Thrombosis - formation of blood clot in vessel Risk Factors Divided into 3 Main Categories

 Causes ischaemia (low blood flow to (Virchows Triad)

organ) 1. Circulatory Stasis - slow blood flow
   2. Endothelial Injury (injury to
Thrombotic Disorders: endothelium)
1. Venous Thrombosis 3. Hypercoagulable State - tendency to
 DVT - in legs form excess clots
 PE - blocked supply to lungs  
2. Arterial Thrombosis Note - THROMBOPHILIA = excess abnormal
 Myocardial infarction clot formation
 Atrial fibrillation  
 Peripheral vascular disease Thrombosis - caused by procoagulant and
 Stroke anti-fibrinolytic mechanisms
Bleeding - caused by anticoagulant +
profibrinolytic mechanisms
 
VTE (venous thromboembolism) - includes Note - Myocardial infarction (heart attack) =
DVT and PE blocked coronary arteries
1. DVT - can lead to Pulmonary  
Embolism (PE) Natural Coagulation Inhibitors in Blood:
 Blood clot around valves in DEEP 1. Antithrombin (AT)
VEINS (around legs/arms)  Inhibits thrombin, 9a and 10a
 Blood clot made of thrombus (fibrin 3. Tissue factor pathway inhibitor (TFPI)
and erythrocyte rich)  Direct inhibitor of 7a/TF and 10a
  4. Activated Protein C (aPC)
2. Pulmonary embolism (PE) - part of  Proteolytically cleaves 5a and 8a for
DVT thrombus called embolus breaks deactivation
off and travels to heart then lungs and 5. Protein S (PS)
blocks the arteries in the lungs =  Cofactor of aPC - helps inactivate 5a
causes low blood supply to tissues and 8a
   
 PE always caused by DVT Deficiency in Coagulation Inhibitors:
 Broken off DVT = embolus Idiopathy - no clear triggering factor
 D-Dimer - chemical released from  50% of idiopathic patients with
fibrin clots (high in PE patients) thrombosis have APC resistance (like
  FVL)
Risk Factors for VTE:  
 Surgery and cancer can cause high TF Factor 5 Leiden (FVL) - mutation in F5 gene
= more clotting (ARGININE 506 to GLUTAMINE 506)
 Immobilisation  Common cause of venous thrombosis
 Genetic risk factors - Factor 5 Leiden  
Mutation + Coagulation inhibitor Normally Activated Protein C (APC) cleaves 3
deficiency peptide bonds in F5 = INACTIVATION = low
  coagulation
Factor 5 Leiden mutation = mutation in factor  mutation in FVL gene = F5 resistance
5 to APC cleavage = more coagulation)
   
Treatment of Venous Thrombosis: (like DVT  Atherosclerosis causes narrowing of
and PE) coronary arteries
 Heparin (ANTITHROMBIN and ANTI  
10) - Unfractionated Heparin or Low Carotid artery - supplies blood to brain, neck
Molecular Weight Heparin and face
(LMWH/Timaparin) - low molecular  
weight heparin cleaves ONLY FACTOR Effects of arterial thrombosis:
10  Coronary artery thrombosis =
 VKA (vitamin K antagonist) - inhibits myocardial infarction
vitamin K (vitamin K dependent  Carotid artery = stroke
factors don’t work)  
 NOACs (non-vitamin K anticoagulants) Drugs used to treat arterial thrombosis:
- antithrombin 1. Anti-platelets
   Aspirin - inhibits COX-1 and
Arterial Thrombosis: (caused by thromboxane production
atherosclerosis)  Anti A2B3 receptor (fibrinogen and
 Inflammation of vessel wall VWF binding)
(macrophages become FOAM CELLS +  Anti P2Y receptor (for ADP induced
LDL fat) creates an atherosclerotic platelet aggregation)
plaque around tunica intima which 2. Fibrinolytics - TPA (TISSUE
narrows artery) PLASMINOGEN ACTIVATOR) and UPA
 Plaque rupture causes myocardial  
infarction or ischaemic stroke  
  Anti A2B3:
Note - thrombus (blood clot) are platelet rich ABCIXIMAB
  TIROFIBAN
Arterial Thrombosis Risk Factors:  
 Smoking Anti P2Y
 Diabetes CLOPIDOGREL
 Hypertension TICAGRELOR
 High cholesterol PRASUGREL

Fibrinolysis - break down of fibrin clot PREVENTION of Stroke in atrial fibrillation:

 VKA (vitamin K antagonists)
Plaque rupture causes clot to develop which  NOACS (either inhibit thrombin or
causes myocardial infarction or ischaemic factor 10a) - named with either XA in
stroke word for anti 10 or 'TRAN' at the end
  for anti thrombin
Plaques are made of lots of TF and Collagen
and LPA TRAN - ANTI THROMBIN + Argatroban
 Big plaques rupture causes TF and  
Collagen leak which activates clotting Heparin - helps NOACs inhibit thrombin and
factors which causes a thrombus 10a
blockage (ARTERIAL THROMBOSIS) +   
ischaemia Problem with anticoagulant drugs:
   Heparin can be impure - can cause
Collagen - activates platelets via GP6 receptor thrombocytopenia
TF expressed by FOAM CELLS - binds factor 7 -  Warfarin - needs close monitoring
activates coagulation  Too much anticoagulant = bleeding
Lysophosphatidic Acid (LPA) activates
platelets via P2Y receptor