Lecture 08_Spring Flashcards
What is heparin’s mechanism of action? Does it cross the Placenta?
Binds to antithrombin III and activates it. It does not cross the placenta (mostly b/c its charged).
What is antithrombin III (AT III)?
A natural anticoagulant. It inactivates thrombin (factor IIa) as well as factors IX, X, XI, XII
If a patient does not respond to heparin, what should you consider doing?
Consider giving them FFP to replenish AT III.
What is used to evaluate heparin activity?
ACT (activated coagulation time) - mix blood with activation substance and measure how long it takes to clot. ACT is measured 3 min after heparin is given and compared to baseline ACT. Usually want ACT = 2x baseline for vascular procedures.
What is used to prevent DVT/PE/acute MIs?
heparin or lovenox
What are Streptokinase and Alteplase used for? What is their mechanism of action?
They are thrombolytic drugs. They are tissue plasminogen activators. activate plasminogen-> plasmin (destroys clots)
Indications: acute coronary syndrome, stroke
Can be be given into a clogged vascular access device (dyalisis, PICC)
What is the mechanism of aspirin and its effects on coagulation?
Antiplatelet drug. NSAID (COX-1 and COX-2 inhibitor).Irreversible prevention of platelet aggregation
What is aspirin commonly prescribed for?
prevent of stroke, MI, occlusion of coronary stents
What is the mechanism of Clopidogrel (Plavix) and its effects on coagulation?
irreverible inhibition of platelet activation and aggregation
What is the mechanism of Amicar (E-aminocaproic acid) and Tranexamic acid and their effects on coagulation?
they are antifibrinolytic drugs - they protect the clot. prevent plasminogen->plasmin AND inactivate plasminplasmin degrades fibrin (fibrin cross-links stabilize platelets)
What is recombinant factor VIIa?
Directly activates Factor X and initiates thrombin burst without requiring Factors VIII or IX. Requires presence of factors V,X,II, fibrinogen, and at least some platelets
What is DDAVP?
causes release of factor VIII, vWF, and t-PA
used in vWD, mild hemophilia, uremia, ASA/NSAIDS/dextran/plavix
Desmopressin (DDAVP), a vasopressin analog, is indicated for control of hemorrhage in patients with mild-to-moderate hemophilia A and von Willeband’s disease. It’s primary mechanism of action is to increase circulating levels of factor VIII and von Willebrand factor (vWf) leading to secondary improvements in platelet adhesion to endothelial defects. It has also been considered for use in patients with uremia and prolonged bleeding time due to decreased expression of vWF and decreased activity of the vWF-factor VIII complex. Two advantages to DDAVP are its relatively quick onset of action (1 hour), similarity to cryoprecipitate, and lack of transfusion-related side effects. However, the effects of DDAVP do not last more than 24 hours and patients are likely to develop tachyphylaxis after a single dose of DDAVP limiting its utility for repeated dosing.
With the increasing use of anti-platelet agents such as clopidogrel and aspirin, interest has been raised for a potential role of DDAVP in the setting of acute bleeding in these patients. The use of desmopressin in patients with normal renal function who have active hemorrhage and a history of recent (within the past 7 days) of aspirin or clopidogrel (Plavix®) administration is mentioned in a number of review articles with positive outcomes
What are the side effects of heparin?
Hemorrhage and hematoma formation
Thrombocytopenia (low platelet level in blood) - this includes mild thrombocytopenia and HITT
Allergic reaction (its derived from animal tissue)
What is HITT?
Heparin Induced Thrombocytopenia and Thrombosis
What is used to reverse heparin?
Protamine - derived from salmon sperm
In the absence of heparin, protamine has what effect?
anticoagulant effect
What are the side effects of heparin?
hTN, pulmonary HTN, allergic rxn
What drug is characterized by the following: Strong base, Combines w/ negatively charged heparin to form a complex, Derived from salmon sperm
Protamine
What 4 factors are part of the extrinsic pathway?
Factors II, V, VII, X
What are the 4 vitamin K dependent factors?
Factors II, VII, IX, X
Factor IIa is also known as what?
thrombin
Hemophilia A is characterized by what factor deficiency?
VIII
Clotting factors are all inactive pro-enzymes that, with the exception of one factor, are all synthesized where? Which factor is the exception?
All synthesized in the liver except fact VIII
What is vWF deficiency characterized by?
poor platelet adhesion AND clinical hemophilia
What are the 3 Phases of Coagulation?
Activation - Amplification - Propogation
Describe the 3 steps involved with the Activation Phase of Coagulation.
Injury->Tissue Factor-> activates VII, X, V, II (thrombin)
Describe the 3 steps involved with the Amplification Phase of Coagulation.
Amplification (“thrombin burst”) - Platelets activated; Thrombin activates V, VIII, IX; platelets bind to collagen
Describe the Propagation Phase of Coagulation.
Propagation: fibrin cross-links stabilize the platelets
Heparin is given as DVT prophylaxis in what group of people most commonly? what is the typical dose?
Hospitalized pts, esp surgical pts (esp hip replacements)
DVT Prophylaxis= 5,000units SQ q8-12h (7,500 for very obese)
What is the heparin dose for treatment of DVT/PE?What PTT are you aiming for?
80 units/kg bolus + infusion at 18 units/kg/hr
PTT: titrate to 1.5-2.5x normal, q6hr
What is Enoxaparin?
Also called Lovenox. It is a LMWH (low molecular weight heparin)