Characterization of Cryofibrinogen Isolated from Patients’ Plasma

Stathakis, N.; Koukoulis, Georgios; Tsianos, Epameinondas V.

doi:10.1159/000214404

Cited by 15 publications

(21 citation statements)

References 11 publications

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“…Cryofibrinogenemia is one such condition, and is a rare disorder arising from the presence of cold-precipitable plasma proteins associated with malignancies, inflammatory processes, and thrombohemorrhagic phenomena. Cryofibrinogen is composed of two proteins, fibrinogen and coldinsoluble globulin that form stable oligomers interlinked through gamma-gamma dimerization (Stathakis et al, 1981), suggesting FXIII transglutaminase activity has occurred. Diagnosis of cryofibrinogenemia in patients is based on clinical cutaneous manifestations, histopathology, and laboratory detection of cryofibrinogen precipitation.…”

Section: Discussionmentioning

confidence: 99%

Safety of Recombinant Human Factor XIII in a Cynomolgus Monkey Model of Extracorporeal Blood Circulation

Ponce¹,

Armstrong

Andrews

et al. 2005

Toxicol Pathol

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Factor XIII (FXIII) is a thrombin-activated plasma coagulation factor critical for blood clot stabilization and longevity. Administration of exogenous FXIII to replenish depleted stores after major surgery, including cardiopulmonary bypass, may reduce bleeding complications and transfusion requirements. Thus, a model of extracorporeal circulation (ECC) was developed in adult male cynomolgus monkeys (Macaca fascicularis) to evaluate the nonclinical safety of recombinant human FXIII (rFXIII). The hematological and coagulation profile in study animals during and after 2 h of ECC was similar to that reported for humans during and after cardiopulmonary bypass, including observations of anemia, thrombocytopenia, and activation of coagulation and platelets. Intravenous slow bolus injection of 300 U/kg (2.1 mg/kg) or 1000 U/kg (7 mg/kg) rFXIII after 2 h of ECC was well tolerated in study animals, and was associated with a dose-dependent increase in FXIII activity. No clinically significant effects in respiration, ECG, heart rate, blood pressure, body temperature, clinical chemistry, hematology (including platelet counts), or indicators of thrombosis (thrombin:antithrombin complex and D-Dimer) or platelet activation (platelet factor 4 and beta-thromboglobulin) were related to rFXIII administration. Specific examination of brain, heart, lung, liver, and kidney from rFXIII-treated animals provided no evidence of histopathological alterations suggestive of subclinical hemorrhage or thrombosis. Taken as a whole, the results demonstrate the ECC model suitably replicated the clinical presentation reported for humans during and after cardiopulmonary bypass surgery, and do not suggest significant concerns regarding use of rFXIII in replacement therapy after extracorporeal circulation.

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Section: Discussionmentioning

confidence: 99%

Safety of Recombinant Human Factor XIII in a Cynomolgus Monkey Model of Extracorporeal Blood Circulation

Ponce¹,

Armstrong

Andrews

et al. 2005

Toxicol Pathol

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“…It contains fibrin, fibrinogen, cold-insoluble globulin (fibronectin), albumin and im munoglobulins [37][38][39]. In adults, it is commonly found in association with malignancy or thrombo-embolic dis ease.…”

Section: Discussionmentioning

confidence: 99%

Cryoglobulinaemia and Cryofibrinogenaemia in IgA Nephropathy: A Follow-Up Study

Nagy

Ambrus

Paál

et al. 1987

Nephron

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Sera and plasmas from 50 patients with IgA nephropathy (IgA-NP) have been investigated for the presence of cryoglobulin (CG) and cryofibrinogen (CF), respectively, 2–5 cryoprotein determinations being made for each patient. CG was transiently found in 20 of 50 patients (40%), but in none of 20 healthy blood donors, whereas CF was found in 37 of 50 patients (74%) and in 4 of 20 healthy blood donors. The cryoprecipitates were of single and mixed component types. All but 2 of the patients with CF had haematuria. Nearly all of them had histories of long exposure to the cold as manual workers at the onset or recognition of their disease. There was no clinical remission during a 2-to-5-year follow-up if cryoproteinaemia persisted. A certain correlation was detected between the composition of the CP and the renal immunohistological findings. It is suggested that renal deposition of circulating CF or local formation of CF might be responsible for the tubulo-interstitial fibrocellular changes, which are of prognostic importance.

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“…1 Cryofibrinogen is a plasma protein complex composed of fibrinogen, fibrin, fibronectin and/or fibrin degradation products. 2 When cooled, cryofibrinogen can precipitate at 4°C and redissolve at 37°C. Cryofibrinogen can be detected only in the plasma, not in the serum, allowing the distinction between cryofibrinogen and cryoglobulin.…”

Section: Introductionmentioning

confidence: 99%

“…Fibronectin has been shown to bind to fibrin and fibrinogen, and acts as a nucleus for the cold-induced precipitation of fibrinogen-fibrin complexes in vitro. 2 Immunoglobins or immune complexes also may interact with fibronectin within the CF complex, forming an inflammatory component that may contribute to the thrombotic events in CF. 12,13 Additionally, increased plasma levels of protease inhibitors, α1-antitrypsin, and α2-macroglobulin have been found in patients with CF.…”

Section: Introductionmentioning

confidence: 99%

Untitled

Chen

Sreenivasan²,

Shojania³

et al. 2015

Exp Clin Transplant

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Cryofibrinogenemia is a rare disorder in which plasma, not serum, forms a cryoprecipitate. Patients with cryofibrinogenemia may be asymptomatic, or they may have painful ulcers, purpura, livedo reticularis, Raynaud phenomenon, perniosis of the extremities, thrombosis, and arthralgia. Cryofibrinogenemia may be primary or secondary to an underlying disorder such as connective tissue disease, malignancy, infection, drugs, or thromboembolic disease.Here, we present a 41-year-old woman with a pancreatic neuroendocrine tumor who underwent a Whipple procedure in 2003 followed by 2 liver transplants for hepatic metastases. Three years posttransplant, we discovered a biopsy-proven metastatic lesion in her femur. Five years posttransplant, she developed acute, severe pain in both feet, and was found to have cryofibrinogenemia despite immunosuppression posttransplant. Testing for connective tissue diseases and hematologic malignancy were negative. She was treated with high-dose prednisone, which completely resolved her symptoms. We also conducted a review of the literature via a PubMed search to summarize the association of cryofibrinogenemia with malignancy and treating cryofibrinogenemia with corticosteroids.Our study is the first reported case of cryofibrinogenemia that developed secondary to a neuroendocrine tumor posttransplant. Our report suggests that cryofibrinogenemia may occur despite immunosuppression adequate to prevent graft rejection, and that high-dose corticosteroids are an effective treatment for posttransplant cryofibrinogenemia.

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Characterization of Cryofibrinogen Isolated from Patients’ Plasma

Cited by 15 publications

References 11 publications

Safety of Recombinant Human Factor XIII in a Cynomolgus Monkey Model of Extracorporeal Blood Circulation

Safety of Recombinant Human Factor XIII in a Cynomolgus Monkey Model of Extracorporeal Blood Circulation

Cryoglobulinaemia and Cryofibrinogenaemia in IgA Nephropathy: A Follow-Up Study

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