Kennedy G, Norris G, Spence VA, McLaren M, Belch JJF
Vascular Diseases Research Unit, The Institute of Cardiovascular Research, Ninewells Hospital and Medical School, Dundee, UK
The study was funded by ME Research UK and the University of Dundee Anonymous Trust, with further support from the Sir John Fisher Foundation (Educational Grant).
Chronic fatigue syndrome (CFS) is a debilitating condition that has no known aetiology or pathophysiology. Recent investigations by others have suggested that individuals with CFS may have a hypercoagulable state, and the aim of the current study was to investigate various aspects of platelet activation and function in CFS.
The study included 17 patients with CFS and 16 age and sex-matched healthy controls. Platelet aggregation was investigated by looking at photometric changes in citrated platelet-rich plasma, whole blood aggregation was calculated as the percentage fall in single platelet counts, and coagulation tests were performed on an automatic microcentrifugal analyser. Platelet volume was also measured.
A trend was observed for patients with CFS to have lower aggregation results and a reduced mean platelet volume, compared with controls. However, this only reached statistical significance for one result: the rate of the aggregation slope by 1.0 mg/mL collagen was 18 (9–28) for ME/CFS patients and 32.5 (19–36) for controls (Mann-Whitney U test, p=0.029). No significant differences were found for any of the measurements of coagulation.
These results are in contrast to previously reported findings. However, due to the heterogeneous nature of the disease, and the resulting lifestyles of the patients, caution should be taken when comparing one group of patients with another. Nevertheless, we certainly found no evidence of increased platelet activation or of a hypercoagulable state in patients with ME/CFS and, on the basis of these results, anti-platelet or anti-coagulant therapy is not warranted.
Platelets are small cells in the blood which are important in wound healing. When tissue is damaged, platelets stick together around the injury forming a clot to prevent further blood loss. This is called coagulation. However, in some conditions (such as pulmonary embolism) clots can form inappropriately, blocking the blood vessel. Some studies have suggested that the platelets of people with ME/CFS are prone to this.
However, we found that patients with ME/CFS actually tended to have fewer platelets than healthy controls, and these were no more prone to coagulation than normal. Therefore, there seems to be no reason to treat ME/CFS patients with anti-platelet drugs.
These findings contrast with those of previous studies, but may have been due to differences in patient selection and in the conduct of the experiments.
Comment by ME Research UK
Although there have been reports pointing to chronic low-level immune activation in ME/CFS patients (1, 2) no relationship has yet been established between such abnormalities and patients’ symptoms. One group of researchers in particular (3), however, has hypothesised ME/CFS to be a hypercoagulable state, in which immunological disturbances (2) and viral infections (4) could play a central role. To investigate this, these researchers set out to investigate platelet function in patients with a well-documented history of ME/CFS and matched controls.
The patients showed no evidence of increased platelet activation or hypercoagulability, contrasting with previously reported findings by Berg and colleagues (3, 5) suggesting ME/CFS to be an immune system activation of coagulation. What factors might have contributed to these contrasting results? First, it is possible — given the heterogeneity of ME/CFS populations — that the research groups were investigating different types of patients, with different aetiologies and symptom expressions. This is entirely possible given that Berg et al conducted “a blinded prospective study of 54 CFS and/or fibromyalgia patients”, whereas Kennedy et al selected patients on the basis of the specific criteria of the Centers for Disease Control 1994 definition: indeed, Kennedy et al have recently reported fibromyalgia patients to be biologically different toME/CFS patients in a number of key ways (6). Again, the patients in the Berg et al study might have had different medication regimens (known to affect coagulation pathways), and there might have been differences in pre-test exercise levels (exercise influences platelet activity, and patients in the Kennedy study were therefore rested supine for 45 minutes before testing). Finally, there are known to be gender differences in platelet aggregation, with higher levels being reported in women: there were equal numbers of each sex in the Kennedy et al study but similar information on gender ratios was not available from the research reported by Berg et al (3).
However, the hypothesis — that ME/CFS patients have platelet activation indicative of a hypercoagulable state that might require treatment — has not been confirmed, and the authors therefore question the need for specific anti-platelet/anti-coagulant therapy.
- Evengard B, Schacterle RS, Komaroff AL. Chronic fatigue syndrome: new insights and old ignorance. J Intern Med 1999; 246: 455–69.
- Patarca R. Cytokines and chronic fatigue syndrome. Ann NY Acad Sci 2001; 933: 185–200.
- Berg D, Berg LH, Couvaras J, Harrison H. Chronic fatigue syndrome and/or fibromyalgia as a variation of phospholipid antibody syndrome: an explanatory model and approach to laboratory diagnosis. Blood Coagul Fibrinolysis 1999; 10: 435–8.
- Ogawa M, Nishiura T, Yoshimura M, Horikawa Y, Yoshida H, Okajima Y et al. Decreased nitric oxide-mediated natural killer cell activation in chronic fatigue syndrome. Eur J Clin Invest 1998; 28: 937–43.
- Berg DE, Brewer JH. A retrospective study of anti-B2-GPI antibodies and soluble fibrin monomer generation and/or platelet activation as seen in chronic fatigue syndrome/fibromyalgia (abstract). J Autoimmun 2000; 15: A86.
- Kennedy G, Spence V, Khan F, Belch JJF. Plasma endothelin-1 levels in chronic fatigue syndrome. Rheumatology 2004; 43: 252–3.