Educational draft · awaiting clinical reviewUse Rapid for revision, not patient-care decisions. Check current national and local guidance and the BNF or BNFC before acting.
2 min synopsisUK scopeSources checked 27 Aug 2026Clinical review pending
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Cryoglobulinaemic organ threat
Rapidly rising creatinine, pulmonary haemorrhage, mesenteric ischaemia, digital necrosis, severe motor neuropathy, hyperviscosity or widespread ulceration can progress before the causal laboratory work is complete.
Action: Admit under rheumatology with renal, haematology, hepatology or critical-care support as indicated; draw correctly handled cryoglobulin and infection samples, secure tissue diagnosis when safe, and begin severity-directed immunosuppression with cause-directed treatment without waiting for a delayed cryoglobulin result.
Synopsis
Recognise immune-complex vasculitis caused by circulating cryoglobulins, preserve specimen integrity, identify hepatitis, autoimmune and clonal drivers, and match antiviral, B-cell and plasma-exchange treatment to organ severity.
Cryoglobulinaemic vasculitis is a clinical syndrome, not simply a positive cryoglobulin test: look for palpable purpura, arthralgia, weakness, neuropathy, glomerulonephritis and acral ischaemia.
Type I disease is usually monoclonal and predominantly occlusive; mixed type II and III disease is immune-complex vasculitis associated with hepatitis C, autoimmunity or another chronic immune stimulus.
A false-negative cryoglobulin result is common when blood cools before clotting and serum separation; contact the laboratory before collection and keep the whole specimen at 37 degrees Celsius during pre-analytical handling.
Key red flags
Haemoptysis, falling haemoglobin, hypoxaemia or new bilateral alveolar shadowing suggests diffuse alveolar haemorrhage and requires immediate respiratory and vasculitis care.
Cryoglobulinaemic glomerulonephritis
Haematuria, proteinuria, hypertension, oedema and falling eGFR with complement consumption suggests an immune-complex membranoproliferative renal process.
Investigation priorities
01
Warm-handled cryoglobulin assay and immunotypingFirst step
Demonstrate a reversible cryoprotein and classify monoclonal or mixed composition.
Management branches
First diagnostic priorityPreserve the specimen and grade organs
Purpura, cold-related ischaemia, neuropathy or glomerular findings raise cryoglobulinaemic disease.
Contact the laboratory before venepuncture, obtain a warm-handled cryoglobulin sample and simultaneously draw complement, infection, autoimmune and monoclonal-protein tests.
Check urine, creatinine, pressure, oxygenation, haemoglobin, neurological power, perfusion and abdominal features to identify kidney, lung, nerve or bowel threat.
Cause-directed first stepEradicate active hepatitis C
HCV-associated disease is present with stable filtration and without nephrotic or rapidly progressive glomerulonephritis.
Key medicines
Glecaprevir 300 mg with pibrentasvir 120 mgGive three 100 mg/40 mg tablets orally together once daily with food; treatment is commonly 8 weeks in treatment-naive adults without decompensated cirrhosis, but duration and suitability must be set by the hepatitis service.
Rituximab intravenous infusionFor significant mixed cryoglobulinaemic vasculitis, a commonly studied specialist off-label regimen is 375 mg/m2 intravenously once weekly for 4 doses; an alternative protocol uses 1 g on days 1 and 15.
National guidance is shown before implementation-dependent detail. Typical adult dose examples remain subject to patient factors, contraindications and the live BNF or specialist protocol. Source check completed 27 Aug 2026; clinical approval remains outstanding.