DRUGDEX® Consults

ANTITHROMBOTIC AND THROMBOLYTIC THERAPY - ACCP GUIDELINES

RESPONSE
This summary of the Seventh American College of Chest Physicians Conference on Antithrombotic
and Thrombolytic Therapy Guidelines (2004) consists primarily of class 1A recommendations (ie,
strongly recommended items that can apply to most patients in most circumstances without
reservation). Class 1C+ guidelines (ie,strongly recommended items that can apply to most patients in
most circumstances) pertaining to pregnant or pediatric patients were also included.
PREVENTION OF VENOUS THROMBOEMBOLISM
The Seventh American College of Chest Physicians (ACCP) Conference on Antithrombotic and
Thrombolytic Therapy developed the following recommendations for the prophylaxis of venous
thromboembolism (VTE) [1]:
General Recommendations:
Use of aspirin alone NOT recommended
Consider manufacturer guidelines for each of the antithrombotic agents
Consider renal impairment and the elderly when deciding on doses of LMWH, fondaparinux, direct
thrombin inhibitors, and other antithrombotic drugs.
General Surgery:
Other than early and persistent mobilization, specific prophylaxis is NOT recommended for low risk
general surgery patients undergoing minor procedures, are under 40 years of age, and have no
additional risk factors
Low dose unfractionated heparin (LDUH), 5000 Units twice daily, or low molecular weight heparin
(LMWH), up to 3400 Units once daily, for moderate-risk general surgery patients; moderate risk
patients: those with risk factors for VTE undergoing a nonmajor procedure, those between 40 to 60
years of age without additional risk factors undergoing a nonmajor procedure, or those less than 40
years of age undergoing major operation with no additional risk factors
LDUH, 5000 Units three times daily, or LMWH, more than 3400 Units daily, for higher-risk general
surgery patients; high risk patients: those greater than 60 years of age undergoing nonmajor surgery,
those with additional risk factors undergoing nonmajor surgery. those greater than 40 years of age
undergoing major surgery or those with additional risk who are undergoing major surgery
LDUH, three times a day, or LMWH, greater than 3400 units daily, combined with graduate
compression stockings (GCS) and/or intermittent pneumatic compression (IPC) for high risk general
surgery patients with multiple risk factors
Vascular Surgery:
LDUH or LMWH for patients undergoing major vascular surgical procedures with additional
thromboembolic risk factors
Thromboprophylaxis NOT routinely recommended on patients without additional thromboembolic risk
factors
Gynecologic Surgery:
Other than early and persistent mobilization, specific prophylaxis is NOT recommended for
gynecologic surgery patients undergoing brief procedures (30 minutes or less) for benign disease.
Thromboprophylaxis for all major gynecologic surgery patients
LDUH, 5000 Units twice daily, for patients undergoing major gynecologic surgery for benign disease
with no additional risk factors
Alternative, LMWH of 3400 Units or less once per day or IPC started just before surgery and
continuously while patient is not ambulating.
LDUH, 5000 Units three times daily, or LMWH, greater than 3400 Units daily, for patients undergoing
extensive surgery for malignancy and for patients with additional risk factors
Alternative, IPC alone until hospital discharge.
Continue treatment until hospital discharge for patients undergoing major gynecological procedures,
and for 2 to 4 weeks after hospital discharge for patients who are at high risk, have undergone cancer
surgery and who are >60 years of age or have previously experienced a venous thromboembolic
event.
Urologic Surgery:
Other than early and persistent mobilization, specific prophylaxis is NOT recommended when the
patients are undergoing transurethral or other low risk urological procedures
LDUH twice daily or three times daily in patients undergoing major, open urologic procedures
Alternative, prophylaxis with LMWH
LDUH or LMWH combined with IPC or GCS for patients with multiple risk factors
Laproscopic Surgery:
Routine thromboprophylaxis, other than aggressive mobilization, NOT recommended in patients
undergoing laproscopic surgery
Thromboprophylaxis with one or more of LDUH, LMWH, IPC, or GCS is recommended for
laparoscopic procedures in patients who have additional thromboembolic risk factors
Total Hip Replacement:
For elective total hip replacement, one of the following:
low molecular weight heparin (LMWH) at usual high-risk dose, started 12 hours before surgery or 12
hours to 24 hours after surgery, or 4 hours to 6 hours after surgery at one-half the usual high-risk
dose then increasing to usual high-risk dose on the following day
fondaparinux 2.5 milligrams started 6 hours to 8 hours after surgery
adjusted-dose vitamin K antagonist (VKA) started preoperatively or evening after surgery; target INR
2.5, range 2 to 3
Administer for at least 10 days
Extended prophylaxis (28 to 35 days postoperatively) with LMWH, a VKA, or fonadaparinux is
recommended
Recommend AGAINST use of aspirin, dextran, low dose unfractionated heparin, graduated
compression stockings, intermittent pneumatic compression, or venous foot pump as only method of
thromboprophylaxis in total hip replacement patients
Total Knee Arthroplasty:
For patients undergoing total knee arthroplasty, routine thromboprophylaxis with low molecular weight
heparin at usual high-risk dose, fondaparinux, or adjusted-dose vitamin K antagonist (target INR 2.5,
range 2 to 3) for at least 10 days
Use of aspirin or low dose unfractionated heparin NOT recommended as sole method of
thromboprophylaxis in patients undergoing total knee arthroplasty
Knee arthroscopy:
Other than early and persistent mobilization, specific prophylaxis is NOT recommended
LMWH for patients undergoing arthroscopic knee surgery who are at a higher than usual risk based
on preexisting VTE risk factors or following a prolonged or complicated procedure.
Hip fracture surgery:
At least 10 days of thromboprophylaxis with low molecular weight heparin (LMWH; using high-risk
dose), fondaparinux (2.5 milligrams daily), a vitamin K antagonist (VKA; target INR 2.5, range 2 ro 3)
or LDUH for patients undergoing hip fracture surgery
Extended prophylaxis (28 to 35 days postoperatively) with fondaparinux, LMWH, or a VKA is
recommended
Use of aspirin NOT recommended as sole method of thromboprophylaxis
LDUH or LMWH to be initiated between hospital admission and surgery, if the surgery is to be
delayed
Other Major Orthopedic Surgery:
Decision about timing of start of pharmacologic thromboprophylaxis based on efficacy-to-bleeding
tradeoffs for that agent; for low molecular weight heparin, only small differences between
preoperative or postoperative initiation of therapy are seen therefore both options are acceptable
Routine use of Doppler ultrasonography screening at time of hospital discharge in asymptomatic
patients NOT recommended
Elective Spine Surgery:
Low dose postoperative LDUH alone as prophylaxis for patients with additional risk factors
Alternative, prophylaxis with LMWH alone or perioperative IPC alone
LDUH or LMWH combined with GCS and/ or IPC for patients with multiple risk factors for venous
thromboembolism (VTE)
Isolated lower extremity injuries:
Thromboprophylaxis NOT recommended in patients with isolated lower extremity injuries
Neurosurgery:
Routine thromboprophylaxis should be used
IPC, with or without GCS, for patients undergoing intracranial neurosurgery
Trauma:
If possible, thromboprophylaxis for patients with at least one risk factor for venous thromboembolism
Low molecular weight heparin prophylaxis should be started as soon as it is safe, if no major
contraindications exist
Thromboprophylaxis should be continued until hospital discharge, including inpatient rehabilitation
LMWH or VKA (target INR: 2.5; INR range 2.0 to 3.0) continued after discharge of patients with major
impaired mobility.
Acute Spinal Cord Injury:
Thromboprophylaxis recommended for all patients
Single modality prophylaxis with low dose unfractionated heparin, graduated compression stockings,
or intermittent pneumatic compression NOT recommended
IPC and/ or GCS recommended when anticoagulant prophylaxis is contraindicated early after injury
Burns:
LDUH or LMWH initiation, as soon as it is considered safe, for burn patients with additional risk
factors for VTE, and who have no other contraindications. Additional risk factors include one or more
of the following: advanced age, morbid obesity, extensive or lower extremity burns, concomitant lower
extremity trauma, use of femoral venous catheter, and/ or prolonged immobility
Mechanical prophylaxis with GCS or IPC for patients who have risk factors for VTE but also have a
contraindication to anticoagulant prophylaxis
Medical conditions:
Prophylaxis with low dose unfractionated heparin or low molecular weight heparin indicated in
acutely ill hospitalized patients with congestive heart failure or severe respiratory disease, or who are
confined to bed and have one or more risk factors, including active cancer, previous venous
thromboembolism, sepsis, acute neurologic disease, or inflammatory bowel disease
Cancer:
Cancer patients undergoing surgery should receive prophylaxis appropriate for their current risk state
Hospitalized, acutely ill cancer patients who are bedridden should receive prophylaxis appropriate for
their current risk state
LMWH and fixed dose warfarin NOT recommended as prophylaxis to thrombosis related to long term
indwelling central venous catheters
Critical Care:
Assess all patients for risk of venous thromboembolism upon admission to critical care unit, most
patients should receive thromboprophylaxis
Mechanical prophylaxis with GCS or IPC for all patients at high risk for bleeding, until the bleeding
risk decreases.
Low dose unfractionated heparin or low molecular weight heparin (LMWH) prophylaxis for patients
in ICU at moderate risk for venous thromboembolism (eg, medically ill or post-operative patients);
LMWH prophylaxis for patients at higher risk (eg, following major trauma or orthopedic surgery)
Long distance travel:
For flights longer than 6 hours duration, avoid constrictive clothing around lower extremities or waist,
avoid dehydration, stretch calf muscles frequently
For travelers with additional risk factors for venous thromboembolism and if active prophylaxis is
being considered, additional measures can be used such as below-knee graduated compression
stockings providing 15 to 30 mm Hg of pressure at the ankle, or single prophylactic dose of low
molecular weight heparin injected prior to departure
Aspirin NOT recommended for venous thromboembolism prophylaxis associated with travel
DEEP VENOUS THROMBOSIS - TREATMENT
The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy developed the following
recommendations for the treatment of acute deep vein thrombosis (DVT) [2]:
Patients with confirmed DVT, short term therapy with subcutaneous low molecular weight heparin
(LMWH) or subcutaneous or intravenous unfractionated heparin (UFH)
Patients with a high clinical suspicion of DVT, begin anticoagulant treatment while waiting for
outcomes of diagnostic testing
Patients with acute DVT, treat initially with LMWH or UFH for at least 5 days
Addition of a vitamin K antagonist (VKA) to LMWH or UFH therapy started on the first treatment day
For intravenous UFH administered by continuous infusion, dose adjust to achieve and maintain an
aPTT prolongation corresponding to plasma heparin levels from 0.3 to 0.7 IU/ml anti-Xa activity by
amidolytic assay
Patients with acute DVT, subcutaneous UFH is an adequate alternative to intravenous UFH
Patients who receive SC UFH, initial dose is 35000 U/24h, with subsequent dosing to maintain a
therapeutic aPTT
Discontinue heparin when the INR is at least 2 and stable
LMWH therapy preferred over UFH as an outpatient if possible and as inpatient if necessary
Routine monitoring with anti-factor Xa levels in patients treated with LMWH, routine use of
intravenous thrombolytic therapy, routine use of vena cava filter in addition to anticoagulants, NOT
recommended
Dose adjustments of VKA to maintain a target INR of 2.5 (range, 2 to 3) for all treatment durations;
high-intensity and low-intensity VKA therapy NOT recommended
Administer longer term treatment with VKA in patients with a first episode of DVT secondary to a
transient risk factor (at least 3 months of treatment), in patients with a first episode of idiopathic DVT
(6 to 12 months of treatment)
Patients with a first episode of DVT with documented antiphospholipid antibodies or who have tow or
more thrombophilic conditions, continue treatment for 12 months, and anticoagulant therapy
indefinitely
Longer term treatment (6 to 12 months) in patients with first DVT episode who also have a
documented protein C or S deficiency, the factor V Leiden or prothrombin 20210 gene mutation,
homocysteinemia or high factor VIII levels (greater than 90th percentile of normal)
LMWH for first 3 to 6 months of long-term anticoagulant therapy in patients with DVT and cancer and
indefinite anticoagulation therapy or until the cancer is resolved.
PULMONARY EMBOLISM - TREATMENT
The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy made the following
recommendations for the treatment of acute pulmonary embolism (PE) [2]:
Patients with confirmed nonmassive PE, short term therapy with subcutaneous low molecular weight
heparin (LMWH) or intravenous unfractionated heparin (UFH)
Patients with a high clinical suspicion of PE, begin anticoagulant treatment while waiting for outcomes
of diagnostic testing
Addition of a vitamin K antagonist (VKA) to LMWH or UFH therapy started on the first treatment day
Discontinue heparin when INR is stable and at least 2
For intravenous UFH administered by continuous infusion, dose adjust to achieve and maintain an
aPTT prolongation corresponding to plasma heparin levels from 0.3 to 0.7 IU/ml anti-Xa activity by
amidolytic assay
LMWH therapy preferred over UFH in patients with acute nonmassive PE
Routine monitoring with anti-factor Xa levels, routine use of systemic thrombolytic therapy, NOT
recommended
Dose adjustments of vitamin K antagonists to maintain a target INR of 2.5 (range, 2 to 3) for all
treatment durations; high-intensity and low-intensity VKA therapy NOT recommended
Longer term treatment with vitamin K antagonists in patients with a first episode of PE secondary to a
transient risk factor (at least 3 months) or in patients with a first episode of idiopathic PE (6 to 12
months)
Patients with a first episode of PE with documented antiphospholipid antibodies or who have two or
more thrombophilic conditions, continue treatment for 12 months, and anticoagulant therapy
indefinitely
Longer term treatment (6 to 12 months) in patients with first PE episode who also have a documented
antithrombin, protein C or S deficiency, the factor V Leiden or prothrombin 20210 gene mutation,
homocysteinemia or high factor VIII levels (greater than 90th percentile of normal). Indefinite
treatment for patients with idiopathic PE
LMWH for first 3 to 6 months of long-term anticoagulant therapy in patients with PE and cancer
ACUTE UPPER EXTREMITY DVT
The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy made the following
recommendations for the treatment of acute upper extremity DVT [2]:
Patients with acute upper-extremity DVT, treat with UFH or LMWH, and long term with VKA.
VENOUS THROMBOEMBOLISM - TREATMENT DURING PREGNANCY
In pregnant women with acute venous thromboembolism, ACCP guidelines recommend adjusted-
dose low molecular weight heparin (LMWH) throughout pregnancy or intravenous unfractionated
heparin (bolus, then continuous infusion to maintain aPTT in therapeutic range) for at least 5 days,
then adjusted-dose unfractionated heparin or LMWH for remainder of pregnancy. Administer
anticoagulants for at least 6 weeks postpartum [3].
ATRIAL FIBRILLATION
The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy made the following
recommendations for the management of atrial fibrillation [4]:
Patients with atrial fibrillation (AF) of at least 48 hours or of unknown length of time and the
pharmacologic or electric cardioversion is planned, anticoagulation with an oral VKA, such as
warfarin, with a range of 2.0 to 3.0 and a target INR of 2.5, for three weeks before elective
cardioversion and for at least four weeks after successful cardioversion.
For patients with persistent or paroxysmal AF at high risk of stroke (prior ischemic stroke, transient
ischemic attack or systemic embolism, age greater than 75 years, moderately or severely impaired
left ventricular systolic function and/or history of congestive heart failure, history of hypertension, or
diabetes mellitus), use an oral vitamin K antagonist, such as warfarin (target INR 2.5, range 2 to 3)
For patients with persistent or paroxysmal AF at intermediate risk of stroke (age 65 to 75 years, no
other risk factors) antithrombotic therapy with either an oral vitamin K antagonist, such as warfarin
(target INR 2.5, range 2 to 3), or aspirin (325 milligrams per day)
ATRIAL FLUTTER
The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy made the following
recommendations for the management of atrial flutter [4]:
Patients with atrial flutter and mitral stenosis, recommend anticoagulation with oral VKA, such as
warfarin, with a range of 2.0 to 3.0 and a target INR of 2.5
Patients with atrial flutter and prosthetic heart valves, anticoagulation with an oral VKA, such as
warfarin
MITRAL VALVE PROLAPSE
The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy recommends long term
aspirin therapy (50 to 162 milligrams per day) for patients with mitral valve prolapse who have
documented but unexplained transient ischemic attacks (TIAs) [5].
PROSTHETIC HEART VALVES - Mechanical Prosthetic Heart Valves
 The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy recommend for all
patients with mechanical prosthetic heart valves VKA, unfractionated heparin or LMWH until the INR
is stable and at a therapeutic level for two consecutive days [4].
Patients with mechanical prosthetic heart valves who suffer systemic embolism despite a therapeutic
INR , use aspirin, 75 to 100 milligrams per day (mg/day), in addition to VKA, and maintenance of the
INR at target of 3.0 and a range of 2.5 to 3.5
Target Range
Type of Heart valve
INR INR
St Jude medical bileaflet valve in the aortic position 2.5 2.0 to 3.0
tilting disk valves and bileaflet mechanical valves in the mitral position 3.0 2.5 to 3.5
CarboMedics bileaflet valve in the aortic position, normal left atrium size and sinus
2.5 2.0 to 3.0
rhythm
Medtronic Hall tilting disk mechanical valves in the aortic position, normal left
2.5 2.0 to 3.0
atrium size and sinus rhythm
mechanical valves and additional risk factors (AF, myocardial infarction, left atrial
3.0 2.5 to 3.5
enlargement, endocardial damage, and low ejection fraction)*
caged ball or caged disk valves* 3.0 2.5 to 3.5
* combined with low doses of aspirin, 75 to 100 mg/day

PROSTHETIC HEART VALVES - Bioprosthetic Valves

The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy made the following
recommendations for the management of patients with bioprosthetic valves [4]:

All patients with who have received bioprosthetic heart valves VKA with unfractionated heparin or
LMWH until the INR is stable and at a therapeutic level for two consecutive days
Patients with bioprosthetic valves in the mitral position, VKA with a target INR of 2.5 and a range of
2.0 to 3.0, for the first three months after valve insertion
Patients with bioprosthetic valves in the aortic position, VKA with a target INR of 2.5 and a range of
2.0 to 3.0, for the first three months after valve insertion or aspirin 80 to 100 mg/day
Patients with bioprosthetic valves who have a history of systemic embolism, VKA for 3 to 12 months
Patients with bioprosthetic valves who have AF, long term treatment with VKA with a target INR of 2.5
(range 2.0 to 3.0)
Patients with bioprosthetic valves who are in sinus rhythm and do not have AF, long term treatment
therapy with aspirin, 75 to 100 mg/day
STROKE
The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy made the following
recommendations for the treatment of acute ischemic stroke [6]:
For eligible patients, within 3 hours of symptom onset, intravenous tissue plasminogen activator (tPA;
0.9 milligrams per kilogram; maximum 90 milligrams), 10% of dose as initial bolus, remainder infused
over 60 minutes
Eligible patients:
At least 18 years old with a clinical diagnosis of stroke with clinically meaningful neurologic deficit
Onset less than 180 minutes
Baseline CT showing no evidence of intracranial hemorrhage
Excluded patients:
Minor or rapidly improving signs and symptoms
Signs of or history of intracranial hemorrhage; symptoms of subarachnoid hemorrhage or post-
myocardial infarction pericarditis
Seizure at onset of stroke
Stroke or serious head injury within 3 months, major surgery or serious trauma within 2 weeks
Gastrointestinal or urinary tract hemorrhage within 3 weeks
Systolic blood pressure greater than 185 mmHg or diastolic blood pressure greater than 110 mmHg
Aggressive therapy used to lower blood pressure, or to treat blood glucose less than 50
milligrams/deciliter (mg/dL) or greater than 400 mg/dL
Arterial puncture at a noncompressible site or lumbar puncture within 1 week
Platelet count less than 100,000/microliter
Heparin therapy within 48 hours associated with elevated activated partial thromboplastin time
Current oral anticoagulant therapy (prothrombin time greater than 15 seconds, INR greater than 1.7)
Pregnant or lactating women
Intravenous streptokinase NOT recommended between 0 and 6 hours of symptom onset
For patients not eligible for thrombolytic therapy, early aspirin therapy (160 to 325 milligrams per day)
For acute stroke patients with limited mobility, prophylactic low-dose subcutaneous heparin or low
molecular weight heparins or heparinoids to prevent deep vein thrombosis and pulmonary
embolism
Antiplatelet treatment consisting of aspirin 50 milligrams (mg) to 325 mg/day OR combination aspirin
25 mg and extended-release dipyridamole 200 mg twice daily OR clopidogrel 75 mg/day
Patients at moderate to high risk of bleeding complications, low doses of aspirin 50 to 100 mg/day in
Patients allergic to aspirin, use clopidogrel
Antiplatelet agents preferred over oral anticoagulation
For patients undergoing carotid endarterectomy, aspirin (81 to 325 milligrams per day) prior to and
following the procedure
The ACCP guidelines for the prevention of cardioembolic cerebral ischemic events are as follows [6]:
In patients with atrial fibrillation with a recent stroke or TIA, long term anticoagulation with target INR
of 2.5 (range, 2 to 3)
For patients with cardioembolic stroke with contraindications to anticoagulant therapy, aspirin should
be used
Patients with stroke associated with aortic atherosclerotic lesions, use antiplatelet therapy
Patients with cryptogenic ischemic stroke and patent foramen ovale (PFO), use antiplatelet therapy
Patients with mitral valve strands or prolapse, with a history of TIA or stroke, use antiplatelet therapy
ACUTE CORONARY SYNDROME
The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy made the following
recommendations for the management of non-ST-elevation acute coronary syndrome (NSTE ACS) [7]:
For patients presenting with NSTE ACS, oral aspirin 75 milligrams (mg) to 325 mg immediately, then
75 mg to 162 mg daily
For NSTE ACS patients with aspirin allergy, immediate treatment with clopidogrel, 300 mg oral bolus,
followed by 75 mg per day indefinitely
If diagnostic catheterization will be delayed or coronary bypass surgery will not occur for at least 5
days following coronary angiography, clopidogrel 300 mg as bolus therapy followed by 75 mg/day for
9 to 12 months with aspirin
In moderate to high-risk NSTE ACS patients, eptifibatide or tirofiban added to aspirin and heparin for
initial treatment
Abciximab treatment NOT recommended as initial therapy except when coronary anatomy is known
and percutaneous coronary intervention (PCI) is planned within 24 hours
Unfractionated heparin preferred over no heparin for short term use with antiplatelet therapies
Weight based dosing of UFH and maintenance of aPTT between 50 s and 75 s
The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy made the following
recommendations for the management of acute coronary syndrome (ACS) with and without ST-
segment elevation [7]:
Aspirin therapy at initial doses of 160 milligrams (mg) to 325 mg, then indefinite therapy of 75 mg to
162 mg per day
Lower doses of aspirin (100mg or less) are recommended if there is a history of aspirin-induced
bleeding or risk factors for bleeding
If aspirin is contraindicated or not tolerated, clopidogrel (75 mg/day) for long term therapy
Oral aspirin therapy (75 milligrams to 162 milligrams) is recommended for the management of
chronic, stable coronary artery disease [7].
The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy recommends patients
with congestive heart failure with or without CAD receive aspirin whether or not they are receiving
ACE inhibitors [7].
ACUTE MYOCARDIAL INFARCTION
For the treatment of acute myocardial infarction, the guidelines developed at the Seventh ACCP
Conference on Antithrombotic and Thrombolytic Therapy recommend [8]:
Use of any approved fibrinolytic agent for patients with ischemic symptoms characteristic of acute
myocardial infarction of 12 hours duration or less and ST-segment elevation or left bundle-branch
block on electrocardiogram; alteplase or tenecteplase is recommended over streptokinase in patients
with a symptom duration of 6 hours or less
Use of streptokinase, anistreplase, alteplase, reteplase, or tenecteplase
For symptom duration of 6 hours or less, alteplase or tenecteplase is recommended
Alteplase, reteplase or tenecteplase are recommended in patients with known allergy or sensitivity to
streptokinase
If prehospital administration of fibrinolytic therapy is feasible and primary angioplasty unavailable,
prehospital fibrinolytic therapy only
For acute myocardial infarction patients who are candidates for fibrinolytic therapy, treatment initiation
within 30 minutes of arrival to the hospital or first contact with health care system
Fibrinolytic therapy NOT recommended if there is a history of intracranial hemorrhage, closed head
trauma, or ischemic stroke in previous three months
For adjunctive treatment in patients with acute ST elevation myocardial infarction, with or without
fibrinolytic therapy, aspirin (160 milligrams (mg) to 325 mg orally) at initial evaluation followed by 75
mg to 162 mg per day indefinitely
If there is a high risk of systemic or venous thromboembolism (anterior MI, pump failure, previous
embolus, atrial fibrillation, or left ventricular thrombus), use intravenous UFH with streptokinase
For patients with known or suspected heparin-induced thrombocytopenia receiving fibrinolytic
therapy, administration of hirudin with tPA
PERCUTANEOUS CORONARY INTERVENTION
The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy made the following
recommendations for patients undergoing percutaneous coronary intervention (PCI) [9]:
Aspirin pretreatment (75 milligrams (mg) to 325 mg), followed by aspirin 75 mg to 162 mg per day for
long term treatment after PCI
Lower doses of aspirin (75 to 100 mg/day) for long term treatment in patients receiving antithrombotic
agents, such as clopidogrel or warfarin
In patients who have undergone stent placement, combination therapy with aspirin and thienopyridine
derivative (ticlopidine or clopidogrel) preferred over systemic anticoagulation therapy; clopidogrel
preferred over ticlopidine
Clopidogrel (75 mg/day) in addition to aspirin for at least 9 to 12 months after PCI
For patients with low atherosclerotic risk (eg, isolated coronary lesion), clopidogrel for at least 2
weeks after bare metal stent placement, for 2 to 3 months after placement of a sirolimus-eluting stent,
and after 6 months after placement of paclitaxel-eluting stent
GP IIb-IIIa antagonist such as abciximab or eptifibatide for all patients undergoing PCI, particularly
those undergoing primary PCI or those with refractory unstable angina or other high-risk features
Abciximab administered as 0.25 mg per kilogram (mg/kg) bolus followed by 12 hour infusion at rate of
10 micrograms per minute
Eptifibatide administered as double bolus (each 180 micrograms per kilogram, 10 minutes apart)
followed by 18 hour infusion of 2 micrograms per kilogram per minute
Tirofiban NOT recommended as alternative to abciximab
For patients with non-ST-segment elevation myocardial infarction/unstable angina (NSTEMI/UA)
rated moderate-to-high risk based on Thrombolysis in Myocardial Infarction (TIMI) score, upstream
use of GP IIb-IIIa antagonist (eptifibatide or tirofiban) started as soon as possible prior to PCI
In NSTEMI/UA patients with elevated troponin level, start abciximab within 24 hours prior to PCI
Patients not receiving a GP IIb-IIIa inhibitor, weight adjusted heparin bolus of 60 to 100 international
units/ kilogram (IU/kg) should be administered in doses to produce an activated clotting time (ACT)
250s to 350s
For uncomplicated PCI, routine postprocedural heparin infusion NOT recommended
For patients who do not receive GP IIb-IIIa antagonist, bivalirudin (0.75 mg/kg bolus followed by
infusion of 1.75 mg/kg per hour for duration of PCI) preferred over heparin during PCI
Routine warfarin or other vitamin K antagonists NOT recommended after PCI in patients with no other
indication for systemic anticoagulation therapy
CORONARY ARTERY BYPASS GRAFTING
The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy made the following
recommendations for the prevention of saphenous vein graft occlusion following coronary artery
bypass grafting (CABG) [10]:
Aspirin (75 milligrams (mg) to 162 mg per day) treatment for indefinite period of time for all patients
with coronary artery disease
Postoperative aspirin (75 mg to 162 mg/day) starting 6 hours after CABG procedure preferred over
preoperative aspirin
Addition of dipyridamole to aspirin therapy NOT recommended in patients undergoing CABG
Clopidogrel 300 mg loading dose 6 hours postoperatively followed by 75 mg/day, for coronary artery
disease patients undergoing CABG and who are allergic to aspirin
Clopidogrel (75 mg/day) in addition to aspirin for 9 to 12 months following procedure, in patients
undergoing CABG for non-ST-segment elevation acute coronary syndrome
Aspirin (75 mg to 162 mg per day) treatment for indefinite period of time for all patients with coronary
artery disease who undergo internal mammary artery bypass grafting
PERIPHERAL ARTERIAL OCCLUSIVE DISEASE
The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy guidelines for the
management of peripheral arterial occlusive disease are as follows [11]:
Chronic limb ischemia:
Lifelong aspirin therapy (75 milligrams (mg) to 325 mg per day) preferred over no antiplatelet therapy
in patients with clinically manifest coronary or cerebrovascular disease and in patients without
clinically manifest coronary or cerebrovascular disease
Clopidogrel recommended over ticlopidine and over no antiplatelet therapy
Anticoagulants NOT recommended in patients with intermittent claudication
Vascular grafts:
Unfractionated heparin at time of application of vascular cross-clamps for patients undergoing major
vascular reconstruction
Aspirin therapy in patients undergoing prosthetic infrainguinal bypass
Vitamin K antagonists plus aspirin NOT recommended for routine use in patients without special risk
factors for occlusion undergoing infrainguinal bypass
Carotid endarterectomy:
Aspirin (75 milligrams (mg) to 325 mg per day) should be given preoperatively and continued
indefinitely
Asymptomatic and recurrent carotid stenosis:
Lifelong aspirin therapy, 75 to 162 mg/day, for nonoperative patients with asymptomatic or recurrent
carotid stenosis
Lower extremity endovascular procedures:
Long-term aspirin therapy, 75 to 162 mg/day, for lower extremity balloon angioplasty, with or without
stenting
HEPARIN-INDUCED THROMBOCYTOPENIA, TREATMENT
Nonheparin anticoagulant (eg, lepirudin, argatroban, bivalirudin, or danaparoid), in confirmed, or
strongly suspected HIT, whether or not complicated by thrombosis. LMWH NOT recommended [12].
HEPARIN-INDUCED THROMBOCYTOPENIA, PREVENTION
Low molecular weight heparin (LMWH) is preferred over unfractionated heparin (UFH) in
postoperative orthopedic surgery patients for the prevention of heparin-induced thrombocytopenia.
For the treatment of thrombosis, porcine UFH or LMWH is preferred over bovine UFH [12].
PEDIATRICS
The Seventh American College of Chest Physicians (ACCP) Conference on Antithrombotic and
Thrombolytic Therapy made the following recommendations for pediatric patients with systemic
venous thromboembolic disease [13]:
When the first thromboembolic event occurs in children older than 2 months, intravenous heparin to
prolong aPTT to range corresponding to an anti-FXa level of 0.35 to 0.7 Units per milliliter, or with low
molecular weight heparin (LMWH) to achieve an anti-FXa level of 0.5 to 1 Units per milliliter 4 hours
after injection is recommended
Initial treatment with heparin or LMWH should continue for 5 to 10 days. If subsequent therapy will
include vitamin K antagonists, begin oral therapy on day 1 and discontinue heparin/LMWH on day 6
if INR is within therapeutic range for 2 consecutive days. Longer duration of heparin/LMWH therapy
is recommended in cases of massive pulmonary embolism or extensive deep vein thrombosis
The ACCP recommends using adult guidelines for pediatric patients with prosthetic heart valves [13].
The use of intravenous heparin prophylaxis is recommended in neonates and children requiring
cardiac catheterization via an artery [13].
To prolong catheter patency in neonates and children with peripheral arterial catheters in situ, low-
dose heparin through the catheter, preferably by continuous infusion, is recommended [13].
For the treatment of Kawasaki disease, the ACCP recommendations are [13]:
High dose aspirin therapy (80 to 100 milligrams per kilogram per day) during acute phase, for up to
14 days as an anti-inflammatory agent, then lower doses (3 to 5 milligrams per kilogram per day) for
at least 7 weeks as an antiplatelet agent
Intravenous gammaglobulin (2 grams per kilogram as a single dose) within 10 days of symptom onset

CONCLUSION
The Seventh ACCP Consensus Conference on Antithrombotic Therapy (2004) extensively reviewed
all related literature and produced a set of recommendations for antithrombotic and thrombolytic
therapy. However, the decision to initiate therapy should be based on the individual patient's particular
risk for thrombosis combined with current knowledge and the recommendations .

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