From: Elizabeth M. Van Cott, M.D., and Michael Laposata, M.D., Ph.D., “Coagulation.” In: Jacobs DS et al, ed. The Laboratory Test Handbook, 5th Edition. Lexi-Comp, Cleveland, 2001; 327-358.
Related Information
D-Dimers and Fibrin Degradation Products
Fibrinogen
Hypercoagulation Panel
Thrombin Time
Abstract Clotting time similar to thrombin time except that a snake venom (Reptilase®) is used instead of thrombin. The Reptilase® time is prolonged by decreased or dysfunctional fibrinogen, or high levels of fibrin degradation products (FDP). Dysfibrinogenemia is an uncommon hereditary or acquired condition characterized by dysfunctional fibrinogen.
Specimen Plasma
Container One blue top (sodium citrate) tube
Collection Routine venipuncture. If multiple tests are being drawn, draw blue top tubes after any red top tubes but before any lavender top (EDTA), green top (heparin), or gray top (oxalate/fluoride) tubes. Immediately invert tube gently at least 4 times to mix. Tubes must be appropriately filled. Deliver tubes immediately to the laboratory.
Storage Instructions Separate plasma from cells as soon as possible. Plasma may be stored at room temperature or on ice for up to 8 hours; otherwise, store frozen.
Causes for Rejection Specimen received more than 4 hours after collection, tube not filled, clotted specimens
Turnaround Time Less than 1 day
Reference Interval 16-24 seconds
Use Performed with thrombin time to diagnose dysfibrinogenemia in patients undergoing evaluation for hypercoagulability and/or a bleeding tendency. Often performed only if an initial panel of tests excludes more common disorders, as dysfibrinogenemia is uncommon. Unlike the thrombin time, Reptilase® time is not prolonged by heparin or hirudin.
Methodology Reptilase® is added to patient plasma and the clotting time is measured in seconds. Reptilase® cleaves fibrinogen, releasing fibrinopeptide A from fibrinogen and converting fibrinogen into fibrin clot. In contrast, when thrombin cleaves fibrinogen, fibrinopeptide A and fibrinopeptide B are both released from fibrinogen.
Additional Information Many different mutations are known to cause hereditary dysfibrinogenemia. Dysfibrinogenemia mutations can cause bleeding, thrombosis, or both, or they may be clinically asymptomatic. If bleeding is present, it is usually mild, but severe bleeding has been reported. Dysfibrinogenemia has an estimated prevalence of 0.8% in patients with venous thrombosis.1 Arterial thrombosis is less frequent than venous thrombosis in these patients. Most patients with hereditary dysfibrinogenemia are heterozygous. Rare homozygous cases have been reported. The Reptilase® time and thrombin time, which measure the clotting time during the conversion of fibrinogen into fibrin, are often prolonged in dysfibrinogenemia because fibrinogen is dysfunctional. Assays that measure fibrinogen function show lower levels than assays that measure fibrinogen quantity (immunological or “antigen” assays), because fibrinogen function is impaired but fibrinogen quantity is not. The PT and PTT may be prolonged in dysfibrinogenemia.1,2,3 Causes of acquired dysfibrinogenemia include liver disease, hepatoma,3 or acute phase reactions with generation of high levels of fibrinogen.4 The bleeding and thrombosis risk with acquired dysfibrinogenemia is uncertain. Prolongation of the thrombin time and Reptilase® time has been commonly observed with amyloidosis due to inhibition of fibrinogen conversion to fibrin.5
Footnotes
1. Haverkate F and Samama M, “Familial Dysfibrinogenemia and Thrombophilia. Report on a Study of the SSC Subcommittee on Fibrinogen,”Thromb Haemost, 1995, 73(1):151-61.
2. Cote HC, Lord ST, and Pratt KP, “gamma -Chain Dysfibrinogenemias: Molecular Structure-Function Relationships of Naturally Occurring Mutations in the gamma Chain of Human Fibrinogen,”Blood, 1998, 92(7):2195-212.
3. Galanakis DK, “Fibrinogen Anomalies and Disease. A Clinical Update,”Hematol Oncol Clin North Am, 1992, 6(5):1171-87.
4. Galanakis DK, personal communication, 1999.
5. Gastineau DA, Gertz MA, Daniels TM, et al, “Inhibitor of the Thrombin Time in Systemic Amyloidosis: A Common Coagulation Abnormality,”Blood, 1991, 77(12):2637-40.
