hematology coagulation chapter 52-56
TRANSCRIPT
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Drugs Affecting Coagulation
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Anticoagulant, Antiplatelet, and Thrombolytic Drugs
Hemostasis Stage 1 Formation of Platelet Plug
Platelet aggregation Stage 2 Coagulation
Intrinsic system Extrinsic system You tube video
https://www.youtube.com/watch?feature=player_embedded&v=xNZEERMSeyM
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Process of Coagulation
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Blood Vessel Injury
Local vasoconstriction seals off small injury
Platelet aggregation forms a platelet plug
Hageman factor is activated
Intrinsic pathway converts prothrombin to thrombin to seal system
Extrinsic pathway clots the blood that has leaked out of the vascular system
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Damaged Vessel Endothelium Stimulates Platelets to Cause Platelet Adhesion
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Types of Blood Disorders
Thromboembolic disorder
Conditions that predispose a person to the formation of clots and emboli
Hemorrhagic disorder
Condition in which excess bleeding occurs
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Anticoagulant TherapiesA. Antiplatelet
1. Aspirin 2. Thienopyridines Clopidogrel (Plavix), Prasugrel (Effient) ,Tichlopidine (Tichlid) 3. GP IIb/IIIa Inhibitors Abciximab (Reopro),Eptifibitide (Integrilin) ,Tirofiban (Aggrastat)
B. Anticoagulants 1. Unfractionated Heparin 2. LMWH
a. Enoxaparin (Lovenox) b. Dalteparin (Fragmin) 3. Direct Thrombin Inhibitors
a. Bivalrudin (Angiomax) b. Argatroban 4. Factor Xa Inhibitors
a. Fondaparinux (Arixtra) 5. Vitamin K Antagonists
(Warfarin, Coumadin)
C. Fibrinolytics
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Actions of Anticoagulants
Antiplatelet Alter the formation of the platelet plug
Anticoagulants Interfere with the clotting cascade and thrombin
formation
Thrombolytic drugs Break down the thrombus that has been formed by
stimulating the plasmin system
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Classification of Cyclooxygenase Inhibitors
Drugs with anti-inflammatory properties NSAIDs (nonsteroidal anti-inflammatory
drugs) Aspirin, celecoxib, ibuprofen, and naproxen
Drugs without anti-inflammatory properties Acetaminophen
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Antiplatelet Drugs
Aspirin (ASA) Inhibition of cyclooxygenase
Ticlopidine (Ticlid) ADP receptor antagonists
Tirofiban (Aggrastat) GP IIb / IIIa receptor antagonists
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Antiplatelets-Aspirin
Action
Inhibit platelet adhesion and aggregation by blocking receptors sites on the platelet membrane-irreversible inhibition of cycloxyenase, an enzyme required by platelets to synthesize thromboxane A2 (TXA2)
Anagrelide: blocks the production of platelets in the bone marrow
Indications
Reduce risk of recurrent TIAs or strokes; reduces death or nonfatal MI; MI and anginal prophylaxis; anti-inflammatory, analgesic, and antipyretic effects
Pharmacokinetics Well absorbed and bound to plasma proteins Metabolized in the liver and excreted in the urine
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Aspirin
Nonselective inhibitor of cyclooxygenaseTherapeutic uses Analgesic, antipyretic, anti-inflammatory Suppression of platelet aggregation
Protects in thrombotic disorders Dysmenorrhea Cancer prevention Prevention of Alzheimer’s disease
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Antiplatelet (cont.)Contraindications
Allergy,
Pregnancy, and lactation
Anemia, postpartum hemorrhage, may prolong labor
Caution
Reye’s syndrome
Bleeding disorder, recent surgery, closed head injury
Adverse effects
Bleeding
Headache, dizziness, and weakness
GI distress
Drug-to-drug interaction Anticoagulants: warfarin and heparin Glucocorticoids Alcohol Ibuprofen ACE inhibitors and ARBs
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Clopidogrel (Plavix)
Therapeutic uses Prevents blockage of coronary artery stents Reduces thrombotic events in patients with
acute coronary syndromes MI, ischemic stroke, and vascular death
Similar adverse effects to those of aspirinUse with caution in combination with other drugs that promote bleeding
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Direct Thrombin Inhibitors
Direct inhibition of thrombin (unlike heparin, which enhances the activity of antithrombin)
Dabigatran- Etexilate (2010)
Oral prodrug- GI Conversion to Dabigatran
Advantages: doesn’t require monitoring of anticoagulation little risk of adverse interactions same dose can be used for all patients regardless of age
or weight
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Other Antiplatelet Drugs
Dipyridamole
Dipyrindamole + aspirin
Aggrenox
Cilostazol
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Anticoagulants
Argatroban (Acova)
Used to treat thrombosis in heparin-induced thrombocytopenia
Bivalirudin (Angiomax)
Used with aspirin to prevent ischemic events in patients undergoing trans luminal coronary angioplasty
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Direct Thrombin Inhibitors
Hiruden Analog: Bivalirudin (Angiomax) Prevents clot formation (combined with aspirin) in patients
with unstable angina who are undergoing coronary angioplasty Mechanism of action
Facilitates the actions of antithrombin Prevents conversion of fibrinogen to fibrin Prevents activation of factor XIII
Adverse effects Bleeding Back pain Nausea, headache
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Other Direct Thrombin Inhibitors
Lepirudin (Refludan)Argatroban (formerly known as Acova)Desirudin (Ipravask)Dabigatran (Pradaxa)
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Selective Factor Xa Inhibitors
Produce selective inhibition of factor XaFondaparinux Activation of antithrombin Injection
Rivaroxaban Binds directly with factor Xa to cause
inactivation Oral
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Rivaroxaban (Xarelto)
Oral anticoagulant approved in 2011Does not require laboratory monitoring Patients who received rivaroxaban were found to be much less likely to experience DVT, VTE, PE, or death
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Anticoagulants
Warfarin (Coumadin) Maintains a state of anticoagulation when the patient is
susceptible to potentially dangerous clot formation
Heparin (generic) Inhibits the conversion of Prothrombin to thrombin
Antithrombin (Thrombate III) Used for hereditary Antithrombin III deficiencies and
replacement therapy in congenital Antithrombin III deficiency
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Anticoagulants
Action
Interfere with the normal cascade of events involved in the clotting process
Pharmacokinetics
Vary based on the drug
Contraindications
Allergy and conditions that could be compromised by increased bleeding tendencies
Pregnancy, renal, and hepatic disorders
Cautions
CHF, thyrotoxicosis, senility, and psychosis
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Anticoagulants (cont.)
Adverse effects Bleeding GI upset Hepatic dysfunction Alopecia, dermatitis, bone marrow suppression, and
prolonged and painful erectionDrug-to-drug interactions Heparin and oral anticoagulants, salicylates,
penicillins, and cephalosporins Heparin and nitroglycerine Warfarin: number of documented interactions
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Heparin
Rapid acting anticoagulantUses Pulmonary embolism Stroke Vein thrombosis
Adverse Effects Hemorrhage Thrombocytopenia Hypersensitivity reactions
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Low-Molecular-Weight Heparins
Inhibit thrombus and clot formation by blocking factors Xa and Iia
Do not greatly affect thrombin, clotting, or prothrombin times; therefore, they cause fewer systemic adverse effects
Block angiogenesis, the process that allows cancer cells to develop new blood vessels
Are indicated for specific uses in the prevention of clots and emboli formation after certain surgeries or bed rest
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Warfarin (Coumadin)
Oral anticoagulantAntagonist Vitamin KEffects synthesis - Factors VII, IX, X, and prothrombinUses Prevents thrombosis formation
Adverse Effects Hemorrhage
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Coumadin(Warfarin)
https://www.youtube.com/watch?feature=player_embedded&v=ucP1OEOGO5E
Patient education video for monitoring and taking Coumadin.
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Thrombolytic Drugs
Streptokinase Binds plasminogen
Uses Myocardial infarction Deep vein thrombosis Massive pulmonary emboli
Adverse Effects Bleeding Hypotension Fever
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Thrombolytic Therapy
Action – to dissolve clots
Thrombolytics Alteplase -Tissue plasminogen activator Reteplase Streptokinase Urokinase Anistreplase
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Thrombolytic Agents
Action
Activate plasminogen to plasmin, which in turn breaks down fibrin threads in a clot to dissolve a formed clot
Indications Acute MI, pulmonary emboli, and ischemic stroke
Pharmacokinetics
Drugs must be injected and are cleared from the body after liver metabolism
Contraindications Allergy
Any condition that worsens through dissolution of clots Pregnancy and lactation
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Streptokinase (Streptase)
Binds to plasminogen to form active complexTherapeutic uses Acute coronary thrombosis (acute MI) Deep venous thrombosis (DVT) Massive pulmonary emboli
Adverse effects Bleeding – excessive fibrinolysis can be reversed with IV
aminocaproic acid (Amicar) Antibody production Hypotension Fever
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Thrombolytic Drugs
Streptokinase (Streptase); Alteplase (tPa)Major adverse effect – bleeding (minor oozing to life-threatening amount) Likely sites of bleeding
Recent wounds, needle puncture sites, invasive procedure sites
Anticoagulants increase the risk for hemorrhageBlood replacement may need to be considered
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Thrombolytic Agents (cont.)
Adverse effects Bleeding Cardiac arrhythmias Hypotension Hypersensitivity: rash, flushing, bronchospasm, and
anaphylactic reaction
Drug-to-drug interactions Anticoagulants Antiplatelet
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Bleeding Disorders Treated With
Clotting Factors
Hemophilia Genetic lack of clotting factors that leaves the patient
vulnerable to excessive bleeding from any injury
Liver disease Clotting factors and proteins needed for clotting are not
produced
Bone marrow disorders Platelets are not formed in sufficient quantity to be
effective
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Antihemophilics
Actions Replace clotting factors that are either genetically
missing or low in a particular type of hemophilia
Indications Prevent blood loss from injury or surgery and to treat
bleeding disorders
Pharmacokinetics Replace normal clotting factors; they are processed as
such by the body
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Antihemophilics (cont.)Contraindications
Allergy
Factor IX in the presence of liver disease
Lactation
Caution
Pregnancy
Adverse effects
Risks associated with use of blood products
Headache, flushing, fever, chills, and lethargy
Nausea and vomiting
Stinging, itching, and burning at the site of injection
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Systemic Hemostatic Agents
Action Stop the natural plasminogen clot-dissolving
mechanism by blocking its activation or by directly inhibiting plasmin
Indication Prevent or treat excess bleeding in hyperfibrinolytic
states
Pharmacokinetics Vary for each drug
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Systemic Hemostatic Agents
Contraindications
Allergy
Acute DIC
Caution
Cardiac disease, renal or hepatic dysfunction, pregnancy, and lactation
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Systemic Hemostatic Agents
Adverse effects
Excessive clotting
CNS: hallucinations, drowsiness, dizziness, headache, and psychotic states
GI: nausea, cramps, and diarrhea
Weakness, fatigue, malaise, and muscle pain
Aprotinin: cardiac arrhythmias, MI, CHF, and hypotension
Drug-to-drug interactions
Heparin
Oral contraceptives and estrogen
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Drugs for Deficiency Anemia
Anemia decrease in erythrocytes (RBC) Number Size Hemoglobin content
Causes Blood loss Hemolysis Bone marrow dysfunction
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Red Blood Cell Development
Stage 1 – Proerythroblasts Lacks hemoglobin
Stage 2 – Erythroblasts Gains hemoglobin
Stage 3 – Reticulocytes Immature erythrocytes
Stage 4 - Erythrocytes Maturity
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Iron Deficiency Anemia
Most common nutritional anemia
Iron essential to hemoglobin
Daily requirements
Dietary sources
Iron supplements
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Iron Deficiency Anemia-Causes
Imbalance in iron uptake and iron demand
Microcytic, hypochromic anemia
Causes Pregnancy Infancy and early childhood Chronic blood loss
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Iron Preparations
Ferrous Sulfate Indications Administration Drug Interactions
Adverse Effects GI disturbances Staining of teeth Toxicity
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Dosage Formula for Iron
Mg Iron =
0.66 x kg body weight x(100- hemoglobin value in g/dl)
14.8
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Vitamin B12 Deficiency
Vitamin B12 (Cobalamins)
Essential for synthesis of DNA
Absorption requires intrinsic factor
Daily requirement
Dietary sources
Diagnostic tests
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Vitamin B12 Deficiency – Causes and Consequences
Causes Regional enteritis Celiac disease Lack of intrinsic factor
Consequences Megaloblastic anemia Neurologic damage GI disturbances
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Vitamin B12 Preparations - Cyanocobalamin
Cyanocobalamin Administration
Oral, parenteral, intranasal Adverse Effects
Hypokalemia Long term treatment
With lack of intrinsic factor, Vitamin B12 lifelong
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Folic Acid Anemia
Folic Acid Found small intestine Daily requirements Dietary sources Administration
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Folic Acid Anemia- Causes and Consequences
Causes Poor dietMalabsorption syndrome
ConsequencesMegaloblastic anemiaNeural tube defects
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Hematopoietic and Thrombopoietic Growth Factors
Acts on bone marrow to stimulate formation of blood cells
Types Hematopoietic growth factor
RBC’s, WBCs Thrombopoietic growth factor
Platelets
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Epoetin Alfa (Erythropoietin)
Epoetin alfa (Epogen) Hematopoietic growth factor Recombinant DNA technology
Uses Chronic renal failure HIV-infected patients Chemotherapy
Adverse Effects Hypertension
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Filgrastim (Neupogen)
Filgrastim Hematopoietic growth factor Recombinant DNA technology
Uses Chemotherapy Bone marrow transplant Chronic neutropenia
Adverse Effects Bone pain
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Oprelvekin (Interleukin – 11)
Oprelvekin (Neumega) Thrombopoietic growth factor Recombinant DNA technology
Uses Chemotherapy
Adverse Effects Fluid Retention Cardiac Dysrhythmias