Information for veterinarians

Delayed Postoperative Hemorrhage (DEPOH)

Presentation

  • Unexpected or excessive bleeding a few hours to a few days AFTER surgery or minor trauma.
  • Dogs with DEPOH form normal blood clots, but the clots break down prematurely.
  • Bleeding may appear as peri-incisional bruising, seeping from the incision, and/or internal bleeding from cut tissues, which may become generalized.
  • Can be fatal if untreated.

Diagnostic tests

  • Routine assays for primary and secondary hemostatic defects are generally normal.
  • PT / aPTT times, platelet counts, and vWF concentration are normal
  • Increased fibrinolysis may be detected using a (modified) thromboelastography (TEG) assay.
  • DEPOHGEN genetic testing can assist in diagnosis.

Affected breeds

  • DEPOH was first documented in Greyhounds and Scottish Deerhounds.
  • DEPOHGEN testing indicates that most other sighthound breeds are at increased risk for DEPOH.
  • The 8 breeds we have tested with the highest DEPOHGEN frequency include: Irish Wolfhounds, Basenjis, Italian Greyhounds, Greyhounds, Scottish Deerhounds, Whippets, and Salukis.
  • The same genetic mutation has been found in about 50% of non-sighthound breeds.
  • The mutation is much rarer in non-sighthounds than in sighthounds.
  • We are actively working to understand the risk for DEPOH among different breeds.

Genetics

  • The first study of the genetics of DEPOH in dogs (Court et al ,2023) identified a novel mutation in the SERPINF2 gene.
  • SERPINF2 encodes for alpha-2 antiplasmin, which inhibits the breakdown of fibrin clots by plasmin (fibrinolysis).
  • Dogs that we have tested with the SERPINF2 mutation have decreased alpha-2 antiplasmin activity, predisposing them to premature clot dissolution.
  • The DEPOHGEN test was developed at WSU to detect this mutation and predict the risk for bleeding after surgery.
  • Possible DEPOHGENgenotypes are MUTANT/MUTANT, MUTANT/Normal, and Normal/Normal.
  • MUTANT/MUTANT dogs are significantly more likely to bleed after surgery than Normal/Normal dogs.
  • MUTANT/Normal dogs have an increased risk for postoperative bleeding than Normal/Normal dogs, but many can have major surgery without bleeding problems.

DEPOHGENgenotype guided prevention/treatment

  • MUTANT/MUTANT Prophylactic administration of tranexamic acid* (preferred) or aminocaproic acid is recommended before surgery in dogs with this genotype. Give either IV or orally at a dosage of 20 mg/kg starting 1 hour (IV) or 2 – 4 hours (orally) prior to the surgical procedure, and then orally three times daily for five days. For IV administration, dilute drug 1:3 with saline, and administer over 20 minutes to avoid vomiting. Diarrhea is occasionally observed with continued antifibrinolytic treatment, which responds to dose reduction or discontinuation.
  • MUTANT/Normal Prophylactic therapy with tranexamic acid or aminocaproic acid should be considered in cases that have a risk for undetected internal hemorrhage such as thoracic and abdominal surgery, including spays and castrations. Closely monitor patients with this genotype especially during the first 24 hours after surgery for signs of unexpected or excessive bleeding. Tranexamic acid or aminocaproic acid should be available and administered as needed. If initiated, treatment for 5 days is recommended.
  • Normal/Normal Antifibrinolytic treatment is not indicated.

*Oral (500 mg or 250 mg capsule) and injectable (10mg/mL; 10 mL vial) tranexamic acid can be sourced through MWI Animal Health, as well as some other veterinary pharmaceutical suppliers.

Note: Factors in addition to DEPOHGEN genotype will influence the risk for DEPOH. Bleeding is more likely to occur after invasive surgical procedures involving highly vascular tissue. Increased age also appears to increase the risk for bleeding. Other causes of unexpected/excessive bleeding cannot be excluded by DEPOHGEN testing.

Special considerations

  • Pregnant bitches: Tranexamic acid is considered safe and effective for the treatment of bleeding during pregnancy in humans. However, antifibrinolytic drugs can cross the placental barrier and the effects on the developing fetus are unclear. Consider avoiding these drugs unless there is a clear need (i.e. dog shows signs of unexpected or excessive bleeding).
  • C-section: Mutant/Mutant dogs should receive prophylactic 20 mg/kg tranexamic acid IV starting 1 hour before surgery and then orally every 8 hours for 5 days. Tranexamic acid is preferred since the transfer of drug into the milk is known to be relatively low.
  • Lactation: Antifibrinolytic drugs can transfer into milk and the effects on nursing pups are unclear. Tranexamic acid is preferred since the transfer of drug into the milk is known to be relatively low.

Questions?

References