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Year : 2013  |  Volume : 2  |  Issue : 2  |  Page : 138-140

Anticoagulation in minor therapeutic procedures: A dilemma?

Department of Medicine, ASCOMS and Hospital, Sidhra, Jammu, Jammu and Kashmir, India

Date of Web Publication10-Sep-2013

Correspondence Address:
Sanjay Bhat
Department of Medicine, ASCOMS & Hospital, Sidhra, Jammu - 180 017, J&K
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2278-0521.117922

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The patient on chronic anticoagulation (warfarin and aspirin) underwent therapeutic pleural paracentesis for massive tubercular pleural effusion, developed thromboembolic stroke within 48 hours after the procedure, after stopping anticoagulants for one day prior to the pleural paracentesis. To examine the rationale and problems associated with preoperative/pre-procedure anticoagulation withdrawl. Review of the medical literature. When anticoagulation(warfarin) is stopped prior to any minor therapeutic procedure where the patient is at increased risk for thromboembolism, the bleeding risk is extremely low and can be easily managed.In view of narrow therapeutic index and the drug interaction between warfarin with anti-tubercular drugs like rifampicin, risk of thromboembolism significantly increases further. Warfarin should not be discontinued prior to any minor therapeutic paracentesis/procedure because the risk of thromboembolism over weighs the risk of bleeding.

Keywords: Anticoagulation, stroke, thrombho-embolism, warfarin

How to cite this article:
Bhat S. Anticoagulation in minor therapeutic procedures: A dilemma?. Saudi J Health Sci 2013;2:138-40

How to cite this URL:
Bhat S. Anticoagulation in minor therapeutic procedures: A dilemma?. Saudi J Health Sci [serial online] 2013 [cited 2022 Jan 22];2:138-40. Available from: https://www.saudijhealthsci.org/text.asp?2013/2/2/138/117922

  Introduction Top

Temporary discontinuation of warfarin is often standard practice prior to any minor surgical procedure to circumvent bleeding complications. Patients on long-term warfarin are generally categorized into those at "high risk" for thromboembolism (e.g., diseased heart valve, prosthetic heart valve, and underlying hypercoagulopathy) and those at "low risk" (e.g., remote myocardial infarction). Usually, for an individual at high risk, warfarin is continued during any minor procedure because the risk of thromboembolism outweighs the risk of bleeding complications than for an individual at low risk, where warfarin is discontinued. [1]

Who is responsible for categorizing patients as "high risk" or "low risk" for thromboembolism is unclear. Also, it is unclear who should be responsible for advising the low-risk minor procedure patient to discontinue warfarin without heparin coverage. Either the hematologist alone or in conjunction with the patient's internist or even the family practitioner acting alone may advocate discontinuing warfarin before the planned procedure. Sometimes, the patient discontinues warfarin because of the advice given during a previous surgery, with the result being that, frequently, patients on long-term anticoagulation (warfarin) arriving for any minor surgery are already off warfarin without the physicians knowledge or advice.

  Case Report Top

A 72-year-old male with history of rheumatic heart diseases (Echocardiograhy documented Mitral stenosis with Mitral regurgitation and Aortic regurgitation) on chronic anticoagulation (warfarin 5 mg once daily and aspirin 75 mg once daily) for the past 5 years presented with a history of fever of 1.5 months duration, pleuritic chest pain on the right side for 1 month and breathlessness for the last 1 week. On examination, he was breathless, with a pulse rate of 110 bpm, which was irregularly irregular, blood pressure of 140/60 mmHg and respiratory rate of 30 breaths/min; the juglar venous pressure was not raised. Pallor was present, pedal edema was absent and icterus was absent.

Respiratory system examination

On inspection, abdomino-thoracic respiration, fullness of right side intercostal spaces and chest movements decreased on the right side were noted. On palpation, decreased vocal fremitus of the right side was seen. Percussion revealed stony dull note on the right side of the chest up to the third intercostal spaces. On auscultation, bronchovesicular breath sounds were noted on the left side and absent breath sounds were noted on the right side up to the third intercostal space wall with decreased vocal resonance on the right side.

Cardiovascular examination

On inspection, the apex beat visible in the sixth intercostal space downwards and outwards was hyperdynamic. On palpation, thrill (diastolic) in the fifth/sixth intercostal space and on auscultation, mid diastolic murmur in the mitral and tricuspid areas and early diastolic murmur in the aortic area with low intensity S1 were noted. The abdominal examination was normal.


Hemoglobin 9 gms %; total leucocyte count 6000/cumm; differential count: Polymorphs 55%, lymphocytes 30%, monocytes 5%, and eosinophills 3%; peripheral blood film normocytic to microcytic anemia; serum urea 44 mg/dL; and serum creatinine 1.3 mg/dL. Liver function test were normal. Urine routine examination was normal. ECG showed atrial fibrillation with rate 80 beat/min. International Normalized Ratio (INR) - 2.8. Chest roentogram showed massive right-sided pleural effusion (images attached 1,2). Diagnostic pleural tap done showed that gross appearance was hemorrhagic. Total leucocyte count was 220/cumm: Polymorphs 4%, lymphocytes 96%, RBC 35-40/HPF; hematocrit 40; protein 3.1 mg/dL; glucose 92 mg/dL; and Adenosine deaminase 49.3 U/L an. A polymerase chain reaction test detected Mycobacterial DNA. The patient was started on anti-tubercular treatment in view of fluid analysis. The dose of warfarin was increased from 5 mg to 7.5 mg and 10 mg alternate days taking into consideration the interaction of warfarin and rifampicin. The patient persisted with respiratory distress; therapeutic paracentesis was planned after stopping warfarin in view of hemorrhagic effusion. The patient developed sudden onset of weakness on the right side of the body on the next day, 48 after stopping warfarin. Computer tomography (CT) of the brain done on the first day, within 1 h, showed effacement of gyri and sulci on the left side in the middle cerebral artery territory. Repeat CT scan on the third day showed large left cerebral hemispheric infarct ( images attached 3). INR done was 1.03. Echocardiography repeated revealed same valvular lesion, with no evidence of any vegetation or thrombous. Low molecular weight heparin with warfarin was restated.

  Discussion Top

Warfarin, one of the most commonly prescribed anticoagulants, to prevent thrombosis, competitively inhibits the hepatic enzyme vitamin K1 2,3-epoxide reductase, which is responsible for the reductive metabolism of vitamin K epoxide to the active hydroquinone form. As a result, in the presence of warfarin, the liver produces decreased amounts of functional vitamin K-dependent clotting factors, thereby anticoagulating the blood. [2],[3],[4] Clinical indications for warfarin include atrial fibrillation, history of stroke, prevention of acute myocardial infarction, deep venous thrombosis or pulmonary embolism, valvular heart disease, presence of a mechanical heart valve, or underlying hypercoagulopathy.

The drug interaction between warfarin and rifampicin is well known. [5] Rifampicin has been reported to increase the warfarin requirements in human subjects ingesting these agents simultaneously. The concomitant administration of rifampicin and warfarin resulted in the need for an unusually high maintenance dose of warfarin (20 mg/day) in order to produce a therapeutic effect. [6] Withdrawal of rifampicin decreases the warfarin requirement by 50%. This effect may be mediated by the ability of rifampicin to induce microsomal enzymes and, thus, the catabolism of warfarin. This interaction appears to be clinically significant, as was noticed in our case report. [7]

The risk of hemorrhage in chronically anticoagulated patients mirrors the intensity level of anticoagulation. [8] Because of the variable activity of commercial tissue thromboplastins, which are used in the prothrombin time test to determine the level of anticoagulation, the World Health Organization in 1983 recommended using an international reference preparation of thromboplastin so that the INR (in place of prothrombin time) could be generated as a means of standardizing the reporting of warfarin anticoagulation. [9] The INR system has resulted in a corrected and reproducible anticoagulation value, provided that the laboratory uses a sensitive thromboplastin. Guidelines for optimal oral anticoagulation therapy were most recently updated by the Fifth American College of Chest Physicians Consensus Conference on Antithrombotic Therapy in 1998. [10] They suggested a target INR of 2.5 (range 2.0-3.0) for most conditions and a target INR of 3.0 (range 2.5-3.5) for most mechanical heart valves, post-myocardial infarction and certain patients with thrombosis and antiphospholipid syndrome. [8] The risk of major bleeding episodes occurs with increasing frequency above an INR of 5.0, which would be considered a supratherapeutic anticoagulation level. [11] Since adopting the INR method of reporting, the major hemorrhagic risks of warfarin therapy have decreased markedly.

Thromboembolism that occurs when warfarin is discontinued may be due to the underlying condition for which the warfarin is prescribed or due to a hypercoagulable state. It has been estimated that the patients with non-valvular atrial fibrillation have a 4.5% yearly incidence of thromboembolism without anticoagulation therapy, which is reduced to 1.5% with warfarin therapy. Likewise, mechanical heart valves have a yearly thromboembolism rate of 8%, which drops to 2% with warfarin anticoagulation therapy. [6],[12]

The phenomenon of rebound hypercoagulation has been described as a hypercoagulant state existing in patients on long-term warfarin who are withdrawn from warfarin anticoagulation. [7],[3],[14] Some authors have reasoned that a hypercoagulable state occurs based on levels of vitamin K-dependent clotting factors and anticoagulants returning to normal levels at different rates. [14] After stopping warfarin, protein C, a normal blood anticoagulant, returns to steady state more slowly than factor VII. [14] These and other findings suggest that more natural blood coagulant is present than natural blood anticoagulant during the first week after stopping warfarin.

The hypercoagulable state after stopping warfarin is not reflected by traditional coagulation tests such as the prothrombin time, activated partial thromboplastin time, and INR. [15] Instead, more sensitive assays to detect the hypercoagulable state are necessary. These assays include thrombin-antithrombin III complex (TAT) and fibrinopeptide A (FpA). [15] These two markers have been measured consistently higher after stopping warfarin than compared with pre-treatment levels. [13] Other markers of hypercoagulation have also been reported to be elevated after warfarin is stopped, including elevated levels of activated factor VII, factor VIII, prothrombin fragments, and D-dimers. [7]

  Conclusion Top

In summary, the literature supports that there is an increased risk of thromboembolism after warfarin is stopped. It is unknown whether the increased risk is due to unmasking of underlying condition for which the warfarin is given or whether the increased risk is due to a rebound hypercoagulation state, or the combination of two. Because thromboembolic events are more likely to occur when warfarin is stopped than if it is simply continued, patients undergoing simple procedure like pleural paracentesis probably should not be discontinued of warfarin, especially when bleeding risk is usually negligible and can be easily managed.

  References Top

1.Hirsch J, Dalen JE, Anderson DR, Poller L, Bussey H, Ansell J, et al. Oral anticoagulants: Mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest 1998;114:445S-69S.  Back to cited text no. 1
2.Choonara IA, Malia RG, Haynes BP, Hay CR, Cholerton S, Breckenridge AM, et al. The relationship between inhibition of vitamin K1 2,3-epoxide reductase and reduction of clotting factor activity with warfarin. Br J Clin Pharmacol 1988;25:1-7.  Back to cited text no. 2
3.Goodman Gilman. Philip. WM and Douglas M. Tollefsen; Edition 10 th Chapter 55. p. 1519-38.  Back to cited text no. 3
4.Ys Longo, Fauci Kasper. Coagulation disorders. Chapter 116, 18 th edition. Harrisons Principle of Internal Medicine. McGraw-Hill Professional: New York, USA, 2012. p. 973- 82.  Back to cited text no. 4
5.Kim KY, Epplen K, Foruhari F, Alexandropoulos H. Update on the interaction of rifampin and warfarin. Prog Cardiovasc Nurs 2007;22:97-100.  Back to cited text no. 5
6.Kearon C, Hirsh J. Management of anticoagulation before and after elective surgery. N Engl J Med 1997:336;1506-11.  Back to cited text no. 6
7.Sise HS, Moschos CB, Gauthier J, Becker R. The risk interrupting long-term anticoagulant treatment. A rebound hypercoagulable state following hemorrhage. Circulation 1961;24:1137-42.987;9:255-62.  Back to cited text no. 7
8.Altman R, Rouvier J, Gurfinke lE, D'Ortencio O, Manzanel R, de La Fuente L, et al. Comparison of two levels of anticoagulant therapy in patients with substitute heart valves. J Thorac Cardiovasc Surg 1991;101:427- 31.  Back to cited text no. 8
9.WHO Expert Committee on Biological Standardization. 33 rd report.World Health Organization: Geneva; 1983. Technical Report Series No. 687. p. 81-105.  Back to cited text no. 9
10.Proceedings of the American College of Chest Physicians 5 th Consensuson Antithrombotic Therapy 1998. Chest 1998;114:439S-769S.  Back to cited text no. 10
11.Cannegieter SC, Torn M, Rosendaal FR. Oral anticoagulant treatment in patients with mechanical heart valves: How to reduce the risk of thromboembolic and bleeding complications. Journal of Int Med 1999;245:369.  Back to cited text no. 11
12.Oake N, Jennings A, Forster AJ, Fergusson D, Doucette S, van Walraven C. Anticoagulation intensity and outcomes among patients prescribed oral anticoagulant therapy: A systematic review and meta-analysis. CMAJ 2008;179:235-44.  Back to cited text no. 12
13.Palareti G, Legnani C. Warfarin withdrawal. Pharmacokinetic-pharmacodynamic considerations. Clin Pharmacokinet 1996;30:300-13.  Back to cited text no. 13
14.Schofield KP, Thomson JM, Poller L. Protein C response to induction and withdrawal of oral anticoagulant treatment. Clin Lab Haematol 1987; 9:255-62.  Back to cited text no. 14
15.Palareti G, Legnani C, Guazzaloca G, Frascaro M, Grauso F, De Rosa F, et al. Activation of blood coagulation after abrupt or stepwise withdrawal of oral anticoagulants: A prospective trial. Thromb Haemost 1994;72:222-6.  Back to cited text no. 15


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