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NDT Advance Access originally published online on May 25, 2008
Nephrology Dialysis Transplantation 2008 23(11):3566-3570; doi:10.1093/ndt/gfn282
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© The Author [2008]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org


Is it necessary to stop antiplatelet agents before a native renal biopsy?

Bruce Mackinnon1, Emily Fraser2, Keith Simpson1, Jonathan G. Fox1 and Colin Geddes2

1 Renal Unit, Glasgow Royal Infirmary 2 Renal Unit, Western Infirmary, Glasgow, UK

Correspondence and offprint requests to: Bruce Mackinnon, Renal Unit, Glasgow Royal Infirmary, Third Floor, Walton Building, 84-86 Castle Street, Glasgow G4 OSF, United Kingdom. Tel: +44-141-211-4007; Fax: +44-141-211-4843; E-mail: bmackinnon{at}hotmail.com



   Abstract
Top
 Abstract
Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Background. The practice of advising patients to stop antiplatelet agents before an elective renal biopsy is widespread. The aim of this study was to compare the rate of bleeding complications in two centres that have different policies regarding the ongoing use of antiplatelet agents in patients undergoing an elective renal biopsy. Neither centre routinely checks bleeding time before renal biopsy. A secondary aim, therefore, was to compare complication rates from this cohort with those reported in the literature where screening for prolonged bleeding time is standard practice.

Methods. A retrospective study of 1120 biopsies performed by nephrologists under direct ultrasound guidance in the two renal units in Glasgow, Scotland (Jan 2000 to May 2007) was undertaken. Antiplatelet agents were stopped 5 days before biopsy in one centre but continued in the other. Bleeding time was not measured before biopsy and pro-coagulants were not routinely administered. Major bleeding was defined as the need for blood transfusion, surgical or radiological intervention. Minor bleeding was defined as an ≥1.0 g/dL fall in haemoglobin following biopsy without the need for transfusion or intervention.

Results. Haemoglobin fell by ≥1.0 g/dL in 221 (19.7%) patients. There were 21 (1.9%) major bleeding complications. No patient died or required nephrectomy. Gender, advancing age or worse renal impairment was not associated with an increased likelihood of bleeding. Bleeding complications in 75 patients continuing antiplatelet agents were compared with those occurring in 60 patients whose antiplatelet agents were discontinued. Minor complications were commoner in the first group (31.0 versus 11.7%; P = 0.008), though there was no difference in the rate of major complications.

Conclusions. The risk of major bleeding following a native renal biopsy under ultrasound guidance is low. Stopping antiplatelet agents before biopsy was associated with a lower rate of minor complications but there was no difference in the rate of major complications. Complication rates compare favourably with other published series in which bleeding time was checked and corrected.

Keywords: bleeding; bleeding time; complications; renal biopsy



   Introduction
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 Abstract
 Introduction
Subjects and methods
 Results
 Discussion
 References
 
A percutaneous native renal biopsy has become safer over the last two decades with the introduction of spring-loaded needles and the widespread use of real-time ultrasound guidance [1,2]. Nevertheless, it remains an invasive procedure with a risk of bleeding complications. Approaches aimed at minimizing the risk of complications vary from centre to centre, though there is a broad consensus that biopsy should be avoided in patients with uncontrolled hypertension or untreated coagulopathy [3].

Most nephrologists would advocate assessing intrinsic and extrinsic clotting times as well as platelet count prior to renal biopsy [3,4]. Some also advise measuring the bleeding time to quantify platelet function although there is evidence that this is a poor predictor of post-operative bleeding complications [5]. Furthermore, where bleeding time is prolonged, practice in some units is to attempt to correct it by administering pro-coagulants such as arginine vasopressin (DDAVP) or oestrogens [6,7]. Others take a more pragmatic approach and administer pro-coagulants to those patients deemed to be at a high risk of bleeding without first measuring the bleeding time [8,9].

In order to reduce the risk of bleeding after an elective renal biopsy, many nephrologists advise their patients to discontinue antiplatelet agents and non-steroidal anti-inflammatory agents 5–7 days before a procedure. However, recent meta-analyses suggest that discontinuing antiplatelet agents, even for a short time, may significantly increase the risk of thrombotic vascular events [10,11]. Moreover, guidelines for patients undergoing cardiac surgery or lower limb peripheral vascular surgery state that aspirin should be continued throughout the peri-operative period [12,13].

The aim of the current study was to clarify the risk of major bleeding complications in a retrospective series of native renal biopsies. Neither of the centres studied routinely measured bleeding time before biopsy. The biopsy technique was the same with the exception that in one centre antiplatelet agents were routinely stopped 5 days before elective biopsy and in the other they were continued.



   Subjects and methods
Top
 Abstract
 Introduction
 Subjects and methods
Results
 Discussion
 References
 
Consecutive native renal biopsies (n = 1145) performed in the two renal units in Glasgow, UK (Glasgow Royal Infirmary—GRI and Western Infirmary, Glasgow—WIG), between January 2000 and May 2007, were studied retrospectively. During this period, 25 patients had a native renal biopsy performed by a radiologist under CT or ultrasound guidance (CT 17, ultrasound 8). These patients were not included for further study. Patients gave informed consent to their details being held for the purposes of future research and audit. The same group of renal pathologists reported the samples.

All biopsies were performed on the renal wards. The lower pole of the kidney to be biopsied was localized and marked by the nephrologist undertaking the procedure using ultrasound (Titan Sonosite, Sonosite Ltd, Herts, UK). The skin over the area in question was then disinfected before local anaesthetic (lignocaine 1%) was infiltrated down to the renal capsule. A disposable spring-loaded biopsy gun (Bard Max Core, CR Bard Inc., Covington, GA, USA) with a 16-gauge needle was then positioned at the renal capsule under direct ultrasound guidance by the operator before deploying the needle to obtain a core of renal cortex. The procedure was repeated until between one and three cores of renal cortex had been obtained. The maximum number of passes did not exceed five in either centre. All patients remained in hospital for at least 24 h for observation. Post-biopsy haemoglobin was checked the morning after the procedure. Further investigations were undertaken if clinically indicated.

Our policy was to defer biopsy when the patient had uncontrolled hypertension (>160/90 mmHg), coagulopathy as demonstrated by a prolonged intrinsic or extrinsic clotting time (ratio >1.4) or thrombocytopaenia (platelet count <100 x 109/L). Bleeding times were not measured, unless clinically indicated by a history of prolonged bleeding after injury and pro-coagulants not routinely administered. In one centre (WIG) all antiplatelet agents and non-steroidal anti-inflammatory drugs were discontinued 5 days before elective biopsy, and in the other (GRI) they were continued.

Demographic data, biopsy indication, details of the biopsy procedure (centre, type of biopsy device and imaging used), pre-biopsy haemoglobin and coagulation parameters, serum creatinine, estimated GFR (according to the four-variable MDRD formula) and post-biopsy haemoglobin were extracted from the electronic patient record. Adequacy of the biopsy sample and diagnosis were extracted from the electronic pathology report. Major bleeding was defined as requirement for blood transfusion, radiological or surgical intervention (including cystoscopy and irrigation for gross haematuria). Minor bleeding was defined as an ≥1.0 g/dL fall in post-biopsy haemoglobin.

The incidence of major bleeding and minor bleeding was compared by urgency of biopsy (urgent versus elective), renal function (eGFR <30 mL/min versus ≥30 mL/min), age (<60 years versus ≥60 years), sex (male versus female) and centre (GRI versus WIG). In addition, the incidence of major bleeding and minor bleeding in the patients who had an elective renal biopsy while continuing to take antiplatelet agents at GRI was compared with the patients who discontinued their prescribed antiplatelet agent 5 days before the elective renal biopsy at WIG. Comparisons were by the unpaired t-test of the mean, chi-squared or Fisher's exact test where appropriate. Continuous data are expressed as mean (±SD) or median (interquartile range) according to the symmetry of their distribution. Statistical analyses were performed using MinitabTM statistical software (Release 15, PA, USA).



   Results
Top
 Abstract
 Introduction
 Subjects and methods
 Results
Discussion
 References
 
Demographic data and clinical features
Nephrologists performed 1120 native renal biopsies between January 2000 and May 2007. Mean age was 56 (±16.8) years and 671 (59.9%) were male. Six hundred and thirty-seven (56.9%) biopsies were performed electively. Median serum creatinine was 184 (110–360) µmol/L and median eGFR, in those patients not in ARF, was 42.9 (23.8–67.7) mL/min. Mean platelet count was 285 (±110) x 109/L, mean haemoglobin was 11.7 (±2.5) g/dL and mean prothrombin time 13 s (±2.2) before the procedure.

Characteristics of patients undergoing a biopsy at the two centres are shown in Table 1. There were no significant differences in baseline characteristics between the two centres, when comparing the whole cohort (Table 1), only those undergoing an elective renal biopsy, or the group prescribed antiplatelet agents before the elective renal biopsy (data not shown).


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  		Table 1 Demographic and clinical data for patients undergoing an elective and emergency native renal biopsy

 
Diagnoses made as a result of the biopsy were similar in each centre, primary glomerulonephritis (GN) being slightly more common among those having a biopsy at GRI, and vascular diseases (ischaemic nephropathy, hypertensive nephrosclerosis and cholesterol microembolic disease) slightly less so, see Table 2. Among the whole cohort, renal biopsy was diagnostic in 1046 (93.4%) patients; an adequate sample was judged, by the renal histopathologist, to have been obtained in 1079 (96.3%) patients.


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  		Table 2 Diagnoses following an elective and emergency native renal biopsy, n (%)

 
Bleeding complications following biopsy
Among the whole cohort undergoing either an elective or emergency native renal biopsy, mean reduction in haemoglobin in 24 h was 0.37 (±0.84) g/dL. Haemoglobin fell by ≥1.0 g/dL in 221 (19.7%) patients. Of this group, 21 (1.9%) were judged to have suffered a major complication, the remainder (200/1120 or 17.9%) a minor complication. In the majority of those suffering a minor complication, the fall in haemoglobin was judged to be clinically insignificant; 13 required an extra night in hospital for observation of whom 3 were shown to have a small perinephric haematoma. Only three of the major complications (two frank haematuria, one significant perinephric haematoma, all requiring transfusion) occurred in patients undergoing an elective biopsy. The remaining 18 major complications occurred in patients in whom the procedure was deemed urgent: 15 were transfused of whom 2 required angiography (1 resulting in embolization of the lower pole of the biopsied kidney), 2 suffered frank haematuria requiring placement of an irrigation catheter and 1 developed a large perinephric haematoma. No patients died or required nephrectomy as a direct result of renal biopsy.

There was no difference in the incidence of major or minor bleeding complications when comparing patients with eGFR <30 mL/min and ≥30 mL/min, patients <60 years old and patients ≥60 years old, or males and females (Table 3). Major bleeding complications were more common among patients undergoing an urgent than elective biopsy. However, there was no difference in the rate of major bleeding complications among those undergoing an urgent biopsy while on an antiplatelet agent compared with those not on one (5.2% versus 3.4%, P = 0.17). There was no difference in the rate of major complications at the two centres but haemoglobin fell by more at GRI than WIG (0.5 versus 0.3 g/dL, P < 0.0001) (Table 4). When comparing the 75 patients who had an elective renal biopsy while continuing to take antiplatelet agents at GRI (aspirin 68, clopidogrel 7) with the 60 patients who discontinued their prescribed antiplatelet agent 5 days before the elective renal biopsy at WIG (aspirin 54, dipyridamole 4, clopidogrel 2), there was no difference in the rate of major complications but a significantly higher proportion of patients who experienced an ≥1.0 g/dL reduction in haemoglobin after the biopsy in the former group (31.0 versus 11.7%; P = 0.008) (Table 4).


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  		Table 3 Comparison of minor and major bleeding according to urgency of biopsy (whole cohort) and renal function, age and gender (elective biopsies only)

 

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  		Table 4 Comparison of bleeding complications following a native renal biopsy in the two centres

 


   Discussion
Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
References
 
Our study demonstrates that a native renal biopsy under real-time ultrasound guidance is a safe procedure. Our study adds to the current knowledge by demonstrating that discontinuing antiplatelet agents before elective renal biopsy did not reduce the rate of major complications, although it was associated with fewer episodes of minor bleeding (defined as a fall in haemoglobin of ≥1.0 g/dL). The risk of minor and major bleeding reported here is similar to that in other series in which bleeding time was routinely checked and corrected if prolonged.

This is the largest contemporary series of native renal biopsies directly addressing the question of safety. Several other series have been reported in the last decade [6,7,14–16], with major complications described as occurring between 0.36 and 5.5% of cases. One series described patients undergoing a biopsy over a 20-year period [16]. During this time, significant changes have taken place in the biopsy technique and the results are therefore difficult to compare with contemporary series. Two other series describe large national [15] or regional [14] biopsy registries but include little information on biopsy technique. There are, however, two contemporary reports of consecutive native renal biopsies that are interesting to compare with our study [6,7]. Each describes several hundred elective native renal biopsies performed in centres where antiplatelet agents and non-steroidal anti-inflammatory drugs were discontinued before the procedure, and bleeding time was routinely measured and corrected if prolonged. In these series, 0.36% [6] and 1.2% [7] of patients experienced a major complication, similar to the 0.5% patients undergoing an elective biopsy in our study. This suggests that correcting abnormalities of platelet function may not be necessary to prevent major bleeding complications. This is an important observation because the administration of a pro-coagulant may increase the risk of a thrombotic vascular event [17,18]. Since many patients undergoing a native renal biopsy will already be at greater risk of such a complication, we believe that the practice of administering pro-coagulants routinely to correct a prolonged bleeding time should be reassessed.

Of those patients in this series undergoing an elective renal biopsy, ongoing ingestion of antiplatelet agents was not associated with an increase in the risk of clinically significant bleeding complications. This is analogous to the situation in other invasive procedures with a similar risk of major bleeding complications such as a trans-bronchial lung biopsy [19]. Furthermore, the withdrawal of antiplatelet agents is not without risk. For example, 10% of patients described in a recent French series, presenting with acute coronary syndrome and previously on long-term aspirin, had stopped it within the preceding month [20]. In addition, a meta-analysis of trials recruiting almost 50 000 patients suggests a mean period between discontinuing aspirin and development of acute coronary syndrome, in those in whom it occurs, of 8.5 days [11].

An important caveat when considering this study is to note its retrospective observational nature. Neither of the centres studied has routinely screened patients for disorders of platelet function prior to an elective renal biopsy in the recent past. It is difficult to be certain that doing so would not have further reduced the risk of bleeding, though given the low rate of major complications observed, we believe this to be unlikely. A criticism that is more difficult to answer is that the rarity of major complications after an elective renal biopsy, even in a large series such as ours, makes it difficult to be confident that a particular intervention such as stopping antiplatelet agents is not associated with a better outcome. In an effort to increase the power of future observational studies in this area, we have set up a national renal biopsy registry. However, definitive answers to the questions raised by this work would require large-scale randomized trials.

In summary, the risks of major bleeding complications in this large contemporary native renal biopsy series compare favourably with other reported series. The risk of minor, but not major, bleeding complications was lower in the small group of patients stopping antiplatelet agents at the time of renal biopsy. Comparison with other published series suggests that correction of prolonged bleeding time with pro-coagulants may not significantly reduce the risk of clinically important bleeding. A further study of these issues, preferably in the setting of randomized trials, is warranted.

Conflict of interest statement. None declared.



   References
Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 

  1. Doyle AJ, Gregory MC, Terreros DA. Percutaneous native renal biopsy: comparison of a 1.2-mm spring-driven system with a traditional 2-mm hand-driven system. Am J Kidney Dis (1994) 23:498–503.[Web of Science][Medline]
  2. Nyman RS, Cappelen-Smith J, al Suhaibani H, et al. Yield and complications in percutaneous renal biopsy. A comparison between ultrasound-guided gun-biopsy and manual techniques in native and transplant kidneys. Acta Radiol (1997) 38:431–436.[Web of Science][Medline]
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  5. Peterson P, Hayes TE, Arkin CF, et al. The preoperative bleeding time test lacks clinical benefit: college of American pathologists’ and American society of clinical pathologists’ position article. Arch Surg (1998) 133:134–139.[Abstract/Free Full Text]
  6. Hergesell O, Felten H, Andrassy K, et al. Safety of ultrasound-guided percutaneous renal biopsy-retrospective analysis of 1090 consecutive cases. Nephrol Dial Transplant (1998) 13:975–977.[Abstract/Free Full Text]
  7. Manno C, Strippoli GF, Arnesano L, et al. Predictors of bleeding complications in percutaneous ultrasound-guided renal biopsy. Kidney Int (2004) 66:1570–1577.[CrossRef][Web of Science][Medline]
  8. Mattix H, Singh AK. Is the bleeding time predictive of bleeding prior to a percutaneous renal biopsy? Curr Opin Nephrol Hypertens (1999) 8:715–718.[CrossRef][Web of Science][Medline]
  9. Stiles KP, Hill C, LeBrun CJ, et al. The impact of bleeding times on major complication rates after percutaneous real-time ultrasound-guided renal biopsies. J Nephrol (2001) 14:275–279.[Web of Science][Medline]
  10. Biondi-Zoccai GG, Lotrionte M, Agostoni P, et al. A systematic review and meta-analysis on the hazards of discontinuing or not adhering to aspirin among 50,279 patients at risk for coronary artery disease. Eur Heart J (2006) 27:2667–2674.[Abstract/Free Full Text]
  11. Burger W, Chemnitius JM, Kneissl GD, et al. Low-dose aspirin for secondary cardiovascular prevention—cardiovascular risks after its perioperative withdrawal versus bleeding risks with its continuation— review and meta-analysis. J Intern Med (2005) 257:399–414.[CrossRef][Web of Science][Medline]
  12. Mangano DT. Aspirin and mortality from coronary bypass surgery. N Engl J Med (2002) 347:1309–1317.[Abstract/Free Full Text]
  13. Neilipovitz DT, Bryson GL, Nichol G. The effect of perioperative aspirin therapy in peripheral vascular surgery: a decision analysis. Anesth Analg (2001) 93:573–580.[Abstract/Free Full Text]
  14. Covic A, Schiller A, Volovat C, et al. Epidemiology of renal disease in Romania: a 10 year review of two regional renal biopsy databases. Nephrol Dial Transplant (2006) 21:419–424.[Abstract/Free Full Text]
  15. Rychlik I, Jancova E, Tesar V, et al. The Czech registry of renal biopsies. Occurrence of renal diseases in the years 1994–2000. Nephrol Dial Transplant (2004) 19:3040–3049.[Abstract/Free Full Text]
  16. Whittier WL, Korbet SM. Timing of complications in percutaneous renal biopsy. J Am Soc Nephrol (2004) 15:142–147.[Abstract/Free Full Text]
  17. Lowe GD. Desmopressin and myocardial infarction. Lancet (1989) 1:895–896.[Medline]
  18. Stratton J, Warwicker P, Watkins S, et al. Desmopressin may be hazardous in thrombotic microangiopathy. Nephrol Dial Transplant (2001) 16:161–162.[Free Full Text]
  19. Herth FJ, Becker HD, Ernst A. Aspirin does not increase bleeding complications after transbronchial biopsy. Chest (2002) 122:1461–1464.[CrossRef][Web of Science][Medline]
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Received for publication: 26. 2.08
Accepted in revised form: 23. 4.08


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