Hematology Flashcards
Heparin
MOA:
Lowers activity of thrombin and factor Xa
Short half life
Use:
Immediate anticoagulation for PE, acute coronary syndrome, MI, DVT
Used during pregnancy (does not cross placenta)
Follow PTT
Adv. effects:
Bleeding, thrombocytopenia (HIT), osteoporosis, drug-drug interactions
Antidote - protamine sulfate (+ charged binds to - charged heparin)
Heparin induced thrombocytopenia - IgG antibodies against heparin-bound platelet factor 4 —> activates platelets –> thrombosis and thrombocytopenia
Low molecular weight heparins (enoxaparin, dalteparin)
Fondaparinux
Act more on factor Xa
Better bioavailability
2-4 x longer half life
Administered subcutaneously w/o lab monitoring
Not easily reversible
Direct thrombin inhibitors (Bivalirudin)
MOA:
Directly inhibits activity of free and clot-assoc. thrombin
Use: Venous thromboembolism Atrial fibrillation Can be used in HIT No lab monitoring required
Adv. effects:
Bleeding
No specific reversal agent (can try prothrombin complex concentrates and/or fibrinolytics)
Warfarin
MOA:
Interferes w/ y-carboxylation of vit. K-dependent clotting factors II, VI, IX, X and protein C and S.
Metabolism affected by polymorphisms in the gene for vit. K epoxide reductase complex (VKORC1)
In lab –> effect on extrinsic pathway, increase PT
Long half-life
Use:
Chronic anticoagulation (VTE prophylaxis, prevention of stroke in A fib)
Not used in preggo women (crosses placenta)
Follow PT/INR
Adv. effects: Bleeding Teratogenic Skin/tissue necrosis (in first few days of large dose, due to small vessel microthromboses) Drug-drug interactions
Shorter half lives of Protein C and S results in early transient hypercoagulability with warfarin use
Reversal —> give vit. K
Rapid reversal —> give fresh frozen plasma
Heparin “bridging”
Heparin frequently used when starting warfarin.
Heparin’s activation of antithrombin enables anticoagulation during initial transient hypercoagulable state caused by warfarin.
Initial heparin therapy reduces risk of recurrent venous thromboembolism and skin/tissue necrosis
Heparin vs. Warfarin
HEPARIN
Structure: large, anionic,a cidic polymer
Route of admin: parenteral (IV, SC)
Site of action: Blood
Onset of action: Rapid
MOA: activates antithrombin –> dec action of IIa and factor Xa
Duration of action: acute (hours)
Inhibits coagulation in vitro: Yes
Agents for reversal: Protamine sulfate
Monitoring: PTT (intrinsic)
Crosses placenta: no
Heparin vs. Warfarin
WARFARIN
Structure: small, amphipathic molecule
Route of admin: Oral
Site of action: Liver
Onset of action: Slow, limited by t1/2 of normal clotting factors
MOA: impairs synthesis of vit. K dependent clotting factors II, VII, IX, X and anti clotting proteins C and S
Duration of action: Chronic (days)
Inhibits coagulation in vitro: no
Agents for reversal: Vit. K, fresh frozen plasma
Monitoring: PT/INR (extrinsic)
Crosses placenta: Yes (teratogenic)
Direct factor Xa inhibitors
Apixaban, Rivaroxaban
MOA: Bind to and directly inhibit factor Xa
Use:
Treatment & prophylaxis of DVT & PE (Rivaroxaban)
Stroke prophylaxis in ptns w/ A fib.
Oral agents do not usually require coagulation monitoring
Adv. effects: Bleeding
Thrombolytics
Alteplase (tPA), Reteplase (rPA), Streptokinasae, Tenecteplase
MOA: Plasminogen —> Plasmin, which cleaves thrombin and fibrin clots
Inc. PT, PTT, no change in platelet count
Use: Early MI, early ischemic stroke, direct thrombolysis of severe PE
Adv. effects: Bleeding
Contraindicates in ptns w/ active bleeding, history of intracranial bleeding, recent surgery, known bleeding diatheses, or severe hypertension
Toxicity - treat w/ aminocaproic acid (inhibitor of fibrinolysis)
factor deficiencies corrected with gresh frozen plasma and cryoprecipitate
ADP receptor inhibitors
Clopidogrel, Prasugrel, Ticagrelor, Ticlopidine
MOA:
Inhibit platelet aggregation by irreversibly (excpt ticargrelor) blocking ADP receptors —> prevent expression of glycoproteins IIb/IIIa on platelet surface
Use:
Acute coronary syndrome
Coronary stenting
Decrease incidence or recurrence of thrombic stroke
Adv. effects:
Neutropenia (ticlopidine)
TTP
Cilostazol, Dipyridamole
MOA:
Phosphodiesterase III inhibitor
Increase cAMP in platelets –> inhibition of platelet aggregation
Vasodilators
Use: Intermittent claudication Coronary vasodilation Prevention of stroke or TIAs (w/aspirin) Angina prophylaxis
Adv. effects: Nausea Headache Facial flushing Hypotension Abdominal pain
Glycoprotein IIb/IIa inhibitors
Abciximab, Eptifibatide, Tirofiban
MOA:
Bind to glycoprotein receptor IIb/IIIa on activated platelets, preventing aggregation
Abciximab - made from monoclonal antibody Fab fragments
Use:
Unstable angina
Percutaneous transluminal coronary angioplasty
Adv. effects:
Bleeding
Thrombocytopenia
