Platelet disorders (Proceedings)

Aug 01, 2010

Platelets are essential for normal hemostasis and serve three main functions. They maintain vascular integrity by forming platelet plugs and promoting endothelial vasoconstriction in areas of disrupted endothelium. Second, they assist with procoagulant activity to help in secondary hemostasis and fibrin formation. Third, they promote vascular healing through platelet-derived growth factor, which works to stimulate endothelial cell migration and smooth muscle production.

Platelets form a hemostatic plug by adhering to exposed subendothelial collagen. This adherence is mediated by vonWillebrand's factor (vWF), which is formed by endothelial cells and megakaryocytes and is found free in the plasma as well as within platelet alpha granules. Substances such as thromboxane A2, thrombin, and endotoxin activate platelets. After platelets adhere to the subendothelial collagen, they go through a shape change, exposing surface receptors to soluble fibrinogen. Platelets release ADP, which activates synthesis of thromboxane A2 and causes irreversible platelet aggregation and intense local vasoconstriction. Decreased number or decreased function of platelets is relatively common causes of bleeding disorders in our patient population.

Diagnosis of Bleeding Disorders

Correct and rapid diagnosis of bleeding disorders is extremely important as delay can lead to possible death of the patient. A thorough history, detailed physical examination, and careful selection of laboratory tests will greatly facilitate a diagnosis. Patients may present with overt bleeding, signs of anemia or hypovolemia, or no obvious symptoms. If there is no explanation for the bleeding, if bleeding is occurring at multiple sites, or if the bleeding seems disproportionate to the injury, a hemostatic defect should be considered.

A thorough, detailed history is vital to the diagnosis. Ascertain the duration of the problem, history of previous bleeding disorders, toxin or medication exposure, and familial history. The age and breed of the patient and the age at which symptoms first appeared may lead the clinician to form a more accurate differential list.

A careful physical examination should be performed. The hallmark clinical sign of thrombocytopenia is the presence of petechiae or ecchymoses. These are most often noted on the abdomen, inguinal area, ear pinnae, sclera, and mucous membranes. Petechiae and ecchymoses are less common in thrombopathias, but they may occur. Signs of clinical hemorrhage in these patients may include melena, hematuria, epistaxis, hyphema or retinal hemorrhage, and prolonged or excessive bleeding at venipuncture, trauma, or surgical sites.

Laboratory tests

The normal platelet count is 200,000-500,000/μl. Simple in-house screens for platelet disorders include the blood smear and the buccal mucosal bleeding time (BMBT). In order to perform a good blood smear, blood should not remain in anticoagulant for more than a few hours or some platelet clumping may occur. The entire smear should be scanned for the presence of platelet clumps, which might result in pseudothrombocytopenia. Clumps are very common in blood smears from cats. Platelets should be counted in the monolayer area of the smear, and the number of platelets counted in the high-powered field (oil) should be averaged. Normal is 8-15 platelets/hpf in dogs and 10-12 platelets/hpf in cats. Each platelet represents approximately 15,000 platelets/μl, so a platelet estimate can be obtained by multiplying the average platelets per hpf by 15,000. Animals rarely bleed spontaneously until platelet count is less than 40,000/μl.

The smear should be evaluated for reticulated or immature platelets and macroplatelets. Small platelets may be seen with early immune-mediated platelet destruction, and large platelets often indicate a regenerative thrombopoiesis. Mean platelet volume (MPV) can be determined from a blood sample collected in citrate anticoagulant and stored at 37°C until evaluation. Platelet distribution width (PDW) may also be performed to assess platelet size.

The BMBT is used to assess platelet and vascular function if the platelet count is within normal range. The Simplate II (Organon Teknika, Durham, NC) contains a triggered blade that makes an incision in the buccal mucosa. Ideally, the upper lip of the patient should be tied in place, as fingers may accidentally move. As bleeding occurs from the site, it is wicked away using filter paper and taking care not to touch the incision site. The time from incision to a clot formation is timed. Normal is less than 4 minutes in the dog. If the BMBT is prolonged, and the platelet count is normal, a platelet or vascular dysfunction syndrome should be suspected.

Further platelet function tests include clot retraction, antiplatelet antibody, platelet adhesion, platelet aggregation, and thromboelastography.