Humans ; Factor XIII/genetics* ; Factor XIII Deficiency/genetics* ; Mutation ; Pedigree

Objective: To explore the relationship between plasma coagulation factor XIII (FXIII) and bleeding events. Methods: A total of 55 cases of acute leukemia (AL) at the myelosuppression phase after chemotherapy hospitalized in our hospital from August 2017 to March 2018 were enrolled, with 35 normal controls. The concentration of plasma coagulation factor XIII (FXIII) was detected by ELISA to determine the relationship between the plasma FXIII levels in AL patients at the myelosuppression phase after chemotherapy with bleeding events. Results: The level of FXIII in AL patients at the myelosuppression phase after chemotherapy was significantly lower than that in controls (P<0.001) . The level of FXIII was inversely related with the bleeding severity (the Spearman correlation coefficient -0.761) . Given the diagnosis cut-off point of FXIII concentration as 103.9 μg/L, the sensitivity of diagnosing bleeding in AL patients at the myelosuppression phase after chemotherapy was 0.939, and the specificity 0.909. Conclusion: AL patients at the myelosuppression phase after chemotherapy had low level of plasma FXIII, and patients with lower plasma FXIII associated with higher incidence and severity of bleeding. FXIII level was an independent influencing factor of bleeding in AL patients at the myelosuppression phase after chemotherapy.
Acute Disease ; Blood Coagulation Tests ; Factor XIII ; Factor XIII Deficiency ; Hemorrhage ; Humans ; Leukemia

OBJECTIVETo provide a comprehensive literature review on roles of coagulation factor XIII (FXIII) in coagulation, wound healing, neoplasm, bone metabolism, and pregnancy.

DATA SOURCESAll articles in PubMed with key words "Coagulation factor XIII", "wound", "leukemia", "tumor", "bone," and "pregnancy" with published date from 2001 to 2016 were included in the study. Frequently cited publications before 2000 were also included.

STUDY SELECTIONWe reviewed the role of FXIII in biologic processes as documented in clinical, animal, and in vitro studies.

RESULTSFXIII, a member of the transglutaminase (TG) family, plays key roles in various biological processes. Besides its well-known function in coagulation, the cross-linking of small molecules catalyzed by FXIII has been found in studies to help promote wound healing, improve bone metabolism, and prevent miscarriages. The study has also shown that FXIII concentration level differs in the blood of patients with leukemia and solid tumors and offers promises as a diagnostic indicator.

CONCLUSIONSFXIII has many more biologic functions besides being known as coagulation factor. The TG activity of FXIII contributes to several processes, including wound healing, bone extracellular matrix stabilization, and the interaction between embryo and decidua of uterus. Further research is needed to elucidate the link between FXIII and leukemia and solid tumors.

Abortion, Spontaneous ; metabolism ; prevention & control ; Animals ; Blood Coagulation ; physiology ; Factor XIII ; metabolism ; physiology ; Female ; Humans ; Leukemia ; metabolism ; Pregnancy ; Wound Healing ; physiology

OBJECTIVETo perform phenotypic diagnosis, genetic diagnosis and prenatal diagnosis of inherited coagulation factor XIII (FXIII)deficiency in a Chinese family also provide a review of inherited coagulation F XIII deficiency.

METHODSThe activity levels of F XIII (F XIII:C) of proband and family members were measured by clot solubility test and REA-chrom F XIII kit. The antigen levels of F XIII(FXIII:Ag) were measured by enzyme-linked immunosorbent assay. Thrombelastography (TEG) test was used to make a comprehensive evaluation of coagulation status in the proband. All 15 exons and exon-intron boundaries of the F13A1 gene were amplified by PCR, and DNA sequencing was performed then. The mutation identified in the proband was screened in the family members. Furthermore, the related literatures were reviewed to provide a profile of clinical manifestation, gene mutations, the relationship between the mutations and phenotype, and treatments of inherited coagulation F XIII deficient cases.

RESULTSThe clot solubility test was positive in the proband. The FXIII:Ag level of the proband was less than 1% and the FXIII:C level was below the lower limit of detection (<3%). Two compound heterozygous missense mutations (p.Arg662* and p.Trp665*) were identified in the proband. Family study showed that the two mutations were both inherited from the parents. The fetus also carried two compound heterozygous mutations, the same as the proband, and was diagnosed with severe F XIII deficiency. As reported in the literatures, most mutations were missense mutations and nonsense mutations, and no hot spot was found. The clinical pattern of F XIII deficiency varied among patients, with potentially fatal consequences from severe bleeding complications.

CONCLUSIONBetter understanding of F XIII biochemical properties and function and developing of FXIII laboratory assays and genetic detection could prevent missed diagnosis, and patients moght benefit from better care.

Asian Continental Ancestry Group ; Base Sequence ; DNA Mutational Analysis ; Enzyme-Linked Immunosorbent Assay ; Exons ; Factor XIII ; genetics ; Factor XIII Deficiency ; genetics ; Female ; Heterozygote ; Humans ; Introns ; Mutation, Missense ; Pedigree ; Phenotype ; Polymerase Chain Reaction ; Pregnancy ; Prenatal Diagnosis

OBJECTIVETo observe the clinical significance of postoperative personalized antithrombotic therapy for patients with hemophilic arthritis (HA) patients after arthroplasty.

METHODSFrom September 2005 to October 2013, 11 cases of arthroplasty for hemophilic arthritis in hip and knee total operation 14 times,including 1 case of double knees (calculated as one operation), operation in left knees 6 times, operation in right knees 5 times, 2 in hip. All the patients were male and the age ranged from 23 to 57 years old,with an average of (36.1 ± 11.0) years old; the average weight was (64.1 ± 8.9) kg. All the patients were preoperatively diagnosed and classified as hemophilic arthritis with the radiological images and laboratory tests. According to the function of joints, the risk of postoperative venous thromboembolism (VTE), and dynamic observation of Factor VIII:C (FVIII:C) activity, patients were treated with personalized antithrombus by adjusting the dosage of recombinant human coagulation factor VIII (Kogenate FS). All the patients were orderly divided into postoperatively distal joints moving group and none-moving group to observe the coagulation function.

RESULTSThe enrolled patients had no postoperative complication of VTE and pulmonary embolism (PE). The APTT and D-2 were different between two groups in the postoperative early stage. Length of hospital day was shorter in the moving group than none-moving group.

CONCLUSIONBecause of the self-coagulation disorder, patients with HA tended to bleed. However it doesn't mean that there is no risk of postoperative thrombosis. Therefore,it's important to determine how to control the balance between postoperative antithrombus, hemostasis,and coagulation factor replacement therapy after arthroplasty for HA. Postoperative moving has proved helpful for HA, especially in reducing the risk of hemostasis and shortening the time in hospital.

Adult ; Arthritis ; surgery ; Arthroplasty ; adverse effects ; Factor XIII ; metabolism ; Hemophilia A ; complications ; Hemostasis ; Humans ; Male ; Middle Aged ; Postoperative Complications ; prevention & control ; Thrombosis ; prevention & control ; Young Adult

OBJECTIVETo investigate the mechanisms of DelCD11-279 of factor XIII subunit A mRNA in the pathogenesis of hereditary factor XIII deficiency.

METHODSThe recombinant plasmids containing pET-22b(+)/FXIIIA of normal subject and proband's mother and pET-22b(+)/FXIIIA-Del of the proband were constructed and transformed into E. coli BL21. Expressing protein was analyzed by the SDS-PAGE and purified by Ni-NTA resin. Purified proteins were detected by the Western-blot. The activity of purified protein was detected by the incorporation test with EZ-LinkTM5-(Biotinamido) Pentylamine.

RESULTSThe recombinant plasmids containing pET-22b(+)/FXIIIA and pET-22b(+)/FXIIIA-Del which constructed and identified successfully by enzyme digestion and PCR, were transformed into E. coli BL21 and efficiently expressed by IPTG induction. The molecular weights of expressing proteins are 83 200 and 51 900 by the SDS-PAGE. Expressing proteins were purified by Ni-NTA resin, and were proved to be human FXIIIA proteins by Western-blot. Purified protein activity of proband's mother and proband was 95.87% and 0 of the purified FXIIIA protein activity from the normal subject, respectively.

CONCLUSIONDelCD11-279 of FXIIIA mRNA which encoding a 464 amino acids of inactive FXIIIA protein is one of the molecular mechanisms resulting in FXIII deficiency in the patient.

Escherichia coli ; Factor XIII ; Factor XIII Deficiency ; Humans ; Polymerase Chain Reaction ; RNA, Messenger ; Sequence Deletion

Blood transfusion is an essential part of medical care, but it has risks, including infectious and immunologic complications. Recent medical practice emphasizes the rationalization of transfusion according to guidelines at the national and local levels. Early transfusions used whole blood, but modern practice commonly uses only components of the blood, such as red blood cells, platelets, plasma, and clotting factors. Red blood cell transfusions are indicated to improve oxygen delivery to tissues and to treat hemorrhage. Platelet transfusion may be indicated to prevent hemorrhage in patients with thrombocytopenia or functionally abnormal platelets. Fresh frozen plasma can be used to correct coagulation abnormalities in order to normalize the fibrinogen level, prothrombin time, and activated partial thromboplastin time. Cryoprecipitate is indicated for bleeding associated with fibrinogen deficiencies, factor XIII deficiency, hemophilia A, or von Willebrand's disease. However, blood transfusion should be based on guidelines as well as the patient's clinical condition. Appropriate use of blood components results in effective transfusion therapy and reduces transfusion-related complications.
Afibrinogenemia ; Blood Platelets ; Blood Transfusion ; Erythrocyte Transfusion ; Erythrocytes ; Factor XIII Deficiency ; Fibrinogen ; Hemophilia A ; Hemorrhage ; Humans ; Oxygen ; Partial Thromboplastin Time ; Plasma ; Platelet Transfusion ; Prothrombin Time ; Rationalization ; Thrombocytopenia ; von Willebrand Diseases

PURPOSE: Factor XIII (FXIII), a thrombin-activated plasma transglutaminase zymogen, is involved in cancer development and progression through a triggered coagulation pathway. The aim of this study was to examine whether FXIII activity levels differed in non-small cell lung cancer (NSCLC) patients according to histological types and TNM stage when compared with healthy subjects. MATERIALS AND METHODS: Twenty-eight NSCLC patients and 28 normal controls who had been individually age-, gender-, body mass index-, smoking status-, and smoking amount-matched were enrolled: 13 adenocarcinomas, 11 squamous cell carcinomas, and four undifferentiated NSCLCs; four stage I, two stage II, 12 stage III, and 10 stage IV NSCLCs. FXIII activity was measured using fluorescence-based protein arrays. RESULTS: The median FXIII activity level of the NSCLC group [24.2 Loewy U/mL, interquartile range (IQR) 14.9-40.4 Loewy U/mL] was significantly higher than that of the healthy group (17.5 Loewy U/mL, IQR 12.6-26.4 Loewy U/mL) (p=0.01). There were no differences in FXIII activity between adenocarcinoma (median 18.6 Loewy U/mL) and squamous cell carcinoma (median 28.7 Loewy U/mL). NSCLC stage significantly influenced FXIII activity (p=0.02). The FXIII activity of patients with stage III NSCLC (median 27.3 Loewy U/mL, IQR 19.3-40.5 Loewy U/mL) was significantly higher than those of patients with stage I or II (median 14.0 Loewy U/mL, IQR 13.1-23.1 Loewy U/mL, p=0.04). FXIII activity was negatively correlated with aPTT in NSCLC patients (r=-0.38, p=0.04). CONCLUSION: Patients with advanced-stage NSCLC exhibited higher coagulation FXIII activity than healthy controls and early-stage NSCLC patients.
Aged ; Carcinoma, Non-Small-Cell Lung/*metabolism/*pathology ; Case-Control Studies ; Factor XIII/*metabolism ; Female ; Humans ; Lung Neoplasms/*metabolism/*pathology ; Male ; Middle Aged ; Neoplasm Staging

Adult ; Factor XIII ; antagonists & inhibitors ; Factor XIII Deficiency ; complications ; etiology ; Female ; Humans ; Sjogren's Syndrome ; complications

OBJECTIVETo analyze the expressed mRNA of the factor subunit A (FA) in monocyte in a hereditary factor (F) deficiency family.

METHODSThe F A mRNA of the proband and the other family members was analyzed by RT-PCR, semi-quantitative RT-PCR, cloning and sequencing. The three dimensional structure of the protein was predicted by SWISS-MODEL and viewed by RASMIOL.

RESULTS(1) A large in frame deletion from codons 11 to 279, spanning from exon 2 to 7 of F A (DelCD11-279), was identified in the proband at mRNA level and a truncated protein is predicted composed of 464 amino acids. Compared with the normal and the other families, the proband showed lower level of F A mRNA in RT-PCR. (2) SWISS-MODEL analysis showed that the truncated protein lacked the β-sandwich and a part of catalytic core, resulting in loss of the normal catalytic domains.

CONCLUSIONDelCD11-279 of F A mRNA is associated with hereditary F deficiency. The reduced expressing level of F A gene is one of the causes resulting in F deficiency in the patients.

Adolescent ; DNA Mutational Analysis ; Exons ; Factor XIII ; genetics ; Factor XIII Deficiency ; genetics ; Female ; Humans ; Male ; Pedigree ; RNA, Messenger ; genetics ; Sequence Deletion