Dysfibrinogenemia

Dysfibrinogenemia: Description, Causes and Risk Factors:Dys?brinogenemia is a coagulation disorder caused by a variety of structural abnormalities in the ?brinogen molecule that result in abnormal ?brinogen function. Fibrinogen is a large plasma protein composed of 2 identical subunits linked by disulfide bonds and divided into 2 outer D domains and a central E domain. Each subunit is formed by 3 polypeptide chains, A alpha,B beta, and gamma, encoded as separate genes on chromosome 4.DysfibrinogenemiaDysfibrinogenemia can thus result in impaired release of fibrinopeptides, defective fibrin polymerization, defects in fibrin cross-linking by factor XIII, or impaired fibrinolysis. The clinical presentation of dysfibrinogenemia can be a bleeding tendency, thrombophilia, impaired wound healing, or no clinically apparent disease.Dysfibrinogenemia can be either hereditary-transmitted as autosomal dominant trait or acquired.Most acquired dysfibrinogenemia are found in the setting of hepatocellular disease, including: cirrhosis, obstructive jaundice, acute liver failure,and hepatoma. The mechanism of acquired dysfibrinogenemia associated with liver disease involves impaired fibrin monomer polymerization. Dysfibrinogenemia in the setting of liver disease not associated with thrombosis. However thrombophilia associated with acquired dysfibrinogenemia without evidence of liver disease has been reported.Other Causes and Risk Factors May Include:Renal cell carcinoma.
  • Allogenic bone marrow transplantation.
  • Medications, includes: mithramycin and L-asparaginase.
  • Acquired dysfibrinogenemia has resolved with treatment of the underlying disease.
Inherited dys?brinogenemia is caused by mutations in the coding region of the ?brinogen A alpha, B beta, or gamma gene.The prevalence of inherited dys?brinogenemia among the general population is unknown; however, the prevalence among patients with a history of venous thrombosis is 0.8%. The pattern of inheritance is almost always autosomal dominant. Most patients have no history of bleeding or thrombosis (55%), while others develop bleeding (25%) or thrombosis (20%). Interestingly, 27% of patients who have had a thrombotic event also have a history of bleeding.Symptoms:Although many patients with inherited dysfibrinogenemia remain asymptomatic, signs that arise tend to be associated with poor wound healing, surgical wound dehiscence, and postsurgical bleeding out of proportion to that expected.Signs may include:Menorrhagia.
  • Postoperative bleeding.
  • Epistaxis.
  • Postoperative wound dehiscence.
  • Defective wound healing.
  • Bruising.
  • Severe hemorrhage (rare).
  • Mild soft-tissue hemorrhage.
Diagnosis:Tests may include:Thrombin clotting time: It is the primary test for dysfibrinogenemia. The thrombin time measures the rate of fibrin clot formation after the addition of a standard concentration of thrombin to citrated plasma. Thrombin cleaves the fibrinogen molecule, releasing 2 molecules of fibrinopeptide A and 2 molecules of fibrinopeptide B. The fibrin monomers are then free to polymerize and form the fibrin clot. Dysfibrinogenemia prolong the thrombin time by inhibiting fibrinopeptide release or by inhibiting fibrin monomer polymerization. However, the specificity of this test is poor. High or low fibrinogen level, amyloidosis, the presence of fibrin degradation products, radiocontrast agents, monoclonal immunoglobulin , acquired antibodies to bovine thrombin, and heparin have all prolong the thrombin time.
  • Reptilase time: the reptilase time is an alternative screening test. Reptilase is a snake venom, that cleaves fibrinogen in a manner that release only fibrinopeptide A. Dysfibrinogenemia prolongs the reptilase time by inhibiting fibrinopeptide release or inhibiting fibrin monomer polymerization. The reptilase time is unaffected by heparin, and it can therefore improve the specificity of this test.
  • Prothrombin time and partial thromboplastin time had sensitivities of 96% and 65% respectively, in detecting dysfibrinogenemia. However, despite their low cost and wide availability, their lack of specificity make them poor screening tests.
  • Confirmatory testing: Fibrinogen concentration measured both functionally and antigenically, then expressed as a fibrinogen activity-antigen ratio,can be used as a confirmatory test if the screening test is positive.
  • Other options include fibrinogen electrophoresis and molecular genetic analysis of the fibrinogen genes.
TESTING FOR INHERITED VERSUS AQUIRED CASES: After the presence of dysfibrinogenemia has been established, whether the abnormality is inherited or acquired must be determined. If the liver function tests (LVTs) are normal and acquired dysfibrinogenemia secondary to renal cell carcinoma, bone marrow transplant, or treatment with mithramycin or L-asparaginase has been excluded, then dysfibrinogenemia is likely inherited.Treatment:The majority of patients with dysfibrinogenemia do not required any specific treatment. Bleeding complications can be managed with transfusion of either plasma or cryoprecipitate. Patients with repeated venous thrombotic episodes may require long term antithrombotic therapy.Other Treatment Options May Include:Fresh frozen plasma (FFP) or cryoprecipitate may be transfused depending on the severity of the bleeding.
  • Patients with recurrent thrombotic events may require long-term anticoagulation with Coumadin or subcutaneous heparin.
  • Administration of prophylactic cryoprecipitate may prevent recurrent miscarriages.
  • Researchers described the use of fibrinogen concentrates to avoid pregnancy loss in women with dysfibrinogenemia. (The obstetric complications of dysfibrinogenemia include first-trimester pregnancy loss, along with hemorrhage, placental abruption, and thrombosis.). The investigators performed a retrospective study of 4 women from the same family, each of whom had dysfibrinogenemia and a history of recurrent pregnancy loss. The patients received fibrinogen concentrates from the start of pregnancy until delivery, with 3 of the 4 women achieving delivery.
NOTE: The above information is for processing purpose. The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition.DISCLAIMER: This information should not substitute for seeking responsible, professional medical care.

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