Cryofibrinogenemia Summary Cryofibrinogenemia Epidemiology: • 40-70 years with a modest female predominance Cryofibrinogenemia: • The precipitation of a complex when plasma is cooled from the normal body temperature of 37°C to the near-freezing temperature of 4°C. • This precipitating complex contains fibrinogen, fibrin, fibronectin, small amounts of fibrin split products, albumin, immunoglobulins and other plasma proteins which can plug blood vessels. • Cryofibrinogen is distinguished from cryoglobulin (CG) since, it precipitates only in plasma and not in serum. • Cryoglobulins precipitate in serum + plasma Cryofibrinogen - Cryofibrinogen is a cold insoluble complex of: • Fibrin • Fibrinogen • Fibrin split products with: - Albumin - Cold insoluble globulin - Factor VIII - Plasma proteins Cryofibrinogenemia Symptoms: • Asymptomatic or combination of: - Hyperviscosity, - Vascular reactivity (Skin necrosis) - Thrombosis (Thrombotic vasculopathy) • Paradoxical spontaneous bleeding may occur due to the depletion of clotting factors Cryofibrinogenemia Can Be Divided Into Two Types: 1. Primary (essential) 2. Secondary form associated with autoimmune diseases, malignancies, vasculitis, sepsis or cryoglobulinemia Associated Disorders: • Malignancy • Infections including coronavirus disease 2019 (COVID-19) • Inflammatory processes: • Systemic rheumatic diseases • Thromboembolic conditions Cryofibrinogenemia Clinical Manifestations - Findings may include: • Cold sensitivity • Painful ulcers • Skin necrosis • Purpura • Livedo reticularis • Painful or pruritic erythema (perniosis) of the extremities • Arthralgias • Raynaud phenomenon • Simulates calciphylaxis clinicopathologically, - Related conditions: Stroke, myocardial infarction, limb and bowel ischemia or infarction, thrombophlebitis, pulmonary emboli, and ocular thrombi including retinal arterial and/or venous occlusions, as well as gangrene Cryofibrinogenemia Diagnosis: • + Clinical findings/Presentation • Asymptomatic: Plasma (CF) cryofibrinogen levels < than 50 mg/L - Significant levels >1g/L • Negative cryoglobulins • Negative causes of secondary cryofibrinogenemia. • Biopsy: Typical pathologic findings on biopsy of affected tissue • Angio: Occlusion of small to medium-sized arteries • Secondary CF: Presence of associated disease Cryofibrinogenemia DDX: • Calciphylaxis • Cryoglobulinemia • TTP, HUS and HIT • Antiphospholipid syndrome • Warfarin-induced skin necrosis • DIC • Septic emboli • Frostbite • Atherosclerotic PVD • Atheroemboli #Cryofibrinogenemia #diagnosis #rheumatology #hematology
