Biology of Factor XIII and clinical manifestations of Factor XIII deficiency

Transfusion ◽  
2012 ◽  
Vol 53 (5) ◽  
pp. 1120-1131 ◽  
Author(s):  
Jerrold H. Levy ◽  
Charles Greenberg
Keyword(s):  
Factor Xiii ◽  
Clinical Manifestations ◽  
Factor Xiii Deficiency

Znaczenie kliniczne niedoboru czynnika XIII

2018 ◽  
Vol 22 (3) ◽  
Author(s):  
Izabela Romanowska ◽  
Paweł Łaguna ◽  
Katarzyna Koch ◽  
Michał Matysiak
Keyword(s):  
Factor Xiii ◽  
Clinical Manifestations ◽  
Fresh Frozen Plasma ◽  
Diagnostic Methods ◽  
Screening Tests ◽  
Factor Xiii Deficiency ◽  
Congenital Deficiency ◽  
Fresh Frozen ◽  
Bleeding Episodes ◽  
Frozen Plasma

Factor XIII deficiency is very rare bleeding disorder with an incidence of one per several milions of population. It can be congenital or acquired in several medical conditions, for example in malignancies, autoimmune diseases and after some medications. The level of factor XIII < 5% causes clinical manifestations. It presents not only with mucosal, cutaneous and soft tissue bleeding, poor wound healing but also with intracranial haemorrhage. The congenital deficiency in women is the reason reccurent miscarriages. The diagnosis of factor XIII deficiency requires specialistic tests because routine screening tests are normal. The patients are treated with fresh frozen plasma, cryoprecipitate and FXIII concentrates. We present the latest diagnostic methods for factor XIII deficiency and treatment during bleeding episodes as well as prophylactic procedures.

The PAI-I Gene 4G/5G Polymorphism and Central Nervous System Bleeding In Factor XIII Deficiency

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4782-4782 ◽  
Author(s):  
Majid Naderi ◽  
Akbar Dorgalaleh ◽  
Shaban Alizadeh ◽  
Shadi Tabibian ◽  
Bamedi Taregh ◽  
...  
Keyword(s):  
Factor Xiii ◽  
Conflicts Of Interest ◽  
Clinical Manifestations ◽  
Control Group ◽  
Severe Bleeding ◽  
Bleeding Tendency ◽  
Intraparenchymal Hemorrhage ◽  
Factor Xiii Deficiency ◽  
History Of ◽  
And Control

Background FXIII deficiency is one of the rare bleeding disorder (RBD) that has a highest incidence in Sistan and Baluchistan province around the world. This disorder represents with different clinical manifestations ranging from mild to severe bleeding tendency including CNS bleeding. The aim of this study is to evaluate the role of PAI-14G/5Gpolymorphism in central nervous bleeding (intra and extracranial hemorrhage) system in factor XIII deficiency. Methods In this case control study was studied 32 FXIII deficient patients with CNS bleeding and also 32 patients with factor XIII deficiency without history of CNS bleeding as control group. Initially both groups were evaluated for the previously reported polymorphism of factor XIII (Trp187Argpolymorphism) in order to confirm their disorder. Then all patients were assessed for PAI-14G/5G polymorphism. Eventually obtained data was analyzed by SPSS software. Results The result of this study revealed that all study patients were homozygote for Trp187Arg polymorphism. We also found that the equal numbers of patients (4 individuals) in case and control groups were heterozygote for PAI-14G/5G polymorphism and none of patients were homozygote for this polymorphism. All heterozygote patients had intracranial hemorrhage and patients with extracranial hemorrhage had no mutation of PAI-14G/5G. Intraparenchymal was the most common site of hemorrhage and was observed in 26 patients (92.8%).We also observed subdural and epidural hemorrhage in two patients (7.1%).Anatomic regions in patients with intraparenchymal hemorrhage, were temporal in nine (32.2%), occipital in eight (28.6%), diffused intraparenchymal hemorrhage in seven (25%), tempro-occipital in two (7.1%) and subdural with temporal in two (7.1%) patients. Conclusion: It seems that PAI-14G/5G polymorphism did not any effect on occurrence of intra and extracranial hemorrhage in patients with factor XIII deficiency. Disclosures: No relevant conflicts of interest to declare.

Molecular Analysis Of The Largest Group Of Patients With Factor XIII Deficiency In Southeast Of Iran

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4780-4780 ◽  
Author(s):  
Majid Naderi ◽  
Akbar Dorgalaleh ◽  
Shaban Alizadeh ◽  
Shadi Tabibian ◽  
Taregh Bamedi ◽  
...  
Keyword(s):  
Molecular Analysis ◽  
Factor Xiii ◽  
Conflicts Of Interest ◽  
Clinical Manifestations ◽  
Molecular Characteristics ◽  
Common Mutation ◽  
Factor Xiii Deficiency ◽  
Large Group ◽  
Number Of Patients ◽  
A Subunit

Background Factor XIII deficiency is an extremely rare hemorrhagic disorder with estimated incidence of 1/3000000 million. Sistan and Baluchistan, southeast of Iran has the highest prevalence of disease worldwide. Thus the aim of this study was to assess molecular characteristics of this large group of patients with factor XIII deficiency. Methods This descriptive study was conducted on one hundred and nineteen patients from same number of unrelated families. Genotype analysis for factor XIII subunit A Val34Leu, Tyr204Phe, and Pro564Leu and Trp187Arg was performed for all patients. Results Molecular analysis of this large group of patients with severe factor XIII deficiency revealed that all studied patients were homozygous for TGG CGG mutation at codon 187, in exon 4 of FXIII-A1 gene. Val34Leu, Tyr204Phe, and Pro564Leu FXIII-A subunit gene polymorphisms were not observed in any of patients. In the study population, umbilical cord bleeding, deep soft tissue and hematoma were the most common clinical manifestations and was observed in 82.5%, 53% and 31% respectively. Conclusion Trp187Arg is the most common mutation of FXIII-A subunit in southeast of Iran and probably due to the large number of patients in this area (352 patients), is the most common mutation of factor XIII worldwide. Disclosures: No relevant conflicts of interest to declare.

Clinical Manifestations and Bleeding Episodes Among Heterozygote Individuals of Factor XIII Deficiency, a Short Term Prospective Study

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2852-2852 ◽  
Author(s):  
Majid Naderi ◽  
Akbar Dorgalaleh ◽  
Shaban Alizadeh ◽  
Shadi Tabibian ◽  
Soudabeh Hosseini ◽  
...  
Keyword(s):  
Factor Xiii ◽  
Normal Population ◽  
Clinical Manifestations ◽  
Control Group ◽  
Case Group ◽  
Bleeding Tendency ◽  
Factor Xiii Deficiency ◽  
History Of ◽  
Bleeding Episodes ◽  
Bleeding Score

Abstract Background Factor XIII deficiency (FXIIID) is a rare bleeding disorder (RBD) with high bleeding tendency. A wide spectrum of bleeding episodes was reported in patients with severe FXIIID. These bleeding diathesis include delay wound bleeding, intracranial hemorrhage, epistaxis and gum bleeding. A plasma level 3% to 10% of factor XIII is sufficient to prevent occurrence of bleeding in these patients. Here we design a study with two groups including heterozygote of FXIIID and normal population as a control group to assessed present of bleeding episodes in heterozygote patients. Method This prospective study was carried out on 53 (50 females and 3 males) heterozygote patients of FXIIID as well as the same number of normal population in duration of 3 months. All heterozygote individuals were selected from homozygote patients’ family. Healthy individuals were selected randomly from different parts of provinces. Both groups were age and sex matched (p=0.3). All individuals were assessed for factor XIII deficiency by FXIII activity assay and molecular analysis for Trp187Arg; the only previously reported polymorphism of factor XIII-A subunit in southeast Iran. Initially the clinical manifestations of all cases were assessed retrospectively and recorded. Then we assessed and compared the bleeding tendency in both groups by using the adult bleeding questionnaire and in one-month intervals. Results The mean ages of study populations were 34.8±8.4 (Ranges from 20 to 48 years) and 33.9±9.1 (Ranges from 21 to 49.5 years) in case and control groups, respectively. FXIII activity of the patient group was between 50-70 % and molecular analysis revealed that all the patients were heterozygote for Trp187Arg mutation. By regards to ethnicity, most of individuals in case group were Baluch (Number: 50 (94.3%)) and remained minority was Zaboli (Number: 3 (5.7%)). Distribution of ethnicity among case group was completely matched with control group (p=0.3). None of study individuals had a history of liver or kidney diseases or other bleeding susceptibility disorders. Clinical investigations indicated that 3 patients had a history of umbilical cord bleeding and delayed separation of the umbilical cord which led to administration of FXIII concentrate. All the 3 patients later presented with delayed post-circumcision bleeding. The mean age of menorrhagia in 50 females was 13.9±1.1 (Ranges from 12 to 16 years). Menstrual intervals range from 20 to 60 days with a mean of 29±5.2 days, but half of the patients had a normal interval of 30 days. Twenty three females had experienced menstruations with the need for a new pad every 2 hours. Among affected females 15 had an abnormal menstruation with duration of more than 7 days. Eight females were complicated by menorrhagia. This phenomenon observed in only one female of control group and therefore a significant difference was found between cases and controls (p<0.014). Sixteen patients had experienced at least one spontaneous miscarriage and the time of abortion in 10 females was in first trimester. One patient had a history of 3 spontaneous abortions. All abortions were followed by prolonged bleedings which led to administration of FXIII concentrate. The incidence of spontaneous abortions between cases and controls was statistically significant (p <0.001). All the observed clinical manifestations and the bleeding score in both groups are given in table1. Conclusion: Our findings indicated that heterozygote carriers of FXIIID may be complicated by substantial bleeding events which may threat the life and lead to the requirement of prophylaxis administration. Key words: Factor XIII deficiency, Heterozygote, Clinical manifestation Abstract 2852. Table 1.Prevalence of clinical manifestations in heterozygote patients of FXIIID and the bleeding score of both groups.Bleeding diathesisNumber of affected patients (%)Mean bleeding score of patients groupMean bleeding score of control groupSurgery *17(32.1%)10Bruising16(30.2%)30Miscarriage**16(32%)--Menorrhagia**8(16%)20Post delivery**8(16%)20After minor trauma6(11.3%)10Epistaxis4(7.5%)3-40Urinary or fecal blood3(5.6%)10Oral cavity3(5.6%)20Dental1(1.9%)40 *Seventeen patients had surgery among which 16 had bleeding during surgery and 1 had bleeding post surgery. **The percentage of these symptoms is calculated among 50 affected females. Disclosures No relevant conflicts of interest to declare.

This Is a Title : Long Term succsesfull Prophylaxis in 190 Patients with Severe Congenital Factor XIII Deficiency, a Four Years Experience. Here Is the Sub-Title: Succsefull Prophylaxis in Factor XIII Deficiency

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2851-2851
Author(s):  
Majid Naderi ◽  
Akbar Dorgalaleh ◽  
Shadi Tabibian ◽  
Shaban Alizadeh ◽  
Maryam Sadat Hosseini ◽  
...  
Keyword(s):  
Factor Xiii ◽  
Clinical Manifestations ◽  
Bleeding Diathesis ◽  
Factor Xiii Deficiency ◽  
Before And After ◽  
Bleeding Episodes ◽  
Group 2 ◽  
Fxiii Activity ◽  
Group 1

Abstract Background: factor XIII deficiency (FXIIID) is an extremely rare bleeding disorder with an estimated incidence of 1 per 1 to 3 million that transmitted in an autosomal recessive manner. The disorder is characterized by severe bleeding diathesis, impaired wound healing and recurrent spontaneous miscarriage. Sistan and Baluchistan Province in south east of Iran with high rate of consanguineous marriages has the highest incidence of FXIIID around the world. The aim of this study was to evaluate clinical manifestations and prophylaxis therapy in FXIII deficient patients with life threatening complications and to assess the risk of FXIII inhibitor development in patients with long term prophylaxis. We also investigated prophylaxis treatment in neonates with FXIIID. Methods: This study was conducted on 190 patients with FXIIID from southeast of Iran. Diagnosis of FXIIID was based on factor activity and molecular investigation of Trp187Arg which is the only reported mutation of FXIII in this region. We also selected some cases for sequencing to confirm the molecular results.Patients underwent regular prophylaxis and the efficacy of prophylaxis was assessed by prospective follow-up in duration of 4 years. The frequency of bleeding episodes as described by Tosetto et al. was recorded before and after prophylaxis each month. Patients with Intracranial hemorrhage (ICH) received Fibrogammin P® in a dose of 30 IU/Kg every 4 day as prophylaxis and in a dose of 10-26 IU/kg when ICH occurred. Patients with miscarriage underwent regular prophylaxis with FXIII concentrate with a dose of 10 IU/Kg every 2 weeks during pregnancy and also received the same dose as prophylaxis before gestation in 4 week intervals.In cases that had a history of prophylaxis for more than 4 years or had more than 50 injections, development of FXIII inhibitor was investigated by Bethesda assay. We evaluated plasma FXIII activity and FXIII inhibitor in day 28 after the last prophylaxis administration by Cobas Mira device. This assay was performed on a large amount of population for the first time. If the result of inhibitor was negative the test was replicated with 3 dilutions.We also enrolled 34 neonates with FXIIID to the study and divided them into two groups. Group 1 (17 neonates) received a standard dose of Fibrogammin (10-26 IU/Kg) while group 2 (17 neonates) received a dose of 60-80 IU/Kg. We followed both groups for 36 months and the frequency of bleeding episodes was recorded for each group and compared using independent t-test. Neonates in group 2 were assessed for thrombotic events promptly after administration of Fibrogammin P®, the following day and one week later. Results: Plasma FXIII activity in all patients was undetectable which is suggestive of severe deficiency. Genetic analysis revealed a homozygous Trp187Arg mutation in all patients and it was in agreement with the sequencing results of selected cases. Clinical manifestation of patients and the bleeding score of different diathesis before and after prophylaxis are indicated in table 1. Forty nine patients had the defined criteria for investigation of FXIII inhibitor development. Among them 14 had experienced ICH. Despite long term prophylaxis in these patients none of them was detected to develop FXIII inhibitors. No patient with ICH experienced this phenomenon after prophylaxis treatment. The majority of patients with miscarriage only experienced this diathesis once (62.5%). The prophylaxis program was successful in management of pregnancy in all 8 patients. Comparison of two neonate groups revealed that bleeding episodes in group 2 were significantly lower than group 1 (p<0.05). We did not observe any thrombotic event in group 2, which is an important finding in safety of Fibrogammin P® also in prevention of potential loss of drug. Conclusion: Fibrogammin P® is effective in the management of FXIIID and surprisingly long term prophylaxis in the patients did not lead to development of FXIII inhibitor. Furthermore higher dose of Fibrogammin P® is safe and effective in neonates. Table 1. Clinical manifestations and Tosetto bleeding scores of different bleeding diathesis before and after prophylaxis. Number of affected patients (%) Score before prophylaxis Score after prophylaxis Umbilical bleeding 157(82.5) 12 3 Hematoma 101 (53) 12 2 ICH 32(17%) 14 3 Epistaxis 26(14%) 11 2 Ecchymosis 25 (12.5%) 12 2 Hemarthrosis 7 (4%) 13 2 Miscarriage 8 (5%) - - Disclosures No relevant conflicts of interest to declare.

Clinical manifestations and management of life-threatening bleeding in the largest group of patients with severe factor XIII deficiency

2014 ◽  
Vol 100 (5) ◽  
pp. 443-449 ◽  
Author(s):  
Majid Naderi ◽  
Akbar Dorgalaleh ◽  
Shaban Alizadeh ◽  
Shadi Tabibian ◽  
Soudabeh Hosseini ◽  
...  
Keyword(s):  
Factor Xiii ◽  
Clinical Manifestations ◽  
Factor Xiii Deficiency ◽  
Life Threatening

New Families with Hereditary Hemorrhagic Trait due to Deficiency of Fibrin Stabilizing Factor (F. XIII)

1968 ◽  
Vol 20 (03/04) ◽  
pp. 534-541 ◽  
Author(s):  
O Egeberg
Keyword(s):  
Factor Xiii ◽  
Family Members ◽  
Recessive Inheritance ◽  
Factor Xiii Deficiency ◽  
History Of ◽  
Congenital Factor

SummarySevere hemorrhagic disorder due to congenital factor XIII deficiency is described in two unrelated Norwegian girls.Plasma cephalin time was for both patients extraordinarily short during episodes of bleeding and hematomas. No such hyperactivity reaction was demonstrable in unaffected condition some months later.Estimations of blood factor XIII levels revealed a partial defect in the parents of both children, and also in some other family members, consistent with an autosomal incompletely recessive inheritance of the defect. Some of the presumptive heterozygotes had a history of light bleeding phenomenons; whether this was related to their partial lack of factor XIII is so far uncertain.

Determination of Factor XIII Activity and of Factor XIII Inhibitors Using an Ammonium-Sensitive Electrode

1983 ◽  
Vol 50 (02) ◽  
pp. 563-566 ◽  
Author(s):  
P Hellstern ◽  
K Schilz ◽  
G von Blohn ◽  
E Wenzel
Keyword(s):  
Factor Xiii ◽  
Normal Subjects ◽  
The Other ◽  
Activity Measurement ◽  
Factor Xiii Deficiency ◽  
Assay Procedure ◽  
Stabilization Factor ◽  
Release Method ◽  
Sensitive Electrode

SummaryAn assay for rapid factor XIII activity measurement has been developed based on the determination of the ammonium released during fibrin stabilization. Factor XIII was activated by thrombin and calcium. Ammonium was measured by an ammonium-sensitive electrode. It was demonstrated that the assay procedure yields accurate and precise results and that factor XIII-catalyzed fibrin stabilization can be measured kinetically. The amount of ammonium released during the first 90 min of fibrin stabilization was found to be 7.8 ± 0.5 moles per mole fibrinogen, which is in agreement with the findings of other authors. In 15 normal subjects and in 15 patients suffering from diseases with suspected factor XIII deficiency there was a satisfactory correlation between the results obtained by the “ammonium-release-method”, Bohn’s method, and the immunological assay (r1 = 0.65; r2= 0.70; p<0.01). In 3 of 5 patients with paraproteinemias the values of factor XIII activity determined by the ammonium-release method were markedly lower than those estimated by the other methods. It could be shown that inhibitor mechanisms were responsible for these discrepancies.

Defective Fibrin Crosslinking in Acute Leukemia

1984 ◽  
Vol 52 (03) ◽  
pp. 343-346 ◽  
Author(s):  
F Rodeghiero ◽  
T Barbui ◽  
A Dal Belin-Peruffo ◽  
E Dini
Keyword(s):  
Acute Leukemia ◽  
Factor Xiii ◽  
Factor Xiii Deficiency ◽  
Coagulation Abnormalities ◽  
Normal Plasma ◽  
Transamidating Activity

SummaryFibrin crosslinking was assayed in 22 patients with acute leukemia showing secondary coagulation abnormalities of variable severity. In 9 patients fibrin crosslinking was found to be normal, whereas 10 patients presented impaired polymerization of α-chains and 3 of both α- and γ-chains.Only a rough correlation was found between transamidating activity of factor XIII and the fibrin crosslinking pattern in these patients. Moreover, incomplete fibrin crosslinkage occurred at levels of factor XIII far in excess of that required for full polymerization of fibrin in “normal” plasma. This latter finding suggests that, in addition to factor XIII deficiency, other causes are responsible for thehigh rate of fibrin crosslinking impairment in acute leukemia.

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