scott@vtx-cpd.com

Hello again!

Here is the reply from Jon:

‘ Hi there,

It’s generally quite clearly twisted if there’s an issue. The mesentery holding the spleen can look spiralled and like a tornado. The spleen itself is enlarged and usually darker than normal. It’s also often kind of folded on itself – it can look quite like a rose!

I don’t think I’ve seen one getting accidentally twisted when exteriorising. I’ve seen this once or twice with the intestines though. I suppose it’s not impossible to accidentally untwist one. To expand on that though, it’d have to be a random grab of one but of spleen through a small hole and pulling, and being very lucky to have grabbed the correct end and it unfurling. Most of the time, the twisting up is fairly tight and the whole thing would probably pull as a ball, if that’s sensible makes sense.

It’s an interesting question.

Thanks

Jon’

Replying to Gemma H. 23/06/2026 - 15:41

Thanks Gemma!

I am so glad you are enjoying the course!

Scott 🙂

Replying to Gemma H. 17/06/2026 - 14:12

Hi Gemma,

Thanks for your question! I’ll make sure Helen sees it, and we’ll get back to you with some recommendations as soon as possible.

In the meantime, how are you enjoying the course so far? We’d love to hear any feedback you have as you work through the lessons.

I hope you’re doing well, and thanks again for reaching out.

Best wishes,

Scott

Replying to Lesley M. 30/05/2026 - 22:43

Hi Lesley,

Thanks for the update.

To answer your main question first, in an ideal world I would absolutely like to have a bone marrow aspirate and core biopsy because it is really the only way to confidently distinguish PIMA from some of the other causes of severe non regenerative anaemia. That said, in the real world I don’t think it is always essential, particularly if the owners are reluctant and the results are unlikely to significantly alter what you are going to do.

In this case, if the owners told me they were happy to pursue immunosuppression regardless of the marrow findings, then I would be reasonably comfortable continuing treatment without a biopsy. The procedure itself is generally very well tolerated and I would not consider it particularly painful compared with many of the things we routinely do, but it is still an anaesthetic or heavy sedation procedure in a severely anaemic dog and there is always some risk and stress involved.

The bigger question I ask myself is whether the result would genuinely change management. If the answer is no, then I think it is entirely reasonable to continue treating presumptively.

The serial PCVs are interesting. Going from 34% post transfusion on the 20th to 21% on the 29th is obviously disappointing, but not necessarily unexpected. Remember that the transfused red cells are only buying you time while the marrow hopefully starts producing its own cells. The fact that she has fallen back down does not necessarily mean treatment has failed. What I would really like to know is whether there is any evidence of emerging regeneration on blood smear review or repeat reticulocyte counts compared with the original sample.

One thing I would say is that we are still very early in the disease course. She is only about 10 days from the transfusion and only around two weeks into immunosuppressive treatment. Based on the PIMA literature, I would not expect many dogs to have shown a convincing response yet. In the Assenmacher study the median time to a regenerative response was 29 days, and some dogs took substantially longer than that. I think we have to be careful not to judge the success or failure of treatment too early.

To be honest, my biggest concern from what you’ve written is not the haematocrit, it is the owners. Unfortunately many of the dogs that do poorly in the published studies are not necessarily the dogs that cannot respond, but the dogs whose owners understandably run out of emotional, financial or practical tolerance before the marrow has had time to recover.

The panting, PU/PD and lethargy are exactly the things that make these cases difficult. From the owner’s perspective they see a dog that was anaemic, then receives treatment, and now appears miserable because of the steroids. Meanwhile the haematocrit has dropped again, which understandably makes them feel nothing is working.

If it were my case, I would probably spend more time setting expectations than changing medications right now. I would explain that the next two to four weeks are really the critical period. If she can remain stable enough to get through that window, then we have a much better chance of knowing whether she is going to respond.

I think adding cyclosporine is entirely reasonable given the mycophenolate intolerance. Most of these dogs ultimately end up requiring combination immunosuppression anyway, and cyclosporine is probably my preferred second line choice in this situation.

If she proves refractory, there are a couple of additional options worth keeping in mind. There is a recent case report by Yuki and colleagues describing two dogs with confirmed PIMA that failed to respond adequately despite prednisolone and conventional immunosuppressive therapy. Both subsequently achieved complete remission following the addition of oclacitinib. Obviously this is only a two case report, so I would not jump to it early, but it is an interesting rescue option if she continues to struggle despite prednisolone and cyclosporine (Yuki et al., 2023).

For the really refractory cases, I have also seen darbepoetin used occasionally as an adjunct. The evidence is limited and it is not addressing the underlying immune mediated process, but in selected dogs that are proving difficult to get regenerative, particularly where owners are committed and repeated transfusions are becoming problematic, it is something I would at least have on the list of possible rescue therapies. I certainly would not be reaching for it yet, but I would keep it in the back of my mind if we find ourselves several weeks down the line with persistent severe non regenerative anaemia.

Keep me posted. I’d genuinely be interested to hear how she gets on.

Best wishes,

Scott

Hi Silvana,

Yeah, this is really interesting. I’ve actually been aware of this drug for a while, but to be quite honest I haven’t seen it used commercially where I’m working in Canada, so I haven’t had any firsthand experience with it.

Your post has definitely made me think about it again though. I actually wonder why it hasn’t taken off more widely. I suppose part of the reason is that many of us are very comfortable using darbepoetin. We use darbepoetin quite a lot in our CKD patients, and I suspect we continue to reach for it because it’s familiar and we’ve generally had good success with it.

That said, the mechanism behind molidustat is fascinating. It belongs to a newer class of drugs called hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs). Rather than supplying exogenous erythropoietin, these drugs work by inhibiting HIF-prolyl hydroxylase enzymes, which stabilizes hypoxia-inducible factor (HIF). This leads to increased endogenous erythropoietin production, along with effects on iron metabolism, including reduced hepcidin concentrations and improved intestinal iron absorption and transport. In theory, this may produce a more physiologic stimulation of erythropoiesis while also addressing some of the iron dysregulation that contributes to anaemia in CKD patients.

The early efficacy data are certainly encouraging. In the pilot study that supported conditional FDA approval, around 50% of cats achieved either a 4% absolute increase in haematocrit or a 25% increase from baseline by day 28. By day 56, approximately 75% of cats had achieved a clinically meaningful response. The most common adverse event was vomiting, and notably hypertension and seizures were not reported in the study population. A subset of cats was followed for an additional eight weeks and maintained their increased haematocrits while also gaining weight and maintaining stable blood pressure.

One thing I find particularly interesting is that HIF-PHIs may offer advantages in cats that are ESA-resistant or hyporesponsive. Because they also improve iron homeostasis and downregulate hepcidin, they may potentially help address some of the inflammatory and iron-restricted components of CKD-associated anaemia. If larger studies continue to show no worsening of hypertension, they may eventually prove especially useful in cats with concurrent CKD and systemic hypertension.

That said, I don’t think we can say it has been shown to be better than darbepoetin at this stage. As far as I’m aware, there are no head-to-head studies comparing molidustat directly with darbepoetin in cats with CKD-associated anaemia. The advantages are currently more theoretical and practical than proven: oral administration, endogenous erythropoietin stimulation, effects on iron regulation, and conditional approval specifically for feline CKD-associated anaemia.

The safety data are also worth considering. In laboratory studies involving healthy cats, higher doses resulted in significant erythrocytosis/polycythaemia, with some cats removed from the studies after haematocrits exceeded 60%. Clinical findings included abnormal mucous membrane colour, prolonged capillary refill time, tachycardia, and evidence of increased blood viscosity. Histopathologic findings included vascular congestion and thrombotic lesions affecting multiple organs, changes that were attributed to the drug’s pharmacologic effect of stimulating erythropoiesis. Other findings included mild increases in creatinine, potassium, vomiting, and occasional elevations in liver enzymes. Most of these effects were observed at doses higher than those intended clinically, but they certainly reinforce the need for careful monitoring.

The current conditional approval specifies administration at 5 mg/kg orally once daily for up to 28 days, followed by a mandatory treatment break of at least seven days. Weekly haematocrit monitoring beginning around day 14 is recommended to ensure the haematocrit does not exceed the upper reference limit, and treatment should be discontinued if polycythaemia develops.

Your post has definitely made me reconsider it, and I think it’s something worth keeping a close eye on. I’d actually be interested in speaking with our inventory manager to see whether it’s available to us, because I do think it could be worth bringing a bottle in and trying it in some selected patients.

I’m already thinking of a handful of CKD cats that are currently receiving darbepoetin where this might represent a reasonable alternative. It would be fascinating to hear from anyone who has used it in practice and how their patients have responded.

Best wishes,

Scott 🙂