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Background This project was undertaken to review patients testing positive for cryoglobulins. We wanted to establish the numbers of patients with different types of cryoglobulins, to determine whether there were any shared characteristics and whether there was any consensus on management. Methods Retrospective review of records of Sheffield Teaching Hospital patients testing positive for cryoglobulins January 2014-December 2018. Results 374 cryoglobulin tests were requested. 43 were positive (in 33 patients).There were 9 Type I cryoglobulins, including IgG and IgM lambda and kappa. Titres ranged from 0.07-47.5g/L. All patients had an underlying haematological condition. 2 patients had rash and 1 acute kidney injury (AKI), but there were no other clinical features of cryoglobulinaemia. 1 patient received treatment for cryoglobulinaemia secondary to MGUS with prednisolone, plasma exchange and Velcade/Thalidomide/Dexamethasone. Otherwise the cryoglobulins appear to be a laboratory finding with minimal clinical significance.There were 17 Type II cryoglobulins in 12 patients. The most common pattern was IgM kappa monoclone with polyclonal immunoglobulin (71%). Titres ranged from 0.03-5.4g/L. Patients’ underlying conditions were malignant, infective and inflammatory. 7 patients had rash, 2 arthralgia/arthritis, 4 Raynaud’s, 3 paraesthesia and 2 AKI. The presence of cryoglobulins was not considered significant in 5 patients (titres 0.03-0.39g/L). 3 patients were treated for underlying malignancy or infection and cryoglobulins monitored. 2 patients (titres 0.16 and 1.97g/L) were treated for renal disease in the presence of cryoglobulins with prednisolone and Rituximab in 1 case and prednisolone, Cyclophosphamide and plasma exchange in the other. 2 patients were diagnosed with cryoglobulinaemic vasculitis (titres 0.5g/L and 0.03g/L). 1 was treated with prednisolone and Azathioprine. The other had previously been treated with prednisolone and cyclophosphamide, then azathioprine maintenance therapy; the relapse during this study period was treated with methylprednisolone, plasma exchange and Rituximab.There were 16 Type III cryoglobulins in 14 patients. By definition all had polyclonal immunoglobulins. Titres ranged from 0.06-4.64g/L. Patients’ underlying conditions were malignant, infective and inflammatory. 7 patients had rash, 4 arthralgia/arthritis, 2 paraesthesia and 1 AKI. The presence of cryoglobulins was not thought significant in 5 patients (titres 0.08 to 0.45g/L). 7 patients were treated for underlying infection or rheumatological condition and the cryoglobulins monitored. 1 patient (already reported in the Type II section) was treated for renal disease in the presence of cryoglobulins. 1 patient (titre 0.12g/L) with a diagnosis of cryoglobulinaemic vasculitis was treated with prednisolone and azathioprine, then mycophenolate. Conclusion The study confirms that cryoglobulins are rare and that clinically significant disease related to them is even rarer. Given the small numbers it is difficult to identify strong trends in presentation or treatment. However, it does show that higher cryoglobulin titres do not correlate with higher rates of disease activity in terms of cryoglobulinaemia or cryoglobulinaemic vasculitis. Disclosures: R. Smith: None. G. Wild: None. S. Carter: None.

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