Haemostasis Flashcards
What are the three principles of haemostasis
- Normal number and function of platelets
- Functional coagulation cascade
- Normal vascular endothelium
What kind of surface do you need for clotting
A phospholipid surface membrane. This usually comes in the form of platelets or monocytes.
What prevents the adherence of platelets or monocytes and therefore prevents clotting
Intact vascular endothelium
What does serotonin do
Brings about vasoconstriction
Why is calcium important in clotting
It helps to activate some of the clotting factors and initiate the clotting cascade.
What are the three distinct phases in the formation of a platelet rich thrombus
- Platelet adhesion
- Platelet activation
- Platelet aggregation
What stabilises the platelet thrombus
The conversion of fibrinogen to fibrin by thrombin and polymerisation of fibrin. This produces a platelet-fibrin (“white”) clot
What do platelets recognise and adhere to in damaged endothelium
Sub-endothelium. They adhere to underlying collagen by glycoproteins.
What are the two processes of haemostatic plug formation
Primary aggregation and secondary coagulation. These occur simultaneously.
What is haemostasis triggered by
The release of tissue factor from the sub-endothelial space.
What do platelet and vessel wall defects lead to
Prolonged bleeding time
What is thrombocytopenia
A reduced number of platelets
What causes thrombocytopenia
Bone marrow failure or lymphoma/disease of the bone marrow or peripheral consumption of platelets, e.g. due to inflammation
What leads to abnormal platelet function
Anti-platelet drugs such as aspirin or clopidogrel. Can also be due to renal failure as uraemia (excess protein in the urine) causes platelet dysfunction.
What are examples of abnormal vessel wall defects
- scurvy
- ehlers-danlos syndrome
- henoch schonlein purpura
- hereditary haemorrhagic telangiectasia
What is an example of a defect which causes abnormal interaction between platelets and the vessel wall
Von Willebrand’s disease
What happens in scurvy to cause abnormal vessel wall
There is a lack of vitamin C in the blood which is vital for the creation of collagen.
What does hereditary haemorrhagic telangiectasia result in
Bleeding in mucous membranes. This often means bleeding in the skin, gut and lungs. Anaemia and blood loss can result.
What are some examples of drugs that inhibit platelet function (anti-platelets)
Aspirin, NSAIDs, dipyridamole, thienopyridines, integrin GPIIb/IIIa receptor antagonists.
How does aspirin work as an anti-platelet drug
Aspirin is an irreversible COX inhibitor. COX enzymes produce prostaglandins which activate platelets.
What is an example of a reversible COX inhibitor
NSAIDs.
What is an example of a thienopyridine
Clopidogrel
How does clopidogrel work as an anti-platelet drug
It inhibits ATP mediated activation of platelets.
What are two examples of integrin GPIIb/IIIa receptor antagonists
abciximab and tirofaban
How do GPIIb/IIIa receptor antagonists work
By preventing platelet aggregation.
What are the three coagulation pathways
Intrinsic pathway, extrinsic pathway and common pathway.
What happens in the intrinsic pathway
- Damaged surface
- Factor XII to factor XIIa
- Factor XI to Factor XIa
- Factor IX to factor IXa
- Activation of factor X to create factor Xa
- Common pathway
What happens in the extrinsic pathway
- Trauma
- Factor VII to factor VIIa
- Activation of factor X to create factor Xa
- Common pathway
What initiates the first step of the common pathway
Activation of factor X
Where are clotting factors produced
The liver
Which factor can be produced elsewhere (not in the liver)
Factor V
Which factors are vitamin K dependent and therefore affected by warfarin
Factors 2, 7, 9 and 10
What factor is important to trigger the clotting cascade
Tissue factor
What happens in the common pathway
- Factor X is converted to factor Xa
- Prothrombin is converted to thrombin
- Fibrinogen is converted to fibrin
- A cross linked fibrin clot is produced.
What is the difference in the production of thrombin between the intrinsic and extrinsic pathways
The extrinsic pathway allows the initial burst of thrombin while the intrinsic pathway involves a slow onset of thrombin.
What two factors are a complex to form extrinsic tenase
Factor VIIa and tissue factor
What two factors are a complex to form intrinsic tenase
Factor VIIIa and factor IXa
What two factors are a complex to form prothrombinase
Factor Xa and factor Va
What are the four phases of the cell based model of coagulation
- Initiation
- Amplification
- Propagation
- Termination
What are three natural inhibitors of the coagulation cascade
Tissue factor pathway inhibitor
Ant thrombin
Protein C pathway
What does tissue factor pathway inhibitor inhibit
The tissue factor-factor VIIa complex and factor Xa
What does antithrombin inhibit
Thrombin and factor Xa activity
What does the protein C pathway inhibit
Factor Va and factor VIIIa
What is the haemostatic balance between
Bleeding and clotting
What are three laboratory measurements for clotting
Prothrombin time (PT), Activated partial thromboplastin time (APTT) and fibrinogen.
What does abnormal prothrombin time reflect
Abnormality in the extrinsic or common pathway
What does an abnormal APTT reflect
Abnormality in the intrinsic or common pathway
What does abnormal APTT and PT indicate
Abnormality in the common pathway
What are the three most common disorders in the coagulation cascade seen in clinical practice
Factor IX deficiency, factor VII deficiency and Von Willebrand disease
Which hereditary coagulation factor deficiency does not cause bleeding
Factor XII
What is the clinical condition brought about by factor XI deficiency
Haemophilia B
What is the clinical condition brought about by factor VIII deficiency
Haemophilia A
What is the role of von willbrand factor
It is involved in binding factor VIII, platelets and constituents of connective tissue to allow the formation of a thrombus.
What is Haemophilia A
An x-linked recessive disorder which is a deficiency or dysfunction of factor VIII.
What are the differences between severe, moderate and mild haemophilia
In severe haemophilia the person will have spontaneous bleeding which may be into the joints. This is when there is less than 1% factor VIII. In moderate haemophilia, there will be bleeding after minor trauma and in mild haemophilia bleeding will occur after major trauma or surgery.
What is haemoarthrosis
Bleeding into the joints. This can occur in people with severe haemophilia.
What is used in the management of haemophilia
Supportive measures, replacement of missing clotting protein and antifibrinolytic agents
What supportive measures are used in the management of haemophilia
Ice or immoblilisation
How is missing clotting protein replaced in haemophilia
Using coagulation factor concentrates or desmopressin.
What is the name of an antifibrinolytic agent used in the management of haemophilia
Tranexamic acid
What are the signs of congenital haemophilia
Haemoarthrosis, muscle bleeds and soft tissue bleeds
How is acquired haemophilia different from congenital haemophilia
In acquired haemophilia, antibodies to factors VIII and IX are developed. This can happen spontaneously or be due to malignancy
What are the bleeding patterns in acquired haemophilia
There is often blood in the urine, large haemotomas, cebrebral haemorrhages and compartment syndromes.
What are the roles of Von Willebrand factor
To promote platelet adhesion to the subendothelium at high shear rates. It is also a carrier molecule for factor VIII.
What is the most common heritable bleeding disorder
Von Willebrand disease
What are the three different types of Von Willebrand disease
Type 1 - Reduction in Von Willebrand Factor
Type 2 - abnormal Von Willebrand factor
Type 3 - no Von Willebrand factor
What is used to manage Von Willebrand disease
Antifibrinolytics (tranexamic acid), DDAVP, Factor concentrated containing von willebrand factor (vaccination against hep A and B), contraceptive pill for menorrhagia.
What may lead to the underproduction of coagulation factors
Liver failure or vitamin K deficiency.
What is disseminated intravascular coagulation (DIC)
An acquired syndrome of systemic intravascular activation of coagulation - “thrombin explosion”. There is out of control systemic activation of the coagulation cascade.
What can be the result of DIC
Widespread deposition of fibrin in the circulation causing ischaemia and multi-organ failure.
How can DIC cause excessive clotting and bleeding
The excessive thrombus formation in DIC uses up the available platelets and coagulation factors to generate the thrombin. This means there are not enough platelets and coagulation factors left, and this can lead to severe bleeding.
What can cause DIC
- Sepsis
- Trauma
- Pancreatitis
- Obstetric
- Transfusion of ABO incompatible cells
What may an examination of the peripheral blood film of someone with DIC show
Red cell fragments
What tests can be used to investigate DIC
- Prothrombin time - will be prolonged
- Activated partial thromboplastin time - will be prolonged
- Fibrinogen - will be low
- D-dimers - will be high
What do raised D dimers indicate
D dimers are fibrin degradation products. D-dimers in the circulation means increased breakdown of fibrin.
