Abnormal rheological properties of red blood cells as a potential marker of Gulf War Illness: A preliminary study

Editor’s comment: In the 1980s, L. O. Simpson studied abnormally shaped red blood cells in patients with ME, which he published in a paper, “Nondiscocyte Erythrocytes in Myalgic Encephalomyelitis.” He later summarized his findings in a paper entitled “The Results from Red Cell Shape Analyses of Blood Samples From Members of Myalgic Encephalomyelitis Organisations in Four Countries.” You can read it HERE.

Abstract:

BACKGROUND: Veterans with Gulf War Illness (GWI) experience chronic symptoms that include fatigue, pain, and cognitive impairment. This symptom cluster may be the consequence of impaired tissue oxygen delivery due to red blood cell (RBC) dysfunction.

OBJECTIVE: The purpose of this preliminary study was to determine whether the microrheological behavior of RBCs is altered in GWI.

METHODS: We recruited 17 cases of GWI (GWI+) and 10 age matched controls (GWI-), and examined RBC deformability and aggregation via ektacytometry along with measurement of complete blood counts.

RESULTS: RBCs were more deformable in GWI+, as indicated by higher elongation indices particularly at higher shear stress values (5.33, 9.49, and 16.89) when compared to GWI-. Aggregation formation, stability and kinetics were similar between GWI+and GWI-. Complete blood counts were also similar, with the exception of mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and RBC distribution width (RDW) which was elevated in GWI+.

CONCLUSIONS: In this preliminary study, we observed increased deformability along with increased MCH, MCHC and RDW in veterans with GWI+, which may contribute to the symptomatology of GWI. Further research is required to confirm our findings and the role of RBC microrheology in GWI.

Source: Falvo MJ, Chen Y, Klein JC, Ndirangu D, Condon MR. Abnormal rheological properties of red blood cells as a potential marker of Gulf War Illness: A preliminary study. Clin Hemorheol Microcirc. 2018;68(4):361-370. doi: 10.3233/CH-170262. https://www.ncbi.nlm.nih.gov/pubmed/29660926

Erythrocyte oxidative damage in chronic fatigue syndrome

Abstract:

BACKGROUND: It has been hypothesized that a link exists between erythrocyte metabolism (particularly redox metabolism) and erythrocyte shape and that both are related to erythrocyte deformability. The aim of this research is to confirm the results of earlier studies and to investigate a correlation between erythrocyte morphology and erythrocyte oxidative damage in chronic fatigue syndrome (CFS).

METHODS: Reduced glutathione (GSH), malondialdehyde (MDA), methemoglobin (metHb) and 2,3-diphosphoglyceric acid (2,3-DPG) were measured in 31 patients suffering from CFS and 41 healthy control subjects. Scanning electron microscopic studies of the erythrocytes from both groups were also carried out.

RESULTS: There was evidence of oxidative damage in CFS with statistically significant increases in 2,3-DPG (p < 0.05), metHb (p < 0.005) and MDA (p < 0.01). The CFS patients in this study also had significantly more stomatocytes in their blood than the normal subjects (p < 0.005).

CONCLUSIONS: There is a strong likelihood that the increase in erythrocyte antioxidant activity is associated with the presence of stomatocytes. The results of this study provide further evidence for the role of free radicals in the pathogenesis of CFS and a link between erythrocyte metabolism and erythrocyte shape.

 

Source: Richards RS, Wang L, Jelinek H. Erythrocyte oxidative damage in chronic fatigue syndrome. Arch Med Res. 2007 Jan;38(1):94-8. Epub 2006 Nov 3. https://www.ncbi.nlm.nih.gov/pubmed/17174731

 

Bioaccumulated chlorinated hydrocarbons and red/white blood cell parameters

Abstract:

The potential relationships between chlorinated hydrocarbon contamination in human serum and red/white blood cell profiles were investigated by multivariate techniques to assess the cellular response patterns to high and low organochlorine levels in the serum.

Twenty-three healthy control subjects and fourteen patients with unexplained and persistent fatigue were divided on the basis of (a) high or low total organochlorine content, (b) high or low DDE (1,1-dichloro-2,2-bis(p-chlorophenyl) ethene) content, and (c) high or low HCB (hexachlorobenzene) content. Discriminant function analysis revealed that the groups with high organochlorine content had significantly different red/white blood cell profiles compared with the low organochlorine groups ((a) P < 0.017, (b) P < 0.015, and (c) P < 0.0002). As a variable, the percentage of neutrophils was the most important discriminant parameter for differentiating between the high and low total organochlorine groups.

Thirteen of the fourteen fatigued patients were characterized as “high total organocholorine content” (P < 0.04). The red cell distribution width was elevated in the high DDE group (P < 0.04) and was the most important discriminant parameter for differentiating between the high and low DDE groups. The percentage of eosinophils and the hemoglobin content were both reduced in the high HCB group (P < 0.009,P < 0.003, respectively) and the percentage of eosinophils was the most important discriminant parameter for differentiating between the high and low HCB groups. Those patients with unexplained and persistent fatigue had significantly higher levels of DDE compared with the controls and had different specific blood cell responses to organochlorines compared with control subjects.

 

Source: Dunstan RH, Roberts TK, Donohoe M, McGregor NR, Hope D, Taylor WG, Watkins JA, Murdoch RN, Butt HL. Bioaccumulated chlorinated hydrocarbons and red/white blood cell parameters. Biochem Mol Med. 1996 Jun;58(1):77-84. http://www.ncbi.nlm.nih.gov/pubmed/8809349

 

Red cell shape changes following trigger finger fatigue in subjects with chronic tiredness and healthy controls

Abstract:

AIMS: To investigate the possibility of a correlation between the percentage of nondiscocytic erythrocytes and muscle fatiguability in subjects with the symptom of chronic tiredness.

METHODS: Sixty nine volunteers suffering from persisting or intermittent tiredness and 72 healthy controls provided 3-drop samples of venous blood for red cell shape analysis before and after inducing fatigue in the trigger finger muscles by repeatedly pulling the trigger of an antique revolver. Elapsed time and the number of pulls were recorded. A work index was calculated from the number of trigger pulls divided by the time in seconds then multiplied by the number of trigger pulls.

RESULTS: Subjects with tiredness had fewer discoid cells (males 62.5% vs 69.2%, p = 0.029; females 65.8% vs 71.8%, p = 0.002) than controls. They also had fewer trigger pulls (males 62.3 vs 84.0, p = 0.003; females 29.5 vs 36.8, p = 0.042) and lower “work indices” (males 75.6 vs 104.7, p = 0.001; females 26.1 vs 39.6, p = 0.001) than controls at the first trigger pulling. After 5 minutes rest the number of trigger pulls for males was fewer than the controls (56.0 vs 64.2) but the difference was not significant, but the female values (24.3 vs 33.2) were significantly different (p = 0.008). Work indices for both sexes were significantly different from controls (males p = 0.020, females p = 0.001).

CONCLUSIONS: The association of increased nondiscocytes and impaired muscle function could indicate a cause and effect relationship. This would be in agreement with the physiological concept of fatigue as a consequence of inadequate oxygen delivery.

 

Source: Simpson LO, Murdoch JC, Herbison GP. Red cell shape changes following trigger finger fatigue in subjects with chronic tiredness and healthy controls. N Z Med J. 1993 Mar 24;106(952):104-7. http://www.ncbi.nlm.nih.gov/pubmed/8474717

 

Myalgic encephalomyelitis

Comment on: Myalgic encephalomyelitis. [J R Soc Med. 1991]

 

The exchange of views between Drs Wessely and Wilson in the correspondence columns of the March issue of the Journal (March 1991 JRSM, p 182) highlights the divergence of opinion concerning the nature of myalgic encephalomyelitis (ME).

Recognition of ME as a significant health problem in New Zealand dates from an outbreak of ‘Tapanui ‘flu’ in a small country town in 1983. As it seemed possible that the wide range of symptoms could be indicative of impaired capillary blood flow, we studied the filtrability of blood samples from members of ME support groups. We found that subjects who were acutely unwell had prolonged blood filtration times which returned towards normal in the chronic state.

More recently it has been shown that ME symptoms are associated with increased percentages of nondiscocytic erythrocytes and the percentage of such cells showed an inverse correlation with wellbeing. The significance of altered red cell shape in the pathogenesis of ME has been discussed and it has been found that an injection of vitamin B12 improved wellbeing within 24 h. The loss of symptoms was associated with reduced percentages of nondiscocytes in about 50% of subjects. Those who failed to perceive a beneficial response from the B12 showed no change in red cell shape. Further studies at varying degrees of completion confirm and extend the published observations.

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1295578/pdf/jrsocmed00119-0075a.pdf

 

Source: Simpson LO. Myalgic encephalomyelitis. J R Soc Med. 1991 Oct;84(10):633. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1295578/

 

Red blood cell magnesium and chronic fatigue syndrome

Abstract:

The hypotheses that patients with chronic fatigue syndrome (CFS) have low red blood cell magnesium and that magnesium treatment would improve the wellbeing of such patients were tested in a case-control study and a randomised, double-blind, placebo-controlled trial, respectively.

In the case-control study, 20 patients with CFS had lower red cell magnesium concentrations than did 20 healthy control subjects matched for age, sex, and social class (difference 0.1 mmol/l, 95% confidence interval [CI] 0.05 to 0.15).

In the clinical trial, 32 patients with CFS were randomly allocated either to intramuscular magnesium sulphate every week for 6 weeks (15 patients) or to placebo (17).

Patients treated with magnesium claimed to have improved energy levels, better emotional state, and less pain, as judged by changes in the Nottingham health profile. 12 of the 15 treated patients said that they had benefited from treatment, and in 7 patients energy score improved from the maximum to the minimum.

By contrast, 3 of the 17 patients on placebo said that they felt better (difference 62%, 95% CI 35 to 90), and 1 patient had a better energy score. Red cell magnesium returned to normal in all patients on magnesium but in only 1 patient on placebo. The findings show that magnesium may have a role in CFS.

Comment in:

Magnesium and chronic fatigue. [Lancet. 1991]

Magnesium and chronic fatigue syndrome. [Lancet. 1991]

Magnesium and chronic fatigue syndrome. [Lancet. 1991]

Intravenous magnesium loading in chronic fatigue syndrome. [Lancet. 1992]

 

Source: Cox IM, Campbell MJ, Dowson D. Red blood cell magnesium and chronic fatigue syndrome. Lancet. 1991 Mar 30;337(8744):757-60. http://www.ncbi.nlm.nih.gov/pubmed/1672392