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SECONDARY HAEMOSTATIC TESTS: COAGULATION TESTS
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Whereas the whole blood clotting time test is insensitive and inaccurate, there are several standardized coagulation screening tests that are useful to define coagulopathies in clinical practice. The screening tests assess coagulation in vitro, which is helpful, but is now known not to be identical with the in vivo coagulation process. Nearly all coagulation tests assess the function of certain parts of the coagulation system in fresh whole blood or fresh (frozen) plasma to generate fibrin in a fibrometer; recalcified citrated plasma is used and many tests are comparing a patient sample directly with a simultaneously obtained control or pool plasma (plasma from 10 animals). Generally coagulation times, the time to clotting (fibrin formation), are much shorter in small animals than in humans; thus, tests need to be validated for the animal species.
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The intrinsic and common pathways are assessed by either the activated coagulation time (ACT) or activated partial thromboplastin time (PTT). Factor XII of the intrinsic cascade is activated by diatomaceous earth (celite) in the ACT test and by kaolin or other contact phase substrates in the PTT test.
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The extrinsic and common pathways can be assessed by either the prothrombin time (PT) or the protein induced by vitamin K antagonism or absence (PIVKA) test. Different tissue factors (thromboplastins) are activating factor VII, which in turn will lead to fibrin formation. It should be noted that the PIVKA test is not specific for the detection of anticoagulant rodenticide poisoning, but detects any coagulation factor deficiency of the extrinsic and common pathway and does not add information to the generally run PT test.
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Until recently the ACT tube test was the only point of care test available for clinical practice, whereas PTT and PT tests were performed in reference laboratories. There are now new point of care coagulation instruments (e.g., SCA2000) introduced that are capable of determining without delay on small amounts (50µl) of fresh citrated whole blood the PTT and PT, thereby making the chilling, rapid separation of citrated plasma and shipment of frozen plasma on dry ice to the laboratory for initial coagulation screening unnecessary.
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In fact, a reasonable and simple approach for a bleeding animal to be screened for a coagulopathy would be to measure the ACT or PTT first as either test detects all coagulopathies (except for hereditary factor VII deficiency in Beagles). If the PTT (or ACT) is prolonged, a PT test would be indicated to differentiate between an intrinsic and common pathway defect or a combined coagulopathy involving several coagulation factors.
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Although hereditary coagulopathies can be suspected based upon the pattern of coagulation test abnormalities, specific factor analyses are needed to confirm a diagnosis. A bleeding male animal with a prolonged PTT (or ACT) and normal PT likely has hemophilia A or B (factor VIII or IX deficiency), an X chromosomal recessive disorder. However, factor XI deficiency is associated with the same test abnormalities and is inherited by an autosomal recessive trait (e.g., Kerry blue terriers). Finally, factor XII deficiency, particularly common in domestic shorthair cats, and prekallikrein deficiency causes marked PTT (ACT) prolongations but no excessive bleeding tendency.
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Rodenticide poisoned animals that are bleeding or are at risk for bleeding will have prolongations in all of the above coagulation tests, but would have a normal thrombin time (TT). The thrombin time is independent of vitamin K-dependent coagulation factors and is a functional assay for fibrinogen to form fibrin. The PIVKA test is not diagnostic, but a toxicological investigation (product identification, blood toxicology analysis) may confirm the rodenticide poisoning. Moderate thrombocytopenia may be associated with rodenticide poisoning.
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All liver diseases may result in varied coagulopathies due to impaired coagulation factor synthesis and vitamin K malabsorption. Similarly, disseminated intravascular coagulopathies (DIC), due to many different disorders is associated with variably prolonged coagulation times. More helpful to the diagnosis of DIC are the recognition of schistocytes, thrombocytopenia, low antithrombin III levels, and increased D-dimers and fibrin split (degradation) products.
Hemostatic Tests in Clinical Practice
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Test
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Normal Dog
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Disorder
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PCV %
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37-55%
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Anemias; May not be evident in first few hours
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Total Protein
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5.5-7.5 g/dl
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Hypoproteinemias with external blood loss
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Platelet estimate
Platelet count
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8-15 per oil field
(1/15,000 per µl)
150-400,000/µl
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Thrombocytopenias also schistocytes
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Buccal mucosal
bleeding time (BMBT)
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< 4 minutes
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Thrombopathias vWD
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von Willebrand factor (vWF)
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65-150% also mutation tests for breeding
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von Willebrand disease
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Activated clotting
time (ACT)
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<110 seconds (tube assay)
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Intrinsic and common coagulopathies
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Partial Thromboplastin Time PTT)
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12-16 seconds (Lab*)
54-94 seconds (SCA 2000)
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Intrinsic and common coagulopathies
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Prothrombin time (PT)
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10-14 seconds (Lab*)
12-16 seconds (SCA 2000)
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Extrinsic and common coagulopathy
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Protein Induced by Vitamin K Antagonism/Absence (PIVKA)
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<25 seconds
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Like PT, not specific for warfarin
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Thrombin time (TT)
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10-12 seconds (Lab*)
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Hypofibrinogenemia functional
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Fibrinogen
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100-300 mg/dl
(precipitated)
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Hypofibrinogenemia
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Fibrin split products
(FSP/FDP)
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<1:5 (Lab*); <5µg/dl (Lab*)
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Fibrin(-ogen) degradation in DIC
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D-dimers
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<250µg/dl;
-/+ with kit
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Fibrin degradation in DIC
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Antithrombin III
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90-120% (Lab*)
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Low levels with thrombosis, DIC
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Participants