Blood component therapy

Blood Component Therapy
Presenter: Dr Manjunath G
Moderator: Dr Jaideep Ravi & Dr Jiju Joseph

• based on the concept that patients are best
treated by administration of the specific fraction
of blood that they lack.
• One donated unit can help multiple patients
– Conserves resources
– Optimal method for transfusing large
amounts of a specific component

PACKED RED CELLS
GRANULOCYTES
PLATELET CONCENTRATE
FRESH FROZEN PLASMA
CRYOPRECIPITATE
COAGULATION FACTOR
CONCENTRATES
PLASMA PROTEIN FRACTION
• ALBUMIN
• GAMMA GLOBULIN
• IVIG

• Blood components are also collected by apheresis,
in which the donor’s blood is processed by ex vivo
centrifugation(apheresis machine), the desired
component(s) are siphoned off into citrate
anticoagulant(to recipient), and the rest returned
to the donor.
• Reduces the number of donor exposures to a
patient.

–Plasmapheresis- to harvest plasma
–Leukapheresis- to harvest leukocytes
–Granulocytapheresis- to harvest granulocytes
–Erythroaphersis- to harvest erythrocytes
–Plateletaphersis- to harvest platelets

Complications
• Sudden fluid shifts – hypotension, volume
overload.
• Paraesthesia and other manifestations of
hypocalcemia (large volume procedures).
• Donor’s discomfort- sit for three hrs
• Associated cost.

Whole blood
Whole blood has a shelf life of 35 days and
typically, 70ml of citrate preservative solution is
added to 420 ml blood.
Whole Blood, Leucocyte Depleted
A unit of blood collected into an
anticoagulant, containing less than 5*106
leucocytes.

Use of whole blood
• Rarely used now a days
• Infrequently used in massive trauma
• Cardiac surgeries
• Post operative bleeding unresponsive to
standard replacement therapy.
• paediatric practice, mostly for neonatal
exchange transfusion or paediatric surgery
(cardiac or craniofacial).

• no compelling evidence was found for its
routine use.
Component vs. Whole Blood Trauma Trial
(COW BITT)
4‐year multicenter prospective randomized trial
300 patients,
Ongoing trial
Conculsion awaited.

PACKED RED BLOOD CELLS
• produced by removing between 150-200ml of
citrated plasma from a unit of whole blood.
• stored under refrigeration at controlled
temperatures of 1 to 6°C to maintain the viability
of the red cells and to prevent the growth of
bacteria.

• Preservative solutions
CPD -21days
CPDA -35 days
SAGM – 42 days
AS-1 (Adsol),
AS-3 (Nutricel),
or AS-5 (Optisol) – 42 days

CPD -21days
Citrate is an anticoagulant,
phosphate serves as a buffer,
dextrose is a red cell energy source

CPDA -35 days
adenine allows RBCs to resynthesize adenosine
triphosphate (ATP), which extends the storage
time from 21 to 35 days.

AS-1 (Adsol)-adenine, glucose, mannitol, and
sodium chloride.
AS-3 (Nutricel)-glucose, adenine, citrate, phosphate,
and NaCl
AS-5 (Optisol)-, adenine, NaCl, and mannitol

Leukoreduced
Irradiated
Saline washed
CMV negative
Antigen Negative
Sickle negative
Frozen thawed

Leukoreduced
A red cell component prepared by removing a
proportion of the plasma from leucocyte depleted
whole blood or by leuco-depleting plasma reduced
red cells.
• Non-LR RBC contain 1-3 x 109 WBC
• LR contain < 5 x 106 WBC and retains 85% of the
original cells.

Leukoreduced
certain complications of PRBCs are likely due to
leukocytes, Eg- HLA alloimmunization against class I
antigens, febrile reactions, and CMV infections.
By leuckoreduction, chances of a febrile reaction
can be reduced, especially (alloimmunized from
pregnancy, risk for HLA alloimmunization from blood
transfusions can be reduced),
which would be especially helpful in minimizing
refractoriness to platelet transfusions, and the risk for
CMV can be reduced (CMV-ve PRBC more safe).

Leukoreduced
Indications are-
chronically transfused patients,
potential transplant recipients,
patients with transplants,
patients with previous febrile nonhemolytic
transfusion reactions,
and CMV-seronegative at-risk patients for
whom seronegative components are not
available.

Leukoreduced
-leukoreduction has been seriously considered or
implemented because of some anticipated
benefits, including decreased transmission of
variant Creutzfeldt-Jakob disease, leukocyte-
induced immunomodulation, and even decreased
postoperative mortality.
-universal leukoreduction is the direction in which
transfusion medicine has gone.

Irradiated
-PRBC units are exposed to gamma irradiation (2,500
cGy) to damage donor WBC DNA.
-prevent a cellular immune proliferative response to
the recipient’s tissues.
-usually performed in cesium-137 blood irradiators,

Irradiated
-PRBC units are exposed to gamma irradiation (2,500
cGy) to damage donor WBC DNA.
-prevent a cellular immune proliferative response to
the recipient’s tissues.
-component must be irradiated within 14 days of
donation and it then has a shelf life of 14 days from
irradiation.

Irradiated
Indications:
– Units from blood relatives
– Allo/Auto HPC Transplant Recipients
– Intrauterine transfusion
– highly immunosuppressed patients at risk for this
complication(GVHD)
– Neonates/Infants undergoing exchange transfusion or
ECMO
– Hodgkin’s Disease
– Cellular immune deficiency
-Solid Organ Transplants

Washed red cells (Microaggregate-free blood)
designed machines are used to wash the red blood
cells (RBCs), which are then suspended in sterile
saline.
Saline washing removes residual plasma (98%), and
reduces the concentration of leucocytes, platelets
and cellular debris.
can carried out at any time during the shelf life of a
unit of blood.

Washed red cells (Microaggregate-free blood)
Washed red cells usually have haematocrits of 70-80% and a
volume of about 180ml.
Indications-
• Patients with recurrent or severe allergic or febrile reactions
to red cells,
• Severely IgA-deficient patients with anti-IgA antibodies for
whom red cells from an IgA deficient donor are not available
• Microaggregate-free blood is used to prevent reactions to
leucocyte and platelet antigens.

CMV negative
Indications-
• All neonates (up to 4 months old)
• Intrauterine Transfusions
• High risk lung transplant (-ve to -ve)
• Allogeneic stem cell transplants (-ve to –ve)
• DiGeorge Syndrome.

• Frozen RBC
Freezing to preserve rare RBC units
RBCs frozen in 40 percent glycerol are approved by
the FDA and the AABB for storage at -80ºC for up to
10 years.

CHANGES DURING STORAGE OF BLOOD
• blood can be stored for 42 days is a mixed
blessing, the obvious advantage is the
increased availability of blood.
• Numerous changes occur during storage and
affect the quality of transfusion.

During storage, RBCs metabolize glucose to lactate, hydrogen
ions accumulate, and plasma pH decreases.
The storage temperatures of 1° to 6° C stimulate the sodium-
potassium pump, and RBCs lose K+ and gain Na.
The osmotic fragility of RBCs increases during storage, and
some cells undergo lysis, resulting in increased plasma Hb
levels.
Progressive decreases in RBC concentrations of ATP and 2,3-
diphosphoglycerate (2,3- DPG) occur during storage.

CLINICAL IMPLICATIONS: DURATION OF BLOOD
STORAGE
• Purdy and colleagues found that patients who
received 17-day-old blood (range, 5 to 35 days) versus
25-day-old blood (range, 9 to 36 days) had a more
frequent survival rate.
• Weiskopf and associates performed studies in healthy
volunteers they concluded that erythrocytes stored
for 3 weeks are as efficacious as those stored for 3.5
hours.
• Postulated that 2,3-DPG levels may not be the key
factor in determining the delivery of O2

CLINICAL IMPLICATIONS: DURATION OF BLOOD
STORAGE
• Although conclusions cannot be definitive, logic
dictates that blood less than 14 days of storage
should be better than older storage.
• The Age of Red Blood Cells in Premature Infants
(ARIPI) trial
• The Age of Blood Evaluation (ABLE) trial
• The Red Cell Storage Duration Study (RECESS).
• Underway, may provide in helping decisions in future.

Transfusion trigger-
Clinical Practice Guidelines
• 1980: The National Institutes of Health
• 1984: The American College of Obstetricians and Gynaecologists (ACOG)
• 1990: The Transfusion Practices Committee of the American Association of
Blood Banks (coronary artery bypass surgery)
• 1992: The American College of Physicians (ACP)
• 1994: The College of American Pathologists (CAP) - fresh frozen plasma
(FFP), cryoprecipitate and platelet transfusion
• 1994: The American Association of Blood Banks
• 1996: American Society of Anaesthesiologists – Task Force on Blood
Component Therapy
• 2006: An Updated Report by the American Society of Anesthesiologists
Task Force on Perioperative Blood Transfusion and Adjuvant Therapies.
• Oct 2015- Awaiting.

The ASA Task Force 2006
• A close watch on assessment of blood loss during surgery
and assessment of tissue perfusion is to be maintained.
• Transfusion is rarely indicated when the haemoglobin
concentration is greater than 10 gm/dl, and is almost
always indicated when it is less than 6 gm/dl.
• For intermediate haemoglobin concentrations (6–10
gm/dl), justifying or requiring RBC transfusion should be
based on the patient's risk for complications of inadequate
oxygenation.

The ASA Task Force 2006
• Use of a single haemoglobin “trigger” for all patients and
other approaches that fail to consider all important
physiologic and surgical factors affecting oxygenation are not
recommended.
• When appropriate, preoperative autologous blood donation,
intraoperative and postoperative blood recovery, acute
normovolemic hemodilution and measures to decrease
blood loss (deliberate hypotension and pharmacologic
agents) may be beneficial.
• The indications for transfusion of autologous RBCs may be
more liberal than for allogeneic RBCs because of the lower
(but still significant) risks associated with the former.

Monitoring for blood loss.
A visual assessment of the surgical field should
be periodically conducted to assess the presence
of excessive microvascular bleeding (i.e ,
coagulopathy).
Standard methods for quantitative
measurement of blood loss (e.g., suction and
sponge) should be used.

Monitoring for inadequate perfusion and
oxygenation of vital organs.
Conventional monitoring systems (e.g. , blood
pressure, heart rate, oxygen saturation, urine
output, electrocardiography) should be used to
assess the adequacy of perfusion and oxygenation
of vital organs.

Monitoring for inadequate perfusion and oxygenation of vital
organs.
Clinical indications of tissue hypoxia
Unstable vital signs
• Tachycardia
• Hypotension
• Tachypnea or dyspnea
Laboratory and invasive monitor indices
• Mixed venous O2 saturation (SVmO2) <50%
• Central venous O2 saturation (SVcO2) <60%
• Increased O2 extraction ratio (O2ER) >50%
• Lactic acidosis (metabolic acidemia with lactate >2 mmol/L)

Clinical indications of tissue hypoxia
Signs of end-organ dysfunction
Electrocardiographic (ST changes, onset of arrhythmias)
or echocardiographic indications of myocardial
ischemia
Electroencephalographic indications of cerebral
hypoperfusion
New onset oliguria (less than 0.5 mL/kg/h for >6 h)

Monitoring for transfusion indications.
• Measure hemoglobin or hematocrit when substantial
blood loss or any indication of organ ischemia occurs.
• Red blood cells should usually be administered when
the hemoglobin concentration is low (e.g. , less than
6 g/dl in a young, healthy patient), especially when
the anemia is acute.
• Red blood cells are usually unnecessary when the
hemoglobin concentration is more than 10 g/dl.

Monitoring for transfusion indications-
• determination of whether intermediate hemoglobin
concentrations (i.e. , 6–10 g/dl) justify or require red
blood cell transfusion
• Based on
– ongoing indication of organ ischemia,
– potential or actual ongoing bleeding (rate and magnitude),
– the patient's intravascular volume status, and
– the patient's risk factors for complications of inadequate
oxygenation.

• The most recent update the Society of Thoracic Surgeons
and the Society of Cardiovascular Anesthesiologists
Blood Conservation Clinical Practice Guidelines
they state that “Transfusion is reasonable in most
postoperative patients whose hemoglobin is less than 7
g/dL.”
For patients with hemoglobin levels between 7 and
10 g/dL they recommend transfusion in patients with
“critical noncardiac end-organ ischemia,”
active blood loss, or
clinical indication of tissue hypoxia (low mixed venous
oxygen saturation or electrocardiographic or
echocardiographic evidence of myocardial ischemia)

MASSIVE TRANSFUSION
• Adults, as a transfusion of half of one blood
volume in 4 hours, or more than one blood
volume in 24 hours (adult blood volume is
approximately 70 mL/kg)
• Children, as a transfusion of more than 40 mL
blood/kg (blood volume of children older than
neonates is approximately 80 mL/kg).

put forward by different groups
• Transfusion which involve 10% blood volume
replaced in 10 min or less(50ml/min in a
average adult).
• Any transfusion in which 1 unit of blood is
given in 5 min.

Indications
• Trauma, crush injury
• Orthopedic surgery
• Liver surgery- transplantation
The decision to start, depends on
the physiological state of patient
evidence of amount of blood loss
potential for ongoing hemorrhage

Complications
• Volume dependent
– Dilutional coagulopathy
– Volume overload
– Micro-aggregates
• Rate dependent
– Hypothermia
– Citrate toxicity
– Electrolyte imbalances
– Acid- base abnormalities

•Massive blood transfusion
is a life saving procedure, it
should not be taken too
lightly

GRANULOCYTE TRANSFUSIONS
• The buffy coat contains a high concentration of
white cells and platelets.
• Buffy coats that are not used to make platelet
concentrates are used for granulocyte production.
• Apheresis technique can also be employed for
collecting granulocytes.

• Granulocytes, Pooled, Buffy Coat Derived, in
Platelet Additive Solution and Plasma, Irradiated.
• Leucocytes, Buffy Coat, Irradiated (If above not
available).

• Granulocytes are stored at 22+2ºC without
agitation.
• Each pack of Leucocytes, Buffy Coat, Irradiated
– 50ml in volume, has a haematocrit of 45%, contains 1-2
x109 white cells, 90x109 platelets and 9.5g of
haemoglobin.

GRANULOCYTE TRANSFUSIONS- Dosing
• A dose of ten packs for adults.
• 10 -20ml / kg for children less than 50kg (to a
maximum of 10 packs).
• Children less than 30Kg should receive 10-20ml/Kg
to a maximum of two packs.

Indications
• Therapeutic granulocyte transfusions indicated
-for patients with a known congenital disorder of
neutrophil function, regardless of neutrophil count with
proven or highly probable fungal or bacterial infection
unresponsive to appropriate antimicrobial therapy,
demonstrated by visible spreading lesions on skin,
mucosa or radiological examination.

Indications
• Severe neutropenia, defined as ANC <0.5 x 109/L1 due to
congenital or acquired bone marrow failure syndromes.
• Receiving active treatment in an attempt to achieve disease
remission.
• Proven or highly probable fungal or bacterial infection that is
unresponsive to appropriate antimicrobial therapy as
demonstrated by visible spreading lesions on skin, mucosa or
radiological examination.
• In whom neutrophil recovery is expected (ANC>0.5x109/l) in
the near future and / or in whom definitive therapy of curative
potential is planned.

PLATELET CONCENTRATES
• Two methods to collect this component
– Random donor pooled platelets
– Single donor Apheresis platelets

• A single unit of platelets can be isolated from
every unit of donated blood, by centrifuging the
blood within the closed collection system to
separate the platelets from the red blood cells
(RBC).
• As the platelet number is inadequate, four to six
units are pooled together. These are called whole
blood-derived or random donor pooled platelets

• Advantages
– lower cost,
– ease of collection and
– processing (a separate donation procedure and pheresis
equipment are not required).
• Disadvantage
-is recipient exposure to multiple donors in a single
transfusion and logistic issues related to bacterial
testing.

Single donor Apheresis platelets
• Platelets are collected in 2-3 hr apheresis
procedure.
• Platelets and some white blood cells are removed,
and red blood cells and plasma are returned to the
donor.
• A typical apheresis platelet unit provides the
equivalent of six or more units of platelets from
whole blood (ie, 3 to 6 x 1011 platelets).

Single donor Apheresis platelets
Advantages
-exposure of the recipient to a single donor
rather than multiple donors,
-and the ability to match donor and
recipient characteristics such as HLA type,
cytomegalovirus (CMV) status, and blood type
for certain recipients.

Forms of PC
• Platelets, Pooled, Buffy Coat Derived, Leucocyte
Depleted
pool of platelets, derived from buffy coats, which contains
less than 5*106 leucocytes.
• Platelets,Apheresis, Leucocyte Depleted – a single donor
platelet component containing less than 5*106
leucocytes.
• Platelets, Suspended in Additive Solution, Leucocyte
Depleted- platelet concentrate ,suspended in additive
solution medium. This component is indicated for
patients with reactions to plasma containing components.

Unit of PC
• Volume: 150–450 ml.
• pH: between 6.4 and 7.4 throughout the shelf-life.
• Leucocyte Count= <5* 106/pool
• Shelf Life - 5 days
• Practical Shelf Life (actually available to clinicians) -
2.5 to 3 days.

Platelets are stored at room temperature,
because cold induces clustering of von Willebrand
factor receptors on the platelet surface and
morphological changes of the platelets, leading to
enhanced clearance by hepatic macrophages and
reduced platelet survival in the recipient.
Platelets are stored at a core temperature of
22°C +/- 2°C with continuous gentle agitation for
up to five days in a closed system.

Platelet are stored at room temperature (20-24oC),
which enhances bacterial growth, and is the third
leading cause of transfusion-related deaths.
The incidence of platelet-related sepsis was
approximately 1 case in 12,000 people.
The estimated incidence of bacterial
contamination of platelets was approximately 1 case in
2000.
For any patient who develops a fever within 6
hours after receiving platelets, sepsis from platelets
should be considered.

ASA Task Force recommendations:
• Prophylactic platelet transfusion is ineffective and rarely
indicated when thrombocytopenia is due to increased
platelet destruction (e.g., idiopathic thrombocytic purpura).
• Prophylactic platelet transfusion is rarely indicated in
surgical patients with thrombocytopenia because of
decreased platelet production when the platelet count is
greater than 100 × 109/L and is usually indicated when the
platelet count is less than 50 × 109/L.
• The determination of whether patients with intermediate
platelet counts (50 to 100 × 109/L) require therapy should
be based on the patient’s risk for bleeding.

ASA Task Force recommendations:
• Surgical and obstetric patients with microvascular bleeding
usually require platelet transfusion if the platelet count is
less than 50 × 109/L and rarely require therapy if it is greater
than 100 × 109/L.
• Vaginal deliveries or operative procedures ordinarily
associated with insignificant blood loss may be undertaken
in patients with platelet counts less than 50 × 109/L.
• Platelet transfusion may be indicated despite an apparently
adequate platelet count if there is known platelet
dysfunction and microvascular bleeding

IndiCations
Stable patients
without evidence of bleeding or coagulopathy <10,000/μL
Prophylaxis for invasive procedures such as
lumbar puncture, neuraxial anesthesia,
central venous catheterization, endoscopy with biopsy,
liver biopsy, or major surgery <50,000/μL
Stable patients with
clinical evidence of bleeding or coagulopathy <50,000/μL

IndiCations
Patients with DIC and signs of ongoing bleeding <50,000/μL
Patients undergoing massive transfusion <75,000/μL
Patients having surgery at critical sites
(eye or central nervous System) <100,000/μL
Microvascular bleeding attributed
to platelet dysfunction such as uremia,
liver disease, post-cardiopulmonary bypass Clinician judgment.

Calculation of dose
• One platelet concentrate is usually given to most
adult patients.
• In small children (< 20 kg), 10–15 ml ⁄ kg up to the
adult dose of one platelet concentrate is used;
• In older children, an adult dose of platelets should
be used.

Dose
Under ideal circumstances, one platelet
concentrate usually produces an increase of
approximately 7000 to 10,000 platelets/mm3 at 1
hour after transfusion to the 70-kg adult.
Ten units of platelet concentrates are required
to increase the platelet count by 100,000
cells/mm3.

The dose of platelets (* 109) can be calculated in more
detail, if required,
desired platelet increment (PI),
the patient’s blood volume in litres (BV, estimated by
multiplying the patient’s body surface area by 2.5, or 70 ml ⁄
kg in an adult) and
a correction factor (F) of 0.67 to allow for pooling of
approximately 33% of transfused platelets in the spleen,
• Dose= PI * BV * F-1
• For example,
if a platelet increment of 40*109 ⁄l is required for a
patient with a blood volume of 5 l, a dose of 300* 109, is
required.

FRESH FROZEN PLASMA
• Frozen plasma (FP) is prepared from whole blood
by separating and freezing the plasma (200–250
ml) within 6 h of donation.
• It may be stored for up to 1 year at –18°C or lower.
• Contains all of the coagulation factors and other
proteins present in the original unit of blood.

• Usage
– On order the FFP should be thawed between 30 and
37°C with constant agitation.
– After thawing,
can be stored at 4oC(refrigerator) and can be used
safely within 24 hours;
when kept at room temperature, must be used within
4 hours.

• Different types of frozen plasmas are available:
Fresh frozen plasma (FFP):
Plasma frozen at - 18oC or colder within 6 hours of donation.
F24 plasma:
Plasma frozen at -18oC or colder within 24 hours
Cryosupernatant or cryo-reduced plasma (CRP):
Solvent-detergent treated plasma
Liquid plasma:

Plasma F24 (PF 24):
Plasma frozen at -18oC or colder within 24 hours.
PF24 maintains all the clotting factors at the same
levels as in FFP, except that factor VIII levels are in
the range of 65 to 80 percent of normal and
protein C is decreased.

Cryosupernatant or cryo-reduced plasma (CRP):
The plasma remaining after removing cryoprecipitate.
This product is also referred to as "Cryo-Poor Plasma.“
Used as plasma replacement in some patients with
thrombotic thrombocytopenic purpura.
vitamin K deficiency or correction of major bleeding in
the setting of warfarin anticoagulation because the
removal of Cryoprecipitate from plasma does not
deplete the vitamin K-dependent clotting factors.

Liquid plasma:
• Plasma not immediately frozen as FFP or F24 and
stored at 1-6oC.
• Used for preparation of plasma derivatives like
albumin, factor concentrate and immunoglobulins.

Solvent-detergent treated plasma (S/D Plasma)
• Treatment of pooled plasma prior to freezing with a solvent
and a nonionic detergent inactivates a number of lipid
envelopes virsues, including HIV, hep B and hep C.
• Non-enveloped viruses (eg, hep A, parvo B19) are not
inactivated by this process, and even prions.
• Solvent/Detergent (S/D) method is similar to that used to
inactivate viruses in immune globulin and coagulation
factors.
• S/D Plasma has similar levels of most clotting factors and
similar hemostatic properties as standard FFP.

Recommendations
Urgent reversal of warfarin therapy.
Correction of known coagulation factor deficiencies
for which specific concentrates are unavailable.
Correction of microvascular bleeding in the presence
of elevated (>1.5-times normal) prothrombin time
(PT) or partial thromboplastin time (PTT).

Recommendations
Correction of microvascular bleeding secondary to
coagulation factor deficiency in patients
transfused with more than one blood volume and
when PT and PTT cannot be obtained in a timely
fashion.
FFP should be given in doses calculated to achieve
a minimum of 30% of plasma factor concentration.

Recommendations
FFP is contraindicated for augmentation of plasma
volume or albumin concentration.
FFP should not be used as a source of proteins or
routinely after cardiopulmonary bypass.
FFP should not be used to reconstitute packed RBCs.

Indications
• Correction of inherited factor deiciencies when there is no
specific factor concentrate (e.g., factor V) and when the PT or
aPTT is >1.5 times the mean control
• Correction of acquired multi-factor deiciencies with clinical
evidence of bleeding or in anticipation of major surgery or an
invasive procedure with PT or aPTT >1.5 times the control
• Liver dysfunction with clinical signs of bleeding
• DIC with clinical signs of bleeding
• Reversal of vitamin K antagonists (warfarin)

Indications
• Microvascular bleeding associated with massive
transfusion and estimated blood loss > one blood volume
(when PT and aPTT are >1.5 times the control or cannot be
obtained)
• Heparin resistance secondary to anti-thrombin deficiency
when AT concentrate is not available
• Treatment of thrombotic microangiopathies (thrombotic
thrombocytopenic Purpura, HELLP syndrome, or hemolytic
uremic syndrome)
• Treatment of hereditary angioedema when C1-esterase
inhibitor is not available.

Dosing of FFP
• The initial therapeutic dose of FFP averages 10 to
15 mL/kg in an attempt to obtain at least 30%
factor activity.
• Repeat dosing should follow the results of serial
diagnostic coagulation tests such as the PT and
aPTT.

• The guidelines for FFP continue to recommend
prophylactic transfusions in patients at risk for
bleeding,
– there is no evidence to support the efficacy of FFP
reducing red cell transfusion, morbidity, or mortality.
• The burden of adverse reactions in conjunction
with limited prophylactic benefits and high
frequency of inappropriate use makes FFP
arguably the riskiest blood component
transfused.

FFP in trauma
• Traditional methods- fluids, RBC, FFP only abnormal
coagulation results.
problem-dilutional coagulopathy resulting in
prolonged microvascular bleeding.
• Recent studies show improved outcomes with higher
ratios of red cell units to FFP (more than 3:2).
• The optimal management strategy for immediate
resuscitation of trauma patients and those with acute
massive hemorrhage is still under investigation.

CRYOPRECIPITATE (Con. AHF)
• Originally it was developed as a therapy
for Haemophilia A (Used for 50 yrs).
• Enriched with fibrinogen, Fac VIII, vWF,
Fac XIII.

• Prepared from processing FFP
- When FFP is thawed at 40C, a precipitate is formed,
this is seperated from the supernatant plasma, and
resuspended in a small volume of plasma and then
refrozen at -180C.
- Can be stored for 1 year

- On ordering the cryoprecipitate is thawed in a 370C
water bath & issued in individual bags or a pooled
product
- After thawing- must be kept in room temperature
- Expiration time- 6hr for un-pooled & 4hr for pooled

• One unit of cryoprecipitate – derived from 1
unit of whole blood/ 250ml plasma- contains
– Volume- 10-20ml
– 150-250 mg Fibrinogen
– 80-100 units of Fac VIII
– 50-100 units of Fac XIII
– 50-60 mg of fibronectin
– 40-70% of vWF Concentrate

Recommendations
• Earlier,
– bleeding patients with hypofibrinogenemia, von Willebrand's disease and
patients with haemophilia A (when factor VIII concentrate is not available).
• Current Recommendations are:
– Prophylaxis in non bleeding perioperative or peripartum patients with
congenital fibrinogen deficiencies or von Willebrand's disease unresponsive to
1-desamino-8-D-arginine vasopressin (DDAVP).
– Bleeding patients with von Willebrand's disease
– Correction of microvascular bleeding in massively transfused patients with
fibrinogen concentrations less than 80–100 mg/dl (or when fibrinogen
concentrations cannot be measured in a timely fashion)

Other Indications-
• As a source of fibrinogen
– Congenital- Hypofibrinogenaemia/ Afibrinogenaemia
– Acquired- severe coagulaopathy, DIC, massive transfusion
• Trauma
– Significant bleeding after major trauma accompanied by a
plasma fibrinogen level < 100mg/dl
– Significant bleeding accompanied with signs of functional
fibrinogen deficit on TEG
• Preparation of Fibrin sealant/fibrin glue used in sealing
large raw surfaces.
– Fibrin glue- Cryoprecipitate, bovine or human thrombin and
calcium chloride.

Dosing-
• 2-3 unit of cryoprecipitate per 10 kg body weight
raises the plasma fibrinogen concentration by
approximately 100 mg/dl in the absence of
continued consumption or massive bleeding.
• Maintenance dose- I bag per 15 kg –can be given
daily till the bleeding is controlled.

• Fibrinogen required(mg)
= (Desired Fb – Current Fb) * plasma volume/
100.
Bags required= Fibrinogen required mg/250mg.
Plasma volume= blood volume * (1- Hemotocrit)
Eg-
Plasma volume=3500ml
Fb required= (150-50)* 3500/100=3500
3500/250=14
14 bags required.

Complications-
• Same risk of transmitting blood borne pathogen
• Cryoprecipitate has been withdrawn from
european countries(Safety concerns), instead,
they advice for commerical fibrinogen
preparations.
• Large volume of ABO-incompatible
cryoprecipitate- can lead to intravascular
hemolysis

COMPLICATIONS OF BLOOD PRODUCT
ADMINISTRATION
• Infectious Risks
• Noninfectious Risks
– Immune-mediated Transfusion Reactions
– Nonimmune-mediated Transfusion Reactions

Infectious Risks
• depends mostly on
– the relative length of the window period determined
by the reproductive rate of each virus and the
prevalence of the disease.
– additional risk of false negatives or mistaken release of
quarantined blood products;
these events account for less than 0.5% of the residual
risk of transfusion-transmitted viral infection.

Noninfectious Risks
• The extensive use of more sensitive methods for
screening and controlling the infectious risks of
blood product transfusion,
noninfectious complications have emerged as
the major source of transfusion-related morbidity
and mortality.

• Hemolytic transfusion reactions (HTRs)
– Acute HTR
– Delayed HTR
they occur with the transfusion of incompatible blood
products when antibodies in recipient plasma complex with
donor cellular antigens causing compliment activation and
subsequent hemolysis.
Classically AHTRs result from ABO incompatibility secondary to
native anti-A or anti-B antibodies, growing evidence exists for
the implication of other RBC antigens such as Kidd, Kell, and
Duffy.

• Manifests as fever, hypotension, and hemodynamic
instability(bradykinin), bronchospasm and urticaria as well as
symptoms of dyspnea, flushing, and severe anxiety(histamine).
• Severe hemolysis may lead to renal failure, disseminated
intravascular coagulopathy, and death in 50% of cases.
• Under anesthesia several signs and symptoms will be masked;
therefore vigilance during transfusion of an anesthetized patient
must remain high.
• confirmed with laboratory analysis of free hemoglobin levels, low
haptoglobin, bilirubin increases, direct antiglobulin (Coombs) test,
and evidence of hematuria.

• Suspicion of a transfusion reaction should
prompt immediate discontinuation of the
transfusion and investigation into the donor and
recipient blood type and antigen–antibody
components.
• Treatment of AHTR involves supportive care for
hemodynamic instability and microvascular
bleeding as well as the maintenance of adequate
urine output to avoid the renal failure.

• Delayed hemolytic transfusion reactions (DHTRs) result
from alloantibodies to minor RBC antigens in the Rh,
Kell, Kidd, Duffy, MNSs, and other blood groups.
• They generally present 3 to 10 days after transfusion
of an apparent “compatible” blood component.
• Typically the recipient has IgG alloantibodies to a
particular RBC antigen and will mount an an amnestic
immune response, but the pre-transfusion antibody
levels are too low for serologic detection.

• Symptoms are much milder than AHTRs and rarely
result in major morbidity or mortality because the
hemolysis occurs extravascularly in the liver and
spleen.
• Patients experience mild fever & rash with laboratory
and clinical signs of hemolysis such as jaundice,
hematuria, low haptoglobin, positive direct Coombs
test, and decreasing hemoglobin levels.
• Symptoms are generally self limited and treated
supportively with hydration to protect the renal
tubules.

Transfusion-related Immunomodulation(TRIM)
• multifactorial pathophysiology
– implicates the role of transfused WBCs, donor plasma
HLA class 1 peptides, cytokines, and immune mediators
released during blood product storage as well as the
immune function of transfused RBCs within the
microvasculature of the recipient.
• Several experts propose a “two-insult” model for
TRIM similar to the patho-physiologic mechanism
for TRALI and acute respiratory distress syndrome.

• Presumably most patients requiring blood products are
suffering from a precondition that “primes” the immune
system and vascular endothelium such as trauma, surgery, or
acute illness.
• This constitutes the first insult and causes active neutrophils
to adhere to vascular endothelial cells and become
hypersensitive to blood-bound immune mediators.
• The second insult occurs with the infusion of transfused
blood products which contain WBCs with HLA class I
antigens as well as soluble immune response modifiers in
the form of cytokines, complement factors, and the
breakdown products of lipid membranes.

Transfusion-related Acute Lung Injury(TRALI)
• as a new acute lung injury (ALI) within 6 hours of
blood component therapy.
• 1994 by the North American-European
Consensus Conference as non-cardiogenic
pulmonary edema with acute bilateral infiltrates
and hypoxemia (PaO2/FiO2 <300 mm Hg or
oxygen saturation <90% on room air and no
evidence of left atrial hypertension)

Transfusion-related Acute Lung Injury(TRALI)
• Management
– supportive measures to limit lung injury and optimize
oxygenation, -maximizing positive end expiratory pressures,
avoiding volume overload, and low tidal volume strategies for
mechanical ventilation.
• Furthermore, subsequent transfusions should be restricted as
much as possible for patients with ALI and although there is
little supportive evidence for the use of washed RBCs,
• all preventative measures should be encouraged for this
high-risk population.

Reference:
 Miller’s Anaesthesia 8 th Ed
 Clinical Anaesthesia – Barash 7 th Ed
 Redbook- 2005
 Postgraudate topics- Dr Mahadevan, Dr
Anil kumar Ashokan
 Handbook of Transfusion Medicine Dr
Derek Norfolk 5 th Ed
 Blood Science-Principles and Pathology
Andrew Blann & Nessar Ahmed
 ASA guidelines 2005
 BJA- August issue 2014

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