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76 Cards in this Set
- Front
- Back
Name 3 anticoagulants
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1. Heparin
2. Low Molecular Weight Heparins (Dalteparin Sodium, Enoxaparin, Tinzaparin) 3. Warfarin (Coumadin) |
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Name 1 procoagulant
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Desmopressin acetate
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Name 4 antiplatelet drugs
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Acetylsalicylic acid (Aspirin)
Clopidogrel bisulfate (Plavix) Abciximab (ReoPro) Ticlopidine |
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Name 2 fibrinolytic drugs
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Tissue Plasminogen Activator (t-PA, Activase)
Streptokinase |
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Name 2 antagonist drugs for anticoagulation.
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Protamine sulfate
Aminocaproic acid |
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What's the difference between a thrombus and an embolus?
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Thrombus: A clot adhering to a vessel wall.
Embolus: A detached thrombus circulating in the vascular system |
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Where do arterial clots occur and what are they triggered by?
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Occurs in medium-sized vessels and is triggered by the chronic effects of atherosclerosis resulting in platelet-rich plaque deposition.
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What are venous clots triggered by?
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Is triggered by static blood and generally results from defective defensive mechanisms against coagulation. Clots are rich in fibrin and contain fewer platelets.
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Why don't clots normally form within vessels?
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Three effects:
Dilution The presence of plasma inhibitors Activated clotting factors are rapidly removed by the liver |
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What physiologic reactions participate to control blood loss?
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Platelet adhesion reaction
Platelet activation Platelet aggregation Formation of a clot (coagulation) Fibrinolysis |
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What are Anticoagulants?
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Substances that prevent the synthesis of a fibrin network which inhibits coagulation and the formation of arterial thrombi and thromboembolic clots.
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What are Antiplatelet agents?
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Substances that reduce the adhesion and aggregation of platelets.
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What are Fibrinolytic agents?
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Substances that promote the destruction of already formed blood clots or thrombi by disrupting the fibrin mesh.
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What are Procoagulants?
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Substances that are used to reduce excessive or abnormal bleeding
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What compounds trigger vasospasms? Where are they released from?
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Thromboxane A2 (TA2) and Serotonin (5-HT)
Released by Platelets |
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What triggers the extrinsic pathway?
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trauma originating from the extra-vascular space (formation of a macromolecular complex involving Thromboplastin or Tissue Factor, and Factor VII)
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What triggers the intrinsic pathway?
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triggered by trauma to the blood itself (from large glycoprotein complexes released by platelets)
HMWK and collagen Ms. Ellen |
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What anticoagulants are direct acting? Indirect?
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Direct: Calcium Chelators (sodium citrate, EDTA)
Heparin (UF and LMWHs) Hirudin compounds (Lepirudin and Bivalirudin) Indirect: Warfarin |
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What is heparin (molecularly) and how's it prepared?
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An anionic mixture of linear mucopolysaccharide molecules with molecular weights in the range of 3,000 to 30,000
Commercially prepared from bovine lung and porcine intestinal mucosa |
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What is heparin's mechanism of action?
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Forms complexes with an α2-globulin (Antithrombin III) and each of the activated proteases of the coagulation cascade (Kallikrein, XIIa, XIa, IXa, Xa, and Thrombin). After formation of the heparin-ATIII-coagulation factor, heparin is released and becomes available again to bind to free ATIII
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How does heparin inhibit blood clotting?
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Blocks conversion of Prothrombin to Thrombin and thus inhibits the synthesis of Fibrin from Fibrinogen
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What factors are inhibited by heparin?
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Factors Xa and Thrombin, but also Factors IXa and XIa
(XII, XI, IX, X, and Thrombin: Activated serine proteases are all inhibited) |
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What factors are inhibited by low doses of heparin?
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Factor Xa
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What factors are inhibited by high doses of heparin?
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Prevents the thrombin-induced activation of platelets, and activation Factors V and VIII
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What does heparin do to platelet function and vascular permiability? What effect does this have?
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Inhibits platelet function and increases vascular permeability; may induce moderate to severe thrombocytopenia
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What is the route of administration for heparin
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Not effective after oral administration - generally administered by IV or subQ; IM should be avoided due to hematoma formation
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What is important to know about the use of heparin in pregnant or breastfeeding mothers?
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Heparin does not cross the placenta and does not pass into the maternal milk
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When is heparin contraindicated?
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Any situation where active bleeding must be avoided: Ulcerative lesions, intracranial hemorrhage, brain or spinal cord surgery, etc.
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What drug can be used in the case of heparin overdose?
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Protamine Sulfate (PS): Highly basic peptide that binds heparin and thus neutralizes its effects
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Dosing of Protamine Sulfate in heparin overdose?
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1 mg of PS for every 100 U of Heparin; not to exceed 50 mg for any 10 min period
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Name 3 examples of low molecular weight heparin (LMWH).
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Dalteparin Sodium (Fragmin)
Tinzaparin Sodium (Innohep) Enoxaparin (Lovenox) |
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What are the clinical uses of LMWH?
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Prevention of Deep Vein Thrombosis post-surgery
Tx of acute venous thromboembolic events and acute coronary artery syndromes |
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What's the difference between heparin and LMWH?
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Heparin accelerates the interaction of antithrombin with thrombin and Factor Xa. LMWH selectively inhibits Xa only.
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What are the advantages of LMWH over regular heparin? (4 things)
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1.Equal efficacy; but more predictable outcome and half-life is about twice that of heparin (4 hours vs. 2 hours)
2. ↓ dosing requirements (QD/BID) 3. ↑ bioavail from the subQ site of injection (LMWH: ~ 90%; UFH: ~ 20%) 4. Less frequent bleeding |
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What is Lepirudin (Refludan)?
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Recombinant form of the natural anticoagulant hirudin: potent and specific Thrombin inhibitor
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What is Bivalirudin (Angiomax)?
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Analog of hirudin: potent and specific Thrombin inhibitor
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How long does it take warfarin to become active?
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12 to 24 hours
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What is warfarin's relation to vitamin K?
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A structural analogues of vitamin K who's effects are like those of vitamin K depletion
(Blocks epoxide reductase) |
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What's the vitamin K-sensitive step in the synthesis of clotting factors?
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the post-ribosomal carboxylation of specific glutamic acid residues. These amino acid residues chelate Ca2+
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How does warfarin inhibit blood clotting?
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Interfers with the hepatic synthesis of the vitamin K- dependent clotting factors (VII, IX, X and Prothrombin)
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What does Protein C do?
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bonds to thrombomodulin on endothelial cells, alters the specificity of Thrombin and favors the degradation of Factors Va and VIIIa into inactive proteases
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What's warfarin's effect on Protein C?
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Down-regulates Protein C = procoagulant activity of warfarin observed in early stage therapy
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What are the half lives of warfarin effected factors?
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Factor VII: 6 hours
Factor IX: 24 hours Factor X: 40 hours Prothrombin: 60 hours |
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What's warfarin bound to and how's it metabolized?
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Largely bound to plasma albumin (> 98%), is metabolized by the liver by Cytochrome P450 into inactive metabolites which are then excreted in the urine
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How do infants react with warfarin?
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Newborn infants are more sensitive to oral anticoagulants than are adults because of lower vitamin K levels and lower rates of metabolism
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Does warfarin pass the placenta?
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Yup
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How do you treat warfarin overdose?
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Vitamin K1 (24 hour delay) supplementation
Transfusion of whole blood or plasma (major bleeding) |
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When is warfarin contraindicated?
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Conditions where active bleeding must be avoided, Vit K deficiency and severe hepatic/renal disease, and where intensive salicylate therapy is required
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What types of drugs diminish the response to warfarin? (3)
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Inhibition of drug absorption (Cholestyramine)
Induction of hepatic microsomal enzymes Stimulation of the synthesis of clotting factors |
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What types of drugs increase the response to warfarin? (5)
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Displacement of anticoagulant from plasma proteins
Inhibition of hepatic microsomal enzymes Reduction in availability of Vitamin K Inhibition of synthesis of clotting factors Decreased platelet aggregation (e.g. Aspirin) |
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What is Desmospressin Acetate?
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a synthetic analogue of the pituitary antidiuretic hormone (ADH)
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What is the mechanism of action of Desmospressin Acetate?
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Stimulates the activity of Coagulation Factor VIII
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What are the clinical uses of Desmospressin Acetate? (5)
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1. hemophilia A with factor VIII levels less than or equal to 5%
2. factor VIII antibodies 3. severe classic von Willebrand's disease (type I) 4. abnormal molecular form of factor VIII antigen is present. 5. type IIB von Willebrand's disease. |
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Mechanism of action for Acetylsalicylic Acid (Aspirin)?
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Acetylates platelet enzymes (cyclo-oxygenases or COX) that synthesize the precursors of Thromboxane A2 (labile inducer of platelet aggregation and a potent vasoconstrictor). Inhibits ADP release.
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What is the effectiveness of low dose Acetylsalicylic Acid?
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Low dose (160-320 mg) may be more effective at inhibiting Thromboxane A2 than PGI2 which has the opposite effect and is synthesized by the endothelium
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Are the effects of Acetylsalicylic Acid reversible?
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Irreversible
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What's the benefit of Acetylsalicylic Acid as a prophlaxis agent??
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Uncertain for primary prevention of MI but beneficial for secondary (in pts with hx of vascular events)
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What is Ticlopidine (Ticlid)?
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an alternative antiplatelet drug for treatment of recurrent stroke in patients intolerant to aspirin
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Ticlopidine (Ticlid) mechanism of action?
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Inhibits the response of ADP on its platelet receptor and thus prevents aggregation by impairing the GPIIb/IIIa receptor.
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Clopidogrel bisulfate (Plavix) mechanism of action?
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Inhibits the response of ADP on its platelet receptor and thus prevents aggregation by impairing the GPIIb/IIIa receptor.
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Clopidogrel bisulfate (Plavix) v. Ticlopidine (Ticlid), side effect wise?
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Clopidogrel bisulfate has less side effects.
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What is Abciximab (ReoPro)?
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A chimeric monoclonal antibody inhibitor (Fab fragment) of platelet glycoprotein IIb/IIIa.
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Abciximab (ReoPro) mechanism of action?
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Prevents binding of fibrinogen and von Willebrand Factor.
Prevents platelet aggregation. |
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Primary use of Abciximab (ReoPro)?
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acute coronary syndromes and percutaneous coronary intervention
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How does the fibrinolytic system work?
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dissolves intravascular clots via Plasmin, an enzyme that digests Fibrin (and other plasma proteins, including coag factors)
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What's a major side effect of thrombolytic agents? why?
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Can produce hemorrhage because they dissolve both pathologic thrombi and fibrin depostis at sites of vascular injury
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When is thrombolytic therapy indicated?
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In patients with extensive pulmonary emboli, severe iliofemoral thrombophlebitis and acute coronary occlusion
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What is Tissue Plasminogen Activator? Where does it come from?
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released from endothelial cells in response to stasis produced by vascular occlusion - binds to Fibrin and converts Plasminogen to Plasmin. (works 100xs better on bound plaminogen than free)
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What's the fate of free v. fibrin-bound plasmin?
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Free Plasmin is rapidly inhibited in the plasma by an α2-antiplasmin. Fibrin-bound Plasmin is protected from inhibition.
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What is Streptokinase (Streptase)?
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A protein produced by β-hemolytic streptococci. No intrinsic enzymatic activity, but forms a stable non-covalent 1:1 complex with Plasminogen = conformational change that exposes the active site on Plasminogen that cleaves a peptide bond to form free Plasmin.
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Thrombolytic therapy contraindications? (5)
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1. Surgery w/in 10 days, including organ biopsy, puncture of noncompressible vessels, serious trauma, cardiopulmonary resuscitation.
2. Serious GI bleeding w/in 3 months. 3. Hx of HTN (diastolic pressure >110 mm Hg). 4. Active bleeding or hemorrhagic disorder. 5. Previous CVA or active intracranial bleeding. |
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What is Aminocaproic acid? (+ mechanism of action)
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Prevents the binding of Plasminogen and Plasmin to Fibrin = potent inhibitor for Fibrinolysis and can reverse states that are associated with excessive Fibrinolysis
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What's PT? What's Normal? What about PTT?
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PT: Reflects alterations in the extrinsic pathway (normal: ~ 12 sec)
aPTT: Reflects the intrinsic pathway (normal: 24 to 34 sec) |
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What's INR?
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Index used to normalize PT: PT patient/PT mean normal; desired therapeutic INR is usually between 2 and 3 (human thromboplastin)
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Signs of a DVT?
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Unilateral leg swelling accompanied by local tenderness and pain
Discoloration of the affected limb: Arterial spasm or Cyanosis from venous obstruction or reddish color from perivascular inflammation |
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Heparin dosing?
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Loading dose: 70-100 U/kg
Maintenance dose: 15-25 U/kg/hr |