CFIDS associated with platelet activation?

Discussion in 'Fibromyalgia Main Forum' started by sues1, Feb 16, 2006.

  1. sues1

    sues1 New Member

    Is chronic fatigue syndrome associated with platelet activation?

    Kennedy, Gwen; Norris, Gillian; Spence, Vance; McLaren, Margaret;
    Belch, Jill JF

    Vascular Diseases Research Unit, University Department of Medicine,
    Ninewells Hospital & Medical School, Dundee, UK

    Received 11 December, 2003
    Revised 8 April, 2004
    Accepted 15 April, 2004

    Correspondence and requests for reprints to Dr Gwen Kennedy, Vascular
    Diseases Research Unit, University Department of Medicine, Ninewells
    Hospital & Medical School, Dundee DD1 9SY, UK Tel: +44 1382 632432;
    fax: +44 1382 632333; e-mail:

    Sponsorship: The study was funded by the charity ME Research Group for
    Education and support (MERGE), Perth, UK and a grant from the
    Anonymous Trust, Ninewells Hospital & Medical School, Dundee, UK.
    Further support was also received 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 other
    workers have suggested that individuals with CFS may have a
    hypercoagulable state. This study investigated various aspects of
    platelet activation and function in 17 patients with CFS and in 16
    age-matched and sex-matched healthy controls. Platelet aggregation,
    platelet volume and coagulation tests were performed. Platelet
    aggregation was investigated by means of the photometric changes using
    citrated platelet-rich plasma, whole blood aggregation was calculated
    as the percentage fall in single platelet counts and the coagulation
    tests were performed on an automatic microcentrifugal analyser.

    A trend was observed for the patients to have lower aggregation
    results and a reduced mean platelet volume. However, this only reached
    statistical significance for one result; the rate of the aggregation
    slope by 1.0 μg/ml collagen [CFS patients, 18 (9-28) versus controls,
    32.5 (19-36); 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 CFS and, on the basis of these
    results, anti-platelet or anti-coagulant therapy is not warranted.

    Chronic fatigue syndrome (CFS) is an illness of unknown aetiology
    associated with debilitating fatigue of at least 6 months duration and
    accompanied by a variety of symptoms suggestive of immune and
    neuroendocrine disturbances and abnormalities within the central
    nervous system. Although there are many reports pointing to chronic
    low-level immune activation within many 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 hypothesized that CFS is a hypercoagulable state based on
    a model linking pathogen activated inflammation to cytokine modulation
    of the coagulation system [3,4]. Their model implicates immunological
    disturbances [2] and viral infections [5] are central to the
    hypercoagulable state, and they have also suggested that anticoagulant
    proteins such as protein C and protein S are associated with defects
    in fibrinolysis in this patient group [6]. They have further suggested
    that activation of coagulation may be a final common endpoint of a
    variety of CFS-like illnesses such as fibromyalgia and Gulf War
    Illness [7].

    In support of this, our group has recently shown that patients with
    CFS had significantly elevated platelet poor plasma levels of
    transforming growth factor-β1 and an increased expression of annexin V
    binding to neutrophils when compared with healthy, matched controls
    [8]. Transforming growth factor-β1 is a multi-functional cytokine that
    is stored in the α granules of circulating platelets, is released
    during platelet activation and may be involved in platelet aggregation
    [9]. Annexin V is an anticoagulant protein that preferentially binds
    to negatively charged phospholipids such as phosphatidylserine, which
    is expressed on the outer leaflet of the cytoplasmic membrane during
    the apoptotic process. Phosphatidylserine can induce procoagulant
    responses [10] so an increased expression of annexin V could also
    reflect a procoagulant tendency. The observation of potential markers
    of platelet activation by us alongside the previous work by Berg and
    colleagues suggest that there may be altered platelet function in
    patients with CFS that requires further investigation.

    In order to elucidate this further we set out to investigate platelet
    function in patients with a well-documented history of CFS alongside a
    comparable group of healthy control subjects.

    [ . . . ]

    The CFS patients in this study showed no evidence of increased
    platelet activation or hypercoagulability when compared with healthy
    matched control subjects. These results contrast with previously
    reported findings in CFS patients and bring into question the
    conclusion by Berg and colleagues [3,4] that CFS is an immune system
    activation of coagulation.

    It is worth examining factors that might have contributed to these
    contrasting results; that is, the results reported here showing no
    differences in coagulation pathways between CFS patients and matched
    controls and those by Berg's group showing hypercoagulation in CFS
    subjects. In the first place CFS is a heterogeneous condition, and it
    is possible that we are looking at an entirely unrelated cohort of CFS
    patients with a different aetiology and symptom expression to that of
    Berg et al. Our CFS patient population has been strictly selected to
    fulfil the specific criteria of the Centers for Disease Control 1994
    definition [11] and are representative of the large cohort of patients
    in our research database. In the paper by Berg et al. [3], however,
    they conducted a blinded prospective study of 54 CFS and/or
    fibromyalgia patients and 23 controls, and this is clearly a broader
    case-definition than that used by us. Indeed, we have recently
    reported that fibromyalgia patients are biologically different to CFS
    patients in a number of key ways [17]. In a further paper, Brewer and
    Berg [18] investigated 30 patients with CFS who have at least had one
    positive blood culture for active human herpesvirus-6, and they report
    that samples were taken in the morning and that none of the patients
    were on anticoagulant therapy. The results in this second study were
    reported as being positive from a panel of tests, with no results or
    equivalent control data provided.

    Of further concern is the fact that there is no information about age,
    gender, smoking status, current medications or blood sampling methods
    in the Berg et al. paper, and all of these are known to affect
    coagulation pathways. It should also be stressed that there are gender
    differences in platelet aggregation, with higher levels being reported
    in women [19]. Although CFS female patients outnumber males by
    approximately 3: 1 [20], we had equal number of both sexes within our
    patient and control populations. Similar information on gender ratios
    is not available in the research reported by Berg et al.

    Exercise also influences platelet activity, especially in those who
    lead a sedentary lifestyle when compared with those who are physically
    trained [21], and an increase in platelet-platelet aggregates occurs
    after exercise [22]. This is of particular significance in a patient
    population who, by definition, have a substantial reduction in
    previous levels of occupational, educational, social or personal
    activities [11]. CFS is also characterized by post-exertional malaise
    with patients having less intense and shorter activity peaks followed
    by longer rest periods [23], often for as long as 24 h after the
    activity. Such an activity cycle might actually be expected to reduce
    platelet aggregation given the finding that 45 min of supine rest in a
    calm environment led to a highly significant decrease in platelet
    activation [24].

    In general, although there were no significant differences between
    platelet aggregation in our CFS population when compared with matched
    control subjects, the trend was for lower activity and caution is
    required when interpreting data from this patient group given the
    gender bias and the fact that many patients have a sedentary lifestyle.

    This study was planned to further investigate the work by Berg and
    colleagues and the tenuous observations made by us from early work. On
    the whole no significant differences in platelet function were found
    between the patients with CFS and control subjects. CFS is, however, a
    heterogeneous illness and patients have a variety of adapted
    lifestyles, so caution is needed when comparing one group of patients
    with another.

    In this study there is certainly no evidence of increased platelet
    activation or that a hypercoagulable state exists in patients with
    CFS, and, on the basis of these results, a study of anti-platelet
    therapy in CFS patients is not warranted.
  2. PVLady

    PVLady New Member

  3. Mikie

    Mikie Moderator

    Is from overgrowth of fibrin in the bloodsteram. Platelets can become entangled in the fibrin mass and not be able to get to wounds as quickly. This means that, despite having hypercoagulation, one can hemmorhage or bruise easily.

    The HEMEX Labs website has excellent info on this. We do suffer hypercoagulation, especially if we have chronic infection in our bodies. Studying platelets does not reveal the type of hypercoagulation we have. The ISAC panel tests for fibrin overgrowth. Taking Heparin at low doses is the standard treatment for our kind of hypercoagulation. Before I took the Heparin injections, I would bruise easily and I hemmorhaged following facial surgery. I no longer bleed or bruise easily.

    Love, Mikie

[ advertisement ]