Blood volume and red blood cell volume in ME/CFS

[ME/CFS Skeptic]

This post and others on the thread have been copied or moved from this thread on MEAction Research Summary 2019

One example: The ME Action research summary suggests that a reduced blood volume has repeatedly been found. That seems to contrast with how the latest study on this topic summarized the findings thus far (I should say that I haven't read all of these studies myself, though). The study by Van Campen et al. (2018) is open access so I can quote it at length:

"Only a limited number of studies on blood volume have been performed in those with ME/CFS. Streeten and colleagues found in 12 female CFS patients that the RBC volumes were lower than that of female control subjects, but found in contrast that plasma and whole blood volumes were not significantly different from control subjects (6). Farquhar identified no significant difference in blood volume between ME/CFS patients and simultaneously studied age-matched controls (4), although there was a non-significant trend toward lower blood volume in those with ME/CFS. Hurwitz and colleagues examined 56 with ME/CFS (30 more severely affected and 26 non-severely affected). Total blood volume, erythrocyte volume, and plasma volume were not significantly different from 21 sedentary controls (5). However, when recalculating the reduction from ideal volumes, the percent total blood, plasma, and RBC volumes were all significantly lower in those with ME/CFS than in sedentary controls and also lower in those with severe ME/CFS compared to less severely affected individuals. Of interest, the mean absolute blood volume in our patient population (59 ml/kg) was mid-way between the values for those with severe ME/CFS (57 ml/kg) and non-severe ME/CFS (61 ml/kg) reported by Hurwitz et al. Newton et al. (16) found no significant difference for whole blood volumes between 41 with CFS and 10 healthy controls, but 68% of those with ME/CFS had a RBC volume below 95% of the expected mean volume for healthy individuals."

 

[Jonathan Edwards]

I think your caveat is right @Michiel Tack. Overegging information when relating to medical providers is not necessarily helpful.

I was reasonably convinced that the low blood volume phenomenon was real so I am interested in your analysis.

 

[ME/CFS Skeptic]

I was reasonably convinced that the low blood volume phenomenon was real so I am interested in your analysis.

I don't really have an analysis. From reading the overview of Van Campen, I got the impression that most studies have found negative results (I haven't read all of those studies though). I think David Bell has stressed reduced blood volume in ME/CFS patients in lectures, but I don't know if this is supported by research data (perhaps I should have a look at the studies - EDIT hope I haven't spoken before my turn).

 

[Jonathan Edwards]

I don't really have an analysis.

Ok, an exposition!

 

[ME/CFS Skeptic]

Ok, an exposition!

Did a quick scan of the papers and I don't think there is a study that reported reduced blood volume in ME/CFS patients compared to controls.

Newton et al. (2016) reported an association between reduced cardiac volumes and blood volume in CFS but the blood volume in patients was not significantly different than in controls.

Hurwitz et al. (2010) could not find significant differences in blood volume ME/CFS patients compared to controls, so they focused on differences from the ideal blood volume which did provide statistically significant results compared to controls.

Van Campen et al. (2018) reported lower blood volume in ME/CFS patients compared to normal reference values, but their study didn't use controls.

Street et al. (2000) found no difference in blood volume in ME/CFS patients compared to controls as did Farquhar et al. (2002).

And Miwa & Fujita (2011) wasn't about blood volume but about cardiac stroke volume if I understand correctly.

 

[RDP]

I think David Bell has stressed reduced blood volume in ME/CFS patients in lectures, but I don't know if this is supported by research data (perhaps I should have a look at the studies - EDIT hope I haven't spoken before my turn).

This topic has interested me so, like Michiel, I've tracked down some of the published work. I think Michiel is correct that David Bell often spoke of CFS patients with dramatically decreased blood volume. I believe I saw this in a YouTube video of a talk he gave in Australia years ago. If this is a common finding, decreased blood volume could account for the 30% decrease in cardiac end-diastolic volume and the 25% decrease in cardiac output reported by Hollingsworth (2012).

In contrast, Vermeulen (2014) reports no significant difference in cardiac index, and Farquhar (2002) found no difference in cardiac output (4.1 vs. 4.2 L/min), no significant difference in blood volume, and no significant difference in plasma volume (58.3 vs. 64.2 mL/kg) in 17 (Fukuda) CFS patients compared to 17 age- and gender-matched controls. Moreover, when Bell and colleagues (Streeten, 2000) revisited this subject, they did not find decreased plasma volume in 12 women with ME/CFS. Streeten et al. do report subnormal erythrocyte volume in CFS but I've not been able to find more than the abstract of this paper online. Seeing the data would help us interpret the conclusion of "subnormal erythrocyte volume" and its relationship to blood volume.

Some of these papers are among those cited by Michiel in another post. The Farquhar study is worth reading.

Hollingsworth, K G, T Hodgson, G A MacGowan, A M Blamire, and J L Newton. “Impaired Cardiac Function in Chronic Fatigue Syndrome Measured Using Magnetic Resonance Cardiac Tagging.” Journal of Internal Medicine 271, no. 3 (March 2012): 264–70.

Vermeulen, R. C., and I. W. Vermeulen van Eck. “Decreased Oxygen Extraction during Cardiopulmonary Exercise Test in Patients with Chronic Fatigue Syndrome.” J Transl Med 12 (2014): 20

Farquhar, William B., Brian E. Hunt, J. Andrew Taylor, Stephen E. Darling, and Roy Freeman. “Blood Volume and Its Relation to Peak O2consumption and Physical Activity in Patients with Chronic Fatigue.” American Journal of Physiology-Heart and Circulatory Physiology 282, no. 1 (January 1, 2002): H66–71.

Streeten, David H. P., Delsa Thomas, and David S. H. Bell. “The Roles of Orthostatic Hypotension, Orthostatic Tachycardia, and Subnormal Erythrocyte Volume in the Pathogenesis of the Chronic Fatigue Syndrome.” The American Journal of the Medical Sciences 320, no. 1 (2000): 1–8

@Jonathan Edwards Is there other evidence for decreased blood volume as a common feature of ME/CFS that we should consider?

 

[Amw66]

This topic has interested me so, like Michiel, I've tracked down some of the published work. I think Michiel is correct that David Bell often spoke of CFS patients with dramatically decreased blood volume. I believe I saw this in a YouTube video of a talk he gave in Australia years ago. If this is a common finding, decreased blood volume could account for the 30% decrease in cardiac end-diastolic volume and the 25% decrease in cardiac output reported by Hollingsworth (2012).

In contrast, Vermeulen (2014) reports no significant difference in cardiac index, and Farquhar (2002) found no difference in cardiac output (4.1 vs. 4.2 L/min), no significant difference in blood volume, and no significant difference in plasma volume (58.3 vs. 64.2 mL/kg) in 17 (Fukuda) CFS patients compared to 17 age- and gender-matched controls. Moreover, when Bell and colleagues (Streeten, 2000) revisited this subject, they did not find decreased plasma volume in 12 women with ME/CFS. Streeten et al. do report subnormal erythrocyte volume in CFS but I've not been able to find more than the abstract of this paper online. Seeing the data would help us interpret the conclusion of "subnormal erythrocyte volume" and its relationship to blood volume.

Some of these papers are among those cited by Michiel in another post. The Farquhar study is worth reading.

Hollingsworth, K G, T Hodgson, G A MacGowan, A M Blamire, and J L Newton. “Impaired Cardiac Function in Chronic Fatigue Syndrome Measured Using Magnetic Resonance Cardiac Tagging.” Journal of Internal Medicine 271, no. 3 (March 2012): 264–70.

Vermeulen, R. C., and I. W. Vermeulen van Eck. “Decreased Oxygen Extraction during Cardiopulmonary Exercise Test in Patients with Chronic Fatigue Syndrome.” J Transl Med 12 (2014): 20

Farquhar, William B., Brian E. Hunt, J. Andrew Taylor, Stephen E. Darling, and Roy Freeman. “Blood Volume and Its Relation to Peak O2consumption and Physical Activity in Patients with Chronic Fatigue.” American Journal of Physiology-Heart and Circulatory Physiology 282, no. 1 (January 1, 2002): H66–71.

Streeten, David H. P., Delsa Thomas, and David S. H. Bell. “The Roles of Orthostatic Hypotension, Orthostatic Tachycardia, and Subnormal Erythrocyte Volume in the Pathogenesis of the Chronic Fatigue Syndrome.” The American Journal of the Medical Sciences 320, no. 1 (2000): 1–8

@Jonathan Edwards Is there other evidence for decreased blood volume as a common feature of ME/CFS that we should consider?

Given the different manifestations between Male and female from recent metabolonic/ protoeiomic studies, is there a way to break down research by gender?
It may just throw up something?

 

[RDP]

Thanks to @Michiel Tack, I now have a PDF of the Streeten (Bell) (2000) paper on erythrocyte volume in ME/CFS. Table 4 of that paper shows that neither plasma volume nor total blood volume is altered significantly in the 12 women with CFS studied. This goes some way toward answering the gender question posed by @Amw66.

In view of the Fu (2010) study on POTS and the van Campen (2018/19) study on ME/CFS patients with orthostatic intolerance, perhaps we can draw the tentative conclusion that reduced plasma volume and reduced total blood volume are features of POTS, but not of ME/CFS in general. Results of blood volume and plasma volume tests would then depend on how many ME/CFS patients in the cohort also have POTS.

References:

Fu, Qi, Tiffany B. VanGundy, M. Melyn Galbreath, Shigeki Shibata, Manish Jain, Jeffrey L. Hastings, Paul S. Bhella, and Benjamin D. Levine. “Cardiac Origins of the Postural Orthostatic Tachycardia Syndrome.” Journal of the American College of Cardiology 55, no. 25 (June 22, 2010): 2858–68.

Campen, C. (Linda) M. C. van, Peter C. Rowe, and Frans C. Visser. “Blood Volume Status in ME/CFS Correlates With the Presence or Absence of Orthostatic Symptoms: Preliminary Results.” Frontiers in Pediatrics 6 (2018)