Fatigue is a condition that is used in our everyday life with subjective importance and great effect

Fatigue is a condition that is used in our everyday life with subjective importance and great effect. Alternatively terms like tiredness, drowsiness, lack of energy, and exhaustion are used while in the literature, the definitions of fatigue vary greatly, making the identification of the condition more difficult, as there are only few differentiating factors between causes, assessment indicators and the results that fatigue causes on human beings 1, 2.
To a large extent, fatigue is defined either as a subjective symptom or as an objective reduction in the individual’s performance 3, but it has also been described as an independent syndrome chronic fatigue syndrome. Through the existing research up to now, it is recognized that fatigue is generally complex and / or multifactorial 4, 5, as it includes both physiological and psychological parameters, but also occupational and life events 5-8.

1.2 Fatigue in hemoglobinopathies
Up to now, there are few studies regarding fatigue as a syndrome in patients with both hemoglobinopathies and Mediterranean anemia in particular. Specifically due to the fact that Mediterranean anemia is a disease that put limits in the patient, as it requires continuous transfusions as well as specific activities that keep the level of hemoglobin stable to reduce the symptoms, the reduced hemoglobin value has been associated with increased fatigue 9. Chronic anemia has also been associated with fatigue as the transfusion itself seems to lead to fatigue in accordance with thalassemia guidelines 10
And while fatigue is a widespread symptom in recent years and its incidence varies between 7% and 45% 11 in the working population, 12 it is also a common symptom in patients with chronic conditions 13-16, especially when there is a comorbidity with another disease 17, 18. There is only one study dealing with fatigue in patients with Mediterranean anemia, exploring the effect of carnitine and folic acid in reducing fatigue and muscle weakness in patients with homozygous Mediterranean anemia with positive results in the reduction of muscle weakness 19. Also, in two case studies, that were published a few years ago, it is reported that paroxysmal nocturnal hemoglobinuria, which is also one of the hemoglobinopathies, may be accompanied by fatigue 20 and the same may happen in the case of other hemoglobinopathies 21. Finally, there is a study that describes the existence of fatigue in sickle cell anemia as one of the major symptoms along with pain 22.
However, there are no systematic reviews on the overall effect of fatigue studying the factors that affect fatigue in thalassemia and other hemoglobinopathies.

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1.3 Rationale and significance
Although anemia is not a disease, it can be characterised as a condition which results from impaired erythrocyte production, inadequate haemoglobin production, blood loss or abnormal erythrocyte maturation which is the case in hemoglobinopathies. The severity of clinical symptoms of anemia varies according to how effective the compensatory activity that is mobilized to increase oxygen delivery to vital tissues will be. As a result, when the anemic condition persists over time, like the case which happens in hemoglobinopathies, those compensatory mechanisms become exhausted and the patient suffers from dyspnea, tachycardia and palpitations, vertigo and fatigue, even when he or she is resting 23. Like other conditions that impairs tissue oxygenation, fatigue when coexists with anemia, reduces patients ability to engage in the everyday normal activities and depression and stress may occur which makes this fatigue an intolerable physiologic and emotional burden 24, 25.
According to the previous information one can realise that it is important to discover whether this fatigue is a symptom of anemia 26 or psychologically related since this can differentiate the treatment which can be used 27 in order to allow patients with hemoglobinopathies to live a life with a better quality of life.
However, there are no systematic reviews searching for the ways to differentiate the reason for fatigue in patients with hemoglobinopathies and further give us standardised measurements for the estimation of fatigue and the factors that may affect it in thalassemia and other hemoglobinopathies.
Consequently, we need to investigate the effectiveness of these measurements in order to plan effective treatment options based on the factors affecting the symptom of fatigue.
This review’s findings will promote the design of measurements to assess fatigue in patients with chronic hemoglobinopathies, that will be based on measurements that can differentiate between symptom and psychology related fatigue.


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