Acute Hemodynamic and Vascular Effects of Transfusion in Chronically Transfused Patients with Sickle Cell Anemia.

Patients with sickle cell anemia (SCA) who are at risk for stroke or develop recurrent episodes of acute chest are often placed on chronic transfusion therapy. The acute hemodynamic and vascular consequences of transfusion are poorly characterized. In order to better characterize chronic changes in these patients, it is important to understand the acute changes involved with this intervention.

We enrolled SCA patients who are on chronic transfusion therapy in a prospective study to determine the cardiovascular effects of a single transfusion. The patients were older than 10 years of age, received chronic transfusions for greater than one year, and were crisis free for more than four weeks. All patients were studied immediately prior to transfusion and repeated within five days. Brachial artery relaxivity, laser doppler capillary blood flow monitoring, and near infrared spectroscopy of the hand was done in the setting of post occlusive reactive hyperemia. Studies included complete cardiac echocardiogram as well as laboratory markers of hemolysis, iron levels, blood count, viscosity and inflammation were obtained pre and post transfusion. Statistics utilized paired t-tests for paired data and for correlative data t-tests and chi square analysis was used.

There are 15 patients enrolled in the study with an average age of 18.7yrs. There are 8 females and 7 males with average ages of 20.6 and 16.4 yrs respectively. With transfusion, hemoglobin increased from 9.4 g/dl to 11.6 g/dl post (p<0.0001), reticulocyte count decreased from 12.4% to 7.8% (p=0.0019) and HbS% decreased from 38.2% to 31.5% (p=0.0001). Markers of hemolysis (LDH, Plasma Free Hemoglobin, Arg/Orn Ratio) do not differ significantly pre and post transfusion. Cardiac index decreased from 5.4L/min/m2 to 4.1 L/min/m2 (p=0.0012), resulting from decreased stroke volume (70.8ml to 58.9ml, p=0.0119) and lower heart rate (84 to 78bpm, p=0.0098). Systolic and diastolic function metrics were unchanged, as was estimates of pulmonary artery pressure. Blood pressure was unchanged, indicating that the change in cardiac output was matched by parallel changes in total vascular resistance. Endothelial function and regional vascular reactivity assessed using laser Doppler capillary flow analysis demonstrated no significant change in hyperemic response pre and post transfusion. Blood viscosity increased with transfusion in a shear-rate dependent manner, for low shear rates the viscosity increased an average of 62% using fully oxygenated samples and at higher shear rates the viscosity increased an average of 25% using fully oxygenated samples.

Transfusion therapy predictably increased oxygen carrying capacity, lowered reticulocyte count and %hemoglobin S. While these changes might improve tissue oxygen delivery, parallel changes in vascular resistance served to maintain relatively constant oxygen delivery. The rise in vascular resistance could result from increased blood viscosity or changes in vascular tone; we are currently conducting studies to try to separate these mechanisms. Despite the 24% reduction in cardiac index, no significant change was observed in microvascular perfusion or its response to forearm occlusion. The vascular system of SCA patients demonstrates chronic endothelial dysfunction but was not acutely influenced by transfusions, consistent with the lack of acute improvement in surrogates for hemolysis or nitric oxide metabolism. Further work is necessary to determine whether transfusion-mediated changes in tissue oxygen delivery vary among different organs and vascular beds.

Wood:Novartis: Research Funding.