For DVT/PE Treatment: for at
least 5 days until warfarin/Coumadin Rx INR>2 (Coumadine/warfarin
may be started within 72 hr of fondaparinux Rx.)
Weight <50 kg: 5 mg once daily
Weight 50-100 kg: 7.5 mg once daiy subc
Weight >100 kg: 10 mg once daily
For Peri-operative DVT Prophylaxis:
* 2.5 mg subc daily for 5-9 days, starting 6-8 hr after surfery,
following abdominal surgery or knee/hip replacement or continuing
for 24 days following hip fracture surgery.
Low molecular weight heparin
Outpatient: 1 mg/kg q12h subc;
Inpatient: 1 mg/kg q12h or 1.5 mg/kg every 24h subc for
or until therapeutic anticoagulation with warfarin/Coumadin is achieved
(INR>2 for 2 consecutive days) .
Warfarin should be started within 72 hr;
For DVT Prophylaxis:
For Medical patients with acute illness DVT Prophylaxis:
40 mg subc once
For Perioperative DVT Prophylaxis:
(For Renal Impaired CCr<30 ml/min: Enoxaparin/Lovenox
30 mg once daily subc)
Knee replacement surgery: 30 mg q12h subc starting 12-24 hr after
Hip replacement surgery: 40 mg subc 12 hr before surgery, then once
daily, may be continued for up to 3 weeks after discharge.
Abdominal surgery: 40 mg 2 hr prior to surgery, then daily post op
for 7-12 days or until ambulatory (up to 14 days)
For Unstable Angina/Non-Q-wave MI (Acute Coronary
Syndrome): 1 mg/kg q12h subc for 2-8 days.
(For Renal Impaired CCr<30 ml/min: 1 mg/kg once daily subc)
- monitor anti-Xa levels (target 0.5 - 1.5 IU/ml)
For Perioperative DVT Prophylaxis:
Average-risk Abdominal Surgery: 2500 IU 1-2
hr before surgery, then once daily for 5-10 days.
High-risk Abdominal Surgery: 5000 IU evening
before surgery, then once daily for 5-10 days OR 2500 IU 1-2 hr before surgery,
another 2500 IU 12 hours later, then 5000 IU daily for 5-10 days
Hip Replacement Surgery: 5000 IU
evening before surgery, then once daily for 5-10 days OR 2500 IU 2 hr before
surgery, another 2500 IU same evening of the day of surgery (~ 6 hr after
first dose), then 5000 IU once daily for 5-10 days.
For Angina/Non-Q-wave MI: 120 IU/kg (not
to exceed 10,000 IU) subc q12h with concurrent aspirin.
(Innohep) 175 anti-Xa IU/kg once daily subc for at least
6 days &
until therapeutic anticoagulation is achieved with warfarin (Coumadin) (INR
>2 for 2 consecutive days)
- (20,000 IU/mL)
IV (PTT 1.5 - 2.3 x control)
- Standard dose: star with 5,000 units (or 75 u/kg) IV bolus, then
IV infusion 800-1,000 u /h (13 u/kg/h) to achieve PTT of 1.5-2x
- Weight-based dose: 80 u/kg IV bolus, then 18 u/kg/h (Ref: Ann IM Nov. 1,
1993:119:875 Raschke RA)
- Check PTT 6 hours after each dose change.
- To reverse heparin effect: Protamine or fresh frozen plasma Rx
2-10 mg/day PO
Keep Protime INR 2.0 - 3.0 for DVT Rx & prophylaxis. PE Rx, atrial
fibrillation, tissue heart valves, cardiomyopathy patients;
Keep Protime INR 2.5 - 3.5 INR for mechanical prosthetic valves, post MI).
Bleeding adverse events will rise from 2/100 patient-years with INR of 2.5-4.9
4.8/100 patient-years with an INR of 5.0-5.5, to
75/100 patient-years when INR is 6.5 or over. (NEJM 1995;333:11 -
Cannegieter SC, etc.)
To reverse coumadin effect:
Fresh frozen plasma Rx (quick reversal of the
excessive anticoagulation in bleeding pts, but risk of potential infectious
Vit. K (Mephyton) 1-2.5 mg PO if INR
is 5-9 in pts without bleeding; 3-5 mg PO if INR is > 9.
(Chest 1998;114 Suppl: 445S - Hirsh J, etc.)
Vit. K1 (AquaMephyton/
Phytonadione) 1 mg IV is effective to correct the INR from
baseline of 8.0 to 4.6 in 8 hours, to 3.1 in 24 hours. While
effective, IV route is associated with a small risk of serious anaphylactic
reactions. Subcutaneous route 1mg is not as effective as IV route, it changed
INR from baseline of 8.5 to 8.0 in 8 hours, and to 5.0 in 24 hours.
IM Dec. 13, 1999;159:2721 - Guna Raj, etc.)
Reversal of Warfarin-Induced Excessive Anticoagulation
with Recombinant Human Factor VIIa Concentrate
Critically prolonged INR and bleeding complications were treated successively
and rapidly in all patients, regardless of rFVIIa
dose (range, 15 to 90 g/kg of body weight). Indications for use
of rFVIIa included an INR greater than 10 in high-risk persons (n = 5), clinical
hemorrhage (n = 4), and diagnostic or therapeutic procedures (n = 4)
Conclusion: Safe, rapid, and effective administration of rFVIIa
corrects critically prolonged INRs and can avert or reverse bleeding associated
with warfarin anticoagulation.
Intern Med. Dec. 3, 2002;137:884-888.
(Pradaxa), administered at a dose of 150
mg PO twice daily
For the treatment of acute venous thromboembolism, a fixed dose
of dabigatran is as effective as warfarin, has a safety profile that is similar
to that of warfarin, and does not require laboratory monitoring.
NEJM December 6, 2009
Dabigatran etexilate is an orally available, potent, direct inhibitor
of thrombin. It is rapidly converted by ubiquitous esterases to the active
drug, is administered in fixed doses without the need for coagulation
monitoring, is excreted by the kidney, and has a half-life of 12 to 17
hours. Dabigatran has similar efficacy and safety to enoxaparin for
the prevention of venous thromboembolism in patients who have had elective
hip or knee arthroplasty. Recently, dabigatran, as compared with warfarin,
was shown to have superior safety with equivalent efficacy (when it was
administered at a dose of 110 mg twice
daily), or superior efficacy with similar safety (when it was
administered at a dose of 150 mg twice
daily), for the prevention of stroke in patients with atrial
Rivaroxaban selectively inhibits factor Xa without the need of cofactor (eg,
anti-thrombin III) for activity
Arthroplasty of knee - Postoperative deep vein thrombosis;
Prophylaxis: 10 mg ORALLY once daily beginning at least 6 to 10 hours
after surgery and continued for 12 days for knee replacement
Postoperative deep vein thrombosis; Prophylaxis - Repair of hip: 10 mg ORALLY
once daily beginning at least 6 to 10 hours after surgery and continued for
35 days for hip replacement
hepatic impairment, moderate or severe (Child-Pugh B or C): avoid use 
renal impairment, severe (CrCl less than 30 mL/min): avoid use 
(with combined p-glycoprotein and strong CYP3A4 inducers): 20 mg ORALLY once
daily with food 
* The use of warfarin reduces the rate of ischemic stroke in patients with
atrial fibrillation but requires frequent monitoring and dose adjustment.
Rivaroxaban, an oral factor Xa inhibitor, may provide more consistent
and predictable anticoagulation than warfarin.
In patients with non-valvular atrial fibrillation,
rivaroxaban (at a daily dose of 20 mg)
was noninferior to warfarin for the prevention of stroke or systemic embolism.
There was no significant between-group difference in the risk of major bleeding,
although intracranial and fatal bleeding occurred less frequently in the
rivaroxaban group. (REF: NEJM August 10, 2011)
(Eliquis) (at a dose of 5 mg twice daily)
- the direct factor Xa inhibitor
In this issue of the NEJM Journal, Granger and colleagues report the impressive
primary results of the Apixaban for Reduction in Stroke and Other Thromboembolic
Events in Atrial Fibrillation trial (ARISTOTLE; ClinicalTrials.gov number,
NCT00412984).1 A total of 18,201 subjects with atrial fibrillation and at
least one additional risk factor for stroke were enrolled in the trial and
were randomly assigned to receive the direct factor Xa inhibitor apixaban
(at a dose of 5 mg twice daily) or warfarin (target international normalized
ratio [INR], 2.0 to 3.0). The trial was designed to test whether apixaban
was noninferior to warfarin with respect to efficacy. The investigators found
that apixaban was not only noninferior to warfarin, but actually superior,
reducing the risk of stroke or systemic embolism by 21% and the risk of major
bleeding by 31%. In predefined hierarchical testing, apixaban, as compared
with warfarin, also reduced the risk of death from any cause by 11%.
REF: This article (10.1056/NEJMe1109748) was published on August 28, 2011,
(Ximelagaran) 36 mg bid PO - oral direct thrombin inhibitor with
a rapid onset of action
JAMA Feb.9, 2005;293:681 Dr. Jean-Noel Fiessinger, etc.
Platelet Glycoprotein IIb/IIIa Receptor
/Eptifibatide For acute coronary syndrome: 180 ug/kg IV
bolus, then infusion of 2 ug/kg/min upto 72 hours, until discharge or
CABG; For percutaneous coronary interventions: 135 ug/kg bolus, then
0.5 ug/kg/min infusion for 24 h.
/Abciximab 0.25 ug/kg bolus, then 0.125 ug/kg/min infusion for 12
hours for before & during percutaneous coronary interventions
/Tirofiban 0.4 ug/kg/min bolus for 30 min, then 0.1 ug/kg/min infusion
for upto 72h for acute coronary synd.
(lepirudin) for injection
- The first direct thrombin inhibitor for anticoagulation in patients
with HIT (heparin-induced thrombocytopenia).
- Initial Dosage :Anticoagulation in adult patients with HIT and
associated thromboembolic disease:
0.4 mg/kg body weight (up to 110 kg) slowly intravenously (eg, over 15
to 20 seconds) as a bolus dose,
followed by 0.15 mg/kg body weight (up to 110 kg)/hour as a continuous
intravenous infusion for 2 to 10 days or longer if clinically needed.
Normally the initial dosage depends on the patient's body weight. This is
valid up to a body weight of 110 kg. In patients with a body weight exceeding
110 kg, the initial dosage should not be increased beyond the 110 kg body
weight dose (maximal initial bolus dose of 44 mg, maximal initial infusion
dose of 16.5 mg/h
Aspirin 81 - 325 mg/d
Plavix/ clopidogrel 75 mg/d
Thrombotic thrombocytopenic purpura can occur after the initiation of clopidogrel
therapy, often within the first two weeks of treatment. Physicians should
be aware of the possibility of this syndrome when initiating clopidogrel
15, 2000 )
FDA warns against giving clopidogrel with PPIs:
Clopidogrel (Plavix), an anti-clotting medication, and omeprazole
(Prilosec), a proton-pump inhibitor (PPI), should not be used together,
because when the drugs are taken together, the effectiveness of clopidogrel
Ticagrelor 180-mg loading dose, 90 mg
twice daily thereafter.
Clopidogrel/Plavix in Patients with Acute
At 12 months, the primary end point a composite of death from vascular
causes, myocardial infarction, or stroke had occurred in
9.8% of patients receiving
ticagrelor (180-mg loading dose, 90 mg twice daily
thereafter) as compared with
11.7% of those receiving
clopidogrel (300-to-600-mg loading dose, 75 mg daily
thereafter) (hazard ratio, 0.84; 95% confidence interval [CI],
0.77 to 0.92; P<0.001). Predefined hierarchical testing of secondary end
points showed significant differences in the rates of other composite end
points, as well as myocardial infarction alone (5.8%
in the ticagrelor group vs. 6.9% in the clopidogrel group, P=0.005)
and death from vascular causes (4.0% vs.
5.1%, P=0.001) but not stroke alone (1.5% vs. 1.3%, P=0.22).
The rate of death from any cause was also reduced
with ticagrelor (4.5%, vs. 5.9% with clopidogrel; P<0.001).
No significant difference in the rates of major bleeding was found between
the ticagrelor and clopidogrel groups (11.6% and 11.2%, respectively; P=0.43),
but ticagrelor was associated with a higher rate of major bleeding not related
to coronary-artery bypass grafting (4.5% vs. 3.8%, P=0.03), including more
instances of fatal intracranial bleeding and fewer of fatal bleeding of other
types. REF: www.nejm.org August 30, 2009
Ticlid/ ticlopidine 250 mg bid