Download G. Couto 1 CLINICAL APPROACH TO THE BLEEDING

CLINICAL APPROACH TO THE BLEEDING PATIENT
C. Guillermo Couto, DVM, dipl. ACVIM
Couto Veterinary Consultants, Hilliard, OH 43026
[email protected]
www.coutovetconsultants.com
The role of the hemostatic system is to maintain the fluidity of the blood (ie; prevent
intravascular coagulation) and prevent blood from escaping outside blood vessels when
injury occurs.
Physiology of Hemostasis for the Clinician
The hemostatic system interacts intimately with the vessel wall. Traditionally, the
hemostatic system is composed of four main arms: primary hemostasis, secondary
hemostasis, fibrinolysis, and natural anticoagulants. Primary hemostasis describes the interaction
between platelets and the vessel wall; secondary hemostasis describes the formation of fibrin
through activation of the coagulation cascade; and fibrinolysis refers to the lysis of a clot or
thrombus through activation of plasminogen into plasmin. The natural anticoagulants oppose the
effects of the components of the intrinsic, extrinsic, and common pathways. The secondary
hemostatic system is traditionally referred to as the "coagulation cascade", which is traditionally
composed of intrinsic, extrinsic, and common pathways.
Clinical Recognition of Hemostatic Disorders in Dogs and Cats
Dogs frequently present for evaluation of spontaneous bleeding tendencies detected by
the owner. A tendency towards excessive bleeding may also be discovered while performing
invasive procedures, such as venipuncture, catheterization, or surgery . In contrast to dogs, cats
with hemostatic disorders usually do not bleed spontaneously, but they tend to bleed excessively
during or shortly after surgery.
When evaluating a dog or cat with a spontaneous bleeding disorder, the information
obtained during history-taking and physical examination usually allows the clinician to differentiate
between disorders of primary and secondary hemostasis (see below). These disorders can then
be confirmed in the majority of the patients by performing simple tests.
As discussed above, the formation of the primary hemostatic plug (ie; vascular-platelet
interaction) is rapid, but short-lived. Therefore, the following occurs in a dog or cat with
thrombocytopenia or platelet dysfunction (or less frequently, with a vasculopathy): millions (or
billions) of endothelial cells die daily in normal individuals, thus exposing the subendothelium to
the circulating blood; in a normal animal, multiple primary hemostatic plugs will be formed,
preventing noticeable bleeding. In a dog or cat with a nonfunctional primary hemostatic plug,
blood starts exiting the superficial (and deep) blood vessels, and it does so during a few seconds
to minutes, until the permanent secondary hemostatic plug (ie; fibrin) is formed. This is analogous
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to what happens when one opens a faucet attached to an irrigator hose (one with multiple
perforations), allows the water to flow for a few seconds to minutes, and then closes it. Upon
examining the ground, the "blood vessel" (in this case the irrigator hose) is surrounded by small
"hemorrhages" (ie; puddles) along its course. These superficial "hemorrhages" along the course
of a "blood vessel" represent petechiae (pinpoint hemorrhages), ecchymoses (hemorrhages of
approximately 1 cm in diameter), or mucosal bleeding in a patient with thrombocytopenia or
platelet dysfunction. Therefore, in dogs and cats with primary hemostatic disorders, the typical
clinical findings include petechiae, ecchymoses, and bleeding from mucous membranes (eg
epistaxis, hematuria, melena, etc); in other words, superficial bleeding (Table 1). These patients
also tend to bleed immediately after venipuncture (ie; upon removing the needle).
In a dog or cat unable to form fibrin (ie; a defect in secondary hemostatic plug formation),
stretching or damage to a vessel wall results in minimal immediate bleeding. For example, upon
performing venipuncture there is almost no immediate bleeding, but the affected animal starts
bleeding profusely after a few minutes. This delayed-onset of bleeding occurs because the
platelet plug temporarily seals the defect (hole) in the blood vessel. However, because this
patient cannot generate fibrin, once the primary hemostatic plug is no longer functional, blood
starts to flow through the defect, and it continues to do so unimpaired, resulting in a large deep
hemorrhage. This is analogous to opening up a faucet connected to a regular garden hose, and
allowing for the water to run for several minutes to hours. Upon closing the faucet, rather than
having multiple small puddles (ie; petechiae and ecchymoses), there is a very large puddle at the
end of the hose (analogous to a hematoma around the defect in the blood vessel or bleeding into
a body cavity). In a patient with a secondary hemostatic defect, this translates into deep bleeding
(ie; formation of large hematomas or bleeding into body cavities)(Table 1). Dogs and cats with
congenital secondary hemostatic defects may also have a high frequency of abortions or
stillbirths, and high perinatal mortality.
Dogs and cats with mixed hemostatic
defects (primary plus secondary) develop a
combination of petechiae, ecchymoses, mucosal
bleeding, hematomas, and intracavitary bleeding.
Mixed hemostatic defects are almost exclusively
associated with DIC, and are common in dogs and
cat.
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Clinicopathologic Evaluation of the Bleeding Patient
Several laboratory tests are available to confirm a presumptive diagnosis in a dog or cat
with spontaneous or excessive bleeding. The screening (or cageside) tests will be discussed in
some detail, since they are frequently performed by the clinician. The routine laboratory tests for
hemostatic evaluation, as well as the specialized hemostatic tests used to confirm specific
defects will be briefly summarized, since they are typically performed by referral laboratories, and
thus, the methodology is not important for the clinician. With the recent development of in-house
hemostasis analyzers, the clinician now has the ability to perform cage-side evaluation of OSPT
and APTT (see below).
Screening (cageside) tests: Four rapid semiquantitative tests are available. These tests
allow for a rapid characterization of the defect as either a primary, secondary, or mixed
hemostatic defect; or as enhanced fibrinolysis. The four tests are: examination of the blood
smear, activated coagulation time (ACT), buccal mucosa bleeding time (BMBT), and
determination of FDPs (Table 2). Currently, the CoagDx (IDEXX Laboratories) is available for
point-of-care evaluation of one stage prothrombin time (OSPT) and activated partial
thromboplastin time (APTT).
Examination of the blood smear:
The first step in evaluating a dog or cat with a bleeding tendency, particularly if the
clinical signs are suggestive of a primary hemostatic defect, is to examine a good quality blood
smear. In normal dogs and cats, there are 10 to 25 platelets per field; each platelet in a
monolayer field under oil immersion is equivalent to approximately 15,000 platelets/µl (ie; number
of platelets/oil immersion field X 15,000= platelets/µl).
Activated coagulation time (ACT):
The ACT evaluates the ability of whole blood to clot when diatomaceous earth, a contact
activator, is added to the sample in a test tube. The test is performed by drawing 3 ml of blood in
a syringe (without anticoagulant) by atraumatic venipuncture; 1 ml of blood is discarded, and the
remaining 2 ml are placed in a tube containing diatomaceous earth (ACT tubes, Beckton
Dickenson). End-point is gelling of the blood. The ACT in normal dogs ranges from 60 to 90
seconds, and in cats is usually below 65 seconds.
Buccal mucosa bleeding time (BMBT):
This test evaluates the interaction between platelets and endothelium (or
subendothelium) that leads to formation of the primary hemostatic plug. After evaluating a blood
smear and making sure that the patient has a relatively normal platelet count, the BMBT is
performed using a template (Simplate II, American Diagnostics), that is used to make a small
incision of standard width and depth in the inner surface of the upper lip (ie; buccal mucosa).
Reference values for normal dogs and cats range from 1 to 3 minutes.
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Fibrin degradation products (FDPs):
Fibrin (fibrinogen) degradation products are formed when plasmin biodegrades one or
both of these coagulation proteins. The ThromboWelcoTest (Welcome Reagents Ltd,
Beckenham, England) is the most widely used assay for FDPs in dogs and cats, and it can be
easily performed in-house.
Routine Laboratory Tests: Several routine tests of hemostatic function are available in
most university and commercial diagnostic laboratories. In general, a hemostasis screen
(coagulation screen or coagulogram) is composed of five tests: a platelet count; the APTT, that
evaluates the intrinsic and common coagulation pathways; the OSPT, that evaluates the extrinsic
and common pathways; fibrinogen concentration; and determination of FDPs (or D-dimer). Some
referral laboratories also perform AT determinations.
In most laboratories, coagulation tests are performed using a concurrent control sample
of pooled canine or feline plasma. When interpreting the results of the APTT and OSPT, it is best
to compare them to the controls. Prolongation (or shortening) of more than 25% above (or below)
the control is considered clinically meaningful. In general, more than 70% decrease in the activity
of an individual clotting factor is necessary to result in prolongation of these assays.
Specialized Laboratory Tests: Some diagnostic laboratories specialized hemostasis can
perform specific assays, such as individual clotting factor determination, platelet function assays,
thromboelastography, etc. Properly collected samples should be mailed overnight (frozen or
refrigerated) to the laboratory for evaluation.
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Table 1: Clinical manifestations of primary and secondary hemostatic defects.
Primary Hemostatic Defect
Secondary Hemostatic Defect
petechiae, ecchymoses common
petechiae, ecchymoses rare
hematomas rare
hematomas common
bleeding from mucous membranes
bleeding into muscles,
joints, and body cavities
bleeding immediately after venipuncture
delayed bleeding after
venipuncture
From Couto CG: Disorders of Hemostasis. In Nelson R and Couto CG: Small Animal Internal
Medicine (5th Edition). Mosby, St. Louis. 2014.
(with permission from the author).
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Table 2: Simple cage-side test for the rapid classification of hemostatic disorders
Test
Most likely disorder/s if prolonged (or
positive)
platelet estimation in blood smear
thrombocytopenia
buccal mucosa bleeding time
thrombocytopenia, thrombocytopathia
activated coagulation time
intrinsic/common pathway defect
fibrin degradation products
DIC, rodenticide toxicity,
enhanced
fibrinolysis (rare)
From Couto CG: Couto CG: Disorders of Hemostasis. In Nelson R and Couto CG: Small Animal
Internal Medicine(4th Edition). Mosby, St. Louis. 2009. pp 1242-1259 (with permission from the
author).
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