OF NORTH AMERICA
Pregnancy and Sickle Cell Disease
Kathryn Hassell, MD
Colorado Sickle Cell Treatment and Research Center, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, C-222, Denver, CO 80262, USA
ith advances in management, men and women with sickle cell disease are enjoying animproved quality of life well into adulthood, when they may elect to plan a family. Pregnancy has been associated with exacerbation of sickle cell disease and may place women, especially those with sickle cell anemia (HbSS), at an additional risk for obstetric complications. Appropriate management by health care providers familiar with sickle cell diseases and high-risk obstetric care can result in asuccessful pregnancy for most women with sickle cell disease. POTENTIAL PATHOPHYSIOLOGIC INTERACTION BETWEEN SICKLE CELL DISEASE AND PREGNANCY Red Blood Cell Sickling Hemoglobin S polymerization and subsequent red blood cell sickling is associated with hypoxia, changes in red blood cell ion content, hydration, and hemoglobin concentration. Physiologic changes in pregnancy include increased cardiacoutput in response to decreased systemic vascular resistance . Increased tidal volume, minute ventilatory volume, and minute oxygen uptake, reduced functional residual capacity and residual volume, and the increased total pulmonary resistance associated with progesterone  may potentially compromise oxygen delivery. A study of 15 women with sickle cell disease revealed an accentuated increasein cardiac output by an increase in left ventricular enddiastolic volume without associated tachycardia, increased fractional shortening, or decompensation of cardiac function . Nevertheless, previously asymptomatic underlying chronic cardiopulmonary dysfunction might be revealed in some women with sickle cell disease by physiologic stressors in pregnancy. Respiratory alkalosis also develops,which optimizes placental gas exchange but may affect red blood cell sickling. Increased plasma renin and aldosterone activity lead to increased plasma volume and decreased plasma osmolality, which might diminish the risk of red cell dehydration . The cumulative
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impact of these pregnancy-related changes on hemoglobin S polymerization and sickling has not been explored. Vascular Occlusion A variety of factors contribute to vaso-occlusion and chronic organ injury in sickle cell disease. They include the adhesion of red blood cells, increased inflammatory, adhesion, and coagulation proteins,endothelial dysfunction, and the dysregulation of vascular tone. Increased release of adhesion and coagulation proteins, including von Willebrand factor, fibrinogen, and factor VIII, during pregnancy  may exacerbate red blood cell adhesion. The maternal placental circulation is susceptible to vaso-occlusion, which may account for the areas of fibrosis, villous necrosis, and infarction observed in theplacenta from pregnancies in women with sickle cell disease [4–6]. Doppler ultrasound studies have demonstrated evidence of restricted uteroplacental blood flow [7,8], indicative of possible vessel injury, narrowing, or vasoconstriction. Fetal circulation is not directly impacted by sickle red blood cells, and blood flow in the umbilical artery and vein seems to be relatively less affected asassessed by Doppler ultrasound . There is little evidence of inflammation in the fetal circulation, with minimal leukocyte recruitment in the umbilical vessel walls from pregnancies in women with sickle cell disease. Interleukin-8 (IL-8) and IL-6 levels are not increased in cord blood ; however, increased von Willebrand factor staining and vascular endothelial growth factor, as well as...