Cardiopulmonary Bypass: Hematologic effect

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This presentation was compiled using articles in
medical journals and textbooks, and therefore is
thought to be accurate to the best of the
authors knowledge. This presentation is to be
used as a guide to better understand the specific
disease(s) and understand their treatment. It is
not in any way meant to imply that the described
procedures are the sole means of treatment for
the entity . PLEASE VERIFY ANY AND ALL
FORMULAS AND TREATMENT SCHEDULES WITH YOUR
LOCAL CLINICIANS BEFORE USING THEM THIS
PRESENTATION IS FOR EDUCATIONAL PURPOSE ONLY
for any additional information please email the
author at atorloni_at_cox.rr.com
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Cardiopulmonary Bypass Effects on Coagulation

• Sergio Torloni MDMedical Director
• Transfusion Service Therapeutic Apheresis
• Inova Fairfax Hospital
• Falls-Church - Virginia

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What do platelets do anyway ?
? Torloni MD 1998
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Endothelium
? Torloni MD 1998
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(No Transcript)
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Kallikrein
VWF
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GP1a (collagen adhesion)
Subendothelial matrix
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Collagen Receptor
Exposed Endothelium
Fibrinogen receptor GPIIb IIIa
von Willebrandt receptor
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Fibrinogen
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Platelet Recruitment
AA
ADP
Tx A2
Cyclooxygenase
promotes Platelet aggregation in the presence
of fibrinogen
ADP
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How and where does this all fit in with the
infamous Clotting Cascade ?
VII
XII
IX
X
XIII
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Intrinsic Pathway
TF is expressed on almost all non vascular cells.
XII
XIIa
Extrinsic Pathway
XI
XIa
IX
IXa
VIIa
VII
TF
VIII
VIIIa
Xa
X
Thrombin
Prothrombin
XIII
Fibrinogen
Fibrin
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XII
XIIa
XI
XIa
acts on IX (bound to plt)
Contact activation phase
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XI
XII
Ca
VIII
IX
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VIII
Ca
IX
X
Ca
V
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(No Transcript)
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XIII
XI
XII
Polymerization
VIII
IX
Ca
Fibrin Clot
V
X
Ca
I
II
Ca
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Intrinsic Pathway
TF is expressed on almost all non vascular cells.
Extrinsic Pathway
TF
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What keeps blood from clotting ?
F A C T O R S
Anti Thrombin III
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What keeps blood from clotting ?
Inactivated Clotting Factor
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Normal
Heparin
Anti Thrombin III
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Clot Lysis
Antiplasmin
Plasminogen
Neutralized Plasmin
Plasmin
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Clot Lysis
Plasminogen

• Circulates in the inactive form
• Converts to Plasmin when activated

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XII
XIIa
XI
XIa
IX
IXa
VIIa
VII
VIIIa
VIII
Xa
X
Thrombin
Prothrombin
XIII
Fibrinogen
Fibrin
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Antiplasmin and Plasmin
plasmin
antiplasmin
Antiplasmin Plasmin thousands 1
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Antiplasmin and Plasmin
plasmin
antiplasmin
Antiplasmin Plasmin 10.000 1
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CLOT
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CLOT
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Fibrin Split Products
LYSED CLOT
FSP can interfere with polymerization of fibrin
(whimpy clots)
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Intrinsic Pathway
TF is expressed on almost all non vascular cells.
Extrinsic Pathway
TF
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Coagulation Disturbances

• Hemodilution
• Platelet dysfunction
• Fibrinolysis
• Hypothermia
• Shear stress

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Perioperative Hemodilution
Hematocrit decreases to 25-30 (sometimes
less !)
- Laminar flow disrupted - Dilution of
clotting factors - Bleeding during hemodilution
aggravates picture
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Platelet disfunction during bypass
1 - Plasma proteins deposit on the tubing wall
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So what happens during bypass ?
1 - Fibrinogen deposits on the tubing wall
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So what happens during bypass ?
Platelets bind to fibrinogen on tubing wall.
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SEM Pictures by Torloni MD
SEM Pictures by Torloni MD
Normal Platelets 18.000 X
Activated Platelets 32.000 X
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Torloni MD
Torloni MD
Platelet Degranulation TEM 12.000 x
Normal Platelet TEM 22.000X
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Fibrinolysis
Exposure to CBP circuit increases
fibrinolysis

• Extrinsic Pathway is activated
• Factor XII further increases plasmin
• Kallikrein directly activates plasminogen

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Shear Stress

• Suction devices
• Pump action
• Turbulent flow

Platelet activation and aggregation
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PTT
TF is expressed on almost all non vascular
cells.
Extrinsic Pathway
TF
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XII
XIIa
PT
XI
XIa
IX
IXa
VIII
VIIIa
VIIa
VII
Xa
X
Thrombin
Prothrombin
Fibrinogen
Fibrin
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Hypothermia Platelet disfunction
Phase I Core temperature 37oC
34oC
37oC
Valery et al Annals of Surgery Vol 285, No 2,
p175-181, 1986
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Phase II Core temperature 32oC
34oC
27oC
27oC
27oC
BT 5.8 min
BT 2.4 min
Valery et al Annals of Surgery Vol 285, No 2,
p175-181, 1986
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39oC
27oC
BT 2.3 min
BT 6.9 min
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Hemostasis Changes During Cardiopulmonary Bypass
Surgery
Eberhart F. Mammen et al

• 63 patients followed

All factors decreased significantly at start
of CPB Hematocrit decreased Platelet counts
decreased in all patients Significant changes
in plt aggregation studies All clotting
defects returned back to normal at 24 hrs
Seminars in Thrombosis and Hemostasis Vol 11,
No 3, 1985
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Hematologic Changes during and after
cardiopulmonary bypass and their relationship to
bleeding time and nonsurgical blood loss
Shukri F. Khuri MD, J. Alan Wolfe MD et al J.
Cardiovasc Surg 1992 10494-107)
Thromboxane B2 6 keto PGF1alpha skin temp CBC
phase plt ct Beta Thromboglob. Total Protein
Globulin VIII, ATIII Fibrinogen

• 85 Patients undergoing CPB

labs at 2, 24, 48 and 72 hours after CPB
the reversal of the exension of the bleeding
time was accompanied by a significant
increase in mean platelet volume and by a
significant increase in levels of Thromboxane
B2 measured from blood shed from the site
where the bleeding time was performed
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Inhibition of Platelet Adhesion During
Cardiopulmonary Bypass Reduces Postoperative
Bleeding. Kay Uthoff MD Kenton J.Zehr MD et al
Circulation 199490, 269-274
Controlled study in dogs using GPIIb-IIIa
inhibitor Results Control group had
significantly lower plt. cts during CPB Plt fx
was better in dogs taking integrilin at 310 min
post CPB Integrilin group had less post op
bleeding from chest tubes.
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Platelet Protection by Low Dose Aprotinin in
Cardiopulmonary bypass Electron Microscopic
Study Jacob Lavee MD, Zvi Raviv MD et al
Ann Thoracic Surg 1993 55 114-9
Placebo vs Aprotinin study
Platelet aggregates were similar in pre
operatary samples
Little diference in aggregation between control
and aprotinin group
Patients on low dose aprotinin had improved
hemostasis
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Integrilin
Inhibition of Platelet Adhesion During CPB
Reduces Postoperative Bleeding
Kay Uthoff, Kenton Zehr et al
GPIIb -IIIa is the fibrinogen receptor Integrili
n is a temporary inhibitor of GPIIb-IIIa
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Summary
All clotting factors are markedly decreased
while on CPB. Platelet counts decrease
throughout the procedure. Platelet aggregation
is significantly decreased during CPB Platelet
response to ADP is absent when protamine is
given
Platelets are activated during CBP but the
clotting system does not appear to be activated.
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THE END