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.
Index of Tests
Reptilase® Time [CO004500]
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
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
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
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,
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,