Preparing for a More Consistent and Indicative PT and Factor VII Test
by Chris Caster & Aprilfawn White

There has been a set of guidelines posted today on the proper testing of AKK for Factor VII and related bleeding disorders.  One thing we would like to acknowledge and applaud is the very quick execution by both the AKKAOA and the UAKKA in writing this up.  To this day we have never seen a health issue in this breed addressed and guided so quickly in order for breeders to make semi-educated decisions on how to help filter this problem out of the AKK breed.  It may have to do with the knowledge that we were going to post this preparative publication the same night and may have had something to do with my being banned from the group the AKKAOA guidelines were posted on.  In any case, bravo to the clubs.  We do hope that any future health issues in the breed are prosecuted with such rigor.  The AKK would very much benefit from that in the future.  And we will jump on any such health issue just to get you to move as fast!

As for the statement of clinical facts there are some inherent problems with the blood test or most any blood factor diagnostic test for that matter.  A 50-150% range “of normal dogs” does not allow for what is to be called a carrier (between 26-49%) or even an affected (0-25%) to be statistically called as such.  When there is a 100% range of “normal” which is based on single scores from a pool of dogs (usually of different breeds other than AKK!) averaged together, you cannot be stating that an AKK carrier has such a small range of only 26-49% and affected 0-25%.  Statistically speaking, based on the stated “normal” range anything as low as 25% should be called normal by definition of noise in the testing.  Making statements other than this is not relevantly or statistically backed by the data.  By definition one can also not scientifically classify a carrier as a dog that scores low in a noisy test but never shows signs of a bleeding problem.  That is a normal dog unless confirmed by a definitive and validated DNA test. 

Let’s take a look at some confirmed results from the single confirmed affected AKK (that little champ of an AKK Butterball!), and his parents.  Now Butterball’s scored a 16% which by the AKKAOA write-up stated range is an affected dog.  I will give you that as a score that fell in its expected range.  The problem is that little guy’s two parents had scores of 61% and 73%.  By the statements made in the AKKAOA write-up these two parents would have been classified as “normal”.  We have a problem with that as would the breeder who would have to pay dearly (in vet bills and heartache!) to have affected pups like Butterball showing up after believing in these guidelines.   We personally would be very upset if we had been told it was o.k. to breed the parents in that situation. 

Now, let’s take a look at the noise of a single dog tested more than once over less than a month period.  A single dog, we shall refer to as female #1, tested once at 111% and the next time at 67%.   Not only did one of the tests for this AKK come out close to the same score of one of the parents of Butterball but the range between two tests on the same AKK is 44%.  Who is to say that Butterball’s parent at 61% couldn’t have retested and scored a 111% by basis of inherent noise in the testing.  Nobody would have ever thought this dog to be a carrier.  Needless to say though the AKKAOA did a great job of quickly getting these guidelines in the hands of breeders but did so without making sure that they weren’t promoting breedings that would produce another Butterball.

As you can see from these example data provided by a very brave breeder this test can be a good indicator of an affected dog but so can the real life scenario where the affected AKK gets injured and has a swollen head the size of a cantalope.  Nobody wants to see one of their precious little AKK in that situation.  Nor does anyone want to be fixing half of their stock based on a not well thought out set of guidelines. 

Now some hardworking scientists at Penn may very likely have found the genetic explanation for the Factor VII deficiency seen in Butterball.  It seems to be the same exact autosomal recessive genetic anomaly seen in beagles with the same condition.  With some more hard work these folks may have a definitive test for Factor VII deficiency ready for use in the next month or two.  Until this definitive tool is ready we should use the blood test as a cautionary tool but also make it the best test it can be.

There is some well defined biology involved with this deficiency that Dr. Jean Dodds has had a great hand in over the last four decades.  She is a well referenced author in this area and has published a plethora of papers on it.   We won’t go into the science in too much detail but give you some facts to allow you to understand our rational for properly preparing your AKK for the blood test.

Factor VII is a Vitamin K dependent cofactor that helps to initiate coagulation in the blood vessels upon injury.  The Vitamin K part is extremely important in this statement and we will tell you why.  Without it Factor VII will not work and in response you will see an affected-like result in a dog that has a vitamin K deficiency normally caused by poisoning with rodenticides (not common).  The same result can be acquired by a vitamin K deficiency that occurs by temporarily killing the bacteria in the gut that supply the vast majority of this needed vitamin to its host.  The latter scenario could very well be caused by something as trivial as giving your dog antibiotics for treatment of a bacterial infection prior to having it tested.  Granted that is more likely than the poisoning scenario, one still would not want to blood test their dogs and get an affected % score that was likely caused by a vitamin deficiency and not the real genetic health problem. 

In order to help rule out these types of scenarios it would be a very good idea for all who are going to blood test their dogs to give a regimen of Vitamin K supplement to the dogs for at least a week prior to testing.  This will help maximize the amount of working Factor VII in the blood and in turn will help separate the affected dog’s scores from all others (carriers and unaffected) as the test is statistically intended to do.  The theory is that if the dog is affected, the working Factor VII level will essentially be unchanged because affected dogs have bad Factor VII and not a vitamin deficiency.  Meanwhile the carrier and unaffected dogs will more likely have Factor VII levels that are boosted out of the range where there is no question that the dog is not affected.  Mind you this supplementation will not make the blood test a perfect test but will help cut out a lot of false results that could be attributed to things other than the real Factor VII deficiency.  As a single point example of this theory, Butterball, who is affected, did not have an elevated Factor VII score even after he was put on vitamin K supplements prior to testing and his recent surgery.

As more people have their vitamin K supplemented AKK tested by this method and we have more genetic data to back this up, it would be a good idea to pool the DNA confirmed unaffected AKK Factor VII blood scores and make them the “normal” data to base all further blood testing on.  That will likely cut down the 50-100% noise range to one more statistically relevant.  It would also allow the blood test to better correlate with the soon to be ready Penn DNA test.  Although the blood test is noisier we do believe that the more data available on a health issue the better.  We are advocating the DNA test as the best way to define the health problem when it is available but blood test data is also valuable in its own right for helping to find affected dogs before they show real bleeding problems after an unfortunate injury.  We plan to have all of our stock tested by both methods if for no other reason than to see the complementation of results from both testing methods. 

Our personal beliefs are that since this is a health issue in such a small breed that everyone should get their AKK tested regardless of whether they think their stock may be affected.  If managed properly in an anonymous and responsible way all of the data can be used to rid the breed of this issue in just a few generations.  Wouldn’t that be nice?  We would all owe Butterball, his breeder, the people involved in creating the tests and the biologists who helped find the problem a lot of gratitude.  We appreciate the AKKAOA and UAKKA for their enthusiasm and for getting the guidelines out there.  We just hope that in the future they thoroughly look through them to make sure no breeders and pups can be put in a bad situation by following them.

Please test your dogs by both methods as responsible breeders and remember to supplement your dogs with Vitamin K prior to blood testing.  It wouldn’t be bad idea to supplement them for the rest of their lives as well.  Like our moms used to say, vitamins are good for you.  They are also good for the dogs we love.  If anyone has any questions on any of this please feel free to contact either of us.  We will post this info on the MAKK group with links to the papers and websites references.  As we have been recently banned from the other groups, I guess they’re not much interested in this information ;-)  Please read and ask questions as there is no good science that comes without questioning.

Chris's email wheresyourcape@gmail.com

Aprilfawn's email thehappyscientist@yahoo.com

Special thanks to:

The miracle AKK Butterball!!

The brave and ethical breeder Karen Street

Brave Foster owner Vickie Lundquist

Dr Jennifer Kaae, University of Wisconsin

Dr. Beth Callan's lab at Penn

Dr. Jean Dodds

Sara J Israels, MD, FRCPC, Professor of Pediatric Hematology/Oncology,
Section Head of Pediatric Hematology/Oncology/BMT, Department of
Pediatrics and Child Health, University of Manitoba

JN MILLS, RH LABUC and MJ LAWLEY
School of Veterinary Studies, Murdoch University, Murdoch, Western
Australia 6150

The Nationals Academy Press

Urs Giger, PD, Dr. Med.Vet., MS, FVH, Dipl. ACVIM & ECVIM

References:

http://www.emedicine.com/ped/topic3041.htm

http://www.ava.com.au/avj/may97/320.htm

http://ctds.info/vitamink.html

http://www.anyvitamins.com/vitamin-k-info.htm

http://darwin.nap.edu/books/0309034965/html/27.html

http://www.vin.com/VINDBPub/SearchPB/Proceedings/PR05000/PR00103.htm