Haemostasis

1. Haemostasis
Haemostasis – control of bleeding
It has 2 phases:
-Reactions of blood vessel and platelets (RAPID)
-Intrinsic coagulation pathway (SLOW)
Stage 1 – blood vessel reaction
Reactions of blood vessels cause:
-Slowing of blood flow (VASOCONTSTRICTION)
-Formation of a platelet mass at the site of injury (PLATELET PLUG
FORMATION)
-Diffusion of TF from extravascular complartment initiaiting extrinsic
pathway (INITIATION)
Vasoconstriction
-Occurs immediately after an injury to vessel
-In response to:
oNervous reflexes – as a result of pain and traumitized vessels
oLocal myogenic spasm
oPlatelet thromboxane A2 (Important in small vessels)
-Smooth muscle in vascular wall contracts
-¯ diameter and blood loss
Formation of platelet plug
-ADHESION – damage to vascular endothelium exposes collagen and
other connective tissue to which platelets adhere.
-ACTIVATION – during activation, platelets change shape (swell then
extend projections that facilitate greater contact with other platelets),
Granule release causing release of substances from granules (ADP,

2. Thromboxane A2 – activate and make platelets more sticky), seratonin
and thrombone A2 (causing vasoconstriction to ¯ blood loss.
-
-AGGREGATION – sticky activated platelets attract one another and
adhere. Blocking small holes making coagulation unnecessary but it is
needed in large vessels.
Stage 2 – coagulation
Definition – A sequence of enzyme catalysed conversion of inactive
factors to active ones, culminating in the conversion of fluid blood into
solid gel or clot.
3 pathway; Intrinsic, Extrinsic and Common.
Activation of pathways
-Intrinsic
oTrauma to blood vessel and exposure to collagen
oIt is slow (minutes)
-Extrinsic
oRequires factors external to blood vessel e.g. TF
oFewer enzymes involved than intrinsic
oIt is limited by amount of TF
oIt is fast (seconds)
Coagulation cascade:

3. Common pathway
Measuring clotting
-PT (Prothrombin time) – 10-14s – Extrinsic pathway
-APPT (Activated partial thromboplastin time) – 30-40s (Intrinsic
pathway)
-TT (thrombin time) – 14-16s – marker of fibrinogen
-Fibrinogen levels – final pathway
-INR – measured therapeutic effectiveness of warfarin
Venous vs. arterial clotting:

4. Anticoagulation
Body’s anticoagulants
-Smooth endothelium – prevents activation of intrinsic pathway
-Protein C – inactivates factors Va and VIIIa
-ProteinS - inactivates factors Va and VIIIa
-Antithrombin III – combines with thrombin => inactivated (blocks XIa,
IXa, Xa)
Anticoagulants:
-Warfarin:
oVit K dependent factors – II, VII, IX, X
oLag time
oLongterm
oINR monitoring
oREVERSE with IV vitamin K, FFP, clotting factors

5. -LMWH:
oEg endoxaparin
oWorks by
potentiating the action of Antithrombin III (100-1000 fold)
Added effects of removing factors XII, XI, X and IX
Works mainly on factor Xa
Predictable so no monitoring needed
-Thrombolysis:

6. -LMWH:
oEg endoxaparin
oWorks by
potentiating the action of Antithrombin III (100-1000 fold)
Added effects of removing factors XII, XI, X and IX
Works mainly on factor Xa
Predictable so no monitoring needed
-Thrombolysis: