
Alloimmunisation to antigens (HPA-1a, HPA-1b and HLA antigens)
have been implicated.
With IVIG, the platelet count is expected to rise in 4 days.

Immune Modulation

Non-immunological effects of transfusion

Viral, parasitic or bacterial infections

Circulatory overload can cause heart failure
Iron overload (hemosiderosis)

Non-immunological effects of transfusion:

Hepatitis (A, B, C, other)

CMV

EBV

HIV

Malaria

Syphilis

Different bacteria

Other organisms

Infections

Safe blood transfusion law, approved by the

Bangladesh Parliament in 2002 makes it
mandatory for all transfusion service centres to
screen all donations for 5 transmissible diseases
through testing for - HBsAg,
- anti-HCV,
- HIV ab1 & 2,

- VDRL and
- malaria.

Anti-HBc, NAT, DNA, CMV, EBV, HTLV

RECENT CONCEPTS

Transfusion situations

Surgical: peri-operative
Critical Care and Sepsis
Coronary disease
GI bleeding
Other general

Transfusion in surgical setting

In the USA, 60 70 % of all RBC units are

transfused in surgical setting.
Despite the common use of RBC transfusions in
surgical patients, the indications for transfusion in
the perioperative setting have not been definitively
evaluated.

Peri-operative TransfusionIndications: in old days

This condition, owing to the lowered oxygen

carrying capacity of the blood interferes with the
adequate transportation of oxygen to the tissues.
When the concentration of Hb is < 8-10 gm/100 cc
blood, it is wise to give blood transfusion

Adams RC, Lundy JS. Anesthesia in cases of poor surgical risk: some suggestions for
decreasing the risk. Surg Gynecol Obstet 1942; 74:10111015

Peri-operative TransfusionIndications: in recent days

NIH Consensus Conference (1988) on Peri-operative RBC

Transfusions suggested

Decision to transfuse is based on patients clinical

condition rather than a given level of Hb
blood transfusion of patients with chronic stable
anemia is probably unjustifiable if Hb is above 7g
per 100ml

The FOCUS study: Liberal or restrictive transfusion in high-risk

patients after hip surgery
Carson JL et al N Engl J Med. 2011 Dec 29;365(26):2453-62.

The FOCUS study: Liberal or restrictive transfusion in high-risk

patients after hip surgery
Carson JL et al N Engl J Med. 2011 Dec 29;365(26):2453-62.

2016 patients 50 years age

history or risk factors for CVD
Hb <10g/dL following surgery for hip fracture

Intervention: Random assignment to

- a liberal transfusion strategy (transfuse RBC to keep the Hb >
10g/dL) or
- a restrictive transfusion strategy (symptoms of anemia or at physician
discretion only if hb is < 8 g/dL).

Outcome: Death or an inability to walk across a room on 60-day follow

up.

The FOCUS study: Liberal or restrictive transfusion in high-risk

patients after hip surgery
Carson JL et al N Engl J Med. 2011 Dec 29;365(26):2453-62

Tx were 3 times higher in liberal group compared to

restrictive group (1,866 vs. 652 units)
Liberal tx strategy, as compared to restrictive strategy,
did not reduce death rate or inability to walk or reduce
in-hospital morbidity in elderly patients at high
cardiovascular risk.
Rates of other complications similar.
Observations: This study demonstrates that limiting
blood tx in this high-risk patient group is not
associated with less favorable outcomes than a liberal
tx policy.

The FOCUS study: Liberal or restrictive transfusion in

high-risk patients after hip surgery
Carson JL et al N Engl J Med. 2011 Dec 29;365(26):2453-62.
As the authors found no differences between 2 groups, they put
forward the advantages of restrictive transfusion regimes as
(1) less viral infections due to less blood transfusion (hepatitis B/C),
(2) less mixed up transfusions,
(3) less bacterial infections due to contaminated blood products and
(4) less influence on the immune system of the blood recipient and
(5) lower costs.

Transfusion in
Critical Care and Sepsis

TRICC trial 1999

ABC trial 2002
Surviving sepsis campaign 2013
TRISS trial 2014

A MULTICENTER, RANDOMIZED, CONTROLLED CLINICAL TRIAL

OF TRANSFUSION REQUIREMENTS IN CRITICAL CARE (TRICC):
INVESTIGATORS FOR THE CANADIAN CRITICAL CARE TRIAL GROUP; N Engl J Med 1999;340:409-17

838 critically ill patients were randomly

assigned within 72 hours after admission to
ICU
418 patients to a restrictive strategy of tx, in
which red cells were transfused if Hb dropped
<7g/dl & Hb was maintained at 7 to 9g/dl
and
420 patients to a liberal strategy, in which tx
was given when Hb fell <10g/dl & Hb was
maintained at 10 to 12g/dl.

TRICC Trial of 838 patients

Hebert, NEJM, 1999

A MULTICENTER, RANDOMIZED, CONTROLLED CLINICAL TRIAL

OF TRANSFUSION REQUIREMENTS IN CRITICAL CARE (TRICC):
INVESTIGATORS FOR THE CANADIAN CRITICAL CARE TRIAL GROUP; N Engl J Med 1999;340:409-17

30-day mortality: Subgroup

analyses demonstrated that a
restrictive transfusion strategy was
associated with significantly lower
mortality in patients with APACHE II
score 20 and age <55 years.

ABC trial in Europe

Anemia and blood transfusion in critically ill patients.

Vincent JL et al

JAMA. 2002;288:14991507

3534 patients from 146 W. European ICUs.

Followed up for 28 days or until hospital discharge/ death.
The mean pretransfusion Hb was 8.4 1.3 g/dl.
Both ICU and overall mortality were significantly higher in
patients who had vs had not received a tx

ICU mortality rates: 18.5% (tx) vs 10.1% (no tx); P<.001;

Overall mortality rates: 29.0% vs 14.9%; P<.001.

For similar degrees of organ dysfunction, patients who had a

transfusion had a higher mortality rate.
This effect again was clear with more than 2 RBC units
transfused

Surviving Sepsis Campaign: International Guidelines for

Management of Severe Sepsis and Septic Shock, 2012
R. P. Dellinger et al; Intensive Care Medicine, February 2013, Volume 39, Issue 2, pp 165-228

Surviving Sepsis Campaign recommendations regarding

blood transfusion in patients with septic shock:

Transfusion to maintain a hct of > 30% in the

presence of hypoperfusion in the first 6 hours.
After that, the transfusion threshold should be a Hb
of <7g/dl, aiming at levels between 7g & 9g/dl in
patients who do not have myocardial ischemia,
severe hypoxemia, hemorrhage, or ischemic CAD.

Multicenter, randomized TRISS trial

N Engl J Med 2014; 371:1381-1391. October 9, 2014

998 ICU (502 in lower- & 496 in higher-threshold group) patients

with septic shock .

{7 g /dl (lower threshold) or 9 g /dl (higher threshold)}.

RESULTS: No differences in mortality at 90 days, in the numbers of

patients with ischemic events or in the use of life support, or in the
numbers of days alive & out of the hospital between the groups.

Similar results were observed in subgroups of patients with chronic

cardiovascular disease, with older age, or with greater disease
severity.

Transfusion in coronary disease

Relationship of Blood Transfusion and Clinical Outcomes in Patients

With Acute Coronary Syndromes
JAMA. 2004;292(13):1555-1562. doi:10.1001/jama.292.13.1555

Relationship of Blood Transfusion and Clinical Outcomes in Patients

With Acute Coronary Syndromes
JAMA. 2004;292(13):1555-1562. doi:10.1001/jama.292.13.1555

Conclusions Blood transfusion in the setting of

acute coronary syndromes is associated with higher
mortality, and this relationship persists after
adjustment for other predictive factors and timing
of events.. ...
We suggest caution regarding the routine use of
blood transfusion to maintain arbitrary hematocrit
levels in stable patients with ischemic heart disease.

Red blood cell transfusion is a determinant of neurological complications after cardiac surgery.
Mariscalco G et al; Interact Cardiovasc Thorac Surg. Nov 2, 2014.

14,956 patients undergoing CABG and valve

surgery at 3 European University Hospitals. The
prognostic impact of RBC transfusion on
postoperative stroke and TIA was investigated.
CONCLUSIONS: Transfusion of more than 2
units of RBCs after cardiac surgery is associated
with a significantly increased risk of postoperative
stroke and TIA.

Transfusion Strategies for Acute Upper GI Bleeding

Cndid Villanueva et al; N Engl J Med 2013; 368:11-21 January 3, 2013

921 patients with severe acute upper GI bleeding:

461 assigned to a restrictive strategy (tx if Hb <7 g/dl)
460 to a liberal strategy (tx when the Hb fell <9 g/dl).
Randomization was stratified according to the presence
or absence of liver cirrhosis.
CONCLUSIONS: As compared with a liberal
transfusion strategy, a restrictive strategy significantly
improved outcomes in patients with acute upper GI
bleeding.

Transfusion thresholds and other strategies for guiding

allogeneic red blood cell transfusion. Carless PA et al. Cochrane Database Syst Rev.
2010 Oct 6;(10):CD002042

17 trials involving a total of 3746 patients. Restrictive

transfusion strategies reduced the risk of receiving a RBC
transfusion by a relative 37%.
Restrictive transfusion strategies were associated with a
statistically significant reduction in the rates of infection.

The existing evidence supports the use of restrictive

transfusion triggers in patients.
In countries with inadequate screening of donor
blood, the data may constitute a stronger basis for
avoiding transfusion.

Take home message

1.

We should be aware of the limitations in transfusion

facilities in our hospitals that compromise the quality
of blood products

2.
3.
4.

5.

infection screening
extended phenotyping
Leucofiltration
Blood product irradiation

Whole blood transfusion should be avoided if possible

Blood from near relatives should be avoided
Increased mortality is a real concern after transfusion
of blood products.
Cause of anemia should be identified before deciding
to transfuse a patient

Last word.
One of the first duties of the
physician is to educate the masses
not to take medicine.... William Osler

Thank you