Term
| a blood clot; an aggregation fo blood factors, primarily platelets and fibrin with entrapped blood cells |
|
Definition
|
|
Term
| a clot (or other plug) carried by the blood from one site to another, smaller vessel, that obstructs the circulation |
|
Definition
|
|
Term
|
Definition
1. maintain blood clot-free in normal vessels
2. induce a rapid and localized hemostasis by forming a clot at a site of vascular injury
KEY POINT: clot should not impair circulation! |
|
|
Term
| pathological extension of hemostasis producing a clot that impedes blood flow |
|
Definition
|
|
Term
| steps in normal hemostasis |
|
Definition
1. vascular phase
2. platelet phase
3. coagulation phase
4. repair phase |
|
|
Term
|
Definition
|
|
Term
|
Definition
| platelet plug (temporary unless significant coagulation phase occurs) |
|
|
Term
|
Definition
| reinforce platelet plug with fibrin |
|
|
Term
|
Definition
| dissolve clot, repair endothelium, phagocytosis of debris |
|
|
Term
| Vasoconstriction occurs by what 3 chemical mediators? |
|
Definition
prostacyclin (PI2)
thromboxane A2 (TXA2)
serotonin (5-HT0 |
|
|
Term
| Vasoconstriction facilitates... |
|
Definition
| interaction of platelets with the endothelium |
|
|
Term
| Platelet aggregation occurs by what 5 chemical mediators? |
|
Definition
thrombin
adenosine diphosphate (ADP)
TXA2
5-HT
prostaglandins |
|
|
Term
| Platelets adhere to ______ and ______ via _______ and _______ receptors. |
|
Definition
collagen; vWF
GP 1a; GP 1b |
|
|
Term
| What do platelets secrete? |
|
Definition
Ca++
ADP
TXA2
epinephrine
5-HT
others |
|
|
Term
| During aggregation, ____ and ____ induce shape change and sticking. |
|
Definition
|
|
Term
| During aggregation, __________ _________ is expressed at the surface. |
|
Definition
|
|
Term
| During aggregation, the coagulation cascade is anchored at ________ _________. |
|
Definition
|
|
Term
| What is the last step of platelet aggregation? |
|
Definition
|
|
Term
| Fibrinogen binds to platelets via _________. |
|
Definition
|
|
Term
| Thrombin converts soluble _____________ to insoluble ________ fibers. |
|
Definition
|
|
Term
| ______ monomers are cross-linked to form a very strong platelet-________ clot. |
|
Definition
|
|
Term
| steps of primary hemostasis |
|
Definition
1. platelet adhesion
2. shape change
3. granule release (ADP, TXA2)
4. recruitment
5. aggregation (hemostatic plug) |
|
|
Term
| steps of secondary hemostasis |
|
Definition
1. tissue factor
2. phospholipid complex expression
3. thrombin activation
4. fibrin polymerization |
|
|
Term
| coagulation cascade has... |
|
Definition
|
|
Term
| contact activation pathway |
|
Definition
|
|
Term
|
Definition
|
|
Term
| primary pathway for the initiation of blood coagulation |
|
Definition
| tissue factor pathway (extrinsic) |
|
|
Term
| Heparin interrupts the _________ pathway. |
|
Definition
|
|
Term
| Warfarin interrupts the _________ pathway. |
|
Definition
|
|
Term
|
Definition
tissue factor-->VIIa-->Xa,Va
Xa,Va takes prothrombin-->thrombin
thrombin takes fibrinogen-->fibrin |
|
|
Term
|
Definition
XIIa-->Xa,Va
Xa,Va takes prothrombin-->thrombin
thrombin takes fibrinogen-->fibrin |
|
|
Term
| With the intrinsic pathway, all clotting factors are... |
|
Definition
|
|
Term
| With the extrinsic pathway, the initiating clotting factor (tissue factor) is... |
|
Definition
| outside the blood vessels |
|
|
Term
| Clotting is slower/faster with the intrinsic pathway. |
|
Definition
|
|
Term
| Clotting is slower/faster with the extrinsic pathway. |
|
Definition
|
|
Term
| test for intrinsic pathway |
|
Definition
| aPTT (activated partial thromboplastin) |
|
|
Term
| test for extrinsic pathway |
|
Definition
|
|
Term
| What is the traditional approach in preventing formation of a pathological thrombus? |
|
Definition
| anticoagulant drugs (heparin, warfarin) |
|
|
Term
| What is the current approach in preventing formation of a pathological thrombus? |
|
Definition
| prevention of arterial damage (atherosclerosis) and inhibition of platelet aggregation (ASA, clopidogrel, abciximab) |
|
|
Term
|
Definition
1. prevent formation of pathological thrombus
2. destroy formed pathological thrombus |
|
|
Term
| What forms the initial hemostatic plug? |
|
Definition
|
|
Term
| key activator of platelet aggregation |
|
Definition
|
|
Term
| TXA2 is a product of the arachidonic acid pathway that involves formation of prostaglandins by the enzyme ___________. |
|
Definition
|
|
Term
At low doses, aspirin...
Since platelets cannot synthesize this new enzyme, aspirin also... |
|
Definition
irreversibly inhibits cyclooxygenase in platelets
inhibits TXA2 formation and platelet aggregation for the life of the platelet |
|
|
Term
|
Definition
|
|
Term
| Endothelial cells can/can not synthesize new cyclooxygenase. |
|
Definition
|
|
Term
| If the dose of aspirin is pushed too high, cyclooxygenase is inhibited in endothelial cells which prevents the formation of _____. |
|
Definition
|
|
Term
|
Definition
| compound that inhibits platelet secretion and stimulates vasodilation |
|
|
Term
| therapeutic uses of aspirin |
|
Definition
-MI
-secondary prevention of MI and stroke
-primary prevention of CVD
-reduction of thromboembolic complications in pts with artificial heart valves, hemodialysis, coronary bypass grafts |
|
|
Term
|
Definition
GI bleeding
allergy can limit use |
|
|
Term
| contraindications of aspirin |
|
Definition
| ASA or NSAID-induced asthma |
|
|
Term
| clopidogrel (Plavix) mechanism of action |
|
Definition
blocks P2Y12 receptor
leads to irreversible blockade of ADP receptor on platelet cell membrane |
|
|
Term
| clopidogrel (Plavix) onset |
|
Definition
|
|
Term
| Clopidogrel (Plavix) is often used in combination with _________ in high risk situations. |
|
Definition
aspirin
(stents, acute coronary syndrome) |
|
|
Term
|
Definition
| prevention of ischemic events in atherosclerosis |
|
|
Term
| ticlopidine (Ticlid) mechanism of action |
|
Definition
| inhibits fibrinogen binding to platelets and blocks platelet aggregation |
|
|
Term
| ticlopidine (Ticlid) indications |
|
Definition
| prevention of thrombotic stroke in patients who have experienced TIAs |
|
|
Term
| dipyridamole (Persantine) mechanism of action |
|
Definition
inhibits platelet aggregation
weak vasodilator |
|
|
Term
| dipyridamole (Persantine) indications |
|
Definition
| may be useful in secondary prevention of MI and stroke (disappointing clinical trials) |
|
|
Term
| abciximab (ReoPro) is a... |
|
Definition
|
|
Term
| abciximab (ReoPro) mechanism of action |
|
Definition
| prevents fibrinogen binding to GP IIb-IIIa, thus inhibiting platelet aggregation |
|
|
Term
| __________ has greater antithrombotic activity than aspirin or heparin. |
|
Definition
|
|
Term
| abciximab (ReoPro) indications |
|
Definition
| antithrombotic during angioplasty |
|
|
Term
| eptifibatide and tirofiban indications |
|
Definition
|
|
Term
| cilostazol (Pletal) mechanism of action |
|
Definition
inhibits PDE-3 which increases cAMP-->inhibits platelet aggregation
stimulates vasodilation |
|
|
Term
| cilostazol (Pletal) indications |
|
Definition
| reduction of symptoms of intermittent claudication |
|
|
Term
| cilostazol (Pletal) contraindications |
|
Definition
| CHF (causes some fluid retention) |
|
|
Term
| pentoxifylline (Trental)... |
|
Definition
| improves blood flow (hemorrheologic agent) |
|
|
Term
| pentoxifylline (Trental) mechanism of action |
|
Definition
enhances RBC flexibility
decreases blood viscosity
may decrease TXA2 levels and increase PGI2 levels |
|
|
Term
| pentoxifylline (Trental) indications |
|
Definition
intermittent claudication
chronic occlusive arterial disease of the limbs |
|
|
Term
|
Definition
|
|
Term
| Heparin is naturally occuring and is produced by _________ and ____ _____ to prevent formation and progression of blood clots. |
|
Definition
|
|
Term
| Heparin does/does not destroy clots that already exist. |
|
Definition
|
|
Term
| Heparin is the DOC for ____________ anticoagulant therapy. |
|
Definition
|
|
Term
| heparin mechanism of action |
|
Definition
binds to antithrombin III
heparin-antithrombin III complex binds to and inactivates coagulation factors
prolongs both the PTT and PT |
|
|
Term
| coagulation factors inactivated by heparin |
|
Definition
thrombin (IIa)
IXa
Xa
XIa
XIIa |
|
|
Term
| What can long-term administration of heparin cause? |
|
Definition
|
|
Term
| heparin contraindications |
|
Definition
any site of active or potential bleeding
severe HTN, known vascular aneurysm, recent head, eye, spinal cord surgery, head trauma, lumbar puncture, regional anesthetic block, TB, visceral carcinoma, GI ulcers |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| continuous IV heparin infusion |
|
Definition
| 2-3 hr delay for full effect unless an initial bolus injection is administered |
|
|
Term
| IV duration of single dose heparin |
|
Definition
|
|
Term
| SQ duration of single dose heparin |
|
Definition
|
|
Term
|
Definition
| metabolized in liver or excreted unchanged |
|
|
Term
|
Definition
-prophylaxis of post-op thrombosis
-MI and unstable angina
-DVT and PE
-extracorporeal circulation
-disseminated intravascular coagulation (DIC)
-TIA (not used if stroke in progress) |
|
|
Term
| Small doses of heparin prevent ___________. |
|
Definition
|
|
Term
| Medium doses of heparin prevent... |
|
Definition
|
|
Term
| Large doses of heparin... |
|
Definition
| inhibit established pulmonary embolus |
|
|
Term
| If prolonged anticoagulation is necessary, the initial heparin therapy is... |
|
Definition
| overlapped with and then replaced with oral anticoagulant (warfarin) |
|
|
Term
| treatment of heparin overdose |
|
Definition
1. stop administration
2. protamine sulfate
3. infusion of fresh-frozen plasma |
|
|
Term
|
Definition
binds to and inactivates heparin
must be given slowly IV |
|
|
Term
| low molecular weight heparin (LMWH) |
|
Definition
|
|
Term
| LMWH has greater _______ activity and less ________ activity. |
|
Definition
|
|
Term
|
Definition
| prophylaxis of DVT associated with hip, knee, and abdominal surgery |
|
|
Term
| LMWH has ______ duration, _______ kinetics, and __________ are not usually required. |
|
Definition
| longer; simpler; clotting tests |
|
|
Term
| most significant adverse effect of heparin after hemorrhage |
|
Definition
| heparin-induced thrombocytopenia (HIT) |
|
|
Term
| test used to monitor heparin therapy |
|
Definition
|
|
Term
| aPTT of ____-____ times control is the typical therapeutic goal for heparin |
|
Definition
|
|
Term
| Monitoring of LMWH may be useful in what situations? |
|
Definition
renal insufficiency
obese pts with altered drug pK
major bleeding risk factors |
|
|
Term
| Why is aPTT not useful in monitoring LMWH? |
|
Definition
|
|
Term
| advantages of LMWH over UH |
|
Definition
-decreased "heparin resistance"
-no need for lab monitoring
-higher bioavailability (90% vs. 30%)
-longer plasma half-life
-don't have to give IV
-less inhibition of platelet function
-lower incidence of HIT syndrome |
|
|
Term
| warfarin mechanism of action |
|
Definition
inhibits vitamin K epoxide reductase
inhibits vitamin K-dependent post-translation modification of clotting factors |
|
|
Term
| clotting factors inhibited by warfarin |
|
Definition
thrombin
VII
IX
X
protein C and S |
|
|
Term
| What can be given to counteract a warfarin overdose? |
|
Definition
|
|
Term
|
Definition
|
|
Term
| How many days does it take to see close to steady state with warfarin? |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
delayed (2-5 days)
*new, active clotting factor must by synthesized |
|
|
Term
| warfarin contraindications |
|
Definition
-pregnancy (congenital abnomalities, fetal hemorrhage)
-unreliable patients
-any recent bleeding
-recent eye, brain, or spinal cord surgery
-head injury
-severe HTN or known vascular aneurysm |
|
|
Term
|
Definition
hemorrhage
anorexia, nausea, vomiting, diarrhea |
|
|
Term
|
Definition
DVT
PE
a-fib
rheumatic heart disease
mechanical prosthetic heart valves |
|
|
Term
| With warfarin therapy, determine PT/INR prior to starting therapy, _____ until response stabilized, and _______ until maintenance dose established. |
|
Definition
|
|
Term
|
Definition
|
|
Term
| goal INR for mechanical heart valve |
|
Definition
|
|
Term
| Warfarin has very high ________ ________. |
|
Definition
|
|
Term
| mechanisms of drug interactions with warfarin |
|
Definition
1. displacement of warfarin protein binding
2. reduction in hepatic metabolism
3. alteration in GI bacterial flora that produce menadiones
4. interference with production of protein C and S (body's natural anticoagulants) |
|
|
Term
| antibiotics that interact with warfarin |
|
Definition
macrolides (esp. erythromycin)
quinolones (cipro)
metronidazole
sulfas
azoles (fluconazole, ketoconazole) |
|
|
Term
| recommendation for pt on warfarin that needs antibiotic treatment |
|
Definition
| obtain INR before starting antibiotic and check the INR more frequently during antibiotic therapy |
|
|
Term
| situations where the risk of hemorrhage is greater than the potential clinical benefits of warfarin therapy |
|
Definition
uncontrolled alcohol/drug abuse
unsupervised dementia/psychosis
increased risk of falls |
|
|
Term
| aPTT measures activity of what pathway? |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| used to standardize PT times between different batches of thromboplastin and between different laboratories |
|
Definition
| INR (international normalization ratio) |
|
|
Term
| factors that can influence INR |
|
Definition
drug interactions
diet
alteration of intestinal flora (inc. INR)
fever (inc. INR)
hepatic failure (inc. INR)
thyroid function
noncompliance |
|
|
Term
| drug interactions that cause increased INR |
|
Definition
thyroid products
metronidazole
fluconazole/azole antifungals
alcohol
amiodarone
any antibiotic has potential
statins
omeprazole (PPIs)
phenytoin
gemfibrozil
fluouroquinolones
cimetidine (H2 blocker for GERD) |
|
|
Term
| drug interactions with NO INR effect |
|
Definition
aspirin
clopidogrel
COX-2 inhibitors
GP IIb/IIIa antagonists
NSAIDs
ticlopidine
small doses of alcohol |
|
|
Term
| thrombolytic therapy indications |
|
Definition
acute MI
PE
DVT
ischemic stroke (special circumstances only) |
|
|
Term
|
Definition
| recombinant tissue plasminogen activator |
|
|
Term
|
Definition
|
|
Term
|
Definition
-shorter, genetically engineered form of rPTA
-diffuses more freely into clot that alteplase
-shorter half-life than alteplase |
|
|
Term
|
Definition
| nonenzymatic activator of plasminogen extracted from hemolytic streptococci |
|
|
Term
| thrombolytic contraindications |
|
Definition
recent major surgery
hemorrhagic stroke
HTN
any potential to bleed |
|
|
