Effects of oral anticoagulation with various INR levels in deep vein thrombosis cases
© Yetkin et al; licensee BioMed Central Ltd. 2004
Received: 12 January 2004
Accepted: 18 February 2004
Published: 18 February 2004
In order to avoid the complications associated with thromboembolic disease, patients with this condition typically are placed on long-term anticoagulant therapy. This report compares bleeding complications in this patient population by level of achieved INR.
Materials and Methods
During the 6-year period between January 1997 and January 2003, 386 patients with venous thromboembolism of the lower extremities were admitted to the Cardiovascular Surgery Outpatient Clinic of Alsancak State Hospital. Of the 386 patients, 198 (51.2%) were women, and the average age was 52.3 years. All diagnoses of venous thromboembolism were confirmed by means of Doppler ultrasonography. Further investigation showed occult neoplasms in 22 (5.6%) of the cases. We excluded the patients with occult disease, and the remaining 364 constituted our study population.
Oral anticoagulation was standardized at 6 months' duration in all cases. We divided the patients into two groups. Group I consisted of 192 patients (52.7%) with INR values between 1.9 and 2.5; Group II comprised 172 patients with INR values between 2.6 and 3.5. Complications in each group were assessed and compared. The minor hemorrhage rate was 1.04% in Group I and 4.06% in Group II. The major hemorrhage rate was also 1.04% in Group I and was 6.3% in Group II. We determined that the complication rates for both minor and major hemorrhage were significant in patients with INR values above 2.5.
Oral anticoagulation must be followed closely in patients with venous thromboembolism. Higher INR levels are associated with significant increases in hemorrhage and associated complications. INR values of 2.0 to 2.5 are sufficient for long-term anticoagulant therapy, ensuring ideal anticoagulation levels and minimizing the complication rate.
KeywordsDeep venous thrombosis Warfarin INR risk of hemorrhage
Deep vein thrombosis (DVT) is the presence in lower-extremity veins of a thrombus that obstructs the branches and blood flow. The natural course of DVT therapy is associated with significant morbidity and mortality rates . Standard therapy for acute DVT consists of heparin followed by oral warfarin . To monitor therapy with coumadin anticoagulants, prothrombin time (PT) was the standard until as recently as the past decade . Because the therapeutic range of PT depends on many factors, comparing patient results and assessing the significance of those results can be difficult. Therefore, the World Health Organization (WHO) developed an international standardization system known as the international normalized ratio (INR) .
We monitored anticoagulation therapy and compared bleeding complications among outpatients with lower-extremity DVTs who were taking oral anticoagulants (OACs) and who exhibited two different ranges of INR values.
Materials and Methods
Characteristics of patients admitted with lower extremity venous thromboembolism prediagnosis and found to have various occult malignancies
System with occult malignancy
Extensive genital Ca + peritonitis carcinomatosa
Complications in both groups, classified due to INR levels.
Group I (INR: 1.9–2.5) (192 Patients)
Group II (INR: 2.6–3.5) (172 Patients)
Minor hemorrhage complications
Major hemorrhagic complications
• INR: prothrombin time rateISI
• Example = found in patient
PT: 17.9 second
PT: 12.2 second
• INR: (17.9 / 12.2)2.3 = 2.4
Since 1983, INR values have been calculated based on randomized study results involving laboratory evaluation of OAC therapy. Based on these study findings, the optimal therapeutic range was narrowed. In 1989, a new guide was prepared by the American College of Chest Physicians. We are now using that guide .
Warfarin is the most frequently used OAC because of its perfect bioavailability and consistent effect in both acute and chronic disease . Today, INR values are used at many institutions to evaluate OAC therapy (2,4,5,7,9). Anticoagulants are used in two different concentrations: low doses for INR values between 2.0 and 2.5 and high doses for INR values between 2.5 and 3.5. A low-dose regimen is used in the treatment of venous thrombosis or pulmonary embolus as well as prophylactically to prevent venous thrombosis. High-dose regimens are recommended for high-risk patients with mechanical prosthetic cardiac valves. Low doses have been shown to be safer than high doses and just as effective for following patients who undergo DVT therapy [3, 7, 9, 10].
In patients whose INR levels exceed 2.5, the incidence of hemorrhagic complications increases significantly [8, 9, 11]. An occult GI lesion accounted for 70% of the GI bleeds, and in 10%, bleeding during anticoagulant therapy was due to malignancy . Even with ideal anticoagulant doses, GI and genitourinary bleeding are seen as a result of underlying disease [4, 12]. In our study, GI bleeding occurred in both groups, and vaginal bleeding occurred as a complication in Group II (Table 2).
Hasenkam and associates proposed an INR between 2.0 and 2.7, even for patients with valve replacements, to minimize the incidence of bleeding as a complication and the risk of thromboembolus .
Many studies address the effectiveness of LMWH in treating DVT, and this form of heparin therapy should be seriously considered. LMWH eliminates many problems related to the use of nonfractionated IV heparin [1, 8, 14]. Its bioavailability is high, and the once-daily subcutaneous injection regimen is sufficient because of its longer half-life. LMWH decreases major hemorrhagic complications and thrombocytopenia as well as the incidence of osteoporosis associated with heparin administration. The single LMWH injection without the necessity of monitoring anticoagulation offers a very attractive treatment method. DVT can be treated without hospitalization, and patients can return to daily activities and to work much more quickly [14, 15]. We used LMWH for 88.5% of our patients.
In conclusion, OAC therapy must be closely monitored during both acute and chronic periods. To compare and standardize results reported by different centers, values should be reported as INR. Bleeding and related complications increase as INR levels are increased. We suggest that, ideally, the anticoagulant dosage should be adjusted to achieve an INR between 2 and 2.5 in patients with DVT. This dose level minimizes complications and is sufficient to control anticoagulant therapy.
- Oger E, EPI-GETBP Study Group: Incidence of venous thromboembolism: A community-based study in Western France. Thromb Haemost. 2000, 83: 657-60.PubMedGoogle Scholar
- Kearon C: Duration of therapy for acute venous thromboembolism. Clin Chest Med. 2003, 24 (1): 63-72. 10.1016/S0272-5231(02)00076-X. ReviewView ArticlePubMedGoogle Scholar
- Hirsh J, Fuster V: Guide to anticoagulant therapy. Part 2. Oral anticoagulants. Circulation. 1994, 89: 1469-1480.View ArticlePubMedGoogle Scholar
- Karabay Ö, Sarýosmanoğlu N, Çatalyürek H, Hazan E, Açýkel Ü, Oto Ö: Anticoagulation With Different INR Level On The Effect Of Postoperative Bileaflet Mitral Prosthesis Valve Cases. Journal of Turkish Thoracic and Cardiovascular Surgery. 1997, 5: 311-4.Google Scholar
- International Committee for standardization in Haematology, International Committee on Thrombosis and Haemostasis: ICSH / ICTH reommendations for reporting prothrombin time in oral anticoagulant control. Thromb Haemost. 1985, 53: 155-6.Google Scholar
- Ridker PM, Goldhaber SZ, Danielson E, et al: Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism. N Engl J Med. 2003, 348 (15): 1425-34. 10.1056/NEJMoa035029.View ArticlePubMedGoogle Scholar
- Litin SC, Gastineau DA: Current concepts in anticoagulant therapy. Mayo Clin Proc. 1995, 70 (3): 266-72. ReviewView ArticlePubMedGoogle Scholar
- Tufano A, Cerbone AM, Di Minno G: The use of antithrombotic drugs in older people. Minerva Med. 2002, 93 (1): 13-26.PubMedGoogle Scholar
- Rosenbaum CC, Woods SE, Hasselfeld KA: Correlation of the change in the International Normalized Ratio and decreasing the Coumadin dosage following total joint arthroplasty. Orthopedics. 2002, 25 (12): 1359-63.PubMedGoogle Scholar
- Ageno W, Steidl L, Ultori C, et al: The initial phase of oral anticoagulation with warfarin in outpatients with deep venous thrombosis. Blood Coagul Fibrinolysis. 2003, 14 (1): 11-4. 10.1097/00001721-200301000-00003.View ArticlePubMedGoogle Scholar
- Caprini JA, Arcelus JI, Reyna JJ, et al: Deep vein thrombosis outcome and the level of oral anticoagulation therapy. J Vasc Surg. 1999, 30 (5): 805-11.View ArticlePubMedGoogle Scholar
- Levesque H: Risk of hemorrhage with oral anticoagulants for deep vein thrombosis. J Mal Vasc. 2002, 27 (3): 129-36. ReviewPubMedGoogle Scholar
- Hasenkam JM, Kimose HH, Knudsen L, et al: Self management of oral anticoagulant therapy after heart valve replacement. Eur J Cardiothorac Surg. 1997, 11: 935-42. 10.1016/S1010-7940(97)01204-9.View ArticlePubMedGoogle Scholar
- Lindmarker P, Holmström M, Granqvist S, et al: Comparison of once-daily subcutaneous Fragmin with continuous intravenous unfractionated heparin in the treatment of deep vein thrombosis. Thromb Haemost. 1994, 72: 186-90.PubMedGoogle Scholar
- Mannucci PM, Poller L: Venous thrombosis and anticoagulant therapy. Br J Haematol. 2001, 114 (2): 258-70. 10.1046/j.1365-2141.2001.02961.x. ReviewView ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.