Anti Clot Medications

Anti Clot Medications

 

1st Stage of Hemostasis:  Formation of Platelet Plug

        Three steps occur in the formation of a platelet plug during hemostasis.  The first step involves platelet activation which requires activation of the glycoprotein (GP) IIb/IIIa receptor site.  GP IIb/IIIa receptors can be activated by thromboxane A₂ (TXA₂), circulating thrombin, collagen, platelet activating factor, and ADP.  Once platelets become activated, then step two involves platelet aggregation–a clumping effect where platelets stick together.  During platelet aggregation, fibrinogen combines with GP IIb/IIIa receptors to connect platelets together.  As platelets aggregate, in the third step they form a platelet plug to stop hemorrhage from a rupture in a vascular wall.

 

ANTIPLATELET MEDICATIONS
Drug Category	Mechanism of Action	Nursing Concerns
Aspirin	Prevents activation of thromboxane A2, a potent vasoconstrictor and GP IIb/IIIa receptor activator.	Contraindicated in children due to risk of Reyes syndrome. Baby aspirin is preferred for acute or prophylactic  management of heart disease. Assess patient for signs of bleeding (petechiae, ecchymosis, bloody or black stools, bleeding gums). Assess for signs of hypersensitivity.
Clopidogrel (Plavix®)	Prevents activation of GP IIb/IIIa receptors by ADP	If ACS patient is hypersensitive or contraindicated for ASA, patient may be considered for clopidogrel. Do not administer clopidogrel to ACS patients if CABG is planned within 5 – 7 days. Platelet function and bleeding time return to baseline in 7 – 10 days. Monitor patient for signs of thrombotic thrombocytopenic purpura (low platelet count, neuro symptoms, renal dysfunction, fever). Monitor for signs and symptoms of bleeding (urine, stool, hematoma, epistaxis, petechiae). May cause elevation of serum liver enzymes–establish baseline enzymes and bilirubin levels. Irreversibly blocks platelet activation for life of platelet.
Glycoprotein (GP) IIb/IIIa Inhibitors                   Eptifibatide (Integrilin®) Abciximab (ReoPro®) Tirofiban (Aggrastat®)	Directly blocks GP IIb/IIIa platelet receptors preventing aggregation of platelets	Evaluate  patient for history of any contraindications to GPIIb/IIIa prior to treatment. Prior to therapy, assess hemoglobin, hematocrit, platelet count, serum creatinine, PT, and aPTT. Maintain aPTT between 50 -70 seconds. Contraindicated if platelet count < 150,000/mm3 Reversibly blocks platelet activation by any mechanism of activation. Assess patient for signs of bleeding before administering GP IIb/IIIa inhibitor and frequently during therapy.

 

 

2nd Stage of Hemostasis:  Coagulation

        Coagulation involves the formation of fibrin as a blood protein that secures platelets into a blood clot.  Fibrin is formed through two different pathways that converge near the end into a common pathway for fibrin formation. 

The contact activation pathway (intrinsic pathway) is triggered by activation of factor XII from exposure to collagen due to damage to a vessel wall.  Activated factor XIIa catalyzes the activation of factor XI to XIa; which in turn catalyzes the activation of factor IX.  IXa works with VIII to catalyze factor X into Xa which catalyzes prothrombin into thrombin.  Thrombin catalyzes fibrinogen into fibrin–the final protein clotting product.

The second pathway is the tissue factor pathway (extrinsic pathway) which is triggered by trauma to the vascular wall.  Tissue factors that are bound intracellularly are released during trauma and activate factor VII.  Together, the tissue factors and VIIa catalyze factor X into Xa.  As with the contact activation pathway, activation of Xa leads to catalyzing of prothrombin into thrombin.  The latter catalyzes fibrinogen into fibrin.

Anticoagulant medications work on different factors of the intrinsic and extrinsic pathways. 

 

ANTICOAGULANT MEDICATIONS
Drug Category	Mechanism of Action	Nursing Concerns
Unfractionated Heparin	Enhances effect of antithrombin on inactivation of thrombin and factor Xa	Only routes of administration are IV or SQ (does not absorb PO; IM causes hematoma) Risk of bleeding increases.  Screen patients for contraindications. Short half-life:  If infusion is turned off, therapeutic effect can be lost. Monitor with activated partial thromboplastin time (aPTT) which normally is around 40 seconds.  Therapeutic goal for aPTT is 1.5 – 2 Ï normal level = 60 – 80 seconds). Does not cross placental barrier during pregnancy or pass into breast milk during lactation.
Low Molecular Weight Heparins Enoxaparin Dalteparin Tinzaparin	Inactivate factor Xa	Risk of bleeding increases.  Screen patients for contraindications. LMW heparins have been associated with neurological injuries (e.g., paralysis) secondary to use concurrent to spinal punctures or epidural anesthesia.
Warfarin	Decreases production of vitamin K dependent clotting factors (VII, IX, X, & prothrombin)	Risk of bleeding increases.  Screen patients for contraindications. Oral anticoagulant medication. Monitor prothrombin time (PT) or international ratio (INR).  Therapeutic ranges vary for INR depending on condition being treated.  Usually, therapeutic goal is 2-3 but may be set as high as 4.5. Teratogenic medication that passes into placenta (Category X).  Passes into breast milk becoming a contraindication for breastfeeding.
Bivalirudin	Inhibits thrombin activity Prevents conversion of fibrinogen to fibrin	An alternative for ACS patients undergoing PCI who are hypersensitive to heparin or low molecular weight heparin. No clinical evidence of effect with glycoprotein IIb/IIIa inhibitors during angioplasty. More expensive than heparin or enoxaparin. Back pain is a common side effect. Intravenous infusion regulated by aPTT like heparin.

 

 

Fibrinolytic Agents:

        Some anti-clot medications are designed to dissolve clots.  They are often referred to as "clot busters".  The human body's natural "clot buster" is an enzyme, plasmin, which facilitates degradation of fibrin.  Plasmin is activated by a precursor, plasminogen.  Fibrinolytic medications facilitate the conversion of plasminogen to plasmin.  Fibrinolytic Therapy is the intravenous administration of “clot busters”.  These are drugs that dissolve existing blood clots.  Remember that heparin only slows clot formation.  And aspirin and glycoprotein IIb/IIIa inhibitors only reduce platelet activation during the coagulation process.  But fibrinolytic drugs DISSOLVE CLOTS!

Contraindications for Fibrinolytic Therapy	Yes/No
Systolic BP > 180 mm Hg
Diastolic BP > 110 mm Hg
Right vs left arm systolic BP  difference > 15 mm Hg (possible aneurysm)
Hx of structural central nervous system disease (e.g., intracerebral hemorrhage, cerebral vascular lesion, intracranial neoplasm, ischemic stroke)
Significant closed head/facial trauma within past 3 months
Recent (within 6 weeks) major trauma, surgery (including laser eye surgery), GI/GU bleed.
Active bleeding (except menses)
Bleeding or clotting problems on blood thinners (anticoagulants)
Traumatic or prolonged (>10min) CPR
Pregnant female
Active peptic ulcer
Serious systemic disease (e.g., advanced/terminal cancer, severe liver or kidney disease)
© Table generated from American Heart Association. (2006). Handbook of emergency cardiovascular care for healthcare providers (p. 27).  Dallas: American Heart Association.

Risk Factors for Hemorrhagic Stroke (Intracranial Hemorrhage)

1. Age ≥ 65 years

2. Low Body Weight (< 70 kg)

3. Presenting Hypertension (systolic ≥ 180 mm Hg or diastolic ≥ 110 mm Hg)

4. Use of tPA (higher risk for hemorrhagic stroke than streptokinase)

Nursing Care during Fibrinolytic Therapy:

1.           Ascertain no contraindications to fibrinolytic therapy exist.

2.           Start IV lines & obtain blood for baseline lab with minimal venipunctures.

3.           Discuss fibrinolytic therapy with patient—probably requires informed consent.

4.           Bleeding is the most common complication during and following therapy:

a.       Mild gingival bleeding and oozing from IV sites is normal.

b.      Monitor for other signs of bleeding:

 i.      Ecchymosis or petechiae

ii.      Hematuria, hematemesis, hemoptysis, melena, epistaxis

iii.      Change in neurological status (intracranial hemorrhage)

 iv.      Deterioration in vital signs, drop in Hgb or Hct (internal bleeding)

5.           Avoid unnecessary injections or venipunctures—use saline or heparin lock for aspiration of blood specimens.

6.           Minimize trauma or movement of patient during fibrinolytic therapy.

a.       Use manual BP cuff instead of NIBP automated machine (requires less pressure during inflation).

b.      Allow patient to rest in position of comfort—no baths or range of motion, etc.

7.           Continuous cardiac monitoring at bedside in leads showing ST segment changes.

8.           One-on-one nursing care with continuous nursing presence and assessment for complications.

9.           Anticipate reperfusion dysrhythmias and be prepared to treat them.

a.       Atropine 1 mg preload injectable syringe at bedside for bradydysrhythmias.

b.      Lidocaine preloade or amiodarone at bedside for ventricular dysrhythmias.

c.       Defibrillator at bedside for ventricular dysrhythmias.

10.       Anticipate hourly 12-lead ECG’s from the initial dose of fibrinolytic medication.

11.       Anticipate a repeat of serum cardiac enzymes in 6 hours.

12.       Evidence of myocardial reperfusion (success of fibrinolytic therapy):

a.       Cessation of chest pain

b.      Reperfusion dysrhythmias (usually ventricular dysrhythmias or bradydysrhythmias)

c.       Restoration of ST segments to baseline

d.      Early and marked peaking of CK-MB cardiac enzyme

 

 

FIBRINOLYTIC AGENTS
Drug Agent	Uses	Nursing Concerns
Alteplase (t-PA)	STEMI Transient ischemic attack Ischemic CVA Acute massive pulmonary embolism (PE) Occluded central venous catheter	Advantages: Short half life (requires concurrent heparinization) Specific for new clots Only fibrinolytic agent approved for stroke (cerebral vascular accident) Disadvantages: Complex dosing schedule Expensive Contraindicated with gentamicin allergy
Reteplase (r-PA)	STEMI	Advantage: 2 IV boluses Disadvantage: Expensive
Tenecteplase (TNK-tPA)	STEMI	Advantage: Higher clot specificity Single IV bolus Disadvantage: Expensive
Streptokinase (SK)	STEMI Acute massive pulmonary embolism (PE) Deep vein thrombosis (DVT) Acute arterial thrombi Occluded arteriovenous cannula	Advantage: Inexpensive Disadvantages: Lacks clot specificity (old clots dissolved too) Allergic reactions 5.8% Occasional hypotension Contraindicated if previous Streptokinase therapy or recent streptococcal infection

 

Recombinent Human Activated Protein C (rhAPC or Xigris^®) is a naturally occurring protein in the human body that regulates the coagulation cascade.  RhAPC facilitates the role of tissue plasminogen activator (t-PA) as a fibrinolytic agent.  Thus it is theorized that rhAPC reduces the clotting cascade that occurs during septic shock in the microvasculature.  Evidence has shown that rhAPC significantly improves survival rates from septic shock.  Recombinant human activated protein C is also referred to as drotrecogin alpha.

 

REFERENCES:

American Heart Association. (2006). Handbook of emergency cardiovascular care for healthcare providers (pp. 27, 36, 52).  Dallas: American Heart Association.

American Heart Association. (2005). Stabilization of the patient with acute coronary syndromes.  Circulation, 112(24), IV-92-102.

Deglin, J.H., & Vallerand, A.H. (2009). Thrombolytic agents.  In Davis' drug guide for nurses (11th ed., pp. 1164-1169).  Philadelphia: F.A. Davis.

Dirks, J.L. (2010). Cardiovascular therapeutic management.  In L.D. Urden, K.M. Stacy, & M.E. Lough's (Eds.) Critical care nursing: Diagnosis and management (6th ed., pp. 510-515).  St. Louis: Mosby Elsevier.

Lehne, R.A. (2010). Pharmacology for nursing care (7th ed., pp. 594-618).  St. Louis: Saunders Elsevier.

 

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