Perioperative blood management of a patient with coagulation factor Ⅴ deficiency and literature review / 中国输血杂志

【Objective】 To explore the perioperative blood management in patients with pancreatic pseudocyst combiend with coagulation factor Ⅴ(FⅤ) deficiency. 【Methods】 Preoperative: In order to determine the effect of cryoprecipitated antihemophilic factor and fresh frozen plasma (FFP) on the elevation level of factor Ⅴ, we alternately infused cryoprecipitate and FFP in the resting state. TEG, coagulation function and coagulation factor activity were monitored before and 1 h, 24 h and 48 h after infusion, and intraoperative and postoperative blood transfusion strategies were formulated. FFP 600 mL and cryoprecipitate 10 U were supplemented preoperatively. Intraoperative: The operation procedure was performed for 7 hours with an infusion of 600 mL FFP without significant bleeding. Postoperative: FFP was infused. 【Results】 Preoperative: The coagulation factor Ⅴ activity on pre-operation was 1.9% and 1.8%. After alternating infusion cryoprecipitate 10 U and FFP 1 200 mL, the FⅤactivity increased to 5.1% and 6.0%, respectively. There was no significant difference in TEG parameters, PT and ATPP results were decreased to varying degrees. Intraoperative: The operation was successful without obvious bleeding. Postoperative: FFP 500 mL was infused 2 h after operation, and FFP 250-500 mL was injected daily from 1 to 7 days after surgery. No significant bleeding was observed in the wound, the results of TEG, PT, APTT and hemoglobin (Hb) did not change significantly compared with those before surgery. The patient was discharged successfully 12 days after surgery. The genetic test results showed that he had inherited coagulation factor Ⅴ deficiency, which was a compound heterozygous variation. 【Conclusion】 Perioperative blood management in patients with FⅤ deficiency combined with surgical disease, requiring pre-transfusion evaluation and post-transfusion evaluation in combination with laboratory investigations and clinical manifestations, cryoprecipitate and fresh frozen plasma can be effective in supplementing coagulation factors. The TEG seems to be better than the Seven items of coagulation function in judging the clotting status of patients with FⅤ deficiency.

Clinical analysis of 6 cases with factor Ⅴ deficiency / 中华全科医师杂志

Six patients with factor Ⅴ deficiency were admitted in Shandong Provincial Hospital Affiliated to Shandong First Medical University from January 2006 to December 2022. All 6 patients presented with symptoms of coagulation dysfunction, 4 patients had recurrent nose bleeding, gingival bleeding, skin ecchymosis as the main manifestations, 1 patient had lower abdominal pain and ovarian active bleeding, and 1 patient had heavy menstruation. The prothrombin time and activated partial thromboplastin time were significantly prolonged, the factor Ⅴ level was significantly lower than normal, and the thrombin time was basically normal in all patients. Four patients received non-surgical treatment and transfusion of fresh frozen plasma; the bleeding symptoms were significantly relieved during hospitalization, and no aggravation of bleeding symptoms was found during follow-up. One patient with active ovarian hemorrhage underwent emergency surgical suture to stop bleeding, and fresh frozen plasma and prothrombin complex were given perioperatively; and no more bleeding occurred during follow-up. One patients with excessive menstruation underwent curettage plus hysteroscopic endometrial ablation, and the amount of menstruation was significantly reduced. It is suggested that the bleeding symptoms of coagulation factor Ⅴ deficiency vary in severity, which can be effectively alleviated by infusion of the fresh frozen plasma in most cases.

Phenotypic and genetic analysis of a pedigree affected with hereditary FⅤ deficiency due to a novel deletional variant of F5 gene / 中华医学遗传学杂志

Objective@#To analyze the phenotype and F5 gene variant in a pedigree affected with hereditary coagulation factor Ⅴ (FⅤ) deficiency.@*Methods@#All of the exons, flanking sequences, and 5′ and 3′ untranslated regions of the F5 gene were subjected to PCR and direct sequencing. Suspected variant sites were confirmed by clone sequencing. Influence of the variants was predicted by using software including ClustalX and Mutation Taster.@*Results@#The prothrombin time (PT) and activated partial thromboplastin time (APTT) of the proband were prolonged to 20.3 s and 59.2 s, respectively, while FⅤ activity (FⅤ∶C) and FⅤ antigen (FⅤ∶Ag) were reduced by 13% and 17%, respectively. The FⅤ∶C and FⅤ∶Ag of his father, sister and daughter were decreased to 35%, 37%, 29% and 42%, 46%, 35%, respectively. The proband was found to carry a heterozygous c. 2851delT variant in exon 13 of the F5 gene, which caused a frameshift and resulted in a truncated protein (p.Ser923LeufsX8). In addition, a heterozygous c. 1538G>A (p.Arg485Lys) variant was found in exon 10. The father, sister and daughter of the proband all carried the p. Ser923LeufsX8 variant, while his mother and son carried the heterozygous p. Arg485Lys polymorphism. His younger brother and wife were of the wild type. Bioinformatic analysis showed that p. Ser923 was highly conserved across various species. Mutation Taster scored 1.00 for the p. Ser923LeufsX8 variant, and the result has predicted a corresponding disease.@*Conclusion@#A heterozygous deletional mutation c. 2851delT in exon 13 of the F5 gene and a heterozygous c. 1538G>A polymorphism harbored by the proband may be associated with the decreased FⅤ level in this pedigree.

Acquired blood coagulation factor Ⅴ deficiency in a patient with severe burn / 中华烧伤杂志

In March 2017, a severely burned male patient aged 36 years with hypovolemic shock was admitted to our hospital. The patient received large quantities of antibiotics and blood products and repeated skin graft after admission, and then he suffered wound errhysis and throat congestion. The patient was healthy before without family history of bleeding or thrombosis disease. Laboratory tests showed that prothrombin time and activated partial coagulation time were remarkably prolonged, blood coagulation factor Ⅴ activity was extremely low, and the result of qualitative test of coagulation factor inhibitor was positive. Acquired blood coagulation factor Ⅴ deficiency was diagnosed. After application of dexamethasone (5 mg, twice per day) and infusion of fresh frozen plasma, blood coagulation indicators of patients recovered in 4 days, the result of qualitative test of coagulation factor inhibitor was negative, and bleeding symptoms were improved.

Procalcitonin combined with coagulation factors in prognosis of cirrhotic patients complicated with spontaneous bacterial peritonitis / 中华临床感染病杂志

Objective To examine the short-term prognostic value of procalcitonin ( PCT ) combined with coagulation factors for cirrhotic patients complicated with spontaneous bacterial peritonitis (SBP).Methods Clinical data of 128 cirrhotic patients complicated with SBP admitted in Jinhua Central Hospital from June 2014 to October 2017 were retrospectively analyzed .In 3 months after admission , 83 patients survived ( survival group ) and 45 patients died ( fatal group ) .The factors related to prognosis were analyzed with Logistic regression and the prediction model was constructed with the weights derived from regression coefficients.The ROC curve and the area under the curve (AUC) of combination of PCT with coagulation factors were used to predict the survival of patients .Results Univariate analysis indicated that the level of PCT , total bilirubin ( TBil ) , serum creatinine ( Scr ) , prothrombin time ( PT ) , prothrombin activity ( PTA ) , blood coagulation factor Ⅱ, Ⅴ, Ⅶ, Ⅸ, Ⅹ, Ⅺ and Ⅻ were factors affecting the prognosis of cirrhotic patients complicated with SBP (P<0.01).Multivariate analysis showed that PCT , blood coagulation factors Ⅴ and Ⅸ were independent factors of short-term prognosis of cirrhotic patients complicated with SBP.The constructed predictive model was Logit (P) =1.200+0.099 ×PCT-0.026 × clotting factor Ⅴ-0.038 ×clotting factor Ⅸ.The sensitivity and specificity of the model were 0.822 and 0.675, respectively, and the AUC was 0.829.Compared with the classic MELD score , the difference was not statistically significant (P>0.05).Conclusions The predictive model based on PCT and coagulation factors Ⅴand Ⅸcan effectively predict the short-term survival of cirrhotic patients complicated with SBP . The overall prognostic ability is not different from MELD score , but the model is more simple and easier to apply.

Factor Ⅴ Leiden mutation is not associated with ischemic stroke in Chinese young adults / 国际脑血管病杂志

Objective To study the correlation between coagulation factor Ⅴ Leiden mutation and ischemic stroke in Chinese young adults. Methods From July 2016 to January 2018, 80 young patients with ischemic stroke (18-45 years) admitted to the Department of Neurology, the First Affiliated Hospital of Shantou University Medical College and 80 controls were enrolled prospectively. The demographic data, vascular risk factors were documented. Sanger sequencing was used to detect factor Ⅴ Leiden mutation. Results The 1691 sites of factor Ⅴ genes in the case group and control group were all wild types. Multivariate logistic regression analysis suggested that hypertension ( odds ratio [ OR ] 4. 308, 95％ confidence interval [CI] 3. 321-5. 067; P = 0. 001), hyperlipidemia (OR 2. 734, 95％ CI 2. 214-3. 378; P = 0. 005), and smoking (OR 5. 293, 95％ CI 3. 003-6. 180; P = 0. 010) were the independent risk factors for ischemic stroke in young adults, and high-density lipoprotein cholesterol (OR 0. 611, 95％ CI 0. 457-0. 709; P = 0. 027) was its independent protective factor. Conclusion Factor Ⅴ Leiden mutation is not associated with ischemic stroke in Chinese young adults. Hypertension, dyslipidemia and smoking are still the main risk factors for ischemic stroke in young adults.

Genetic diagnosis of four combined deficiency of factor Ⅴ and Ⅷ patients / 中华检验医学杂志

Objective To investigate the genetic diagnosis and molecular pathogenesis of four patients with combined deficiency of coagulation factor Ⅴ and Ⅷ and their family members. Methods The APPT, FT, FⅤ: C, FⅧ: C were detected for phenotypic diagnosis. Thrombin generation assay was applied to determine the generation condition of thrombin in patients and healthy controls. Cenomic DNA was extracted from peripheral blood using the TianGen RelaxCene Blood DNA System;amniotic fluid DNA was extracted with phenol-ethyl ether method. The LMAN1 and MCFD2 genes were analyzed by PCR. Gene mutations were detected with nucleotid sequences by using end-labeling dideoxy method. Results The APTT of Proband 1 was significantly prolonged to 88. 2s and her PT was prolonged to 19. 6 s. The combined deficiency was identified with FⅧ (FⅧ: C 24. 2% ) and FV(FⅤ: C 9. 1% ). Proband 2 and 3 were sisters. The coagulation studies revealed that both of them had prolonged APTT (71.6 s and 74.6 s respectively) and PT (22. 1 s and 18. 3 s respectively). The combined deficiency of FⅤ (FⅤ: C 7. 6% and 14. 5% respectively) and FⅧ( FⅧ: C 25% and 19.6% respectively) were identified. Proband 4 was detected to have the prolonged APTT (70.3 s),PT (18.2 s) and the deficiency of FⅤ(FⅤ: C 9. 4% ) and FⅧ (15. 7% ). The remaining phenotype indicators test of the 4 probands were normal. The diagnosis for the 4 probands was combined deficiency of factor Ⅴ and Ⅷ. The proband 1 was detected to have compound heterozygous mutations in LMAN1 gene while having the LMAN1 and MCFD2 direct gene sequencing. One mutation was a small insertion located on exon 8 [ nt912insA (X71661. 1)] that resulted in p. 305frameshiftX20 and her mother was detected to have the same heterozygous mutation on the the locus. The other mutation was located on exon 11: nt1366C > CT ( X71661. 1 ) , p. 456Arg > Stop which was inherited from her father. Amniocyte DNA was detected to have only one heterozygous mutaion [nt1366C > CT (X71661. 1) , 456Arg > Stop] inherited from the father. No mutation in MCFD2 gene was found in proband 1 and her parents. The analysis of the MCFD2 gene in proband 2 and 3 revealed a novel homozygous single base substitution (nt411T>C) in exon 4, which results in the exchange of the amino acid isoleucine by the amino acid threonine at amino acid position 136 (p. Ile136Thr). Sequencing of the whole LMAN1 gene showed that the proband 4 had one homozygous nonsence mutation in the exon 5 of the LMAN1 ( nt615C >T,p. 202 Arg> Stop). All of the 4 probands with combined deficiency of FⅤ and FⅧ showed declined endogenous thrombin potential in the thrombin generation tests. Conclusion The combined deficiency of FⅤ and FⅧ in the proband 1 results from the compound heterozygous mutations ( nt1366C > CT and nt912insA) in LMAN1 gene, which are inherited from her parents respectively. The prenatal genetic investigation for the patient mother with preganency indicates that the fetus is a female carrier with one mutation (nt1366C > CT) inherited from the father. The homozygous missence mutation ( nt411T > C, p. Ile136Thr) in the MCFD2 gene accounts for the proband 2 and 3. The daughter of the proband 2 is a carrier with a heterozygous mutation inherited from her mother. The homozygous nonsence mutation in the LMAN1 gene of the proband 4 results in the deficency of F Ⅴ and FⅧ.

FⅤ Leiden mutation,the anticardiolipin antibodies and ischemic cerebrovascular disease in Chinese patients / 中华神经科杂志

Objective To study the prevalence of FⅤ Leiden mutation and its relationship to anticardiolipin antibodies (aCL) and ischemic cerebrovascular disease (ICVD). Methods The factor Ⅴ Leiden mutation was analyzed in 75 healthy and 118 ICVD patients using PCR-RFLP analysis.The anticardiolipin antibodies level was also measured by enzyme-linked immunosorbent assay along with international standards in 86 patients with ICVD.The resistance to activated protein C(APC-R )was measured in 27 patients. Results The mutation, in heterozygous form, was found in 6 cases out of 118 ICVD patients, with a prevalence of 5.1%.None of the 75 healthy were found to carry the FⅤ Leiden mutation.The patients who carried the FⅤ Leiden mutation were young, whose average age was 50 years old.In 27 patients whose APC-R was measured , 8 patients were positive.In 86 patients whose aCL level was also measured simultaneously, an elevated aCL level was found in 26 cases, of whom 3 cases were found carrying the FⅤ Leiden mutation as well, making the group of patient possess a prevalence of 11.5 %, showing no strongly statistical significance in contrast to the patients without elevated aCL 5.0%.However, within the total of 6 cases with FⅤ Leiden mutation found in this group, 3 cases were patients with elevated aCL.Conclusions It was suggested that although FⅤ Leiden mutation was accounted for a small proportion of patients with ICVD, it might play a crucial role in thrombosis. The prevalence of young patients who carried FⅤ Leiden mutation should be higher.The final combined analysis revealed FⅤ Leiden mutation which is of highly significant relation to aCL in this group of Chinese patients with ICVD.It's detection should be of greatly clinical significance in finding cause, predicting the progress, prevention and treatment.