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76 Cards in this Set

  • Front
  • Back
Name 3 anticoagulants
1. Heparin
2. Low Molecular Weight Heparins (Dalteparin Sodium, Enoxaparin, Tinzaparin)
3. Warfarin (Coumadin)
Name 1 procoagulant
Desmopressin acetate
Name 4 antiplatelet drugs
Acetylsalicylic acid (Aspirin)
Clopidogrel bisulfate (Plavix)
Abciximab (ReoPro)
Ticlopidine
Name 2 fibrinolytic drugs
Tissue Plasminogen Activator (t-PA, Activase)
Streptokinase
Name 2 antagonist drugs for anticoagulation.
Protamine sulfate
Aminocaproic acid
What's the difference between a thrombus and an embolus?
Thrombus: A clot adhering to a vessel wall.
Embolus: A detached thrombus circulating in the vascular system
Where do arterial clots occur and what are they triggered by?
Occurs in medium-sized vessels and is triggered by the chronic effects of atherosclerosis resulting in platelet-rich plaque deposition.
What are venous clots triggered by?
Is triggered by static blood and generally results from defective defensive mechanisms against coagulation. Clots are rich in fibrin and contain fewer platelets.
Why don't clots normally form within vessels?
Three effects:
Dilution
The presence of plasma inhibitors
Activated clotting factors are rapidly removed by the liver
What physiologic reactions participate to control blood loss?
Platelet adhesion reaction
Platelet activation
Platelet aggregation
Formation of a clot (coagulation)
Fibrinolysis
What are Anticoagulants?
Substances that prevent the synthesis of a fibrin network which inhibits coagulation and the formation of arterial thrombi and thromboembolic clots.
What are Antiplatelet agents?
Substances that reduce the adhesion and aggregation of platelets.
What are Fibrinolytic agents?
Substances that promote the destruction of already formed blood clots or thrombi by disrupting the fibrin mesh.
What are Procoagulants?
Substances that are used to reduce excessive or abnormal bleeding
What compounds trigger vasospasms? Where are they released from?
Thromboxane A2 (TA2) and Serotonin (5-HT)
Released by Platelets
What triggers the extrinsic pathway?
trauma originating from the extra-vascular space (formation of a macromolecular complex involving Thromboplastin or Tissue Factor, and Factor VII)
What triggers the intrinsic pathway?
triggered by trauma to the blood itself (from large glycoprotein complexes released by platelets)

HMWK and collagen Ms. Ellen
What anticoagulants are direct acting? Indirect?
Direct: Calcium Chelators (sodium citrate, EDTA)
Heparin (UF and LMWHs)
Hirudin compounds (Lepirudin and Bivalirudin)

Indirect: Warfarin
What is heparin (molecularly) and how's it prepared?
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
What is heparin's mechanism of action?
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
How does heparin inhibit blood clotting?
Blocks conversion of Prothrombin to Thrombin and thus inhibits the synthesis of Fibrin from Fibrinogen
What factors are inhibited by heparin?
Factors Xa and Thrombin, but also Factors IXa and XIa

(XII, XI, IX, X, and Thrombin: Activated serine proteases are all inhibited)
What factors are inhibited by low doses of heparin?
Factor Xa
What factors are inhibited by high doses of heparin?
Prevents the thrombin-induced activation of platelets, and activation Factors V and VIII
What does heparin do to platelet function and vascular permiability? What effect does this have?
Inhibits platelet function and increases vascular permeability; may induce moderate to severe thrombocytopenia
What is the route of administration for heparin
Not effective after oral administration - generally administered by IV or subQ; IM should be avoided due to hematoma formation
What is important to know about the use of heparin in pregnant or breastfeeding mothers?
Heparin does not cross the placenta and does not pass into the maternal milk
When is heparin contraindicated?
Any situation where active bleeding must be avoided: Ulcerative lesions, intracranial hemorrhage, brain or spinal cord surgery, etc.
What drug can be used in the case of heparin overdose?
Protamine Sulfate (PS): Highly basic peptide that binds heparin and thus neutralizes its effects
Dosing of Protamine Sulfate in heparin overdose?
1 mg of PS for every 100 U of Heparin; not to exceed 50 mg for any 10 min period
Name 3 examples of low molecular weight heparin (LMWH).
Dalteparin Sodium (Fragmin)
Tinzaparin Sodium (Innohep)
Enoxaparin (Lovenox)
What are the clinical uses of LMWH?
Prevention of Deep Vein Thrombosis post-surgery
Tx of acute venous thromboembolic events and acute coronary artery syndromes
What's the difference between heparin and LMWH?
Heparin accelerates the interaction of antithrombin with thrombin and Factor Xa. LMWH selectively inhibits Xa only.
What are the advantages of LMWH over regular heparin? (4 things)
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
What is Lepirudin (Refludan)?
Recombinant form of the natural anticoagulant hirudin: potent and specific Thrombin inhibitor
What is Bivalirudin (Angiomax)?
Analog of hirudin: potent and specific Thrombin inhibitor
How long does it take warfarin to become active?
12 to 24 hours
What is warfarin's relation to vitamin K?
A structural analogues of vitamin K who's effects are like those of vitamin K depletion

(Blocks epoxide reductase)
What's the vitamin K-sensitive step in the synthesis of clotting factors?
the post-ribosomal carboxylation of specific glutamic acid residues. These amino acid residues chelate Ca2+
How does warfarin inhibit blood clotting?
Interfers with the hepatic synthesis of the vitamin K- dependent clotting factors (VII, IX, X and Prothrombin)
What does Protein C do?
bonds to thrombomodulin on endothelial cells, alters the specificity of Thrombin and favors the degradation of Factors Va and VIIIa into inactive proteases
What's warfarin's effect on Protein C?
Down-regulates Protein C = procoagulant activity of warfarin observed in early stage therapy
What are the half lives of warfarin effected factors?
Factor VII: 6 hours
Factor IX: 24 hours
Factor X: 40 hours
Prothrombin: 60 hours
What's warfarin bound to and how's it metabolized?
Largely bound to plasma albumin (> 98%), is metabolized by the liver by Cytochrome P450 into inactive metabolites which are then excreted in the urine
How do infants react with warfarin?
Newborn infants are more sensitive to oral anticoagulants than are adults because of lower vitamin K levels and lower rates of metabolism
Does warfarin pass the placenta?
Yup
How do you treat warfarin overdose?
Vitamin K1 (24 hour delay) supplementation
Transfusion of whole blood or plasma (major bleeding)
When is warfarin contraindicated?
Conditions where active bleeding must be avoided, Vit K deficiency and severe hepatic/renal disease, and where intensive salicylate therapy is required
What types of drugs diminish the response to warfarin? (3)
Inhibition of drug absorption (Cholestyramine)
Induction of hepatic microsomal enzymes
Stimulation of the synthesis of clotting factors
What types of drugs increase the response to warfarin? (5)
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)
What is Desmospressin Acetate?
a synthetic analogue of the pituitary antidiuretic hormone (ADH)
What is the mechanism of action of Desmospressin Acetate?
Stimulates the activity of Coagulation Factor VIII
What are the clinical uses of Desmospressin Acetate? (5)
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.
Mechanism of action for Acetylsalicylic Acid (Aspirin)?
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.
What is the effectiveness of low dose Acetylsalicylic Acid?
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
Are the effects of Acetylsalicylic Acid reversible?
Irreversible
What's the benefit of Acetylsalicylic Acid as a prophlaxis agent??
Uncertain for primary prevention of MI but beneficial for secondary (in pts with hx of vascular events)
What is Ticlopidine (Ticlid)?
an alternative antiplatelet drug for treatment of recurrent stroke in patients intolerant to aspirin
Ticlopidine (Ticlid) mechanism of action?
Inhibits the response of ADP on its platelet receptor and thus prevents aggregation by impairing the GPIIb/IIIa receptor.
Clopidogrel bisulfate (Plavix) mechanism of action?
Inhibits the response of ADP on its platelet receptor and thus prevents aggregation by impairing the GPIIb/IIIa receptor.
Clopidogrel bisulfate (Plavix) v. Ticlopidine (Ticlid), side effect wise?
Clopidogrel bisulfate has less side effects.
What is Abciximab (ReoPro)?
A chimeric monoclonal antibody inhibitor (Fab fragment) of platelet glycoprotein IIb/IIIa.
Abciximab (ReoPro) mechanism of action?
Prevents binding of fibrinogen and von Willebrand Factor.
Prevents platelet aggregation.
Primary use of Abciximab (ReoPro)?
acute coronary syndromes and percutaneous coronary intervention
How does the fibrinolytic system work?
dissolves intravascular clots via Plasmin, an enzyme that digests Fibrin (and other plasma proteins, including coag factors)
What's a major side effect of thrombolytic agents? why?
Can produce hemorrhage because they dissolve both pathologic thrombi and fibrin depostis at sites of vascular injury
When is thrombolytic therapy indicated?
In patients with extensive pulmonary emboli, severe iliofemoral thrombophlebitis and acute coronary occlusion
What is Tissue Plasminogen Activator? Where does it come from?
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)
What's the fate of free v. fibrin-bound plasmin?
Free Plasmin is rapidly inhibited in the plasma by an α2-antiplasmin. Fibrin-bound Plasmin is protected from inhibition.
What is Streptokinase (Streptase)?
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.
Thrombolytic therapy contraindications? (5)
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.
What is Aminocaproic acid? (+ mechanism of action)
Prevents the binding of Plasminogen and Plasmin to Fibrin = potent inhibitor for Fibrinolysis and can reverse states that are associated with excessive Fibrinolysis
What's PT? What's Normal? What about PTT?
PT: Reflects alterations in the extrinsic pathway (normal: ~ 12 sec)
aPTT: Reflects the intrinsic pathway (normal: 24 to 34 sec)
What's INR?
Index used to normalize PT: PT patient/PT mean normal; desired therapeutic INR is usually between 2 and 3 (human thromboplastin)
Signs of a DVT?
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
Heparin dosing?
Loading dose: 70-100 U/kg
Maintenance dose: 15-25 U/kg/hr