Because the formation of sickle cells is dependent on the intracellular concentration of deoxyhemoglobin S, we investigated the possibility of altering or preventing sickle-cell crises by reducing serum sodium so as to cause red cells to swell. In three patients with sickle-cell anemia who had been disabled by recurrent painful crises, sustained dilutional hyponatremia was induced by 1-desamino-8-D-arginine vasopressin (DDAVP) in combination with a high fluid intake. Mean corpuscular hemoglobin concentration fell, and the degree of sickling at low partial oxygen pressure was reduced, as determined by morphologic criteria and by increased oxygen affinity of blood. Chronic hyponatremia (serum sodium, 120 to 125 mmol per liter) reduced the frequency of painful crises, whereas acutely induced hyponatremia abbreviated the duration of crises. These results, although preliminary, are encouraging enough to warrant further study of the safety and effectiveness of induced hyponatremia in the prevention and treatment of sickle-cell crises.

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Background Hydroxyurea (HU) increases fetal hemoglobin (HgbF) and ameliorates sickle cell disease (SCD) symptoms. Studies have demonstrated the safety and efficacy of HU in infants and children. Initiation of HU in infancy for children with SCD needs to be implemented in community practice. Procedure Starting in 2011, the Pediatric Sickle Cell Program of Northern Virginia initiated HU in infants with SCD. A prospective longitudinal database tracked the clinical course and outcomes. Results Twenty‐four children with HgbSS who started HU by age 1 were continuously followed for a total of 95 person‐years. Age at the time of analysis ranged from 2 to 7 years. Average hemoglobin at 6‐month intervals ranged from 9.5 + 1.9 to 10.7 + 0.8 g/dL, and average HgbF ranged from 27.8 + 5.0% to 34.1 + 6.6%. Twenty‐seven hospitalizations occurred (0.28/person‐year), all before age 3, including 19 (70%) for fever or infection, five (19%) for splenic sequestration, and one (4%) for pain in an infant prior to starting HU. The treat‐and‐release emergency department visits totaled 68 (0.72/person‐year), including 62 visits (91%) for fever, infection, or viral illness, and two visits (3%) for pain/dactylitis in infants before HU initiation. Splenic sequestration accounted for all five transfusions. No pain episodes requiring medical attention were documented after HU initiation. No complicated acute chest syndrome, no abnormal or conditional transcranial Doppler ultrasound, and no overt strokes occurred. Conclusion Implementation of HU in infancy for patients with SCD in community practice is feasible and is highly effective in preventing disease complications.

We report the case of a 31-year-old woman with protein S deficiency and heterozygosity for the prothrombin 3' UTR mutation who developed an internal jugular vein thrombosis despite therapeutic anticoagulation with a low molecular weight heparin, following in-vitro fertilization. This case indicates that the stimulus to thrombosis in such women is intense and can occur despite apparent therapeutic anticoagulation. Close attention should, therefore, be paid to any women with a personal or family history of thrombosis and the potential thrombotic risks associated with assisted conception must be discussed.

Introduction Approximately 2000 babies are born with sickle cell disease annually in the US. Children with severe forms of sickle cell disease (SCD), such as Hemoglobin SS and Hemoglobin S beta 0 thalassemia (Sbeta0), are at risk for severe anemia, vasoocclusive pain crisis, acute chest syndrome, splenic sequestration, central nervous system ischemia, and shortened life expectancy. The drug Hydroxyurea (HU) increases Hgb F, is effective in ameliorating many sickle cell symptoms, and improves survival. Safety and efficacy of HU in children and infants have been demonstrated. Methods Following publication of the BABY HUG trial results in 2011, the Comprehensive Pediatric Sickle Cell Program of Northern Virginia implemented HU initiation for all infants with Hgb SS or Hgb Sbeta0. HU was prescribed at age 6-7 months for 2 patients and at 9-12 months of age for 22 patients. HU dosage was diligently adjusted at clinic visits to maximize Hgb F. An IRB-approved prospective, longitudinal database was launched to follow each patient's clinical course and outcome in 6-month increments. Data are reported for children born after January 2011 who were started on HU by 12 months of age, followed on HU therapy continuously in this clinic, and were at least 2 years of age by June 2018. Results All 24 children in the analysis have Hgb SS. Sixteen children have been followed for 3 years or more, 11 children have been followed for 4 years or more, 7 children have been followed for 5 years or more, 4 children have been followed for 6 years or more, and 3 children have been followed for 7 years. Average Hgb at 6 months of age was 9.5 g/dL, and ranged between 9.5 and 10.7 g/dL for age 1-7. Average Hgb F was 34.1% at 6 months of age and dipped to 29.1% at 1 year of age, but was maintained above 30% from age 1.5 - 3 years and at 27.8% - 30.5% for age 3.5 - 7 years. For a total of 92 person-years, there were 27 hospitalizations, all within the first 3 years of life. 20/27 (74%) hospitalizations were for fever, pneumonia without hypoxia or need for transfusion, or other infections, 5/27 (19%) were for splenic sequestration, and only 1/27 (4%) hospitalization was for pain that occurred before HU initiation. ED visits totaled 68, 53/68 (78%) were for fever and 47/68 (69%) occurred in the first 3 years of life. Only 2/68 (3%) ED visits were attributed to dactylitis/pain, occurring prior to HU initiation. ED visits after age 3 were all for fevers. The most common complication specific to sickle cell disease was splenic sequestration, which is not preventable by HU. All 4 transfusions given were for splenic sequestration. Conclusion Continuous tracking in a single center observational study demonstrated that continuous HU therapy starting in infancy maintained Hgb and Hgb F at or above pre-HU levels into childhood, is associated with no hospitalizations after age 3 and no ED visits for pain after HU initiation by age 1. No acute chest syndrome requiring oxygen or transfusion, no abnormal or conditional TCD, and no overt strokes occurred in this cohort. Implementation of HU for children with sickle cell disease starting in infancy is feasible in the community and is effective in maintaining high fetal hemoglobin and preventing disease complications. Table. Table. Disclosures No relevant conflicts of interest to declare.