Transcript Hemostasis - Blood CME Center

The Biology of Bleeding and
Clotting to Death
Jeffrey H. Lawson, MD, PhD
Director, Vascular Surgery Research Lab
Director of Clinical Trials in Vascular Surgery
Duke University Medical Center
Durham, North Carolina
What Are the Challenges of Hemostasis in Surgery?
1. Who is likely to bleed or clot too much?
2. How do we optimize the physiology of the patient?
3. Which topical agents are effective?
4. Which biologic agents are effective? When? How much?
How not to overshoot?
Thrombosis
Clotting
Surgery
Post-op
Recovery
Bleeding
Hemorrhage
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Bleeding, Clotting, and Surgery
•
D&C for 2 years at Duke University = 358 complications
•
Total bleeding and thrombosis complications: 197/358 = 55%
•
114 of 358 cases could not be well adjudicated with respect to
complications
 Well-documented data reveal 197/244 = 81%
•
Total perioperative bleeding complications: 131/244 = 54%
•
Total perioperative thrombosis complications: 75/244 = 31%
•
Total deaths: 67
•
Bleeding as cause of death: 18/67 = 27%
•
Thrombosis as cause of death: 22/67 = 33%
D&C=dilation and curettage.
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Coagulation Cascade: Tissue Factor Pathway
VII(VIIa)
XIII
II
X
IIa
XIIIa
Xa
TF·VII(VIIa)
IXaß VIIa
TF·VIIa
Ca2:PL
Va·Xa
Ca2:PL
Xa
(IXα)
TF
VIIIa-IXaß
Ca2:PL
XIa
XI
IIa
IX
Xa
PL
IXaß
VIII
IIa
IIa
V
FN (cross-linked)
IIa
Fn
Fg
Xa
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The Problem
Most complications are at the dark interface between:
•
Biology
•
Clinical skill
•
Medical therapy
•
Sick patients
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Hemostasis
“The arrest of bleeding”
 Stedman’s Medical Dictionary
But is hemostasis more than that?
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Hemostasis
In surgery—hemostasis is …
•
About bleeding
•
About clotting
•
About timing
•
About balance
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Hemostasis
“Life in the Balance”
Bleeding
to Death
Clotting
to Death
Trauma
Major Surgery
Hemophilia
Stroke
MI
Thrombosis
Lawson JH, et al. Semin Hematol. 2004;41(suppl 1):55-64.
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Hemostasis
“Too thick or too thin”
 Dr. Richard McCann
Hemostasis in cardiovascular surgery
“Knowing when to be thick and when to be thin”
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Hemostasis
•
Blood coagulation
•
Anticoagulation
•
Fibrinolysis
•
Antifibrinolysis
•
Vascular tone and blood flow
•
Endothelial cells and platelets
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Keeping on Center
Antifibrinolytic
Activity
Procoagulant
Activity
Bleeding
Clotting
Normal
Hemostasis
Fibrinolytic
Activity
Adapted from Lawson JH, et al. Semin Hematol. 2004;41(suppl):55-64.
Anticoagulant
Activity
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What About Hemostatic Swings During Surgery?
Thrombosis
Clotting
Surgery
Post-op
Recovery
Bleeding
Hemorrhage
Adapted from Lawson JH, et al. Semin Hematol. 2004;41(suppl 1):55-64.
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Keeping on Center
Factor V falls
IIase increase
Procoagulant
Activity
Bleeding
Clotting
Fibrinolytic
Activity
TF increase
Antifibrinolytic
Activity
PAI-1 increase
Normal
Hemostasis
Inflammatory
Cytokines
t-PA increase
Adapted from Lawson JH, et al. Semin Hematol. 2004;41(suppl):55-64.
Anticoagulant
Activity
Heparin falls
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Keeping on Center
Topical Hemostatics
Purified Factors, FFP, Cryo, PLTs
Antifibrinolytic
Activity
Procoagulant
Activity
Bleeding
Clotting
Aminocaproic acid,
Aprotinin
Normal
Hemostasis
Fibrinolytic
Activity
t-PA, SK, UPA
FFP=fresh frozen plasma; Cryo=cryoprecipitate; PLTs=platelets; SK=streptokinase;
UPA=urinary-type plasminogen activator; LMWH=low-molecular-weight heparin.
Anticoagulant
Activity
Heparin, Warfarin
LMWH, Argatroban
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Adapted from Lawson JH, et al. Semin Hematol.
2004;41(suppl):55-64.
Operative Management
Thrombosis
Clotting
Physiology and Good Surgery
Bleeding
Hemorrhage
Topical Hemostatic Agents
Systemic Biologic Therapies
Adapted from Lawson JH, et al. Semin Hematol. 2004;41(suppl):55-64.
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