source: American Society of Hematology

year: 2018

authors: Ugochi Olivia Ogu, Ashley Buscetta, Elena Crouch, Shuo You, Christopher Bradford, Moonseong Heo, Khadijah Abdallah, Giacomo Vinces, Vence L. Bonham, Caterina Minniti

Leg ulcers are a serious complication of Sickle Cell Disease (SCD), often linked to a hemolytic phenotype that includes priapism, pulmonary hypertension (PH) and renal disease. In the SCD pathogenesis, hemolysis and ischemia-reperfusion injuries lead to white blood cell (WBC), platelet and endothelial cell activation, pro-inflammatory cytokine production and subsequent activation of coagulation that tips the balance towards a prothrombotic and inflammatory state. Decreased levels of the naturally occurring anticoagulants (NOACs): protein C (PC), protein S (PS), antithrombin III (ATIII), have been observed in patients with SCD in steady state, with some reports stating no differences between steady state and crisis. This occurs due to decreased production, increased consumption, or a combination of both. However, the definite mechanisms have not yet been elucidated. Factor V Leiden (FVL) and prothrombin G20210A mutations are rare in African Americans and in patients with SCD. We speculated that patients with leg ulcers would have a more pronounced pro-thrombotic phenotype than patients who never developed them.

Conclusions: In SCD patients with leg ulcers, PC and PS levels are significantly lower than in SCD patients without leg ulcers. Additionally, in SCD patients with leg ulcers, there is a trend towards decreased levels of AT III and increased LA positivity. FVL and prothrombin gene mutations were rare in our cohort, consistent with the general population. The above findings did not correlate clinically with a history of DVT/PE in the same population.

Our results of decreased NOACs confirm previous reports from our group that demonstrated similar findings. Of greater significance, however, is our finding that sickle cell patients with leg ulcers have further decreased levels of the NOACs compared to their counterparts without leg ulcers. This finding lends credence to the hypothesis that sickle cell patients with leg ulcers have a procoagulant phenotype (Am J Hematol. 2011 Aug; 86: 705–8, Am J Hematol. 2014 Jan; 89: 1–6). Whether this translates to an increased risk of thromboembolic events remains uncertain. From our findings, it may not be the case for DVTs and PEs. However, further studies evaluating other clinical manifestations such as priapism, PH, stroke, avascular necrosis, and retinopathy, are still needed. Future directions include further correlation with the above-mentioned manifestations to provide a more comprehensive picture.

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