Objective: To analyze the clinical characteristics, laboratory examination, diagnosis, treatment, and outcome of hereditary factor Ⅹ (FⅩ) deficiency. Methods: Clinical data of 11 patients with congenital FⅩ deficiency were retrospectively analyzed from July 2009 to February 2021. Results: There were 3 males and 8 females. Median age was 39 (5-55) years. The media duration of follow-up was 81.67 (1.87-142.73) months. Of the 11 patients, 10 had bleeding symptoms, 7 had ecchymosis or hemorrhage after skin bump, 7 had nosebleed, 6 had gingival hemorrhage, and 1 had muscle hematoma. Among the female patients, 6 had menorrhagia and 1 experienced bleeding after vaginal delivery. Family history of FⅩ deficiency was found in one case. Eight patients had a history of surgery, and four had postoperative bleeding. Laboratory findings were characterized by significantly prolonged activated partial thromboplastin time, prothrombin time, and decreased FⅩ activity (FⅩ∶C) . Four cases underwent gene mutation analysis and five new mutations were found. Four cases were treated with prothrombin complex concentrates (PCC) and seven cases with fresh frozen plasma (FFP) . One female patient had significantly reduced menstrual volume after PCC prophylactic therapy. One patient received FFP for prophylactic infusion with no bleeding during and after the operation. Conclusion: Most patients with congenital FⅩ deficiency had bleeding symptoms and there was no significant correlation between severity of bleeding symptoms and FⅩ∶C. Prophylaxis should be applied in patients with severe bleeding tendencies. Gene mutation test is significant for screening, diagnosis, and prognosis prediction of congenital FX deficiency.
Adolescent ; Adult ; Blood Coagulation Factors/therapeutic use* ; Blood Coagulation Tests ; Child ; Child, Preschool ; Factor X Deficiency/genetics* ; Female ; Hemorrhage/drug therapy* ; Humans ; Male ; Middle Aged ; Plasma ; Retrospective Studies ; Young Adult

OBJECTIVETo identify potential mutation underlying coagulation factor X (FX) deficiency in a consanguineous Chinese pedigree.

METHODSProthrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, FX activity (FX:C) and other coagulant parameters were determined with a one-stage clotting assay. The FX antigen (FX:Ag) was determined with an ELISA assay. All coding exons and exon-intron boundaries of the F10 gene were amplified with PCR and subjected to direct sequencing. Suspected mutation was confirmed by reverse sequencing and analyzed with CLC Genomics Workbench 7.5 software.

RESULTSThe PT and APTT in the proband were prolonged to 67.2 s and 102.9 s, respectively. Further study showed that her FX:C and FX:Ag were reduced by 1% and 8%, respectively. The PT of her father, mother, and little brother were slightly prolonged to 14.5 s, 14.4 s and 14.4 s, respectively. The FX:C and FX:Ag in her father, mother and little brother were all slightly reduced. Genetic analysis of the proband has revealed a homozygous G>A change at nucleotide 27881 in exon 8 of the F10 gene, which predicted a p.Val298Met substitution. The proband's father, mother, and little brother were all heterozygous for the p.Val298Met mutation. The proband has inherited the homozygous mutation from her parents by consanguineous marriage. Other family members were all normal. Bioinformatics analysis has indicated that this mutation may result in changes in the secondary structure of the FX protein.

CONCLUSIONA homozygous mutation g.27881G>A(p.Val298Met) of the F10 gene has been identified, which probably accounts for the low FX concentrations in this pedigree.

Adult ; Amino Acid Sequence ; Consanguinity ; Factor X ; genetics ; Factor X Deficiency ; genetics ; Female ; Homozygote ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Mutation, Missense ; Pedigree ; Prothrombin Time

OBJECTIVETo identify potential mutations and explore the molecular mechanism underlying combined inherited coagulation factors VII(FVII) and X(FX) deficiency for a family featuring consanguineous marriage between maternal cousins.

METHODSProthrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, FVII activity (FVII:C), FX activity (FX:C), FVII antigen (FVII:Ag), FX antigen (FX:Ag) and other coagulant parameters of the proband and 5 family members were measured. Potential mutations in exons, exon-intron boundaries and 5', 3' untranslated sequences of F7 and F10 genes were screened by polymerase chain reaction and direct sequencing. Suspected mutations were confirmed by sequencing the opposite strand.

RESULTSPT and APTT of the proband were obviously prolonged to become 76.4 s and 60.2 s, respectively. FVII:C, FVII:Ag,FX:C and FX:Ag of the proband were obviously reduced to become 4%, 6%, 6% and 33%, respectively. Both PT and APTT of her grandmother, father, mother and daughter were slightly prolonged, which have measured 16.4 s, 15.8 s,16.9 s, 16.5 s, and 44.0 s, 42.1 s, 41.1 s, 43.5 s, respectively. And their FVII:C (34%, 39%, 31%, 40%, respectively), FX:C (50%, 58%, 47%, 42%, respectively) and FX:Ag (51%, 54%, 58%, 47%, respectively) were slightly reduced, while FVII:Ag was in the normal range. The coagulant parameters of her younger brother were within normal range. Two homozygous mutations, g.11267C to T in exon 8 of F7 gene, which resulted in an Arg277Cys substitution, and g.28139G to T in exon 8 of F10 gene which led to a Val384Phe substitution, were identified in the proband. The proband's grandmother, parents and daughter were heterozygous for both Arg277Cys and Val384Phe mutationss. Wild-type alleles of both F7 and F10 genes were also found in the younger brother.

CONCLUSIONA homozygous Arg277Cys mutation and a Val384Phe mutation have been respectively identified in the F7 and F10 genes, which can explain the low levels of FVII and FX in this family. The former has been inherited from the consanguineous parents.

Adult ; Aged ; Consanguinity ; Factor VII Deficiency ; genetics ; Factor X Deficiency ; genetics ; Female ; Genotype ; Humans ; Male ; Middle Aged ; Mutation ; Pedigree ; Phenotype

OBJECTIVETo deepen the understanding of acquired coagulation factor X (F X) deficiency.

METHODSThe clinical data of 3 patients were analyzed and related literature were reviewed.

RESULTSCase 1, a 57-year-old male, secondary to multiple myeloma and amyloidosis, was presented with spontaneous mucous hemorrhage with the level of FX:C 1.8%, which kept unchanged after chemotherapy with melphalan, glucocorticoid, and thalidomide, and died of primary disease progression. Case 2, a 41-year-old male with psoriasis, was presented with cerebral and retinal hemorrhage with the level of FX:C 26.8%. The signs of hemorrhage were alleviated after the supplement of folic acid, vitamin B12, and vitamin K, and transfusion with red blood cells, platelets, and fresh frozen plasma. Case 3, a 63-year-old female, associated with high level of lupus anticoagulant, was presented with repeated ecchymosis and haemarthrosis with the level of FX:C 6.1%, which was refractory to prothrombin complex concentrate, methyprednisolone, azathioprine, and rituximab.

CONCLUSIONAcquired FX deficiency is a rare disorder with variable symptoms. The diagnosis relies on history of disease and laboratory test. Currently, there is no standardized treatment. The prognosis of acquired FX deficiency is mainly related to the underlying disease.

Adult ; Factor X Deficiency ; Female ; Humans ; Male ; Middle Aged

Aged ; Amyloidosis ; complications ; Factor X Deficiency ; complications ; Humans ; Immunoglobulin Light-chain Amyloidosis ; Male

Amyloidosis is a heterogeneous group of diseases in which misfolding of extracellular proteins is the pathogenic factor. Light chain amyloidosis (AL) is the most common form of amyloidosis, and the causative proteins in AL are the immunoglobulin light chains produced by clonal plasma cells. Hemorrhagic events, ranging from mild subcutaneous hemorrhage to life-threatening bleeding, account for a significant proportion of morbidities and mortality in AL patients. Deficiency of factor X from deposition into amyloid fibrils has been reported to be the most common acquired factor deficiency in AL. We herein report 2 patients with acquired factor X deficiency in AL. A 55-yr-old woman with AL had a prolonged prothrombin time (PT) and an activated partial thromboplastin time (aPTT) of 2.51 International Normalized Ratio (INR) and 75.1 sec, respectively, which were corrected on mixing with normal plasma. Factor X activity was markedly decreased at 5%. The other patient was a 67-yr-old man with AL with a PT of 1.63 INR and an aPTT of 50.3 sec, which were corrected on mixing with normal plasma. Factor X activity was decreased at 17%. Neither of the patients had apparent hemorrhagic manifestations. Identification of acquired factor deficiency and timely coagulation tests are needed in the diagnostic workup and management in AL.
Aged ; Amyloidosis/*complications ; Factor X/*metabolism ; Factor X Deficiency/*diagnosis/etiology/therapy ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunoglobulin Light Chains/*metabolism ; Male ; Middle Aged ; Republic of Korea ; Transplantation, Autologous

Amyloidosis is a heterogeneous group of diseases in which misfolding of extracellular proteins is the pathogenic factor. Light chain amyloidosis (AL) is the most common form of amyloidosis, and the causative proteins in AL are the immunoglobulin light chains produced by clonal plasma cells. Hemorrhagic events, ranging from mild subcutaneous hemorrhage to life-threatening bleeding, account for a significant proportion of morbidities and mortality in AL patients. Deficiency of factor X from deposition into amyloid fibrils has been reported to be the most common acquired factor deficiency in AL. We herein report 2 patients with acquired factor X deficiency in AL. A 55-yr-old woman with AL had a prolonged prothrombin time (PT) and an activated partial thromboplastin time (aPTT) of 2.51 International Normalized Ratio (INR) and 75.1 sec, respectively, which were corrected on mixing with normal plasma. Factor X activity was markedly decreased at 5%. The other patient was a 67-yr-old man with AL with a PT of 1.63 INR and an aPTT of 50.3 sec, which were corrected on mixing with normal plasma. Factor X activity was decreased at 17%. Neither of the patients had apparent hemorrhagic manifestations. Identification of acquired factor deficiency and timely coagulation tests are needed in the diagnostic workup and management in AL.
Aged ; Amyloidosis/*complications ; Factor X/*metabolism ; Factor X Deficiency/*diagnosis/etiology/therapy ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunoglobulin Light Chains/*metabolism ; Male ; Middle Aged ; Republic of Korea ; Transplantation, Autologous

OBJECTIVETo perform gene analysis and family survey of a patient with combined inherited FVII and FX deficiency, and to identify the gene mutation of this patient.

METHODSThe phenotype diagnosis was validated by coagulant parameter assay on prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, FVII and FX activity (FVII:C, FX:C) and FVII and FX antigen (FVII:Ag, FX:Ag). FVII and FX gene mutations were analyzed in the proband and other family members by DNA direct sequencing of all exons, exon-intron boundaries and 5', 3' untranslated sequences. One hundred and six health examination participants were selected as control.

RESULTSThe values of PT and APTT of the proband showed significantly prolonged, which were 84.5s and 63.4s, respectively. The levels of FVII:C, FVII:Ag, FX:C and FX:Ag were 6%, 7%, 4% and 30%, respectively. The PT of his father, mother and sister was prolonged slightly while both APTT and FVII:Ag were in the normal range. Two homozygous mutations, g.11267C→T in exon 8 of FVII gene resulting in the substitution of Arg277Cys and g.28139G→T in exon 8 of FX gene leading to the substitution of Val384Phe, were identified in the proband. The proband's parents and sister were heterozygous for Arg277Cys and Val384Phe mutations.

CONCLUSIONHomozygous mutation Arg277Cys in FVII gene and Val384Phe in FX gene were the molecular mechanism causing combined inherited FVII and FX deficiency. The Val384Phe substitution was a novel mutation, which may affect the synthesis or secretion of FX protein.

Adolescent ; Adult ; Base Sequence ; DNA Mutational Analysis ; Factor VII ; genetics ; Factor VII Deficiency ; complications ; genetics ; Factor X Deficiency ; complications ; genetics ; Female ; Heterozygote ; Humans ; Male ; Middle Aged ; Mutation ; Pedigree ; Young Adult

PURPOSE: Clotting factor X deficiency is one of the least common coagulation disorders. The authors describe a case of cleft palate in a patient with a congenital clotting factor X deficiency. METHODS: In pediatric patients with a cleft palate, the coagulation problem is more worrisome, because they are more sensitive to blood than adults, and because postoperative bleeding can cause blood ingestion with subsequent vomiting, aspiration, and airway obstruction. To prevent hemorrhagic complications in the described case, fresh frozen plasma (FFP) was administered every 24 hours from the day before surgery to the second postoperative day. RESULTS: Good hemostasis, normal healing, and no complications was shown postoperatively. CONCLUSION: The replacement of fresh frozen plasma was useful in the case of congenital clotting factor deficiency for bleeding prophylaxis in cleft palate operation.
Adult ; Airway Obstruction ; Cleft Palate ; Eating ; Factor X ; Factor X Deficiency ; Hemorrhage ; Hemostasis ; Humans ; Plasma ; Vomiting

We report a case of nephrotic syndrome and factor X deficiency secondary to primary amyloidosis. A 58-year-old man was referred to our hospital for evaluation of nephrotic syndrome and bleeding tendency. He was confirmed to have primary amyloidosis by renal biopsy, immunofixation electrophoresis and bone marrow findings. His bleeding tendency was due to prothrombin time prolongation caused by isolated factor X deficiency. If any patient with nephrotic syndrome has bleeding tendency due to coagulation abnormalities, that patient should be considered to have factor X deficiency secondary to primary amyloidosis.
Amyloidosis ; Biopsy ; Bone Marrow ; Electrophoresis ; Factor X ; Factor X Deficiency ; Hemorrhage ; Humans ; Middle Aged ; Nephrotic Syndrome ; Prothrombin Time