Journal of Nephrology & Renal Therapy Category: Clinical Type: Case Report
Spontaneous Perinephric Hematoma with Newer Oral Anticoagulation in Kidney Transplant Recipient
- Sandesh Parajuli1*, Nishkarsh Saxena2
- 1 Department Of Medicine, Division Of Nephrology, University Of Wisconsin School Of Medicine And Public Health, Madison, WI 53705, United States
- 2 Department Of Medicine, Division Of Nephrology, University Of Wisconsin School Of Medicine And Public Health, Madison, Wisconsin, United States
*Corresponding Author:Sandesh Parajuli
Department Of Medicine, Division Of Nephrology, University Of Wisconsin School Of Medicine And Public Health, Madison, WI 53705, United States
Received Date: Dec 30, 2015 Accepted Date: Feb 11, 2016 Published Date: Feb 26, 2016
DVT : Deep Vein Thrombosis
Hb : Hemoglobin
NOAC : New Oral Anti-coagulants
PE : Pulmonary Embolism
P-gp : P-glycoprotein
VTE : Venous Thromboembolism
VKA : Vitamin K Antagonist
Direct Thrombin Inhibitors (DTIs), dabigatran, and the direct Factor Xa inhibitors apixaban and rivaroxaban are newer oral anticoagulants that were approved for the treatment of non-valvular atrial fibrillation in October 2010 and Venous Thromboembolism (VTE), specifically Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE), in April 2014.
When compared to traditional therapy with warfarin, these agents have the advantage of not requiring regular blood draws for monitoring along with minimal food and drug interactions . The major drawback of these agents is absence of a reversal agent in cases of clinically significant bleeding, although the FDA has recently approved a reversal agent, idarucizumab (Praxbind), for emergent or life-threatening bleeding associated with dabigatran .
Renal dose adjustment is very important with New Oral Anticoagulants (NOACs) as these medications are cleared by the kidneys to variable extent (about 30% for apixaban and rivaroxaban and up to 85% for dabigatran) . The product inserts for these drugs recommends avoiding use in the patients with creatinine clearance of less than 15 ml/min.
Dabigatran is a reversible inhibitor of Factor IIa (thrombin) with a half life of 12 to 17 hours . Inhibition of factor IIa prevents conversion of fibrinogen to fibrin and cross-linking of fibrin clot . It is a substrate of the efflux transporter P-glycoprotein (P-gp) which affects absorption of the prodrug . There is a potential of increased drug exposure and bleeding risk with concomitant exposure to P-gp inhibitors (e.g., cyclosporine, carvedilol, amiodarone etc.) . About 80% of the drug elimination is via kidneys .
Dabigatran has shown non-inferiority to warfarin for the treatment of VTE, along with reduction of major bleeding . However, there is very limited information on special subgroups such as patients with renal impairment, cancer or fragile patients, who may be at higher risk of bleeding .
Dabigatran showed non-inferiority in reduction of recurrent VTE when compared with warfarin in RE-COVER trial [2.4% vs 2.2% Hazard Ratio (HR) 1.1, 95% CI = 0.65 -1.84; P < 0.001] . A similar trend was observed in RE-COVER 2 trial [2.3 vs 2.2%; HR = 1.08; 95% CI 0.45 -1.48] [2,5].
In both of these studies, dabigatran had similar rates of bleeding when compared with warfarin [RE-COVER trial (1.6% vs 1.9%; HR 0.82; 95% CI 0.45 -1.48); RE-COVER 2 trial (1.2% vs 1.7%; HR 0.69; 95% CI 0.36 - 1.32)] [2,5].
A pooled analysis of these studies consisting of about 5100 patients showed results consistent with the individual studies with similar benefit risk profile, irrespective of renal insufficiency and cancer; however, there is no data on clinical risks in kidney transplant recipients . Also, these studies excluded patients with severe renal insufficiency. The drug should be used cautiously in patients with fluctuating renal function and advanced kidney disease . Both the clinical efficacy and risk of bleeding increases with age . Data from RE-LY trial shows a higher bleeding risk in patients aged 75 and above .
Our patient was on cyclosporine (P-gp inhibitor) which may have increased the bleeding risk with dabigatran. Initial CT angiogram was negative for ruptured arterial aneurysm or pseudo-aneurysm. Also, there was no evidence of renal/adrenal mass on repeat CT scan.
More studies are needed to assess the clinical efficacy and safety of non-VKA anticoagulants in this subgroup of patients, as use of NOACs is rising.
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- Schulman S, Kakkar AK, Goldhaber SZ, Schellong S, Eriksson H, et al. (2014) Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation 129: 764-772.
- Burness CB (2015) Idarucizumab: First Global Approval. Drugs 75: 2155-2161.
- Iyer V, Singh HS, Reiffel JA (2012) Dabigatran: comparison to warfarin, pathway to approval, and practical guidelines for use. J Cardiovasc Pharmacol Ther 17: 237-247.
- Prandoni P (2014) Treatment of patients with acute deep vein thrombosis and/or pulmonary embolism: efficacy and safety of non-VKA oral anticoagulants in selected populations. Thromb Res 134: 227-233.
Citation:Saxena N, Parajuli S (2016) Spontaneous Perinephric Hematoma with Newer Oral Anticoagulation in Kidney Transplant Recipient. J Nephrol Renal Ther 2: 002.
Copyright: © 2016 Sandesh Parajuli, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.