Oral Anticoagulant Therapy

The optimal therapeutic range for oral anticoagulant therapy as determined by prothrombin time is expressed in terms of the international normalized ratio (INR). The INR is the prothrombin time ratio (patient s prothrombin time divided by the mean of the normal prothrombin time) that would have been obtained had a World Health Organization reference thromboplastin preparation been used to determine the prothrombin time. The sensitivity of the various reagents (thromboplastins) used to determine the prothrombin time is related to the international sensitivity... 

Venous thrombectomy may be performed to remove a massive obstructive thrombus in a patient with significant iliofemoral venous thrombosis, particularly if the patient is either not a candidate for or has not responded to thrombolysis. Full-dose anticoagulation therapy is essential during the entire operative and postoperative period. These patients need indefinite oral anticoagulation therapy targeted to an INR of 2.5 (range 2.0 to 3.0). 

Converting to oral anticoagulant therapy Perform baseline coagulation tests to determine prothrombin activity when heparin activity is too low to affect PT or INR. When the results of the initial prothrombin determinations are known, initiate the oral anticoagulant in the usual amount. Thereafter, perform coagulation tests and prothrombin activity at appropriate intervals. When the prothrombin activity reaches the desired therapeutic range, discontinue heparin and continue oral anticoagulants. 

Following are the recommended therapeutic ranges for oral anticoagulant therapy from the ACCP and the National Heart, Lung, and Blood Institute (NHLBI) ... 

ACCP/NHLBI Recommended Therapeutic Range for Oral Anticoagulant Therapy ... 

Coumarin-induced skin necrosis is a rare complication of oral anticoagulant therapy. Especially patients suffering from a rare and life-threatening blood disorder known as protein C deficiency are at risk. In these cases Protein C Concentrate (human). 

Cesar J, Garcia-Avello A, Navarro J, Herraez M. Aging and oral anticoagulant therapy using acenocoumarol. Blood Coagul Fibrinolysis 2004 15(8) 673-6. 

McLintock LA, Dykes A, Tait RC, Walker ID. Interaction between hormone replacement therapy preparations and oral anticoagulant therapy. Br J Obstet Gynaecol 2003 110 777-9. 

Peyvandi F, Spreafico M, Siboni SM, Moia M, Mannucci PM. CYP2C9 genotypes and dose requirements during the induction phase of oral anticoagulant therapy. Clin Pharmacol Ther 2004 75 198-203. 

European Atrial Fibrillation Trial Study Group (1995). Optimal oral anticoagulant therapy in patients with nonrheumatic atrial fibrillation and recent cerebral ischemia. New England Journal of Medicine 333 5-10 Halkes PH, van Gijn J For the ESPRIT Study Group (2006). Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT) randomised controlled trial. Lancet 367 1665-73 [Erratum in Lancet (2007) 369 274]... 

The prothrombin time (FT), which is usually expressed as the International Normalised Ratio (INR) for control of oral anticoagulant therapy, primarily evaluates the extrinsic system. 

Mayer GA. Blood viscosity and oral anticoagulant therapy. Am J Clin Pathol 1976 65(3) 402-6. 

Launbjerg J, Egeblad H, Heaf J, Nielsen NH, Fugleholm AM, Ladefoged K. Bleeding complications to oral anticoagulant therapy multivariate analysis of 1010 treatment years in 551 outpatients. J Intern Med 1991 229(4) 351-5. 

Gadisseur AP, Van Der Meer FJ, Rosendaal FR. Sustained intake of paracetamol (acetaminophen) during oral anticoagulant therapy with coumarins does not cause chnicaUy important INR changes a randomized double-blind clinical trial. J Thromb Haemost 2003 1(4) 714-17. 

Ansell JE, Buttaro ML, Thomas OV, Knowlton CH. Consensus guidelines for coordinated outpatient oral anticoagulation therapy management. Anticoagulation Guidelines Task Force. Ann Pharmacother 1997 31(5) 604-15. 

In 42 patients who required immediate reversal of oral anticoagulant therapy by prothrombin complex concentrate, no laboratory and clinical evidence for coagulation activation was found (7). The authors suggested that the concentration of protein C within the prothrombin complex concentrate is an important factor for preventing thrombosis. The activated form of protein C is an important natural anticoagulant. 

A 32-year-old woman with acute promyelocytic leukemia developed severe retinoic acid syndrome after 3 days, with respiratory failure, fever, and bilateral lung infiltrates. Withdrawal of tretinoin and treatment with dexamethasone and antibiotics rapidly ameliorated the syndrome, and on day 10 tretinoin was restarted. However, routine echocardiography showed a 3 cm pedunculated mass in the right ventricle. There was consistent and stable reduction of the mass after 1 year of oral anticoagulant therapy. 

Shields RC, McBane RD, Kuiper JD, Li H, Heit JA. Efficacy and safety of intravenous phytonadione (vitamin Kl) in patients on long-term oral anticoagulant therapy. Mayo Clin Proc 2001 76(3) 260-6. 

Andrew M, Marzinotto V, Adams M, Cimini C. LaDuca F. Monitoring of oral anticoagulant therapy in pediatric patients using a new microsample PT device. Blood 1995 86(Suppl) 863. 

Managing Oral Anticoagulation Therapy Clinical and Operational Guidelines, 2nd Ed. Ansell, J.E., Oertel, L.B., Wittowsky, A.K., Eds. Aspen Publishers, Inc. Gaithersburg, Maryland, 1998 lA-2 4. 

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