Platelet Disorders

Linda L. Werner, DVM, Ph.D., ACVIM, ACVP
IDEXX Veterinary Services, Inc.

2825 KOVR Drive
West Sacramento, CA 95691

 

Bleeding due to platelet deficiency or dysfunction generally appears clinically as one or more of the following:  

  1. Petechiae, ecchymoses, purpuras (spontaneous small vessel-type bleeding)
  2. Trauma-induced bleeding of many types, including venipuncture, surgical, pressure or abrasion
  3. Mucosal bleeding (GI, gingival, epistaxis, urogenital)
  The most common causes of clinical bleeding from simple platelet disorders are severely thrombocytopenic states where platelet counts fall well below the 20-40 thousand/ul range. Most common are the following:  
  1. Immune Mediated Thrombocytopenia - IMT
    • Primary* (idiopathic)
    • Secondary* -- infectious, drug or vaccine-induced (many drugs, FeLV*, FIV, EIAV*, rickettsial*, Babesiosis)
  2. Defects in Hematopoiesis (reduced megakaryocyte production)
    • Neoplasia* - myelo- or lymphoproliferative
    • Infectious* - FeLV, E. Canis, EIAV, sepsis
    • Drugs – estrogens, chloramphenicol, sulfas, cytotoxic drugs, many can cause idiosyncratic myelosuppression
    • Immune Mediated*

  Platelet-type bleeding can also occur with defects of platelet function, both congenital and acquired. The most common is von Willebrand's Disease, which clinically can be described as an extrinsic failure of platelet function due to lack of VWF, an important protein functioning in the adhesion step of platelet activation. Platelet function defects include the following types:  

Acquired (most common except for VWD):

  • Drugs -- aspirin, NSAIDs
  • Immune Mediated* – primary, secondary
  • Uremia, endotoxemia
  • Paraproteinemia such as multiple myeloma*
  • Neoplasias* – myeloproliferative, others
 Heritable (uncommon except for VWD):
  • VWD (many breeds)
  • Glanzmann’s thrombasthenia (Great Pyrenees)
  • Otterhound thrombasthenia
  • Storage or granule pool defects (Persian cats, cattle, Gray collies and American Cocker Spaniels)
  • Basset hound thrombopathia (adhesion defect)
Many of the causes of thrombocytopenia listed above (*) can involve both failures of production and peripheral destruction of platelets. Many can also cause platelet function defects. For this reason (multiple platelet abnormalities from a single cause or agent), patients with subnormal platelet counts in a more moderate range (40-120 thousand/ul), or even with normal to increased platelet counts, can occasionally show significant clinical bleeding. In addition milder thrombocytopenias or platelet function defects that are subclinical may be unmasked by potentiating bleeding when other clotting defects appear (mixed disorders).   The following initial screening tests should be considered when working up a patient for bleeding problems:  
  • CBC, chemistry panel, urinalysis
  • Platelet Count**
  • Mucosal Bleeding Time (MBT)**
  • Von Willebrand’s Factor
  • Prothrombin Time (PT)
  • Partial Thromboplastin Time (PTT)
  • Fibrinogen (by thrombin consumption)
  • Fibrin Degradation Products (FDPs)

Those tests denoted by “**” can indicate platelet-type problems and consideration of the etiologies described above.

  When screening tests show normal results for platelet parameters, a coagulation factor problem should be suspected; or, when a patient with abnormal platelet parameters also shows other screening abnormalities (clotting functions not denoted by “**”), the patient likely has bleeding caused by a mixed clotting  disorder, covered in the second session.  

When a patient shows screening test abnormalities denoting a simple or complex platelet problem only (normal clotting factor screens), ancillary tests for the above listed etiologies can be initiated according to those warranted by the history and clinical findings. Further tests might often include a bone marrow aspirate (antimegakaryocyte IFA antibody testing, myeloproliferative or myelosuppressive disease), infectious disease testing, other antibody tests for IMT (flow cytometry where available), and specialized tests for heritable platelet function defects. The latter two types of tests require specialized testing facilities usually located within veterinary or medical school clinical or research laboratories.

REVIEW OF TESTS FOR HEMOSTASIS BY PHASE OF CLOTTING

Platelets:  
  1. Count or estimate (1/100x = 15,000)
  2. Mucosal Bleeding Time – MBT or BT (1-5 minutes most species); ASSESSES PLATELET FUNCTION and/or capillary integrity
  3. Bone marrow evaluation for megakaryocyte activity, etc.
  4. Von-Willebrand’s Factor – VWF
  5. Specialized Platelet Function Tests (aggregometry, receptor expression, etc.)

Vessels:

  Cases of excessive bleeding (ex. Epistaxis, petechiae, purpura) due to abnormal vessel functions or fragility are most often attributed to acquired causes of vasculitis or defective collagen. Such cases may show a prolonged MBT. Mild to moderate thrombocytopenias are commonly seen in the vasculitis group of disorders. Clinical bleeding is rarely severe unless a vasculitis-type presentation also manifests DIC. Routine tests for vasculitis include screens for commonly incriminated pathogens and biopsy of involved tissue.  

Clotting Factors:              

Screening tests:  

  1. PTT or APTT (intrinsic and common path) – Partial Thromboplastin Time
    The ACT (activated clotting time or coagulation time) is a rough and quick estimate for this test that can be performed in-clinic by a number of methods.
  2. PT (extrinsic and common path) – Prothrombin Time
  3. Some laboratories include Stypven and Thrombin Time to screen for common pathway defects.
  4. PIVKA – especially indicated in early warfarin intoxication, before significant elevation(s) in PT or PTT; can be problematic for interpretation due to lack of specificity for rodenticide anticoagulant toxicity.
Special tests:  
  1. Individual Clotting Factors – requires specialized lab expertise, usually at universities
  2. Tests for Disseminated Intravascular Coagulation (DIC) – evaluate as a panel
    • Platelet count
    • MBT
    • Fibrinogen
    • PTT and PT
    • FDPs
    • AT III (antithrombin III)
  3. Tests for Inhibitor(s) of Clotting Factors (rare indications)
  4. Tests for Fibrinolysis (rare indications)  
    • DIC panel (#2 above)
    • Clot retraction/lysis
    • Euglobulin lysis
    • Protamine sulfate test – a test for “clottable” FDPs

CLASSIFICATION SYSTEM FOR BLEEDING DISORDERS

  Resolution of excessive bleeding, whether spontaneous or post-traumatic, can be achieved most effectively by employing a systematic approach that involves four sequential steps (and often a minimum of laboratory analysis).  
  1. Initial application of routine hemostatic measures for patients in hemorrhagic crisis.
  2. Perform the routine screening tests designated in bold print above.
  3. Apply the results of the routine screening tests to the diagnostic classification system (below) based upon the involved phase(s) of hemostasis.
  4. Having classified the bleeding problem, further specific diagnostic tests can be submitted, where appropriate, to establish a definitive diagnosis.
  Decisions regarding therapy, especially fresh whole blood transfusion, can be implemented at any time during this four-step process, so long as all diagnostic samples are drawn pre-treatment.  
  1. Simple Platelet Problem
    • Decreased numbers:
      • Decreased Production:  drugs/toxins, infectious, myeloproliferative, myelodysplastic or aplastic marrow disease; some cases of IMT
      • Increased Consumption/Destruction:  IMT primary & secondary, infectious, parasitic, vasculitis, splenic sequestration
    • Decreased function:
      • VWD – most common; extrinsic platelet function problem
      • Aspirin-type compounds most common acquired cause
      • Also myeloproliferative disease, paraproteinemias, uremia, immune complexes
    • Both numbers and function decreased:
      • IMT, especially secondary to drugs or infectious agents, ex. E. canis, FeLV
      • Aspirin ingestion plus some cause of thrombocytopenia
      • VWD plus acquired cause of thrombocytopenia, ex. IMT, myeloproliferative disease, aspirin
  2. Simple Clotting Factor Problem            
    • Single factor:
      • Intrinsic:VIII (hemophilia A) most common; Hemophilia B (IX); XII
      • Extrinsic:VII
      • Common:X, V, I
      • Rarely acquired inhibitor, ex. SLE or multiply transfused patient
    • Multiple factors:
      • Vitamin K antagonism or deficiency
      • Liver disease/failure
      • Hemophilia plus inhibitor(s)
  3. Combined or mixed clotting factor/platelet problem
    • DIC syndromes
    • Liver disease
    • VWD with hemophilia
    • Many potential disaster combinations – as far as the imagination can stretch!