Transcript Transfusions in Surgery

Transfusions in Surgery
Dr. Carolyn Faught
November 28, 2006
FACT
• Approximately 60% of all red cell
transfusions are administered to surgical
patients
• Therefore need to understand indications
and risks of transfusion
Main Objectives
• Be aware of the adverse effects of transfusion
• Discuss “transfusion triggers” in surgical patients
• Treatment of massive transfusion
• Indications for recombinant FVIIa in surgical
patients
Blood Components
• Blood components made by physical separation
from whole blood:
–
–
–
–
Packed red blood cells (PRBCs)
Platelets
Plasma ( FFP, cryoprecipitate)
Granulocytes
• Blood derivatives:
– Fractioned, virally inactivated product (ie. albumin,
IVIG)
– Recombinant products (VIII, IX, VIIa)
Universal donor/
Universal recipient
• Group O RBCs: universal donor, can be given to
patients of all blood groups, because no A or B
antigens on surface of RBCs
• Group AB person is the universal recipient for RBCs,
because has no anti-A or anti-B antibodies in plasma
• Group AB plasma can be given to all recipients, as it
has no anti-A or anti-B antibodies
• Emergency (uncrossed) products = O neg RBCs
and AB plasma
• Still best to give Group specific blood
Blood Products:
Universal leukoreduction of
all blood products in Canada
• ‘third generation’ filters to remove WBCs
from blood (leukoreduction) to less than
5x106 WBC/bag of RBCs
• Leukoreduction reduces CMV
transmission, HLA alloimmunization,
febrile non-hemolytic transfusion
reactions
Adverse Effects
of Transfusion
• Transfusion Reactions
– Infectious
– Non-infectious
• Immunologically mediated
• Non-immunologic
– Immediate
– Delayed
Infectious risks of transfusion
•
•
•
•
•
Bacterial contamination of platelets 1:40,000*
HBV - 1/250,000
HIV - 1/1,900,000
HCV - 1/1,800,000
HTLV1 - 1/1,000,000
Less clear
• CJD (Creutzfeldt-Jakob disease)
• West Nile 1/4,000
Non-infectious risks
•
•
•
•
•
•
Febrile reactions
Allergic/anaphylactoid reactions
Hemolytic reactions – 1/20,000
Volume overload
Acute lung injury (TRALI)
Serologic sensitization
– Alloimmunization to red cell antigens (delayed
hemolytic transfusion reaction)
– Graft-versus host disease
– Platelet refractoriness, post-transfusion purpura
• Immunomodulation - ? Increased risk of
infection, cancer recurrence
TRALI
•
•
•
•
Transfusion-Related Acute Lung Injury
Non-cardiogenic pulmonary edema after transfusion
Incidence up to 1:5000 transfusions
Antibodies in donor plasma against HLA or
neutrophils react with recipient leukocytes
• Leukoagglutination in lungs, increase in vascular
permeability, fluid enters alveolar spaces
• Need to identify, to remove donor from donor pool
TOH Blood Conservation Program
• 800 patients a year assessed at Civic
• Best candidates are hips, backs, prostate, some
gynecologic surgery
• Patients assessed 4 wks prior to surgery so they
can benefit
• Liberal use of Epo and iron
• Autologous or 2 unit collection with TRIMA
• If Hb > 130 g/L, no Epo
• If Hb < 125-130 g/L, no autologous donation
Transfusion Rates Across Canada
• Locally, transfusion rates are ~ 45% in
hips, 35% in prostate, 25% in knee
• Across Canada:
– Cardiac: 43.8% female 65% vs male 37%
– Hip: 34.4%
– ICU (post-op and trauma): 36.9%
Can J Anesth 2005: 52(6); 581-590
Transfusion Practices in Surgery
• Little evidence to support age-old practice of
keeping Hb > 100g/L
• General trend towards conservative RBC
transfusion practices in elective circumstance
• TRICC Trial largest RCT showed RBC
transfusion threshold of 70 g/L was as safe as
100 g/L in terms of morbidity and mortality in the
critical care setting
Hebert, P.C., NEJM 340(6), 1999;409-418
Red blood cell transfusion practices amongst
Canadian anesthesiologists: a survey
• A threshold above 70 g/L chosen by 48% for general
surgery, 56% for orthopedic surgery and 9% for vascular
surgery
• History of coronary artery disease associated with
threshold of 100 g/L
• Very young age associated with threshold of </= 60 g/L
• Conclusion: general adoption of TRICC trial even in
surgical patients
Can J Anesth 2006: 53(4); P 344-352
Platelet storage
Fresh Frozen Plasma (FFP)
• Fresh Frozen Plasma
contains the clotting
factors necessary for the
hemostatic process
• Plasma also has volume
expansion and oncotic
properties
• Typical adult dose = 10-20
ml/kg, 4-6 units
• Unlikely to be beneficial if
PT and/or aPTT <1.5x
normal
Massive Transfusion (MT) and
Coagulopathy
• Definition: replacement of one blood mass in a
24 hour period
• More practical definition: transfusion of four or
more PRBCs within one hour or replacement of
50% blood volume in three hours
• Uncontrolled bleeding causes 40% of deaths in
severe trauma
Hemorrhage
• Symptoms relate to amount lost
• Blood volume (adult) = 75 ml/kg
= 5 liters
• 10% loss:
few symptoms
• 20% loss:
postural hypotension
• 40% loss:
shock
• 50% loss:
irreversible shock
Massive Transfusion and Coagulopathy
• Hypothermia – slows activity of coagulation
cascade, increases fibrinolysis and alters
platelet function
• Dilutional coagulopathy – exacerbated by initial
volume contraction, fluid resuscitation and
transfusion of factor and platelet-deficient
PRBCs
• Fibrinogen < 1.0 g/L when blood loss 142%
• DIC
The contribution of red cells to
hemostasis
Disseminated Intravascular Coagulation
• Hemostatic defects related to the exaggerated
generation of thrombin and fibrin and the
excessive consumption of platelets and
coagulation factors
• Low incidence in elective surgery
• In trauma patients:
• Due to degree of tissue trauma and tissue
anoxia
• 40% incidence in brain injury, 25% without
head injury
Disseminated Intravascular Coagulation
• Incidence of coagulopathy 98% if all of the
following:
pH less than 7.10
Temperature less than 34C
SPB less than 70 mm Hg
Injury severity score greater than 25
Ferrara A, J Trauma 1997;42:857-61
Management of Coagulopathy in MT
• PT/PTT increase when factors V, VIII and
IX < 50%
• Both PT/PTT increased if fibrinogen is low
• PT or PTT ratio ≥1.8 means factors are <
30% and leads to high rate of bleeding
• No prophylactic regimen of FFP/platelets
concentrates has been shown to be
effective in MT
Management of Coagulopathy in MT
• Correct hypothermia
• Correct low Hb – optimum Hb in MT to maintain
hemostasis unknown but probably higher than
required for O2 delivery
• Correct markedly prolonged INR/PTT with FFP
( ratio > 1.5)
• Typical use 4-6 units (800-1500 ml) in average
adult or 10-20 ml/kg;
– gross underestimate in severely depleted,
actively bleeding, hypothermic patient and
should be 1-1.5:1 ratio of FFP to PRBCs
Management of Coagulopathy in MT
• If fibrinogen < 1.0 g/L despite FFP
administer cryoprecipitate: 10-20 units
• Platelets for decreased platelet count with
clinical coagulopathy
• Consider rFVIIa if above not sufficient to
control bleeding
J.F.Hardy,Can J Anesth 2004;51(4):293-310
Recombinant factor VIIa (Niastase) Background
• Recombinant factor VIIa developed to treat
hemophilia patients with inhibitors
– By-passing agent in patients not responding
to factor replacement
• Recombinant factor VIIa used for treatment and
prophylaxis of hemophiliacs with inhibitors
• Use expanded to other bleeding patients
Factor VIIa in Normal
Hemostasis
II
X
TF VIIa
Xa
VIII/vWF
Va
IIa
VIIIa
TF-Bearing Cell
TF VIIa
IXa
V
IX
X
Va
Platelet
II
Xa
VIIIa
Va
IXa
Activated Platelet
VIIa
Va
IXa VIIIa
Xa
IX
X
II
IIa
Fibrin
Clot
IIa
Hoffman M, et al. Blood Coagul Fibrinolysis. 1998;9(suppl 1):S61-S65.
FVIIa – FVIII and FIX Independant
II
X
TF VIIa
Xa
Va
IIa
TF-Bearing Cell
TF
V
Va
Platelet
II
X
VIIa
Xa
Va
Activated Platelet
IIa
Fibrin
Clot
Hoffman M, et al. Blood Coagul Fibrinolysis. 1998;9(suppl 1):S61-S65.
High-Dose FVIIa Enhances IIa
Generation Without TF
Relative IIa
generation
4
Normal
Hemophilic
3
2
1
0
0
1
10
100
[FVIIa] (nM)
Monroe DM, et al. Br J Haematol 1997;99:542-547.
Niastase: Licensed Indications
• Treatment of bleeding in hemophilia
patients with inhibitors
• Surgical management of hemophilia
patients with inhibitors
• Congenital factor VII deficiency (USA)
• Glanzmann’s Thrombasthenia (UK)
Pharmacology of Recombinant
Factor VIIa
• 50,000 MW molecule with t ½ of 2 hrs
• Normal concentration of factor VII: 10-20
nm
• 1% of factor VII circulates in activated form
• Standard dose in hemophilia 90 ug/kg
– maximum concentration 50 nm
– 500 x normal concentration of VIIa
• Dosing q 2-3 h to maintain hemostatic
levels
Expanded Use of VIIa
•
•
•
•
•
•
•
•
•
•
•
Factor VII deficiency
Other factor deficiencies (FXI, acquired FX)
Von Willebrand’s disease
Thrombocytopenia
Platelet function defects
Reversal of oral anticoagulation
Coagulopathy of liver disease
Surgical bleeding
Surgical prophylaxis
Intracranial hemorrhage
Trauma
VIIa in Partial Hepatectomy:
Placebo Controlled RCT
Design:
• RCT comparing 20, 80 ug/kg or placebo in noncirrhotic patients with 2nd dose for OR > 6 hrs
• Monitored for bleeding for 7 days
Results:
• 185 patients
Lodge et al. Hepatology 2002;36:Abst177
VIIa in Partial Hepatectomy
Placebo
Blood loss
1000
% transfused 37%
Thrombosis
3
20 ug/kg
800
41%
3
Trend but no significant difference
80ug/kg
700
25%
3
Effect of rVIIa on Perioperative Blood Loss
During Prostatectomy Friederich. Lancet 2003
Design
• 36 pts randomized to placebo or rVIIa (20 ug/kg or 40
ug/kg)
• Followed for 10 days post-op
Results
Placebo 20
40
Blood loss
(ml)
RBC units
% transfused
OR time (min)
ug/kg
ug/kg
2688
1235*
1089*
1.5
58%
180
0.6*
38%
126
0*
0%*
120
RecombinantVIIa for Adjunctive
Hemorrhage Control in Trauma
Patients
• 7 patients with coagulopathic bleeding treated under
compassionate use program
• Age 17-75
• No atherosclerosis/thromboembolic disease
• Received 20-70 units RBCs + FFP and platelets
Intervention
•
1-3 doses of 60-120 ug/kg of rVIIa
Matinowitz et al. J Trauma 2001;51:431
Recombinant VIIa for Adjunctive
Hemorrhage Control in Trauma
Results
• Bleeding stopped/reduced in all patients
• Further transfusions limited to 1-2 units of
RBCs
• Significant shortening of coagulation tests
• 4 of 7 patients survived
• No thrombotic events
Multicentre RCT of rVIIa in
Trauma
• 280 pts with blunt or penetrating trauma
• All patients receive 3 doses
– 200 ug/kg followed by 100ug/kg 1h and 3h later
trauma
Arrive
at ER
randomize
0
6
rVIIa
8
48h
30d
48h
30d
placebo
Units of RBCs
Transfusion
ICU/Hosp LOS
Survival
Adverse Events
Boffard et al. J Trauma. 2005: 59: 8-15
Multicentre RCT of rVIIa in Trauma
• Non significant reduction in RBC units transfused
– Significant reduction in RBC units (2.6 units)
and incidence of massive transfusion (14% vs
33%) in blunt trauma when early deaths
excluded
• Similar overall survival - 25% vs 30%
– Composite outcome incl organ dysfunction
showed increased trend favouring rVIIa (29 vs.
43%)
• No difference in adverse events
Boffard et al. J Trauma. 2005: 59: 8-15
Complications Associated with Factor
VIIa
FDA report of adverse events from trials and
voluntary reporting from 1999-2005
• 220 thromboembolic complications
– 193 in non-hemophiliac patients
• 129 arterial thrombosis
• 103 venous thrombosis
• Approx. 50% of reports within 24 hrs of
infusion
• 43 of 67 deaths reported secondary to
thrombosis