Molecular basis of rare congenital bleeding disorders

Dorgalaleh, Akbar; Bahraini, Mehran; Shams, Mahmood; Parhizkari, Fereshteh; Dabbagh, Ali; Naderi, Tohid; Fallah, Aysan; Fazeli, Alieh; Ahmadi, Seyed Esmaeil; Samii, Amir; Daneshi, Maryam; Heydari, Farshad; Tabibian, Shadi; Tavasoli, Behnaz; Noroozi-Aghideh, Ali; Tabatabaei, Tahere; Gholami, Mohammad Saeed

doi:10.1016/j.blre.2022.101029

Cited by 12 publications

(11 citation statements)

References 126 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although early studies showed that most variants in heterozygous FXIII deficiency are in domains other than the catalytic core, the current pattern of gene variants in heterozygous FXIII deficiency is comparable to the spectrum of F13A gene variants in homozygous (severe) FXIII deficiency, in which 48.8% of variants are missense and 10.5% are nonsense. 78 Most of these gene variants were observed in the catalytic core (52.1%), whereas only one variant was observed in the activation peptide [80][81][82][83][84][85] (►Fig. 1).…”

Section: Molecular Basis Of Heterozygous Fxiii Deficiencymentioning

confidence: 99%

“…Also we found a significant bleeding among heterozygous individuals; these also were common among healthy individuals, except for miscarriage and impaired wound healing. 6 In the literature review, we found 308 individuals with heterozygous FXIII deficiency, of whom almost all bleeding episodes were due to hemostatic challenges such as trauma, surgery, pregnancy, and childbirth 3 11 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 ( Tables 1 and 2 ).…”

Section: Heterozygous Fxiii Deficiencymentioning

confidence: 99%

See 1 more Smart Citation

Novel Insights into Heterozygous Factor XIII Deficiency

Dorgalaleh¹

2023

Semin Thromb Hemost

Self Cite

View full text Add to dashboard Cite

The prevalence and clinical significance of heterozygous factor XIII (FXIII) deficiency has long been debated, with controversial reports emerging since 1988. In the absence of large epidemiologic studies, but based on a few studies, a prevalence of 1 per 1,000 to 5,000 is estimated. In southeastern Iran, a hotspot area for the disorder, a study of more than 3,500 individuals found an incidence of 3.5%. Between 1988 and 2023, a total of 308 individuals were found with heterozygous FXIII deficiency, of which molecular, laboratory, and clinical presentations were available for 207 individuals. A total of 49 variants were found in the F13A gene, most of which were missense (61.2%), followed by nonsense (12.2%) and small deletions (12.2%), most occurring in the catalytic domain (52.1%) of the FXIII-A protein and most frequently in exon 4 (17%) of the F13A gene. This pattern is relatively similar to homozygous (severe) FXIII deficiency. In general, heterozygous FXIII deficiency is an asymptomatic condition without spontaneous bleeding tendency, but it can lead to hemorrhagic complications in hemostatic challenges such as trauma, surgery, childbirth, and pregnancy. Postoperative bleeding, postpartum hemorrhage, and miscarriage are the most common clinical manifestations, while impaired wound healing has been rarely reported. Although some of these clinical manifestations can also be observed in the general population, they are more common in heterozygous FXIII deficiency. While studies of heterozygous FXIII deficiency conducted over the past 35 years have shed light on some of the ambiguities of this condition, further studies on a large number of heterozygotes are needed to answer the major questions related to heterozygous FXIII deficiency.

show abstract

Section: Molecular Basis Of Heterozygous Fxiii Deficiencymentioning

confidence: 99%

Section: Heterozygous Fxiii Deficiencymentioning

confidence: 99%

Novel Insights into Heterozygous Factor XIII Deficiency

Dorgalaleh¹

2023

Semin Thromb Hemost

Self Cite

View full text Add to dashboard Cite

show abstract

“…5,37 Of the first gene variants identified in the F13A gene, a total of 197 variants have now been detected, 172 in the F13A gene and 25 in the F13B gene. 38 Both F13A and F13B genes have been cloned by several groups, with the first cloning of the F13A accomplished by two separate groups. 23,39 Recombinant XIII-A (rFXIII) was expressed, for the first time, in megakaryocytes, a cell line especially relevant to the study of the biosynthesis of FXIII-A.…”

Section: Discovery Of Fibrin Stabilizing Factormentioning

confidence: 99%

The History of Factor XIII Deficiency

Dorgalaleh¹

2023

Semin Thromb Hemost

Self Cite

View full text Add to dashboard Cite

Despite the early discovery of factor XIII (FXIII) in 1944, the diagnosis of FXIII deficiency was not made until 1960, after all the other coagulation factor deficiencies, most likely due to the normality of routine coagulation testing in FXIII deficiency. Although the first case was detected by the clot solubility test and this test has long since been used to detect FXIII deficiency, the test is no longer recommended by experts. Over the past 60 years, knowledge about FXIII deficiency has expanded considerably, between 1992, when the first variant was identified, and 2022, 197 mutations have been reported. Almost all missense mutations have a similar effect on FXIII, leading to instability and faster degradation of mutant FXIII protein. Therapeutic options have evolved from historical fresh frozen plasma (FFP), old plasma, whole blood, and cryoprecipitate, to plasma-derived and recombinant FXIII concentrates, respectively available since 1993 and 2012. These concentrate products were respectively approved by the Food and Drug Administration in 2011 and 2013. This historical review covers various aspects of FXIII related disorders, including the discovery of the FXIII, associated disorders, molecular basis, diagnosis, and treatment of FXIII deficiency.

show abstract

“…The severity of the bleeding disorder can vary widely, ranging from mild bleeding tendencies to life-threatening hemorrhages. [2] The presence of an acquired deficiency to factor VII is a rare but potentially serious complication. This inhibitor is an antibody that targets FVII and prevents its activation, leading to a prolonged bleeding time.…”

Section: Introductionmentioning

confidence: 99%

“…The severity of the bleeding disorder can vary widely, ranging from mild bleeding tendencies to life-threatening hemorrhages. [ 2 ]…”

Section: Introductionmentioning

confidence: 99%

Acquired isolated factor VII deficiency in a patient with myxoid pleomorphic liposarcoma, case report

Aljabry,

Aleid,

Almutairi

et al. 2023

Medicine

View full text Add to dashboard Cite

Introduction: Acquired factor VII (FVII) deficiency is a rare condition with various causes, including acquired inhibitors to FVII, liver disease, and malignancies. Myxoid pleomorphic liposarcoma is a rare and aggressive form of soft tissue sarcoma that can cause a range of clinical manifestations, including bleeding and clotting disorders. Patient concerns and diagnosis: We present a case report of a 21-year-old man with severe acquired FVII deficiency due to mediastinal myxoid pleomorphic liposarcoma. The patient presented with elevated International normalized ratio (INR) and a severe reduction in FVII coagulant activity, unresponsive to conventional therapy. While an acquired inhibitor to FVII was initially suspected, negative results from laboratory testing, including protein G sepharose adsorption and a Bethesda assay using Immunoglobulin G purified from patient plasma, made the diagnosis of an acquired inhibitor to FVII uncertain. Interventions and outcome: The patient underwent surgical resection of the tumor, supported by recombinant FVII infusion, leading to the normalization of coagulation parameters. However, a relapse of the disease was detected 6 months later when he was noted to have a decline in FVII levels. Conclusion: This case highlights the importance of considering rare causes of bleeding and clotting disorders, particularly in unresponsive or atypical presentations. It also underscores the need for close monitoring and follow-up in patients with acquired FVII deficiency, even after successful treatment.

show abstract

Molecular basis of rare congenital bleeding disorders

Cited by 12 publications

References 126 publications

Novel Insights into Heterozygous Factor XIII Deficiency

Novel Insights into Heterozygous Factor XIII Deficiency

The History of Factor XIII Deficiency

Acquired isolated factor VII deficiency in a patient with myxoid pleomorphic liposarcoma, case report

Contact Info

Product

Resources

About