Thrombo embolic disease Flashcards
Normal clot formation - 2 types
1) Primary clotting
2) Secondary clotting
Components of primary clot
-platelet plug
Components of secondary clot
- coagulation cascade
- negative feedback
The clotting cascade components
1) Intrinsic
2) Extrinsic
3) Common
enzymes (proteases) = most of the factors
coenzymes = V & VIII
cofactors = calcium , phopholipids
Coagulation cascade
X
Negative feedback mechanisms
- Anticoagulants
- antithrombin (inhibits proteases)
- TFPI (inhibits proteases, mainly VIIa/TF) - Fibrinolysis
why called D-dimers
-2 D globulins and one E subunit
Classification of diseases of clotting
1) Which vessels they occur in
- venous thromboembolism (VTE)
- arterial thrombosis
- capillary thrombosis
Why venous system is high risk of clotting
-Stuff is sitting there for awhile
Common cause arterial thrombosis
Atherosclerosis
Cause Capillary thrombosis
Mainly due to microangioathic hemolytic anemias
Types of VTE diseases
- Superficial vein thrombosis (SVT)
- Migratory SVT
- Deep vein thrombosis (DVT)
- DVT complicatins
SVT causes
-from IV, catheters etc
Complications from SVT
Are rare
What are migratory SVT a sign of
Malignancy
DVT common complications
- pulmonary embolism
- postphlebitic syndrome
Etiology /Risk of VTE- acquired VTE
- immobility
- age
- pregnancy (to compensate for excess breathing in birth)
- obesity
- trauma
- surgery
- malignancy
- meds -birth control pill
- inflammation (autoimmune disorders)
- hyperviscosity (blood get thicker occuring in rare disorders -i.e. get lots of RBCs)
- antiphospholipid antibody syndrome (APLAS)- make autoantibody to phospholipids
Etiology/Risk of VTE - hereditary
- factor V leiden
- prothrombin gene mutation
- protein C deficiency
- protein S deficiency
- antithrombin-3 deficiency
- increased factor 8
- increased homocysteine
Virchows triad
1) Stasis
2) Vascular injury
3) Hypercoag
What risks propagate clotting through vascular injury
1) Surgery
2) Trauma
3) Malignancy
4) Inflammation
5) Homocysteine
What risks propagate clotting through stasis
- immobility
- age
- pregnancy
- obesity
What risks propagate clotting through hypercoag
- hereditary thrombophilias
- pregnancy
- age
- malignancy
- hyperviscosity
- meds -OCP
Risks with multiple mechanisms leading to clotting
- pregnancy
- age
- malignancy
Unknown mechanisms of clotting
- hyperhomocysteinemia ( does it cause the clot or is it consequence)
- antiphopholipid antibody syndrome (APALS)
Classification of hereditary thrombophilias
- Loss of anticoagulant function
- antithrombin 3 deficiency
- protein C deficiency
- protein S deficiency - Gain of factor function
- factor V leiden
- prothrombin gene
- elevated Factor VIII
Accumulative risk
2 or more risk factors - risk of clot goes up exponentially
Postphlebitic synrome MOA
Chronic venous insufficiency leads to venous hypertension which then causes edema, hypoxia, inflammation
Signs of DVT
- swelling, painful
- red, warm (inflmmation signs)
Signs of PE
typical: SOB, chest pain, hemoptysis
Atypical: abdominal pain, syncope, fever, cough, seizure
Postphlebetic syndrome
- swelling
- pain
- ulcers
- rash
Radiological testing
1) Ultrasound
2) CT
Lab testing
- DDimers
- high sensitivity
- low specificity - Etiologic testing
DD dimers high sensitiivity
If negative, excludes VTE
DD dimer low specificity
If positive, can be due to thrombosis, infection, trauma, surgery
Etiologic testing
Figure out what could be the trigger for the clot
What ??(tests for)
a) is it hereditary?
b) is it acquired?
When to do these panel of testing
1) unprovoked +/-recurrent VTE
2) Strong family history
3) Purpura fulminans in neonates and children (requires urgent protein C and S testing)
When not to test for hereditary factors
1) provoked (obvious trigger)
2) not recurrent
3) Arterial thrombosis
General guideline when to test for hereditary disorder
1) Change in management
- duration of anticoagulant
- prophylaxis required
- alternative to OCP or HRT required
Goal of treatment
To prevent further clot formation
dont want to bust clot because huge risk of emboli-travelling to the lungs
Treatment
-heparin + coumadin (warfarin)
-5 day overlap
because:
heparin acts more rapidly (increases AT-3 activity) but is given IV
-Coumadin is PO but acts slower and has potential transient procoagulant state (inhibts vitamin K dependent factors + protein C&S)
How long continue treatment
Typically 6 months on coumadin 3 months (with transient risk factor) Indefinite (for recurrent DVT)
