br Factor Xa an enzyme in the coagulation cascade has

Factor Xa, an enzyme in the coagulation cascade, has recently been identified as having a role in inflammation, generating interest in factor Xa inhibitors as anti-inflammatory agents beyond their established use as anticoagulants [, , , ]. We report sustained clinical and electrophysiologic improvement of the distal acquired demyelinating symmetric (DADS) neuropathy phenotype, which shares some features with sensory chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), in a patient treated with the factor Xa inhibitor rivaroxaban for deep venous thrombosis (DVT). Case presentation Nerve conduction studies (NCS) revealed absent right median, ulnar, and radial sensory responses, and an absent right median motor response. The right ulnar, left peroneal, and left tibial distal motor latencies were prolonged (7.2, 10.0, and 13.0 ms, respectively), with preserved amplitudes (Fig. 1). Conduction block was not seen. The findings met the European Federation of Neurological Societies/Peripheral Nerve Society diagnostic criteria for atypical CIDP. The distal demyelinating pattern and clinical features including sensory ataxia and distal pattern of sensory deficits suggested DADS neuropathy. Repeat SPEP and IFE were negative. Serum anti-myelin-associated glycoprotein (MAG) antibody testing could not be performed due to financial constraints. The patient declined immunomodulatory treatment. Repeat NCS demonstrated reemergence of the previously absent median and radial sensory responses and median motor response. The right ulnar and left peroneal and tibial motor responses showed improved distal latencies of 6.3, 8.4 and 10.0 ms, respectively, with essentially unchanged amplitudes (Fig. 1).
Discussion In addition to its role in the coagulation cascade, factor Xa participates in the meclizine hcl through activation of proteinase-activated receptors and thrombin, leukocyte activation, recruitment of mast cells, T cell modulation, and potentiation of mononuclear cell proliferation [1]. Rivaroxaban is a direct factor Xa inhibitor used as an oral anticoagulant. Rivaroxaban's potential anti-inflammatory properties are currently being investigated by evaluating the effects of the medication on inflammatory markers in patients with sickle cell anemia [2], type 2 diabetes mellitus [3], and non-valvular atrial fibrillation [4]. DADS neuropathy shares features with the sensory variant of CIDP and is characterized by primarily distal demyelination. Sensory ataxia is the most common presentation of DADS neuropathy. The DADS-I (idiopathic) subtype is not associated with monoclonal gammopathy, as in this case, and may respond to immune therapy like classical CIDP. Pathological nerve damage in DADS neuropathy may be similar to classical CIDP [[5], [6], [7]]. Proposed mechanisms of nerve damage in CIDP include migration of activated T cells with breakdown of the blood-nerve barrier and defective suppressor regulatory T-cell function. Pro-inflammatory cytokines may mediate demyelination and axon loss [7,8]. Antibody to MAG is present in many DADS cases and may be a pathogenic factor [8,9]. Only 60–80% of patients with CIDP improve with current immunomodulatory therapies [8]. We report clinical and electrophysiologic improvement of DADS neuropathy in a patient receiving rivaroxaban for treatment of a DVT. While it is possible that the patient's remission was spontaneous (although data on the natural history of DADS neuropathy are scarce), 20–35% of patients with CIDP have a relapsing-remitting course [9], the proposed anti-inflammatory actions of rivaroxoban may have played a role. If so, to our knowledge, this would be the first report of a potential therapeutic response of an inflammatory condition to a factor Xa inhibitor.
Conclusions This case provides potential support to the hypothesis that factor Xa inhibition may be a strategy to reduce inflammation [[2], [3], [4]]. Post-marketing surveillance for remission or improvement of inflammatory disorders in patients receiving rivaroxaban, apixaban, or edoxaban as treatment for nonvalvular atrial fibrillation would be of clinical and scientific interest.