Warfarin Dosing Calculator

Variables and formula

The warfarin maintenance dose is most commonly calculated based on patient body surface area and INR results.

There are some risk factors that could be accounted for in the calculation, which is exactly what this calculator does.

The age of the patient is weighted as bleeding risk factor, along with smoking status and possible history or current diagnosis of deep venous thrombosis (DVT) or pulmonary embolism (PE).

It is also checked whether the patient undergoes therapy with Amiodarone (usually for a heart rhythm dysfunction) as there is a strong interaction between that and Warfarin.

The formula used is:

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)]

Where:

DuBois BSA formula (m²) = (Weight in kg)^0.425 x (Height in cm)^0.725 x 0.007184

Warfarin dosing

Anticoagulation therapy with Warfarin carries associated bleeding risk that can be exacerbated by the presence of other individual haemorrhage risk factors, therefore thorough assessment is required before initiation and during the treatment.

Warfarin has vitamin K antagonist properties which means it affects the synthesis of active factors II, VII, IX, X and protein C, which are all involved in clotting processes.

Initial doses may vary between 2.5 and 10 mg (depending on the number and importance of bleeding risk factors).

Patients with no risk factors are usually started on a 10 mg/per day dosage for 2 days and treated as outpatients. After the 2 days, INR is measured and a new dosage is established.

Patients with multiple risk factors are started on an initial dose of 2.5 – 3 mg.

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

In case an accidental overdose occurs, vitamin K is administered to rapidly correct INR or infusion of fresh frozen plasma is used to further correct the coagulation disorder.

Bleeding risk factors

Patients older than 65 with chronic heart failure or other comorbidities are at a higher risk of haemorrhage.

Risk assessment is used for patients who undergo surgery or need anticoagulant medication. Some common bleeding risk factors include:

■ Bleeding history, anemia or predisposition;

■ Previous history of stroke;

■ Labile INR;

■ Drug therapy, especially with NSAIDs;

■ 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.

Therapy recommendations based on INR

The function of the factors II, V, VII and X in the coagulation pathway can be evaluated through the International Normalized Ratio and the prothrombin time (PT).

There are different dosing recommendations depending on the INR value which is regularly determined for patients who undergo anticoagulation therapy with Warfarin or other substances.

References

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

2. Holbrook A, Schulman S, Witt DM, Vandvik PO, Fish J, Kovacs MJ, Svensson PJ, Veenstra DL, Crowther M, Guyatt GH; American College of Chest Physicians. Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012; 141(2 Suppl):e152S-84S.

3. 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.

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

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