scholarly journals Acquired Factor XIII Deficiency in a Patient with Metastatic Lung Cancer

2022 ◽  
Vol 3 (1) ◽  
pp. 01-03
Author(s):  
Ana Sofia Mendes ◽  
Marco Dias ◽  
Sara Morais ◽  
Raque Romão ◽  
Bernardo Teixeira ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Neutralizing Antibodies ◽  
Factor Xiii ◽  
Process Analysis ◽  
Clinical Report ◽  
Bleeding Tendency ◽  
Metastatic Nsclc ◽  
Immune Mediated ◽  
Clinical Records ◽  
Fxiii Deficiency

Acquired factor XIII (FXIII) deficiency can result in life-long bleeding tendency and can be caused by enhanced consumption, impaired synthesis, or as an immune-mediated process. The latter can be related with solid neoplasms, through neutralizing or non-neutralizing antibodies. The relationship between FXIII activity and non-small cell lung cancer (NSCLC) is not well established. This case report is about a patient with NSCLC and acquired FXIII deficiency. Materials and Methods: Clinical records were obtained through the electronic process analysis, and the confidentiality of the patient was always assured. Results and Discussion: A 70-year-old male with no relevant past medical history and a recently diagnosed metastatic NSCLC was admitted for priapism. Five days later, a he developed a bleeding disorder, with slightly elevated coagulation times and normal fibrinogen levels and platelets count. FXIII level was found to be decreased (0.24 IU/mL) and FXIII plasma mixing studies did not confirm the presence of a neutralizing inhibitor. The FXIII level correction with standard plasma mixing studies was in favour of a non-neutralizing antibody. Despite treatment, haemorrhage control was not achieved and the patient died. Conclusion: This clinical report describes a rare case of a patient with metastatic NSCLC presenting a severe haemorrhagic event caused by FXIII deficiency immune-mediated by non-neutralizing antibodies and subsequent increased clearance.

Relevant bleeding diathesis due to acquired factor XIII deficiency

2013 ◽  
Vol 33 (S 01) ◽  
pp. S50-S54 ◽  
Author(s):  
M. Janning ◽  
K. Holstein ◽  
B. Spath ◽  
C. Schnabel ◽  
P. Bannas ◽  
...  
Keyword(s):  
Factor Xiii ◽  
False Lumen ◽  
Surgical Patients ◽  
Major Surgery ◽  
Severe Bleeding ◽  
Acute Type ◽  
Activity Levels ◽  
Bleeding Tendency ◽  
Limited Information ◽  
Fxiii Deficiency

SummaryAcquired factor XIII (FXIII) deficiency is associated with reduced clot firmness and increased bleeding in patients undergoing major surgery. In contrast, only limited information is available on the haemostatic relevance of acquired FXIII deficiency in non-surgical patients.An 81-year-old patient, who had experienced acute type-A dissection of the aorta eight years earlier, presented with a 3-year history of progressive mucocutaneous and softtissue bleeding. Diagnostic work-up was unremarkable for global coagulation tests, but FXIII and alpha2-antiplasmin were decreased to 33% and 27%, respectively, while plasma D-dimer was elevated to > 35 mg/l. A FXIII inhibitor was excluded by mixing studies. CT scanning revealed a massively elongated and progressively dilated aorta with a false lumen reaching from the left carotid artery to the iliac bifurcation. Bleeding control was achieved by single doses of FXIII at 20-30 IU/ kg body weight and tailored oral tranexamic acid.Acquired FXIII deficiency with activity levels of 30–35% may confer a severe bleeding tendency in non-surgical patients, especially in the context of increased thrombin an fibrin generation.

A Novel 3-Base Pair 1834–1836 AAG-Deletion (Lys570Del) Mutation In Factor XIII A Subunit Associated with Factor XIII Deficiency

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1412-1412
Author(s):  
Anamika Singh ◽  
A. Koneti Rao
Keyword(s):  
Factor Xiii ◽  
Bleeding Tendency ◽  
Compound Heterozygosity ◽  
Factor Xiii Deficiency ◽  
Catalytic Core ◽  
A Subunit ◽  
A Chain ◽  
The Impact ◽  
Fxiii Activity ◽  
Fxiii Deficiency

Abstract Abstract 1412 Factor XIII is a transglutaminase that cross-links proteins in plasma, vascular matrix, endothelial cells, platelets and monocytes, and plays a role in atherosclerosis, wound healing, and inflammation. Plasma FXIII molecule is a hetero-tetramer consisting of two catalytic A-subunits and two B-subunits that act as carrier molecules. The gene encoding FXIII A subunit comprises of 15 exons spanning 160 kb and the mature protein contains 731 amino acids. FXIII deficiency is a rare autosomal recessive disorder affecting ∼1 in 1–3 million people. It is characterized by bleeding, impaired wound repair and spontaneous abortions. We report studies from a family where two children son (13 yrs) and daughter (11 yrs) have had a lifelong bleeding tendency and spontaneous intracranial hemorrhages. Both parents were asymptomatic and there was no consanguinity. The results of routine laboratory tests, prothrombin time and activated partial thromboplastin time were normal in all subjects. The plasma FXIII activity by a commercially available chromogenic assay was 5% in the son and <3% in the daughter (normal range 57–192%). The FXIII activity in the father and mother were 198% and 74%, respectively. We have identified a novel deletion mutation, which has not been reported so far in FXIII deficiency. Leukocyte RNA was isolated from the buffy-coat and cDNA was obtained by reverse-transcription PCR using SuperScript First-Strand Synthesis System. The amplified products were cloned in pGEM-T vector (Promega) and sequenced on an automated gene-sequencer. Both children and the father have a novel 3 bp AAG-deletion position 1834–1836 nt in FXIII A chain. This mutation causes a lysine 570 deletion in the ß-barrel 1 of Factor XIII A subunit and has not been reported so far. It may lead to protein misfolding resulting in an unstable protein, and low levels of FXIII. The second major change detected in the two siblings was a A/T substitution at position 737 nt causing Tyr204Phe substitution in the two siblings; this was present in the mother in a heterozygous condition. This mutation has been previously reported in FXIII deficiency and linked to increased risk of haemorrhagic stroke in young women and of miscarriages. The compound heterozygosity for Lys570Del and Tyr204Phe substitution observed in both children is the likely cause of Factor XIII deficiency leading to lifelong bleeding condition. In addition to above, the father had Val34Leu polymorphism, previously reported to be associated with resistance to myocardial infarction. This polymorphism is present in ∼20% of white European, 40% of Pima Native American and 13% of South Asian populations. The mother also had a known A/C polymorphism at 1119 nt position for a synonymous Pro332Pro change. We also found 3 other variations in FXIII A chain in this family. The daughter has Glu216Gly and Asp267Asn change in the protein corresponding to alterations at nucleotide 773 (A/G) and 925 (A/G), respectively. The son and mother had a substitution at 1442 nt (T/C) leading to a Leu439Pro change. These variations, Glu216Gly, Asp267Asn and Leu439Pro found in the two children (Leu439Pro also in mother) are present in the catalytic core domain of the Factor XIII A chain. All of the polymorphisms or mutations reported in this study were heterozygous in the studied subjects. FXIII gene mutations and polymorphisms result in a high level of heterogeneity of disease presentation. Other point mutations in the FXIII A catalytic core as well as mutations in ß-barrel 1 region have been described in association with a hemorrhagic state in FXIII deficiency. Our study documents a new 3-bp 1834–1836 nt AAG-deletion (Lys570Del) in association with FXIII deficiency. We suggest that compound heterozygosity for Lys570Del and Tyr204Phe is the cause of FXIII deficiency in our patients. Further structure-function studies will aid in understanding the impact of these amino acid substitutions or deletions on FXIII function and on the associated bleeding diathesis. Disclosures: No relevant conflicts of interest to declare.

Establishment of an International Registry of Patients with Inherited FXIII Deficiency.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2149-2149
Author(s):  
Vytautas Ivaskevicius ◽  
Rainer Seitz ◽  
Hans P. Kohler ◽  
Laszlo Muszbek ◽  
Robert A.S. Ariens ◽  
...  
Keyword(s):  
Factor Xiii ◽  
Working Party ◽  
Splice Site Mutation ◽  
Autosomal Recessive Disorder ◽  
Bleeding Tendency ◽  
Site Mutation ◽  
Impaired Wound Healing ◽  
Thrombosis Research ◽  
The Impact ◽  
Fxiii Deficiency

Abstract Inherited factor XIII (FXIII) deficiency is a rare autosomal recessive disorder affecting approximately one out of one to three million people. FXIII deficiency is characterized by a lifelong bleeding tendency, impaired wound healing and spontaneous abortions in females. In 1993, the European Thrombosis Research Organization (ETRO) Working Party on FXIII initiated a Europe-wide questionnaire on inherited FXIII deficiency. Since 2005, the registry has been endorsed by the Factor XIII Subcommittee of the Scientific and Standardization committee (SSC) of the ISTH. The analysis of 104 European patients demonstrated that the most common bleeding symptoms were subcutaneous bleeding (57%) followed by delayed umbilical cord bleeding (56%), muscle hematoma (49%), hemorrhage after surgery (40%), hemarthrosis (36%), and intracerebral bleeding (34%). Prophylactic treatment was initiated in about 70% of all patients. FXIII-B subunit-deficient patients had a milder phenotype than patients with FXIII-A subunit deficiency.The most frequent mutation affecting the F13A gene was a splice site mutation in intron 5 (IVS5-1G&gt;A).This mutation was found in eight (17%) of 46 analyzed families.The haplotype analysis of patients carrying the IVS5-1A allele was consistent with a founder effect. Recently, we created a new FXIII database website (http://www.f13-database.de) with information about FXIII proteins, genes, mutations and polymorphisms. This website also includes a new questionnaire. Information provided by this questionnaire will allow better understanding of the differences of diagnostic and treatment possibilities in various parts of the world, and it will help to understand the impact of reduced FXIII activity in heterozygous relatives and finally, it will generally increase our knowledge on this rare disease. We hope that our initiative to establish a new international FXIII registry will be actively supported by the community involved in caring for FXIII deficient patients.

Factor XIII: Congenital Deficiency Factor XIII, Acquired Deficiency, Factor XIII A-Subunit, and Factor XIII B-Subunit

2014 ◽  
Vol 138 (2) ◽  
pp. 278-281 ◽  
Author(s):  
Anita Tahlan ◽  
Jasmina Ahluwalia
Keyword(s):  
Factor Xiii ◽  
Recurrent Miscarriage ◽  
Fresh Frozen Plasma ◽  
Screening Tests ◽  
Bleeding Tendency ◽  
Thrombin Time ◽  
Congenital Deficiency ◽  
Fresh Frozen ◽  
B Subunits ◽  
Fxiii Deficiency

Factor XIII (FXIII) is a transglutaminase consisting of 2 catalytic A subunits and 2 noncatalytic B subunits in plasma. The noncatalytic B subunits protect the catalytic A subunits from clearance. Congenital FXIII deficiency may manifest as a lifelong bleeding tendency, abnormal wound healing, and recurrent miscarriage. Acquired FXIII deficiency, with significant reductions in FXIII levels, has been reported in several medical conditions. The routine screening tests for coagulopathies—prothrombin time, activated partial thromboplastin time, and thrombin time—do not show abnormalities in cases of FXIII deficiency. A quantitative, functional, FXIII activity assay that detects all forms of FXIII deficiency should be used as a first-line screening test. Treatment consists of recombinant FXIII or FXIII concentrate. If these are unavailable, then fresh-frozen plasma and cryoprecipitates may be used. Factor XIII has a long half-life; therefore, the patients can lead near-normal lives with regular replacements. Patients with acquired FXIII deficiency with inhibitors need immunosuppressive therapy in addition to factor replacements.

scholarly journals Differential influence of antibiotic therapy and other medications on oncological outcomes of patients with non-small cell lung cancer treated with first-line pembrolizumab versus cytotoxic chemotherapy

2021 ◽  
Vol 9 (4) ◽  
pp. e002421
Author(s):  
Alessio Cortellini ◽  
Massimo Di Maio ◽  
Olga Nigro ◽  
Alessandro Leonetti ◽  
Diego L Cortinovis ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Objective Response ◽  
Multivariable Analysis ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Metastatic Nsclc ◽  
The Impact

BackgroundSome concomitant medications including antibiotics (ATB) have been reproducibly associated with worse survival following immune checkpoint inhibitors (ICIs) in unselected patients with non-small cell lung cancer (NSCLC) (according to programmed death-ligand 1 (PD-L1) expression and treatment line). Whether such relationship is causative or associative is matter of debate.MethodsWe present the outcomes analysis according to concomitant baseline medications (prior to ICI initiation) with putative immune-modulatory effects in a large cohort of patients with metastatic NSCLC with a PD-L1 expression ≥50%, receiving first-line pembrolizumab monotherapy. We also evaluated a control cohort of patients with metastatic NSCLC treated with first-line chemotherapy. The interaction between key medications and therapeutic modality (pembrolizumab vs chemotherapy) was validated in pooled multivariable analyses.Results950 and 595 patients were included in the pembrolizumab and chemotherapy cohorts, respectively. Corticosteroid and proton pump inhibitor (PPI) therapy but not ATB therapy was associated with poorer performance status at baseline in both the cohorts. No association with clinical outcomes was found according to baseline statin, aspirin, β-blocker and metformin within the pembrolizumab cohort. On the multivariable analysis, ATB emerged as a strong predictor of worse overall survival (OS) (HR=1.42 (95% CI 1.13 to 1.79); p=0.0024), and progression free survival (PFS) (HR=1.29 (95% CI 1.04 to 1.59); p=0.0192) in the pembrolizumab but not in the chemotherapy cohort. Corticosteroids were associated with shorter PFS (HR=1.69 (95% CI 1.42 to 2.03); p<0.0001), and OS (HR=1.93 (95% CI 1.59 to 2.35); p<0.0001) following pembrolizumab, and shorter PFS (HR=1.30 (95% CI 1.08 to 1.56), p=0.0046) and OS (HR=1.58 (95% CI 1.29 to 1.94), p<0.0001), following chemotherapy. PPIs were associated with worse OS (HR=1.49 (95% CI 1.26 to 1.77); p<0.0001) with pembrolizumab and shorter OS (HR=1.12 (95% CI 1.02 to 1.24), p=0.0139), with chemotherapy. At the pooled analysis, there was a statistically significant interaction with treatment (pembrolizumab vs chemotherapy) for corticosteroids (p=0.0020) and PPIs (p=0.0460) with respect to OS, for corticosteroids (p<0.0001), ATB (p=0.0290), and PPIs (p=0.0487) with respect to PFS, and only corticosteroids (p=0.0033) with respect to objective response rate.ConclusionIn this study, we validate the significant negative impact of ATB on pembrolizumab monotherapy but not chemotherapy outcomes in NSCLC, producing further evidence about their underlying immune-modulatory effect. Even though the magnitude of the impact of corticosteroids and PPIs is significantly different across the cohorts, their effects might be driven by adverse disease features.

scholarly journals Revisiting multiple erroneous genetic testing results and clinical misinterpretations in a patient with Li-Fraumeni syndrome: lessons for translational medicine

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Tatiana N. Sokolova ◽  
Valeriy V. Breder ◽  
Irina S. Shumskaya ◽  
Evgeny N. Suspitsin ◽  
Svetlana N. Aleksakhina ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Genetic Testing ◽  
Dna Analysis ◽  
Germ Line ◽  
Bilateral Breast Cancer ◽  
Daily Practice ◽  
Medical Laboratory ◽  
Clinical Expertise ◽  
Li Fraumeni Syndrome ◽  
Clinical Records

Abstract Background Many cancer patients undergo sophisticated laboratory testing, which requires proper interpretation and interaction between different specialists. Case presentation We describe a patient with an extensive family history of cancer, who was diagnosed with bilateral breast cancer and two lung cancer lumps by the age of 40 years. She submitted a lung cancer specimen to a genetic profiling service, which reported the presence of the EGFR mutation (a combination of G719S and L833V substitutions) and the TP53 с.322_327del (p.G108_F109del) mutation in the tumor tissue. Possible therapeutic options were discussed at a medical conference, where one of the discussants raised a concern that the identified TP53 mutation may not necessarily be somatic, but reflect the germ-line status of the gene. Review of clinical records and follow-up dialog with the patient revealed, that she previously provided her blood for DNA analysis in two laboratories. The first laboratory utilized a custom NGS assay and did not detect the TP53 mutation, instead pointed to a potential pathogenic significance of the MSH6 c.2633 T > C (p.V878A) allele. The second laboratory revealed the TP53 с.322_327del (p.G108_F109del) allele but stated in the written report that it has an unknown pathogenic significance. To resolve the possible uncertainty regarding the role of the TP53 с.322_327del (p.G108_F109del) variant, we suggested that the patient invite her second cousin for genetic testing, as she was affected by neuroblastoma at the age of 3 years. This analysis revealed the presence of the same TP53 variant. Conclusion We provide point-by-point discussion, reviewing multiple laboratory mistakes and clinical misinterpretations occurred with this patient. This case report exemplifies the need to involve rigorous clinical expertise in the daily practice of medical laboratory facilities.

Factor XIII Deficiency and Intracranial Bleed: Surgical Management and Prophylaxis with Cryoprecipitate

2021 ◽  
Author(s):  
Sunil V. Furtado ◽  
Pranoy Hegde ◽  
Rasmi Palassery ◽  
B. P. Karunakara
Keyword(s):  
Factor Xiii ◽  
Perioperative Management ◽  
Severe Headache ◽  
Resonance Imaging ◽  
Factor Xiii Deficiency ◽  
Limb Weakness ◽  
High Propensity ◽  
Intracranial Bleed ◽  
The Brain ◽  
Fxiii Deficiency

AbstractFactor XIII (FXIII) deficiency is a rare bleeding disorder with affected patients having high propensity for intracranial hemorrhage. A 12-year-old girl presented with severe headache, limb weakness, and rapidly worsening sensorium over 4 days. Magnetic resonance imaging of the brain and computed tomography (CT) of the head showed intraparenchymal bleed. Patient had normal coagulation profile and abnormal FXIII level. The perioperative management included cryoprecipitate transfusion to bring the FXIII value to 74%. She underwent craniotomy and evacuation of the hematoma. Postoperatively, she received prophylaxis against rebleed with cryoprecipitate. In the absence of FXIII concentrate, correction of FXIII deficiency is possible with cryoprecipitate in emergent situations.

Improving time to molecular testing results in patients with newly diagnosed, metastatic non-small cell lung cancer (NSCLC).

2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 244-244
Author(s):  
Stephanie Ossowski ◽  
Elad Neeman ◽  
Charles Borden ◽  
Amy Ying Ju Lin ◽  
Raymond Liu
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Turnaround Time ◽  
Small Cell ◽  
Pathological Diagnosis ◽  
Genomic Testing ◽  
Newly Diagnosed ◽  
Small Cell Lung ◽  
First Line ◽  
Metastatic Nsclc

244 Background: Next generation sequencing (NGS) is a crucial component of evaluation of newly diagnosed patients with metastatic non-small cell lung cancer (NSCLC) to determine appropriate first line treatment. Delays in NGS can lead to psychologic distress for patients and can affect choices in first line therapy, especially for patients with underlying targetable mutations. While more data is needed to benchmark turnaround time for NGS results, guidelines and expert consensus suggest time from diagnosis to treatment should be 15 days and turnaround time for genomic testing 10-14 days. This study was aimed at reducing time to NGS results in a large integrated health care system. Methods: Through the ASCO Quality Training Program, we reviewed electronic medical records of 25 patients with newly diagnosed, untreated metastatic NSCLC from 12/2018 to 9/2020 and determined number of days from pathological diagnosis to NGS results. We reviewed process maps for oncology, pathology, the internal data management division, and a genomic testing company to determine factors leading to significant preventable delays. Since 11/2020, we created an automated weekly report using CoPath to identify new pathological diagnoses of potential metastatic NSCLC. The oncology department reviewed these cases weekly and NGS orders were placed for patients with metastatic NSCLC. Eleven additional patients with newly diagnosed metastatic NSCLC were included in the prospective cohort. Results: Demographic characteristics are noted in Table. Our intervention reduced median time from pathological diagnosis to NGS results from 24 to 19 days. Median time from biopsy results to NGS order was reduced from 7 to 1 day. Time from specimen being sent from pathology to NGS vendor was a median of 6 days in both cohorts. Total time from pathological diagnosis to appropriate treatment was reduced from a median of 33 to 25 days. Conclusions: Delays in time to NGS results can be reduced by improved communication between departments and simple, automated interventions to ensure results are efficiently released to an oncologist. Additional Plan-Do-Study-Act cycles are currently being developed to further reduce time from biopsy results to NGS results. [Table: see text]

scholarly journals Relationships of Coagulation Factor XIII Activity with Cell-Type and Stage of Non-Small Cell Lung Cancer

2013 ◽  
Vol 54 (6) ◽  
pp. 1394 ◽  
Author(s):  
Seung Heon Lee ◽  
In Bum Suh ◽  
Eun Joo Lee ◽  
Gyu Young Hur ◽  
Sung Yong Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Factor Xiii ◽  
Coagulation Factor ◽  
Small Cell ◽  
Cell Type ◽  
Small Cell Lung ◽  
Coagulation Factor Xiii

scholarly journals Electronic Clinical Records for Physiotherapists

2006 ◽  
Author(s):  
Christine Barry ◽  
Mark Jones ◽  
Karen Grimmer
Keyword(s):  
Legal Protection ◽  
Data Retrieval ◽  
Electronic Record ◽  
Electronic System ◽  
Electronic Records ◽  
Clinical Report ◽  
Record System ◽  
Clinical Records ◽  
The Impact ◽  
Electronic Record System

Purpose: This pilot study compared traditional (paper-based) and electronic (computerized) clinical physiotherapy records. The content of the records and the software’s user acceptability were considered. Methods: A neuro-musculoskeletal patient scenario involving two encounters (initial and follow-up) was scripted and role-played to each of three experienced physiotherapists (A, B and C). Participants assessed the patient and made traditional clinical records. After basic training in an electronic record system, they repeated the assessments and made electronic records via a laptop computer. Three experienced physiotherapists (A, D and E) each used their usual method to write a clinical report and an electronic record to write a report with the aid of the software’s report tool. The two participants who wrote reports but did not assess the patient (D and E) received a brief software demonstration just prior to writing the electronic record report. The electronic and traditional clinical records and reports were compared regarding their content and completion time. Participants recorded their expectations and experience of learning and using the electronic record system via questionnaires. Results: Participants expressed initial apprehension regarding an unfamiliar documentation system, but generally found the electronic system easy to learn and use. Some would have preferred additional customization options. All traditional records contained pages that lacked patient identification details. The electronic records contained more details related to symptoms, social circumstances and physical examination findings. The participants used more time for assessment and recording the initial examination when using the electronic system. Participants reported easier data retrieval from the computerized records than from the traditional records. Conclusions:The electronic clinical record system may prompt more complete recording and facilitate better patient record identification. These effects have implications for patient care, communication between providers and clinicians’ medico-legal protection. Further research is needed to determine the system’s efficiency and to clarify the impact of other characteristics of electronic record systems for physiotherapists.

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