Warfarin Dosing Calculator

How does this warfarin dosing calculator work?

This is a health tool that estimates the warfarin maintenance dose based on patient data and target INR in cases with bleeding risk where the patient’s condition needs to be stabilized through anticoagulant medication.

In order to compute the dosage, the warfarin dosing calculator requires the BSA, body surface area, an indicator often used in assessing drug doses for individual patients. The Dubois BSA formula used is presented below:

■ BSA in m² = Weight in kg^0.425 x Height in cm^0.725 x 0.007184

The user is asked to input the age, racial background, target INR, under amiodarone medication (because of strong interaction), smoking status and eventual presence of DVT and PE. All these are used in the dosing formula where certain weights are given to check whether the answer is positive or not.

■ Warfarin dose in mg = exp [0.613 + (0.425 x BSA) - (0.0075 x Age) + (0.156 x African-American race) + (0.216 x Target INR) - (0.257 x Amiodarone) + (0.108 x Smoker) + (0.0784  x  DVT/PE) ]

Warfarin therapies have their own associated risks therefore the patient data needs to be carefully analyzed before the treatment is initiated and to ensure there are enough indicators to start on warfarin.

The currently available tablets are 1mg, 2mg, 2.5mg, 3mg, 4mg, 5mg, 6mg, 7.5mg and 10mg. Initial doses may vary between 2.5 and 10mg depending on how many are and how much importance carry the bleeding risk factors present.

When there aren’t any risk factors, usually patients are started on a 10mg/per day dosage for 2 days and treated as outpatients. After the 2 days, INR is measured and a new dosage is established.

Patients that present a high risk of bleeding receive an initial dosage of 2.5 – 3mg.

Warfarin action is based on the fact that it uses its vitamin K antagonist properties to affect the synthesis of active factors II, VII, IX, X and protein C, which are the clotting factors, therefore interfering in the coagulation process.

The warfarin dose should be titrated against measured INR when used in treating established thromboembolism.

Accidental overdoses are resolved with infusion of fresh frozen plasma to correct the coagulation disorder or administration of vitamin K to rapidly correct INR, however, this method does interfere with subsequent treatment efforts if the therapy is to be reinstated.

Bleeding risk

Age – elderly patients over 65, chronic heart failure, liver disease, after major surgery are amongst the most common bleeding risk factors.

Hemorrhage risk assessment usually results in finding one or more of the below:

■ Bleeding history, anemia or predisposition;

■ Labile INR;

■ Drug therapy, especially with NSAIDs;

■ Previous history of stroke;

■ Hypertension (with SBP more than 160 mmHg);

■ Abnormal liver function, cirrhosis or significant impairment usually with AST/ALT/ALP more than 3 times higher;

■ Abnormal renal function (chronic dialysis or serum creatinine more than 2.3 mg/dL);

■ Malignancy;

■ Genetic factors.

INR ranges and recommendations

The International Normalized Ratio and the prothrombin time (PT) provide means to measure the function of factors II, V, VII and X in the coagulation pathway. The normal clotting time (10-14 seconds) is compared to the control, the INR. Below there are several therapeutic recommendations based on the INR value.

INR < 1.5

■ If non-compliant: resume therapy at previous dose;

■ OR increase maintenance dose by 5%- 20%.

INR 1.5 - 1.9

■ If non-compliant: resume therapy at previous dose;

■ OR increase maintenance dose by 5 - 15%;

■ Re-dosage after 3 – 7 days.

INR 2.0 - 3.0

■ Maintain current dose;

■ Re-dosage after 1 month.

INR 3.1 - 3.4

■ Maintain dosage but re-check after 3 – 7 days;

■ Consider decreasing dose by 5 - 10% and/or holding one dose.

INR 3.5 - 3.9

■ Consider holding one dose;

■ OR consider decreasing the maintenance dose by 5 -15% depending on magnitude of the INR elevation;

■ Re-dosage after 1 – 3 days.

INR 4.0 - 4.9 with no significant bleeding

■ Hold warfarin until INR reaches therapeutic range;

■ Consider lowering maintenance dose by 5%- 20%;

■ Monitor daily.

INR > 5.0

■ Monitor daily.

References

1) Gage BF, Eby C et al. (2008) Use of pharmacogenetic and clinical factors to predict the therapeutic dose of warfarin. Clin Pharmacol Ther; 84(3):326-31.

2) Baglin TP et al. British Committee for Standards in Haematology - Guidelines on oral anticoagulation (warfarin): third edition - 2005 update. British Journal of Haematology 2006; 132 (3): 277-285.

3) Du Bois D, Du Bois EF. (1989) A formula to estimate the approximate surface area if height and weight be known 1916. Nutrition; 5(5):303-11; discussion 312-3.

4) Bennett ST, Critchfield GC. (1994) Examination of International Normalised Ratio (INR) imprecision by comparison of exact and approximate formulas. Intermountain Laboratory Data Project. J Clin Pathol; 47(7): 635–638.