7. Bleeding Clotting
Hemostasis
Under normal conditions, blood circulates
through the intact vasculature without
thrombus formation or haemorrhage
8. Hemostasis
State of fluid equilibrium within the blood vessels
Vessels
Coagulation
Proteins Platelets
Fibrinolysis/ Inhibitors
9. Hemostasis
A process which causes bleeding to stop
Primary Hemostasis
Arteriolar vasoconstriction
Formation of platelet plug
Secondary Hemostasis
Activation of coagulation cascade
Formation of permanent plug
11. Constriction of vessels
There are 2 mechanisms for vessel
constriction:
– Local smooth muscle contractile response
– Thromboxane A2 release from endothelium
12. Formation of platelet plug
Exposure of the subendothelial layers cause platelets
to adhere.
They release ADP and TxA2, inducing further platelet
aggregation and activation
Adhesion requires von Willebrand factor (vWf) from
the subendothelial layers.
13. The time taken for platelet plug to form
(Bleeding Time - BT) gives a non-specific
indication of:
• The state of the vascular endothelium
• The number of platelets in the circulation
• The platelets are functioning correctly (can
release granules and produce pseudopodia)
• Demonstrates the presence of vWF
14. Coagulation Factors
Factor I Fibrinogen
Factor II Prothrombin
Factor III Tissue Thromboplastin
Factor IV Calcium Ions
Factor V Labile Factor, Proaccelerin
Factor VII Stable Factor, Proconvertin
Factor VIII Antihemophilic Factor
Factor IX Christmas Factor
Factor X Stuart-Prower Factor
Factor XI Plasma Thromboplastin Antecedent
Factor XII Hageman Factor
Factor XIII Fibrin Stabilizing Factor
All coagulation factors are made in the
liver, except for vWF
15. Clotting cascade
Intrinsic Pathway
– All factors occur from within the circulation
– in vivo, the pathway is triggered by exposure of "contact factors"
to collagen or basement membrane at the site of injury or a
foreign substance such as a prosthetic device
Extrinsic Pathway
– Requires tissue thromboplastin to be released from damaged
cells (outside the circulation)
Both pathways lead to the activation of prothrombin
(factor II)
Final common pathway converts fibrinogen to fibrin
19. Natural inhibitors of the coagulation cascade
Antithrombin III is a large protease inhibitor that inhibits
thrombin and factors IXa, Xa, XIa, and XIIa but does not
inhibit thrombin within clots
Heparin accelerates the reaction time of
antithrombin III 1000 fold
20. Natural inhibitors of the coagulation cascade
Protein C and Protein S
Vitamin K-dependent serine proteases synthesized
in the liver
Circulate as inactive forms (zymogens)
Protein C
inhibits the activity of factors Va and VIIIa
Protein S
cofactor that potentiates the action of Protein C
23. Defects of Hemostasis
Congenital disorders
Hemophilia A,B
von Willebrand disease
Acquired disorders
Hepatic disorders
DIC
Vitamin K defeciency
Anticoagulants
Massive blood transfusion
Platelet disorders
25. Preoperative screening for bleeding risk
Complete history and physical
Eckman et al. Ann Intern Med Vol 138, No 5
26. Preoperative screening for bleeding risk
Incidence of a significant hereditary deficiency of a
coagulation factor is low (1 per 10,000-40,000)
approximately 1/3 of these are asymptomatic
Acquired deficiencies of factors should be suspected in the
presence of advance hepatic disease, malabsorption, or
malnutrition
27. Hemostasis Screening Tests
• Bleeding Time
• Clotting Time
-Vascular
Platelet Count -Platelet
PT -Coagulation factors
-Fibrinolysis
APTT
TT
Euglobulin Clot Lysis Time
D = Dimer
28. Clinical testing and preoperative screening
Prothrombin time (PT)
measure extrinsic and common pathways
affected by low concentrations of fibrinogen, prothrombin
and factors II, V, VII, X
Activated partial thomboplastin time (aPTT)
measures intrinsic and common pathways
deficiencies in all clotting factors except factors VII and
XIII may prolong the aPTT
34. Thrombin + Gelfoam + CaCl
Thrombin for cleavage/activation
Gelfoam as matrix
Very useful in vascular surgery
35. Fibrin glue
Tiseel
FDA approved in 1998
Concentrated fibrinogen and f VIII
Thrombin and calcium
Aprotinin to prevent clot dissolution
Takes time to prepare
Good for diffuse oozing, needle punctures,
parenchymal injuries