BACKGROUND Rheumatoid arthritis(RA)is a common chronic inflammatory autoimmune disease with the main clinical feature of progressive joint synovial inflammation,which can lead to joint deformities as well as disabilit...BACKGROUND Rheumatoid arthritis(RA)is a common chronic inflammatory autoimmune disease with the main clinical feature of progressive joint synovial inflammation,which can lead to joint deformities as well as disability.RA often causes damage to multiple organs and systems within the body,including the blood hemostasis system.Few reports have focused on acquired coagulation dysfunction resulting from vitamin K-dependent coagulation factor deficiency associated with RA.CASE SUMMARY A 64-year-old woman with a history of RA presented to our hospital,complaining of painless gross hematuria for 2 wk.Blood coagulation function tests showed increased prothrombin time,international normalized ratio,and activated partial thromboplastin time.Abnormal blood coagulation factor(F)activity was detected(FII,7.0%;FV,122.0%;and FX,6.0%),indicating vitamin K-dependent coagulation factor deficiency.Thromboelastography and an activated partial thromboplastin time mixed correction experiment also suggested decreased coagulation factor activity.Clinically,the patient was initially diagnosed with hematuria,RA,and vitamin K-dependent coagulation factor deficiency.The patient received daily intravenous administration of vitamin K120 mg,etamsylate 3 g,and vitamin C 3000 mg for 10 d.Concurrently,oral leflunomide tablets and prednisone were administered for treatment of RA.After the treatment,the patient's symptoms improved markedly and she was discharged on day 12.There were no hemorrhagic events during 18 mo of follow-up.CONCLUSION RA can result in vitamin K-dependent coagulation factor deficiency,which leads to acquired coagulation dysfunction.Vitamin K1 supplementation has an obvious effect on coagulation dysfunction under these circumstances.展开更多
This study examined the changes of activities of vitamin K-dependent clotting factors(VKDCF) under various pathological conditions and explored the relationship between acquired deficiency of VKDCFs and hemorrhage.Cli...This study examined the changes of activities of vitamin K-dependent clotting factors(VKDCF) under various pathological conditions and explored the relationship between acquired deficiency of VKDCFs and hemorrhage.Clinical data of 35 patients who were diagnosed as having acquired deficiency of VKDCF were retrospectively analyzed.Coagulation factors involved in the intrinsic and extrinsic pathways were detected in these patients and 41 control subjects.The results showed that the average activities of VKDCFs were decreased in the patients in comparison to the control subjects and significantly increased after treatment of these patients with vitamin K and blood products.Multivariate regression analysis indicated that decreased activity of VKDCF was not an independent risk factor for bleeding disorders owing to deficiency or metabolic disturbance of vitamin K.It was concluded that acquired deficiency of VKDCF occurs under a variety of pathologic conditions and is closely associated with hemorrhagic events.Administration of vitamin K and transfusion of blood products containing high concentrations of VKDCFs helps alleviate the hemorrhagic diseases.展开更多
目的:研究肿瘤诱发的获得性凝血因子Ⅴ缺乏症(acquired factor V deficiency, AFVD)临床表现特点,探讨肿瘤诱发的AFVD的治疗选择。方法:报道1例肿瘤诱发AFVD患者的临床特征、实验室检查指标、诊治经过并进行相关的文献复习及讨论。结果...目的:研究肿瘤诱发的获得性凝血因子Ⅴ缺乏症(acquired factor V deficiency, AFVD)临床表现特点,探讨肿瘤诱发的AFVD的治疗选择。方法:报道1例肿瘤诱发AFVD患者的临床特征、实验室检查指标、诊治经过并进行相关的文献复习及讨论。结果:老年男性,临床表现为黑便,无遗传性凝血因子缺乏病史及家族史。实验室检查提示凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)显著延长,凝血因子V活性(Factor V∶C)降低,Ⅴ因子抑制物水平升高。PET/CT:结肠及回肠末段代谢增高,提示肿瘤性疾病。对症输注新鲜冰冻血浆(FFP)后疗效欠佳。应用糖皮质激素治疗后出现血压明显升高,继而出现急性硬膜下出血,紧急给予Ⅶ因子抢救,最终放弃治疗出院,院外患者死亡。结论:获得性凝血因子Ⅴ抑制物所致的凝血障碍是一种少见疾病,预后与患者基础疾病相关。对于老年患者需注意除外肿瘤性疾病继发的AFVD以及糖皮质激素治疗的副作用。展开更多
目的:通过检测复合杂合突变导致遗传性凝血因子Ⅴ(FⅤ)缺陷家系的表型和基因突变分析,探讨其分子发病机制。方法:检测先证者及其家系成员(共3代10人)血浆凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、纤维蛋白原(FIB)、FⅤ促凝活性(...目的:通过检测复合杂合突变导致遗传性凝血因子Ⅴ(FⅤ)缺陷家系的表型和基因突变分析,探讨其分子发病机制。方法:检测先证者及其家系成员(共3代10人)血浆凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、纤维蛋白原(FIB)、FⅤ促凝活性(FⅤ∶C)、FⅤ抗原(FⅤ∶Ag)及其他相关凝血指标以明确诊断。采用DNA直接测序分析F5基因的所有外显子、侧翼、5'和3'非翻译区及家系成员相应的突变位点区域,发现突变位点用反向测序证实。使用ClustalX-2.1-win软件分析突变氨基酸的保守性,PROVEAN和MutationTaster在线生物信息学软件预测突变对蛋白质功能的影响,Swiss-PdbViewer软件在突变位点上进行蛋白质模型和氨基酸相互作用分析。结果:先证者PT和APTT较正常对照健康体检者显著延长,分别为34.2 vs 13.2 s和119.3 vs 36.0 s;FⅤ∶C和FⅤ∶Ag极度降低,分别为3%和6%。先证者的第二子、第三子、女儿和孙子的PT和APTT略有延长,FⅤ∶C和FⅤ∶Ag均有不同程度的降低,其他家庭成员的相关凝血参数均在正常范围内。先证者6号外显子上存在c.911G>A杂合错义突变,导致p.Gly276Glu;16号外显子上存在c.5343C>G杂合错义突变,导致p.Ser1781Arg。其第二子、第三子和孙子均携带p.Gly276Glu的杂合子,其女儿携带p.Ser1781Arg的杂合子,其他家庭成员均为野生型。保守分析结果表明,Gly276和Ser1781在同源物种中高度保守。2种生物信息学软件的预测结果相同,PROVEAN(得分-6.214和-12.79)表明,该复合杂合突变是一种有害突变;MutationTaster(得分0.976和0.999)提示,这些突变可能引起相应疾病。p.Gly276Glu蛋白质模型分析显示,Glu侧链延长,分子量变大,这将增加它与周围氨基酸之间的空间位阻,影响FⅤ蛋白的正常局部折叠,最终导致蛋白质活性和含量降低。由于尚无16号外显子FⅤ的X射线3D结构文件,本研究无法对p.Ser1781Arg突变蛋白进行空间结构分析。结论:在本研究中鉴定的新型复合杂合突变(p.Gly276Glu和p.Ser1781Arg)是该家系FⅤ水平下降的主要原因,其中p.Ser1781Arg国内外鲜见报道。展开更多
BACKGROUND Multiple myeloma patients usually present with CRAB symptoms(hypercalcemia,renal disease,anemia and bone diseases)as initial manifestations.Bleeding symptoms are less common,most of which result from thromb...BACKGROUND Multiple myeloma patients usually present with CRAB symptoms(hypercalcemia,renal disease,anemia and bone diseases)as initial manifestations.Bleeding symptoms are less common,most of which result from thrombocytopenia or infiltration of plasmacytoma.Relatively,coagulopathy is not so common,especially isolated coagulopathy without CRAB manifestations,which is very rare.Herein,we report a 54-year old female who was hospitalized for intermittent and recurrent mild oral mucosal hemorrhage without other bleeding symptoms for almost one month or typical myeloma features.CASE SUMMARY Two months before admission,the patient underwent implantation of a permanent pacemaker due to sick sinus syndrome.Prothrombin time and activated partial thromboplastin time were significantly prolonged.Factor X deficiency was demonstrated to account for the coagulation dysfunction.An M protein peak was shown by serum protein electrophoresis.26.11%of abnormal plasma cells were detected in bone marrow by flow cytometry,expressing CD38,CD138,CD56 and intracellular immunoglobulin Kappa light chain.Bone marrow biopsy also proved the presence of abnormal plasma cells,but Congo red stain was negative.The patient was finally diagnosed with multiple myeloma IgA-κtype.A literature review indicated that factor X deficiency was highly related to amyloidosis.Before bleeding signs,the patient had cardiac arrhythmia,enlargement of the heart,and progressive heart failure;thus,cardiac amyloidosis was suspected.CONCLUSION Bleeding related to coagulation dysfunction is uncommon in multiple myeloma,especially as the initial manifestation.Amyloidosis is a well-recognized cause of isolated acquired factor X deficiency.展开更多
基金the National Natural Science Foundation of China,No.81803917 and 81904024.
文摘BACKGROUND Rheumatoid arthritis(RA)is a common chronic inflammatory autoimmune disease with the main clinical feature of progressive joint synovial inflammation,which can lead to joint deformities as well as disability.RA often causes damage to multiple organs and systems within the body,including the blood hemostasis system.Few reports have focused on acquired coagulation dysfunction resulting from vitamin K-dependent coagulation factor deficiency associated with RA.CASE SUMMARY A 64-year-old woman with a history of RA presented to our hospital,complaining of painless gross hematuria for 2 wk.Blood coagulation function tests showed increased prothrombin time,international normalized ratio,and activated partial thromboplastin time.Abnormal blood coagulation factor(F)activity was detected(FII,7.0%;FV,122.0%;and FX,6.0%),indicating vitamin K-dependent coagulation factor deficiency.Thromboelastography and an activated partial thromboplastin time mixed correction experiment also suggested decreased coagulation factor activity.Clinically,the patient was initially diagnosed with hematuria,RA,and vitamin K-dependent coagulation factor deficiency.The patient received daily intravenous administration of vitamin K120 mg,etamsylate 3 g,and vitamin C 3000 mg for 10 d.Concurrently,oral leflunomide tablets and prednisone were administered for treatment of RA.After the treatment,the patient's symptoms improved markedly and she was discharged on day 12.There were no hemorrhagic events during 18 mo of follow-up.CONCLUSION RA can result in vitamin K-dependent coagulation factor deficiency,which leads to acquired coagulation dysfunction.Vitamin K1 supplementation has an obvious effect on coagulation dysfunction under these circumstances.
基金supported by grants from the Ministry of Health of China(No.[2007]353)the National Natural Sciences Foundation of China (N0.30700332)+1 种基金the National Outstanding Youth Foundation(No.30825018)the National Basic Research Program(973 Program,No.2007CB935803)
文摘This study examined the changes of activities of vitamin K-dependent clotting factors(VKDCF) under various pathological conditions and explored the relationship between acquired deficiency of VKDCFs and hemorrhage.Clinical data of 35 patients who were diagnosed as having acquired deficiency of VKDCF were retrospectively analyzed.Coagulation factors involved in the intrinsic and extrinsic pathways were detected in these patients and 41 control subjects.The results showed that the average activities of VKDCFs were decreased in the patients in comparison to the control subjects and significantly increased after treatment of these patients with vitamin K and blood products.Multivariate regression analysis indicated that decreased activity of VKDCF was not an independent risk factor for bleeding disorders owing to deficiency or metabolic disturbance of vitamin K.It was concluded that acquired deficiency of VKDCF occurs under a variety of pathologic conditions and is closely associated with hemorrhagic events.Administration of vitamin K and transfusion of blood products containing high concentrations of VKDCFs helps alleviate the hemorrhagic diseases.
文摘目的:通过检测复合杂合突变导致遗传性凝血因子Ⅴ(FⅤ)缺陷家系的表型和基因突变分析,探讨其分子发病机制。方法:检测先证者及其家系成员(共3代10人)血浆凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、纤维蛋白原(FIB)、FⅤ促凝活性(FⅤ∶C)、FⅤ抗原(FⅤ∶Ag)及其他相关凝血指标以明确诊断。采用DNA直接测序分析F5基因的所有外显子、侧翼、5'和3'非翻译区及家系成员相应的突变位点区域,发现突变位点用反向测序证实。使用ClustalX-2.1-win软件分析突变氨基酸的保守性,PROVEAN和MutationTaster在线生物信息学软件预测突变对蛋白质功能的影响,Swiss-PdbViewer软件在突变位点上进行蛋白质模型和氨基酸相互作用分析。结果:先证者PT和APTT较正常对照健康体检者显著延长,分别为34.2 vs 13.2 s和119.3 vs 36.0 s;FⅤ∶C和FⅤ∶Ag极度降低,分别为3%和6%。先证者的第二子、第三子、女儿和孙子的PT和APTT略有延长,FⅤ∶C和FⅤ∶Ag均有不同程度的降低,其他家庭成员的相关凝血参数均在正常范围内。先证者6号外显子上存在c.911G>A杂合错义突变,导致p.Gly276Glu;16号外显子上存在c.5343C>G杂合错义突变,导致p.Ser1781Arg。其第二子、第三子和孙子均携带p.Gly276Glu的杂合子,其女儿携带p.Ser1781Arg的杂合子,其他家庭成员均为野生型。保守分析结果表明,Gly276和Ser1781在同源物种中高度保守。2种生物信息学软件的预测结果相同,PROVEAN(得分-6.214和-12.79)表明,该复合杂合突变是一种有害突变;MutationTaster(得分0.976和0.999)提示,这些突变可能引起相应疾病。p.Gly276Glu蛋白质模型分析显示,Glu侧链延长,分子量变大,这将增加它与周围氨基酸之间的空间位阻,影响FⅤ蛋白的正常局部折叠,最终导致蛋白质活性和含量降低。由于尚无16号外显子FⅤ的X射线3D结构文件,本研究无法对p.Ser1781Arg突变蛋白进行空间结构分析。结论:在本研究中鉴定的新型复合杂合突变(p.Gly276Glu和p.Ser1781Arg)是该家系FⅤ水平下降的主要原因,其中p.Ser1781Arg国内外鲜见报道。
文摘BACKGROUND Multiple myeloma patients usually present with CRAB symptoms(hypercalcemia,renal disease,anemia and bone diseases)as initial manifestations.Bleeding symptoms are less common,most of which result from thrombocytopenia or infiltration of plasmacytoma.Relatively,coagulopathy is not so common,especially isolated coagulopathy without CRAB manifestations,which is very rare.Herein,we report a 54-year old female who was hospitalized for intermittent and recurrent mild oral mucosal hemorrhage without other bleeding symptoms for almost one month or typical myeloma features.CASE SUMMARY Two months before admission,the patient underwent implantation of a permanent pacemaker due to sick sinus syndrome.Prothrombin time and activated partial thromboplastin time were significantly prolonged.Factor X deficiency was demonstrated to account for the coagulation dysfunction.An M protein peak was shown by serum protein electrophoresis.26.11%of abnormal plasma cells were detected in bone marrow by flow cytometry,expressing CD38,CD138,CD56 and intracellular immunoglobulin Kappa light chain.Bone marrow biopsy also proved the presence of abnormal plasma cells,but Congo red stain was negative.The patient was finally diagnosed with multiple myeloma IgA-κtype.A literature review indicated that factor X deficiency was highly related to amyloidosis.Before bleeding signs,the patient had cardiac arrhythmia,enlargement of the heart,and progressive heart failure;thus,cardiac amyloidosis was suspected.CONCLUSION Bleeding related to coagulation dysfunction is uncommon in multiple myeloma,especially as the initial manifestation.Amyloidosis is a well-recognized cause of isolated acquired factor X deficiency.
