When a small vessel is injured, hemorrhage is prevented by vasospasm, the formation of a platelet plug and fibrin clot.
After the vessel is repaired, the clot is removed via the process of fibrinolysis.
Pathologic formation of a platelet plug and/or fibrin clot due to venous pooling, sluggish blood flow or inflammation of veins.
A dislodged arterial or venous thrombus that travels through the circulation & eventually occludes a smaller vessel in the lungs or brain.
Retard coagulation and thereby prevent the occurrence or enlargement of a thrombus.
Structurally related to vitamin K
INHIBITS synthesis of clotting factors II (prothrombin), VII, IX & X whose carboxylation is dependent on a reduced form of vitamin K.
Warfarin Time Frame
Delayed onset of action due to the time needed to deplete the pool of circulating clotting factors.
Optimal effect is not observed for 3-5 days after starting therapy.
Most common adverse effect of oral anticoagulants.
Can range in severity from a mild nosebleed to life threatening hemorrhage.
Oral anticoagulants are contraindicated
Pregnancy, and have a large number of potential drug interactions.
Clinical indications for use of warfarin
- Long term Tx of thromboembolic disorder such as DVT or Afib
- Patients with artificial heart valve.
- Used in conjunction with a heparin-type anticoagulant for the treatment of MI
PT prothrombin time
Used to monitor anticoagulant Tx
PT should be monitored when adding or deleting drugs with persons taking warfarin.
- The dosage of oral anticoagulants is based on maintaining the patient's prothrombin time (PT) - clotting time
- Control: Draw blood, add tissues thromboplastin prep to initiate coag, and compare the vitro clotting time in the sample with that in standardized control prep.
- General Rule: Dosage of warfarin should prolong the PT so that it's 1.3 to 1.5 times the PT of the control PT.
INR International Normalized Ratio
Used to monitor anticoagulant Tx
- When the international reference thromboplastin preparation is used as the standardized control preparation the ratio is expressed as the international normalized ratio (INR).
Tx: Warfarin-induced bleeding
Withhold anticoag until bleeding can be evaluated & the patient's PT can be determined.
Treatment of bleeding can include:
- Reduction in drug dosage
- Administration of phytonadione (vitamin K1)
- Fresh frozen plasma or factor IX concentrate if the bleeding is serious or if the INR is > 20.
New oral anticoagulant
- Lower doses can be used versus warfarin
- Results in significantly fewer strokes versus warfarin
- Causes significantly less bleeding versus warfarin
- Causes significantly less Intracranial hemorrhage versus warfarin
- INR monitoring is not necessary
- 80% renally metabolized > exclude those with kidney disease > May cause more myocardial infarction in these patients
Inactivates clotting factors
Heparin Time Frame
Not absorbed from the gut and so must be administered parenterally.
Administered IV with a rapid onset.
Enoxaparin (Lovenox) MOA
Lower molecular weight fraction, has less affinity for thrombin.
Primarily inactivates active factor X.
Enoxaparin (Lovenox) Time Frame
Administered subcutaneously maximal effect occurs between 3-5 hours after injection.
Activated partial thromboplastin time (aPTT) to monitor heparin therapy.
Heparin dose generally determined by monitoring the activated partial thromboplastin time (aPTT).
- The dosage is considered adequate when the aPTT is 1.5 to 2 times normal.
ID advantages of low-molecular-weight heparins vs. standard heparin.
LWMH, ex Enoxaparin > Primarily inactivates active factor X with less affinity for thrombin (more selective).
- No need to monitor aPTT because their anticoagulant activity is more predictable.
Most common adverse effects of parenteral anticoagulants.
- Heparin can cause two types of heparin-induced thrombocytopenia
- Heparin occasionally causes hyperkalemia due to suppression of aldosterone.
Clinical indications for use of parenteral anticoagulants
- Acute thromboembolic disorders including peripheral & pulmonary embolism, venous thrombosis & coagulopathies such as DIC.
- Prophylactically to prevent clotting in arterial & heart surgery, during blood transfusions, and in renal dialysis & blood sample collection.
- Prevention of embolus in patients with acute Afib
- Low doses > prevention of DVT & PE in high-risk patients
- LMWH > Prevent venous thromboembolism associated with abdominal surgery & hip/knee replacement.
- LMWH > Approved for use to prevent ischemic complications of unstable angina or NSTEMIs [non-ST segment elevation (non-Q wave) MI].
Antidote for heparin-induced bleeding.
Administer protamine sulfate
> a positively charged basic protein that physically combines with the negatively charged heparin & inactivates it.
- Severe bleeding may require fresh frozen plasma.
NSAID with analgesic, antipyretic & anti-inflammatory effects.
Inhibits platelet aggregation and is used to prevent and treat arterial thromboembolic disorders.
- Inhibits the synthesis of prostaglandins
Prevent arterial thrombosis in pts with ischemic heart disease and stroke.
o Prevents MI in unstable angina
o Pts with recent MI, used to prevent enlargement of a coronary thrombus and potentially reduce the severity of cardiac damage
o Used to prevent strokes in those with previous stroke
o Prevent thrombosis in pts with artificial heart valves
o Also to tx peripheral arterial occlusive disease and chronic limb ischemia
Alternative anti-platelet drug to aspirin.
A protein obtained from streptococci
t-PA, recombinant forms of human tissue plasminogen activator
Fibrinolytic drugs: Indications
Administer IV to degrade an existing thrombus in patients having myocardial infarction, thrombotic stroke or pulmonary embolism
- Reduces the neurologic sequelae of stroke
- The primary means of restoring coronary blood flow in STEMI (ST segment elevation MI) patients in hospitals without facilities for angioplasty.
Principal adverse effects of fibrinolytic drugs.
- Most common > HEMORRHAGE
- Hypersensitivity reactions
- Reperfusion arrhythmias (brady and tachy)
- Increased risk of bleeding associated with anticoagulant & antiplatelet drugs
Tissue Plasminogen Activator
Adv: Causes less bleeding than streptokinase
No allergic Rxns
Adv: Synthetic, make lots
Dis: Create a general lytic state that can lyse both normal and pathologic thrombi
- May cause arrhythmias (brady and tachy) due to free radical generation
- Can cause hypersensitivity and fatal anaphylactic shock
Administration of phytonadione (vitamin K1)
Treatment for Warfarin-induced bleeding