Use of Conventional Transfusion Thresholds Contributes to Ongoing Iron Overload Issues in Patients with Homozygous (SS) Sickle Cell Disease

Introduction: Homozygous sickle cell disease is characterized by chronic anemia which contributes to a clinical course characterized by recurrent pain crisis episodes. These episodes are usually managed with the use of packed red blood cell products. Randomized data is currently available that supports lower transfusion thresholds in non-sickle cell related conditions including but not limited to patients undergoing orthopedic procedures, cardio-vascular interventions and those needing intensive care. Due to lack of similar randomized trials in patients with sickle cell disease, recommendations from other trials are applied to patients with sickle cell diseases as well. However, this has the potential of worsening iron overload states that patients with sickle cell disease usually suffer from.

Methods: Patients with homozygous SS sickle cell disease were evaluated with regarding to transfusion support given during hospitalization for vaso-occlusive pain crisis episodes. The hemoglobin threshold that was used for deciding whether or not to give packed red cell transfusion was studied in patients who were previously getting periodic red blood cell exchange procedures for chronic sickle cell related pain. Serum ferritin levels during the period of exchange transfusion support was compared with levels during simple transfusions. 8 patients were selected from the cohort of patients with homozygous sickle cell disease who had been receiving elective packed red blood cell exchanges. Patients with ferritin levels persistently remaining above 1000 ng/ml were then evaluated with regard to transfusion thresholds used for simple transfusion support during hospitalization for pain crisis episodes.

Results: Six patients had persistently high ferritin levels. Thresholds for simple transfusion in this group were studied. A total of 30 units of packed red blood cells were found to be transfused over a 6-month period. During this period only one patient required an exchange transfusion session. 2 out of 30 units were given for a Hgb level above 7 g/dl. The majority, representing 24 out of the total 30 pack red blood cell units were given above a Hgb threshold of 6.0 g/dl. Only 4 units were given using a Hgb threshold less than 6 g/dl. Mean ferritin level before and after the period of simple transfusion support was 6097 ng/ml and 6076 ng/ml respectively. Mean Hgb level in while on exchange transfusion was 7.4 g/dl and it was 6.9 g/dl in those receiving a simple transfusion protocol.

Conclusions: Transfusion threshold used in patients with homozygous SS sickle cell disease appears to be similar to patients without sickle cell disease. Current practice based on studies including TRICC and TRISS is to keep the Hgb level above 7 g/dl. This has been shown to be safe and in fact even improves patient outcomes. However, in patients with sickle cell disease this may not be appropriate since their baseline Hgb levels are lower to begin with. Also, transfusions don't appear to improve Hgb levels considerably. These patients also tend to have iron overload at baseline which likely will not improve unless all transfusions are limited. Therefore, applying a lower transfusion threshold would be recommended to avoid acute transfusion related issues and long-term iron overload problems in patients with SS disease.