12 Thrombosis Flashcards
Q: What’s the positive and negative possibilities of the haemostatic system?
A: will stop you bleeding to death but may kill you with thrombosis (powerful system)
Q: What’s normal haemostasis described as? Draw diagram. What are the factors involved? (4)
A: state of equilibrium
between:
fibrinolytic factors, anticoagulant proteins
= prevent clotting prematurely/ innappropriately
coagulation factors, platelets
= cause clotting
Q: How does the balance of haemostasis change in relation to bleeding? More of? (2) Less of? (2)
A: arrow of diagram pointing to 10 o clock
bleeding could be caused by
- more fibrinolytic factors, anticoagulant proteins
- less coagulation factors, platelets
Q: What are the characteristics of abnormal bleeding? (4) Why do you need to be careful when diagnosing? Solution?
A: -spontaneous esp in severe hereditary blood disorders eg haemophilia
- Out of proportion to the trauma/injury
- Unduly prolonged= doesn’t stop
- Restarts after appearing to stop
there are some common indications such as easy bruising but that doesn’t necessarily mean they have abnormal bleeding
-use history when diagnosing
Q: What would be included to constitute significant bleeding? (history) (6)
A: Epistaxis/nosebleed not stopped by 10 mins compression or requiring medical attention/transfusion
Cutaneous haemorrhage or bruising without apparent trauma (esp. multiple/large)
Prolonged (>15 mins) bleeding from trivial wounds, or in oral cavity or recurring spontaneously in 7 days after wound
Spontaneous GI bleeding= leading to anaemia which allows it to be spotted
Menorrhagia requiring treatment or leading to anaemia, not due to structural lesions of the uterus
Heavy, prolonged or recurrent bleeding after surgery or dental extractions
Q: Outline the haemostatic mechanism. Name and describe the 4 steps and include the result of each.
A: (Response to injury to endothelial cell lining)
- Vessel constriction
- Vascular smooth muscle cells contract locally
- Limits blood flow to injured vessel - primary haemostasis= Formation of an unstable platelet plug (primary haemostatic plug)
- platelet adhesion
- platelet aggregation
- Limits blood loss + provides surface for coagulation - secondary haemostasis= coagulation system = Stabilisation of the plug with fibrin
- Stops blood loss - Vessel repair and dissolution of clot
- Cell migration/proliferation and fibrinolysis
- Restores vessel integrity
Q: What are the 3 types of defects of primary haemostasis? Common examples (3,1,3).
A: (platelet plug formation)
deficiency/defective
- Collagen - vessel wall -> hereditary/ difficulty making it
- > steroid therapy
- > age
- > scurvey - Von Willebrand factor
- > von willebrand disease (genetic deficiency)= failure of primary haemostasis - Platelets
- > may not make enough eg bone marrow problems
- > use them up too quickly eg immune destruction = Thromobocytopenia
- > may stop them working properly via aspirin / ibuprofen
Q: Outline the process of primary haemostasis. (5) What can cause this process to fail? Describe.
A: 1. vessel wall damage
2. blood is exposed to 2 things that it isn’t normally exposed to
-collagen= triggers primary haemostasis
-tissue factor= triggers secondary haemostasis
=> both trigger haemostasis
3. von willebrand factor circulating in blood binds to collagen and unravels
4. vWF binds to platelets
5. forms primary platelet plug
Von Willebrand Disease= no vWF so platelet plug doesn’t form
- majority of platelets continue to flow past
- very few with bind directly to collagen
Q: What are the clinical signs of defects of primary haemostasis- pattern of bleeding? (7) Give a typical symptom. Typical of?
A: - Immediate
- Easy bruising
- Nosebleeds (prolonged: >20 mins)
- Gum bleeding (prolonged)
- Menorrhagia (anaemia)
- Bleeding after trauma/surgery
- Petechiae (specific for thrombocytopenia)
Petechiae (small (1–2 mm) red or purple spot on the skin) – typical of thrombocytopenia
Q: What’s the key output of the blood coagulation system? What’s its role? End result?
A: thrombin (factor IIa)
process= amplification cascade to make more thrombin
thrombin has to convert fibrinogen to fibrin
Fibrin mesh binds and stabilises platelet plug and other cells -> fibrin is needed to bind together and secure in vivo a solid plug
Q: What does haemophilia A mean? Result? (2) How does it vary in different sized vessels?
A: no FVIII - get inadequate thrombin generation
- primary haemostasis is okay
- BUT can’t make mesh to stabilise it
small: it’s okay- can make a small plug
normal: plug falls apart
larger: will bleed
Q: What does it mean to have defects in secondary haemostasis? (2) Common examples? (5)
A: -Deficiency or defect of coagulation factors
-Poor thrombin burst, poor fibrin mesh
Genetic:
- Haemophilia: FVIII or FIX deficiency
Acquired:
- Liver disease (most coagulation factors are made in the liver)
- Drugs (warfarin – inhibits synthesis, other block function)
- Dilution (results from volume replacement): often as a result og giving saline and RBC etc without plasma after resuscitation from major haemorrhage
- Consumption (DIC= disseminated intravascular coagulation) (acquired)
Q: What is DIC? (2) Cause? (2) Associated with? (3) What does it involve? (2) Consequences? (2)
A: type of acquired coagulation disorder
-disseminated intravascular coagulation
get expression of tissue factor inside blood on monocytes/ neutrophils (maybe endothelial cells)= Generalised activation of coagulation inside circuation
- Associated with (pathological situations) sepsis (bacteriaemia), major tissue damage, inflammation
- Consumes and depletes coagulation factors and platelets
- Activation of fibrinolysis depletes fibrinogen
Consequences
- Widespread bleeding, from iv lines, bruising
- Deposition of fibrin in vessels causes organ failure
Q: What are the clinical signs of defects of secondary haemostasis- pattern of bleeding?
A: - Often delayed (after primary haemostasis) -> Prolonged
- Deeper: joints and muscles
- Not from small cuts (primary haemostasis ok) = normal bleeding time
- Nosebleeds rare
- Bleeding after trauma/surgery
- After i/m injections
- bleeding often stops to begin with-> get break down and bleed again (on and off)
Q: What is ecchymosis? What is haemarthrosis?
A: Easy bruising
-Virtually all bleeding disorders
- hallmark of haemophilia - bleeding into joint spaces
Q: Aside from less coagulation factors, what can cause bleeding (EQM diagram)? (2)
A: increased fibrinolytic factors, anticoagulant proteins
Q: What causes defects in clot stability? (2) Common examples? (3)
A: Excess fibrinolytic (plasmin, tPA)
eg- Therapeutic administration of fibrinolytic drugs
- Some tumours
or
deficient antifibrinolytic (antiplasmin) eg- Antiplasmin deficiency (genetic)
Q: What usually causes excess anticoagulant? eg (3). Result?
A: therapeutic administration:
Eg heparin or thrombin and Xa inhibitors (given to suppress coagulation mechanism)
unbalanced haemostasis= bleeding
Q: Bleeding time test. What is the likely outcome of making a small blade incision on the forearm of a haemophilia patient?
A: normal bleeding that stops after 10 minutes
Q: What is thrombosis in terms of the EQM model? Too much? (2) Too little/deficiency? (2)
A: arrow at 2 o clock
too many coagulation factors eg VIII and IV, platelets
too little fibrinolytic factors, anticoagulant proteins eg antithrombin, protein C or S
Q: What is thrombosis? Result? Can be? (2)
A: ‘inappropriate coagulation’ event that doesn’t need to occur- in intact vessel (‘Intravascular coagulation’) with no break and no exposure to collagen
- ‘Coagulation not preceded by bleeding’
- Thrombi may be Venous or Arterial = different
Q: What are the effects of thrombosis? (2) What can happen after? Define. Describe (2).
A: Obstructed flow of blood
- Artery – myocardial infarction, stroke, limb ischaemia
- Vein – pain and swelling (can’t drain)
second thing that can happen to clots in blood vessels
-> susceptible to effects of blood flow = will embolise
Embolism: movement of something in circulation form one place to another
- Venous emboli, to lungs (pulmonary embolus)
- Arterial emboli, usually from heart, may cause stroke or limb ischaemia
Q: How do venous and artierial thrombi differ?
A: venous- blood factors are a major driver of thrombotic events
arterial- a lot more to do with arterial wall (cholesterol and plaques affect)
Q: Why is deep vein thrombosis dangerous? What does the result mean? What does the patient present with? (3)
A: danger= clot will come up to heart and lodge in lung -> can kill (pulmonary embolism)
part of lung doesn’t receive blood
shortness of breath, collapse and maybe chest pain
Q: What’s the prevalence of venous thrombo-embolism? How does that change with age? What percentage of all hospital deaths does it contribute to? How many estimated preventable deaths are there per annum?
A: - Overall 1 in 1000 - 10 000 per annum
- Incidence doubles with each decade
- PE is cause of 10% of hospital deaths
- Estimated 25k preventable deaths per annum
Q: What are the consequences of thrombo-embolism? (4) Include figures
A: Death - VT (venous thrombosis) case mortality 5%
Recurrence - 20% in first 2 years and 4% pa thereafter
Thrombophlebitic syndrome - Severe TPS in 23% at 2 years (11% with stockings)
=> permanent disturbance of circulation = recurrent swellings, pain and sometimes ulcers
Pulmonary hypertension - 4% at 2 years
=> in lungs and circulation doesn’t get back to normal -> gets worse
Q: Why do some people get thrombosis? (3) 2 models?
A: Genetic constitution
Effect of age and previous events, illnesses, medication
Acute stimulus
- compound life model
- virchows triad = more pathological model
Q: How can the causes of thrombosis be described? Diagram.
A: Thrombosis is Multi-Causal Arising from Interacting Genetic and Acquired Risk Factors
- age by risk
- thrombotic threshold= means you’ll get one
- risk from ageing (cumulative)
- acquired risk
- genetic risk factor
Q: Describe virchows triad. (5) Variation?
A: shows that there are three contributory factors to thrombosis:
blood dominant in venous thrombosis
vessel wall dominant in arterial thrombosis
flow complex, contributes to both
These may be inherited or acquired
varies person to person
Q: Name 3 anticoagulant factors. 4 coagulant proteins?
A: Antithrombin
Protein C
Protein S
Factor VIII
Factor II and others
Factor V Leiden (increased activity due to activated protein C resistance)
Thrombocytosis (increased platelets)
Q: The increased risk of thrombosis associated with the COCP is likely to be the result of…
A: reduced concentration of protein S
Q: Risk of thrombosis in terms of vessel wall. What’s the usual role of the vessel wall? What does it express? Examples (3). What alters expression? how? result? Examples that alter expression (3).
A: we know it has an anticoagulating role
Many proteins active in coagulation are expressed on the surface of endothelial cells eg:
- Thrombomodulin
- Tissue factor
- Tissue factor pathway inhibitor
Expression altered in inflammation= down regulates anticoagulant activity of endothelium and increases procoagulant
=> risk of thrombosis increases
examples of causes of inflam:
- Malignancy
- Infection
- Immune disorders
Q: Risk of thrombosis in terms of flow. How can it increase the risk? which thrombosis? Causes? (5)
A: Reduced flow (stasis) increases the risk of venous thrombosis.
- surgery
- fracture
- long haul flight
- bed rest
Q: What is thrombophilia? Clinical signs? (4) Role of laboratory? Example causes? (2) both are?
A: increased thrombosis risk often caused by hereditary disorders
- Thrombosis at young age
- ‘idiopathic thrombosis’
- Multiple thromboses
- Thrombosis whilst anticoagulated
Laboratory
- Identifiable cause of increased risk
- AT deficiency, Factor V Leiden, global measures of coagulation activity.
Q: What can cause combined risks for thrombosis? Examples (4). Describe one example (3).
A: Numerous conditions will alter blood coagulation, vessel wall and/or flow to precipitate thrombosis or make it more likely.
Eg:
- Pregnancy= blood and flow changes
- Malignancy= will have inflam response, may produce tissue factor and secrete into circulation, tumour could obstruct flow
- Surgery
- Inflammatory response
Q: What can cause post operative risk of VTE to vary?
A: inpatient surgery= higher risk
day case surgery= lower
Q: How can you treat venous thrombosis? (2-1,3) Include example for each and 3 for last one.
A: Treatment: to lyse clot
- eg tPA (high risk of bleeding)
Treatment: to limit recurrence/extension/emboli
- Increase anticoagulant activity
e. g: heparin (immediate acting, parenteral) - Lower procoagulant factors
e. g.: warfarin (oral, slow acting for long term therapy)
- Inhibit procoagulant factors– direct inhibitors eg Rivaroxaban (Xa), Apixaban (Xa), Dabigatran (IIa) = new drug class
Q: How will VTE be prevented? (3) 2 examples.
A: (NICE Guidelines 2010)
- Assess individual risk and circumstantial risk- look at age, genetic/acquired predispositions
- All patients admitted should have VTE risk assessment
- (hospital target >90%)
- Give prophylactic antithrombotic therapy (most)
- consider their bleeding risks
- (eg heparin for in-patients)
- +/ TED stockings (improve flow)
Q: Use the EQM diagram to show thrombosis treatment and prevention. 3 examples.
A: need to do reverse
currently facing 2 o clock, want 12 o clock
-since coag factors and platelets are increase
=> DECREASE coagulants eg warfarin and antiplatelets
-since fibrinolytic and anticoag are down
=> INCREASE anticoagulants eg heparin
