Clinical Analysis and Mental Health Survey of Hemophilia Carriers: a Cross-sectional Study.

OBJECTIVE: Hemophilia carriers (HCs), who are heterozygous for mutations in the clotting factor VIII/clotting factor IX gene (F8 or F9), may have a wide range of clotting factor levels, from very low, similar to afflicted males, to the upper limit of normal, and may experience mental health issues. The purpose of this study was to provide genetic information on mothers of hemophilia patients and to understand the clotting factor activity and phenotype of HCs. Additionally, we aimed to investigate the mental health status of HCs in China. METHODS: A total of 127 hemophilia mothers, including 93 hemophilia A (HA) mothers and 34 hemophilia B (HB) mothers, were enrolled in this study. Long distance PCR, multiplex PCR, and Sanger sequencing were used to analyze mutations in F8 or F9. Coagulation factor activity was detected by a one-stage clotting assay. The Symptom Checklist 90 (SCL-90, China/Mandarin version) was given to HCs at the same time to assess their mental health. RESULTS: A total of 90.6% of hemophilia mothers were diagnosed genetically as carriers, with inversion in intron 22 and missense mutations being the most common mutation types in HA and HB carriers, respectively. The median clotting factor level in carriers was 0.74 IU/mL (ranging from 0.09 to 1.74 IU/mL) compared with 1.49 IU/mL (ranging from 0.93 to 1.89 IU/mL) in noncarriers, of which 14.3% of HCs had clotting factor levels of 0.40 IU/mL or below. A total of 53.8% (7/13) of HA carriers with low clotting factor levels (less than 0.50 IU/mL) had a history of bleeding, while none of the HB carriers displayed a bleeding phenotype. The total mean score and the global severity index of the SCL-90 for surveyed HCs were 171.00 (±60.37) and 1.78 (±0.59), respectively. A total of 67.7% of the respondents had psychological symptoms, with obsessive-compulsive disorder being the most prevalent and severe. The pooled estimates of all nine factors were significantly higher than those in the general population (P<0.05). CONCLUSIONS: The detection rate of gene mutations in hemophilia mothers was 90.6%, with a median clotting factor level of 0.74 IU/mL, and 14.3% of HCs had a clotting factor level of 0.40 IU/mL or below. A history of bleeding was present in 41.2% of HCs with low clotting factor levels (less than 0.50 IU/mL). Additionally, given the fragile mental health status of HCs in China, it is critical to develop efficient strategies to improve psychological well-being.

Case Report: Hemophagocytic Lymphohistiocytosis Prior to the Onset of Leukemia in a Boy With CDK13-Related Disorder.

Cardinal features of CDK13-related disorders are characterized by intellectual disability, developmental delay, dysmorphic facial features, structural heart defect and structural brain abnormality. A 9-year-old boy presented with intellectual disability, development delay, characteristic craniofacial features, brain malformation, cryptorchidism, autism spectrum disorder, and recently, recurrent hemophagocytic lymphohistiocytosis (HLH) in a half year period. Further investigation revealed the diagnosis of CDK13-related disorder. Finally, we found the underlying cause of HLH is acute lymphoblastic leukemia. Probably leukemia was a coincidental finding in this boy with CDK13-related disorder, but the case herein suggests that individuals with CDK13-related disorder also face risk of developing cancers. Further detailed information could enable us to clarify this presentation because of only limited investigation in affected cases.

[Analysis of a patient with severe Hemophilia A due to a large duplication of F8 gene].

OBJECTIVE: To report on a case with severe hemophilia A (HA) due to a large duplication of F8 gene. METHODS: Inversion detection, Sanger sequencing, and multiplex ligation-dependent probe amplification (MLPA) were used to detect the mutation in the proband and his mother. RESULTS: The patient, a 7-year-old boy, was diagnosed with severe HA at 8 months. No inhibitor was developed over 150 exposure days. Intronic inversion detection and Sanger sequencing have failed to identify pathogenic variants, while MLPA revealed a large duplication [Ex 1_22 dup (2 copies)] in the proband, for which his mother was a carrier [Ex 1_22 dup (3 copies)]. Large duplications of the F8 gene have so far been found in 24 HA patients, all of whom had a severe phenotype, only one had a history of inhibitors. CONCLUSION: Large duplications of F8 gene are associated with severe HA. The diagnostic rate for HA may be increased by MLPA.

Capillary blood reference intervals for platelet parameters in healthy full-term neonates in China.

BACKGROUND: No consensus has been reached on capillary blood reference intervals for platelet parameters in full-term neonates. We aimed to establish neonatal capillary blood reference intervals for platelet parameters and evaluate influences of sex, gestational age and postnatal age on platelet parameters. METHODS: This study was a prospective investigation and implemented in 594 healthy full-term neonates from 12 to 84 h of age, using SYSMEX XN-9000 haematology automatic analyser by means of capillary blood. Reference intervals for platelet parameters were defined by an interval of 2.5th - 97.5th percentiles. RESULTS: Capillary reference interval for platelet count was (152-464) × 109/L. No significance was found between sex-divided reference intervals for platelet parameters. The values of platelet count changed minimally across gestational age (37-41 weeks) and postnatal age (12-84 h). Reference intervals for other platelet parameters were affected by these factors to a different extent. CONCLUSIONS: We established capillary blood reference intervals for platelet parameters in the first days after birth of full-term neonates in China.