Investigating bleeding disorders

Chilled EDTA plasma and citrated whole blood

May involve clotting factors and/or platelets
Usually suspected because of petechial or ecchymotic haemorrhages, persistent bleeding after venipuncture, recurrent/persistent epistaxis or multiple haematomas.
- Clotting factor problems
  - Hepatic failure
  - DIC
  - specific (genetic) clotting factor deficiencies are also reported rarely
- Platelet problems (bleeding disorders)
  - Immune mediated thrombocytopaenia
  - DIC
  - Bone marrow aplasia
  - EIA, Piroplasmosis and Anaplasmosis
Testing – should be compared with a control horse. Values greater than 20% longer than the control are considered abnormal.
- Prothrombin time (PT) (extrinsic pathway)
  - usually around 10-15 secs
  - depends on factors I, II, V, VII, and X
  - affected by coumarin-type anticoagulants, vitamin K deficiency, liver damage and DIC.
- Activated partial thromboplastin time (APTT) (intrinsic and common pathways)
  - usually around 30-45 secs
  - depends on factors I, II, V, VIII, IX, X, XI, & XII
  - affected by heparin treatment, general consumptive coagulopathies (DIC), von Willebrand disease, haemophilia and probably severe hepatic failure.
- Platelet count
  - usually >100 x 109/L
  - equine platelets prone to aggregating in vitro resulting in artefactually low measured numbers (repeat with citrated sample).
  - bleeding disorders generally have platelet counts < 20 x 109/L.
  - immune-mediated disease, DIC and liver failure.
- Bleeding time
  - crude test of platelet function
  - small stab incision and blood removed every 30 secs with tissue (without touching the skin).
  - Bleeding should cease within 5 minutes in normal horses.
  - affected by thrombocytopaenia, thrombasthenia, DIC, vasculitis, aspirin, liver and kidney failure.

Clinical signs of bleeding disorders may include petechial or ecchymotic haemorrhages, persistent bleeding after venipuncture, recurrent/persistent epistaxis or multiple haematomas. Terminology often describes problems with clotting factors as clotting disorders, and problems with platelets as bleeding disorders.

CAUSES
Disseminated Intravascular Coagulation (DIC) – a procoagulant status, typically associated with sepsis or neoplasia, leads to consumption of clotting factors and initial thrombotic disease (e.g. at catheter sites) is followed by haemorrhages (eg epistaxis post nasogastric tubing).
Hepatic disease – Although the liver produces a large number of factors important in coagulation, clinical bleeding disorders are uncommon as a consequence of hepatic disease – quite severe hepatic failure is needed before any problems arise.

Specific factor deficiencies

Vitamin K deficiency may occur as a result of ingesting rat bait although this generally requires prolonged exposure and is very uncommon in equids
Factor VIII deficiency (classic haemophilia) has been identified in Thoroughbreds, Standardbreds, Quarter Horses and Arabs
Deficiency of Von Willebrand’s factor has been identified in Thoroughbreds and a Quarter Horse
Prekallikrein deficiency has been identified in Belgian horses, American Miniature horses and a Quarter Horse

Thrombocytopaenia

Immune-mediated (primary or secondary to infection/neoplasia/drugs) – may be associated with immune mediated anaemia
DIC
Bone marrow disease (see anaemia)
Chronic excessive haemorrhage
Equine Infectious Anaemia (NOTIFIABLE!)
Anaplasmosis
Piroplasmosis

Functional platelet disorder

Glanzmann’s thrombasthenia is a rare congenital disorder of platelet function

DIAGNOSTIC TESTS FOR COAGULATION DISORDERS
Tests available in practice are somewhat crude and comprise prothrombin time (PT), activated partial thromboplastin time (APTT) and bleeding time. Further functional tests are used as research tools but are not available commercially. All tests should be compared with a control horse as reference ranges are unreliable due to the number of external factors that may affect the test, especially if there is a time delay (post). Generally values greater than 20% longer than the control are considered abnormal.

Tests of clotting factors – PT and APTT are used to assess functionality of the clotting factor cascade. Most clotting disorders (e.g. liver failure or DIC) will have abnormalities in both pathways although changes in PT often precede changes in APTT dye to the short half life of factor VII.
- PT – (extrinsic pathway) is usually around 10-15 secs and depends on factors I, II, V, VII, and X and will be affected by coumarin-type anticoagulants, vitamin K deficiency, liver damage and general consumptive coagulopathies (DIC).
- o APTT – (intrinsic and common pathways) is usually around 30-45 secs and depends on factors I, II, V, VIII, IX, X, XI, & XII and will be affected by heparin treatment, general consumptive coagulopathies (DIC), von Willebrand disease, haemophilia and probably severe hepatic failure.
Platelet count – is usually >100 x 109/L but equine platelets are prone to aggregating in vitro resulting in artefactually low measured numbers. If thrombocytopaenia is identified in EDTA samples then measurement can be repeated on a citrated sample as the likelihood of artefactual platelet clumping is reduced. Bleeding disorders are generally associated with platelet counts < 20 x 109/L. Primary differentials for thrombocytopaenia include immune-mediated disease, DIC and liver failure.
Bleeding time – is a crude test of platelet function whereby a small stab incision is made in the skin and blood removed every 30 secs with tissue (without touching the skin). Bleeding should cease within 5 minutes in normal horses. Bleeding time is affected by several processes including thrombocytopaenia, thrombasthenia, DIC, vasculitis, aspirin, liver and kidney failure. Worth comparing with a control horse.
D-Dimer is a product of fibrin breakdown and is increased in horses with colic, laminitis, jugular thrombosis and other inflammatory disorders. Increased concentrations may therefore give an indication of coagulopathy. In plasma, concentrations above 1000 ng/mL are considered to indicate a coagulopathy and in colic cases a concentration > 4000 ng/mL is associated with reduced likelihood of survival.