Case Of Factor XIII Deficiency Research Articles

Factor XIII deficiency, a rare coagulopathy: case reports

Introduction: Hereditary Factor XIII (FXIII) deficiency is a rare autosomal recessive hemostatic disorder with an estimated incidence of one case per two million individuals and a higher prevalence in descendants of consanguineous relationships. Possible clinical manifestations include intracranial hemorrhage, umbilical cord bleeding at birth, hematoma, spontaneous abortions, and menometrorrhagia. Objective: To highlight the peculiarities of this hemostatic disorder, as well as the recommended management. Case Report: The authors describe two cases of FXIII deficiency with different hemorrhagic manifestations. Case 1 presented extensive spontaneous hematoma in the right thigh, while Case 2 had umbilical cord bleeding at birth and intracranial hemorrhage, requiring hemotherapy support. Both patients had normal results in screening laboratory tests for coagulation disorders. Coagulation factor serum levels and diagnostic assessments identified mild Factor XIII deficiency in Case 1 and severe deficiency in Case 2. The patient in Case 1 is under regular control and follow-up, while the patient in Case 2 is on a monthly prophylactic regimen with FXIII infusion. Conclusion: The diagnosis of FXIII deficiency in patients with significant bleeding should be considered if screening coagulation tests are normal. The Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis has established an algorithm for laboratory diagnosis and identification of different forms of FXIII deficiency. Quantitative determination of FXIII activity, antigenic assays, and molecular studies are necessary.

A rare case of factor XIII deficiency presenting with scrotal hematoma in an adolescent

Background: Factor XIII deficiency is a rare disorder that may be congenital or acquired and is considered if a coagulation disorder is suspected, but the initial laboratory investigations are normal. Clinical Description: A 10-year-old boy presented with a scrotal swelling and pain following minor trauma. Local examination showed redness of overlying scrotal skin with tenderness on palpation. Management: Initial laboratory investigations for coagulation (prothrombin time/activated partial thromboplastin time/thrombin time) were normal. The diagnosis of factor XIII deficiency was clinched by abnormal clot solubility test. Child was treated with fresh-frozen plasma. Conclusion: Scrotal hematoma is a rare site for bleeding in factor XIII deficiency, which must be suspected if clinical suspicion of coagulation disorder is high and initial laboratory tests for coagulation are normal.

Impact of Rare Bleeding Disorders during Pregnancy on Maternal and Fetal Outcomes: Review of 29 Pregnancies at a Single Center.

Objective This study aims to give information about the relationship between different types of factor deficiencies and maternal/obstetric outcomes. Methods We retrospectively reviewed the medical records of eight women with factor deficiency disorders. The demographic and clinical features of the patients after their last pregnancies were registered retrospectively. Results There were 29 pregnancies among the 8 patients. The spontaneous abortion rate was relatively high in two patients with factor XIII deficiency (80% and 57.1%) compared with the other factor deficiency groups. There were 16 births, which included 1 set of twins, and 2 deaths (1 stillbirth and 1 postpartum exitus occurred in the same patient). Intrauterine growth restriction was noted in five cases; four of these occurred in factor X deficiency cases. The mean decrease in hemoglobin level of all patients after birth was 1.7 g/dL (range, 0.2-3.6 g/dL). Red blood cell transfusion was required only in one case of factor XIII deficiency. Conclusions There is currently no consensus on the pregnancy management of women with factor deficiencies because of the limited knowledge due to the rarity of such disorders. Labor should be managed in a dedicated unit with a team consisting of an obstetrician, a hematologist, an anesthesiologist, a midwife, and a pediatrician to minimalize the complications.

Factor XIII Deficiency, Review of the Literature and Report of a Case

Introduction: Factor XIII deficiency is a relatively rare hereditary bleeding disorder, which is usually found during infancy or early childhood. This condition may involve both genders within different races in an equal manner. Its incidence is estimated at approximately 1 in 106 live births. Patients with factor XIII deficiency are presented with a pattern of neonatal hemorrhage and lifelong bleeding diathesis. Case Presentation: A five-year-old female is presented here, who was diagnosed as a definite case of factor XIII deficiency, based on the clinical and laboratory findings at a medical specialist clinic. Typical clinical features of the disorder were the chief complaint of the patient, which was severe bleeding when she was brought into a specialized dental office following an earlier dental procedure. Conclusions: The case was fully investigated and diagnosed as a case with factor XIII deficiency causing such uncontrolled bleeding after extraction of a tooth.

A Novel Nonsense Mutation of F13A1 Gene Causing Inherited Factor XIII Deficiency in a Chinese Han Family

Abstract 4661 Introduction:Coagulation factor XIII (FXIII) is a protransglutaminase that has a major role in the final stage of blood coagulation process by forming cross-links between γ-glutamyl and ε-lysine residues of fibrin chains. The plasma FXIII (pFXIII) circulates in plasma as a heterotetramer (FXIII-A2B2) consisting of two catalytic A subunits (FXIII-A2) and two carrier B subunits (FXIII-B2). Inherited FXIII deficiency is a rare autosomal recessive disease with lifelong bleeding. Most cases of FXIII deficiency are heterogeneous due to mutations in the F13A gene. Currently, more than 100 mutations have been reported. Aim:To identify the genetic defect of inherited coagulation factor XIII (FXIII) deficiency in a Chinese Han family. Methods and Results:A 13 year-old patient complained of poor wound healing after operation and had a history of an excessive bleeding from the umbilical cord stump after her birth. The routine laboratory tests are normal. Her bleeding time is more than 15 minutes and fibrin clot was solubilized very quickly in 5mol/L urea, and became insoluble when normal plasma was mixed with her plasma in vitro. Her plasma FXIII activity was zero with the amine incorporation assay and plasma FXIII antigen was also near zero by one-step sandwich ELISA method, the plasma FXIIIA antigen was zero using an indirect competitive ELISA assay. The plasma FXIIIA antigen, FXIII activity and antigen were assayed in all available family members. The testing results of patient's grandfather and maternal grandmother were within normal range. But the other pedigree members' results were lower in different level compare with normal ranges. All members of her family had normal coagulation test.All the exons of F13A gene as well as F13B gene and their flanking regions were amplified by PCR for direct sequencing to identify the mutations in the proband. Direct DNA sequencing of all purified amplification products from the patient's F13A gene demonstrated a homozygous nonsense mutation in exon8 (C to A transversion at nucleotide 98531 which caused Cys327X). And the patient didn't have the Val34Leu polymorphism. In the pedigree except of the proband, the Cys327X mutation was found in the heterozygous state in all investigated members except for her grandfather and maternal grandmother. A family study revealed that the mutation was inherited from both parents.The identified mutation was validated by PCR-RFLP technique in the family members and healthy people. Restriction enzyme analysis of amplified exon 8 DNA fragment confirmed that the patient was homozygous for this mutation. Then the quantitative RT-PCR method was used for studying the mRNA expression level of mutant FXIIIA. And the results indicated that F13A mRNA transcripts in heterozygous mutant were reduced by 25% when compared to transcripts in wild-type one, while the homozygous mutant level of F13A mRNA transcript was nearly zero relative to the normal transcript. Conclusion:We have identified a novel Cys327X nonsense mutation in human FXIIIA gene which we have not found in the FXIII database (www.f13-database.de) or in previous publications.And the identified nonsense mutation is causative for severe factor XIII deficiency with a bleeding disorder. Further, in vitro expression studies of the factor XIII mutation is required to confirm their pathological mechanism. Disclosures:No relevant conflicts of interest to declare.

Fatal Bleeding Caused by Congenital Factor XIII Deficiency and Development of An Inhibitor in a Hispanic Male

We report a case of fatal bleeding in a patient with mild congenital Factor XIII deficiency who also developed an inhibitor that interfered with fibrin stabilization. Plasma Factor XIII circulates as a tetramer composed of two A-chain and two B-chains and is bound to fibrinogen. After thrombin cleaves the A-chain at Arg 37, the B-chain dissociate producing Factor XIIIa. Factor XIIIa catalyzes covalent linkages between the fibrin molecules aligned in the fibrin clot. Factor XIIIa makes the fibrin resistant to disruption by urea and plasmin. Factor XIIIa levels greater than 1 % are needed to covalently stabilize a clot. We studied a 39 year old Hispanic male that presented with altered mental status, headache and a large left frontal parietal hemorrhage. Ultimately, he became non-responsive and was intubated. He had no major bleeding history but did have frequent nosebleeds. Routine blood counts and coagulation laboratory tests were normal. However, a qualitative Factor XIII assay was abnormal and the clot dissolved in 5M Urea. Furthermore, a 1:1 mixing study did not correct the defect suggesting the presence of an inhibitor. A small dose of cryoprecipitate was administered to the patient and this corrected the clot stability defect. Four days later, the defect recurred and 150 ml of cryoprecipitate was administered and despite correction of the fibrin stabilizing abnormality the patient died. Two of his sisters had a history of repeated hemorrhagic miscarriages in Mexico a finding consistent with congenital Factor XIII deficiency. DNA sequencing of the factor XIII a-chain gene was performed from the propositus' mononuclear cells. A reverse transcription was done using an oligo(dT) 12–18 primer followed by nested PCR amplification and a heterozygous missense mutation was observed at codon 35 (G226T; Val35Leu). This mutation was than confirmed in propositus' platelet cDNA. The Val35Leu substitution is close to the thrombin cleavage site, the G226T substitution is in the catalytic core domain. This case demonstrates that in some cases of Factor XIII deficiency there is residual Factor XIIIa activity in the mutant molecule that can prevent serious bleeding. However, patients may develop autoantibodies that further interfere with Factor XIII function and may suffer serious bleeding complications. Additional cases of Factor XIII deficiency may exist in patients that have mild bleeding problems.

Déficit en facteur XIII chez un nouveau-né

Factor XIII deficiency is an uncommon inherited disorder which is characterized by umbilical cord bleeding and an unusually high incidence of intracranial hemorrhage. We report here a case of Factor XIII deficiency in a child that presented a caput. succedaneum as the first manifestation of the disease and then an umbilical cord bleeding. The importance of performing a quantitative FXIII assay in the presence of strong clinical suspicion is strengthened because of the normality of the standard screening tests and the important therapeutic consequences.

Recombinant factor VIIa use in patients with the rarest forms of inherited coagulation-factor deficiencies: a study of cases from the www.haemostasis.com registry

Rare inherited coagulation disorders (RICDs) with a prevalence of ≤1/1,000,000 include deficiencies in factor II, factor V, combined factor V/factor VIII, factor X, factor XI and factor XIII. These abnormalities are associated with spontaneous haemorrhage and excessive bleeding after surgery or trauma. Management is complicated by limited information and variations in biochemical characteristics and bleeding phenotypes. The independently managed international registry, http://www.haemostasis.com , was established to collect data on investigational use of activated recombinant factor VII (rFVIIa) in preventing or treating severe bleeding episodes. Patients suffering from the rarest forms of RICDs and receiving rFVIIa as treatment were identified from the http://www.haemostasis.com registry. Case providers were contacted to verify data and obtain consent for inclusion in this study. Eleven patients were identified; permission for inclusion was declined in two cases. The nine cases reported in this study included patients with factor II, factor V, combined factor V/factor VIII, combined factor V/von Willebrand’s disease, factor X, factor XI, factor XI with inhibitors and factor XIII deficiencies. The median individual dose of rFVIIa was 105.9 μg/kg body weight (range: 55–508 μg/kg), whereas the median total dose was 327.3 μg/kg body weight (range: 78.4–880 μg/kg). rFVIIa treatment was associated with a decrease, cessation or prevention of bleeding in eight cases; bleeding after trauma remained unchanged in one case of factor XIII deficiency. Positive pro-coagulatory responses were shown to occur at a wide range of anatomical sites. No deaths or rFVIIa-related adverse events were reported. In conclusion, this study suggests that rFVIIa has a favourable safety profile and that it may be used to treat or prevent haemorrhage in patients with RICDs.

Factor XIII deficiency: Concentrations inrelatives of patients and in normal infants

Since 1960 when Duckert and associates² observed a familial bleeding disorder caused by a deficiency of Factor XIII, 21 cases of Factor XIII deficiency, involving 10 families, have been reported. A 6-year-old boy with Factor XIII deficiency has been diagnosed and an assay technique with the patient's plasma as deficient substrate has been devised. In vivo survival studies, after transfusion of the patient with Factor XIII, indicate a half life of 5 to 7 days. Factor XIII assays in 50 infants and children from birth to 20 months of age reveal, a significantly lower level in the newborn infant and normal levels by 1 month of age. Factor XIII levels in the parents and siblings were significantly lower than in 20 normal individuals, suggesting an autosomal recessive inheritance of Factor XIII deficiency.