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Massive Transfusion Protocols
in Trauma Victims
DR SHADAB KAMAL
Patient Presentation to ER
• 64 Year old male, passenger, suffered Motor Vehicle
Crash with high-speed rollover presented to ER with
drowsiness, SBP 60 and tachypnea.
• Crystalloid fluid resuscitation initiated for hemorrhagic
shock.
• Airway control to avoid hypoxemia and Emergent
Endotracheal intubation was done in ED.
• Blood (PRBC, FFP) transfusion initiated for hypotension
and hemorrhagic shock.
Patient Presentation to ER
• On physical exam Severe Flail chest was found along
with Bilateral hemo-pneumothorax.
• Bilateral closed tube thoracostomy(ICTD) was done.
• Transient responder to blood transfusion.
• FAST – Positive for hemoperitoneum
• Pelvic fracture (unstable) was found on X ray of pelvis
• Plan: To Operating Room for emergent laparotomy
Management of Injuries in OR (DCS)
• Laparotomy was done and splenectomy, repair of diaphragmatic
injury, repair of liver lacerations, abdominal packs, Vaccum Assisted
Closure of abdominal wall done.
• Blood pressure normalized after abdominal hemorrhage controlled,
liver & pelvis packed.
• 18 Unit of PRBCs, 15 Unit of FFP, 3-5pk Platelets, 2 Cryoprecipate was
transfused to the patient
• Patient shifted to angiography for pelvis fractures, then to CT head
and then ICU.
• Chest CT scan obtained postop to evaluate intra- thoracic injuries
Time Arterial
pH
pCO2 pO2 HCO3 Hct iCa++ Lactate
0712am 7.04 22 351 6 24 0.46 11.9
0805am 7.29 29 413 14 29 0.58 9.3
0849am 7.28 32 332 14 30 0.65 8.4
0712am Hb 6.9
Platelet 90000/mm3
PT 17.4 sec
INR 1.8 sec
PTT 77.8 sec
Patient investigations
Hospital Course
• Persistent need for mechanical ventilation with the risk of ARDS, VAP
• Need for further operation for removal of abdominal packs, transgastric
jejunostomy for enteral nutrition and abdominal wall closure
• ECHO confirmed blunt myocardial injury.
• Tracheostomy was done
• ICU Length Of Stay > 3 weeks
• Eventual full recovery.
Massive transfusion: Introduction
• MT are needed in trauma, obstetrics, and major surgery.
• According to CDC >120 000 deaths in 2010 due to trauma
• About 40% of trauma-related mortality is due to uncontrolled
bleeding.
• Among the injured patients admitted to trauma centres, up to 10%
of military and up to 5% of civilian patients require MT.
• In general, injury severity and transfusion requirement are associated
with mortality. Most (99%) of the patients receiving <10 RBC units
within the first 24 h survived, whereas only 60% of patients who
received >10 RBC units within the first 24 h survived.
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Prehospital First 24 hours After 24 hours
Percentageofdeaths
Hemorrhage CNS Other
Hemorrhagic Mortality
• While bleeding is the
#2 cause of mortality,
hemorrhage is the #1
reversible cause for
mortality
• Almost all mortality
from hemorrhage
occurs within 1st 24
hours
Massive Blood Transfusuin
Transfusion of ≥10 red blood cell
(RBC) units, which approximates
the total blood volume (TBV) of
an average adult patient, within
24 h,
Transfusion of >4 RBC units in 1
h with anticipation of continued
need for blood product support
Replacement of >50% of the TBV
by blood products within 3 h.
Transfusion support to loss of
blood >150ml/min
In Paediatric pts
Transfusion of >100%
TBV within 24 h,
Transfusion support to
replace ongoing
haemorrhage of >10%
TBV /min
Replacement of>50%
TBV by blood products
within 3 h.
Definition of Massive Transfusion
Trauma Resuscitation
• Determine severity of hemorrhagic shock (admission arterial
lactate)
• Expedite control of hemorrhage
• Damage Control Surgery
• Early blood and blood product resuscitation
• Blood product resuscitation ratio – PRBCs/FFP/platelets, 1:1:1
• Minimize crystalloid (prevent coagulopathy, thrombocytopenia)
• SBP 80-100 mm Hg
• Frequent labs (Type & Crossmatch, CBC, Plts, Coagulation profile,
INR, PT, PTT, Fibrinogen, Electrolytes, BUN/Creatinine, ionized
calcium, Lactate, TEG if available)
• Consider TXA and additional coagulation factors (rFVIIa etc)
Predictor of massive transfusion
Trauma Associated Severe
Hemorrhage (TASH)-score
incorporated seven clinical and
laboratory variables into a composite
score to predict the need for MT.
• Haemoglobin,
• Base excess,
• Systolic arterial pressure,
• Heart rate,
• Presence of free intra-abdominal
fluid and/or
• Complex fractures, and
• Gender
Nunez and colleagues demonstrated
that simple parameters also appears
to be as good as other more complex
scoring systems to predict MT.
• Presence of penetrating trauma,
• Systolic arterial pressure <90 mm Hg,
• Heart rate >120 beats min, and
• a positive focused abdominal
sonography for trauma,
• If any two of the above four
parameters are positive, the patient
is likely going to require MT.
Early trauma induced coagulopathy (ETIC) or
Acute coagulopathy of Trauma
Historically, Early Trauma Induced
Coagulopathy or acute coagulopathy of
trauma was attributed to crystalloid
and RBC transfusion without
administration of platelets, plasma, or
both.
However, subsequent studies in both
adult and paediatric trauma patients
demonstrated that ETIC was present in
24%, and up to 56% in severely injured
patients, usually within 30 min of
injury, even before receiving RBC and
fluid resuscitation.
Breaking the
“Bloody Vicious
Cycle”
 Control hemorrhage
 Use best possible
resuscitation
products
 Prevent hypothermia
 Prevent
hemodilution
 Treat coagulopathy
• In the past, trauma patients were given colloid or
crystalloid fluid initially.
• Blood products were administered after 2 litre of fluid
resuscitation, usually guided by laboratory results to keep
haemoglobin >10 g/dl, platelet count >50000, and INR
≤1.5.
• Using these guidelines, blood loss continued because of
delay in laboratory turn around time and dilutional
coagulopathy.
• Recent studies with consideration of resuscitation, and
better understanding the pathophysiology of ETIC has led
to early use of RBCs, plasma, and platelets and reduced
crystalloid use in resuscitation.
J TRAUMA 2010
• Current component therapies in the USA suggested that
when administering RBC, plasma, and platelets in a 1:1:1
ratio, this 630-650 ml product has a haematocrit of 29%,
coagulation factor activity of 65%, and a platelet count of
90000/mm3.
• With storage defects taken into account, this mixed product
would have a haematocrit of 26%, coagulation factor activity
of 40–50%, and platelet count of 90000/mm3
• Furthermore, any attempt to increase the concentration of
one component would lead to dilution of the other two.
• The administration of RBC:plasma:platelets at 1:1:1 ratio was first
proposed by the US military and subsequently supported by military and
then civilian studies. The rationale for the 1:1:1 ratio is that it more closely
resembles whole blood, which would help to treat and prevent ETIC.
• A retrospective review of patients receiving MT at a US combat hospital
demonstrated reduced mortality from 66% to 19% when the RBC:Plasma
ratio decreased from 8:1 to 2:1.38
Ann of Surg 2008; 248:447-458.
Resuscitation with a
1:1:1 ratio of RBCs,
plasma, and platelets
is the
recommendation of
the Army Surgeon
General and his
Trauma Consultant.
However, these studies, and multiple
others, are retrospective, and are
affected by survival bias which is
resulting from the fact that surviving
patients are more likely to receive more
plasma and platelets in relation to RBCs
compared with nonsurviving patients
because they lived long enough to
receive those blood products.
• In June 2011, the Canadian National Advisory Committee on
Blood and Blood Products determined that the retrospective
evidence available at the time was insufficient to recommend a
RBC:Plasma:Platelet transfusion ratio of 1:1:1 as the standard of
care for MT.
• They also stated that subsequent retrospective studies would be
unlikely to overcome survivorship bias and would not be able to
make further contributions to the determination of the most
effective ratio.
• Recently, the Prospective Observational Multicenter
Major Trauma Transfusion (PROMMTT) study examined
the association between mortality rates in trauma
patients and transfusion ratios; this cohort study
demonstrated improved in-hospital mortality with
RBC:plasma and RBC:platelet ratios <2:1 in the first 6 h.
•In the first 6 hours, patients with ratio < 1:2 were 3 to 4
times more likely to die than patients with ratios of 1:1
or higher.
•After 24 hours, plasma and platelet ratios were
unassociated with mortality, when non-hemorrhagic causes
prevailed.
1 July 2009 - 15 Oct 2010
• The follow-up Pragmatic Randomized Optimal Platelet and
Plasma Ratios (PROPPR) trial is a randomized trial to evaluate
ratios, MT patients receive either a 1:1:1 (higher ratio) or a 2:1:1
(lower ratio) RBC: Plasma: Platelet with primary outcome of
survival, and also complications and length of hospital stay.
• The results of this study should further elucidate the optimal
ratios of blood product administration during MT.
8/2012 – 8/2015
..extensive lab analysis will be done to evaluate the influence of
fluid resuscitation on traumatic induced coagulopathy.
What is MTP?
MTP is a way to coordinate the care for patients requiring MT, to
facilitate communication between different services (trauma,
nursing, transfusion medicine, and other laboratories), avoid delay
in clinical care, laboratory testing and blood product transfusion,
and nursing care.
MTP is a way to assure good patient care by having a standard
protocol on specific actions to take for each service involved.
MTPs have demonstrated improved patients survival and reduced rates
of organ failure and post-trauma complications.
Component of MTP
(i) When and who should initiate MTP.
(ii) Notification of the transfusion service and laboratory regarding
start and stop of MTP.
(iii) Laboratory testing algorithm [prothrombin time (PT), activated
partial thromboplastin time (aPTT), fibrinogen level, blood gas, and
complete blood count], and thromboelastography if available.
(iv) Blood product preparation and delivery (i.e. predetermined
transfusion packages).
(v) Other patient care needs (such as blood warmers, nursing care).
• MTPs can include preparation and administration of blood
products based on laboratory test results, predetermined
transfusion packages
• Although the number and timing of blood component delivery,
laboratory testing algorithms, and other aspects of the MTPs
varies between institutions, most current MTPs use
predetermined transfusion packages.
• MTPs vary in their predetermined transfusion packages, but all
include platelet and plasma units with RBC units.
43 Cotton BA,GuyJS, MorrisJAJr,AbumradNN.Thecellular,metabolic, and systemic consequences of aggressive fluid resuscitation strategies.
Shock 2006; 26: 115–21
45 Dente CJ, Shaz BH, Nicholas JM, et al. Improvements in early mortalityandcoagulopathyare sustained better in patients with blunt
Trauma after institution of amassive transfusion protocol in acivilian level I trauma center. J Trauma 2009; 66: 1616–24
46 Nunez TC, Young PP, Holcomb JB, Cotton BA. Creation, implementation, and maturation of a massive transfusion protocol for the
exsanguinating trauma patient. J Trauma 2010; 68: 1498–505
47 O’Keeffe T, Refaai M, Tchorz K, Forestner JE, Sarode R. A massive transfusion protocol to decrease blood component use and costs. Arch
Surg 2008; 143: 686–90; discussion 90–1
48 Riskin DJ, Tsai TC, Riskin L, et al. Massive transfusion protocols: the role of aggressive resuscitation versus product ratio in mortality
reduction. J Am Coll Surg 2009; 209: 198–205
Whole Blood vs Blood components
• In the recent military experiences in Iraq and Afghanistan, whole blood
transfusion compared with RBC, plasma, and apheresis platelet use reduced
pulmonary and tissue oedema, which decreased the ventilation time and also
allowed closure of the abdomen with minimal delay.
• Furthermore, retrospective analysis suggested that patients who received both
fresh whole blood and component therapy had better clinical outcomes
compared with those who received only component therapy.
• However, concern for transfusion transmitted infections and transfusion-
associated graft vs host disease remains.
Paediatric MTPs
• The data on paediatric MTPs are limited, and thus practices vary
significantly among institutions.
• In the majority of institutions, a single MTP is used for both
adult and paediatric patients.
• Published studies on paediatric MTPs did not show
improvement in mortality in the group receiving blood products
according to the institutional MTP compared with the historical
control or the group receiving blood products at physician
discretion.
• Despite obtaining null results in both studies, probably due to
small sample sizes, it was suggested that implementation of
MTP to increase the Plasma: RBC ratio is feasible in paediatric
patients.
Considerations in MTP
• Group O RBCs and AB plasma products should be given until the
patient’s blood type can be determined.
• Use of D-positive products in D-negative or D-unknown patients
• Thawed plasma units
• Prothrombin complex concentrate (PCC)
• fibrinogen concentrate
• Tranexamic acid (TXA) given early in the resuscitation process (<3
h from injury to treatment, preferably within 1 h from injury).
• When to consider rFVIIa?
Blood Product until result of Type and Crossmatch
• In many trauma situations, there is excessive blood loss,
and transfusion is needed before the ability to perform
pre transfusion testing. In these cases, group O RBCs and
AB plasma products should be given until the patient’s
blood type can be determined.
• It is important to obtain and test a patient sample as soon
as possible after admission so that type-specific products
can be administered when available.
• This helps to preserve the inventory of group O RBCs and
AB plasma, and minimizing potential for ABO typing
discrepancies when a patient has received multiple units
of group O RBCs and AB plasma.
Use of D-positive products in D-negative or D-unknown patients
• Each institution should have a policy determining the use
of D-positive products in D-negative or D-unknown
patients, including the use of D-positive products for men
and women past childbearing age (usually >50 yr old), and
after a set number of D-negative RBC units.
• The frequency of anti-D formation after transfusion of D-
positive blood products to a D-negative patient is about
20% for RBCs and ,4% for platelets (likely lower for
apheresis platelets).
• It is especially important to prevent anti-D formation in females
of childbearing potential because anti-D can cause haemolytic
disease of the fetus and newborn in future pregnancies.
• Therefore, females of childbearing potential should receive D-
negative RBCs.
Thawed plasma units
• Thawed plasma units are not available for patients requiring MT.
It takes about 20 min to thaw frozen plasma.
• Hence, in order to facilitate early transfusion of plasma in the
resuscitation process, many institutions keep some units of
thawed plasma available for immediate issue.
• Many trauma patients arrive in the trauma bay with unknown
blood type; thus, AB plasma is prepared since it is the universal
donor type.
• However, AB plasma is rare since only 4% of the population is
group AB. Once plasma is thawed, it can only be kept for 5 days.
• Therefore, maintaining an inventory of thawed AB plasma at all
times might be a challenge.
Prothrombin complex concentrate (PCC)
• used to treat congenital coagulation disorders and for warfarin reversal
in patients with active bleeding or undergoing urgent procedures.
• PCC contains factors II, VII, IX, and X, and proteins C and S,
• PCC can be three-factor, such as Profilnine SD (lacking factor VII), or
four-factor, such as Kcentra.
• To date, there has not been any prospective randomized controlled
trial to evaluate the efficacy and safety of PCC in massively bleeding
patients.
• Hence, risks and benefits of using PCC as an adjunctive therapy should
be discussed in any institutional MTP and it is recommended that PCC
usage should be continually evaluated.
Fibrinogen concentrate
• Fibrinogen concentrate has been shown to reduce peri-
operative bleeding and transfusion requirement.
• Fibrinogen concentrates, in conjunction with PCC, also
have been shown in a few prospective studies to decrease
the transfusion requirements and mortality in trauma
patients.
• It has not been approved to be used as an adjunctive
therapy in patients requiring MT.
• Therefore, it is recommended to discuss the risk and
benefit of using fibrinogen concentrate as part of the MTP
in any institution.
• Tranexamic acid (TXA), were demonstrated to reduce mortality in
trauma patients in both civilian and military settings, especially if
given early in the resuscitation process (<3 h from injury to
treatment, preferably within 1 h from injury).
• In the military setting, the MATTERs study, mortality in the TXA
group was lower than in the group not receiving TXA.
J Trauma Acute Care Surg 2013;75(6):1575-1586
Conclusion:
Tranexamic acid safely reduced the risk of death in bleeding
trauma patients in this study.
On the basis of these results, tranexamic acid should be
considered for use in bleeding trauma patients.
But…No difference in blood transfusion rates.
Lancet 2010;376:23‐32
• Moreover, TXA was also shown to be a cost-effective therapy in all
low-, middle-, and high-income countries using data from the
randomized controlled CRASH-2 trial done in a civilian population.
• TXA should be part of the early resuscitation process.
Boffard KD et al. J Trauma 2005 Jul;59(1):8-15
Conclusion:
In blunt trauma, RBC transfusion was significantly reduced with rFVIIa
(estimated reduction 2.6 RBC units, p=0.02) and the need for massive
transfusion was reduced (14% vs. 33% of patients, p=0.03)
Lab monitoring in MTP
• MTP requires adequate laboratory support to oxygen-carrying capacity,
haemostasis, and metabolic status in order to address and correct
abnormalities.
• In addition, laboratory results can be used retrospectively to assess the
need for MTP adjustment.
• For example, if all patients have low fibrinogen values upon ICU
admission, increased cryoprecipitate or fibrinogen concentrate use is
indicated during MTP. A metabolic panel should be used to monitor
metabolic abnormalities during MT, such as hyperkalaemia and
hypocalcaemia.
• Point-of-care ABG measurement is helpful in monitoring oxygenation.
Conventional coagulation assay vs TEG/ROTEM
• Monitoring haemostasis in patients with MT is challenging because
there is no validated coagulation assay that can detect accurately
the coagulopathies in massively bleeding patients in a timely
manner.
• Conventional coagulation assays, such as PT, aPTT, and fibrinogen
levels, are likely not available in real-time fashion.
• In addition, these tests do not detect some haemostatic
abnormalities, such as platelet dysfunction, hyperfibrinolysis, and
factor XIII deficiency.
• They also do not quantify the relative contribution of pro-coagulant
and anti-coagulant factors.
• These conventional coagulation assays do not predict the future
need for MTP.
TEG/ROTEM
• Recently, it has been suggested that such as thromboelastography
(TEG) and rotational thromboelastometry (ROTEM), might be
better at assessing coagulopathy inpatients requiring MT.
• These assays offer clinicians a graphic representation of the
coagulation process
• In addition, the parameters obtained from TEG/ROTEM could
provide a quantitative measure of individual components of the
haemostatic process in adult patients.
• Hence, the use of TEG/ROTEM can provide information to guide
blood component therapies in a more timely manner.
Advantages of using TEG/ROTEM
• Turn around time for these assays is shorter compared with
conventional assays (15–30 min); thus, they can be used in
combination with clinical assessment for the decision-making process.
• These assays can detect hyperfibrinolysis, an important component of
haemostatic abnormalities in patients with MT that cannot be detected
by PT and aPTT assays.
• Unlike the PT and aPTT that can only test secondary haemostasis,
TEG/ROTEM assess all phases of coagulation, such as the contribution
of platelets to primary haemostasis and factor XIII to cross-linking the
fibrin clot.
• TEG/ROTEM can be performed at the patient’s true temperature, which
makes it more sensitive for detection of coagulopathy due to
hypothermia.
Plasma Transfusion
• a. Consider transfusion when rapid blood loss exceeding
100ml/min continues after transfusion of crystalloids,
colloids and 4u RBC’s.
• b. After loss of one circulation blood volume when PT,
aPTT, and fibrinogen cannot be obtained in time.
• c. Transfuse 10-15 ml/kg rapidly (this corresponds to
1000ml of plasma, or 4 units of FFP).
• d. It takes 20 minutes to thaw and transport 4u FFP.
Platelet Transfusion
• a. On the achievement of surgical hemostasis, do not let platelets
fall below 50,000 mm3 in acutely bleeding patients.
• b. Target of 100,000 mm3 recommended for patients with multiple
high energy trauma or CNS injury.
• c. Platelet count of 50,000 mm3 can be anticipated when
approximately 2 blood volumes have been replaced with plasma-
poor RBC’s.
• d. Platelets are quickly lost through wounds until surgical
hemostasis obtained.
Short-term coagulation goals:
• Hct>20-24%
• Plts >50,000 mm3 (>100,000
for CNS injury or multiple
high energy trauma)
• Fibrinogen>100mg/dL
• APTT<45 sec
• PT<18 sec
Long-term coagulation goals:
• Hct>24%
• Plts>100,000mm3
• Fibrinogen>150mg/dL
• APTT<40 sec
• PT<17 sec
 Although the number and timing of blood component delivery,
laboratory testing algorithms, and other aspects of the MTPs varies
between institutions, most current MTPs use predetermined
transfusion packages.
 MTPs vary in their predetermined transfusion packages, but all include
platelet and plasma units with RBC units.
Massive Transfusion Protocol (MTP)
• Intravenous access – 2 large bore IVs and CVC
• Crystalloid -3:1/colloid- 1:1 ratio with Expected blood loss
• Limited crystalloid - avoid dilutional coagulopathy
• Labs: Type & Crossmatch, CBC, Platelets, INR, PT, PTT, Fibrinogen,
Electrolytes, BUN/Creatinine, ionized calcium
• Continuous monitoring: Volume Status, U/O, Acid-base status
• Aggressive re-warming.
• Prevent / Reverse acidosis
• Correct hypocalcemia: Calcium Gluconate or Calcium Chloride: 1 gm iv
10 slowly(Target goal ionized calcium 1.2 – 1.3)
• Transfuse with unmatched group O RBCs on hand.
• Repeat lab testing to evaluate coagulopathy
Appropriate Initial Interventions:
Other considerations:
• Heparin reversal: Protamine 1mg IV/100 U heparin
• Warfarin reversal: Vitamin K 10 mg IV; Consider PCC(prothrombin
complex concentrate)
• Consider antifibrinolytics: by Tranexamic acid 10 mg/kg IV or
Amicar(EACA) 5 gm IV bolus then 1 gm/hr IV infusion
• Intraoperative RBC salvage techniques
General Guidelines for Lab-based Blood
Component Replacement in Adults:
Components Thershold Dose
RBCs
No Thershold Physician Discretion
FFP INR>1.5 4 Units FFP
Platelets <100000 5- Pack Platelets
Cryoprecipate Fibrinogen<100
Two 5-pack
Cryoprecipate
Identify and Manage bleeding
(Surgery, angiographic embolization, endoscopy)
4 unit RBCs in <4 hour and ongoing uncontrolled Bleeding
Clinical team activates MTP and designates clinical contact
Clinical contact phones blood bank(BB) and:
• Provides name of clinical contact person to BB
• Provides MR#, sex, name, location of patient
• Records name of BB contact, calls if location/contact information
changes
• Ensures that MTP protocol electronic order is entered in CareLink
BB Prepares MTP Pack; Transfuse as 1:1:1 Ratio
MTP Pack: 6U RBCs; 4U FFP ; One (1) 5-pack Platelets
Stop MTP
Notify BB & return any
unused blood ASAP
Resume standard
orders
D/C MTP Electronic
order
BB Prepares MTP Pack; Transfuse as 1:1:1 Ratio
MTP Pack: 6U RBCs; 4U FFP ; One (1) 5-pack
Platelets
Hemostasis &
resolution of
coagulopathy?
Repeat Labs
• CBC, plts
• INR, PT, PTT
• Fibrinogen
• Ionized Calcium
• Consider rapid
coagulation tests
Consider rFVIIa,
If persistent
coagulopathy
• 40 to 100
ug/kg dose
• Round up to 1,
2, 5 mg vial
Clinical designate
contacts Blood Bank
for another MTP pack
** emergency
physician can adjust
pack based on labs PRN
No
Yes
Transfusion reactions:
• Allergic: Range from simple urticarial to anaphylaxis, Steroid and
diphenhydramine might be given to patients with allergic
transfusion
• Haemolytic transfusion reaction (acute and delayed): Might be
reduced by giving group O RBCs and AB plasma for emergency
release of blood products
• Febrile non-haemolytic transfusion reaction: Diagnosis of
exclusion
Complication of Massive Transfusion
Immunological reactions:
• Transfusion-related acute lung injury (TRALI): Incidence can be
reduced by transfusing male-only plasma
• Transfusion-related immunomodulation (TRIM): Might be
responsible for increased risk of bacterial infection
• Transfusion-associated graft vs host disease (Ta-GVHD):
Irradiation of cellular blood products in patients at risk (such as
neonates and immunosuppressed patients) to prevent Ta-GVHD
• Post-transfusion purpura (PTP): Can be treated with IVIg infusion,
steroid, or plasma exchange
Metabolic complications
• Hypocalcaemia: Because of citrate overload from rapid
transfusion of blood products. (Each unit PRBCs – approx 3gm
citrate)
• Healthy adult liver metabolizes 3gm citrate every 5 minutes.
Transfusion rates higher than 1 unit every 5 minutes or impaired
liver function may lead to hypocalcemia (Manifest by transient
hypotension or tetany).
• Neonates and patients with pre-existing liver disease are at risk
for hypocalcemia. Monitor ionized calcium level and correct if
necessary
• Hypomagnesaemia: Because of large volume of magnesium-poor
fluid and citrate overload. Monitor ionized magnesium level and
correct if necessary
• Hyperkalaemia: Because of haemolysis of RBC from storage,
irradiation, or both.
• Neonates and patients with pre-exisiting cardiac and renal
diseases are at risk for hyperkalaemia.
• Monitor potassium level and correct if necessary.
• Fresh RBCs (<5–10 days old), irradiated<24 hbefore transfusion or
washing may decrease risk
• Hypokalaemia: Because of re-entry into transfused RBCs, release
of stress hormones, or metabolic alkalosis. Monitor potassium
level and correct if necessary
• Metabolic alkalosis: Because of citrate overload. Monitor acid–
base status
• Acidosis: Because of hypoperfusion, liver dysfunction, and citrate
overload. Monitor acid–base status
• Hypothermia: Because of infusion of cold fluid and blood
products, opening of body cavities, decrease heat production, and
impaired thermal control. Neonates and infants are at increased
risk. Blood warmer should be used
• Other: infections
Weight
Red cells FFP
<5kg 2 paediatric units
(80-100ml)
2 ‘neonatal’ units
methylene blue (MB)
treated FFP (100ml) or
1 unit Octaplas
5-10.9kg 1 adult unit
(250ml) , will
require LVT unit if
<12 months old
1 unit MB FFP
(225ml)or 1 unit
Octaplas
11-20kg 2 adult units
(500ml) or 2 LVT if
<12 months old
2 units MB FFP
(450ml)or 2 units
Octaplas
> 20 kg 4 adult units
(1000ml)
4 units MB FFP
(900ml)or 4 units
Octaplas
Weigh
t
Red cells FFP Cryoprecipita
te
Platelets
<5kg 2 paediatric
units
(80-100ml)
2 ‘neonatal’
units
methylene
blue treated
(MB) FFP
(100ml)or 1
unit Octaplas
1 single MB
donor unit
(40ml)
1 paediatric
pack of
platelets
(50ml)
5-10kg 1 adult unit
(250ml), will
require LVT if <
12 months old
1 unit MB FFP
(225ml)or 1
unit Octaplas
2 single MB
donor units
(80ml)
2 paediatric
packs of
platelets
(100ml)
11-
20kg
2 adult units
(500ml) will
require LVT if
less than 12
months old .
2 units MB
FFP (450ml)or
2 units
Octaplas
5 single MB
donor units
(200ml)
1 adult
apheresis
pack (200ml)
> 20 kg 4 adult units
(1000ml)
4 units MB
FFP (900ml)or
4 units
10 single MB
donor units
(400ml)
1 adult
apheresis pack
(200ml)
Senior clinician
• Request:a
o 4 units RBC
o 2 units FFP
• Consider:a
o 1 adult therapeutic dose platelets
o tranexamic acid in trauma patients
• Include:a
o cryoprecipitate if fibrinogen < 1 g/L
a Or locally agreed configuration
Massive transfusion protocol (MTP) template
Senior clinician determines that patient meets criteria for MTP activation
Baseline:
Full blood count, coagulation screen (PT, INR, APTT, fibrinogen), biochemistry,
arterial blood gases
Notify transfusion laboratory (insert contact no.) to:
‘Activate MTP’
Bleeding controlled?
Laboratory staff
• Notify haematologist/transfusion specialist
• Prepare and issue blood components
as requested
• Anticipate repeat testing and
blood component requirements
• Minimise test turnaround times
• Consider staff resources
Haematologist/transfusion
specialist
• Liaise regularly with laboratory
and clinical team
• Assist in interpretation of results, and
advise on blood component support
NOYES
Notify transfusion laboratory to:
‘Cease MTP’
OPTIMISE:
• oxygenation
• cardiac output
• tissue perfusion
• metabolic state
MONITOR
(every 30–60 mins):
• full blood count
• coagulation screen
• ionised calcium
• arterial blood gases
AIM FOR:
• temperature > 350C
• pH > 7.2
• base excess < –6
• lactate < 4 mmol/L
• Ca2+ > 1.1 mmol/L
• platelets > 50 × 109/L
• PT/APTT < 1.5 × normal
• INR ≤ 1.5
• fibrinogen > 1.0 g/L
The information below, developed by consensus, broadly covers areas that should be included in a local MTP. This
template can be used to develop an MTP to meet the needs of the local institution's patient population and resources
The routine use of rFVIIa in trauma patients is not recommended due to
its lack of effect on mortality (Grade B) and variable effect on morbidity
(Grade C). Institutions may choose to develop a process for the use of
rFVIIa where there is:
• uncontrolled haemorrhage in salvageable patient, and
• failed surgical or radiological measures to control bleeding, and
• adequate blood component replacement, and
• pH > 7.2, temperature > 340C.
Discuss dose with haematologist/transfusion specialist
b rFVIIa is not licensed for use in this situation; all use must be part of practice review.
• Warfarin:
• add vitamin K, prothrombinex/FFP
• Obstetric haemorrhage:
• early DIC often present; consider cryoprecipitate
• Head injury:
• aim for platelet count > 100 × 109/L
• permissive hypotension contraindicated
• Avoid hypothermia, institute active warming
• Avoid excessive crystalloid
• Tolerate permissive hypotension (BP 80–100 mmHg systolic)
until active bleeding controlled
• Do not use haemoglobin alone as a transfusion trigger
• Identify cause
• Initial measures:
- compression
- tourniquet
- packing
• Surgical assessment:
- early surgery or angiography to stop bleeding
• If significant physiological derangement, consider
damage control surgery or angiography
• Consider use of cell salvage where appropriate
• Actual or anticipated 4 units RBC in < 4 hrs, + haemodynamically unstable, +/– anticipated ongoing bleeding
• Severe thoracic, abdominal, pelvic or multiple long bone trauma
• Major obstetric, gastrointestinal or surgical bleeding
Specific surgical considerations
ResuscitationInitial management of bleeding
Dosage
Cell salvage
Considerations for use of rFVIIab
Special clinical situations
Suggested criteria for activation of MTP
ABG arterial blood gas FFP fresh frozen plasma APTT activated partial thromboplastin time
INR international normalised ratio BP blood pressure MTP massive transfusion protocol
DIC disseminated intravascular coagulation PT prothrombin time FBC full blood count
RBC red blood cell rFVlla activated recombinant factor VII
Platelet count < 50 x 109/L 1 adult therapeutic dose
INR > 1.5 FFP 15 mL/kga
Fibrinogen < 1.0 g/L cryoprecipitate 3–4 ga
Tranexamic acid loading dose 1 g over 10
min, then infusion of 1 g
over 8 hrs
a Local transfusion laboratory to advise on number of units
needed to provide this dose
Hemorrhagic shock requiring Massive transfusion is associated with
high mortality.
Massive transfusion protocols are associated with improved outcomes.
Early blood product tranfusion with plasma:platelet:RBC ratio close to
1:1:1 is associated with reduced 6-hour mortality
Goal-directed transfusion with TEG/TEM is feasible.
Fibrinogen concentrates, PCC and other factor concentrates require
further study.
When hemorrhage control is complete, stop transfusion.
Summary
Thank you…

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Massive transfusion protocol

  • 1. Massive Transfusion Protocols in Trauma Victims DR SHADAB KAMAL
  • 2. Patient Presentation to ER • 64 Year old male, passenger, suffered Motor Vehicle Crash with high-speed rollover presented to ER with drowsiness, SBP 60 and tachypnea. • Crystalloid fluid resuscitation initiated for hemorrhagic shock. • Airway control to avoid hypoxemia and Emergent Endotracheal intubation was done in ED. • Blood (PRBC, FFP) transfusion initiated for hypotension and hemorrhagic shock.
  • 3. Patient Presentation to ER • On physical exam Severe Flail chest was found along with Bilateral hemo-pneumothorax. • Bilateral closed tube thoracostomy(ICTD) was done. • Transient responder to blood transfusion. • FAST – Positive for hemoperitoneum • Pelvic fracture (unstable) was found on X ray of pelvis • Plan: To Operating Room for emergent laparotomy
  • 4. Management of Injuries in OR (DCS) • Laparotomy was done and splenectomy, repair of diaphragmatic injury, repair of liver lacerations, abdominal packs, Vaccum Assisted Closure of abdominal wall done. • Blood pressure normalized after abdominal hemorrhage controlled, liver & pelvis packed. • 18 Unit of PRBCs, 15 Unit of FFP, 3-5pk Platelets, 2 Cryoprecipate was transfused to the patient • Patient shifted to angiography for pelvis fractures, then to CT head and then ICU. • Chest CT scan obtained postop to evaluate intra- thoracic injuries
  • 5. Time Arterial pH pCO2 pO2 HCO3 Hct iCa++ Lactate 0712am 7.04 22 351 6 24 0.46 11.9 0805am 7.29 29 413 14 29 0.58 9.3 0849am 7.28 32 332 14 30 0.65 8.4 0712am Hb 6.9 Platelet 90000/mm3 PT 17.4 sec INR 1.8 sec PTT 77.8 sec Patient investigations
  • 6. Hospital Course • Persistent need for mechanical ventilation with the risk of ARDS, VAP • Need for further operation for removal of abdominal packs, transgastric jejunostomy for enteral nutrition and abdominal wall closure • ECHO confirmed blunt myocardial injury. • Tracheostomy was done • ICU Length Of Stay > 3 weeks • Eventual full recovery.
  • 7. Massive transfusion: Introduction • MT are needed in trauma, obstetrics, and major surgery. • According to CDC >120 000 deaths in 2010 due to trauma • About 40% of trauma-related mortality is due to uncontrolled bleeding. • Among the injured patients admitted to trauma centres, up to 10% of military and up to 5% of civilian patients require MT. • In general, injury severity and transfusion requirement are associated with mortality. Most (99%) of the patients receiving <10 RBC units within the first 24 h survived, whereas only 60% of patients who received >10 RBC units within the first 24 h survived.
  • 8. 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Prehospital First 24 hours After 24 hours Percentageofdeaths Hemorrhage CNS Other Hemorrhagic Mortality • While bleeding is the #2 cause of mortality, hemorrhage is the #1 reversible cause for mortality • Almost all mortality from hemorrhage occurs within 1st 24 hours
  • 9. Massive Blood Transfusuin Transfusion of ≥10 red blood cell (RBC) units, which approximates the total blood volume (TBV) of an average adult patient, within 24 h, Transfusion of >4 RBC units in 1 h with anticipation of continued need for blood product support Replacement of >50% of the TBV by blood products within 3 h. Transfusion support to loss of blood >150ml/min In Paediatric pts Transfusion of >100% TBV within 24 h, Transfusion support to replace ongoing haemorrhage of >10% TBV /min Replacement of>50% TBV by blood products within 3 h. Definition of Massive Transfusion
  • 10. Trauma Resuscitation • Determine severity of hemorrhagic shock (admission arterial lactate) • Expedite control of hemorrhage • Damage Control Surgery • Early blood and blood product resuscitation • Blood product resuscitation ratio – PRBCs/FFP/platelets, 1:1:1 • Minimize crystalloid (prevent coagulopathy, thrombocytopenia) • SBP 80-100 mm Hg • Frequent labs (Type & Crossmatch, CBC, Plts, Coagulation profile, INR, PT, PTT, Fibrinogen, Electrolytes, BUN/Creatinine, ionized calcium, Lactate, TEG if available) • Consider TXA and additional coagulation factors (rFVIIa etc)
  • 11. Predictor of massive transfusion Trauma Associated Severe Hemorrhage (TASH)-score incorporated seven clinical and laboratory variables into a composite score to predict the need for MT. • Haemoglobin, • Base excess, • Systolic arterial pressure, • Heart rate, • Presence of free intra-abdominal fluid and/or • Complex fractures, and • Gender Nunez and colleagues demonstrated that simple parameters also appears to be as good as other more complex scoring systems to predict MT. • Presence of penetrating trauma, • Systolic arterial pressure <90 mm Hg, • Heart rate >120 beats min, and • a positive focused abdominal sonography for trauma, • If any two of the above four parameters are positive, the patient is likely going to require MT.
  • 12. Early trauma induced coagulopathy (ETIC) or Acute coagulopathy of Trauma Historically, Early Trauma Induced Coagulopathy or acute coagulopathy of trauma was attributed to crystalloid and RBC transfusion without administration of platelets, plasma, or both. However, subsequent studies in both adult and paediatric trauma patients demonstrated that ETIC was present in 24%, and up to 56% in severely injured patients, usually within 30 min of injury, even before receiving RBC and fluid resuscitation.
  • 13.
  • 14. Breaking the “Bloody Vicious Cycle”  Control hemorrhage  Use best possible resuscitation products  Prevent hypothermia  Prevent hemodilution  Treat coagulopathy
  • 15. • In the past, trauma patients were given colloid or crystalloid fluid initially. • Blood products were administered after 2 litre of fluid resuscitation, usually guided by laboratory results to keep haemoglobin >10 g/dl, platelet count >50000, and INR ≤1.5. • Using these guidelines, blood loss continued because of delay in laboratory turn around time and dilutional coagulopathy.
  • 16. • Recent studies with consideration of resuscitation, and better understanding the pathophysiology of ETIC has led to early use of RBCs, plasma, and platelets and reduced crystalloid use in resuscitation. J TRAUMA 2010
  • 17. • Current component therapies in the USA suggested that when administering RBC, plasma, and platelets in a 1:1:1 ratio, this 630-650 ml product has a haematocrit of 29%, coagulation factor activity of 65%, and a platelet count of 90000/mm3. • With storage defects taken into account, this mixed product would have a haematocrit of 26%, coagulation factor activity of 40–50%, and platelet count of 90000/mm3 • Furthermore, any attempt to increase the concentration of one component would lead to dilution of the other two.
  • 18. • The administration of RBC:plasma:platelets at 1:1:1 ratio was first proposed by the US military and subsequently supported by military and then civilian studies. The rationale for the 1:1:1 ratio is that it more closely resembles whole blood, which would help to treat and prevent ETIC. • A retrospective review of patients receiving MT at a US combat hospital demonstrated reduced mortality from 66% to 19% when the RBC:Plasma ratio decreased from 8:1 to 2:1.38 Ann of Surg 2008; 248:447-458.
  • 19. Resuscitation with a 1:1:1 ratio of RBCs, plasma, and platelets is the recommendation of the Army Surgeon General and his Trauma Consultant. However, these studies, and multiple others, are retrospective, and are affected by survival bias which is resulting from the fact that surviving patients are more likely to receive more plasma and platelets in relation to RBCs compared with nonsurviving patients because they lived long enough to receive those blood products.
  • 20. • In June 2011, the Canadian National Advisory Committee on Blood and Blood Products determined that the retrospective evidence available at the time was insufficient to recommend a RBC:Plasma:Platelet transfusion ratio of 1:1:1 as the standard of care for MT. • They also stated that subsequent retrospective studies would be unlikely to overcome survivorship bias and would not be able to make further contributions to the determination of the most effective ratio.
  • 21. • Recently, the Prospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study examined the association between mortality rates in trauma patients and transfusion ratios; this cohort study demonstrated improved in-hospital mortality with RBC:plasma and RBC:platelet ratios <2:1 in the first 6 h. •In the first 6 hours, patients with ratio < 1:2 were 3 to 4 times more likely to die than patients with ratios of 1:1 or higher. •After 24 hours, plasma and platelet ratios were unassociated with mortality, when non-hemorrhagic causes prevailed. 1 July 2009 - 15 Oct 2010
  • 22. • The follow-up Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial is a randomized trial to evaluate ratios, MT patients receive either a 1:1:1 (higher ratio) or a 2:1:1 (lower ratio) RBC: Plasma: Platelet with primary outcome of survival, and also complications and length of hospital stay. • The results of this study should further elucidate the optimal ratios of blood product administration during MT. 8/2012 – 8/2015 ..extensive lab analysis will be done to evaluate the influence of fluid resuscitation on traumatic induced coagulopathy.
  • 23. What is MTP? MTP is a way to coordinate the care for patients requiring MT, to facilitate communication between different services (trauma, nursing, transfusion medicine, and other laboratories), avoid delay in clinical care, laboratory testing and blood product transfusion, and nursing care. MTP is a way to assure good patient care by having a standard protocol on specific actions to take for each service involved. MTPs have demonstrated improved patients survival and reduced rates of organ failure and post-trauma complications.
  • 24. Component of MTP (i) When and who should initiate MTP. (ii) Notification of the transfusion service and laboratory regarding start and stop of MTP. (iii) Laboratory testing algorithm [prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen level, blood gas, and complete blood count], and thromboelastography if available. (iv) Blood product preparation and delivery (i.e. predetermined transfusion packages). (v) Other patient care needs (such as blood warmers, nursing care).
  • 25. • MTPs can include preparation and administration of blood products based on laboratory test results, predetermined transfusion packages • Although the number and timing of blood component delivery, laboratory testing algorithms, and other aspects of the MTPs varies between institutions, most current MTPs use predetermined transfusion packages. • MTPs vary in their predetermined transfusion packages, but all include platelet and plasma units with RBC units.
  • 26. 43 Cotton BA,GuyJS, MorrisJAJr,AbumradNN.Thecellular,metabolic, and systemic consequences of aggressive fluid resuscitation strategies. Shock 2006; 26: 115–21 45 Dente CJ, Shaz BH, Nicholas JM, et al. Improvements in early mortalityandcoagulopathyare sustained better in patients with blunt Trauma after institution of amassive transfusion protocol in acivilian level I trauma center. J Trauma 2009; 66: 1616–24 46 Nunez TC, Young PP, Holcomb JB, Cotton BA. Creation, implementation, and maturation of a massive transfusion protocol for the exsanguinating trauma patient. J Trauma 2010; 68: 1498–505 47 O’Keeffe T, Refaai M, Tchorz K, Forestner JE, Sarode R. A massive transfusion protocol to decrease blood component use and costs. Arch Surg 2008; 143: 686–90; discussion 90–1 48 Riskin DJ, Tsai TC, Riskin L, et al. Massive transfusion protocols: the role of aggressive resuscitation versus product ratio in mortality reduction. J Am Coll Surg 2009; 209: 198–205
  • 27.
  • 28. Whole Blood vs Blood components • In the recent military experiences in Iraq and Afghanistan, whole blood transfusion compared with RBC, plasma, and apheresis platelet use reduced pulmonary and tissue oedema, which decreased the ventilation time and also allowed closure of the abdomen with minimal delay. • Furthermore, retrospective analysis suggested that patients who received both fresh whole blood and component therapy had better clinical outcomes compared with those who received only component therapy. • However, concern for transfusion transmitted infections and transfusion- associated graft vs host disease remains.
  • 29. Paediatric MTPs • The data on paediatric MTPs are limited, and thus practices vary significantly among institutions. • In the majority of institutions, a single MTP is used for both adult and paediatric patients. • Published studies on paediatric MTPs did not show improvement in mortality in the group receiving blood products according to the institutional MTP compared with the historical control or the group receiving blood products at physician discretion. • Despite obtaining null results in both studies, probably due to small sample sizes, it was suggested that implementation of MTP to increase the Plasma: RBC ratio is feasible in paediatric patients.
  • 30. Considerations in MTP • Group O RBCs and AB plasma products should be given until the patient’s blood type can be determined. • Use of D-positive products in D-negative or D-unknown patients • Thawed plasma units • Prothrombin complex concentrate (PCC) • fibrinogen concentrate • Tranexamic acid (TXA) given early in the resuscitation process (<3 h from injury to treatment, preferably within 1 h from injury). • When to consider rFVIIa?
  • 31. Blood Product until result of Type and Crossmatch • In many trauma situations, there is excessive blood loss, and transfusion is needed before the ability to perform pre transfusion testing. In these cases, group O RBCs and AB plasma products should be given until the patient’s blood type can be determined. • It is important to obtain and test a patient sample as soon as possible after admission so that type-specific products can be administered when available. • This helps to preserve the inventory of group O RBCs and AB plasma, and minimizing potential for ABO typing discrepancies when a patient has received multiple units of group O RBCs and AB plasma.
  • 32. Use of D-positive products in D-negative or D-unknown patients • Each institution should have a policy determining the use of D-positive products in D-negative or D-unknown patients, including the use of D-positive products for men and women past childbearing age (usually >50 yr old), and after a set number of D-negative RBC units. • The frequency of anti-D formation after transfusion of D- positive blood products to a D-negative patient is about 20% for RBCs and ,4% for platelets (likely lower for apheresis platelets).
  • 33. • It is especially important to prevent anti-D formation in females of childbearing potential because anti-D can cause haemolytic disease of the fetus and newborn in future pregnancies. • Therefore, females of childbearing potential should receive D- negative RBCs.
  • 34. Thawed plasma units • Thawed plasma units are not available for patients requiring MT. It takes about 20 min to thaw frozen plasma. • Hence, in order to facilitate early transfusion of plasma in the resuscitation process, many institutions keep some units of thawed plasma available for immediate issue. • Many trauma patients arrive in the trauma bay with unknown blood type; thus, AB plasma is prepared since it is the universal donor type. • However, AB plasma is rare since only 4% of the population is group AB. Once plasma is thawed, it can only be kept for 5 days. • Therefore, maintaining an inventory of thawed AB plasma at all times might be a challenge.
  • 35. Prothrombin complex concentrate (PCC) • used to treat congenital coagulation disorders and for warfarin reversal in patients with active bleeding or undergoing urgent procedures. • PCC contains factors II, VII, IX, and X, and proteins C and S, • PCC can be three-factor, such as Profilnine SD (lacking factor VII), or four-factor, such as Kcentra. • To date, there has not been any prospective randomized controlled trial to evaluate the efficacy and safety of PCC in massively bleeding patients. • Hence, risks and benefits of using PCC as an adjunctive therapy should be discussed in any institutional MTP and it is recommended that PCC usage should be continually evaluated.
  • 36. Fibrinogen concentrate • Fibrinogen concentrate has been shown to reduce peri- operative bleeding and transfusion requirement. • Fibrinogen concentrates, in conjunction with PCC, also have been shown in a few prospective studies to decrease the transfusion requirements and mortality in trauma patients. • It has not been approved to be used as an adjunctive therapy in patients requiring MT. • Therefore, it is recommended to discuss the risk and benefit of using fibrinogen concentrate as part of the MTP in any institution.
  • 37. • Tranexamic acid (TXA), were demonstrated to reduce mortality in trauma patients in both civilian and military settings, especially if given early in the resuscitation process (<3 h from injury to treatment, preferably within 1 h from injury). • In the military setting, the MATTERs study, mortality in the TXA group was lower than in the group not receiving TXA. J Trauma Acute Care Surg 2013;75(6):1575-1586
  • 38. Conclusion: Tranexamic acid safely reduced the risk of death in bleeding trauma patients in this study. On the basis of these results, tranexamic acid should be considered for use in bleeding trauma patients. But…No difference in blood transfusion rates. Lancet 2010;376:23‐32 • Moreover, TXA was also shown to be a cost-effective therapy in all low-, middle-, and high-income countries using data from the randomized controlled CRASH-2 trial done in a civilian population. • TXA should be part of the early resuscitation process.
  • 39. Boffard KD et al. J Trauma 2005 Jul;59(1):8-15 Conclusion: In blunt trauma, RBC transfusion was significantly reduced with rFVIIa (estimated reduction 2.6 RBC units, p=0.02) and the need for massive transfusion was reduced (14% vs. 33% of patients, p=0.03)
  • 40. Lab monitoring in MTP • MTP requires adequate laboratory support to oxygen-carrying capacity, haemostasis, and metabolic status in order to address and correct abnormalities. • In addition, laboratory results can be used retrospectively to assess the need for MTP adjustment. • For example, if all patients have low fibrinogen values upon ICU admission, increased cryoprecipitate or fibrinogen concentrate use is indicated during MTP. A metabolic panel should be used to monitor metabolic abnormalities during MT, such as hyperkalaemia and hypocalcaemia. • Point-of-care ABG measurement is helpful in monitoring oxygenation.
  • 41. Conventional coagulation assay vs TEG/ROTEM • Monitoring haemostasis in patients with MT is challenging because there is no validated coagulation assay that can detect accurately the coagulopathies in massively bleeding patients in a timely manner. • Conventional coagulation assays, such as PT, aPTT, and fibrinogen levels, are likely not available in real-time fashion. • In addition, these tests do not detect some haemostatic abnormalities, such as platelet dysfunction, hyperfibrinolysis, and factor XIII deficiency. • They also do not quantify the relative contribution of pro-coagulant and anti-coagulant factors. • These conventional coagulation assays do not predict the future need for MTP.
  • 42. TEG/ROTEM • Recently, it has been suggested that such as thromboelastography (TEG) and rotational thromboelastometry (ROTEM), might be better at assessing coagulopathy inpatients requiring MT. • These assays offer clinicians a graphic representation of the coagulation process • In addition, the parameters obtained from TEG/ROTEM could provide a quantitative measure of individual components of the haemostatic process in adult patients. • Hence, the use of TEG/ROTEM can provide information to guide blood component therapies in a more timely manner.
  • 43. Advantages of using TEG/ROTEM • Turn around time for these assays is shorter compared with conventional assays (15–30 min); thus, they can be used in combination with clinical assessment for the decision-making process. • These assays can detect hyperfibrinolysis, an important component of haemostatic abnormalities in patients with MT that cannot be detected by PT and aPTT assays. • Unlike the PT and aPTT that can only test secondary haemostasis, TEG/ROTEM assess all phases of coagulation, such as the contribution of platelets to primary haemostasis and factor XIII to cross-linking the fibrin clot. • TEG/ROTEM can be performed at the patient’s true temperature, which makes it more sensitive for detection of coagulopathy due to hypothermia.
  • 44. Plasma Transfusion • a. Consider transfusion when rapid blood loss exceeding 100ml/min continues after transfusion of crystalloids, colloids and 4u RBC’s. • b. After loss of one circulation blood volume when PT, aPTT, and fibrinogen cannot be obtained in time. • c. Transfuse 10-15 ml/kg rapidly (this corresponds to 1000ml of plasma, or 4 units of FFP). • d. It takes 20 minutes to thaw and transport 4u FFP.
  • 45. Platelet Transfusion • a. On the achievement of surgical hemostasis, do not let platelets fall below 50,000 mm3 in acutely bleeding patients. • b. Target of 100,000 mm3 recommended for patients with multiple high energy trauma or CNS injury. • c. Platelet count of 50,000 mm3 can be anticipated when approximately 2 blood volumes have been replaced with plasma- poor RBC’s. • d. Platelets are quickly lost through wounds until surgical hemostasis obtained.
  • 46. Short-term coagulation goals: • Hct>20-24% • Plts >50,000 mm3 (>100,000 for CNS injury or multiple high energy trauma) • Fibrinogen>100mg/dL • APTT<45 sec • PT<18 sec Long-term coagulation goals: • Hct>24% • Plts>100,000mm3 • Fibrinogen>150mg/dL • APTT<40 sec • PT<17 sec
  • 47.  Although the number and timing of blood component delivery, laboratory testing algorithms, and other aspects of the MTPs varies between institutions, most current MTPs use predetermined transfusion packages.  MTPs vary in their predetermined transfusion packages, but all include platelet and plasma units with RBC units.
  • 48.
  • 49. Massive Transfusion Protocol (MTP) • Intravenous access – 2 large bore IVs and CVC • Crystalloid -3:1/colloid- 1:1 ratio with Expected blood loss • Limited crystalloid - avoid dilutional coagulopathy • Labs: Type & Crossmatch, CBC, Platelets, INR, PT, PTT, Fibrinogen, Electrolytes, BUN/Creatinine, ionized calcium • Continuous monitoring: Volume Status, U/O, Acid-base status • Aggressive re-warming. • Prevent / Reverse acidosis • Correct hypocalcemia: Calcium Gluconate or Calcium Chloride: 1 gm iv 10 slowly(Target goal ionized calcium 1.2 – 1.3) • Transfuse with unmatched group O RBCs on hand. • Repeat lab testing to evaluate coagulopathy Appropriate Initial Interventions:
  • 50. Other considerations: • Heparin reversal: Protamine 1mg IV/100 U heparin • Warfarin reversal: Vitamin K 10 mg IV; Consider PCC(prothrombin complex concentrate) • Consider antifibrinolytics: by Tranexamic acid 10 mg/kg IV or Amicar(EACA) 5 gm IV bolus then 1 gm/hr IV infusion • Intraoperative RBC salvage techniques
  • 51. General Guidelines for Lab-based Blood Component Replacement in Adults: Components Thershold Dose RBCs No Thershold Physician Discretion FFP INR>1.5 4 Units FFP Platelets <100000 5- Pack Platelets Cryoprecipate Fibrinogen<100 Two 5-pack Cryoprecipate
  • 52. Identify and Manage bleeding (Surgery, angiographic embolization, endoscopy) 4 unit RBCs in <4 hour and ongoing uncontrolled Bleeding Clinical team activates MTP and designates clinical contact Clinical contact phones blood bank(BB) and: • Provides name of clinical contact person to BB • Provides MR#, sex, name, location of patient • Records name of BB contact, calls if location/contact information changes • Ensures that MTP protocol electronic order is entered in CareLink BB Prepares MTP Pack; Transfuse as 1:1:1 Ratio MTP Pack: 6U RBCs; 4U FFP ; One (1) 5-pack Platelets
  • 53. Stop MTP Notify BB & return any unused blood ASAP Resume standard orders D/C MTP Electronic order BB Prepares MTP Pack; Transfuse as 1:1:1 Ratio MTP Pack: 6U RBCs; 4U FFP ; One (1) 5-pack Platelets Hemostasis & resolution of coagulopathy? Repeat Labs • CBC, plts • INR, PT, PTT • Fibrinogen • Ionized Calcium • Consider rapid coagulation tests Consider rFVIIa, If persistent coagulopathy • 40 to 100 ug/kg dose • Round up to 1, 2, 5 mg vial Clinical designate contacts Blood Bank for another MTP pack ** emergency physician can adjust pack based on labs PRN No Yes
  • 54. Transfusion reactions: • Allergic: Range from simple urticarial to anaphylaxis, Steroid and diphenhydramine might be given to patients with allergic transfusion • Haemolytic transfusion reaction (acute and delayed): Might be reduced by giving group O RBCs and AB plasma for emergency release of blood products • Febrile non-haemolytic transfusion reaction: Diagnosis of exclusion Complication of Massive Transfusion
  • 55. Immunological reactions: • Transfusion-related acute lung injury (TRALI): Incidence can be reduced by transfusing male-only plasma • Transfusion-related immunomodulation (TRIM): Might be responsible for increased risk of bacterial infection • Transfusion-associated graft vs host disease (Ta-GVHD): Irradiation of cellular blood products in patients at risk (such as neonates and immunosuppressed patients) to prevent Ta-GVHD • Post-transfusion purpura (PTP): Can be treated with IVIg infusion, steroid, or plasma exchange
  • 56. Metabolic complications • Hypocalcaemia: Because of citrate overload from rapid transfusion of blood products. (Each unit PRBCs – approx 3gm citrate) • Healthy adult liver metabolizes 3gm citrate every 5 minutes. Transfusion rates higher than 1 unit every 5 minutes or impaired liver function may lead to hypocalcemia (Manifest by transient hypotension or tetany). • Neonates and patients with pre-existing liver disease are at risk for hypocalcemia. Monitor ionized calcium level and correct if necessary • Hypomagnesaemia: Because of large volume of magnesium-poor fluid and citrate overload. Monitor ionized magnesium level and correct if necessary
  • 57. • Hyperkalaemia: Because of haemolysis of RBC from storage, irradiation, or both. • Neonates and patients with pre-exisiting cardiac and renal diseases are at risk for hyperkalaemia. • Monitor potassium level and correct if necessary. • Fresh RBCs (<5–10 days old), irradiated<24 hbefore transfusion or washing may decrease risk • Hypokalaemia: Because of re-entry into transfused RBCs, release of stress hormones, or metabolic alkalosis. Monitor potassium level and correct if necessary
  • 58. • Metabolic alkalosis: Because of citrate overload. Monitor acid– base status • Acidosis: Because of hypoperfusion, liver dysfunction, and citrate overload. Monitor acid–base status • Hypothermia: Because of infusion of cold fluid and blood products, opening of body cavities, decrease heat production, and impaired thermal control. Neonates and infants are at increased risk. Blood warmer should be used • Other: infections
  • 59.
  • 60.
  • 61. Weight Red cells FFP <5kg 2 paediatric units (80-100ml) 2 ‘neonatal’ units methylene blue (MB) treated FFP (100ml) or 1 unit Octaplas 5-10.9kg 1 adult unit (250ml) , will require LVT unit if <12 months old 1 unit MB FFP (225ml)or 1 unit Octaplas 11-20kg 2 adult units (500ml) or 2 LVT if <12 months old 2 units MB FFP (450ml)or 2 units Octaplas > 20 kg 4 adult units (1000ml) 4 units MB FFP (900ml)or 4 units Octaplas Weigh t Red cells FFP Cryoprecipita te Platelets <5kg 2 paediatric units (80-100ml) 2 ‘neonatal’ units methylene blue treated (MB) FFP (100ml)or 1 unit Octaplas 1 single MB donor unit (40ml) 1 paediatric pack of platelets (50ml) 5-10kg 1 adult unit (250ml), will require LVT if < 12 months old 1 unit MB FFP (225ml)or 1 unit Octaplas 2 single MB donor units (80ml) 2 paediatric packs of platelets (100ml) 11- 20kg 2 adult units (500ml) will require LVT if less than 12 months old . 2 units MB FFP (450ml)or 2 units Octaplas 5 single MB donor units (200ml) 1 adult apheresis pack (200ml) > 20 kg 4 adult units (1000ml) 4 units MB FFP (900ml)or 4 units 10 single MB donor units (400ml) 1 adult apheresis pack (200ml)
  • 62.
  • 63. Senior clinician • Request:a o 4 units RBC o 2 units FFP • Consider:a o 1 adult therapeutic dose platelets o tranexamic acid in trauma patients • Include:a o cryoprecipitate if fibrinogen < 1 g/L a Or locally agreed configuration Massive transfusion protocol (MTP) template Senior clinician determines that patient meets criteria for MTP activation Baseline: Full blood count, coagulation screen (PT, INR, APTT, fibrinogen), biochemistry, arterial blood gases Notify transfusion laboratory (insert contact no.) to: ‘Activate MTP’ Bleeding controlled? Laboratory staff • Notify haematologist/transfusion specialist • Prepare and issue blood components as requested • Anticipate repeat testing and blood component requirements • Minimise test turnaround times • Consider staff resources Haematologist/transfusion specialist • Liaise regularly with laboratory and clinical team • Assist in interpretation of results, and advise on blood component support NOYES Notify transfusion laboratory to: ‘Cease MTP’ OPTIMISE: • oxygenation • cardiac output • tissue perfusion • metabolic state MONITOR (every 30–60 mins): • full blood count • coagulation screen • ionised calcium • arterial blood gases AIM FOR: • temperature > 350C • pH > 7.2 • base excess < –6 • lactate < 4 mmol/L • Ca2+ > 1.1 mmol/L • platelets > 50 × 109/L • PT/APTT < 1.5 × normal • INR ≤ 1.5 • fibrinogen > 1.0 g/L The information below, developed by consensus, broadly covers areas that should be included in a local MTP. This template can be used to develop an MTP to meet the needs of the local institution's patient population and resources
  • 64. The routine use of rFVIIa in trauma patients is not recommended due to its lack of effect on mortality (Grade B) and variable effect on morbidity (Grade C). Institutions may choose to develop a process for the use of rFVIIa where there is: • uncontrolled haemorrhage in salvageable patient, and • failed surgical or radiological measures to control bleeding, and • adequate blood component replacement, and • pH > 7.2, temperature > 340C. Discuss dose with haematologist/transfusion specialist b rFVIIa is not licensed for use in this situation; all use must be part of practice review. • Warfarin: • add vitamin K, prothrombinex/FFP • Obstetric haemorrhage: • early DIC often present; consider cryoprecipitate • Head injury: • aim for platelet count > 100 × 109/L • permissive hypotension contraindicated • Avoid hypothermia, institute active warming • Avoid excessive crystalloid • Tolerate permissive hypotension (BP 80–100 mmHg systolic) until active bleeding controlled • Do not use haemoglobin alone as a transfusion trigger • Identify cause • Initial measures: - compression - tourniquet - packing • Surgical assessment: - early surgery or angiography to stop bleeding • If significant physiological derangement, consider damage control surgery or angiography • Consider use of cell salvage where appropriate • Actual or anticipated 4 units RBC in < 4 hrs, + haemodynamically unstable, +/– anticipated ongoing bleeding • Severe thoracic, abdominal, pelvic or multiple long bone trauma • Major obstetric, gastrointestinal or surgical bleeding Specific surgical considerations ResuscitationInitial management of bleeding Dosage Cell salvage Considerations for use of rFVIIab Special clinical situations Suggested criteria for activation of MTP ABG arterial blood gas FFP fresh frozen plasma APTT activated partial thromboplastin time INR international normalised ratio BP blood pressure MTP massive transfusion protocol DIC disseminated intravascular coagulation PT prothrombin time FBC full blood count RBC red blood cell rFVlla activated recombinant factor VII Platelet count < 50 x 109/L 1 adult therapeutic dose INR > 1.5 FFP 15 mL/kga Fibrinogen < 1.0 g/L cryoprecipitate 3–4 ga Tranexamic acid loading dose 1 g over 10 min, then infusion of 1 g over 8 hrs a Local transfusion laboratory to advise on number of units needed to provide this dose
  • 65. Hemorrhagic shock requiring Massive transfusion is associated with high mortality. Massive transfusion protocols are associated with improved outcomes. Early blood product tranfusion with plasma:platelet:RBC ratio close to 1:1:1 is associated with reduced 6-hour mortality Goal-directed transfusion with TEG/TEM is feasible. Fibrinogen concentrates, PCC and other factor concentrates require further study. When hemorrhage control is complete, stop transfusion. Summary