Dabigatran-induced upper intestinal bleeding in a patient with chronic kidney disease
Hemorragia digestiva alta por dabigatran en paciente con enfermedad renal crónica
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However, in the subgroup study, patients who were 75 years of age or older had a higher risk of extracranial bleeding, probably in relation to high concentrations of the drug.<span class="elsevierStyleSup">4</span> With a peak plasma concentration 2 hours<span class="elsevierStyleSup">5,6</span> after intake and a half-life of 12-17 hours,<span class="elsevierStyleSup">5,6</span> it has a renal clearance of 80%.<span class="elsevierStyleSup">5,6</span> It is recommended to reduce the dose for patients with an estimated glomerular filtration rate between 30 and 50ml/min/1.73m<span class="elsevierStyleSup">2</span>. If the GFR falls below 30ml/min/1.73m<span class="elsevierStyleSup">2</span>, the drug is contraindicated.<span class="elsevierStyleSup">7</span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">We present the case of an 84-year-old female with high blood pressure, type 2 diabetes mellitus, atrial fibrillation, hypertensive heart disease with preserved systolic function, stage 3 chronic kidney disease with an estimated glomerular filtration rate of 30ml/min/1.73m<span class="elsevierStyleSup">2</span> and normocytic normochromic anaemia, who presented with progressive general deterioration in recent months, without abnormalities in the characteristics of urine or the diuresis rate. She was being treated with several antihypertensive drugs (including angiotensin II receptor antagonists and beta-blockers), a statin and fibrate combination and dabigatran (75mg every 12 hours). Her general appearance was poor. The cardiac examination was normal, but auscultation revealed crackles in both lung bases. No abdominal abnormalities or increases in dependent oedema were found. The digital rectal examination was negative for melena and rectal bleeding. Blood pressure was 94/36mmHg. The electrocardiogram showed sinus rhythm of 54 beats per minute with V4-V6 straight ST segment not suggestive of acute myocardial ischaemia. The test results are displayed in Table 1. The x-ray showed cardiomegaly, bilateral posterior pleural effusion and vascular redistribution. There were no significant abnormalities in the abdominal x-ray. Due to the low blood haemoglobin concentration (5g/dl), she received an initial transfusion of three packed red blood cell units and antibiotic treatment with ceftriaxone and ciprofloxacin was started due to findings consistent with urinary tract infection and she was admitted to the Nephrology Department for studies. Due to the suspicion of upper intestinal bleeding, we decided to perform haemodialysis to clear dabigatran. Hours later, she produced melenic stools. A gastroscopy was performed, showing friable erythematous mucosa and a small clot in the angular notch. We performed another haemodialysis session twelve hours later. Clotting times gradually normalised over the following days and the patient did not display more bleeding.</p><p class="elsevierStylePara">Our case is an example of the potential disadvantages of administering dabigatran to patients with chronic kidney disease, since they have a higher risk of acute renal failure<span class="elsevierStyleSup">8</span> and a critical increase in levels of the drug in serum. The patient received a dose adjusted to the glomerular filtration rate and displayed excessive anticoagulation due to exacerbation of her condition. Moreover, although it is often said that it does not require monitoring, there is no parameter that adequately assesses the anticoagulant activity of this new drug. Although the use of activated partial thromboplastin time or thrombin time have been established, these may underestimate the anticoagulant activity and are only useful for their negative predictive power. Prothrombin time is not useful either because it may be normal despite high serum dabigatran concentrations. The parameter that displays the best relationship with the level of dabigatran in serum is ecarin clotting time, which is not very useful because it requires a number of days for results to be obtained and it is not easy to perform. Despite the use of recombinant activated factor VIIa for patients with bleeding due to dabigatran, the only useful strategy for overdose management is clearing the drug via haemodialysis, taking advantage of its low molecular weight (471Da) and its low plasma protein binding rate (35%).<span class="elsevierStyleSup">9</span> It should be taken into account that there is a rebound phenomenon for dabigatran concentration in plasma after the procedure, given its high distribution volume.<span class="elsevierStyleSup">9</span> It is important to be aware that there are patients whose clinical condition is liable to change in a short period of time and that they will require regular check-ups. In these patients, such as those affected by chronic kidney disease, who are prone to erratic changes in drug concentrations, we should rationally consider the benefit/risk balance of using dabigatran.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">Conflicts of interest</span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">The authors declare that they have no conflicts of interest related to the contents of this article.</p><p class="elsevierStylePara"><a href="grande/12040_16025_53072_en_t1120402.jpg" class="elsevierStyleCrossRefs"><img src="12040_16025_53072_en_t1120402.jpg" alt="Data of test on admission"></img></a></p><p class="elsevierStylePara">Table 1. Data of test on admission</p>" "pdfFichero" => "P1-E562-S4415-A12040-EN.pdf" "tienePdf" => true "PalabrasClave" => array:1 [ "en" => array:4 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec439674" "palabras" => array:1 [ 0 => "Haemodialysis" ] ] 1 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec439676" "palabras" => array:1 [ 0 => "Chronic kidney disease" ] ] 2 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec439678" "palabras" => array:1 [ 0 => "Bleeding" ] ] 3 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec439680" "palabras" => array:1 [ 0 => "Dabigatran" ] ] ] ] "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "fig1" "etiqueta" => "Tab. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "12040_16025_53072_en_t1120402.jpg" "Alto" => 1220 "Ancho" => 1418 "Tamanyo" => 260652 ] ] "descripcion" => array:1 [ "en" => "Data of test on admission" ] ] ] "bibliografia" => array:2 [ "titulo" => "Bibliography" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:9 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Eriksson BI, Dahl OE, Büller HR, Hettiarachchi R, Rosencher N, Bravo ML, et al. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 9 | 9 | 18 |
| 2024 October | 64 | 36 | 100 |
| 2024 September | 67 | 25 | 92 |
| 2024 August | 96 | 73 | 169 |
| 2024 July | 67 | 22 | 89 |
| 2024 June | 75 | 42 | 117 |
| 2024 May | 83 | 34 | 117 |
| 2024 April | 71 | 30 | 101 |
| 2024 March | 64 | 22 | 86 |
| 2024 February | 48 | 32 | 80 |
| 2024 January | 49 | 21 | 70 |
| 2023 December | 43 | 21 | 64 |
| 2023 November | 35 | 29 | 64 |
| 2023 October | 56 | 38 | 94 |
| 2023 September | 60 | 22 | 82 |
| 2023 August | 31 | 30 | 61 |
| 2023 July | 41 | 22 | 63 |
| 2023 June | 47 | 24 | 71 |
| 2023 May | 38 | 34 | 72 |
| 2023 April | 23 | 18 | 41 |
| 2023 March | 31 | 19 | 50 |
| 2023 February | 26 | 18 | 44 |
| 2023 January | 42 | 25 | 67 |
| 2022 December | 38 | 26 | 64 |
| 2022 November | 61 | 28 | 89 |
| 2022 October | 39 | 34 | 73 |
| 2022 September | 39 | 33 | 72 |
| 2022 August | 31 | 38 | 69 |
| 2022 July | 30 | 38 | 68 |
| 2022 June | 33 | 26 | 59 |
| 2022 May | 38 | 37 | 75 |
| 2022 April | 30 | 57 | 87 |
| 2022 March | 34 | 43 | 77 |
| 2022 February | 47 | 41 | 88 |
| 2022 January | 28 | 22 | 50 |
| 2021 December | 33 | 41 | 74 |
| 2021 November | 38 | 39 | 77 |
| 2021 October | 54 | 33 | 87 |
| 2021 September | 54 | 42 | 96 |
| 2021 August | 49 | 45 | 94 |
| 2021 July | 49 | 26 | 75 |
| 2021 June | 19 | 17 | 36 |
| 2021 May | 33 | 31 | 64 |
| 2021 April | 50 | 65 | 115 |
| 2021 March | 65 | 46 | 111 |
| 2021 February | 66 | 20 | 86 |
| 2021 January | 41 | 20 | 61 |
| 2020 December | 38 | 17 | 55 |
| 2020 November | 27 | 16 | 43 |
| 2020 October | 22 | 10 | 32 |
| 2020 September | 21 | 8 | 29 |
| 2020 August | 29 | 16 | 45 |
| 2020 July | 29 | 11 | 40 |
| 2020 June | 25 | 18 | 43 |
| 2020 May | 29 | 10 | 39 |
| 2020 April | 26 | 15 | 41 |
| 2020 March | 26 | 11 | 37 |
| 2020 February | 38 | 18 | 56 |
| 2020 January | 61 | 17 | 78 |
| 2019 December | 47 | 23 | 70 |
| 2019 November | 35 | 23 | 58 |
| 2019 October | 26 | 14 | 40 |
| 2019 September | 33 | 14 | 47 |
| 2019 August | 38 | 13 | 51 |
| 2019 July | 45 | 23 | 68 |
| 2019 June | 55 | 17 | 72 |
| 2019 May | 48 | 18 | 66 |
| 2019 April | 91 | 43 | 134 |
| 2019 March | 33 | 23 | 56 |
| 2019 February | 18 | 13 | 31 |
| 2019 January | 32 | 22 | 54 |
| 2018 December | 87 | 42 | 129 |
| 2018 November | 102 | 14 | 116 |
| 2018 October | 77 | 13 | 90 |
| 2018 September | 53 | 17 | 70 |
| 2018 August | 41 | 22 | 63 |
| 2018 July | 41 | 16 | 57 |
| 2018 June | 48 | 16 | 64 |
| 2018 May | 36 | 14 | 50 |
| 2018 April | 41 | 8 | 49 |
| 2018 March | 46 | 10 | 56 |
| 2018 February | 31 | 8 | 39 |
| 2018 January | 35 | 7 | 42 |
| 2017 December | 46 | 13 | 59 |
| 2017 November | 31 | 13 | 44 |
| 2017 October | 39 | 6 | 45 |
| 2017 September | 41 | 14 | 55 |
| 2017 August | 41 | 12 | 53 |
| 2017 July | 25 | 21 | 46 |
| 2017 June | 37 | 21 | 58 |
| 2017 May | 41 | 20 | 61 |
| 2017 April | 33 | 18 | 51 |
| 2017 March | 34 | 15 | 49 |
| 2017 February | 27 | 13 | 40 |
| 2017 January | 18 | 14 | 32 |
| 2016 December | 57 | 6 | 63 |
| 2016 November | 64 | 18 | 82 |
| 2016 October | 108 | 8 | 116 |
| 2016 September | 149 | 4 | 153 |
| 2016 August | 181 | 12 | 193 |
| 2016 July | 194 | 7 | 201 |
| 2016 June | 131 | 0 | 131 |
| 2016 May | 153 | 0 | 153 |
| 2016 April | 109 | 0 | 109 |
| 2016 March | 102 | 0 | 102 |
| 2016 February | 107 | 0 | 107 |
| 2016 January | 121 | 0 | 121 |
| 2015 December | 129 | 0 | 129 |
| 2015 November | 92 | 0 | 92 |
| 2015 October | 100 | 0 | 100 |
| 2015 September | 71 | 0 | 71 |
| 2015 August | 68 | 0 | 68 |
| 2015 July | 66 | 0 | 66 |
| 2015 June | 48 | 0 | 48 |
| 2015 May | 44 | 0 | 44 |
| 2015 April | 5 | 0 | 5 |
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