anticoagulation/reversal Flashcards
describe basic hemostasis
- adhesion of platelets to damaged vessel wall
- activation of platelets
- aggregation of platelets: fibrinogen links platelets together, but clot still water soluble and fragile
- production of fibrin (secondary hemostasis): extrinsic, intrinsic, and final common pathways
what is the MOA of Heparin?
- binds to antithrombin (naturally occurring anticoagulant)
- increases antithrombin ability 1000x
- inactivates thrombin (IIa), factors X, XII, XI, IX
- inhibits platelet function (not main effect)
describe heparin
- poorly lipid soluble (cant cross lipid barriers)
- given IV or SubQ (IM causes hematoma)
- binds to plasma proteins, only 1/3 binds to antithrombin
- duration increases as dose increases
- elimination not completely understood, some in the urine
- endogenous in basophils, mast cells, and liver (“HEP”)
- one unit = vol. of solution that will prevent 1 ml of sheep blood from clotting for 1 hr after 0.2 ml CaCl added
what is the ACT? and describe proper procedure
activated coagulation time
- monitors the heparin effect
- get a baseline measurement prior to giving heparin (control is usually 90-120 seconds)
- measurement 3 minutes after admin. (for CPB want ACT > 300 seconds)
- measure every 30 minutes
- mix blood with an activation substance which initiates the clotting cascade; measure the onset of clot formation
what affects the ACT?
- hypothermia, hemodilution prolong ACT (two major factors in bypass)
- thrombocytopenia (heparin may induce)
- presence of contact activation inhibitors (aprotinin)
- preexisting coagulation deficiencies (hemophilia, etc; do a baseline)
what should be given if ACT is not increasing?
FFP
-heparin can not work without antithrombin to activate so may need to be given antithrombin
what are clinical uses of heparin?
- venous thrombosis, PE
- prevention of mural thrombosis after MI
- unstable angina, acute MI
- prevention of coronary artery rethrombosis after thrombolysis
- prevention of thrombosis formation during CPB
- treat fetal growth retardation in pregnancy (prevent thrombosis of placental arteries)
what are side effects of heparin?
- hemorrhage (most serious): greater risk if pt. on aspirin; avoid with intraocular or intracranial surgery (a little bleeding and cause serious damage); avoid epidural or spinal, axillary block (chance of hematoma on spinal cord or deep plexus block can cause nerve damage)
- thrombocytopenia: mild- platelet
what are CV effects of heparin?
- decreased MAP, PAP
- decrease in SVR d/t relaxant effect on smooth muscle of vessels
- drop in BP seen especially with large doses given before bypass
what is protamine?
reversal of heparin
-positively charged protein (salmon sperm)
what is MOA of protamine?
- combines with negatively charged heparin
- resulting complex has no anticoagulation effect
- removed by reticuloendothelial system
- if given and there is no heparin to bind to, acts as an anticoagulant
what is the dose of protamine?
1 mg per every 100 U of heparin circulating
*calculated off of ACT if doing bypass
what are CV effects of protamine?
- hypotension: histamine release, tachycardia (pt. with decreased LV function may not be able to compensate)
- to minimize hypotension give over 5 minutes and give peripherally to dilute the complex that causes histamine release in the lungs
what are respiratory effects of protamine?
-pulmonary hypertension: thromboxane release causing pulmonary vasoconstriction, pulmonary HTN, and bronchoconstriction
what is another possible effect of protamine?
allergic reaction
- protamine-containing insulin (NPH)
- fish, shellfish
- pre treat with H1 and H2 blockers and steroid
how do platelets normally function?
- thrombin activates the platelet
- phospholipase converts a membrane phospholipid to arachidonic acid
- cyclooxygenase converts arachidonic acid to prostaglandin G2
- PGG2 is metabolized to PGH2
- PGH2 is converted to multiple prostaglandins and thromboxane A2
- thromboxane A2 uncovers fibrinogen receptors allowing attachment of fibrinogen to link platelets together
what is the MOA of aspirin?
interfere with the activity of cyclooxygenase (COX) and with the release of ADP, which interrupts the synthesis of thromboxane A2, thus causing impaired platelet aggregation
*doesn’t affect platelet count, just function; no need to check labs if on ASA
what is the duration of action of aspirin?
irreversible effect for the life of the platelet (8-12 days)
*recommended to stop 7 days prior to surgery if at low risk for cardiac events
describe MOA of clopidogrel (Plavix) and ticlopidine (Ticlid)
block ADP receptors (irreversibly) on the platelets which inhibits the platelet activation, aggregation for the life of the platelet
- used in combination with aspirin to maintain patency of coronary stents
- Prilosec decreases Plavix function
when should Plavix and Ticlid be stopped?
Plavix: 7 days prior to surgery
Ticlid: 14 days prior to surgery
*both must be stopped
what normally happens to fibrin after the clot is formed and bleeding has stopped?
- clot needs to be broken down
- plasminogen is produced in the liver and stored in the clot
- tissue-type plasminogen activator (tPA) and urokinase convert plasminogen to plasmin
- plasmin breaks down fibrin
what is the MOA of the anti fibrinolytic agent aprotinin (Trasylol)?
- naturally occurring plasma kinin
- inhibits plasmin
- a more stable clot is formed b/c fibrin breaks down slowly and bleeding is decreased
- may protect platelets
- inhibits inflammatory response to CPB by preventing the movement of leukocytes through vascular lining
- not seen often, risks thrombus formation
what are some uses of aprotinin?
- “redo” cardiac operations
- prevention and treatment of hemorrhage during surgery (decreases blood loss and transfusion requirements by 40-80% in cardiac surgery pt. with aspirin and “redo”s
- contraindication: shouldn’t be given if a known or suspected exposure within past 12 months
describe aminocaproic acid (Amicar)
- synthetic anti-fibrinolytic
- forms a reversible complex with plasminogen which prevents fibrinolysis
- used to decrease postop bleeding and transfusions needed (CPB, scoliosis, orthotopic liver transplant, lower urinary tract surgery
- avoid with renal or ureteral bleeding (may lead to obstruction of the ureter d/t clotting)
describe tranexamic acid
- synthetic anti-fibrinolytic
- prevents the interaction b/w plasminogen and fibrin
- studies show similar effects as aprotinin
