Coagulation Disorders

Objectives Define terms associated with coagulation disorders Identify coagulation disorders that are indications for coagulation modifiers State the primary mechanism of action by which the four classes of anticoagulation modifiers act Recall monitoring parameters and common adverse effects for starred coagulation modifiers

BACKGROUND AND DEFINITIONS

Epidemiology Incidence for coagulation disorders increases with INCREASE WITH AGE Many conditions increase risk for coagulation disorders: - Atrial fibrillation - Cerebrovascular accident

- Congestive heart failure - Previous DVT/PE - Myocardial infarction - Serious hepatic impairment

- Immobilization/paralysis - Post-operative/surgery - Vascular injury/trauma - Valvular heart disease - Indwelling catheters - Clotting component deficiency - Pregnancy - Malignancy

Nursing Role in Coagulation Disorders Obtaining a HISTORY PRIOR to administration of coagulation modifiers Performing regular physical assessments Assessing for signs and symptoms of BLEEDING Recognizing medication-related adverse effects

 Laboratory monitoring for both efficacy and safety Recognizing monitoring parameters for classes of coagulation modifiers Identifying potential drug-drug interactions Patient and care-giver EDUCATION

Definitions Coagulation the formation of an INSOLUBLE CLOT Coagulation cascade series of complex reactions that creates a fibrin meshwork Intrinsic pathway Injury to vessel Extrinsic pathway When blood leaks out of vessel Final common pathway: Prothrombin Thrombin Fibrinogen Fibrin Formation of FIBRIN CLOT

 Hemostasis the stopping of BLOOD FLOW Key Balance between fluidity and coagulation Steps: Vessel injury Vessel spasm Adherence of platelets to form plug

Fibrin strands form and coagulate

Fibrinolysis the process of CLOT REMOVAL Initiated within 24-48 hours of clot formation Steps Fibrin clot is formed Blood vessel cells secrete enzyme Tissue plasminogen activator (TPA) TPA converts inactive protein plasminogen to active enzyme plasmin Plasmin digests fibrin strands to remove the clot

Disorders in Hemostasis Thromboembolic disorders body forms undesirable clots Thrombus STATIONARY clot

 Arterial thrombi deprive tissue of adequate blood flow tissue ischemia Myocardial Infarction (MI) Cerebrovascular Accident (CVA) Embolus - TRAVELING clot Venous system thrombi Deep Venous Thrombosis (DVT) Thrombi formation in atria Right atrium Pulmonary Emboli (PE) Left atrium CVA

 Bleeding disorders abnormal CLOTTING FACTORS Non-hereditary Thrombocytopenia deficiency in platelets Conditions that suppress bone marrow function Drug-induced chemotherapy, immunosuppressants Hereditary genetic deficiencies in specific clotting factors Hemophilia A deficiency in factor VIII (80% of cases) Hemophilia B deficiency in factor IX (20% of cases) Von Willebrands disease (vWD) deficiency in von Willebrands factor Most common Plays role in platelet aggregation

Diagnosis of coagulation Disorders Health history Physical examination Laboratory tests Activated clotting time Activated partial thromboplastin time (aPTT) Bleeding time Heparin anti-Xa Platelet count Prothrombin time (PT) / International Normalized Ratio (INR) Thrombin time Liver function tests (LFTs)

TREATMENT OPTIONS
Treatment: Coagulation Modifiers Class Anticoagulan ts Antiplatelets Mechanism of Action Modification

Inhibit clotting factors Prevent clot formation

Inhibit platelet action

Prevent clot formation Removal of existing clot Promote clot formation

Thombolytics Dissolve clot Hemostatics Inhibit fibrin destruction

Anticoagulants
MOA Prevent clot formation Inhibit specific CLOTTING FACTORS Diminish action of platelets All act to PROLONG bleeding time

IV/Subcutaneous heparin (Heplock) fondaparinux (Arixtra) Direct Thrombin Inhibitors: argatroban (Novastan) bivalirudin (Angiomax) desirudin (Iprivask) Low Molecular Weight Heparins: enoxaparin (Lovenox) dalteparin (Fragmin)

 tinzaparin (Innohep) Oral warfarin (Coumadin)

Heparin (Heplock) MOA - enhances action of antithrombin III to inactivate circulating THROMBIN Given as IV infusion or subcutaneous (SC) Adverse Effects Hemorrhage, anaphylaxis, thrombocytopenia, nausea/vomiting Drug Interactions Oral anticoagulants, aspirin, NSAIDs (indomethacin, ibuprofen), nicotine, digoxin, tetracyclines, antihistamines, herbals (ginkgo, ginger, garlic, green tea) Monitoring Lab test: aPTT Activated partial thromboplastin time Normal: 25-35 seconds Therapeutic: 1.5 2 times baseline (pretreatment) Frequency Baseline then every 6 HOURS until stabile (2 consecutive therapeutic aPTTs) then daily thereafter With each dosage change Every 6 hours until stable then daily thereafter Hold _6 HOURS prior to procedure Ideal time for planned procedures

 Minimum of 2 hours if procedure unplanned Platelet Count Every other day until day 14 of therapy Signs of _BLEEDING__ Bruising, nosebleeds, excessive menstrual flow, coffee-ground emesis, tarry stools, tea-colored urine, rectal bleeding, dizziness, fatigue, pale skin Reversal of antocoagulation effects: Protamine sulfate 1mg for every 100 units of heparin

Enoxaparin (Lovenox) Low Molecular Weight Heparin (LMWH) MOA similar to heparin, but more specific inhibition of factor Xa. Given as SUBCUTANOUS INJECTION Adverse effects Hemorrhage, anaphylaxis, thrombocytopenia, nausea/vomiting, pain at injection site

Drug interactions Oral anticoagulants, aspirin, NSAIDs (indomethacin, ibuprofen,) herbals (ginkgo, ginger, garlic, green tea) Monitoring Lab test NOT REQUIRED Cannot use aPTT or INR (like heparin and warfarin) Platelet count (Inpatient daily / Outpatient monthly)

 Anti-factor Xa Drawn 4 hours after dose, costly, and takes days Not often performed Signs of bleeding *MOST IMPORTANT MONITORING PARAMETER Bruising, nosebleeds, excessive menstrual flow, coffee-ground emesis, tarry stools, tea-colored urine, rectal bleeding, dizziness, fatigue, pale skin Patient education Rotate injection sites Use alcohol swab to sterilize area before injection DO NOT RUB SITE after injection Report bleeding or abnormal bruising to MD Avoid hazardous activities Pregnancy category B

Warfarin (Coumadin) MOA VIT K____ antagonist Given orally Adverse reactions Hemorrhage, nausea/vomiting, purple toe Drug interactions Other anticoagulants, alcohol, NSAIDs, diuretics, antidepressants, steroids, antibiotics, vaccines, vitamins containing vitamin K, herbals (ginkgo, ginger, garlic, green tea), foods containing vitamin K (green leafy vegetables) Monitoring Lab test: International Normalized Ratio (INR) Therapeutic: 2.0-3.0_, high risk: 2.5-3.5 Frequency:

 Initiation: every 1-3 days Once begin to stabilize: every 7 days x2 stable INRs Once stable: every 4 weeks Signs of bleeding Bruising, nosebleeds, excessive menstrual flow, coffee-ground emesis, tarry stools, tea-colored urine, rectal bleeding, dizziness, fatigue, pale skin Reversal of anticoagulation effects Vitamin K given PO, IV or SQ Preferred route PO!! Patient education Take at the same time every day (usually QPM) Avoid changes in Vit K INTAKE Green leafy vegetables (e.g. broccoli, asparagus, spinach) Vitamins containing vitamin K Avoid hazardous activities Report abnormal bleeding or bruising to MD Do not start new medications before discussing with MD (Rx and OTC) Pregnancy category __________

Antiplatelets

MOA Prevent clot formation Oral aspirin Interfere with platelet aggregation All act to PROLONG bleeding time

 dipyridamole (Persantine) ADP receptor blockers clopidogrel (Plavix) prasugrel (Effient) ticlopidine (Ticlid) ticagrelor (Brilinta) ?? Intermittent Claudication Agents: cilostazol (Pletal) pentoxifylline (Trental)

 IV Glycoprotein IIb/IIIa Inhibitors abciximab (ReoPro) eptifibatide (Integrilin) tirofiban (Aggrastat)

Aspirin MOA: Inhibits platelet aggregation Irreversibly binds to COX in platelets inhibits formation of TXA2 inhibits platelet aggregation Given PO once daily Sold over the counter Adverse reactions Increased clot time, GI bleed, anaphylaxis, nausea/vomiting, diarrhea, abdominal pain Drug interactions Other antiplatelets, thrombolytics, NSAIDs, some antidepressants, herbals (ginkgo, ginger, garlic, green tea) Dose 81mg daily (chewed or PO enteric coated) 325mg daily (PO enteric coated) Take _AS PRESCRIBED_ by MD as antiplatelet agent even though sold OTC Monitoring Lab test NONE Signs of bleeding

 Bruising, nosebleeds, excessive menstrual flow, coffee-ground emesis, tarry stools, tea-colored urine, rectal bleeding, dizziness, fatigue, pale skin

Clopidogrel (Plavix) ADP receptor blocker MOA Inhibits platelet aggregation by directly inhibiting ADP binding to its receptor Given PO once daily Adverse effects Increase clot time, GI bleed, blood dyscrasias, dyspepsia, abdominal pain, rash/pruritis, diarrhea, headache, dizziness, flulike syndrome Must be stopped ______________________ prior to surgery due to bleeding risk Drug Interactions Other antiplatelets, thrombylytics, NSAIDs (including aspirin), antifungals (fluconazole), erythromycin, verapamil, herbals (ginkgo, ginger, garlic, green tea) Monitoring Lab test NONE Signs of bleeding Bruising, nosebleeds, excessive menstrual flow, coffee-ground emesis, tarry stools, tea-colored urine, rectal bleeding, dizziness, fatigue, pale skin

Thrombolytics

MOA Promote fibrinolysis to remove an _EXISTING______clot Dissolves the insoluble fibrin within the clot IV (only available IV)

 alteplase (Activase, TPA) reteplase (Retavase) streptokinase (Kabikinase) tenecteplase (TNKase) Use with CAUTION_ in the following situations: Recent trauma or surgery Arterial emboli or recent cerebral embolism Hemorrhage Thrombocytopenia Septic thrombophlebitis Childbirth

Alteplase (Activase, TPA) MOA Identical to enzyme human tissue plasminogen activator (TPA) Given _IV Within 12 hours of onset of symptoms of MI Within 3 hours of thrombotic CVA Adverse effects Bleeding (superficially at injection sites or internal), intracranial hemorrhage (rare, but serious), allergic reactions Drug interactions Anticoagulants, antiplatelets, NSAIDs (including aspirin), herbals (green tea, ginkgo, garlic, ginger) Monitoring Lab tests obtain BASELINE Hemoglobin/Hematocrit Platelet count

 aPTT/INR Contraindications: Active internal bleeding History of CVA in last 2 months Recent trauma or surgery Severe uncontrolled hypertension Intracranial neoplasm

Hemostatics

MOA PROMOTE_ clot formation Prevents thrombin from dissolving clot, thus enhancing stability of clot SHORTENS_ bleeding time IV: aminocaproic acid (Amicar), aprotinin (Trasylol) PO: tranexamic acid (Cyklokapron) Monitoring Clotting assessment Peripheral pulse changes, paresthesias, chest pain, SOB Thromboplebitis and extravasation Muscle wasting Myopathy, myoglobinuria

CONCLUSION AND SAMPLE QUESTIONS

Review learning objectives Define terms associated with coagulation disorders Identify coagulation disorders that are indications for coagulation modifiers State the primary mechanism of action by which the four classes of anticoagulation modifiers act Recall monitoring parameters and common adverse effects for starred coagulation modifiers

Sample Questions

1) Which of the following drugs is an antiplatelet agent? A. warfarin B. heparin C. aspirin D. enoxaparin

2) Which of the following choices represents the mechanism of action of warfarin (Coumadin)? A. Inhibits clotting factors B. Inhibits platelet action C. Dissolves clots D. Inhibits fibrin destruction

3) Which of the following lab tests should be monitored when using heparin? A. PT B. Thrombin time C. INR D. aPTT 4) When should the aPTT be checked when monitoring heparin therapy? A. Every 2 hours B. Every 2 hours until stable C. Every 6 hours D. Every 6 hours until stable

5) It is an important role of a nurse to recognize medication-related adverse effects when managing coagulation disorders. Which of the following is a potential adverse effects of anticoagulant agents? A. Abdominal pain

B. Allergic reaction C. Hemorrhage D. Headache