MO168MANAGEMENT OF ANTICOAGULANT RELATED NEPHROPATHY: SLOVENIAN CASE SERIES AND REVIEW OF CURRENT KNOWLEDGE

Background and Aims Anticoagulant-related nephropathy is a recently recognized form of acute kidney injury associated with previously underdiagnosed kidney damage in addition to (usually) excessive anticoagulation. It occurs in patients receiving warfarin as well as those receiving direct oral anticoagulants. Method We collected and analyzed cases of Slovenian patients with pathohistologically documented anticoagulant-related nephropathy associated with all types of anticoagulant treatment from the first case in 2014 to 2020. We also performed an analysis of previously documented cases of anticoagulant-related nephropathy in the global literature (PubMed) in the period from their first mention until recently. Results In Slovenia, 13 patients with anticoagulant-related nephropathy have been histologically verified so far. All patients were diagnosed with concomitant underlying renal disease, and 80% had IgA nephropathy, which was disproportionately mild according to the degree of renal function impairment. After supportive measures and reversal of excessive anticoagulation, 8 of 13 patients were further treated with corticosteroids, resulting in significant improvement in renal function. During the follow-up period, a total of one steroid-treated patient died due to infectious complications and one patient progressed to end-stage renal failure. In the worldwide literature, we found 46 case reports or case series of patients with anticoagulant-related nephropathy. Failure of restitution of renal function with the need for maintenance dialysis was reported much more frequently compared to the results of our cohort (up to 67% vs. 8.3%) Conclusion To our knowledge, the Slovenian cohort of patients with histologically established anticoagulant-related nephropathy is the largest reported series to date that received corticosteroid therapy in addition to conservative measures. Our results indicate that steroids have a beneficial effect, likely exerted via suppression of hemoglobin-associated oxidative stress and inflammation. However, considering the polimorbidity of these patients, the benefit of additional steroid therapy must be weighed against the potential risks of side effects, especially life-threatening infections.

Management of Anticoagulant-Related Nephropathy: A Single Center Experience

Background: Anticoagulant-related nephropathy (ARN) is a form of acute kidney injury that mainly occurs in patients with previously unrecognized glomerular disease in addition to excessive anticoagulation. Since a renal biopsy is not performed in most cases, the diagnosis is often presumptive. Methods: Here, we present the characteristics of a national Slovenian patient cohort with histologically verified ARN, from the first case in 2014 to December 2020, and a review of the current literature (Pubmed database). Results: In Slovenia, ARN has been detected in 13 patients, seven of whom were treated with coumarins, and others with direct oral anticoagulants. In seven patients, ARN appeared after excessive anticoagulation. As many as 11 patients had underlying IgA nephropathy. Similar to the global data presented here, the pathohistological impairment associated with pre-existing glomerulopathy was mild and disproportionate to the degree of functional renal impairment. The majority of our patients with ARN experienced severe deterioration of renal function associated with histological signs of accompanying acute tubular injury, interstitial edema, and occlusive red blood cell casts. These patients were treated with corticosteroids, which (in addition to supportive treatment and discontinuation of the anticoagulant drug) led to a further improvement in renal function. Conclusions: Anticoagulant therapy combined with a pre-existing glomerular injury may lead to ARN. In addition to discontinuation of the anticoagulant and supportive care, corticosteroids, which are currently listed in only a few cases in the world literature, may have a positive influence on the course of treatment. However, the benefits of steroid treatment must be weighed against the risk of complications, especially life-threatening infections.

Bioptically Proven “Anticoagulation-Related Nephropathy“ Induced by Dual Antiplatelet Therapy

Anticoagulation-related nephropathy (ARN) is a significant and underdiagnosed complication in patients who receive anticoagulation therapy. It is characterized by acute kidney injury in the setting of excessive anticoagulation defined as an international normalized ratio > 3.0 in patients treated with warfarin. A definitive diagnosis is made by renal biopsy showing acute tubular necrosis with obstruction of the tubuli by red blood cell casts. However, the evidence shows that ARN can occur during treatment with novel oral anticoagulants as well. Although it has been suggested that antiplatelet therapy, such as aspirin, might contribute to coagulopathy (and therefore the hypothetical risk of ARN), there are no reports of ARN induced by antiplatelet therapy according to our knowledge. It is also reported that glomerular lesions (i.e., kidney disease) represent a risk factor for ARN. We present a case of an 82-year-old man who developed biopsy-proven ARN after the administration of dual antiplatelet therapy with no previous anticoagulation treatment and normal coagulation tests.

Management of pulmonary embolism in patients with cancer

Pulmonary embolism (PE) is a frequent complication in patients with cancer. Clinicians have to maintain a high index of suspicion to reduce the large proportion of PEs that remain undiagnosed in the cancer population. Thrombolysis is not a standard treatment for haemodynamically unstable patients with cancer-associated PE because the risk of haemorrhage can be excessive. Anticoagulation with a low-molecular-weight heparin (LMWH) for at least 6 months is the current standard of care for the treatment of cancer-associated PE, while vitamin K antagonists are a reasonable second choice for patients with contraindications against LMWH or a strong preference towards an oral agent. Although an indirect network meta-analysis suggests that non-vitamin K-dependent oral anticoagulants may be comparably efficacious and safe as LMWH for treating PE in cancer patients, these agents cannot be recommended as a standard first-line treatment at this time because a head-to-head comparison to the standard of care has not yet been reported. Anticoagulation beyond 6 months is an emerging concept; however, the patient population that may benefit from this intervention still needs to be defined. Guidance statements facilitate the management of challenging patients with brain metastases, unsuspected PE, thrombocytopenia, and recurrent PE.

Combined Acute Haemolytic and Secondary Angle Closure Glaucoma following Spontaneous Intraocular Haemorrhages in a Patient on Warfarin

Background: To report the first described case of combined haemolytic and acute angle closure glaucoma secondary to spontaneous intraocular haemorrhages in a patient on excessive anticoagulation. To the best of our knowledge, this is the first case reported in the literature presenting with raised intraocular pressure due to both mechanisms. Case Description: A 90-year-old woman presented with acute pain and reduction in vision in the left eye. Her intraocular pressure (IOP) was 55 mm Hg. There were red tinted blood cells in the anterior chamber giving it a reddish hue. The patient was known to have advanced wet macular degeneration. She was taking oral warfarin for atrial fibrillation. Her international normalised ratio (INR) was 7.7. B-scan ultrasound of posterior segment showed vitreous and suprachoroidal haemorrhages. An ultrabiomicroscopic examination confirmed open angles. A diagnosis of haemolytic glaucoma secondary to intraocular haemorrhages was made. The IOP was controlled medically. Warfarin was withdrawn and oral vitamin K therapy was initiated leading to a rapid INR reduction. Three days later, her anterior chamber became progressively shallower causing a secondary acute angle closure which was managed medically. After 2 months, the left IOP was well-controlled without any medications and the eye was not inflamed. Her vision in that eye remained perception of light. Conclusion: Patients with suprachoroidal haemorrhages should be closely monitored as they might subsequently develop acute angle closure despite an initially open angle and well-controlled INR and IOP. Excessive anticoagulation needs to be prevented to minimise the risk of sight-threatening complications.

Medication error when switching from warfarin to rivaroxaban leading to spontaneous large ecchymosis of the abdominal and chest wall

Non-vitamin K oral anticoagulant (NOAC) therapy may be inappropriate if prescription was incorrect, the patient's physiological parameters change, or interacting concomitant medications are erroneously added. The aim of this report was to illustrate inappropriate NOAC prescription in a 78-year-old woman with non-valvular atrial fibrillation and borderline renal dysfunction who was switched from warfarin to rivaroxaban and subsequently developed bruising with hemorrhagic shock and acute on chronic renal failure. Administration of 4-factor prothrombin complex concentrate effectively reversed coagulopathy and stopped bleeding. Retrospective determination of circulating plasma levels of rivaroxaban and warfarin confirmed that excessive anticoagulation was likely due to warfarin that the patient probably continued to take although rivaroxaban was initiated. Pharmacodynamic interaction between rivaroxaban and warfarin may not only be additive but synergistic. In patients at high risk of complications, judicious prescribing and dosing of NOACs, and regular monitoring of concomitant medications and renal function are highly recommended.

Experience of individualization of oral anticoagulants use and dosage in personalized medicine centre conditions

The application of pharmacogenetic testing was analyzed in patients treated at the center of personalized medicine, in order to analyze gene polymorphism frequency - response predictors to indirect anticoagulants therapy, estimation of the warfarin dose selection time, the hospitalization duration. The presence of VKORC1 and CYP2C9 polymorphisms or homozygous polymorphisms combinations is quite common in the Russian population: CYP2C9*2 polymorphism (15.3%) was observed in 8 patients, CYP2C9*3 (9.6%) in 5 patients. VKORC1 gene A allele was detected in 18 patients, accounting for 34.6% of the whole group. In patients with this polymorphism warfarin administration according to the traditional algorithm often leads to excessive anticoagulation and bleeding. Initiation of warfarin therapy according to the scheme taking into account genotyping significantly increases the treatment safety and reduces the adverse events incidence in this group of patients.