Pregnancy in women with congenital coagulation factor deficiencies has been associated with adverse fetal outcomes. Recurrent spontaneous abortions, placental abruptions, and premature births are reported, the exact reasons for which are not clear, and management of such patients continues to be a challenge. We reviewed the outcome of four pregnancies in a patient with factor X deficiency, and looked at the effect of factor replacement therapy on pregnancy. Her first two pregnancies resulted in the birth of extremely premature babies at 21 and 25 weeks of gestation, both of which died in the neonatal period. The patient was treated with fresh frozen plasma for acute bleeding episodes during these pregnancies. In addition during her second conception she was given factor IX complex [Konyne] prophylactically, but only in the latter half of her pregnancy. During her next two pregnancies she was treated early on during pregnancy, with prophylactic replacement of factor X. She delivered healthy babies at 34 and 32 weeks of gestation, and they are both doing well. We therefore suggest possible mechanisms by which aggressive prophylactic factor support in a female with severe congenital coagulopathy, may improve on fetal outcome.

Introduction We tested the hypothesis that subcutaneous nerve activity (SCNA) of the thorax correlates with the stellate ganglion nerve activity (SGNA) and can be used to estimate the sympathetic tone. Methods and Results We implanted radiotransmitters in 11 ambulatory dogs to record left SGNA, left thoracic vagal nerve activity (VNA) and left thoracic SCNA, including 3 with simultaneous video monitoring and nerve recording. Two additional dogs were studied under general anesthesia with apamin injected into the right stellate ganglion while the right SGNA and the right SCNA were recorded. There was a significant positive correlation between integrated SGNA (iSGNA) and integrated SCNA (iSCNA) in the first 7 ambulatory dogs, with correlation coefficient of 0.70 (95% confidence interval, CI, 0.61 to 0.84, p < 0.05 for each dog). Tachycardia episodes (heart rate exceeding 150 bpm for ≥3 s), were invariably preceded by SGNA and SCNA. There was circadian variation of both SCNA and SGNA. Crosstalk was ruled out because SGNA, VNA and SCNA bursts had different timing and activation patterns. In an 8th dog, closely spaced bipolar subcutaneous electrodes also recorded SCNA, but with reduced signal to noise ratio. Video monitoring in additional 3 dogs showed that movement was not a cause of high frequency SCNA. The right SGNA correlated strongly with right SCNA and heart rate in 2 anesthetized dogs after apamin injection into the right stellate ganglion. Conclusions SCNA recorded by bipolar subcutaneous electrodes correlates with the SGNA and can be used to estimate the sympathetic tone.

The outcomes of children with congenital hemolytic anemia (CHA) undergoing total splenectomy (TS) or partial splenectomy (PS) remain unclear. In this study, we collected data from 100 children with CHA who underwent TS or PS from 2005–2013 at 16 sites in the Splenectomy in Congenital Hemolytic Anemia (SICHA) consortium using a patient registry. We analyzed demographics and baseline clinical status, operative details, and outcomes at 4, 24, and 52 weeks after surgery. Results were summarized as hematologic outcomes, short-term adverse events (AEs) (≤ 30 days after surgery), and long-term AEs (31–365 days after surgery). For children with hereditary spherocytosis, after surgery there was an increase in hemoglobin (baseline 10.1 ± 1.8 gm/dl, 52 week 12.8 ± 1.6 gm/dl; mean ± SD), decrease in reticulocyte and bilirubin as well as control of symptoms. Children with sickle cell disease had control of clinical symptoms after surgery, but had no change in hematologic parameters. There was an 11% rate of short-term AEs and 11% rate of long-term AEs. As we accumulate more subjects and longer follow-up, use of a patient registry should enhance our capacity for clinical trials and engage all stakeholders in the decision-making process.

Purpose The purpose of this study was to define the hematologic response to total splenectomy (TS) or partial splenectomy (PS) in children with hereditary spherocytosis (HS) or sickle cell disease (SCD). Methods The Splenectomy in Congenital Hemolytic Anemia (SICHA) consortium registry collected hematologic outcomes of children with CHA undergoing TS or PS to 1 year after surgery. Using random effects mixed modeling, we evaluated the association of operative type with change in hemoglobin, reticulocyte counts, and bilirubin. We also compared laparoscopic to open splenectomy. Results The analysis included 130 children, with 62.3% (n = 81) undergoing TS. For children with HS, all hematologic measures improved after TS, including a 4.1 g/dl increase in hemoglobin. Hematologic parameters also improved after PS, although the response was less robust (hemoglobin increase 2.4 g/dl, p < 0.001). For children with SCD, there was no change in hemoglobin. Laparoscopy was not associated with differences in hematologic outcomes compared to open. TS and laparoscopy were associated with shorter length of stay. Conclusion Children with HS have an excellent hematologic response after TS or PS, although the hematologic response is more robust following TS. Children with SCD have smaller changes in their hematologic parameters. These data offer guidance to families and clinicians considering TS or PS.

Postthrombotic syndrome (PTS) is a chronic morbidity of venous thromboembolism (VTE) in children. Information about the evolution of PTS is lacking in children. Present study was aimed to evaluate the time-course of extremity PTS in children who were serially followed in a hematology clinic. This retrospective cohort study included 69 consecutive children with documented VTEs that presented with symptoms of extremity VTE: 67 extremity VTEs with or without extension to vena cava, 2 inferior vena cava VTEs. Severity of PTS was assessed using modified Villalta scale. Median age of the cohort was 12.6 years (interquartile range 1.6-15 years) while median follow-up was 28.7 months (interquartile range 13.3-33.4 months. PTS prevalence was 46.8% [95% confidence interval (CI) 37.9-57.7%]. Lower extremity VTE was associated with development of PTS compared to upper extremity VTE regardless of catheter use (P = 0.002). The time-course of PTS fluctuated in 11 of 33 children (33%; 95% CI 20-47%) at a median interval of 12 months from diagnosis of VTE (range 4-14 months): three progressed from mild/moderate to severe, one improved from moderate to mild, seven fluctuated between mild and moderate. Recurrence and incomplete resolution of VTE were associated with variability in PTS severity (P < 0.05). In summary, this study suggested that almost 50% of study cohort developed PTS, and the time-course of PTS was not static in one third of children. Future research should focus on identifying the predictors contributing to the worsening of PTS and developing risk-stratified treatment interventions so as to improve the outcome of children with VTE.