Bleeding Disorder Testing for Dogs

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 DEPOHGEN^®genotypes 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 a slightly higher risk for postoperative bleeding than Normal/Normal dogs.

DEPOHGEN^™genotype guided prevention/treatment

• MUTANT/MUTANT Prophylactic administration of tranexamic acid* 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 treatment with antifibrinolytics is not indicated. Patients with this genotype should be monitored for signs of unexpected or excessive bleeding, especially during the first 24-48 hours after major surgery. Tranexamic acid or aminocaproic acid (20 mg/kg orally every 8 hours) should be given 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.

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 or aminocaproic 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?

• Email: Dr Court

References

• Court MH, Kiser JN, Neibergs HL, Zhu Z, Dillberger JE. Identification by whole genome sequencing of genes associated with delayed postoperative hemorrhage in Scottish deerhounds. J Vet Intern Med. 2023 Feb 13. doi: 10.1111/jvim.16643. Epub ahead of print. PMID: 36780177.
• Lara-García A, Couto CG, Iazbik MC, Brooks MB. Postoperative bleeding in retired racing greyhounds. J Vet Intern Med. 2008 May-Jun;22(3):525-33. doi: 10.1111/j.1939-1676.2008.0088.x. Epub 2008 May 2. PMID: 18466249.
• Marín LM, Iazbik MC, Zaldivar-Lopez S, Lord LK, Stingle N, Vilar P, Lara-Garcia A, Alvarez F, Hosoya K, Nelson L, Pozzi A, Cooper E, McLoughlin MA, Ball R, Kisseberth WC, London CA, Dudley R, Dyce J, McMahon M, Lerche P, Bednarski R, Couto CG. Retrospective evaluation of the effectiveness of epsilon aminocaproic acid for the prevention of postamputation bleeding in retired racing Greyhounds with appendicular bone tumors: 46 cases (2003-2008). J Vet Emerg Crit Care (San Antonio). 2012 Jun;22(3):332-40. doi: 10.1111/j.1476-4431.2012.00735.x. Epub 2012 May 21. PMID: 22612729.
• Marín LM, Iazbik MC, Zaldivar-Lopez S, Guillaumin J, McLoughlin MA, Couto CG. Epsilon aminocaproic acid for the prevention of delayed postoperative bleeding in retired racing greyhounds undergoing gonadectomy. Vet Surg. 2012 Jul;41(5):594-603. doi: 10.1111/j.1532-950X.2012.00965.x. Epub 2012 Jun 19. PMID: 22712787.
• Saavedra PV, Stingle N, Iazbik C, Marín L, McLoughlin MA, Xie Y, Couto G. Thromboelastographic changes after gonadectomy in retired racing greyhounds. Vet Rec. 2011 Jul 23;169(4):99. doi: 10.1136/vr.d2671. Epub 2011 Jul 1. PMID: 21724753; PMCID: PMC3856634.
• FDA approved label information for Amicar (aminocaproic acid)
• FDA approved label information for tranexamic acid

Yes. Customs regulations make it challenging to ship biological samples (especially blood) into the USA. We encourage our international clients to test using cytology brushes (instead of blood) since the samples are stable and less costly to ship. We also recommend finding a local source of cytology brushes since it is much quicker and more efficient than waiting for our brushes to reach you. Widely available interdental brushes work just as well if the medical variety are not available. The next FAQ provides additional information about using your own brushes.

Once you are ready to send the samples, complete the online submission form and credit card payment.  Print the submission form and mail it with your samples to the Post Office address provided on the form. You can also use a faster courier service if you prefer. We have a different address for couriers provided on the form.

Results will be sent to the email address provided on the submission form.  It usually takes about a week to test the sample after it is received.

DEPOHGEN^® tests are run in batches on Thursdays. If your test arrives in time to be included in Thursday’s batch, you should receive your results by Friday evening of that same week. Any test samples received after Wednesday are included in the next week’s batch.

DNA from your pet’s cheek cells using a swab is the same as DNA obtained from your pet’s blood. We offer tests using either type of sample because cheek swabs are an easy way for dog owners to collect DNA samples in their own homes, while blood samples are often preferred by veterinary clinics and hospitals.

Refunds may be requested only for samples that have not been processed. All refunds must be requested within 60 days of the date of purchase. The date of purchase is defined as the day the customer’s card is charged. Please contact us at cvm.depohgen@wsu.edu to request a refund.

DEPOHGEN^® genotype results are reported only to the contact on the submission form. Collective data reports generated for public distribution have no identifiable features other than breed.