Analysis of seven cases of multiple myeloma with initial manifestation of bleeding / 中华内科杂志

A retrospective analysis of 7 patients of multiple myeloma (MM) with initial manifestation of bleeding and coagulation abnormalities were performed. Clinical manifestations, laboratory and imaging examinations were collected. The activity of coagulation factors was measured before the treatment. Single factor X deficiency was seen in one patient. Two cases had factor Ⅶ deficiency, while four other patients had multiple factor deficiency. The time from onset of symptoms to diagnosis ranged from 2 to 10 months. After anti-MM treatment started and plasma or coagulation factors were transfused, the prolonged coagulation time returned to normal from 28-84 days. Most of these patients presented large, deep and multiple sites of hematoma, which caused concerns of bone marrow puncture and may direct to other differential diagnoses. This is helpful to improve physicians′ understanding of the special clinical characteristics in MM patients.

Congenital factorⅦdeficiency:a report of two cases and literature review / 临床儿科杂志

Objective To study the pathogenesis, clinical characteristics, laboratory tests, treatments and prognosis of con-genital factorⅦdeficiency. Methods The clinical data of two cases of congenital factorⅦdeficiency diagnosed at the Chil-dren’s Hospital of Fudan University and 9 cases reported in the past 10 years retrieved from Pubmed, Web of Knowledge and CNKI, Wangfang database by using the factorⅦdeficiency , congenital, newborn and case report as keyword were reviewed and analyzed. Results All cases were full term birth with normal birth weight (>2 500 g), including 4 females and 7 males. Pa-rental consanguinity was found in 3 cases, and a family history was found in 3 cases. The laboratory tests were characterized by significantly prolonged prothrombin time, normal partial thromboplastin time, and decreased coagulation factorⅦactivity. The coagulation factorⅦactivity of 10 cases were less than 5%. Five cases (45.5%) were treated with human recombinant activated factorⅦ. Four cases (36.4%) treated with plasma or human recombinant activated factorⅦare currently in normal growth and development. Four cases (36.4%) died during the hospitalization. Conclusions A diagnosis of congenital factorⅦdeficiency should be considered in the neonates with severe bleeding, prolonged prothrombin time, normal partial thromboplastin time, and being intractable to vitamin K treatment. Human recombinant activated factorⅦis the first choice of the treatment of congenital factorⅦdeficiency. The further study of gene mutation type will be of great significance for disease screening, diagnosis, treat-ment and prognosis prediction.

Molecular mechanism of a pedigree with inherited coagulation factor Ⅶ deficiency / 中华检验医学杂志

Objective To identify gene mutations and explore the molecular mechanism of a pedigree with inherited coagulation F Ⅶ deficiency. Methods The levels of F Ⅶ: Ag in the proband and other family members were measured by ELISA assay. The values of PT, F Ⅶ: C and other coagulant parameters were determined by one-stage clotting for laboratory phenotype diagnosis. All the exons,exon-intron boundaries and 5',3' untranslated sequences of F7 gene were amplified by direct sequencing. The detected mutations were further confirmed by sequencing the other stand. The CLC Protein Workbench software was used to analyze the species conservation of the mutated site and the protein secondary structure. 100 healthy individuals were selected to exclude gene polymorphism. Results PT, FⅦ∶C and FⅦ: Ag in the proband and his sister were abnormal, which were 36. 3 s, 5.0%, 40. 7% and 33.4 s,5. 0%, 37.4%, respectively. Both PT and FⅦ∶C in the proband's father, mother, daughter and niece were slightly abnormal, which were 14.9 s, 14. 6 s, 15.5 s, 14. 6 s and 70%, 85%, 59%, 79%, respectively.The heterozygous mutations c. 784T ＞ C and c. 964T ＞ G in exon 8 of F7 gene were found in the proband,resulting in the substitutions of Ser269Pro and Cys329Gly respectively. Compound heterozygous mutations c. 784T ＞ C and c. 964T ＞ G were found in the proband's sister. The proband's mother was heterozygous for c. 784T ＞ C. His father, daughter and niece were heterozygous for c. 964T ＞ G. The protein biological characteristics analysis revealed that the Cys329Gly caused the change of spatial configuration, and Ser269Pro led to the change of amino acid polarity and hydrophobicity. Conclusion Compound heterozygous mutations of Cys329Gly and Ser269 Pro in F7 gene may be the underlying molecule mechanism of FⅦ deficiency in this pedigree.

The identification of R152Q and IVS6+1G→T double heterozygous mutation in a Chinese family with inherited F Ⅶ deficiency / 中华检验医学杂志

Objective To identify the gene mutations of an inherited coagulation factor Ⅶ deficiency pedigree.Methods PCR and DNA sequencing were used to identify the FⅦ gene mutations in the proband.The identified mutations were validated by PCR followed by restriction fragment length polymorphism technique or DNA sequencing.100 healthy volunteers were chosen randomly as controls. Results R1S2Q and IVS6+1G→T double heterozygous mutations were discovered in the Droband.The pedigree analysis showed that R152Q missense mutation inherited from his father,and IVS6+1G→Twas from his mother. The R1S2Q missense mutation in exon 6 was not found in 100 healthy volunteers. Conclusion The congenital deficiency of F Ⅶ in the proband might be caused by the coinheritance of the R152Q missense mutation in exon 6 and the splicing donor site mutation ( ⅣS6+1G→T)in intron 6.