Question re: Mildly Elevated Cytochrome B5 Reductase
My symptoms have been ongoing since January 2023, and include chronic profound fatigue with unrefreshing sleep, inappropriate sinus tach, frequent and symptomatic non-sustained vtach, syncope/near-syncope, SOB, transient episodes of hypoxia where SpO2 will drop to the low or mid 80s, and sometimes my doctors can’t get a pulse ox on me at all (my lips, fingertips and toes will be cold and blue when this happens), persistently and increasingly elevated d-dimer for ~2.5 years (started at 592 after first infection, peaked at 2240), which only began to decrease after clinically diagnosed PE and starting on 2x/day LMWH injections (there’s obvs a longer story there but the minute details aren’t really relevant), suspected TIA ~6 months before the PE, persistently mildly elevated platelets (480-585), recurrent pleurisy and pericarditis, and multiple recurrent pleuropericardial effusions, post-exertional malaise with exacerbation of basically all underlying symptoms (for example, I had 3 doctor’s appts in one week recently, which was apparently somehow “too much” strain for me, so within about 2 days of the last appt I wound up in the ED and was admitted with new recurrence of bilateral pleural effusions, persistent tachycardia to the 130s at rest even on 100mg metoprolol, SOB, transient episodes of hypoxia with blue nails/lips, horrible pains in large muscles in my legs, labs during admission again only showed elevated d dimer and platelets and mild metabolic acidosis).
In late October, we’d tried stopping the LMWH after ~4 months of improvement in almost all of my symptoms, and within 2 weeks not only had everything come roaring back and put me back in the hospital again where my d-dimer and platelets had hit their respective peaks, but I also developed another pericardial effusion and new-onset heart failure (LVEF at admission was 38%, despite a totally normal outpatient echo literally a week prior where my EF was 55-60%). This was all part of the same November hospital admission where the screenshotted lab above was drawn. Restarted the LMWH and started GDMT and symptoms again improved. I know that’s kind of a lot and all over the place, but that’s ultimately exactly the issue— the clinical picture just doesn’t make a ton of sense. Everyone’s best guess at present (meaning my PCP, cardiologist, pulmonologist, heart failure specialist, the November hospitalist, and a hospital hematologist who didn’t want to follow me outpatient), is that my symptoms are all post-acute sequelae of Covid-19. But the Cytochrome B5 reductase was ordered as kind of a Hail Mary, let’s throw everything that might fit at the wall and see if anything sticks. When the result came back, the hospitalist said he was only even more confused, because the only clinical significance is if the result is low, as that would suggest methemoglobinemia. He said he’d never seen an elevated result and didn’t quite know what to make of it. But idk if that was bc he was a young attending, or bc it’s actually not a common result, and I just didn’t think to ask him at the time to clarify.
Obviously I’ve been trying to do what I can on my end to figure this out too, and to that end have been reading through (or more like trying and mostly failing to read through) long covid research. But I’m not a doctor or anyone with training, so I’m really just way out of my depth here. That said, I keep coming back to these ideas of microclots, endothelial damage, and mitochondrial dysfunction, because as best I can tell, they seem to offer at least plausible explanations for a lot of what I’ve been experiencing. So trying to put it all together, I guess I’m wondering whether it might be biologically plausible for someone’s cytochrome b5 reductase level to be paradoxically elevated in this type of setting? Like could my body have up-regulated production of this enzyme (is it even an enzyme??) as a way to try to compensate for inadequate oxygen delivery/utilization caused by microclots/endothelial damage/mitochondrial dysfunction, and if so is that something a hematologist might have some ideas on medications or treatment options to try to address it? Or is that just a total nonsense idea wholly unrooted in human biology, that I should def never bring up with my doctors if I don’t want them to think I’m completely batshit crazy? Basically just looking for a temp/sanity check here.