Lecture 9 - Intro To Haemostasis Flashcards
What is haemostasis?
Maintenance of fluid status in normal vessels whilst permitting rapid formation of a haemostatic clot at a sit of vascular injury
What are the 3 components of haemostasis?
Vascular wall
Platelets
Coagulation cascade:
-Coagulation factors
-Anticoagulant factors
What is the basic aim of normal haemostasis?
Stopping bleeding following trauma to blood vessel
What are the 3 general processes of stopping normal bleeding?
Vessel wall contracts
Platelet plug forms
Fibrin clot forms to stabilise
How does vessel size relate to bleeding from the vessel?
larger vessel = more bleeding
What cells are platelets made from?
Megakaryocytes
Where are megakaryocytes/platelets made?
In the bone marrow
What is the normal platelet count?
150 - 400 x 10^9/L
What 3 stages do platelets go through when a vessel is injured?
Adhesion
Activation
Aggregation (Forms platelet clot)
How do platelets adhere to blood vessels?
Collagen from tunica adventitia exposed
Von Willebrand factor produced by vascular endothelial cells binds to platelets binding the platelets to the collagen fibres adhering them
When platelets are activated what do they secrete?
Granules containg:
-Fibrinogen
-ADP
-Thromboxane
-Some coagulation factors
And more substances to activate other platelets
What is platelet aggregation?
When platelets cross link to form a platelet plug
Platelet plug adds some stability but is quite weak
What is the role of collagen in platelets action?
Binds platelets to vessel wall
What is the role of Von Willebrand factor?
To get platelets to adhere to the collagen
What is the role of ADP and Thromboxane?
Cause platelets to interact and form a platelet plug
What is the role of Thrombin?
Converts fibrinogen to fibrin
Why is formation of fibrin important?
It is insoluble so is what forms the stable clot
What is a zymogen?
A proenzyme (enzyme that is not active)
What is the clotting cascade aiming to produce?
What is the point of producing this?
Thrombin
Thrombin needed to convert fibrinogen into fibrin
Why does fibrinogen need to be converted into fibrin?
Fibrinogen is soluble
Fibrin is insoluble
Why do natural anticoagulants exist?
To carefully balanced the clotting cascade to prevent over clotting
What are the 2 pathways of the clotting cascade that lead to the common pathway?
Intrinsic pathway (contact activation pathway
Extrinsic pathway (tissue factor pathway)
What do both the intrinsic pathway and the extrinsic pathway produce which is the common insertion point into the common pathway?
Factor X (10)
What does Factor X (10) do in the common pathway?
Convert prothrombin to thrombin
Where are most the coagulation factors made?
The Liver
What are the 3 coagulation tests for clotting defects?
APTT (Activated partial Thromboplastin time)
PT (Prothromin time)
TT (Thrombin time)
What pathways does PT (prothrombin time) measure?
Extrinsic pathway
The function of what clotting factor is assed by PT (extrinsic pathway)?
Factor VII
What pathway is the (Activated partial thromboplastin time) APTT measuring the functioning of?
Intrinsic pathway
What does increased/abnormal APTT and PT indicate?
Problem in common pathway
(From factor X downwards)
Usually deficient Factor V, X, thrombin an fibrinogen
What does Thrombin clotting time measure?
Conversion of fibrinogen to fibrin via action of thrombin
If somebody has Haemophilia A or B what anticoagulation test is abnormal?
APTT (activated partial thromboplastin)
What happens to the vessel wall when damaged?
Vasoconstriction (Reduce blood flow/bleeding)
Producing Von Willebrand factor (so platelets stick to the collagen)
Exposure of platen and tissue factor initiates activation of clotting factors
What is the goal of haemostasis?
Make a clot
Control clotting
Break down clot
What 3 natural anticoagulants?
Protein C
Proteins S
Antithrombin
What Factors does Protein C inactivate?
Factor VIIIa
Factor Va
How is protein S related to Protein C?
Proteins S is a cofactor for protein C
Protein S must be activated in order for Protein C to be activated
What vitamin is the synthesis of Protein C and Protein S dependant on?
Vitamin K dependant
What does Antithrombin inactivate?
Thrombin
Other clotting factors
What activates Antithrombin?
Heparin
What is the function of Antithrombin on the body as a whole ?
Prevents spread of clot (rapidly inactivates travelling clotting factors)
Where does Tissue Factor Pathway Inhibitor act?
Start of Extrinsic pathway inhibiting Factor VII
Extrinsic pathway = tissue factor activation pathway
What is Fibrinolysis?
Break down of the final clot
What takes place in fibrinolysis?
Plasminogen converted to plasmin
Plasmin breaks down clot forming D-Dimers
What is the clinical significance of measuring D-Dimers in the blood?
Indicates clotting is taking place
What causes bleeding disorders?
Abnormalities in:
-Vessel wall
-Platelets
-Coagulation factors
What is Thrombocytopenia?
Deficiency of platelets in the blood resulting in bleeding into the tissues, bruising and slow blood clotting after injury
What are the signs of Thrombocytopenia?
Purpura
Petechiae
Mucosal bleeding
Epistaxis
Menorrhagia
What are the signs of Thrombocytopenia?
Purpura
Petechiae
Mucosal bleeding
Epistaxis
Menorrhagia
What is Purpura?
Haemorrhages in skin
What is petechiae?
Red dots/rash on skin
What is epistaxis?
Nose bleeds
What is menorrhagia?
Heavy menstrual periods
On a basic level, how does Thrombocytopenia happen?
Decreased production
Increased consumption
What are some causes of decreased production of platelets?
Marrow aplasia
Megaloblastic anaemia
Sepsis
What are some immun causes of thrombocytopenia?
Immune Thrombocytopenic Purpura
Thrombotic Thrombocytopenic Purpura
What is Immune Thrombocytopenic Purpura?
Low platelet count with a normal bone marrow and any other cause of low platelets has been ruled out
What is Thrombotic Thrombocytopenic Purpura?
Many small blood clots forming in small vessels are ounce the body
Leads to platelets and RBCs being used up and consumed
What are some non immune causes of thrombocytopenia?
Haemolytic-uraemic syndrome (HUS)
Hypersplenism
Disseminated Intravascular Coagulation
What’s characteristic of Haemoytic-uraemia syndrome (HUS)?
Low RBCs
Acute kidney injury
Low platelets
Who often get Haemoytic-uraemia syndrome?
Children more than adults
Associated with E.Coli infection
What are the symptoms of Haemoytic-uraemia syndrome?
Bloody diarrhoea
Fever
Vommiting
Weakness
Kidney failure
Low platelets
How does Hypersplenism cause Thrombocytopenia?
Enlarged overactive spleen removes too many platelets from blood
(Bone marrow tries to proliferate more to compensate)
What are the 3 most common congenital Coagulation factor disorders?
Haemophilia A
Haemophilia B
Von Willebrand’s disease
What are the 3 most common congenital Coagulation factor disorders?
Haemophilia A
Haemophilia B
Von Willebrand’s disease
What type of genetic inheritance are both forms of Haemophilia?
X linked recessive
What Factor is lacking in Haemophilia A?
Factor VIII
Why in Haemophilia A is APTT longer but PT normal?
Factor VIII is normally present in intrinsic pathway which is measured by APTT
PT measures the extrinsic pathway (factor VII)
How is Haemohillia A treated?
Recombinant Factor VIII
What Factor is deficient in Haemophilia B?
Factor IX
Why is APTT prolonged but PT normal with Haemophilia B?
Factor IX involved in intrinsic pathway
What is the only way to distinguish between Haemophilia A and B and why?
Presence of Factor VIII or IX
Both have same results of prolonged APTT and normal PT
How does Haemophilia present?
Prolonged bleeding post dental extraction
Muscle haematomas
Life threatening post operative an post traumatic bleeding
Easy bruising
Mass haaemorrhaging
What type of disease is Von WIllebrand disease?
Autosomal dominant
What is reduced in Von Willebrand disease?
Reduced platelet adhesion to vessel walls
Reduced Factor VIII
How does Von Willebrand Disease present?
Spontaneous nose bleeds
Excessive wound bleeding
Menorrhagia
What do vessel wall abnormalities usually lead to?
Easy bruising
SPontaeous small vessel bleeds
Mainly from skin but can be mucous membranes
What are 2 examples of vessel wall abnormalities?
Ehlers Danlos (connective tissue disorders)
Scurvy
What is Disseminated Intravascular coagulation (DIC)?
Lots of small blood thrombi form and get broken down
Platelets and clotting factors get consumed
When actually need to form clots (Haemostasis) you can so you haemorrhage
What would the levels of fibrinogen and D dimers be in someone with DIC and why?
Low fibrinogen
High D dimers
Lots of fibrinogen converted to fibrin due to overactive clotting
Lots of fibrolysis happening so high D-Dimers
There is always a trigger to cause DIC, what are some?
Malignancy
Massive tissue injury (burns)
Infections (gram - sepsis)
Massive haemorrhage
Obstetric cause (amniotic fluid embolism, preeclampsia)
What are Thrombophilias?
Congenital or acquired defects of haemostasis which can increase a patients risk of thrombosis
What is a congenital cause of thrombophilia?
Deficient in anticoagulants
What is more likely to happen in antiphospholipid syndrome?
Who is more likely to get this defect?
Clot development
A thrombophilia
Afro-Caribbean’s, Hispanics, Asians and Native Americans
What are some Anticoagulant drugs?
Vitamin K inhibitors (Warfarin)
Direct oral anticoagulants
Heparin
What are some Direct oral anticoagulants?
How do they work?
Dabigatran
Rivaroxaban
Apixaban
Rivaroxaban and Apixaban inhibit Factor X, this means that less prothrombin is converted to thrombin so less fibrinogen to fibrin
Why is warfarin being moved away from as an anticoagulant?
Needs constant patient monitoring
What are 2 anti platelet drugs?
Aspirin
Clopidogrel
How does Aspirin act as an anti platelet drug?
Blocks formation of Thromboxane
Therefore preventing formation of platelet plug
How does Clopidogrel act as an anti platelet drug?
Blocks ADP produced by platelets
Preventing the formation of the platelet plug
What is the main risk of anticoagulants?
BLEEDING
What is the most common Inherited Thrombophilia in Caucasians?
What type of inheritance?
Factor V Leiden
Autosomal dominant
