Haemostasis Flashcards
What is haemostasis?
Arrest of bleeding and maintenance of vascular patency
What is the lifespan of platelets?
7-10 days
When is Von Willebrand Factor released?
When there is vessel endothelial damage which exposes collagen.
What is the screening test for primary haemostats?
Platelet count
can measure von Willebrand factor if history indicates it
What converts plasminogen to plasmin? When can it be used as a treatment?
tissue plasminogen activator (tPA)
To break down clots e.g. acute stroke
What are D-dimers?
Cross-linked Fibrin Degradation Products (FDPs)
What 2 factors convert prothrombin to thrombin?
Factor V and Xa
What factors are affected in prolonged PT?
Tissue factor
Factor VIIa
What factors are affected in prolonged APTT?
Factor VIII
Factor IXa
What condition can cause isolated prolonged APTT?
Haemophilia
What is thrombophilia?
Deficiency of naturally occurring anticoagulants (may be hereditary). Therefore, increased tendency to develop venous thrombosis.
What proteins are involved in natural anticoagulation by switching off factor V and VII?
Protein S and Protein C
What is primary haemostats?
Formation of platelet plug
What is secondary haemostats?
Formation of fibrin clot
What are the causes pf platelet functional defects?
Hereditary (rare)
Acquired:
- drugs (aspirin, NSAIDs etc)
- renal failure
Where are all the clotting factors produced?
Liver
What is the significance of low albumin in the context of abnormal bleeding?
Liver produces both albumin and clotting factors, so if there is low albumin due to liver disease, suggests the liver won’t be producing enough clotting factors either.
What are the multiple clotting factor deficiencies?
Liver failure
Vitmain K deficiency/Warfarin therapy
Complex coagulopathy: DIC
What is the effect of multiple clotting factor deficiencies on PT and APTT?
Both prolonged
What causes Haemorrhagic disease of the newborn and how is it prevented?
Babies don’t have dietary intake of vitamin K or any gut flora to make vit K so they have clotting deficiency. Newborns get IM vitamin K to prevent this
Why do you get end organ failure in DIC
Microvascular thrombus formation
If both PT and APTT are prolonged, what does this suggest?
Multiple clotting factors problem
What happens to D-dimer levels in DIC and why?
Increase, due to excess fibrinolysis
What are the PT and APTT in haemophilia?
PT: normal
APTT: very prolonged (because the problem is with Factor VIII or IX)
What is the main component of arterial thrombus vs venous thrombus and what are the targeted treatments in each case?
arterial: platelet-rich clot - treat with anti-platelets
Venous: fibrin-rich clot - treat with fibrinolytics and drugs that interfere with fibrin clots (heparin, warfarin etc)
What are the complications of PE?
pulmonary infarction pleuritic chest pain cardiovascular collapse/sudden death hypoxia right heart strain
What are the risk factors of VTE?
age marked obesity pregnancy puerperium oestrogen therapy previous DVT/PE trauma/surgery malignancy paralysis infection thrombophilia
Which naturally occurring anticoagulant binds to thrombin?
Anti-Thrombin III
What is the commonest hereditary thrombophilia?
Factor V Leiden (Impairs protein C/S)
When would you consider hereditary thrombophilia screening?
Venous thrombosis
How is hereditary thrombophilia managed?
Advice on avoiding risk
Short term prophylaxis - to prevent thrombotic events during periods on known risk (e.g. pregnancy)
Short term anticoagulation - to treat thrombotic events
Long term anticoagulation - if recurrent thrombotic events
What is acquired thrombophilia?
Antiphospholipid antibody syndrome
What happens to ATPP in Antiphospholipid syndrome?
It is prolonged
- paradoxical as you would expect this make pt prone to bleeding but the clotting factors are unaffected and pts are actually prone to thrombosis
How is anti-phospholipid syndrome treated and why?
aspirin and warfarin
anti-platelet and anti-coagulant because there is activation of primary and secondary haemostasis
What are the immune causes of thrombocytopenia?
ITP
Drugs (penicillin, thiazides, oral hypoglycaemics, heparin, blood transfusion)
SLE
HIV
What drugs are used to prevent strokes?
Atherosclerosis - anti-platelets
AF (fibrin-rich clot in LA) - anti-coagulants
What do you monitor in patients on Warfarin?
PT (INR)
What do you monitor in patients on unfractionated Heparin?
APTT
Give an example of a coumarin anticoagulant
Warfarin
What is a complication of long term heparin therapy?
Osteoporosis
What is the target INR for most patients in warfarin?
What might make you aim for higher?
2 - 3
Further event despite warfarin treatment - aim for a max of about 3.5 - 4
What are the bleeding complications of warfarin therapy?
Mild: - skin bruising - epistaxis - haematuria Severe: - GI bleeds - intracranial bleeds (risk is about 1 in 200) - significant drop in Hb
How long does it take for vitamin K to reverse the effects of warfarin therapy?
6 hours
What can you given for immediate reversal of warfarin therapy in a life-threatening situation?
Administer clotting factors (FFP or factor concentrates)
What are the 2 groups of new anticoagulants? Give an example of each
Oral direct thrombin inhibitors e.g. Dabigatran
Oral Factor Xa inhibitors e.g. Rivaroxaban, Apixaban
What is the risk of giving Dabigabtran to elderly patients?
Dabigatran is renally excreted so patients with renal impairment are at risk of build-up of the drug - risk of bleeding.
What do platelets do in arterial thrombosis?
Plaque rupture due to high pressure environment of arteries
Platelets adhere to exposed endothelium and there is release of vWF
Platelets become activated - release granules that activate coagulation and recruit other platelets to developing platelet plug
platelet aggregation via membrane glycoproteins
A 21 year old girl has a history of heavy periods and investigations indicate a defect in primary haemostasis. Her blood count is normal. What is the most likely diagnosis?
Von Willebrand’s Disease (primary haemostats failure but normal platelet count)
What does an isolated prolonged APTT suggest?
Deficiency of factors involved in the ‘intrinsic’ pathway of coagulation (Factor VIII, IX, vWF [as it binds Factor VIII]) or the presence of an anti-phospholipid antibody (lupus anticoagulant) that is not associated with a bleeding phenotype
