Exam 2: Walenga 3 Flashcards
Thrombosis is defined as the transition of blood from a state of ____ to ______
The stationary clot (_______) may grow in size and eventually break into smaller pieces, which when released into circulation are called _______
______ are dangerous because they can cause stroke, MI, PE
Thrombosis is defined as the transition of blood from a state of fluidity to non-fluidity
The stationary clot (thrombus) may grow in size and eventually break into smaller pieces, which when released into circulation are called emboli
Emboli are dangerous because they get lodged into smaller vessels and cause MI, Stroke, PE
Define the terms
DVT
PE
DVT is a blood clot (thrombus) that forms in a deep vein of the leg or pelvis either partially or fully blocking the flow of blood
PE or pulmonary embolism is when :
- DVT or part of it breaks off from the vein
- breakaway clot travels through blood stream, into heart and towards lung
- Clot blocks a vessel in the lung
Virchow’s Triad:
Explain the three major factors that lead to thrombosis
What is the “double hit theory”
Virchow’s Triad:
Three major factors that contribute to fibrosis:
- injury to blood vessel wall or endothelium (resulting in release of TF)
- alterations in blood composition
- blood flow stasis
Double hit theory: having two of the three greatly increases the risk of thrombosis
Define the term thrombophilia
Thrombophilia is defined as the predisposition to to thrombis, secondary to
- congenital risk factors
- acquired risk factors (age, smoking, diet, AFib, Anti-Phospholipid Syndrome)
Certain hemostatic factors increase in circulation in response to stress and inflammation
Which hemostatic factors lead to enhanced clot formation?
Which factors lead to supressed fibrinolysis?
Enhanced clot formation: Fibrinogen, FVIII, FXIII, VWF, C4bBP
Supressed clot breakdown: PAI-1
What are some clinical conditions associated with thrombosis?
Clinical conditions associated with thrombosis:
AFib
Antiphospholipid Syndrome
What are five conditions known to cause a hypercoagulable state:
- Factor ___ Leidein
- _______ mutation
- Deiciency or defect in ____
- Deficiency in ____
- Deficiency in ____
Cause a hypercoagulable state:
Factor V Leiden
Prothrombin 2021 Mutation
Defeciency or defect in AT
Deficiency in Protein C
Deficiency in Protein S
Coagulation Factor Inhibitors:
Important for maintaining the balance of the coagulation cascade, to control the amount of _____ generated
List them
Coagulation Factor Inhibitors:
Important for maintaining the balance of the coagulation cascade, to control amount of thrombin generated
Antithrombin (AT), Protein C (APC), Protein S, TFPI
Antithrombin/ (AT)
It will bind to _____, increasing the activity of AT
AT will bind to and inactivate ______
A deficiency in AT allows for too much ______
Antithrombin/AT
AT binds to heparin, enhancing its activity
AT then will bind to and inactivate thrombin and FX
A deficiency in AT allows for too much coagulation and an increased risk of thrombosis
Protein C Pathway:
Protein C cirulates in blood
The Protein C pathway is the only pathway in which thrombin acts as a ______
Thrombin binds to PC, creating APC
APC with the help of _______ then cleaves which Factors?
Protein C Pathway:
This is the only pathway in which thrombin acts as an anticoagulant
Thrombin binds to PC, activating it (APC)
APC then with the help of protein S will cleaves activated FV and activated FVIII
thereby reducing the generation of thrombin in the coagulation pathway
Draw out the protein C pathway
Explain Factor V Leiden
Also called Activated Protein C Resistance
A mutation of the FV gene substitutes _____ for ____ on FV
This substitution slows the inactivation of FV from _____ and _____
The resistant FVa remains active and promotes the formation of _______
Factor V Leiden: (Activated Protein C Resistance)
A mutation of the FV gene substitutes glutamine for arginine at position 506 on FV
That substitution slows the inactivation of FV from protein c and protein s
The resistant FVa remains active and still promotes the formation of thrombin
Patients with FVL are at a risk for thrombosis
What is the most common identified cause of thrombosis?
Patients with FVL are at a risk for thrombosis
FVL is the most identified cause of thrombosis (roughly 25% of all patients with thrombosis)
PAI-1
it is an inhibitor of _______
High PAI-1 levels are associated with _______ of thrombosis
PAI-1
PAI-1 is an inhibitor of TPA (remember tpa is the main activator of plasmin, the enzyme that breaks down clots)
High PAI-1 levels are associated with increased risk of thrombosis
What is the ONLY assay for the detection of active thrombosis?
How do levels of it increase with disease?
What does this test rule out clinically?
Only assay for the detection of active thrombosis:
D-Dimers
Normal level is 500, with DVT and PE are greater than 500
D-Dimer levels are used to rule out a PE (normal D-Dimer levels mean no thrombosis)
Explain what Antiphospholipid Syndrome is (APS)
The presence of antiphospholipid autoantibodies is consistent with ____
APAs mistakenly target the body’s own ______
Presence of an APA is a risk factor for thrombosis; persistant APAs are a larger concern
Clinically, APAs cause ________
APS:
The presence of antiphospholipid auto-antibodies is consistent with APS
APAs mistakenly targe the body’s own protein phospholipid complexes
Clinically, APAs cause unexpected thrombosis: recurrent thrombosis, or obstetric complications
Explain what Heparin Induced Thrombocytopenia is (HIT)
How is it a paradox?
Heparin Induced Thrombocytopenia:
a relatively common drug induced thrombocytopenia
Adverse reaction to heparin treatment
Paradox: Thrombocytopenia without bleeding,
HIGH RISK OF THROMBOSIS
HIT:
Heparin is a widely used anti-coagulant
Heparin binding to platelet Factor 4 is a _____ response
In some individuals, antibodies bind to PF4/heparin complex
That PF4/heparin/antibody complex binds to ____ and causes _______
Heparin Induced Thrombocytopenia:
Heparin is widely used as an anti-coagulant
Heparin binding to platelet factor 4 is a normal physiological response
In some individuals, antibodies bind to PF4/heparin complex
That PF4/heparin/antibody complex binds to Fc receptors on platelets and activates platelets, generating thrombin and creating a highlycoagulant state
HIT is a medical emergency due to the ______
that can occur and the high ______
Clinically, patients experience _____ and ______
What is the clinical definition of HIT?
HIT is a medical emergency due to the severe thrombosis that can develop and the high mortality rate
Clinically, patients experience thrombocytopenia and thrombosis develops (venous or arterial)
Clinical Definition of HIT:
Thrombocytopenia (platelets less than 100,000) or a 50% decrease from baseline with exposure to heparin
Thrombocytopenia usually develops 5-10 days after heparin exposure
Lab Tests for HIT:
Labratory Tests to support a diagnosis of HIT are performed in this order
1.
2.
3.
Lab Tests for HIT:
- Repeat Platelet Counts
- Immunoassay to find HIT antibodies (negative result rules out HIT, but there are false positives)
- Platelet function assay confirms positive immunoassay for the diagnosis of HIT
Clinical Management of HIT:
Platelets are not given since there is no risk of bleeding
Due to life-threatening thrombosis ________
Often a non-heparin anticoagulant is used as a ________ against development of thrombosis
If thrombosis is present, an anticogulant is given that is not heparin (_______)
Clinical Management of HIT:
Platelets aren’t given , no risk of bleeding
Heparin treatment must be stopped
Often a non-heparin anticoagulant is used as a prophylaxis against the development of a thrombosis
If thrombosis is present, an anticogulant that is not heparin is given (thrombin inhibitor)
Explain the difference between an venous thrombosis and an arterial thrombosis in terms of composition:
Venous thrombosis are rich in ___
Arterial thrombosis are rich in____
Venous thrombosis: rich in fibrin (anticoagulants target thrombin generation)
Arterial thrombosis are rich in platelets and vWF (anticogulants target thrombin generation platelet function inhibitors)
Vitamin K antagonist drugs like warfarin target which coagulation factors?
Heparin drugs target which coagulation factors?
Vitamin K antagonists (warfarin) target F2, 7, 9, 10
Heparin targets intrinsic factors, X, and AT
Anticoagulant Drugs for treatments against an established venous thrombosis
1,
2,
Anticoagulant Drugs for treatments against an established venous thrombosis:
- Heparin
- Thrombin inhibitors (good to use to treat HIT)
Anticoagulants used in prophylaxis to prevent venous thrombosis:
1.
2.
3.
4.
Anticoagulants used in prophylaxis to prevent venous thrombosis:
- low molecular weight heparin
- coumadin/warfarin
- thrombin inhibitors
- FXa inhibitors
HEPARIN:
- Catalyzes the inactivation of multiple _____
- How does it work?
- Heparin needs to be monitored, how is it monitored and what is the preferred monitoring method?
HEPARIN:
Catalyzes the inactivation of multiple coagulation factors
It works by activating Anti-Thrombin, which then binds to thrombin and inactivates it
Heparin monitoring is done by APTT assay, but the preferred way is a anti-FXa heparin assay
The ultra low molecular weight heparins such as fondaparinux:
Only inhibits _____
Assess plasma levels with _____ assay
Ultralow molecular weight heparins such as fondaparinux:
Only inhibit FXa
Assess plasma levels with anti-FXa heparin assay
Coumadin/Warfarin:
Inteferes with vitamin ____
Thereby reducing the synthesis of factors……
Those factors are unable to bind ____ and ___
Result is a decreased functionality of these coagulation factors (like a defeciency)
Coumadin/warfarin:
Intereferes with vitamin K
Thereby reducing the synthesis of factors 2, 7, 9, 10
Those factors are unable to bind Ca and phospholipids
Result is a decreased functionality of those coagulation factors (like a defeciency)
Effect of Warfarin on Coagulation Assay:
_____ is the first factor to decrease and _____ is the last
Takes roughly ___ days for full anticoagulation effect
Effect of warfarin on coagulation assay:
FVII is the first factor to decrease and prothrombin is the last
Takes roughly 5 days for full anticoagulation effect
The ______ test is the test to measure therapeutic levels of coumadin/warfarin
PT test (extrinsic factors and common pathway)
is used to analyze warfarin effects
For DOACs what two kinds of mechanisms do they do? What are two ways in which they work?
What are they approved for?
DOACs: are either thrombin inhibitors drugs that only block thrombin
or
FXa inhibitor drugs that only block activated FX
DOACs are approved for thrombis prevention in patients with AFIb
Direct Acting Thrombin Inhibitors:
Direct Acting Thrombin Inhibitors are small molecules that ______
DTIs are small molecules that directly bind to thrombin
Arterial thrombosis is a platelet mediated disorder, therefore anti-platelet drugs have to be used
The most common anti-platelet drug is _____
Explain how it works
How long is the inhibitory effect of just one
Most common anti-platelet drug is aspirin
Aspirin irreversibly blocks cyclo-oxygenase, thereby preventing the production of thromboxane (which is the most potent platelet activating substance)
Inhibitory effect of aspirin is permanent for the entire lifespan of the platelet (7-10 days)
Aspirin for arterial thrombosis:
Can detect the anti-platelet effect with:
the _______ test using ______ as the agonist
OR the ______
Aspirin for arterial thrombosis:
Can detect anti-platelet effect with:
The platelet aggregation test using arachnoic acid as the agonist
OR the VerifyNow ASA assay
