Functional and Mechanistic Characterization of Limb Ulcers in Patients With Sickle Cell Disease
Condition: Ulcer; Anemia; Sickle Cell Disease
MeSH terms: Anemia, Sickle Cell; Ulcer
Study type: Interventional

Summary: 
      Sickle Cell Disease is the most frequent genetic disease in the world (representing one birth
      over 1900, in France). The polymerization of the abnormal hemoglobin (i.e., HbS) when
      deoxygenated is at the origin of a mechanical distortion of red blood cells (RBC) into a
      crescent-like shape. Sickled RBCs are very fragile and rigid, which lead patients to have
      severe anemia and to develop frequent and repeated painful vaso-occlusive crises.
      Furthermore, the repetition of sickling-unsickling cycles causes irreversible damages to the
      RBCs, which shorten their half-life. Accumulation of free hemoglobin and heme in the plasma
      is involved in blood vessels lesions in both the macro- and micro- circulation.

      The resulting vascular dysfunction could explain why limb ulcers are 10 fold more frequent in
      patients with sickle cell disease compared to the general population and may happen at a
      younger age. Limb ulcers induce significant morbidity (delay of healing between 9 and 26
      weeks in the french cohort), and are associated to significant pain (needing opioid
      pain-killer) and increase the risk of infection. Cost of care is also increased. Moreover,
      ulcers induce missed school and work days.

      Data on cutaneous microcirculation and ulcers physiopathology in patients with sickle cell
      disease are scarce. We want to realise a microcirculatory and neurological functional study
      of patients with with and without ulcers and a characterization of biomarkers present in the
      blood or in the wound fluid which can participate to ulcers physiopathology.

      To ensure healing, adapted therapeutics are essential. Several strategies are proposed such
      as: lifestyle measures (venous compression, lower limb elevation, rest), dressings,
      hyperbaric oxygenotherapy (also used in diabetic ulcers). The project is devoted to study the
      mechanisms involved in leg ulcers and the effects of therapeutical/behavioral strategies.
    


Intervention name(s): patients with limb ulcers; For patients without limb ulcers
Intervention type(s): Diagnostic Test; Diagnostic Test
Intervention description(s): For patients with limb ulcers : at inclusion visit and after healing or at 6 months if ulcer does not heal:
Microvascular analysis (laser doppler, TcPO2),
Neurological analysis ( sensitivity testing with thermal and mechanical test),
Analysis of physical characteristics of red blood cells and inflammatory marks,
Analysis of cytokine and metalloproteases in the wound fluid,
Assessment of healing according usual treatment; For patients without limb ulcers : at inclusion visit only
Microvascular analysis (laser doppler, TcPO2),
Neurological analysis (sensitivity testing with thermal and mechanical test),
Analysis of physical characteristics of red blood cells and inflammatory marks
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: limb ulcers; sickle cell disease; microcirculation; cytokine; wound fluid