Haemostasis and thrombosis Flashcards
Desribe the 2 clotting mechanisms
Intrinsic — occurs when blood passes over roughened damaged endothelium causing collagen to be exposed e.g due to hypertensive damage
Results in release of clotting factors
Extrinsic - occurs when damage to tissue e.g via cut releases thromboplastin
What occurs after activation of factor X is the same for both :
Prothrombin —> thrombin + factor XIII (via factor X)
Thrombin converts fibrinogen —> fibrin
Factor XIII converts fibrin to stable fibrin
Mediated by serine proteases
Describe the action of platelets
Clotting factors and platelets work in conjunction
Adhere to damaged smooth muscle below endothelial cell of damaged/disease vessel via vWF
Release aggregation factors - ADP and thromboxane (vasoconstrictor)
This leads to expression of glycoproteins IIb-IIIa which allow cross-linking of platelets via fibrinogen and vWF
Describe the lab tests used to investigate platelet dysfuncton and thrombocytopenia (not enough platelets)
Incision to forearm with venous cuff
Increased time for coagulation to occur (denoted by INR)
Healthy INR is 1
Also measure liver function as liver produces many clotting factors
Compare venous and arterial thrombosis
Venous thrombosis are a problem of the coagulation factors event due to blood stasis - anticoagulants used
Arterial thrombosis are a platelet event due to atheroma - antiplatelet drugs
What is a transient ischaemic attack*
Temporary reduction of blood flow to brain
Vascular cause
Symptoms last <24h
No evidence of infarction on imaging
pathophysiology of AF
Spontaneous firing of non pacemaker cells in atria
Abnormal discoordination of ventricular contraction
Disrupted SAN —> AVN conduction
Haemophilia What is it Causes Symptoms Treatment
Genetic - males predominantly affected and female carries
Low/no factor VIII of clotting cascade
Haemorrhage and prolonged bleeding risk
Treated with factor VIII from blood donors or analogue of vasopressin (this increases factor VIII release) ; new monoclonal antibody drug available now as well
Von willebrands disease What is it Causes Symptoms Treatment
Hereditary lack or defect of vWF
Symptoms - increasing bruising, nose bleeds, mucosal bleeding
Treatment - analogue of vasopresssin, factor VIII or vWF from donors
Liver disease can result in reduced synthesis of ____ ____
This leads to increased _____
Clotting factors
Bleeding
Thrombocytopenia
What is it
Causes
Symptoms
Reduced platelet number
Spontaneous skin bleeding
Causes - idiopathic, viral, drug-induced, toxins
What is disseminated intravascular coagulation
Large amount of fibrin made by procoagulant material such as amniotic fluid/infection or massive trauma
Results in widespread haemorrhage and large consumption of platelets/clotting factors but also may be thrombosis
Treat by giving platelets and fresh plasma
What condition increases risk of venous thrombosis
Factor V Leiden mutation
Why does atheroma formation only occur in arteries
Low pressure of blood in veins ; less turbulence
What are the different types of ischaemic strokes ?
Small vessel disease
Large artery atherosclerosis
Cardio-embolic stroke (due to AF)
Unknown causes
Haemorrhagic stroke
Causes
Symptoms
Caused by rupture of artery in brain
Intracebral or subarachnoid (on surface)
Symptoms - headache, nausea, vomiting, reduced consciousness/weakness in one part of body
What are the risk factors of stroke
Hypertension Diabetes mellitus Hyperlipidaemia Cardiovascular disease Haematological conditions such as factor VIII/sickle cell Inflammatory issues Obesity Alcohol/smoking
The hearts normal rhythm is called ___ ____
Sinus rhythm
What are the causes of AF
Cardiovascular causes : Hypertension Atherosclerosis Congenital heart disease Heart valve disease
Respiratory diseases
asthma , COPD, lung cancer
Diabetes
Overactive thyroid gland
Treatment of AF
Anticoagulants to reduce stroke risk
Beta blockers / anti-arrhythmics drugs to control AF
Electric shock treatment (cardio version)
Catheter ablation - involves placing a tube through the blood vessels to the heart
Pacemaker
Symptoms of stroke
Sudden weakness and numbness in face arm or leg (specificallyy one side of body)
Sudden confusion and difficulty spreaking
Sudden vision problems
Sudden loss of balance
Loss of memory
Sudden difficulty swallowing
Personality changes
Describe the process of diagnosis of stroke
History
BP,HR,cholesterol chest
Neurological examination
If right hemisphere affected symptoms : difficulties with attention, perceptions, memory, learning
If left hemisphere affected symptoms : language, and logical functions such as analytical thinking and maths
How do ischaemic and haemorrhagic strokes look like on CT scans ?
Haemorrhage seen as bright white area
Ischaemic area is slightly darker grey
How is ischaemic stroke treated ?
Recombinant tissue plasminogen activator
Mechanical thrombectomy - physical removal of blood clot
Carotid endarterectomy - removal of carotid plaques (arteries that delver blood to brain)
Describe briefly how thrombosis occurs
Damaged vessel wall exposes collagen
Circulating platelets aggregate and release coagulation factors
Fibrinogen —> fibrin
Long fibrin molecules bind together platelets and trap RBC/WBC
Describe normal fibrinolysis
Plasminogen is an inactive pro enzyme within the plasma ; plasminogen —> plasmin by tissue plasminogen activator (t-PA) secreted by endothelial cells
Plasmin breaks down fibrin dissolving the thrombus
The fragmented bits of fibrin are called fibrin degradation products (FDPs)
Pathological thrombosis occurs when …
The thrombus enlarges past vessel healing requirements
What is the D-dimer test?
Breakdown product of a fibrin mesh, stabilised by factor XIII
Increased blood levels in thrombosis
What arr the 3 factors that predispose thrombus formation?
1) damage to vessel wall
2) stasis (slow or turbulent flow)
3) change in character of blood (increased platelets/RBCs/viscosity)
What are the main predisposing factors in :
Arteries , veins, ventricles, atrium, heart valves
Arteries- vessel wall damage Veins-stasis Ventricles-chamber wall damage Atrium-stasis Heart valves - valve surface damage
Infarction
Tissue death due to ischaemia
Consequences of DVT
Congestion (swelling from the accumulation of fluid in nearby tissue )
Infarction may occur ; typically haemorrhagic in nature
When would a thrombus occur on the wall of a heart chamber ?
Post MI - scarring of heart wall makes thrombus formation more likely to occur due to stasis of the blood (scarred vessel walls can’t contract as well)
What might happen to a thrombus ?
Broken down by intrinsic fibrinolysis
Occlusion - completely block the lumen
Organisation and recanalisation (formation of new blood vessels, through an obstruction such as a clot )
Propagate
Thromboembolism - break off and travel elsewhere
What two materials typically embolise?
Thrombus and cancer cells (we would call this metastasis)
Thromboemboli in the following regions are called: A)Lower limb arteries B)Mesenteric arteries C)Renal arteries D)Splenic artery
A)gangrene of legs
B)bowel necrosis
C)kidney infarct
D)splenic infarct
What increases the risk of venous thromboembolism ?
Use of hormone replacement therapy Oestrogen-containing contraceptive therapy Varicose veins Pregnancy or post partum <6 weeks Obesity Dehydration Being bed bounds Thrombophilias Age >60 Cancer Comorbidities
What other materials are capable of embolising ?
Fat and bone marrrow
Air (from putting in a central line or lung surgery)
Nitrogen (form diving)
Amniotic fluid (abortion or placental abruption)
