Definition

Pinpoint (petechia) or larger (ecchymosis) hemorrhage in the skin or mucous membranes most often secondary to abnormal primary hemostasis (platelet or vessel-wall mediated); may appear spontaneously or following minimal trauma. Spontaneous development often occurs at sites of increased capillary trauma or increased pressure, e.g., ventrum.

Pathophysiology

• Thrombocytopenia and/or defective platelet function (i.e., thrombocytopathia) cause impaired primary hemostasis (failure of platelet plug formation). Platelet numbers below 50 × 10⁹/L and more often below 25 × 10⁹/L are associated with an increased risk of spontaneous hemorrhage.
• Main mechanisms of thrombocytopenia-increased destruction, e.g., immune mediated (ITP); decreased production, e.g., myelophthisis or chemotherapy-induced myelosuppression; increased consumption, e.g., DIC; and sequestration in the spleen or liver, e.g., splenic torsion or neoplasia.
• Main mechanisms of congenital thrombocytopathia-deficient or abnormal von Willebrand factor (most common); defects in platelet membrane glycoproteins, e.g., Glanzmann's thrombasthenia in otter hounds and Great Pyrenees (rare); defects in platelet storage granules, e.g., storage pool disease (Chédiak Higashi) in Persian cats or American cocker spaniels (rare); defects in signal transduction, e.g., in basset hounds or spitzes (rare).
• Main mechanisms of acquired platelet dysfunction are drugs (e.g., NSAIDs) or uremia-induced inhibition of prostaglandin metabolism. Other causes are anti-platelet antibodies, paraproteinemia, liver disease, immune-mediated causes, some snake venoms, and various other drugs/exogenous agents
• Vascular hemostatic defects-generally caused by increased capillary permeability, e.g., RMSF or FIP-associated vasculitis, or altered dermal vascular support, e.g., hyperadrenocorticism or Ehlers-Danlos syndrome.

Systems Affected

• Gastrointestinal-melena/hematochezia/hematemesis
• Hemic/Lymphatic/Immune-ITP may be associated with IMHA; concurrent gastrointestinal bleeding can cause significant anemia.
• Neurologic-variable depending on location of bleeding.
• Ophthalmic-scleral/retinal hemorrhage, secondary glaucoma, and uveitis.
• Renal/Urologic-hematuria.
• Respiratory-epistaxis/hemoptysis.
• Skin/Exocrine-petechia/ecchymosis/bruising.

Signalment

• Doberman pinschers and Scottish terriers are overrepresented for von Willebrand deficiency. Many other breeds have vWD. Note bruising and mucosal hemorrhage is common and petechiation is rare in association with vWD.
• See specific thrombopathias for breed-associated disorders.
• Note: an inherited macrothrombocytopenia (giant platelets) is seen in Cavalier King Charles spaniels and several other breeds; it does not cause bruising. Greyhounds have a lower than normal platelet count causing a mild thrombocytopenia.
• ITP shows a possible genetic predisposition because of the high prevalence in cocker spaniels, toy poodles, and Old English sheepdogs. Middle-aged female dogs also are at increased risk.
• Cats-Primary ITP is rare.

Causes

Risk Factors

• The occurrence of any of the aforementioned diseases or breed predispositions. Severe vWD is seen in German shorthaired pointers, Shetland sheepdogs, Scottish terriers, and Chesapeake Bay retrievers.
• History of NSAID use.
• Recent vaccination has not been proven but remains a concern for ITP.
• Geography/travel history, e.g., arthropod-borne diseases.

Differential Diagnosis

Petechia are generally not mistaken for anything else. Some inflammatory skin lesions may look like petechia. Diascopy can be used to help distinguish between the two. Vasculitis lesions may have associated edema. Unwitnessed trauma may cause ecchymoses/bruising.

CBC/Biochemistry/Urinalysis

• Platelets are low, either by direct count or by estimation on a well-made blood smear. One platelet per high power field (hpf) represents approximately 15 × 10⁹/L. An average of 10–30 platelets per hpf corresponds to a normal platelet count. If the platelet count is greater than 100 × 10⁹/L, consider other causes of primary hemostasis abnormalities.
• RBC fragmentation is associated with DIC or microangiopathies.
• Ehrlichia morulae or other hemoparasites may be seen on a peripheral blood smear.
• Patients with myeloproliferative or lymphoproliferative disease, myelofibrosis, or a history of chemotherapy or administration of drugs such as estrogens may be concurrently leukemic or have other cytopenias.
• Biochemical analysis-identify renal or liver disease as well as hyperglobulinemia.
• Urinalysis-identify hematuria. Proteinuria-may suggest concurrent immune-mediated disease, such as glomerulonephritis, and increase the suspicion of systemic lupus erythematosus.

Other Laboratory Tests

• Coagulation studies (APTT, PT, FDP, D-dimer, antithrombin III concentration) help diagnose DIC. Platelet counts less than 10 × 10⁹/L will interfere with ACT assay.
• Von Willebrand factor antigen assay-necessary to confirm vWD.
• Platelet function tests-may be necessary to rule out platelet function disorders, e.g., BMBT, thromboelastography, platelet aggregometry, flow cytometry, and DNA testing at Auburn University.
• Antiplatelet antibody tests will not distinguish primary from secondary ITP.
• Serum and urine protein electrophoresis (looking for Bence-Jones proteins)-indicated if hyperglobulinemia noted.
• Protein: creatinine ratio-if proteinuria noted on urine analysis. An elevated ratio >1 may be suggestive of concurrent glomerulonephritis.
• FeLV/FIV testing-underlying cause of thrombocytopenia.
• Antinuclear antibody titer-helps to diagnose systemic lupus erythematosus if there is evidence of other immune-mediated disease.
• Adrenal function testing may be indicated if hyperadrenocorticism is suspected.
• Serology-aid to diagnose ehrlichiosis, Anaplasma platys, Bartonella vinsonii, or RMSF.
• PCR-for underlying infections such as Ehrlichia spp., Anaplasma platys or Babesia spp., Mycoplasma spp.

Imaging

• Three-view thoracic radiography-look for evidence of metastasis or primary neoplasia/effusion. Identify enlarged lymph nodes or signs suggestive of underlying infectious disease.
• Abdominal radiography to assess spleen and liver size/abdominal detail. Identify enlarged sublumbar lymph nodes or an abdominal mass consistent with hemangiosarcoma.
• Abdominal ultrasonography to note architectural abnormalities in various organs that suggest underlying neoplasia, infection, or inflammation and to evaluate organ blood flow. Evaluate mesenteric lymph nodes for signs of neoplasia, infection, or inflammation.

Diagnostic Procedures

• BMBT is indicated if the platelets are above 100 × 10⁹/L; prolonged BMBT suggests a thrombopathia. Thrombocytopenic patients also have a prolonged BMBT. Normal range is <4 minutes in dogs and <2 minutes in cats.
• Most invasive procedures are contraindicated in patients with bleeding disorders, except bone marrow aspiration and core biopsy. These procedures are indicated if there are cytopenias, hypergammaglobulinemia, or evidence of leukemia.
• Invasive diagnostic procedures may be performed with less risk if platelet concentrate can be administered during the procedure to decrease the risk of hemorrhage.

Drug(s)

• Depends on the underlying diagnosis.
• Prednisone ± vincristine for immune-mediated thrombocytopenia.
• Doxycycline ± enrofloxacin/pradofloxacin (cats) for infectious causes or until infectious causes have been ruled out.
• Desmopressin acetate (DDAVP) for mild platelet function defects, e.g., Type 1 VWD.

Contraindications

Avoid subcutaneous and intramuscular injectable medications whenever possible.

Precautions

Avoid NSAIDs and other drugs that inhibit hemostasis, other than heparin in DIC.

Possible Complications

• Death or morbidity caused by hemorrhage into brain, gut, lung, or other organs.
• Shock caused by hemorrhagic hypovolemia.
• Blindness secondary to hyphema, retinal detachment, and/or glaucoma.

Synonyms

• Bleeding
• Hemorrhagic diatheses

See Also

• Disseminated Intravascular Coagulation
• Hyperadrenocorticism (Cushing's Syndrome)-Cats
• Hyperadrenocorticism (Cushing's Syndrome)-Dogs
• Myeloproliferative Disorders
• Thrombocytopathies
• Thrombocytopenia
• Thrombocytopenia, Primary Immune-Mediated
• von Willebrand Disease

Abbreviations

• ACT = activated clotting time
• ACTH = adrenocorticotropic hormone
• APTT = activated partial thromboplastin time
• BMBT = buccal mucosal bleeding time
• DDAVP = deamino-8-d-arginine vasopressin
• DIC = disseminated intravascular coagulation
• FDP = fibrinogen degradation product
• FeLV = feline leukemia virus
• FIP = feline infectious peritonitis
• FIV = feline immunodeficiency virus
• IMHA = immune-mediated hemolytic anemia
• ITP = immune-mediated thrombocytopenia
• LDDST = low-dose dexamethasone suppression test
• NSAID = nonsteroidal anti-inflammatory drug
• PCR = polymerase chain reaction
• PT = prothrombin time
• RBC = red blood cell
• RMSF = Rocky Mountain spotted fever
• VWD = von Willebrand disease

Internet Resources

• http://www.cvm.ncsu.edu/vth/ticklab.html.
• www.diaglab.vet.cornell.edu/service/.
• www.vet.upenn.edu/penngen.

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