Thrombophilia and Anticoagulant Therapy Flashcards
Discuss the mechanism by which coagulation is inhibited by tissue factor pathway inhibitor (TFPI)
- Inhibits the TF pathway by inactivating Factor VIIa
- Due to the action of TFPI: TF-VIIa is short lived and coagulation amplification occurs primarily through XI
Origin of Protein C (and Protein S)
Synthesized in the liver
What are Protein C and S dependent upon?
Vitamin K
What is the principle of Protein C and S by which coagulation is inhibited and affected factors?
It inactivates Va and VIIIa and may cause recurrent thromboses (blood clot)
State the mutation that is responsible for the most commonly inherited form of thrombophilia
Activated Protein C resistance (APCR) → called Factor V Leiden mutation
Origin of antithrombin
Liver
Is antithrombin dependent upon Vitamin K?
No
Principle of antithrombin (AT) by which coagulation is inhibited, including affected factors
- Serine protease inhibitor (SERPIN)
- Irreversibly binds and neutralizes the serine proteases `in the intrinsic pathways: XIIa, XIa, IXa, Xa, thrombin (IIa)
In the antithrombin, when no heparin is present, AT’s binding w/ the serine proteases is a ____ reaction
Slow, progressive
When either endothelial cell heparan or exogenously administered ____ is present, ____ binding w/ the serine proteases is ____ and enhanced 1,000-fold!!
Heparin is present; AT’s binding; immediate
The effect of deficiency states of antithrombin (AT) and protein C (protein S)
May cause recurrent thromboses
Eight factors that predispose a person to thrombosis
- Age
- Hereditary
- Immobilization/stasis
- Smoking
- Malignancy
- Injury to vessels (trauma, surgery)
- Elevated estrogens (low protein S, C, AT)
- Inflammation
- Antiphospholipid syndrome
Three types of thomboses
- Arterial thromboses
- Microcirculatory (TTP, HUS, DIC)
- Venous thromboses
What is the process by which arterial thrombosis are formed?
Result of a disease process which causes major damage in a vessel wall (myocardial infarction, arteriosclerosis)
Arterial thrombosis
- Major component
Platelets
Arterial thrombosis
- Treatment
Anti-platelet drugs (aspirin, plavix)
Process by which venous thrombosis are formed?
Result of a major stasis in blood flow (DVT, pulmonary embolus)
Venous thrombosis
- Major component
Fibrin
Venous thrombosis
- Treatment
Antifibrin drugs (heparin, coumadin)
Defined as a predisposition of thrombosis secondary to a congenital or acquired disorder
Thrombophilia
Defined as the inappropriate formation of platelet or fibrin clots that obstruct vessels
Thrombosis
Defined as any foreign object in the bloodstream such as air, bullet, clot
Embolus
Four types of anticoagulant therapy
- Standard unfractionated heparin (UFH)
- Low molecular weight heparin (LMWH)
- Coumadin drugs
- Thrombolytic agents (clot busters)
Standard unfractionated heparin (UFH)
- Mechanism of action
Heparin by itself is NOT and anticoagulant must complex w/ AT and ATP is called the “heparin co-factor”
Standard unfractionated heparin (UFH)
- Indication for therapy
Treatment of thrombosis to prevent propagation
Standard unfractionated heparin (UFH)
- Administration
IV or subcutaneously (SQ)
Standard unfractionated heparin (UFH)
- Monitoring
APTT
- Target for therapy
- Prophylaxis
- Daily platelet counts to detect HIT
Standard unfractionated heparin (UFH)
- Overdose
Treat w/ protamine sulfate
Low molecular weight heparin (LMWH)
- Mechanism of action
Increases the inhibitor effect of AT on thrombin and Xa (mainly Xa)
Also known as Lovenox
Low molecular weight heparin (LMWH)
Low molecular weight heparin (LMWH)
- Administration
SQ
Low molecular weight heparin (LMWH)
- Indication for therapy
Treatment of thrombosis to prevent propagation; not as commonly used but great for those needing to go home on heparin
Low molecular weight heparin (LMWH)
- Monitoring
Anti-Xa heparin assay (APTT is insensitive)
Why is monitoring Low molecular weight heparin (LMWH) necessary?
For infants, children, obese or underweight patients, those w/ renal disease, or unexpected bleeding
Which brand is most common for long-term anticoagulant therapy?
Coumadin
Which brand is the oldest brand name for long-term anticoagulant therapy
Warfarin
Coumadin
- Mechanism of action
Coumadin blocks the action of vitamin K which is needed for the synthesis of the vitamin K dependent factors. Therefore, slowing thrombin formation
What are the vitamin K dependent factors?
Prothrombin group (II, VII, IX, X)
Coumadin
- Administration
Oral
Coumadin
- Delayed reaction or immediate reaction?
Delayed reaction (3-5 days)
Coumadin
- Indication for therapy
Treatment of thrombosis to prevent propagation; prevention of thromboembolic disease in thrombophilia, mechanical heart valves, and high risk surgery.
Coumadin
- Monitoring
PT and INR
Coumadin
- Overdose
Treat by giving vitamin K and FFP if major bleeding
Standard Unfractionated Heparin (UFH)
- Immediate or delayed reaction?
Immediate reaction
List sources of vitamin K
- Diet: green leafy vegetables, fish, and liver
- Normal gut flora: E. coli, B. fragilis
Three situations in which vitamin K deficiency may occur
- Poor diet
- Long-term antibiotic therapy
- Newborns
Vitamin K makes the prothrombin factors functional by ____
By adding a 2nd carboxyl group on the γ carbon. In vitamin K deficiency or in the presence of a vitamin K antagonist, these factors are released from the liver without the γ-carboxylation rendering them nonfunctional
Thrombolytic agents (clot busters) - Mechanism of action
Indiscriminately induce in vivo fibrinolysis by activating plasminogen to plasmin; not only get rid of bad clots but good clots too
Types of thrombolytic agents
- Tissue plasminogen activator (TPA)
- Streptokinase
- Urokinase
Why is TPA considered the best/safest clot buster?
B/c it will NOT activate circulating (free) plasminogen…only fibrin bound
When is the therapeutic agent TPA used?
- Life threatening thromboses
- Must be given w/in 4-6 hours of onset
