1
Resuscitation from Massive Hemorrhage &
Development of the MTP:
Perspective of an Obstetrical
Anesthesiologist
From the ED to the battlefield and back to the ED/bedside
Alan I. Frankfurt, MD
Partner, ATLAS Anesthesia
Irving, Texas
Department of Anesthesiology
TH Dallas-Presbyterian Hospital
2
Learning Objectives






History lesson
Incidence of MT
Alan I. Frankfurt, MD
DCR & “5 H’s”
Coagulopathy and morbidity in hemorrhagic shock
Lethal triad
Evolution of the MTP: responding to an iatrogenic coagulopathy
 Maryland Shock Trauma
 Somalia & Iraq/Afghanistan
 1:1:1 vs. 1:1:2-it’s a math thing
 PROMMTT
 PROPPRR
 Thoughts for your day to day practice in the ED.
HISTORY OF WARTIME PREHOSPITAL/ER
SHOCK RESUSCITATION
WW I/WW II
50 years of
Plasma,
Albumin and
Whole Blood
Vietnam Korea
40 years of Crystalloid/
Clear Fluids & WB:
1. 3rd space resuscitation
2. Fractionation of WB
OIF/OEF
Forward to the past(
DCR):
1. Early plasma
2. ”WB” equivalent
3. FWWB
4
Damage Control Resuscitation
“5 H’s”
• Hemorrhage control
▫ OR timely fashion
 Definitive solution to bleeding is in the OR/IR
• Hypotensive resuscitation
▫ Systolic BP=80-90 torr
 “Tolerate” shock vs. Popping clots
• Hemostatic resuscitation
▫ Blood products early and often: Plasma
 Prevention of coagulopathy
 Dilution
 ACoTS
▫ Minimize crystalloid administration
• Homeostasis
▫ Hypothermia
▫ Acidosis
• Hypnosis: having our cake and eating it too
▫ DCA
 Vasoconstriction
Vasorelaxed
5
Alan I. Frankfurt, MD
Elements of hemostatic resuscitation, and
level of evidence in support:
R. Dutton; BJA 2012, Vol109 no. suppl 1 i39
Recommendations
Evidence
 Expedited anatomic control in
OR
Strong; widely accepted
 Deliberate (permissive)
hypotension
Several prospective trials;
widely accepted
Early support of coagulation

Antifibrinolytic therapy
One large prospective
trial, several smaller
studies; emerging standard
 Early use of early plasma and
platelets in massively bleeding
patients 1:1:1
Controversial; variable
application in clinical
practice (PROMMTT);
PROPPR trial
 Vasodilation with anesthetic
agents aka (DCA)
Theory only. Minimal
clinical data
6
Hypotensive Resuscitation
A Historical Perspective
Alan I. Frankfurt, MD
7
Hypotensive Resuscitation:
A Balancing Act
Alan I. Frankfurt, MD
Permissive ischemia
Tolerating short period
of hypotension
Vs.
Popping a clot
Minimize the risk of
increased bleeding
8
Blood Pressure at which Rebleeding Occurs
after Resuscitation in Swine with Aortic Injury
Jill L. Sondeen, PhD
J of Trauma 54: (5) May Supp 2003
• Reproducible blood pressure at which rebleeding
occurred in test animals.
Keep the SBP 80-90
▫ Systolic 94 mmHG
torr until the bleeding
is controlled.
▫ Diastolic 45 mmHG
▫ MAP 64 mmHG
 Similar to resuscitation pressures suggested by Drs. Cannon
(WW1) and Beecher (WW2), respectively.
 Stern SA; Ann Emerg Med 1993 Feb; 22: 155
 Burris D.; J Trauma 1999;46:216-223
 Stern SA; Prehosp Emerg Care. 2002;6:81-91
• Standard component of DCR
Alan I. Frankfurt, MD
73,000 foot view of Hemorrhage
Resuscitation:
9
Keeping the Resuscitation Fluids
Administered to a Hemorrhaging Patient,
Looking Like Blood Coming Out
 Early blood product
administration (MTP)
 Early Plasma
 ? Cryoprecipitate &
Platelets
 Minimize IV
crystalloids
 Avoid coagulopathy
Alan I. Frankfurt, MD
10
Basics
Alan I. Frankfurt, MD
 How much do young healthy trauma patients bleed before the
patient demonstrates changes in routine vital signs (BP, P,
RR, LOC).
 Do routine vital signs reflect EBL & occult shock?
 If not, what should we be following?
 What kills you when you “bleed to death”?
11
ACS ATLS
Clinical Signs Associated with Blood Loss:
Alan I. Frankfurt, MD
Class
Class I
EBLestimated
blood loss.
<750cc
%EBV
Lost
<15%
Pulse Rate
Blood
Pressure
Mental
Status
Normal
Slightly
anxious
<100
Normal
Class II
750-1500cc
Class III
Life
threatening
1500(2000)cc
Class IV
Life
Threatening
15-30%
30-40%
>2000cc
40-50%
>100
>120
Weak or
intermittent
Radial pulse
>140
Absent radial
pulse.
Decrease
Decrease
Mildly
Loss of
anxious
Effective
Compensatio
n
Confused
Lethargic,
Confused,
Unconscious
13
Alan I. Frankfurt, MD
Classification of Shock Using ED Admission Arterial
Base Deficit Values Defined by
JW Davis, MD et al.
Admission Base Deficit Predicts Transfusion Requirements
and Risk of Complications
James W. Davis, MD; Jour of Trauma, Vol. 3, No. 5: 769
14
Alan I. Frankfurt, MD
Questioning the validity of the ATLS
classification in hypovolemic shock:
the role of (venous) BD/Lactate
15
Alan I. Frankfurt, MD
Mutschler et al. Critical Care 2013, 17:R42
16
Alan I. Frankfurt, MD
Mutschler et al. Critical Care 2013, 17:R42
17
Alan I. Frankfurt, MD
Mutschler et al.
Critical Care 2013,
17:R42
18
Hemorrhagic death is the result
of systemic vascular collapse
Alan I. Frankfurt, MD
19
EBV~5000cc/70 kg person
Venoconstriction
Arterial constriction
Baseline
vascular
tone
Vascular capacitance= X3 EBV
MAP
Increasing blood loss
•
Endothelial ischemia & Acidosis pH<7.2
•
Loss of vascular reactivity
•
Catecholamines
•
Systemic vasodilatation
•
Vascular collapse
10%
20%
30%
Systemic
vascular
collapse
40%
50-60%
20
Alan I. Frankfurt, MD
Pathway to Vascular Collapse and
Decompensated Shock
Compensated shock:
no cellular damage
Vasoconstriction:
Ischemia tolerant tissue:
Skin, skeletal muscle and
bone
Continuing hemorrhage
Exhaustion of physiologic
compensatory
mechanisms
Pathway to vascular
collapse:
Decompensated
shock:
cellular damage
Vasoconstriction
Ischemia intolerant
tissue: Brain and heart
LETHAL TRIAD:
Acidosis, Hypothermia,
Coagulopathy
21
Lethal Triad of Trauma:
Marker of Physiologic Exhaustion
Alan I. Frankfurt, MD
Coagulopathy
INR
Acidosis
Hypothermia
Best single
live/die
predictor in
trauma &
hemorrhage
patients.
22
The Lethal Triad
Coagulopathy
•External bleeding
•Consumption of
clotting factors
•Dilution IV fluids/MTP
•Fibrinolysis
•Dysfunction:
H+/Temperature
Massive
Hemorrhage
Lethal
Triad
Acidosis(Lactate)
•Oxygen debt
•pH < 7.2
•50% Factor
dysfunction
•Vascular paralysis
Alan I. Frankfurt, MD
Hypothermia
•Cold fluids
•Vasodilation
•Room temp
•Open abdomen
23
The Lethal Triad Drives Resuscitation
Efforts
• Hemorrhage control (stop the bleeding)
▫
▫
Operating room
Interventional radiology
• Volume administration (fill the tank)
▫
Coagulopathy
•Floor
•Consumption
•Dilution
•Fibrinolysis
•Dysfunction
Damage Control
Resuscitation
Preload/Cardiac output/MAP
• CaO2 (oxygen carrying capacity)
▫
Hg x SpO2 x K
 pRBC
• Coagulation (make clots)
▫
MTP
 FFP
 Cryoprecipitate
 Platelets
 Antifibrinolytics
Lethal
Triad
• Homeostasis (keep the patient warm)
▫
Normal physiologic environment
 Hypothermia
 Acidosis
 Calcium
Alan I. Frankfurt, MD
Acidosis
•Oxygen debt
•pH <7.2
•50% Factor
dysfunction
•Vascular paralysis
Hypothermia
•Cold fluids
•Vasodilation
•Room temp
•Open abdomen
24
Damage Control
Alan I. Frankfurt, MD
25
Damage Control Resuscitation
• Resuscitative
measures that are
taken to prevent
physiologic exhaustion
(lethal triad) and
patient death.
Alan I. Frankfurt, MD
26
Damage Control Resuscitation
“5 H’s”
• Hemorrhage control
▫ OR timely fashion
• Hypotensive resuscitation
▫ Systolic BP=80 torr
 Ischemia vs. Popping a clot
• Hemostatic resuscitation
▫ Early plasma administration
 Fibrinogen/EG
▫ Minimize crystalloid
administration
▫ MTP
 1:1:1:(1) ratio
 riaSTAP
 TXA
 rF7
▫ RBC
 Hct 35-40%
▫ Platelets
 >100,000
• Homeostasis
▫
▫
▫
▫
Hypothermia
Acidosis
Ionized calcium
Labs
 INR/TEG
 ABG
 Base deficit
 Lactate
 CBC/Chem 7/platelets
 Fibrinogen
• Hypnosis: having our cake and
eating it too
▫ DCA
 Hypotension
 Vasoconstriction/Hypovole
mia
 Hypotension
 Vasodilatation/Euvolemia
27
Massive Transfusion Protocols
Alan I. Frankfurt, MD
28
Alan I. Frankfurt, MD
Massive Transfusion Protocol Version 1.0
Composition and Implementation
Shipment #
pRBCs
Plasma
1
5
5
2
5
5
3
5
5
4
5
5
Platelets
1 apheresis
1 apheresis
Role of : rF7a vs. TXA
MTP initiation: Bleeding and in hypovolemic shock
•
•
•
•
Not sure what is bleeding.
How long it will take to stop the bleeding.
What it is going to take to stop the bleeding.
When you’re bleeding too fast to wait for the labs.
29
Massive Transfusion Protocol Version 2.0
(Modify based upon severity of blood loss & institutional capabilities)
Last in,
first out:
<14 days
old
Early
plasma
Day 1-3
Plasma
ratio vs.
Plasma
deficit
Fibrinogen
vWB
F8
F13
Fibronectin
Europe vs.
USA
Lyophilized
fibrinogen
Antifibrinolytic
Fibrinogen is the
first factor to reach
critically low levels
during massive
bleeding
Is there a role
for rF7 in
massive
hemorrhage?
30
Alan I. Frankfurt, MD
Advanced Trauma Life Support (ATLS)
1.Continue IV
crystalloids and
2.pRBC
2 large bore PIV
Hemorrhaging
patient
Evidence of shock:
Pulse > 100/min
SBP < 100 torr
Shock persist
2000 cc
crystalloid fluids
to normalize BP
Transient
responders
> 100cc/min
blood loss
Frequent labs
(guide FFP and
platelet
administration)
31
Advanced Trauma Life Support (ATLS)
Hemorrhage resuscitation circa1980
• Crystalloid infusion:
▫
▫
▫
▫
Dilution clotting factors
Does not carry oxygen
Hypothermia
Worsening of bleeding
• pRBC administration:
▫ Signs of shock
• Playing catch up with coagulation
▫ FFP/Cryoprecipitate
 Driven by PT/PTT lab test
 20” lab result turn around
 20 minutes to dethaw
▫ Continued crystalloid fluid
administration and pRBC
▫ Platelets
Iatrogenic driven
coagulopathy
32
Alan I. Frankfurt, MD
Bloody Vicious Cycle
of Biblical Proportion
Hemorrhage
Resuscitation
with IV fluids
Coagulopathy
Hemodilution
Hypothermia
Acidosis
33
Breaking the Bloody Vicious Cycle
Damage Control Resuscitation“5 H’s”
• Hemorrhage control
▫ OR timely fashion
 Definitive hemorrhage control
• Hypotensive resuscitation
▫ Systolic BP=80-90 torr
 “Tolerate” shock vs. Popping clots
• Hemostatic resuscitation
Year 2000 (limited trauma
centers)
DCS
DCR:
“WB equivalent”
Early plasma
▫ Blood products early and often: Plasma
 Prevention of coagulopathy
▫ Minimize crystalloid administration
• Homeostasis
▫ Hypothermia
▫ Acidosis
34
Keeping Fluids Going Into
our Patients Looking Like
Blood Coming Out During a
Hemorrhage Resuscitation
Is There a Role for Whole
Blood in Civilian
Hemorrhage Resuscitation?
35
Alan I. Frankfurt, MD
Civilian Use of Whole Blood is Limited
• Military: (Fresh Warm) Whole
Blood
▫ Warm: 20-24 C*
▫ Fresh if < 24 hours old
▫ Walking blood bank
 Pre-tested
• Civilian: Whole Blood
≠
▫ Cold: 1-4C*
▫ Formal testing for
transmissible disease.
 72 hours
▫ Licensed for 21 days
▫ Difficult to obtain from blood
centers
 Fractionation of WB
▫ Efficient use of blood
product
▫ Financial
36
Is the MTP (1:1:1) the Modern Day
Whole Blood Equivalent:
• Crystalloid fluid
▫ Poor volume expander
▫ Carries no oxygen,
coagulation factors
• What if we administer the
fractionated parts of WB
as a 1:1(:1) ratio?
▫ Volume
▫ Oxygen delivery
▫ Coagulation factors
37
Origin of the (Civilian) MTP 1:1:1
transfusion ratio
Alan I. Frankfurt,
MD
•
•
•
John Hess, MD; Richard Dutton, MD: From ISR to Maryland STU
2000
Transfusion Vol. 44, Issue 6 pp. 809-813, June 2004
•
Blood transfusion rates in the care of acute trauma
John J. Como, Richard Dutton, Thomas M. Scalea, Bennette B.
Edelman, John R. Hess
Transfus Med Rev. 2003; 17: 223-31
•
•
•
Treating coagulopathy in trauma patients
• Armand R., Hess JR
38
Alan I. Frankfurt, MD
Origin of the MTP 1:1:1 Ratio
Maryland Shock Trauma, Baltimore Md.
• Early plasma administration
▫ Dr. Como et al.(Transfusion 2004);
 “Blood transfusion rates in the care of acute trauma”
 8% (479/5645 trauma admissions 2000) received RBC transfusion
 3% > 10U RBC/24 hours
▫ 90% ultimately received plasma
 5645 trauma admissions to Shock Trauma Center in 2000
 5219 units of RBC
 5226 units of FFP
 RBC
 FFP
1:1 ratio
ED
ICU
 Lack of immediate availability of plasma
39
Alan I. Frankfurt, MD
Birth of the Massive Transfusion Protocol (MTP)
▫ Question:
 “Are we using FFP in the ICU to rescue an iatrogenic (ATLS) induced
coagulopathy from the ED/OR resuscitation?”
 “What if we gave the FFP at the same time as the pRBC in patients
with massive hemorrhage?” (personal communication, Richard
Dutton, MD)
▫ Drs. Dutton, Hess & Holcomb
 1:1 RBC/FFP in ED
 Baltimore, Md. 2000
 Bagdad, Iraq 2005
40
Is the Massive Transfusion Protocol
1:1:1 ratio the WB equivalent?
(Kinda)
1 unit pRBC:
1 unit FFP:
1 unit (apheresis) platelets
=
1 unit “whole blood”
equivalent?
41
Alan I. Frankfurt, MD
MTP 1:1:1
“Hemotherapy induced hemodilution”
Whole
Blood
500cc
Temp
Hct
Platelets
Coagulation
Factor %
Fibrinogen
Amount of
anticoagulant
and additives
37* C
3850%
150,000
to
400,000
100%
1500 mg
63cc
-30-0*C
29%
88,000
65%
950 mg
205cc
WFWB
Component
Therapy
680cc
1 unit:
PRBC,
FFP,
Platelet
42
Alan I. Frankfurt, MD
MTP 1:1:1
“Hemotherapy induced hemodilution”
Whole
Blood
500cc
Temp
Hct
Platelets
Coagulation
Factor %
Fibrinogen
Amount of
anticoagulant
and additives
37* C
3850%
150,000
to
400,000
100%
1500 mg
63cc
-30-0*C
29%
(10%
)
26%
88,000
(30%)
55,000
65%
750 mg
205cc
WFWB
Component
Therapy
680cc
1U:
PRBC,
FFP,
Platelet
43
Alan I. Frankfurt, MD
MTP 1:1:2
“Hemotherapy induced hemodilution”
Whole
Blood
500cc
Temp
Hct
Platelets
Coagulation
Factor %
Fibrinogen
Amount of
anticoagulant
and additives
37* C
3850%
150,000
to
400,000
100%
1500 mg
63cc
-30-0*C
29%
88,000
65%
750 mg
205cc
WFWB
Component
Therapy
680cc
2PRBC,
1FFP,
1Platelet
40%
55,000
1:1:2
36%
37,000
1:1:1
26%
55,000
52%
Storage related losses
52%
65%
Any crystalloid
administered will
further dilute all 3 blood
components.
44
PROPPR Trial:
JAMA 2015, 313(5): 471-482
Study Question
Alan I. Frankfurt, MD
In patients with severe trauma and predicted to require
massive transfusion, does the use of a transfusion
protocol using a 1:1:1 ratio of plasma to platelets to red
blood cells (RBCs) compared to 1:1:2 improve mortality?
45
Alan I. Frankfurt, MD
PROPPR Trial: Results
• 24 hour/30 day all cause mortality
▫ No difference between 1:1:1 vs 1:1:2
• Reduced mortality in 1:1:1 group from
exsanguination in the first 24 hours.
• The Kaplan-Meier survival curves for a 3 hour
endpoint:
▫ Statistically significant mortality difference between
the two groups.
 This was not one of the allowed primary outcomes.
• Our current definitions of massive transfusion are
outdated.
▫ Critical Administration Threshold (CTA): 3 units/hour
46
Cryoprecipitate
1:1:1:1(?)
Alan I. Frankfurt, MD
D
U
D
1United
3 Washington
States Army Institute of Surgical Research, Fort Sam Houston, TX 78234-6315, 2San Antonio Military Medical Center, Fort Sam Houston, TX 78234
University in St. Louis, St. Louis, MO 63108, 4 Baltimore CSTARS, R. Adams Cowley Shock Trauma Center / University of Maryland School of Medicine,
Baltimore, MD 21201, 5 Nellis Air Force Base, NV 89191
ED
I CAT I O
TY
E
Andrew P. Cap1, Philip C. Spinella1,3, Nichole K. Ingalls5, Christopher E. White1,2, Alejandra G. Mora1, Heather F.
Pidcoke1, Nicolas Prat1, Lorne H. Blackbourne1, Joseph J. DuBose4
N
ROTEM Radically Alters Transfusion in Combat Casualty Resuscitation
S ERV
IC
MTP RATIO DRIVEN
RESUSCITATION
50
Percent of subjects
ROTEM DRIVEN RESUSCITATION
40
x5
30
PRE
POST
20
10
0
pRBC
FFP
Cryo
*There were 16 and 15 transfused patients respectively in each period that did not receive RBC.
PLT
D
U
D
1United
3 Washington
States Army Institute of Surgical Research, Fort Sam Houston, TX 78234-6315, 2San Antonio Military Medical Center, Fort Sam Houston, TX 78234
University in St. Louis, St. Louis, MO 63108, 4 Baltimore CSTARS, R. Adams Cowley Shock Trauma Center / University of Maryland School of Medicine,
Baltimore, MD 21201, 5 Nellis Air Force Base, NV 89191
ED
I CAT I O
TY
E
Andrew P. Cap1, Philip C. Spinella1,3, Nichole K. Ingalls5, Christopher E. White1,2, Alejandra G. Mora1, Heather F.
Pidcoke1, Nicolas Prat1, Lorne H. Blackbourne1, Joseph J. DuBose4
N
ROTEM Radically Alters Transfusion in Combat Casualty Resuscitation
S ERV
IC
Conclusions
1. DCR utilizing a 1:1:1 ratio driven MTP may
underestimate the need for cryoprecipitate
and platelets
2. ROTEM driven resuscitation more
closely approximated a 1:1:1:1
transfusion ratio.
*There were 16 and 15 transfused patients respectively in each period that did not receive RBC.
49
How Much Difference Does Additional
Cryoprecipitate and Platelets Make?
2003 Iraq
2012 Afghanistan
• Mortality: >20%
▫ No platelets and
cryoprecipitate available in
theater
• Mortality: <10%
▫ Greater cryoprecipitate and
platelets availability.
Evolving MTP
1:1:1:1
 ISS scores higher in
casualties in 2012 than those
in 2003.
50
Alan I. Frankfurt, MD
Putting it all together
Massive Transfusion Protocol
THR Dallas
51
Alan I. Frankfurt, MD
MTP & Uncontrolled Hemorrhage
PYXIS/L&D resuscitation
BLOOD BANK resuscitation
• TXA
▫ 1-2 grams IV slowly
▫ 1 gram IVPB over 8 hours
• riaSTAP
▫ 2-4 grams IV
• O negative pRBC
• (+/- Liquid Plasma)
• iSTAT
▫ Hgb; ABG/VBG; ionized Ca
▫ Lactate
• Round 1 MTP
▫ O negative pRBC
▫ AB negative FFP
▫ (+/- cryoprecipitate)
▫ (+/- platelets)
• Round 2 MTP
▫ Type specific pRBC
▫ Type specific FFP
▫ (+/- cryoprecipitate)
▫ ( +/- platelets)
52
Rethinking the Acceptable Hematocrit
and Platelet marginalization during
massive hemorrhage
• Higher Hct increased platelet
interaction with the endothelium.
• Platelet concentrations along the
endothelium remains almost x7
that of the average blood
concentration.
Uijttewall WS et al., Am J Physiol
1993, 264: H1239-H1244
53
Maintain a Hct 35%:
Shear stress & platelet margination
Alan I. Frankfurt, MD
35%
21%
Hardy JF et.
Can J Anaesthe 2006, 53: S40-S58
54
HCT & Platelet count:
Synergistic Effect on Clotting
Hct level
Platelet count
Percentage platelet
interaction with
subendothelium
Hct =40%
200,000
19.3 +/- 7.8
100,000
7.5 +/- 2.8
50,000
2.5 +/- 0.8
200,000
3.3 +/- 4.0
100,000
2.8 +/- 0.7
50,000
0.6 +/- 0.2
Hct=20%
Transfusion 1994, Vol. 34, No.6
55
Plasma
Alan I. Frankfurt, MD
56
Alan I. Frankfurt, MD
Thawed
FFP/FP
<24 hrs
Thawed
plasma 24
hrs-5 days
Frozen: “FFP” < 8 hrs;
“FP” < 24 hrs
RBC
Plasma
Never Frozen:
“Liquid
Plasma”
Thawed
shelf life:
5 days
Platelets
Shelf life: 26 days
57
Plasma deficit vs. Plasma ratio
Plasma ratio:
pRBC:FFP
Vs.
Plasma deficit:
(Total RBC)-(Total FFP)
58
BLOOD PRODUCT USE IN TRAUMA RESUSCITATION:
Plasma deficit versus plasma ratio as predictors of
mortality in trauma
Andreas R. de Biasis, Lynn G. Stansbury, Richard P. Dutton, Debra M. Stein, Thomas Ml
Scalea, and John R. Hess
• Plasma deficit
▫ (Total RBC)-(Total FFP)<2
 Mortality was related to plasma deficit, not plasma ratio
 0-3 hours post injury
 Early plasma availabililty
• Gold:Red:Gold:Red…..
• Simultaneous administration of plasma along with pRBC
• Thawed plasma/Liquid (never frozen) plasma in ED/L&D
• Lyophilized plasma
• Unavailable in USA
• ? Lyophilized fibrinogen
59
Future Developments
Lyophilized FFP
Alan I. Frankfurt, MD
• Logistic requirements:
▫ Storage
 No refrigeration required
 Room temperature
 Easily transported
▫ Quickly reconstituted
• Rapid volume expansion
▫ Rapid 1:1 pRBC/FFP ration obtained
• Contains all clotting factors
• Shelf life
▫ 2 years
 Clotting factor
• ABO considerations
▫ No blood typing required
• French military medicine
▫ 1994
• FDA: compassionate approval for the US military
▫ Special forces
60
Plasma & the Endothelium
(The other 50% of making a strong clot)
Alan I. Frankfurt, MD
61
Alan I. Frankfurt, MD
Role of the Endothelia Glycocalyx and
Resuscitation Fluids Choice
• Extremely fragile
• Composition
▫ Glycoproteins
▫ Proteoglycans
• Key determinants of
membrane permeability in
various vascular organ
systems.
• 0.2-1.0 mm thickness
• 1000 cc plasma embedded in
the EG.
62
Alan I. Frankfurt, MD
63
Plasma: 1000 different proteins
Coagulation factors
Immunoglobulin
Albumin
 Coagulation
 Procoagulant
 Anticoagulants
 Overall health of the endothelium
 Resuscitation/Repair of the EG

Hemorrhagic shock
64
Alan I. Frankfurt, MD
Early Plasma vs Crystalloid
Effects of Resuscitation Fluids on the Integrity of the
Endothelial Glycocalyx:
65
Review:
Transfusion Protocol Version 2.0
We are here
66
Platelets
Alan I. Frankfurt, MD
67
Platelets
Platelet Storage: “One size does not fit all”
Decisions that shaped the policy on PLT storage temperature
Platelet Aggregation
2
hours
Flowing
disc-shaped
platelet
Rolling
ball-shaped
platelet
22*C
Scanning electron micrograph
of discoid, dormant platelets
Hemisphere-shaped
platelet
Spreading
platelet
FIRM, BUT REVERSIBLE
ADHESION
IRREVERSIBLE
ADHESION
Activated, aggregating platelets
illustrating fibrin strands
Adapted from: Kuwahara M et al. Arterioscler Thromb Vasc Biol 2002; 22: 329–34.
69
Platelet Storage:
Effects of temperature
• 22*C
▫ 5 day life span
▫ 1-2 hours to “activate”
• 4*C
▫ 48 hour life span
▫ Immediately “activated”
 Refrigeration of platelets abandoned in 1970’s.
• Logistics vs. Patient requirements
70
Historical perspective
on platelet storage
2 patient populations
with different
platelet
requirements
Patient population:
Trauma, OB(PPH,
Abruption, Accreta)
Requirement:
Immediate
bleeding problem
Patient population:
Patients receiving
chemotherapy
Immediate clot
formation &
hemostasis
(activated platelets)
Requirement:
prophylaxis against
future bleeding
4*C platelets
Immediately
primed
Survival time:
hours
Long circulation
time
(platelet survival)
22*C platelets
1-2 hours for priming
Survival time:
days
71
Fibrinogen & Clot strength
The 80% Solution
Non pregnant state: 200-400 mg%
Pregnant state: 400-700(1000) mg%
72
Alan I. Frankfurt, MD
Fibrinogen (F1) is the Weak Link
in the Clotting System
• Hemorrhage
▫ Rapid depletion of F1 (fibrinogen)
• Clot formation
▫ Fibrin precursor
• Platelet interaction
▫ Activation
▫ Binding
▫ Aggregation
73
What is the Optimal Fibrinogen
Threshold for Optimal Clot
Formation?
74
Plasma Fibrinogen levels & Optimal
Hemostasis
• 150-300 mg/dl
▫ Linear increase in clot
strength with increasing F1
levels.
• 625 mg/dl
▫ Clot strength equal to whole
blood
 Pregnancy level > 28 weeks
• 1000 mg/dl
▫ Clot strength equal to x3
whole blood
Clot strength vs.
Hypercoagulability
Nielsin V, Levy J: Fibrinogen and Bleeding: Old Molecule-New Ideas
Anesth Analg 2007; 105: 902-3
75
Sources of Fibrinogen:
• Fresh frozen plasma (FFP)
• Cryoprecipitate
• Fibrinogen concentrate
▫ riaSTAP
 1 grams of riaSTAP/bottle
 50cc sterile water
▫ US “off label”
 Acquired hypofibrinogenemia
▫ Europe
 Eliminated cryoprecipitate
International Journal of Obstetric Anesthesia
(2010) 19, 218-234
Volume considerations &
Preparation time.
Allogenic blood products
Thawing
Typing (ABO if possible)
Infection
76
Fibrinogen Concentrate
RiaSTAP
• Human donor
▫ Pooled plasma product
 Lyophilized
• Viral inactivation
• Predictable mg
content/vial
▫ 1000 mg/vial
• No thawing required
▫ Pyxis storage
• ? Thrombogenic potential
77
Tranexamic Acid (TXA)
Lysine analogue antifibrinolytics
Resuscitation in a drawer (pyxis)
Mode of Action of Lysine Analogue Tranexamic Acid (TXA)
Mannucci PM, Levi M. N Engl J Med 2007;356:2301-2311
TXA
80
Alan I. Frankfurt, MD
CRASH-2 Study
81
Alan I. Frankfurt, MD
Resuscitation in a drawer
• Factor 1 (fibrinogen)
•
•
•
•
•
▫ riaSTAP
TXA
rF7a
Combat gauze
Calcium
Factors: 2, 7, 9, 10
Located in the ED/L&D
unit pyxis
▫ PCC (prothrombin concentrate complex)
 Vitamin K dependent factors
▫ Factor 8/vWB
 Endothelium
▫ Lyophilized plasma
▫ Platelets
 Factor 5
 Entegrion
 Lyophilized platelets
Future
82
Alan I. Frankfurt, MD
Citrate Intoxication & “ionized
"Calcium
• Citrate intoxication
▫ 90% citrate
 FFP & Platelets
▫ Calcium & Magnesium
• Rate of transfusion, not total blood products
• Measured calcium vs. Ionized calcium
▫ Total calcium is normal even when ionized
calcium of critically low
 Total calcium measures both calcium bound to
citrate and free, ionized calcium
83
Summary
Alan I. Frankfurt, MD
84
Alan I. Frankfurt, MD
Damage control:
Maintain or re-establishing a
survivable physiologic state
Damage Control
Surgery
Hemostasis
(definitive)
If you need to be in
the OR, get there
quickly
Damage Control
Resuscitation
Hypotension
(permissive)
Avoid popping
clots
Hemostatic
resuscitation
Clotting factors early
and often:
MTP
Plasma deficit
Pharmacologic
Damage Control
Anesthesia
Homeostasis
Hypnosis
Keep the patient
warm
Get them
anesthetized
85
Damage Control
Resuscitation Goals
•
Fibrinogen
▫
•
>250-400 mg%
 FFP
 Cryoprecipitate
 risSTAP: fibrinogen concentrate
Hct
▫ 35-40%

•
Platelet concentration
▫
•
>100,000
Plasma
▫
Plasma deficit < 2

▫
▫
▫
•
Endothelial glycocalyx
Coagulation factors
Anticoagulants
Base deficit & Lactate
Temperature
▫
•
Early plasma administration
pH
▫
•
Platelet interaction
Active warming measures
Ionized calcium
▫ 4 will get you 4

Hypotension unresponsive to volume
86
Questions??
Alan I. Frankfurt, M.D.
F7040@aol.com