FIBRINOGEN
There are three main proteins in the blood: Albumin, Globulin and Fibrinogen. These
three proteins make up the Total Protein. Plasma contains all three proteins while serum
contains only the albumin and globulin; the fibrinogen having been used and retained in the
blood clot. If the TP is measured by refractometer using the plasma from a microhematrocrit
tube or a QBC tube, the fibrinogen is present. If the TP determination is done from an SS or
red top tube, the fibrinogen is not present and the subtraction of the albumin from the TP
gives an accurate measurement of the globulin.
Fibrinogen is produced in the liver just as the albumin and alpha globulin's are
(beta and gamma globulin's increase in chronic conditions from antigenic stimulation).
Fibrinogen occurs in smaller amounts than the other body proteins.
Normals:
Dog:0.1-0.25g/dl Cat:0.1-0.25g/dl Horse: 0.1 -0.4 g/dl
Bovine: 0.1 -0.5g/dl
100-250 mg/dl
100-250 mg/dl
100-400 mg/dl
200-500 mg/dl
In its every day use, fibrinogen is part of the coagulation cascade. On a daily basis,
fibrinogen, platelets and von Willebrand's Factor repair the inner surface of the constantly
wearing blood vessels. The loss of fibrinogen will result in the inability of the blood to clot
properly. This happens in only two cases. First, a total liver failure may reduce the production
of fibrinogen. In this case, albumin, TP and BUN will also be reduced (BUN is made in the
liver by converting ammonia produced in the intestinal tract during digestion and sent to the
liver for transformation ). The other condition is called DIC: disseminated intravascular
coagulapathic disease. DIC, in domestic animals, has a relatively low incidence and usually
presents as a secondary disease following recovery from a severe inflammatory condition (i.e.
Parvo, Virus). In the DIC, the body begins to attempt to clot blood in spite of a
non-hemorrhagic situation. The clots are only partly formed and break down causing a rapid
loss of both fibrinogen and platelets. A fibrinogen markedly below the normal (<60 mg/dl)
and low platelets with the patient bleeding is typical of DIC. DIC is usually fatal unless found
early and treated aggressively. It is only the concurrent low fibrinogen that clinically defines
DIC from other thrombocytopenias. The disease process is rapid and early diagnosis is
essential. Waiting for outside laboratory confirmation is fatal.
The more common use of a fibrinogen measurement is as a first phase inflammatory
marker. In all species, fibrinogen increases begin within 24 hours of tissue injury. The
amount of the fibrinogen response is different in each species but usually proportional to the
amount of inflammation. In an acute condition, the amount of fibrinogen increases and the
longer it remains increased, the more guarded the prognosis becomes. In a favorable
response, the fibrinogen rapidly returns to normal ranges. In chronic disease, the fibrinogen
increases and remains increased as long as the disease is present.
In human medicine, the erythrocytic sedimentation rate (ESR) is commonly used as a
marker for disease presence and indications of the seriousness of that disease. The ESR is
most influenced by fibrinogen. Fibrinogen is a large molecule that draws RBC's to
it. The RBC/fibrinogen mass is heavier than a single RBC and, thus, falls faster in a standing
column. The ESR is complete and read after one hour in human medicine. Because of its ease
of measurement and reproducibility in the VetAutoRead™ systems, it has been proposed to
use the fibrinogen as a substitute for ESR in human medicine. The ESR has seldom been used
in veterinary medicine because of the wide species differences ( i.e. horse 30 min., cat & dog
I hr., cow 24 hr.). Fibrinogen has always been used as an inflammatory marker in veterinary
medicine instead of the ESR but, in the past, its use has been limited by the poor accuracy of
the traditional heat precipitation methods or the expense and time interval of receiving results
from the programmed analyzers.
The heat precipitation method has been the standard method of producing a fibrinogen
in veterinary medicine. Two microhematocrit tubes are prepared from an EDTA blood and
spun down. A total protein is read on the refractometer from one specimen. The other
specimen is then subjected to 56"s of heat in a water bath for 5 minutes to precipitate the
fibrinogen from the other proteins. The tube is re-spun for 5 minutes to separate the
precipitated fibrinogen from the albumin and globulin. The remaining plasma is then read on
the refractometer. The difference between the first and second specimens is the fibrinogen.
Because the refractometer can only read in 100 mg/dl units, any reading between 100 units of
fibrinogen is purely interpretive. Therefore repeatability is poor, small reactions are not
recognized and low fibrinogens are not identifiable. Only in a species where very high
fibrinogen reactions are seen during disease, like the horse and cow, has fibrinogen enjoyed
any popularity. Its value in the cow is most recognized because the cow shows little WBC or
Hct reaction in response to disease states. With both these inflammatory parameters showing
little change and no practical ESR, the fibrinogen is of great value to bovine practitioners. The
horse, whose WBC responses to disease, while greater than the cows, are far from impressive.
Therefore, the horse has also been a subject for fibrinogen measurements. The dog and cat
have been sadly neglected where fibrinogen measurements are involved. The importance of
fibrinogen is just as great in these animals as the horse and cow but external laboratories do
not report fibrinogen as part of the blood count and, when asked, charge an additional fee for
its measurement. Because the changes in dog and cat fibrinogen are not as high as that seen in
the horse and even more so in the cow, crude measures of fibrinogen give little information. In
recent years, many veterinary schools are now reporting fibrinogen as part of the homeroom.
Dr. Bernie Feldman (Virginia-Maryland Regional College of Veterinary Medicine) and Dr.
John Harvey (U of FD, College of Veterinary Medicine) are among the veterinary
hematologist's who support the reading of fibrinogen with every blood count.
Fibrinogen increases in the cow are commonly in the area of 1000 mg/dl and can go
>2000 mg/dl in severe inflammations. In the horse, while fibrinogens are high, they do not
reach the limits of the cow. A past study done on the horse showed that horses with
fibrinogens under 800 mg/dl are liable to cure while those with fibrinogens >800 mg/dl are
more likely to die or be euthanized. In inflammation, dog and cat fibrinogens are lower than
the cow or horse. Fibrinogens in the 400 - 500 mg/dl range are seriously high, while >250 400 mg/dl are commonly seen in the average inflammatory disease state. The value of the
fibrinogen is dramatic in conditions like chronic infections where destruction and replacement
of WBC's have balanced over the elongated disease course and returned to normal numbers
but the fibrinogen remains high indicating the need to continue treatment
or surveillance. Another remarkable use is to identify a non-specific inflammation after all
other routine biochemical and hematological results have analyzed normal. It gives the
practitioner a positive result which can be shown to the owner and a reason to continue the
investigation.
Causes for increased fibrinogen include but are not limited to:
Viral & Bacterial Infections
Traumatic Injuries
Malignancies
Kidney Disease
Surgery
Heart Disease
Post Abortion
Some Poisons
*Pregnancy
*circulating malignancies with no solid tumor state may have normal fibrinogens
Pregnancy in the dog can be determined at 28 to 30 days after breeding by
Fibrinogen levels. Significant levels occur at that time. After 30 days, levels begin to
decrease but usually do not reach normal until after 50 days.
Fibrinogen is the best and simplest inflammatory parameter to use in veterinary
medicine. In the QBC VetAutoRead System™, it is done by a modern, repeatable heat
precipitation method that can report accurate results in both the high and low ranges in all
species.
NORMAL
HIGHWBC
HIGH
WBCWBC
>17.5
> are
17.5
5.0-17.5
HIGH
NORMAL
HIGH
FIBRINOGEN
FIBRINOGEN
FIBRINOGEN
>250
> 250
mg1dl
100-250
mg/dI mg/dl
The following
from a collection
of dogs
that were
presented
at our hospital in a 10-day period. The most
Pneumonia
= 14 and the dogs with
Chronic
Tumor
Infection in which
===444 inflammationKidney
important groups are
the pre-surgeries
was notDisease
primarily suspected
Autoimmune
Myosists
= 81 high100-250
ATPcounts
&OUO
AU-IA
=4
LOW
5.0 Periodontal
HIGH
Disease
FIBRINOGEN
=
mg/dl
Fever
normalWBC
WBC< counts
and high
fibrinogens.
The
or low WBC
with high fibrinogens
confirms
Tumors
==324
Trauma
Hepatic
Parvo Disease
CNS
FUO(Unknown Origin)
= 2 ==21
inflammation.
Pancreatitis
===14 1
Myasthenia
Gravies = 1 = 1
Respiratory
Renal Failure
Malignancies
Vomiting/diarrhea
=
3
Infections
=4
LOW FIBRINOGEN
100-50
mg/dI
SURVEY = 122 Dogs (From Pre-Surgicals)
Hepatic
Disease
DICPeriodontal Disease == 35
Total
Liver Failure
= =2
1
WELL DOGS = 107
SICK DOGS = 15
DISTRIBUTION (Well)
<100 mg/dl
100-150 mg/dl
150-200 mg/dl
200-250 mg/dl
>250 mg1dl
=2
= 27
= 52
= 25
=1
RANGE = 99 - 252 mg/dl
DISTRIBUTION (SICK): 255 - 349 mg/dl
CAUSES (Sick): 15 [ Two dogs with more than I problem
DENTAL'S (Infection)
CNS Disease
Hemangiopericytoma
Inflammatory Bowel Disease
Tumor (Thoracic/abdominal)
Cystitis
=7
=1
=2
=1
=3
=3
[5 with normal WBC's]
DOGS PRESENTED FOR ILLNESS 85 Cases
NORMAL WBC 5.0-17.5 NORMAL FIBRINOGEN 100-250 mg/dl
Heartworm
=2
D3D
Muscular Degeneration = 1
Cough
Not III
=1
Tumors
Anorexia,
=1
Cardiac
=1
=1
= 3 (Benign)
=1
CARDIAC
CHRONIC DISEASE
FIBRINOGEN SUMMARY
In general, it has been noted that the higher the fibrinogen, the more guarded the
PREGANACY
CANCER
IN DOGS
prognosis.
INCREASES:
SEDMIENTATION RATE REPLACEMFENT
INFLAMMATION
Bacterial
DECREASES: Viral
Traumatic
DIC