Haemostasis And Bleeding Flashcards
What is haemostasis?
The process of stopping bleeding and maintaining vascular patency
What are the requirements for effective haemostasis?
Permanent state of readiness
Prompt and localised response
Protection against unwanted thrombosis
What are stages of normal haemostatic response?
Primary haemostasis - platelet plug formation
Secondary haemostasis - secondary haemostasis
Fibrinolysis
Anticoagulant defences
Platelets- lifespan, formation
Small anucleate discs with a 7-10 day lifespan
Formed in marrow via budding of megakaryocytes
Describe the process of primary haemostasis
Vasoconstriction at injury site to reduce blood flow
Endothelial wall damage -> VWF release
Platelets adhere to VWF at injury site, and the platelets secrete various chemicals which cause aggregation
What causes failure of platelet plug formation?
Vascular-
Hereditary eg Marian’s and Ehlers Danos
Acquired eg HSP, age, vitamin C deficiency
Thrombocytopenia-
DIC
Autoimmune- ITP
Hypersplenism
Reduced production
Acquired reduced function-
Drugs ie aspirin/NSAIDs, renal failure
Von Willerbrand disease
What are the consequences of platelet plug formation abnormalities?
Spontaneous purpura and easy bruising
Epistaxis and menorrhagia
Petechiae (pinpoint spots due to capillary bleeding)
Eye symptoms
Screening test primary haemostasis activity
Platelet count
What are the clotting factors in the clotting cascade?
I- fibrinogen
II- prothrombin
IIa- thrombin
IV- calcium ions
V- proaccelerin (labile factor)
VI- part of factor 5
VII- proconvertin (stable factor)
VIII- antihemophillic factor
IX- Christmas factor (plasma thromboplastin component)
X- Stuart-Prower factors
XI- plasma thromboplastin antecedent
XII- Hagemans factor
What is secondary haemostasis ?
The fibrin clot formation- stabilisation of the temporary platelet plug
Made up of extrinsic intrinsic and common pathway, which are all interlinked
Explain process of extrinsic pathway
Initiation of the process
Tissue Factor (III) exposed when blood vessel is injured
Binds to factor VII which activates it to VIIa
The VIIa-TF complex activates factor X to Xa, which triggers common pathway
Explain the process of intrinsic pathway
Endothelium damage exposes it to subendothelial collagen
Activates factor XII to XIIa -> activates Factor XI to Factor XIa -> activates IX to IXa
IXa along with VIIIa amplifies X -> Xa activation
Explain the common pathway
Xa and Va forms prothrombinase complex
Converts II to IIa (prothrombin to thrombin)
Thrombin coverts I to Ia (fibrinogen to fibrin), forming a mesh that stabilises a platelet plug
XIIIa cross links fibrin strands to create a stable clot
What causes failure of a fibrin clot formation?
Single clotting factor deficiencies eg haemophilia
Isolated prolonged APTT
Multiple clotting factor deficiencies eg DIC
Vit K deficiency/warfarin
Liver disease
Prolonged PT and APTT
Increased Fibrinolysis- seen as part of complex coagulopathies
How do we test for fibrin clot formation deficiencies?
PT and APTT time
What is PT?
Prothrombin time
Tests to see if extrinsic pathway is working
Affected in anticoagulant use, liver failure, and DIC
What is APTT?
Activated partial thromboplastin time
Tests to see if intrinsic pathway is working Affected
Measures VIII, IX, XI, XII
Haemophilia A and VWD increases time
What could it mean if both PT and APTT are altered?
Multiple clotting factor deficiencies
What factors are carboxylated by vitamin K?
2 7 9 10
Sources of vitamin K
Diet
Intestinal synthesis
Absorbed in upper intestine
What are some causes of vitamin K deficiency
Poor dietary intake
Malabsorption
Obstructive jaundice
Warfarin (Vit K antagonists)
Haemorrhaging diseases of the newborn
What is Fibrinolysis?
The process of breaking down a blood clot after injury has been repaired
Needed for prevention of thrombosis
What is the process?
Plasminogen binds to fibrin within the clot
Tissue plasminogen activator (tPA) and urokinase “ “ (uPA) leads to activation of Plasmin
Plasmin breaks down fibrin into various things
How can clot breakdown be assessed and by what product?
one of the degradation products is D-dimers
Measured to clinically assess clot breakdown
What binds to free plasmin to prevent excess Fibrinolysis?
Alpha 2 antiplasmin
What inhibits tPA and uPA and why?
PAI-1 (plasminogen activator inhibitor)
Controls plasminogen activation
What are the consequences of impaired/excessive fibrinolysis?
Impaired- pathological clot persistence -> DVT/PE
Excessive- uncontrolled bleeding (DIC)
What are the anticoagulant defences?
Protein C and S- circulating plasma protein from liver
Combine to form thrombomodulin
Thrombomodulin inactivates factor V and VIII to slow down coagulation
Antithrombin III -> affects factors 2 7 9 10 12
