Fibrinogen [CO002800]
Related Information
Synonyms Factor I
Applies to Acute Phase Reactant; Afibrinogenemia; Dysfibrinogenemia;
Plasmin; Sedimentation Rate; Thrombin
Abstract Fibrinogen is converted into fibrin clot by thrombin.
Fibrinogen levels <100 mg/dL can be associated with bleeding.
Acquired decreases in fibrinogen (eg, with liver dysfunction or
DIC) are much more common than hereditary deficiencies.
Specimen Plasma
Container 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. Store plasma at room temperature for up to 2 hours, at
2degrees C to 8degrees C for up to 4 hours, or store frozen.
Causes for Rejection Specimen received more than 4 hours
after collection, tubes not filled, clotted specimen
Turnaround Time Less than 1 day
Reference Interval Approximately 150-400 mg/dL
Use One of several tests performed in a DIC panel, a prolonged
PT or PTT evaluation, and an evaluation of a patient with an unexplained
bleeding history
Limitations Heparin concentrations >0.6 units/mL can falsely
decrease the result with the Clauss method (described below). Usual
therapeutic doses of heparin do not significantly affect PT-based
methods. The Ellis method is more sensitive to heparin than the
Clauss method. Some reagents contain hexadimethrine bromide (Polybrene)
to neutralize heparin, allowing fibrinogen to be measured in specimens
containing heparin. Fibrin degradation products (FDP) >30-100
microg/mL may decrease fibrinogen values with the Clauss method.
Hirudin or argatroban anticoagulation may falsely decrease fibrinogen
levels levels with the Clauss and Ellis method, and possibly the
PT-based method.
Methodology
Functional (activity) assays: The majority of clinical laboratories
use the Clauss1 method, which is essentially a
dilute thrombin time. A high concentration of thrombin is added
to dilute patient plasma, which converts fibrinogen into fibrin
clot. The clotting time is inversely proportional to the amount
of fibrinogen in the sample. In the Ellis2method,
a lower amount of thrombin is added to undiluted patient plasma
and change in turbidity is measured in a spectrophotometer. In the
PT-based method,3,4 thromboplastin (tissue factor
with phospholipid) is added to undiluted patient plasma to generate
endogenous thrombin, and light scatter or turbidity is measured.
The measured optical change (before and after fibrin clot formation)
is proportional to the amount of fibrinogen in the sample.
Antigen assays (immunoassays) for fibrinogen measure the
quantity of fibrinogen without assessing fibrinogen function. This
method is not routinely indicated and is usually a send-out test
(see Additional Information for its use in dysfibrinogenemia evaluations).
Additional Information Fibrinogen decreases with liver disease,
due to decreased hepatic synthesis. However, fibrinogen may be normal
or even elevated until late stages of hepatic disease. Fibrinogen
decreases in DIC due to excessive thrombin generation, which converts
fibrinogen into fibrin. Fibrinogen also decreases with thrombolytic
therapy and fibrinolysis because plasmin breaks down fibrinogen
in addition to fibrin.
Fibrinogen becomes elevated during acute phase reactions and during
pregnancy. As with certain other acute phase reactants (eg, C-reactive
protein), elevated fibrinogen has been associated with an increased
risk of myocardial infarction.5
Hereditary deficiencies of fibrinogen are rare. The PT and PTT
may be prolonged. Bleeding symptoms may include bruising, epistaxis,
menorrhagia, bleeding with surgery, trauma, dental extractions,
and postpartum, and bleeding in the gastrointestinal or genitourinary
tract. Miscarriage and poor wound healing are also complications
of fibrinogen deficiency. Umbilical stump bleeding and bleeding
with circumcision may be noted in newborns with afibrinogenemia.
Intracranial hemorrhage has been reported with afibrinogenemia.6,7,8
In general, deficiencies of fibrinogen tend to be milder than factor
VIII or IX deficiencies (hemophilia).
There are three major types of fibrinogen deficiency. The homozygous
quantitative form, called afibrinogenemia, results in a severe quantitative
deficiency of fibrinogen and an increased risk for bleeding. The
heterozygous form of this deficiency is hypofibrinogenemia, with
less severe reductions in the fibrinogen level and little or no
bleeding.7 Fibrinogen consists of two copies of each
of three polypeptide chains called alpha, beta , and gamma . Among
the afibrinogenemia mutations that have been characterized thus
far, most have been found in the alpha-fibrinogen chain gene.9
Dysfibrinogenemia is a qualitative fibrinogen deficiency,
characterized by the production of dysfunctional fibrinogen.6,8,10
Many different mutations are known to cause hereditary dysfibrinogenemia.
Most patients with hereditary dysfibrinogenemia are heterozygous.
Rare homozygous cases have been reported. Dysfibrinogenemia patients
are usually asymptomatic or have mild bleeding, but severe bleeding
has been reported. Interestingly, some dysfibrinogenemia cases are
associated with thrombosis, with or without bleeding. Dysfibrinogenemia
has an estimated prevalence of 0.8% in patients with venous thrombosis.6
Arterial thrombosis is less frequent than venous thrombosis in these
patients. Acquired forms of dysfibrinogenemia, of uncertain clinical
significance, can be seen with liver disease or acute phase reactions
with generation of high levels of fibrinogen (Galanakis D, personal
communication 1999). The thrombin time and Reptilase® time,
which measure the clotting time during the conversion of fibrinogen
into fibrin, are often prolonged in dysfibrinogenemia. The PT and
PTT may also be prolonged. In dysfibrinogenemia, 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. This potentially
diagnostic disparity between functional and antigen levels may be
less pronounced with PT-based functional fibrinogen assays than
with Clauss-based functional assays.3 See Table 3 in
Coagulation Factor Assays.
See Thrombin Time.
Footnotes
1. Clauss A, "Rapid Physiological Coagulation Method for the Determination
of Fibrinogen [German],"Acta Haematol, 1957, 17:237-46.
2. Ellis BC and Stransky A, "A Quick and Accurate Method for the
Determination of Fibrinogen in Plasma,"J Lab Clin Med, 1961,
58:477-88.
3. Rossi E, Mondonico P, Lombardi A, et al, "Method for the Determination
of Functional (Clottable) Fibrinogen by the New Family of ACL Coagulometers,"Thromb
Res, 1988, 52(5):453-68.
4. Tan V, Doyle CJ, and Budzynski AZ, "Comparison of the Kinetic
Fibrinogen Assay With the von Clauss Method and the Clot Recovery
Method in Plasma of Patients With Conditions Affecting Fibrinogen
Coagulability,"Am J Clin Pathol, 1995, 104(4):455-62.
5. Ma J, Hennekens CH, Ridker PM, et al, "A Prospective Study of
Fibrinogen and Risk of Myocardial Infarction in the Physician's
Health Survey,"J Am Coll Cardiol, 1999, 33(5):1347-52.
6. 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.
7. Al-Mondhiry H and Ehmann WC, "Congenital Afibrinogenemia,"Am
J Hematol, 1994, 46(4):343-7.
8. Galanakis DK, "Fibrinogen Anomalies and Disease. A Clinical
Update,"Hematol Oncol Clin North Am, 1992, 6(5):1171-87.
9. Neerman-Arbez M, de Moerloose P, Bridel C, et al, "Mutations
in the Fibrinogen Aalpha Gene Account for the Majority of Cases
of Congenital Afibrinogenemia,"Blood, 2000, 96(1):149-52.
10. 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.
References
Giangrande PLF, "Other Inherited Disorders of Blood Coagulation,"Haemophilia
and Other Inherited Bleeding Disorders, Rizza C and Lowe G,
eds, London: WB Saunders Co, 1997, 291-307.
|
