|LETTER TO THE EDITOR
|Year : 2016 | Volume
| Issue : 3 | Page : 418-419
Dabigatran Induced spontaneous macroscopic hematuria
Altug Osken1, Ercan Aydin2, Selcuk Yaylaci3, Regayip Zehir1, Tugba Kemaloglu Oz1, Isil Atasoy1, Sennur Unal Dayi1
1 Department of Cardiology, Siyami Ersek Thoracic and Cardiovascular Surgery Center, Training and Research Hospital, İstanbul, Turkey
2 Department of Cardiology, Trabzon Vakfikebir State Hospital, Trabzon, Turkey
3 Department of Internal Medicine, Rize Findikli State Hospital, Rize, Turkey
|Date of Web Publication||17-May-2016|
19 Mayis Mahallesi, Bayar Cad., İpek Apt., No:9/5, Kozyatagi, Kadikoy, İstanbul
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Osken A, Aydin E, Yaylaci S, Zehir R, Oz TK, Atasoy I, Dayi SU. Dabigatran Induced spontaneous macroscopic hematuria. Med J DY Patil Univ 2016;9:418-9
|How to cite this URL:|
Osken A, Aydin E, Yaylaci S, Zehir R, Oz TK, Atasoy I, Dayi SU. Dabigatran Induced spontaneous macroscopic hematuria. Med J DY Patil Univ [serial online] 2016 [cited 2022 Dec 2];9:418-9. Available from: https://www.mjdrdypu.org/text.asp?2016/9/3/418/168006
Dabigatran is a nonVitamin K antagonist anticoagulant drug approved for stroke prevention in atrial fibrillation (AF) patients in most of the countries worldwide. The randomized evaluation of long-term anticoagulation therapy trial  compared the efficacy and safety of dabigatran in two doses (110 mg and 150 mg twice daily) with open-label, dose adjusted warfarin. Dabigatran 110 mg twice daily was noninferior to warfarin, and dabigatran 150 mg twice daily was superior to warfarin in terms of the prevention of any stroke and systemic embolism. The former was safer than warfarin and the latter was as safe as warfarin with respect to major bleeding, while both doses significantly reduced the risk of intracranial hemorrhage. Nonetheless, dabigatran induced major and minor bleeding can be seen in routine clinical practice.
A 64-year-old female patient was admitted to our emergency department with complaints of bleeding from urine. She had a history of hypertension and coronary artery disease. She was applied percutaneous coronary intervention of the circumflex artery with a diagnosis of acute coronary syndrome at May 2011. She has used dual antiplatelet therapy for 1-year and then warfarin was started at July 2013 with the indication of nonvalvular paroxysmal AF. Subsequently, the patient was switched from warfarin to dabigatran (110 mg twice daily) due to poor control of her International Normalized Ratio (INR). She was also taking irbesartan + hydrochlorothiazide 300/12.5 mg, metoprolol 50 mg, atorvastatin 20 mg, and acetylsalicylic acid 100 mg.
The initial physical examination was unremarkable. A chest radiograph was normal, and transthoracic echocardiography revealed normal left ventricular systolic and diastolic function, slight enlargement of the left atrium and mild mitral and tricuspid regurgitation. A complete blood count showed normal hemoglobin level of 14.4 g/dL (normal range for women, 13.8-17.2 g/dL), with normal platelet and white blood cell counts. Laboratory tests showed normal renal function, including normal creatinine (0.73 mg/dL; normal for women 0.56-1.0 mg/dL) and normal glomerular filtration rate of 93.98 mL/min/1.73 m.
Routine coagulation test showed prolonged activated partial thromboplastin time (aPTT), 77.7 s.
Dabigatran prolongs the aPTT, which targets the intrinsic pathway of coagulation; the thrombin clotting time (TT), which directly assesses the activity of thrombin in a plasma sample; and the ecarin clotting time, which is a specific assay for thrombin generation. However, at clinically relevant plasma concentrations, dabigatran has relatively little effect on the prothrombin time and INR, which targets the extrinsic coagulation pathway. The TT assay is the most sensitive to prolongation by the dabigatran, followed by the ecarin clotting time and aPTT. The relationship between plasma concentrations of dabigatran and the aPTT concentration-response curve is curvilinear and flattens at higher concentrations (>200 ng/ml). 
There was no major or clinically relevant nonmajor bleeding in our patient, and, therefore, a conservative treatment was applied. Ultrasound examination of urinary tract revealed normal findings. Dabigatran was suspended for 2 days, control urine analysis revealed findings within normal limits. After this, patient refused to use dabigatran medication. Therefore the patient was pursued with the higher dose of warfarin to achieve target INR.
In our patient, this can be considered that the concomitant use of acetylsalicylic acid and dabigatran may have increased the risk of bleeding. 
Unlike warfarin and heparin, no specific antidote is available to reverse the anticoagulant effects of dabigatran. The management of bleeding complications in patients receiving dabigatran etexilate should be individualized according to the location and severity of the hemorrhage. In the absence of well-known causes that may lead to bleeding, use of anticoagulants should be kept in mind and the use of new anticoagulant therapy must be individualized by re-evaluating the risk of bleeding in patients.
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