Thrombophilia Flashcards
What is thrombophilia?
Thrombophilia is a group of disorders of the haemostatic mechanism, which are likely to dispose to thrombosis
What are some potential mechanisms of thrombophilia?
- Increased coagulation activity
- Decreased fibrinolytic activity
- Decreased natural anticoagulant activity
What are hereditary thrombophilias?
Hereditary thrombophilias are a group of genetic defects in which affected individuals have an increased tendency to develop premature, unusual and recurrent thromboses
What are some causes of hereditary thrombophilia?
- Factor V leiden
- Prothrombin 20210 mutation
- Antithrombin deficiency
- Protein C deficiency
- Protein S deficiency
Who is genetic screening for thrombophilia considered in?
- Venous thrombosis <45 y/o
- Recurrent venous thrombosis
- Unusual venous thrombosis
- Family history of venous thrombosis or thrombophilia
What management do all hereditary thrombophilia patients receive?
Advise on avoiding risk factors
What management option is given to thrombophilia patients in periods of known risk (e.g. pregnancy)
Short term prophylaxis to prevent thrombotic events
What management is given to thrombophilia patients in cases of thrombotic events?
Short term anticoagulation
What management option is given to thrombosis patients with recurrent thrombotic events?
Long-term anticoagulation
How do multiple risk factors increase risk of thrombotic events in thrombophilia?
Some people with hereditary thrombophilias may never have a thrombosis, as it is a multifactorial disease, so is usually caused by a combination of risk factors (Risk factors multiply, not add e.g. if contraceptive increases risk by 5x and obesity by 3x, then both together will increase risk by 15x)
What are some factors that increase risk of recurrent thrombosis?
- History of previous thrombosis
- Spontaneous thrombosis without transient risk factors
- Family history
- Thrombophilia screen results
What is a common cause of acquired thrombophilia?
Anti-phospholipid syndrome
What are some clinical features of anti-phospholipid syndrome?
- Recurrent thromboses (Arterial and venous)
- Recurrent foetal loss
- Mild thrombocytopenia
Describe the pathophysiology of anti-phospholipid syndrome
Antibodies lead to a conformational change in ß2 glycoprotein 1 (A protein with unknown function in health), which leads to activation of both primary and secondary haemostasis and vessel wall abnormality
Anti-phospholipid antibodies are autoantibodies which have specificity for anionic phospholipids and which prolong phospholipid dependant coagulation tests in vitro
What other name is given to anti-phospholipid autoantibodies?
Lupus anticoagulants
How will APTT and PT be affected in anti-phospholipid syndrome?
This will cause a prolonged APTT but normal PT
What are some conditions associated with anti-phospholipid syndrome?
- Autoimmune disorders
- Lymphoproliferative disorders
- Viral infections
- Drugs
- Primary
What anti-bodies may be present in anti-phospholipid syndrome?
Lupus anticoagulants (Anti-phospholipid)
Anti-cardiolipin antibodies
Anti-ß2 glycoprotein antibodies
What are some venous thrombotic symptoms and signs of thrombophilia?
- DVT/PE
- Recurrent pulmonary emboli leading to pulmonary hypertension
- Lived reticularis
How does venous thrombosis lead to livedo reticularis?
Blood clots in capillaries lead to swelling of the venue’s, resulting in purple, net-like discolouration of the skin
What are some arterial thrombotic symptoms and signs of thrombophilia?
- Stroke or MI risk
- Libman-Sacks endocarditis (Can further increase stroke risk)
What are some non-specific signs and symptoms of anti-phospholipid syndrome?
- Catastrophic APS - Multi-organ infarctions over a period of days to weeks
- Miscarriage
- Migraine
When can miscarriages occur in anti-phospholipid syndrome?
Most commonly in second or third trimester, but can occur at any time in pregnancy
Recurrent early foetal loss (<10 weeks) may also occur
How is an episode of thrombosis in patients with APS managed?
Treatment requires management of both primary and secondary haemostasis and thus arterial and venous thrombosis:
Acute LMWH then warfarin or aspirin prophylaxis
How are patients who are positive for APS antibodies, but who have never had an episode of thrombosis managed?
No treatment required
How are pregnant patients with a history of recurrent pregnancy loss treated in APSS?
LMWH and aspirin
