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Home , Thrombocytopenia

Interpreting Thrombocytopenia and Holly M. Brown, DVM, PhD, DACVP ([email protected])

Platelet evaluation • Automated counts are performed on CBC analyzers o Difficult to get accurate platelet counts, especially in cats . Platelet clumping is common . Large are often counted as small RBCs • Esp. for cats, where platelets are large relative to their small RBC volume • Accurate estimates may be made from a stained smear o Platelet estimate/µL = avg. platelet #/10hpf X 15,000 (X 20,000 in cats) o 10-15 platelets per HPF is generally within the reference interval (adequate) o Estimates of “decreased”, “adequate”, or “increased” are often given for the overall platelet mass, based on blood smear review • Always examine the feathered edge of the blood smear for the presence of platelet clumps o You cannot determine how many platelets are in a clump, but you can assume that with clumps, the machine-generated platelet count is a minimum value o Cats are the most common offenders with platelet clumps • Remember: PLATELET MASS IS THE KEY! o A low number of very large platelets can do the same job as many tiny platelets o The patient doesn’t know how many platelets it has - it just needs sufficient functional platelet mass to get the job done!

• (MPV) reflects average platelet size o Platelet clumping will increase MPV o Increased MPV with severe thrombocytopenia → consider reactive thrombopoiesis (ITP) o Decreased MPV → consider decreased platelet production from insufficient , bone marrow dz, steroids; most commonly this is clinically insignificant

• Platelet morphology o Platelets that are the same size or larger than an RBC are called shift platelets, giant platelets, or megaplatelets . They are less mature, and their presence supports active thrombopoiesis

• Platelets form the temporary hemostatic plug. The permanent hemostatic plug is formed when the clotting cascade gets activated and the platelet plug gets made more permanent by the glue known as fibrin. This fibrin clot forms the needed bulk and anchoring mechanism. Hemostatic disorders • Hemostatic disorders are broken down into two broad categories o Failure of primary hemostasis (something wrong with the platelets) o Failure of secondary hemostasis (something wrong with clotting factors)

• Common testing for disorders of hemostasis o Primary hemostasis . Platelet count and volume (discussed above) . Platelet function: Buccal mucosal time (BMBT; discussed shortly) . (vWF; measured at reference labs) • von Willebrand’s disease (vWD) causes bleeding because vWF is needed to bind platelets to damaged endothelium. Lack of this factor results in variably sized bleeds, commonly of mucosa or oozing at surgical incisions. o Secondary hemostasis . Evaluation of factors . In-house tests: • Activated clotting time (ACT) • Prothrombin time (PT) • Partial thromboplastin time (PTT) • Algorithms for interpretations below . Send-out tests: • induced by vitamin K antagonism (PIKVA) • Specific factor activity (like hemophilia A, B, or C)

• Buccal mucosal (BMBT) o BMBT is mostly used as a screening tool for primary hemostatic defects. It is only performed in animals with bleeding attributable to a primary hemostatic defect (usually mucosal bleeding) but with normal platelet counts, coagulation screening tests (PT, PTT) and vWf concentrations (i.e. it is used to detect possible thrombopathia--platelet function defect). The BMBT is also not predictive of surgical hemorrhage; therefore, its use for this purpose is not recommended. Only prolonged BMBT are clinically relevant. o BMBT method: . Specific lancets are needed that produce standardized cuts in the mucosa, the depth of which are sufficient to provoke (and thus evaluate) platelet plug formation but are not deep enough to necessitate fibrin formation, making the test specific for primary hemostasis (if it is performed properly) . The upper lip is folded up and secured with a gauze strip tied around the maxilla . A small incision is made in the mucosa using the desired device . Areas with visibly engorged vessels should be avoided (the gauze strip is likely too tight if vessel engorgement is obvious) . Blood that wells up from the incision is blotted with filter paper applied near (but not touching) the incision . A stopwatch is started when the incision is made and stopped when a crescent of blood no longer develops on the filter paper o BMBT interpretation: . Reference intervals are device specific, so use the information provided with your lancets . Prolonged BMBT could reflect any of the following disorders: • Thrombocytopenia: The BMBT may be prolonged in dogs with <90k platelets/μL • vWD: The BMBT will be prolonged in dogs with moderate to severe deficiencies in vWf. Since dogs with vWf concentrations higher than 20% may not have prolonged BMBT, the test is not recommended for use as a screening tool for this inherited defect, and vWf concentrations should be measured instead. • Thrombopathia: Platelet function defects can be inherited or acquired (e.g. uremia and anti-platelet ).

Coagulation testing (PT, PTT) interpretation: