Venous insufficiency is not the cause of leg ulcers in sickle cell disease

Abstract

Leg ulcers are a well recognized complication of sickle cell disease that has been attributed to venous insufficiency. We studied 16 patients with sickle cell disease and active ulcers using venous pulse volume recordings and photoplethysmography (Doppler studies). Based on hemodynamic monitoring, all 16 patients exhibited rapid refilling times, findings that imply venous insufficiency but are also compatible with high-output syndrome or arteriovenous shunting. Direct invasive venous pressure measurements of these patients demonstrated normal pressures in all of the four patients tested. A different set of four patients underwent venography, which also failed to demonstrate venous incompetence. We hypothesize that anemia results in an increase in peripheral arteriovenous shunting in the extremities and that this, together with the high-output syndrome of sickle cell disease, produces plethysmography readings that may be confused with findings observed in venous insufficiency. We conclude that measurements of vascular stasis, as recorded by plethysmography, are usually misinterpreted in sickle cell disease. Normal manometric pressure readings and normal venographic studies suggest that venous insufficiency is not a primary factor in sickle cell leg ulcer formation.

Chronic leg ulceration in homozygous sickle cell disease: the role of venous incompetence

“…Although leg ulcers commonly complicate SS disease, there is controversy on the role of venous incompetence in their genesis or maintenance. Studies in 16 SS patients with leg ulcers in the USA noted rapid venous refilling times but invasive venous pressure measurements were normal in four patients and a further four patients failed to show incompetence on venous angiography (Billett et al , 1991), findings interpreted as secondary to a high cardiac output rather than to venous incompetence. On the other hand, formal physiological studies of venous function in 30 SS patients in Jamaica (15 with leg ulcers, 15 without) showed that ankle refilling times and post‐exercise flux recovery times were shortened in patients with ulcers (Mohan et al, 2000).…”

“…Consistent with venous hypertension are the pigmentary skin changes similar to those in venous ulcers, prominence of superficial veins, the development of ulcers following acute thrombophlebitis, and the tendency for ulcers to heal on bed rest and deteriorate on prolonged standing. Formal studies of venous function in SS disease have reached conflicting conclusions (Billett et al , 1991; Mohan et al, 2000; Chalchal et al, 2001). We have used a hand‐held Doppler to study venous incompetence in patients from the Jamaican Cohort, which provided a representative sample of patients with SS disease, and of controls with a normal haemoglobin (AA) genotype, followed from birth and aged 19–27 years at the time of the study.…”

Venous-Like Leg Ulcers without Venous Insufficiency in Congenital Anemia: Successful Treatment Using Compression Bandages

“…Among other factors, hemolysis‐induced inflammation resulting from greater osmotic fragility of erythrocytes seems to act as a trigger for underlying tissue damage. The fact that the localization of the ulcers corresponds exactly to typical venous ulcers suggests an underlying venous pathology, and based on this similarity, several authors have postulated venous incompetence as the deciding underlying lesion, 3 although others have not identified venous flow disturbances in a majority of patients 5 …”

Sickle cell leg ulcers: associations with haemolysis and SNPs in Klotho, TEK and genes of the TGF‐β/BMP pathway

“…Chronic venous ulcers have been associated with thrombophilia, perhaps because of the relationship between thrombophilia and venous thrombosis (Mackenzie et al , 2002). Whether or not venous pressure abnormalities contribute to the development of sickle cell leg ulcers is inconclusive (Billett et al , 1991; Mohan et al , 2000; Chalchal et al , 2001; Clare et al , 2002). We hypothesised that leg ulcers, similar to other complications of sickle cell disease, might be related to the severity of haemolytic anaemia and be effected by polymorphic genes that could modulate the subphenotypes of sickle cell disease (Adams et al , 1994; Ohene‐Frempong et al , 1998; Sarnaik & Ballas, 2001; Gladwin et al , 2004).…”