Chapter 25: Thrombosis and antithrombotic therapy Flashcards
What is thrombophilia?
Thrombophilia are inherited or acquired disorders that predispose to thrombosis?
What are the strongest independent predictors of coronary events?
The levels of factor VII and fibrinogen. Hyperhomocysteinemia has also been associated with increased risk.
What is Virchow’s triad?
Virchow’s triad is composed of three components that are extremely important for thrombus formation.
(1) Slowing of blood flow
(2) hypercoagulability of the blood
(3) Vessel wall damage.
What events suggest a hereditary thrombophilia?
Younger patients that suffer from spontaneous and recurrent thromboses in abnormal locations.
What is the most common disorder that increases the risk of thrombosis?
Factor V leiden mutation. (4% of caucasians)
With what protein deficiency is skin necrosis due to dermal vessel occlusion after warfarin administration associated?
Protein C deficiency
Why does warfarin cause vessel occlusion associated with protein C deficiency?
Because Warfarin inhibits vitamin K dependent factors. Vitamin K is necessary for protein C to function.
How does prothrombin allele G20210A lead to thrombophilia?
There is increased levels of prothrombin which leads to increased thrombin and down regulation of fibrinolysis.
What enzyme is responsible for hyperhomocysteinemia?
A defect in cystathione beta synthase is responsible for hyperhomocysteinemia.
What are some causes of acquired hyperhomocysteinemia?
(1) Folate or B12 deficiency
(2) B6 deficiency
(3) drugs (ciclosporin)
(4) renal damage.
(5) smoking.
Do defects in fibrinogen lead to thrombosis?
Not usually, bleeding is more likely.
What are some common acquired risk factors for thrombosis?
(1) surgical opperations
(2) Venous stasis and immobility
(3) Malignancy
(4) Inflammation
(5) polycythemia and ET
(6) increased estrogen
What is antiphospholipid syndrome?
The occurrence of repeated thromboses/miscarriages with the presence of anti phospholipid antibodies. These antibodies are in some cases secondary to autoimmune disease.
Why does glucosylceremide deficiency lead to thrombosis?
Because glucosylceremide modulates the protein C pathway.
Why are factor IX concentrates sometimes complicated by thrombosis?
Because factor IX concentrates often contain activated coagulation factors.
What factors should increase the clinical suspicion of deep vein thrombosis?
Bedridden patients with unilateral swelling or tenderness.
What is the first line test when DVT is suspected?
Serial compression ultrasonography
What is the second line test if ultrasonography is negative yet clinical signs point to DVT?
Contrast venography
What is a plasma D-dimer concentration assay?
Plasma D-dimers are the breakdown products of fresh thromboses. They are elevated if DVT has occured. However they may be elevated in some other conditions as well.
When should a pulmonary embolus be suspected?
When the patient has
(1) history of DVT
(2) immobilization for more than 2 Days
(3) surgery
(4) hemoptysis
What methods may be used to diagnose pulmonary embolism?
(1) chest X-ray
(2) ventilation perfusion scintigraphy
(3) Computed tomography pulmonary angiographty
(4) MRI angiography
(5) Pulmonary angiography
How is heparin administered?
intravenously
How is heparin eliminated by the body?
Heparin is inactivated by the liver and excreted in the urine.
What is the biological half-life of heparin?
Approximately 1 hour.
What is heparin’s mechanism of action?
Heparin potentiates the formation of complexes between antithrombin and thrombin, IXa, Xa, and XIa. This leads to the irreversible inactivation of these factors.
What are the indications for Heparin?
(1) DVT
(2) Pulmonary embolism
(3) unstable angina pectoris
(4) Prophylaxis during pregnancy (does not cross the placenta)
What is the treatment of choice for acute pulmonary embolus?
Continuous intravenous heparin
What is the preferred prophylacitic treatment for venous thrombosis?
Intermittent subcutaneous heparin.
What is the difference between regular heparin and low molecular weight fractionated heparin?
LMWFH has a longer half life, more predictable dose response, and has less severe side effects (50% less side effects).
What are some adverse effects associated with heparin?
(1) Bleeding
(2) Heparin induced thrombocytopnenia
(3) Osteoporosis (with more than 2 months use)
What are the oral anticoagulants?
Derivatives of coumarin or indandione
Warfarin is most commonly used.
What is the mechanism of warfarin?
Warfarin is a vitamin K antagonist.
Between warfarin and heparin which one is preferred during pregnancy?
Warfarin is teratogenic therefore heparin is preferred because it does not cross the placenta.
How is warfarin eliminated?
Warfarin is inactivated in the liver and then excreted in the bile.
What drug interactions are important for Warfarin?
(1) alterations in albumin binding (warfarin is 97% bound
(2) Interactions involving the excretion of warfarin
(3) interactions altering vitamin K absorbtion
What is protamine?
Protamine is able to inactivate heparin and can be used as an antidote in the event of heparin overdose/excessive bleeding.
How can warfarin overdose be managed?
Giving vitamin K can overcome the effects of warfarin overdose.
How is warfarin therapy managed during surgery?
For minor surgery tranexamine acid (an anti-fibrinolytic) can be used as a mouth rinse. However, for major surgery the warfarin must be stopped.
What are the ‘New’ anticoagulants?
(1) fondaparinux (a factor Xa inhibitor)
(2) Bivalirudin (thrombin inhibitor)
(3) Ximelagraten (thrombin inhibitor
What drugs can be used as thrombolytic agents?
(1) streptokinase
(2) Acylated plasminogen streptokinase activator complex (APSAC)
(3) tissue plasminogen activator (tPA)
(4) Urokinase type plasminogen activator
What are the antiplatelet agents that can be used to fight thrombosis?
(1) aspirin (irreversible COX inhibitor)
(2) Dipryidamole (phosphodiesterase inhibitor)
(3) Sulfinpyrazone (competitive inhibitor of COX)
(4) Ticlopidine (is mostly replaced by clopodigrel)
(5) Clopodigrel (ADP receptor antagonist)
What are the GPIIb/IIIa inhibitors?
(1) abciximab
(2) eptifibatide
(3) tirofiban
They can only be used once.
