AngioJetTM rheolytic thrombectomy induced intravascular haemolysis leading to Acute Kidney Injury requiring Dialysis

Background: AngioJetTM rheolytic thrombectomy has been used in the treatment of deep vein thrombosis (DVT) to prevent post-thrombotic syndrome. Though not widely appreciated, it has the potential to cause intravascular haemolysis. Report: A 37 year old man with no previous medical history presented to his GP with a three week history of progressive right upper limb swelling. Doppler imaging confi rmed right upper limb DVT and CT scan demonstrated thoracic outlet syndrome. The patient underwent AngioJetTM thrombectomy followed by IV heparin infusion. Successful revascularisation of the occluded vein was achieved. Overnight he developed haematuria, which was initially attributed to IV heparin. Urinalysis however revealed no red cells or casts. Apart from an Hb drop from 134 to 117 his blood profi le and blood fi lm showed no abnormality. He subsequently developed progressive oliguria with marked oedema and acute kidney injury (AKI). His creatinine peaked at 1070umol/l at 96 hours post procedure and he was started on intermittent dialysis. He remained dialysis dependent for 6 days. Ultrasound imaging excluded urinary obstruction. Autoimmune and vasculitic serology were negative. Intravascular haemolysis and haemoglobinuria was confi rmed by raised LDH (1714u/L) and low haptoglobin (<0.1units). Direct Coomb’s test, Cold agglutinin test and paroxysmal nocturnal haemoglobinuria screen were negative. The patient’s renal function normalised over 3 months. Conclusions: The likely cause of this man’s AKI is heme pigment nephropathy from intra-vascular haemolysis. Increased awareness of this condition may allow early identifi cation and intervention to reduce the risk of renal injury from AngioJetTM associated haemolysis. Case Report AngioJetTM rheolytic thrombectomy induced intravascular haemolysis leading to Acute Kidney Injury requiring Dialysis Hultin Sebastian1*, Nguyen Tam2 and Murali Karumathil1 1The Wollongong Hospital, Department of Renal Medicine, Australia 2The Wollongong Hospital, Department of Vascular Surgery, Australia *Address for Correspondence: Sebastian Hultin, The Wollongong Hospital, Department of Renal Medicine, Australia, Email: sebastian.hultin@doctors.org.uk Submitted: 11 July 2018 Approved: 02 August 2018 Published: 03 August 2018 Copyright: 2018 Sebastian H. et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite this article: Sebastian H, Tam N, Karumathil M. AngioJetTM rheolytic thrombectomy induced intravascular haemolysis leading to Acute Kidney Injury requiring Dialysis. J Clini Nephrol. 2018; 2: 025-028. https://doi.org/10.29328/journal.jcn.1001015 Introduction We report a case of dialysis-requiring acute kidney injury AKI following AngioJetTM rheolytic thrombectomy in a 37 year old mine worker, likely secondary to mechanical haemolysis induced by the procedure. The increasing availability of percutaneous mechanical thrombectomy (PMT) has offered a novel avenue for management of both venous and arterial thromboses. Bene it has been demonstrated in lower limb DVTs particularly in the prevention of post thrombotic syndrome [1]. Although its bene it in upper limb DVT is less clear [2], the presence of a large symptomatic thrombus prompted decision to proceed with thrombolysis and PMT in addition to anticoagulation. Targeted therapy for thrombus dissolution also remains an attractive strategy in patients with signi icant bleeding risk or where systemic thrombolysis is not an option [3]. AngioJetTM, available at our facility, creates a hydrodynamic vortex through retrogradely oriented high speed luid jets allowing selective trapping and dissolving of thrombi [4]. While AngioJetTM thrombectomy is recognised as an effective treatment for DVT, adverse effect data has focused on mortality (0%), thromboembolic events AngioJetTM rheolytic thrombectomy induced intravascular haemolysis leading to Acute Kidney Injury requiring Dialysis Published: August 03, 2018 26/28 (<1%) and requirements for blood transfusion (4.2-14%) despite an insigni icant incidence of major bleeding [5]. A systematic case series review in 2011 concluded that PMT was a feasible treatment for DVT and possibly safe, although the authors concluded that the level of evidence was for adverse events was lacking [5]. A more recent systematic review of percutaneous thrombectomy in pulmonary embolism in 2013 highlighted signi icant cardiovascular risk associated with AngioJetTM with cardiovascular complications reported in 21.1% of all cases with massive embolism and 17.4% of cases with submissive embolism [6]. There was also a signi icant risk of risk of bradyarrhythmia (11.6%) and asystole (1%) in addition to a higher rate of bleeding (14.5%). The same review found an incidence of 11.7% of renal impairment, which may have been signi icantly under reported due to post intervention routine biochemical testing not always taking place. Although PMT induced haemolysis is well described in the literature, there has been historical under-appreciation of the potential for severe AKI largely due to lack of in-vivo trials evaluating renal function as an outcome and lack of reporting on renal function change as a complication [7]. Early studies have demonstrated intravascular haemolysis following procedure with clinically insigni icant drops in Hb concentrations, elevated LDH and low haptoglobin consistent with haemolysis, and less frequently an increase in creatinine [8]. In 2009 [3] reported a presumed irst case of severe AKI requiring dialysis following AngioJetTM PMT in a patient with pulmonary embolus [3]. Prior to this in 2007, however, a prior paediatric case of AKI involving PMT had already been reported in a 16 year old patient with severe clot burden DVT and multiple administration of contrast resulting in severe AKI requiring peritoneal dialysis [9]. More recently in 2016 a further case of AKI requiring dialysis following PMT treatment of an extensive lower limb and IVC DVT [10] was reported. Our case adds to a growing case series of severe AKI requiring short to medium term RRT.


Introduction
We report a case of dialysis-requiring acute kidney injury AKI following AngioJet TM rheolytic thrombectomy in a 37 year old mine worker, likely secondary to mechanical haemolysis induced by the procedure. The increasing availability of percutaneous mechanical thrombectomy (PMT) has offered a novel avenue for management of both venous and arterial thromboses. Bene it has been demonstrated in lower limb DVTs particularly in the prevention of post thrombotic syndrome [1]. Although its bene it in upper limb DVT is less clear [2], the presence of a large symptomatic thrombus prompted decision to proceed with thrombolysis and PMT in addition to anticoagulation. Targeted therapy for thrombus dissolution also remains an attractive strategy in patients with signi icant bleeding risk or where systemic thrombolysis is not an option [3]. AngioJet TM , available at our facility, creates a hydrodynamic vortex through retrogradely oriented high speed luid jets allowing selective trapping and dissolving of thrombi [4].
While AngioJet TM thrombectomy is recognised as an effective treatment for DVT, adverse effect data has focused on mortality (0%), thromboembolic events (<1%) and requirements for blood transfusion (4.2-14%) despite an insigni icant incidence of major bleeding [5]. A systematic case series review in 2011 concluded that PMT was a feasible treatment for DVT and possibly safe, although the authors concluded that the level of evidence was for adverse events was lacking [5]. A more recent systematic review of percutaneous thrombectomy in pulmonary embolism in 2013 highlighted signi icant cardiovascular risk associated with AngioJet TM with cardiovascular complications reported in 21.1% of all cases with massive embolism and 17.4% of cases with submissive embolism [6]. There was also a signi icant risk of risk of bradyarrhythmia (11.6%) and asystole (1%) in addition to a higher rate of bleeding (14.5%). The same review found an incidence of 11.7% of renal impairment, which may have been signi icantly under reported due to post intervention routine biochemical testing not always taking place.
Although PMT induced haemolysis is well described in the literature, there has been historical under-appreciation of the potential for severe AKI largely due to lack of in-vivo trials evaluating renal function as an outcome and lack of reporting on renal function change as a complication [7]. Early studies have demonstrated intravascular haemolysis following procedure with clinically insigni icant drops in Hb concentrations, elevated LDH and low haptoglobin consistent with haemolysis, and less frequently an increase in creatinine [8]. In 2009 [3] reported a presumed irst case of severe AKI requiring dialysis following AngioJet TM PMT in a patient with pulmonary embolus [3]. Prior to this in 2007, however, a prior paediatric case of AKI involving PMT had already been reported in a 16 year old patient with severe clot burden DVT and multiple administration of contrast resulting in severe AKI requiring peritoneal dialysis [9]. More recently in 2016 a further case of AKI requiring dialysis following PMT treatment of an extensive lower limb and IVC DVT [10] was reported. Our case adds to a growing case series of severe AKI requiring short to medium term RRT.

Case Report
Mr. CM, a 37 year old caucasian male, irst presented to his general practitioner complaining of progressive right upper limb swelling. His past medical history was unremarkable except for a 20 pack year history of smoking. He was not taking regular medications and had no allergies. Outpatient ultrasound of the upper limb revealed extensive thrombus within the right subclavian vein and he was referred to the emergency department for further management. Clinical examination at presentation revealed distended proximal axillary veins with swelling of the distal limb. He was haemodynamically stable with a normal cardiopulmonary examination, a blood pressure of 110/74mmHg, heart rate of 72 beats per minute, respiratory rate of 14 breaths per minute and oxygen saturation of 98% on room air. His haematological and biochemical pro iles at presentation were unremarkable. Computed tomography excluded pulmonary embolism, but con irmed a proximal subclavian thrombus with attenuation of the subclavian vein between the medial aspect of the right clavicle and the irst rib with arms elevated, suggestive of thoracic outlet syndrome. He was started on intravenous heparin but due to the size of the thrombus and perceived bene its of thrombolysis in deep venous thrombosis (DVT) with regards to post thrombotic syndrome [5], decision to proceed to rheolytic thrombolysis was made. AngioJet TM thrombolysis was undertaken, during which he received 3000u of Heparin followed by 500'000u Urokinase, preceding suction thrombectomy and venoplasty of the proximal subclavian stenosis using an 8x20mm balloon. Standard non-iodinated contrast was administered as per protocol during procedure and to con irm vessel patency post procedure. There were no intraoperative complications. Post operatively intravenous heparin was continued for the next 72hours and he also received intravenous luids at 80mL/h. There were no documented episodes of hypotension. 24 hours post procedure, the patient developed sudden onset painless haematuria, suspected initially to be secondary to the urinary catheter in the presence of heparin anticoagulation. He remained haemodynamically stable. Blood pro ile at 48 hours, however, indicated an AKI with a rise in creatinine to 436 μmol/L (baseline creatinine 90 umol/L), associated with drop in haemoglobin from 134g/L to 117 g/L. His biochemistry also revealed mild liver function test derangement with ALP 113U/L, ALT 90U/L, AST 348U/L, but normal bilirubin. He became progressively oliguric, despite a positive luid balance (5000mL over 72 hours) and progressively worsening signs of luid overload. His creatinine peaked at 1020 umol/L at 72 hours post procedure, necessitating commencement of haemodialysis for symptomatic luid overload, uraemia and metabolic acidosis, despite optimal medical therapy. Investigation to evaluate his AKI revealed proteinuria with urine albumin:creatinine ratio of 202.6mg/mmol and protein:creatinine ratio of 471mg/mmol -nonspeci ic in the setting of oliguric renal failure. Urinalysis showed 3+ blood, but urine microscopy was repeatedly negative for microhaematuria or casts. Serum creatine kinase (CK) and serum myoglobin were raised at 348U/L and 254ng/L respectively. Renal imaging revealed bilateral peri-nephric stranding without evidence of infarction or ureteric obstruction. Renal vasculature was without abnormality on duplex ultrasound. Autoimmune and vasculitic serology were negative. Further biochemical investigations con irmed intravascular haemolysis with LDH markedly raised at 1714u/L and very low haptoglobin (<0.1u/L). Direct Agglutinin Test (DAT / Coombs test) and cold agglutinin tests were negative. Peripheral blood lowcytometry showed normal GPI-linked protein pro ile. Renal biopsy was not undertaken due to risk of bleeding from anticoagulation therapy. His urine output improved over the ensuing week and renal replacement therapy (RRT) was discontinued. The patient's creatinine continued to improved and normalised over the next 3 months. He was maintained on warfarin whilst awaiting irst rib resection.

Discussion
We present a case of a heme pigment AKI following rheolytic thrombectomy induced haemolysis. This case adds to a growing cohort of cases of AngioJet TM related renal impairment with signi icant morbidity. In the setting of lack of appreciation for potentially severe intravascular haemolysis from the PMT device, AKI was initially attributed to dehydration and contrast nephropathy. Haemoglobinuria was suspected following a positive urinalysis for haematuria but negative urine microscopy and a positive haemolysis screen. Elevated serum myoglobin raised the possibility of myoglobinuria from rhabdomyolysis, but made unlikely by the relatively modest elevation of CK. The relative low titres and low speci icity of serum myoglobin titres was non-speci ic. Paroxysmal nocturnal haemoglobinuria screen was negative and negative Direct Agglutinin and Cold Agglutinin tests supported PMT mechanical haemolysis as the primary aetiology, and a diagnosis of haeme pigment nephropathy was made. The lack of cardiovascular and renal comorbidities in our case and previously reported cases of AngioJet TM related AKI requiring RRT, makes the severity of kidney injury unexpected. There are, however, some similarities which may offer avenues for future research and risk strati ication for AKI in patients undergoing PMT. The concomitant contrast administration from both CT angiography prior to PMT may have contributed to the severity of the AKI [8,9]. The prolonged use of PMT, particularly in a patent vessel, has been further identi ied as potentially increasing risk of haemolytic and heme pigment nephropathy with a haematocrit drop >10% independently increasing odds for AKI [7]. Using short bursts of thrombolysis rather than prolonged activation may further limit haemolysis burden [11].
Consideration surrounding the uncertainty of risk strati ication should be taken into account when referring a patient for PMT of both venous and arterial thromboses. Appropriate intravenous luid administration pre-and post-AngioJet TM thrombectomy as well as avoidance of other nephrotoxic insult followed by close biochemical monitoring to identify clues to haemolysis and AKI would be prudent steps, because once AKI sets in, the treatment options are limited to largely supportive and symptomatic measures.