Page 1416 - Small Animal Internal Medicine, 6th Edition

1388 PART XIII Hematology

by the platelet plug; once it has been activated, fibrin, or the • Has the patient had any surgeries before this and, if so,
secondary hemostatic plug, forms. Prekallikrein (Fletcher did it bleed excessively? If the pet has had previous bleed-
VetBooks.ir factor) and high-molecular-weight kininogen (HMWK) ing episodes during elective surgeries as a young animal,
a congenital coagulopathy is suspected.
are important co-factors for factor XII activation. The role
of the contact phase of coagulation in vivo is questionable.
litter have an increased perinatal mortality rate? These
The secondary hemostatic plug is stable and long-lasting. • Do any littermates have similar clinical signs? Did the
In addition, whenever tissue trauma occurs, the release of findings also support a congenital coagulopathy.
tissue procoagulants (collectively referred to as TF) results in • Has the animal recently been vaccinated with modified-
activation of the extrinsic coagulation cascade, also leading live vaccines? Modified-live vaccines can cause thrombo-
to the formation of fibrin (see Fig. 87.2). As discussed earlier, cytopenia, platelet dysfunction, or both.
all these steps occur almost simultaneously, and fibrin for- • Is the patient currently receiving any medication that may
mation starts within seconds of the endothelial damage. TF cause thrombocytopenia or platelet dysfunction (e.g.,
is ubiquitous and present on the membrane of most cells, nonsteroidal antiinflammatory drugs [NSAIDs], sulfas,
with the exception of normal endothelium. As noted, this antibiotics, phenobarbital)?
pathway is now thought to be responsible for initiating clot- • Does the patient have access to rodenticides or does it
ting in mammals. roam freely? This may indicate rodenticide toxicity.
The stimuli that activate coagulation also activate the
fibrinolytic and kinin pathways. Fibrinolysis is extremely The clinical manifestations of primary hemostatic abnor-
important as a safeguard mechanism because it prevents malities are different from those of secondary hemostatic
excessive clot or thrombus formation. When plasmin lyses abnormalities (Box 87.1). The clinician should be able to
fibrinogen and fibrin, it generates fibrin degradation prod- classify the type of coagulopathy on the basis of the physical
ucts (FDPs), which impair additional platelet adhesion and examination findings before submitting any samples for
aggregation in the site of injury. Once fibrin has been sta- clinicopathologic evaluation. This is easy to conceptualize by
bilized by complexing factor XIII, plasmin biodegradation thinking about the normal coagulation mechanisms. For
generates D-dimers instead. The activation of plasminogen example, a functional primary hemostatic plug cannot form
into plasmin results in the destruction (lysis) of an existing in a cat or dog with severe thrombocytopenia or platelet
clot (or thrombus) and interferes with the normal clotting dysfunction. Because this plug is short-lived and eventually
mechanisms—inhibition of platelet aggregation and clot- covered with fibrin (generated through the secondary hemo-
ting factor activation in the affected area. Therefore exces- static mechanisms), the patient experiences multiple, short-
sive fibrinolysis usually leads to spontaneous bleeding. Two lived bleeds that are arrested as soon as fibrin is formed,
molecules stimulate plasminogen activation into plasmin, resulting in multiple small and superficial hemorrhages
tissue plasminogen activator (tPA) and urokinase-type plas- around blood vessels. This is analogous to turning on and off
minogen activator. Three plasminogen activator inhibitors a faucet connected to a garden hose with multiple perfora-
(PAIs), PAI-1, PAI-2, and PAI-3, inhibit fibrinolysis, thus tions (an irrigator); multiple spurts of water (blood) form
leading to thrombosis. adjacent to the hose (the vessel; Fig. 87.3, A). On the other
Other systems that oppose blood coagulation also become hand, a short-lived primary hemostatic plug can form in a
operational once intravascular clotting has occurred. The cat or dog with severe clotting factor deficiencies (e.g., hemo-
best characterized include antithrombin (AT), a protein syn- philia, rodenticide poisoning); enough functional platelets
thesized by hepatocytes that acts as a co-factor for heparin are present, but fibrin cannot be generated. The result of this
and inhibits the activation of factors IX, X, and thrombin.
AT also inhibits tPA. Proteins C and S are two vitamin K–
dependent anticoagulants also produced by hepatocytes. BOX 87.1
These three factors are some of the natural anticoagulants
that prevent excessive clot formation. Clinical Manifestations of Primary and Secondary
Hemostatic Defects
CLINICAL MANIFESTATIONS OF
SPONTANEOUS BLEEDING DISORDERS Primary Hemostatic Defect
Petechiae common
In the evaluation of a cat or dog with spontaneous or exces- Hematomas rare
sive bleeding, the clinician should ask the owners the follow- Bleeding in skin and mucous membranes
ing questions, which may provide additional clues to the Bleeding immediately after venipuncture
pathogenesis of the coagulopathy: Secondary Hemostatic Defect
Petechiae rare
• Is this the first bleeding episode? If it is occurring in a Hematomas common
mature animal, an acquired coagulopathy is suspected. Bleeding into muscles, joints, and body cavities
(Note: We have seen dogs with hemophilia A present with Delayed bleeding after venipuncture
their first bleeding episode at 8 years of age.)