Hrev_master Veins and Lymphatics 2016; volume 5:5985 [Veins and Lymphatics 2014; 3:5985] [page 11] Ulcers in congenital anemia Enzo Fracchia,1 Carla Cantello,1 Amerigo Gori,1 Hugo Partsch,2 Gianluca Forni3 1Department of Vascular and Endovascular Surgery, Galliera Hospital, Genova, Italy; 2Department of Dermatology and Angiology, Medical University of Vienna, Vienna, Austria; 3Department of Thalassemia, Congenital Anemia and Iron Dysmetabolism, Galliera Hospital, Genova, Italy Introduction Survival rates in patients with chronic forms of anemia such as sickle cell disease and tha- lassemia have improved, but the management of comorbidities, such as leg ulcers, remains a challenge. Recalcitrant leg ulcers are a com- mon complication of such conditions and may occur early in life. The incidence of leg ulcers in adults with sickle cell disease is reported to be approximately 30%; ulcers in these patients can last for very long time.1-3 The pathogenesis of ulcerations in congenital anemia is multi- factorial: hypoxia due to anemia, increase of blood viscosity because of bone marrow stimu- lation, changes in the coagulation and fibri- nolytic system, rheological effects, iron over- load, venous stasis causing red blood cell dia- pedesis, followed by extravascular hemoglobin catabolism. The higher intravenous pressure in the upright position acts as a predisposing factor even in the absence of a venous pathol- ogy. Among other factors, hemolysis-induced inflammation resulting from greater osmotic fragility of erythrocytes seems to act as a trig- ger for underlying tissue damage.4 Usually classic treatment is directed against all these pathological factors, by general and local means, which is still considered the basic management. However, the results are rather poor.5-9 The fact that the localization of the ulcers corresponds exactly to typical venous ulcers suggests an underlying venous patholo- gy. Based on this similarity, several authors have postulated venous incompetence as the deciding underlying lesion, although others have not identified venous flow disturbances in a majority of patients. None of our patients had large varicose veins, and venous reflux or venous obstruction was excluded according to duplex ultrasonography in all cases.10 Using the most recent version of clinical severity, eti- ology, anatomy, pathophysiology classification, these cases can be categorized as C6 Ec An Pn, describing active leg ulcers (C6) based on a congenital etiology (Ec) with no anatomical or pathophysiological venous abnormality (An, Pn).11 Doppler ultrasound screening for throm- bophilia was normal in our patients, the ankle brachial pressure index was greater than 1.0. Since every type of treatment had been done and these ulcers seemed to be similar in pathology to venous ulcers the author decided to treat these lesions as if they were venous ulcers. We started to treat these patients with inelastic multicomponent bandages. At the beginning the bandage was difficult to apply (Rosydal sys®; Lohmann and Rauscher, Regensdorf, Germany) but many patients lived far away form the hospital and it was neces- sary to find a single component bandage which was inelastic, cheap and simple applicable by the patients themselves at home. Peha Haft® (Paul Hartmann, Österreich, Austria) was cho- sen: when properly applied it is able to exert a strong pressure and a strong massaging effect due to its stiffness. Walking exercises were encouraged. Non-adherent, absorbent material was used for local dressings. Case Series Ten patients affected by congenital dysery- thropoietic anemia, sikle cell anemia and Thalassemia intermedia with chronic leg ulcers persisting between 12 and 29 years (mean 16 years) without venous out flow dis- turbances in the lower extremities. Compression therapy was able to heal the ulcers in 5 to 8 months (average 7 months) after several attempts of purely local treatment had failed. Once the ulcers had healed, com- pression stockings were prescribed to prevent recurrences. The common denominator in these ten cases was high venous pressure due to gravity. High intravenous pressure caused by sitting and standing without movement is sufficient to trigger chronic inflammation, leading to skin defects on the legs of patients with addi- tional hematological risk factors associated with several microcirculatory abnormalities, as discussed above. Trauma may play an addition- al role by stimulating the damage of red blood cells. The prolonged average healing time of 7 months in our ten patients points is due to the chronic, recalcitrant nature of the ulcers, which had persisted for several years before compression treatment was initiated. Only compression treatment with short-stretch bandages and walking exercises made the ulcers heal. The therapeutic success of good compression therapy in our cases shows that this treatment is able not only to act against venous reflux but also to counteract gravity in cases with normal valve function. Compression not only reduces edema, it also releases vasoactive enzymes from the endothelial cells, improving microcirculation, reducing inflammation, and promoting lymph drainage. This is especially true for non-yield- ing, inelastic bandages, which exert a consid- erable massage effect during walking.12-17 These mechanisms may also explain the bene- ficial effects of compression treatment in patients with other non-venous lesions on the leg, such as vasculitis, cellulitis, and lesions after trauma or surgery. In conclusion, compression therapy was successful in the treatment of the reported cases and should be considered as a compo- nent of treatment strategies for patients with hematological ulcers. In our cases, this simple, inexpensive approach was the winning strate- gy for resolving a longstanding problem. References 1.Trent JT, Kirsner RS. Leg ulcers in sickle cell disease. Adv Skin Wound Care 2004;17:410-6. 2.Josifova D, Gatt G, Aquilina A, et al. Treatment of leg ulcers with platelet- derived wound healing factor (PDWHFS) in a patient with beta thalassaemia inter- media. Br J Haematol 2001;112:527-9. 3.Clare A, FitzHenley M, Harris J, et al. Chronic leg ulceration in homozygous sickle cell disease: the role of venous incompetence. Br J Haematol 2002;119: 567-71. 4.Ackerman Z, Seidenbaum M, Loewenthal E, Rubinow A. Overload of iron in the skin of patients with varicose ulcers. Possible contributing role of iron accumulation in progression of the disease. Arch Dermatol 1988;124:1376-8. 5.Miles MG, Murphy RX Jr. Chronic, nonheal- ing, lower extremity ulcers responsive to splenectomy in a patient with thalassemia major. Plast Reconstr Surg 2003;112:1734- 5. 6.Velez A, Garcia-Aranda JM, Moreno JC. Hydroxyurea-induced leg ulcers: ismacroerythrocytosis a pathogenic fac- Correspondence: Enzo Fracchia, Department of Vascular and Endovascular Surgery, Galliera Hospital, via Ciro menotti 44-45, 3° piano, Sestri Ponente (GE), Italy. E-mail: fracchiaenzo@gmail.com This work is licensed under a Creative Commons Attribution 4.0 License (by-nc 4.0). ©Copyright E. 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