Unfractionated and low-molecular-weight heparin for hypercoagulability in dogs and cats - Veterinary Medicine
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Unfractionated and low-molecular-weight heparin for hypercoagulability in dogs and cats
A new type of heparin, low-molecular-weight heparin, shows promise as an effective and easier-to-use form of therapy for people prone to thromboembolism. Does the same hold true for dogs and cats?


VETERINARY MEDICINE


DIAGNOSING HYPERCOAGULABILITY

Definitive diagnosis of hypercoagulability has been a challenge to both researchers and clinicians. Standard coagulation testing (prothrombin time, activated partial thromboplastin time [aptt], and thrombin time) assesses the presence and function of coagulation factors, but hypercoagulability does not correlate with shortened coagulation times.19

Antithrombin activity, protein C assay, and platelet aggregation studies

Antithrombin activity of 60% to 75% of the normal control value for the species is associated with hypercoagulability; however, animals with conditions that predispose them to hypercoagulability may have normal antithrombin activity, and antithrombin activity can be decreased secondary to thrombus formation even in the absence of hypercoagulability.24 Furthermore, antithrombin measurement is not widely available for routine and rapid clinical use.

Likewise, although protein C deficiency has been associated with hypercoagulability in people, a protein C assay is also not routinely available to veterinarians. Platelet aggregation studies are mainly helpful to monitor the effectiveness of antiplatelet therapy rather than to detect hypercoagulability. A variety of other tests used to detect hypercoagulable states in people (e.g. detection of lupus anticoagulant, genetic tests for enzyme defects) are simply not available for veterinarians.

Thromboelastography

One test that can help detect hypercoagulation is thromboelastography, which provides information about coagulation, from initiation to clot formation (including clot quality) and fibrinolysis.25

A thromboelastography tracing provides four primary values. The first two values, R and K, are measures of the time to clot generation.1 The R value is a measure of the precoagulation time and is thought to represent the intrinsic pathway. The K value is the clot formation time, and it is affected by factor II and VIII activities, platelet count and function, thrombin formation, fibrin precipitation, fibrinogen concentration, and hematocrit.1 The third value, which is the angle or alpha value, reflects the rate of clot formation and is affected by the same factors that influence K. The fourth value is the maximum amplitude, which reflects the clot's maximum strength. It is affected by fibrin and fibrinogen concentrations, platelet count and function, thrombin concentration, factor VIII activity, and hematocrit.1 These four values are used to calculate a coagulation index that indicates hypercoagulability or hypocoagulability.

The advantage of this technology is the global view of hemostasis that it provides, but this test is not practical for use with clinical patients outside of select academic environments. In people, thromboelastography can be performed intraoperatively to guide blood product and anticoagulant administration.25 In animals, thromboelastography is currently used primarily as a research tool because of the procedure's technical demands.5,26

MECHANISM OF ACTION OF HEPARINS

When hypercoagulability is suspected or thromboembolism is diagnosed, heparin therapy is often indicated. Unfractionated and low-molecular-weight heparins achieve similar anticoagulant effects by enhancing antithrombin activity but differ in their ability to bind and inhibit thrombin. This difference causes variations in drug use and monitoring that are important in clinical patients.

Unfractionated heparin


Figure 4
Heparins, which are glycosaminoglycans, were first discovered in 1916.27 There is considerable heterogeneity of molecules, with a molecular weight range of 5,000 to 30,000; the average molecular weight of unfractionated heparin is 12,000 to 15,000.2 Anticoagulant activity is due to a unique pentasaccharide sequence with a high affinity for binding to antithrombin (Figure 4). This sequence occurs in about one-third of unfractionated heparin molecules. Distribution of the sequence in the molecule is random.


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Source: VETERINARY MEDICINE,
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