A low-dose therapy of fibrinogen supplement during perioperative period of total knee arthroplasty in an asymptomatic man with congenital dysfibrinogenemia: A case report.

RATIONALE: Congenital dysfibrinogenemia (CD) is a rare coagulation system disease that is often treated without unified management. Individualized treatment thereof presents clinicians with great challenges. PATIENT CONCERNS: A patient who was about to undergo total knee arthroplasty was found to have CD. DIAGNOSES: Coagulation screening revealed low fibrinogen, prolonged thrombin time, minor prolonged prothrombin time, and normal activated partial thromboplastin time were detected during admission, but no abnormal personal and family history findings were observed. Therefore, CD and hypofibrinogenemia were suspected. The gene sequencing confirmed the diagnosis of CD. INTERVENTIONS: The patient received plenty and low level of fibrinogen concentrate during 2 perioperative periods, respectively. OUTCOMES: Successful clinical outcomes were obtained using different treatment strategies. LESSONS: In contrast to prior case reports, this case illustrates the feasibility of low dosing of fibrinogen supplements within an asymptomatic patient in a selective operation. Changes in the level of fibrinogen and fibrin degradation product are of great importance for individualized treatment after supplementation.

A dysfibrinogenemia leading to resistance to bovine thrombin.

INTRODUCTION: A 26-year-old woman presented to our institute for a routine check-up. Nothing was abnormal excepted a prolonged Thrombin Time and a low fibrinogen concentration determined by the Clauss method. Fibrinogen concentration was then measured by PT-derived method, and revealed normal levels. This was therefore suggestive for a dysfibrinogenemia. The patient had no history of haemostatic problems and was under no medication. Her family history revealed nothing relevant, but death of her father from a cerebrovascular accident. METHODS AND RESULTS: Complementary tests were performed: Platelet Function Assay, Factor VIII coagulant activity, von Willebrand antigen quantification, Ristocetin Cofactor activity, thromboelastogram and euglobulin lysis time were all within normal ranges. Finally, thrombin time and Clauss fibrinogen using a human thrombin instead of a bovine thrombine revealed normal results. DNA was then extracted for sequencing the genes coding for fibrinogen. This revealed the presence of a substitution Arg>Cys in position 275 of the γ-chain of the fibrinogen. DISCUSSION: This mutation has already been reported in the literature with four cases of thrombosis, three cases of haemorrhage and eight had no clinical signs. The gamma chain is implicated in several crucial interactions such as the primary polymerization 'a', the binding to calcium, the factor XIIIa-induced cross-linking, the binding to plasminogen and to tissue plasminogen activator. Results of the literature show that this mutation has several impacts on in vitro tests, and we proved that those can be corrected by the use of human thrombin.

The role of urokinase in idiopathic pulmonary fibrosis and implication for therapy.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and frequently fatal form of interstitial lung disease for which there are no proven drug therapies. The pathogenesis of IPF is complex and the urokinase-type plasminogen activator (uPA)/plasminogen system participates in the repair process. The balance between the activating enzyme uPA, and its inhibitor PAI-1, is a critical determinant of the amount of scar development that follows. OBJECTIVE: To address the role of urokinase in the pathogenesis of pulmonary fibrosis and its implications for therapy. METHODS: We reviewed a spectrum of therapeutic strategies and focused on fibrinolytic and anticoagulant drugs for IPF patients. RESULTS/CONCLUSION: There is currently a search for new pharmacotherapeutic agents that may modulate the fibrogenic pathways in IPF. Either blocking PAI-1 or using uPA itself may be a promising new therapeutic strategy.

A gamma Gly-268 to Glu substitution is responsible for impaired fibrin assembly in a homozygous dysfibrinogen Kurashiki I.

A new type of gamma Gly-268 (GGA) to Glu (GAA) substitution has been identified in a homozygous dysfibrinogen by analyses of the affected polypeptide and its encoding gene derived from a 58 year-old man manifesting no major bleeding or thrombosis. The functional abnormality was characterized by impaired fibrin assembly most likely due to failure to construct properly aligned double-stranded fibrin protofibrils. This presumption was deduced from the following findings: (1) Factor XIIIa-catalyzed cross-linking of the fibrin gamma-chains progressed in a normal fashion, indicating that the contact between the central E domain of one fibrin monomer and the D domain of another took place normally; (2) Nevertheless, factor XIIIa-catalyzed cross-linking of the fibrinogen gamma-chains was obviously delayed, suggesting that longitudinal association of D domains of different fibrin monomers, ie, D:D association was perturbed; (3) Plasminogen activation catalyzed by tissue-type plasminogen activator was not as efficiently facilitated by polymerizing fibrin monomer derived from the patient as by the normal counterpart. Therefore, gamma Gly-268 would not be involved in the 'a' site residing in the D domain, which functions as a complementary binding site with the thrombin-activated 'A' site in the central E domain, but would be rather involved in the D:D self association sites recently proposed for human fibrinogen. Thus, the gamma Glu-268 substitution newly identified in this homozygous dysfibrinogen seems to impair proper alignment of adjacent D domains of neighboring fibrin molecules in the double-stranded fibrin protofibril, resulting in delayed fibrin gel formation.