CVS 10: Thrombosis Flashcards
What needs to be in balance for haemostasis?
- Fibrinolytic factors, anticoagulant proteins
vs - Coagulation factors, platelets
What happens if fibrinolysis > coagulation?
- Describe the features of this condition
Bleeding that is:
- spontaneous
- out of proportion to the trauma/ injury
- unduly prolonged
- restarts after appearing to stop
- prolonged nose bleeds (epistaxis)
What forms the primary haemostatic plug?
Platelet- Von Willebrand Factor- Collagen
What are the defects of primary haemostats?
- Platelets- Aspirin can affect platelet activity, thrombocytopenia is a relative decrease in the number of platelets in the blood
- Von Willebrand Factor- VW disease= genetic deficiency of the factor
- Collagen- steroid therapy makes the collagen and vessel wall weak, raging weakens the vessel wall as well
What are the defects of primary haemostasis and its pattern of bleeding?
- Immediate
- Easy bruising
- Nosebleeds (>20mins)
- gum bleeding
- menorrhagia
- bleeding after trauma/ surgery
- Petechiae (specifically for thrombocytopenia)
What are petechiae?
- small blood spots which occur in people who are thrombocytopenic
- Appear spontaneously
- platelets are constantly busy plugging small holes in blood vessels= continuous process of repair
What is Secondary Haemostasis?
- generation of thrombin from prothrombin
- This converts fibrinogen to fibrin to form the insoluble mesh around platelets
==> blood coagulation, stops blood loss
How can you visualise the process of coagulation?
- measure thrombin generation over time using a THROMBOGRAM
Why is there a lag in the thrombogram after the TF trigger?
During this time cofactors and anticoagulant enzymes are being generated and then you get the burst of thrombin
What happens during Haemophilia A on the thrombogram?
Factor 8 is missing
- you don’t get the thrombin burst on the thrombogram
- slower increase in thrombin
- not much thrombin produced
What is the consequence of Haemophilia A?
- Thrombin not produced
- fibrinogen not converted to fibrin
- fibrin mesh not formed
- clot not stabilised
- only left with primary platelet plug which falls apart easily
Name some causes of defects in secondary haemostasis
Genetic:
- Haemophilia A/B: F8/9
Acquired:
- Liver disease (most coagulation factors made in the liver)
- Drugs (warfarin- inhibits synthesis of coagulation factors)
- Dilution (results from volume replacement)
- Consumption (disseminated intravascular coagulation- DIC)
What is disseminated intravascular coagulation also known and what causes it?
CONSUMPTIVE COAGULOPATHY
- generalised activation of coagulation- Tissue Factor
- Consumes and depletes coagulation factors and platelets
- activates fibrinolysis which depletes fibrinogen
What is DIC associated with?
Sepis, major tissue damage and inflammation
What are the consequences of DIC?
- Widespread bleeding (from IV lines) bruising (internally)
- Deposition of fibrin in vessels causes organ failure
What is the pattern of bleeding when there is a defect in secondary haemostats?
- often delayed
- prolonged
- deeper bleeding (in joints and muscle) because primary haemostasis insufficient in big vessels
- small vessels are okay
- nosebleeds are rare
- bleeding after trauma/ surgery
- bleeding after intramuscular injections
What is haemarthrosis and with which condition is it often associated?
associated with Haemophilia A/B
- bleeding into the joints
- pressure builds up and joint becomes stoles and painful
Other than a decrease in coagulation, what could cause excessive bleeding?
Excess fibrinolysis
- excess fibrinolytic (plasmin, tPa): therapeutic administration and some tumours
- Deficient antifibrinolytic (antiplasmin): antiplasmin deficiency
Give some examples of substances which are administered therapeutically and could cause an anticoagulant excess if administered at incorrect levels
Heparin
Thrombin
Factor Xa inhibitors
What happens when coagulation factors> fibrinolytic factors?
Thrombosis
What is thrombosis?
- Inappropriate intravascular coagulation
What are the effects of thrombosis?
- Obstructed Flow of blood
- Artery: MI, stroke and limb ischaemia
- Vein: pain and swelling - Embolism
- Venous emboli= pulmonary embolism
- Arterial emboli= usually from the heart, may cause limb ischaemia or stroke
What is deep vein thrombosis?
Thrombus in one of the deep veins mainly in the lower limbs where venous return of blood is obstructed
What are the consequences of a thrombosis-embolism?
- After the first thrombosis, the valve system might be damaged meaning, there is more stasis
- THROMBOPHLEBITIC SYNDROME= swelling and ulcers in the leg due to damage to valve leading to stasis
- Pulmonary hypertension
