Journal bits 'n' pieces 001 Dog blood types and Methocarbamol CRI

These ‘journal bits ‘n’ pieces’ blogs are meant to be summaries of the background to and findings of interesting journal articles I come across without any intention to discuss the methodology or critique the papers.
 

Dog erythrocyte antigens:

Acierno MM, Raj K, Giger U. DEA 1 Expression on Dog Erythrocytes Analyzed by Immunochromatographic and Flow Cytometric Techniques. J Vet Int Med 2014.  28:592-598.

Blood types refer to antigenic (glyco)proteins on the surface of red blood cells that are genetically determined and lifelong. Although not the only system, the DEA (Dog Erythrocyte Antigen) system is by far the most widely used canine blood type classification system. It is taught that blood types based on this system are DEA 1.1 and 1.2 (possibly a 1.3) as well as DEA 3, 4, 5 and 7. A dog is considered either positive or negative for each blood type. The importance of the blood types for transfusion medicine depends on their antigenic potential: DEA 1.1 is considered to be the most antigenic DEA 1-type and this is the type we test for clinically. However it is acknowledged that limitations of testing undoubtedly mean that there is more to the canine blood types story than we currently appreciate.

If we focus on DEA 1 blood type, the theory has been that a dog is either DEA 1.1 +ve or DEA 1.1 –ve (i.e. he/she either has the DEA 1.1 antigen on the red cells or does not); a DEA 1.1 +ve dog is DEA 1.2 –ve. The antigen strength (antigenic potential) of DEA 1.1 antigens is considered stronger than for DEA 1.2 antigens.

“In the past the DEA 1 blood group system was identified and assessed by polyclonal alloantibodies and was thought to be composed of 2–3 types known as DEA 1.1, 1.2, and possibly 1.3 (A3), with decreasing antigen strengths.”

The study above used flow cytometry and immunochromatographic strip (with densitometry) techniques to further assess the DEA 1 expression among dogs.
66 dogs were tested prospectively.
Immunochromatographic typing kits were provided by Alvedia, Lyon, France

“Using the same monoclonal anti-DEA 1 antibody, there was a significant correlation between test results from both methods, with a complete agreement between strip and flow methods categorizing dogs as DEA 1+ and DEA 1-.”

Based on their results the authors conclude that rather than there being 2-3 sub-types within DEA 1, dogs are in fact on a continuum in terms of the red cell surface antigens they express and it is therefore no longer considered valid to stick with the traditional classification. Until and unless further information comes to light to refute or expand on this study, the authors conclude that we should now just be referring to dogs as DEA 1 +ve or DEA 1 –ve; this is because rather than having different antigens it is in fact about the degree of expression of the same antigen, i.e. a DEA 1 –ve dog does not have the DEA 1 antigen; a DEA 1 +ve dog has the DEA 1 antigen but how strongly it is expressed will vary.

“Utilizing quantitative flow cytometry and an immunochromatographic technique with one monoclonal anti-DEA 1 alloantibody, we found greatly varied, but stable [over time and with prolonged storage] quantitative DEA 1 expression on erythrocytes in 66 dogs. This continuum of DEA 1- to weakly to strongly DEA 1+ is in sharp contrast to the originally described DEA 1 system.”

“…we conclude that a more appropriate typing scheme for the DEA 1 system would be simply DEA 1- and DEA 1+ with weak to strong antigen expression (if a standardized PCV of 20% is used), thus eliminating the poorly defined DEA 1.2 and 1.3 (A3) types.”

The authors’ recommendations:

  • Typing results should be recorded not only as DEA 1 +ve or DEA 1 -veas currently outlined by the manufacturer’s guidelines, but include the degree of DEA 1 +ve (weak to strong).
  • DEA 1 –ve dogs should only receive DEA 1 –ve blood
  • Any donor of any degree of DEA 1 positivity should be considered DEA 1 +ve
  • Because it has been suggested that DEA 1 -ve dogs will mount immune responses against weakly DEA 1 +ve erythrocytes, we recommend classifying any weakly to moderately DEA 1 +ve donor dog as DEA 1 +ve.
  • It is advisable to transfuse weakly DEA 1 +ve dogs with DEA 1 –ve blood, as it is yet unclear if weakly DEA 1+ve dogs could mount an alloantibody response when given strongly DEA 1 +ve erythrocytes.

And the authors acknowledge:

“Little is known about the biochemical and molecular basis of the DEA 1 blood group system… clearly, additional work is required to define the biochemical and molecular genetic characteristics of this erythrocytic antigen.”
 

Methocarbamol:

Methocarbamol is a centrally-acting muscle relaxant related to guaiphenesin whose precise mechanism of action remains unclear. It is recommended as adjunctive therapy in the management of patients with neuromuscular tremorgenic intoxication. To my knowledge there is no good quality published evidence for its use but it is considered to have a favourable risk-benefit profile and therefore widely recommended. An injectable preparation exists but is not (easily) available in the United Kingdom and I have no personal experience of using the injectable preparation. The oral preparation (tablets) can be crushed, dissolved in water and given via orogastric or nasogastric intubation in patients that are unable to swallow; alternatively it can be administered per rectum using a feeding tube or Foley catheter for example.

I was interested to come across this paper:

Draper WE, Bolfer L, Cottam E, et al. Methocarbamol CRI for symptomatic treatment of pyrethroid intoxication: a report of three cases. J Am Anim Hosp Assoc 2013. 49(5):325-328.

“In this report, three cases [2 cats, 1 dog] of pyrethroid toxicity successfully treated with methocarbamol using a continuous rate infusion (CRI) technique are described. To the authors’ knowledge, there have not been any studies previously published regarding the use of a methocarbamol CRI in animals presenting with pyrethroid intoxication.”

“All three patients responded well to methocarbamol IV boluses, and a complete resolution of muscle tremors was achieved after starting a methocarbamol CRI.”

“To the authors’ knowledge, methocarbamol has not been used as a CRI in humans, dogs, or cats; therefore, specific information regarding pharmacodynamics and pharmacokinetics of a CRI are lacking at this point.”

“The dose of methocarbamol used by the authors was based on the published maximum safe dose of 330 mg/kg/day. The initial bolus of methocarbamol administered to the patient was subtracted from the total daily dose, and the remainder was administered as a CRI. The CRI can be administered either as the drug alone on a syringe pump…or as the drug added to a fluid bag…then tapered as necessary. The decision of when to taper, and by how much, is dependent on the clinician and patient. The decision to use a CRI instead of multiple boluses is made for a number of reasons, including reduced stress on the patient (because the tremors rarely return), reduced need for the ICU staff to monitor for recurrence of tremors, and the routine need for less total medication when given as a CRI.”

“Because all three patients were treated with diazepam and/or phenobarbital, it is not entirely clear that the resolution was due to methocarbamol alone. When giving IV boluses of methocarbamol, the muscle tremors should become less intense but the action appears to be short lived…a CRI of methocarbamol should be started immediately after the IV bolus.”

We obviously have to be weary of changing clinical practice on the basis of one uncontrolled case series of 3 patients. That said there is a paucity of evidence for the use of methocarbamol in the first place and intuitively in these patients the use of constant rate infusions seems sensible. So until and unless contradictory information exists, IF I had access to injectable methocarbamol I would use it as an initial dose followed by an infusion with other (more evidenced? Maybe!) therapies as indicated – and also start intravenous lipid emulsion early in these cases but that is a topic for another time!