Cryofibrinogenemia: new insights into clinical and pathogenic features.
OBJECTIVE
Cryofibrinogenemia is an under-recognized cryoprotein that can be life-threatening when untreated. Our aim was to describe the prevalence and clinical findings of patients with cryofibrinogenemia and to clarify the mechanisms involved.


METHODS
Between 1996 and 2006, 2312 patients were tested for cryofibrinogenemia in a single university hospital. A total of 515 patients had positive test results, of whom 455 (88.3%) had an associated cryoglobulin.


RESULTS
Sixty patients (11.7%) with persistent cryofibrinogenemia and without cryoglobulin were included in the study. Main clinical manifestations related to cryofibrinogenemia included purpura (46.6%), skin necrosis (36.6%), and arthralgia (31.6%) with cold sensitivity in 40%. Overall thrombotic events occurred in up to 40% of cases. Cryofibrinogen plasma concentration was 2 times greater in patients with thrombotic events (P=.012). Complications included gangrene (5%), septicemia (5%), and leg amputation (3.3%). Complete remission of cryofibrinogenemia was achieved in 78% of patients receiving antithrombotic agents, steroids, or immunosuppressants, whereas 41.6% of patients experienced a relapse after a median time of 9 months (range 7-42 months). After a mean follow-up of 85 months, 3 patients died of sepsis (n=2) and cardiovascular disease (n=1). Fibrinolysis status analyzed in a patient with cryofibrinogenemia showed an increase in fibrinolysis inhibitor levels, plasminogen activator inhibitor-1, alpha-2 macroglobulin, and euglobulin lysis time, which normalized after fibrinolytic therapy.


CONCLUSIONS
Essential cryofibrinogenemia represents 12% of all the cryoproteins at Pitie-Salpêtriere Hospital. Thrombotic events are frequent and could be associated with the amount of plasma cryofibrinogen. Defects in the fibrinolysis process might lead to cryofibrinogen accumulation and clotting in small and medium arteries.
Saadoun
David
D
Pierre et Marie Curie-Paris 6 University, Department of Internal Medicine, Hôpital Pitié-Salpétrière, Paris, France.
Elalamy
Ismail
I
Ghillani-Dalbin
Pascale
P
Sene
Damien
D
Delluc
Aurelien
A
Cacoub
Patrice
P
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000671:Amputation, Surgical / Q000706:statistics & numerical data; D018771:Arthralgia / Q000453:epidemiology; D003080:Cold Temperature / Q000009:adverse effects; D003449:Cryoglobulinemia / Q000175:diagnosis* / Q000453:epidemiology / Q000209:etiology / Q000628:therapy*; D003450:Cryoglobulins / Q000032:analysis; D005260:Female; D005342:Fibrinolysis; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D005734:Gangrene; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007866:Leg / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D010956:Plasmapheresis; D017395:Plasminogen Activator Inhibitor 1; D011693:Purpura / Q000453:epidemiology; D011928:Raynaud Disease / Q000453:epidemiology; D012008:Recurrence; D012074:Remission Induction; D018805:Sepsis / Q000453:epidemiology / Q000401:mortality; D012712:Serum Globulins / Q000378:metabolism; D012867:Skin / Q000473:pathology; D013927:Thrombosis / Q000453:epidemiology; D014581:Urticaria / Q000453:epidemiology; D000511:alpha-Macroglobulins / Q000032:analysis
D000305:Adrenal Cortex Hormones; D003450:Cryoglobulins; D005343:Fibrinolytic Agents; D007166:Immunosuppressive Agents; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D012712:Serum Globulins; D000511:alpha-Macroglobulins