Flashcards in Coagulants, Anticoagulants, and Thrombolytics Deck (48):
What are 3 general causes of coagulation deficiencies?
1. genetic disorders (ex. hemophilia)
2. acquired disorders (ex. decubitus ulcer; aka bed sores)
For what can we use fresh blood and plasma?
replacement and supplement
What do we use factor 8 to treat?
this is a plasma precipitate (fresh or frozen) or made via recombinant DNA (8-12 hour half-life) and used for hemophilia A.
What do we use factor 9 to treat?
this is purified human factor (from plasma) that is heat treated, or made via recombinate DNA and used to treat hemophilia B.
What do we use facto 7a to treat?
hemophilia A and B because it activates coagulation factor 10 as well as coagulation factor 9.
What are the 4 vitamin K-dependent clotting factors?
2, 7, 9, and 10. Thus, if vitamin K is missing, the clotting cascade would not progress.
From where does thrombin (that we use to treat) come?
bovine (cattle) plasma. It is available to use topically and comes in a powdered form that you shake over the laceration to arrest severe bleeding.
What is absorbable gelatin (GELFOAM)?
denatured collagen that activates platelets to form a clot. It comes in a powder or sponge form and is nonantigenic :) This is used in surgery and trauma. You leave it there when you are done because the clot forms around it. It will then be reabsorbed by the body.
What can cause unwanted coagulation?
1. thromboembolic diseases
2. extracorporeal devices (renal dialysis)
3. prophylactic treatment for previous thrombotic event
What are the injectable anticoagulants?
Can you give heparin intramuscularly?
NO. It will cause a hematoma at the site.
Only give it IV or SC.
What does heparin do?
potentiates antithrombin III, leading to more inactivated thrombin
What are the side-effects of heparin?
unwanted bleeding from mucous membranes, unwanted wounds, intracranially, or GI areas.
For what is heparin used?
prevention and treatment of DVT, PE, and arterial thrombosis
What are the in vitro (outside of the body) uses of heparin?
hemodialysis, indwelling vascular catheters, laboratory blood samples
What is the antagonist to heparin?
What is Lepirudin?
highly specific direct IRREVERSIBLE inhibitor of thrombin. Used when heparins are contra-indicated because of HIT (heparin inducted thrombocytopenia)
What are the side effects and what must you monitor with Lepirudin?
- hemorrhage can occur at any site in patients.
- an unexpected fall in hemoglobin, fall fall in BP or any unexplained symptom should lead to consideration of hemorrhage.
- must closely monitor anticoagulation status via PTT
What is Bivaliruden?
specific direct REVERSIBLE inhibitor of thrombin, thus inhibiting platelet activation. It has a rapid onset and rapid offset.
When are the direct thrombin inhibitors used?
percutaneous coronary angioplasty
What is warfarin?
oral anticoagulant that inhibits vitamin K decreasing synthesis of factors 2, 7, 9, and 10
**What factors DECREASE the effect of warfarin?
- p450 induction because this enzyme metabolizes warfarin
- increased production of clotting factors (leafy green vegetables).
- increased vitamin K absorption
- inhibition of biotransformation
**What factors INCREASE the effect of warfarin?
-decrease vitamin K absorption
- drugs that displace warfarin from plasma proteins (NSAIDS like piroxicam, indomethacin, diflunisal)
- inhibition of platelet aggregation
- decreased production of clotting factors
What is Dibigatran?
direct inhibitor of thrombin, used to prevent venous thromboembolic events in adults following total hip or total knee replacement surgery. Better than warfarin in pts with atrial fibrillation.
What is Idarucizumab?
reversal agent for dabigatran, by binding to it and its acylglucuronide metabolites with higher affinity than the binding affinity of dabigatran to thrombin, neutralizing its anticoagulant effect.
What is Rivaroxaban (Xarelto)?
inhibits free factor 10a and clot-bound 10a prothombinase activity, thus inhibiting platelet aggregation.
It is used for thromboembolism prevention after orthopedic surgeries. and pts with non-valvular atrial fibrillation.
Does Rivaroxaban have a reversing agent?
NO. Currently lots of law suits for excessive bleeding.
What is edoxaban?
selective factor 10a inhibitor for prevention of thromboembolism; simialr to rivaroxaban.
Does edoxaban have a reversing agent?
Is aspirin use recommended to prevent the risk of a SECOND heart attack?
Is there evidence that taking aspirin prophylactically will reduce the risk of a FIRST heart attack?
What is Clopidogrel (plavix)?
IRREVERSIBLE (covalent binding) of the ADP receptor on platelets, thus inhibiting ADP-induced binding of fibrinogen to platelet.
For what is clopidogrel used?
cardiovascular conditions prone to clot formation.
What major side effect does clopidogrel have?
What is Ticlopidine?
inhibits platelet function by inducing a thrombasthenia-like state. It irreversibly inhibits ADP-induced platelet-fibrinogen binding and subsequent platelet-platelet interactions (same as clopidogrel).
What is the main use for Ticlopidine?
acute cerebral ischemia
What is Prasugrel?
inhibits platelet activation and aggregation mediated by the P2Y ADP receptor.
What is the main use for Prasugrel?
to prevent clots in angioplasty patients.
What is Ticagrelor?
REVERSIBLE antagonist of P2Y ADP receptor and does NOT require bioactivation; faster onset. Used for cardiovascular conditions prone to clot formation.
What is dipyridamole?
increases cellular concentration of cAMP in platelets via inhibition of phosphodiesterase. Used in combination with warfarin as prophylaxis of thromboemboli for prosthetic heart valves.
What is prostacyclin (PGI2)?
increases intra-platelet cAMP by stimulating adenylate cyclase and thus blocks platelet adhesion and aggregation.
So, what happens anytime you increase cAMP?
you decrease platelet adhesion and aggregation
When would we want fibrinolysis?
for venous or arterial thromboembolism
What is streptokinase?
activates plasminogen to plasmin to break up clots. (NOT CLOT SPECIFIC; it will do this all over the body, duh).
What is urokinase?
comes from humane urine or kidney cells and cleaves arg-arg 560-561 peptide bond in plasminogen, thus activating it to plasmin. Again NOT CLOT SPECIFIC.
What is tissue plasminogen activator (t-PA)?
binds to fibrin and activates bound plasminogen, cleaving its arg-arg 560-561 bond. This is CLOT SPECIFIC :)
Usually is directed via a catheter to be given directly at the site of the clot.
What is aminocaproic acid?
This is the antidote to the fibrinolysis drugs (streptokinase, urokinase, t-PA). It binds to lysine binding sites on plasminogen and plasmin blocking the binding of plasmin to target fibrin. This is a potent inhibitor of fibrinolysis; aka it keeps clots around.