scholarly journals Primary Immunodeficiency with double strain break DNA (DSBs) and radiosensitvity: clinical, diagnostic and therapeutic implications

2018 ◽  
Vol 72 ◽  
pp. 449-460 ◽  
Author(s):  
Barbara Pietrucha ◽  
Hanna Gregorek ◽  
Edyta Heropolitańska-Pliszka ◽  
Ewa Bernatowska
Keyword(s):  
Dna Repair ◽  
Radiation Treatment ◽  
Genetic Disorders ◽  
Malignant Neoplasms ◽  
Dna Double Strand Breaks ◽  
Hematopoietic Stem ◽  
Therapeutic Implications ◽  
Treatment Regimens ◽  
Increased Risk ◽  
Immune Deficiencies

Primary Immunodeficiencies (PNO) are a group of about 300 genetic disorders which result from the absence or dysfunction of the major components of the immune system. Among them an important subgroup constitute deficiencies associated with defects in DNA double strand breaks (DSBs) recognition and repair. These are primarily radiation-sensitive severe combined immune deficiencies (SCIDs) and combined immune deficiencies (CIDs) associated with genetic defects in the DNA-repair genes, which encode proteins necessary for T-cell and B cell maturation/differentiation. Due to increased risk of developing malignant neoplasms, mainly from hematopoietic origin, and over-reaction to standard anticancer radiotherapy and chemotherapy, treatment of these patients is a real challenge for clinicians. Clinical and laboratory manifestations, which may indicate increased radiosensitivity include: microcephaly, telangiectasias, lymphopenia, and translocation of chromosomes 7 and 14 in karyotype. A basic test showing increased radiosensitivity of lymphoblastoid cells lines or skin fibroblasts is percentage evaluation of their survival after exposition to ionizing radiation. Treatment of patients with impaired DNA repair depends on the clinical picture, immunological findings and type of immunodeficiency. Patients with SCID require immediate hematopoietic stem cell transplantation (HSCT) using reduced intensity conditioning (RIC). In patients with CID, standard treatment regimens require modification and/or avoidance of radiotherapy and some radiomimetic agents.

scholarly journals Current recommendations for clinical surveillance and genetic testing in rhabdoid tumor predisposition: a report from the SIOPE Host Genome Working Group

2021 ◽  
Author(s):  
M. C. Frühwald ◽  
K. Nemes ◽  
H. Boztug ◽  
M. C. A. Cornips ◽  
D. G. Evans ◽  
...  
Keyword(s):  
Working Group ◽  
Soft Part ◽  
Genetic Disorders ◽  
Panel Discussion ◽  
Rhabdoid Tumor ◽  
Host Genome ◽  
Cancer Surveillance ◽  
Malignant Neoplasms ◽  
Pathogenic Variants ◽  
Increased Risk

AbstractThe rhabdoid tumor (RT) predisposition syndromes 1 and 2 (RTPS1 and 2) are rare genetic conditions rendering young children vulnerable to an increased risk of RT, malignant neoplasms affecting the kidney, miscellaneous soft-part tissues, the liver and the central nervous system (Atypical Teratoid Rhabdoid Tumors, ATRT). Both, RTPS1&2 are due to pathogenic variants (PV) in genes encoding constituents of the BAF chromatin remodeling complex, i.e. SMARCB1 (RTPS1) and SMARCA4 (RTPS2). In contrast to other genetic disorders related to PVs in SMARCB1 and SMARCA4 such as Coffin-Siris Syndrome, RTPS1&2 are characterized by a predominance of truncating PVs, terminating transcription thus explaining a specific cancer risk. The penetrance of RTPS1 early in life is high and associated with a poor survival. However, few unaffected carriers may be encountered. Beyond RT, the tumor spectrum may be larger than initially suspected, and cancer surveillance offered to unaffected carriers (siblings or parents) and long-term survivors of RT is still a matter of discussion. RTPS2 exposes female carriers to an ill-defined risk of small cell carcinoma of the ovaries, hypercalcemic type (SCCOHT), which may appear in prepubertal females. RT surveillance protocols for these rare families have not been established. To address unresolved issues in the care of individuals with RTPS and to propose appropriate surveillance guidelines in childhood, the SIOPe Host Genome working group invited pediatric oncologists and geneticists to contribute to an expert meeting. The current manuscript summarizes conclusions of the panel discussion, including consented statements as well as non-evidence-based proposals for validation in the future.

Benzene metabolite hydroquinone promotes DNA homologous recombination repair via the NF-κB pathway

2019 ◽  
Vol 40 (8) ◽  
pp. 1021-1030 ◽  
Author(s):  
Xuejing Yang ◽  
Yedan Lu ◽  
Fuhong He ◽  
Fenxia Hou ◽  
Caihong Xing ◽  
...  
Keyword(s):  
Dna Repair ◽  
Homologous Recombination ◽  
Molecular Mechanisms ◽  
Chromosomal Rearrangements ◽  
Critical Role ◽  
Environmental Pollutants ◽  
Environmental Pollutant ◽  
Osteosarcoma Cell ◽  
Dna Double Strand Breaks ◽  
Hematopoietic Stem

Abstract Benzene, a widespread environmental pollutant, induces DNA double-strand breaks (DSBs) and DNA repair, which may further lead to oncogenic mutations, chromosomal rearrangements and leukemogenesis. However, the molecular mechanisms underlying benzene-induced DNA repair and carcinogenesis remain unclear. The human osteosarcoma cell line (U2OS/DR-GFP), which carries a GFP-based homologous recombination (HR) repair reporter, was treated with hydroquinone, one of the major benzene metabolites, to identify the potential effects of benzene on DSB HR repair. RNA-sequencing was further employed to identify the potential key pathway that contributed to benzene-initiated HR repair. We found that treatment with hydroquinone induced a significant increase in HR. NF-κB pathway, which plays a critical role in carcinogenesis in multiple tumors, was significantly activated in cells recovered from hydroquinone treatment. Furthermore, the upregulation of NF-κB by hydroquinone was also found in human hematopoietic stem and progenitor cells. Notably, the inhibition of NF-κB activity by small molecule inhibitors (QNZ and JSH-23) significantly reduced the frequency of hydroquinone-initiated HR (−1.36- and −1.77-fold, respectively, P < 0.01). Our results demonstrate an important role of NF-κB activity in promoting HR repair induced by hydroquinone. This finding sheds light on the underlying mechanisms involved in benzene-induced genomic instability and leukemogenesis and may contribute to the larger exploration of the influence of other environmental pollutants on carcinogenesis.

scholarly journals A Sublime Technique to Solve DNA-Repair Model

2020 ◽  
Vol 8 (6) ◽  
pp. 3339-3343
Keyword(s):  
Dna Repair ◽  
Decomposition Method ◽  
Genetic Disorders ◽  
Adomian Decomposition Method ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Adomian Decomposition ◽  
Life Threatening ◽  
Comparison Table

Deoxyribonucleic acid (DNA) is an essential macromolecule for all known varieties of life and its damage is a life-threatening structure. The DNA double-strand breaks (DSBs) are considered as one of the most rigorous kinds of DNA damage and an error in its repairing mechanism stimulates cancer and also causes lethality in cells with various genetic disorders. In this article, we have exhibited a numerical solution of an ordinary differential equation based biological model to overcome the error for estimating the average number of DSBs per cell time. This model is called DNA repair Model (DRM) and to solve this model a Modified Adomian decomposition method with new polynomials (MADMNP) is applied. The convergence of the aforesaid method is established and the order of error is also dissertated. To solve DRM, this method provides an improved scheme to estimate the average number of DSBs per cell time in comparison to Adomain decomposition method (ADM) and Laplace ADM with Pad`e approximation (LADM-Pad`e). In this respect, a comparison table and a two-dimensional comparison graph are provided by considering a numerical example.

scholarly journals Rare Variants Affecting the Fanconi Anaemia DNA Repair Genes Associate with Increased Risk for AML

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 41-41
Author(s):  
Kyaw Ze Ya Maung ◽  
Paul Leo ◽  
Anna L Brown ◽  
Mahmoud A Bassal ◽  
Debora A. Casolari ◽  
...  
Keyword(s):  
Dna Repair ◽  
Bone Marrow Failure ◽  
Subsequent Development ◽  
Fanconi Anaemia ◽  
Gene Variants ◽  
Healthy Controls ◽  
Hematopoietic Stem ◽  
Germline Variants ◽  
Mutational Burden ◽  
Increased Risk

Abstract While there have been extensive studies to define the roles of recurrent somatic mutations in AML, the contribution of germline variants to AML initiation and progression is less well established. DNA repair disorders often predispose patients to developing myeloid malignancies. In particular, biallelic mutations affecting FANC genes cause the recessive heritable bone marrow failure syndrome Fanconi Anemia (FA), which is associated with >800-fold increased risk of progression to AML. A recent explosion of cancer predisposition studies has also revealed the importance of germlineFANC variants in elevated cancer risk (Cancer Treat Rev 2012; 38:89). To investigate the role of FANC gene variants in AML we have performed a case-control study, analyzing rare, deleterious somatic and germline variants for the 19 FANC genes in adult AML and healthy controls cohorts. Whole exome sequencing was performed on diagnosis samples from 131 adult Caucasian AML patients from two major Australian centers, and a cohort of 329 healthy females. We identified rare Tier 1 variants using a minor allele frequency (MAF) < 0.001, as reported in common dbSNP137, 1000 Genome and NHLBI-ESP project databases. Combined Annotation Dependent Depletion algorithm (CADD, Nat Genet 2014; 46: 310) >10 was used to filter for FANC gene variants with high probability of pathogenicity. Sanger sequencing of matched tumour/non-tumour DNA showed the large majority of variants tested to be germline (90%), consistent with previous studies reporting that somatic FANC genes variants are extremely rare in AML (< 1%). Overall, we identified 52 FANC gene variants in 44 cases with 34% of AML cases carrying one or more variant. For independent validation we determined the presence of somatic and germline FANC variants in the TCGA AML cohort using an identical pipeline and filtering analysis. In line with our results, we found that 36% of TCGA AML patients carry at least one germline FANC variant. We investigated known disease-causing (D-C) variants in these two AML cohorts using the FA (FAMutdb) and breast cancer (kConFab and BIC) mutation databases. We found 8 D-C FANC variants in the Australian AML cohort and 5 in the TCGA cohort, with 1 variant present in both cohorts. Moreover, the frequency of D-C variants in our cohort of females with AML (n=51) is 13.7%, while the frequency in the healthy female cohort is 4.5%, comparable to that reported in the ESP database for female European-Americans (2.1%, Hum Mol Genet 2014; 23: 6815). Accordingly, we determined that deleterious FANC germline variants confer a significant increased risk of AML (P=0.018, OR=3.3 for the Australian AML cohort). Finally, we performed mutational burden analysis to investigate enrichment of variants associated with particular FANC genes across the AML cohort. This revealed a significant enrichment of FANCL variants in AML vs healthy controls (P=0.008, Figure 1). FANCL is the enzymatic component of the FA core complex that monoubiquitinates the FANCD2/I heterodimer initiating DNA repair, and its down-regulation has been linked to AML (Oncogene 2016; doi:10.1038). Several FANCL variants, found in our AML cohort, affect the catalytic RING domain and are of particular interest. These include a D-C null variant present in 2 patients, a frame shift variant in 2 patients who presented with AML at a very early age (27 and 46 years old), and a variant affecting a critical conserved residue required for monoubiquitination of FANCD2/I. In conclusion, we show enrichment of rare potentially deleterious FANC gene mutations in AML, associated with a 3-fold increased risk of developing the disease. We hypothesise that, in hematopoietic stem/progenitor cells, these variants confer a subtle defect in interstrand cross-link repair leading to an increased accumulation of mutations and subsequent development of AML. Consistent with this there have been several reports of defective DNA damage repair and increased sensitivity to DNA damaging agents in cells from FANC carriers compared to normal controls (Nat Commun 2014; 5:5496; Mutagenesis 2009; 24:67). Importantly, it is possible to target defects in several DNA repair pathways, and our finding identifies a group of AML patients who may benefit from approaches that target defective FA and homologous recombination pathways. Figure 1. A significant increase mutational burden of FANCL was observed in our AML cohort (line represents P=0.05). Figure 1. A significant increase mutational burden of FANCL was observed in our AML cohort (line represents P=0.05). Disclosures Gill: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees.

scholarly journals Prognostic and therapeutic implications of measurable residual disease in acute myeloid leukemia

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Marisa J. L. Aitken ◽  
Farhad Ravandi ◽  
Keyur P. Patel ◽  
Nicholas J. Short
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Study Endpoint ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Therapeutic Implications ◽  
Increased Risk ◽  
Measurable Residual Disease ◽  
Acute Myeloid

AbstractQuantification of measurable residual disease (MRD) provides critical prognostic information in acute myeloid leukemia (AML). A variety of platforms exist for MRD detection, varying in their sensitivity and applicability to individual patients. MRD detected by quantitative polymerase chain reaction, multiparameter flow cytometry, or next-generation sequencing has prognostic implications in various subsets of AML and at various times throughout treatment. While it is overwhelmingly evident that minute levels of remnant disease confer increased risk of relapse and shortened survival, the therapeutic implications of MRD remain less clear. The use of MRD as a guide to selecting the most optimal post-remission therapy, including hematopoietic stem cell transplant or maintenance therapy with hypomethylating agents, small molecule inhibitors, or immunotherapy is an area of active investigation. In addition, whether there are sufficient data to use MRD negativity as a surrogate endpoint in clinical trial development is controversial. In this review, we will critically examine the methods used to detect MRD, its role as a prognostic biomarker, MRD-directed therapeutics, and its potential role as a study endpoint.

Increased γH2AX Foci in Old Hematopoietic Stem Cells Are Independent of the DNA Damage Response and Linked to Inefficient DNA Replication/Transcription

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1207-1207
Author(s):  
Johanna Flach ◽  
Sietske Bakker ◽  
Pauline Conroy ◽  
Damien Reynaud ◽  
Michelle M. Le Beau ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Dna Replication ◽  
Dna Damage Response ◽  
Dna Double Strand Breaks ◽  
Hematopoietic Stem ◽  
Strand Breaks ◽  
Γh2ax Foci ◽  
Damage Response

Abstract Abstract 1207 Hematopoietic stem cells (HSCs) are responsible for the life-long production of all blood cells. Changes in the biological function of old HSCs have been directly linked to the occurrence of age-related blood defects including immunosenescence, anemia and the development of a broad spectrum of hematological disorders (i.e., myeloproliferative neoplasms, leukemia, bone marrow failure). Gene expression studies and analysis of genetically modified mice have also suggested that error-prone DNA repair as well as a decrease in genomic stability are one of the driving forces for the reduced functional capacity of old HSCs. Here, we used HSCs (Lin-/c-Kit+/Sca-1+/Flk2-/CD48-/CD150+) isolated from the bone marrow of old (20–24 months old) and young (6–12 weeks old) C57Bl/6 mice to directly investigate the DNA damage response of old HSCs. Using immunofluorescence, we first confirmed that freshly isolated quiescent old HSCs have an increased number of γH2AX foci, which is a well-established indicator for DNA double-strand breaks. In addition, we found that these intrinsically occurring γH2AX foci specifically co-localized with nucleolar markers (i.e., UBF, fibrillarin and nucleolin) and were a cell-intrinsic feature of old HSCs as demonstrated by transplantation experiments of old HSCs into young recipient mice. However, we could not demonstrate that nucleolar γH2AX foci in old HSCs represent sites of DNA damage. Neither did known DNA repair-associated markers like 53BP1 co-localize with nucleolar γH2AX foci, nor were other DNA damage markers such as phospho-ATM or PARP1 increased in old HSCs. In addition, none of the other methods we used to measure DNA fragmentation such as TUNEL or COMET assays revealed elevated levels of DNA damage in old HSCs, and spectral karyotyping (SKY) analysis of in vitro cultured old HSCs did not provide evidence for DNA damage-associated chromosomal alterations. We then used 2Gy ionizing radiation (IR) to directly induce DNA double-strand breaks and measured the DNA repair capacity of old HSCs. Strikingly, we observed a similar DNA damage response and DNA repair kinetics in young and old HSCs. These results provide evidence that old HSCs can respond adequately to DNA damage and that accumulation of γH2AX at the nucleolus is not the consequence of an activated DNA damage response. The nucleolus consists of a highly regulated repetitive sequence of rDNA units and is the site of ribosomal DNA transcription. Both young and old quiescent HSCs have well-formed nucleoli as shown by electron microscopy analyses. Strikingly, we found a complete disappearance of nucleolar γH2AX foci when old HSCs are forced into cell cycle upon in vitro culture. Furthermore, we observed a significant delay in the onset of the first cell division and timing of nucleolar reformation following mitosis in old HSCs. In addition, cycling old HSCs displayed higher levels of DNA replication/transcription-associated γH2AX foci compared to cycling young HSCs. We are currently investigating how defects in the DNA replication machinery could contribute to the nucleolar γH2AX foci and cell cycle features of old HSCs, and whether old HSCs maintain similar levels of rRNA transcription as compared to young HSCs. Taken together, our results demonstrate that the increased numbers of γH2AX foci observed in old HSCs is not caused by an accumulation of DNA damage. Instead, nucleolar γH2AX foci appear to be a hallmark feature of quiescent old HSCs that could reflect epigenetic changes in rDNA chromatin structure linked to inefficient DNA replication/transcription. Disclosures: No relevant conflicts of interest to declare.

Co-Transplantation of HLA-Haploidentical, Bone Marrow Derived Mesenchymal Stem Cells Prevents Graft Failure and Improves Hematological Recovery in T-Cell Depleted Haploidentical Stem Cell Transplantation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3073-3073 ◽  
Author(s):  
Lynne M. Ball ◽  
Maria-Ester Bernardo ◽  
Helene Roelofs ◽  
Arjan Lankester ◽  
Angela Cometa ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Failure ◽  
Patient Characteristics ◽  
Underlying Disease ◽  
P Value ◽  
Hematopoietic Stem ◽  
Increased Risk ◽  
Immune Deficiencies

Abstract Haploidentical CD34+ purified peripheral blood stem cell transplantation (PBSCT) is associated with an increased risk of graft failure/rejection. Animal models suggest that MSCs may promote engraftment after hematopoietic stem cell transplanation (HSCT) but there role in overcoming graft failure in human HSCT is still unclear. We recently reported our initial findings in 13 children receiving MSCs in conjunction with haplo-PBSCT. Here we report our extended series of 20 patients, now including those with MDS known to have an increased risk of rejection. MSCs were isolated from marrow of PBSCT donors and expanded under GMP conditions using same batch FCS containing medium and a standardized protocol, approximately 4–5 weeks before transplantation. MSCs (fresh or cryopreserved) were administered i.v. 4 hours before the allograft. Conditioning depended on underlying disease. No pharmacological GvHD prophylaxis was given after PBSCT. Characteristics of the patients and results are summarized in table 1. In comparison to historical controls (20% graft failure), all patients given MSCs showed successful and stable engraftment (p=0.03). Hematological recovery was accelerated (see table 2). Viral reactivations did not differ between patients and controls. MSC use was feasible and safe without infusion toxicities. In contrast to our initial findings, our extended analysis shows a statistically significant reduction in graft failure rates for patients cotransplanted with MSCs. Moreover, MSC cotransplantation may also prevent graft rejection in patients with MDS. In view of these findings, cotransplantation of MSCs could become standard practice for optimizing the outcome of children given this type of allograft. Table 1: Patient characteristics and summary of results PATIENT (n=20) CONTROL (n=52) P VALUE Male/female 14/6 (70/30%) 31/21 (60/40%) 0.6 Age (range) 8 years (2–16) 8 years (1–17) NS All hematological malignancies 16 (80%) 40 (70%) 1.0 MDS 2 (10%) 5 (10%) 1.0 Immune deficiencies 2 (10%) 2 (4%) NS Other 2 (10%) 10 (9%) NS Donor male/female 10/10 29/23 NS Conditioning TBI/Chemo based 12/8 30/22 1.0 N of CD34+cells infused (median, range) 21.3 (11.2–38.6) 23 (12.1–47.5) NS N. of CD3+ cells infused (mean, SD) 0.3 (0.30) 0.5 (0.7) NS aGvHD 0.2 I-II 2 12 III-IV 0 2 Relapse 4/16 (25%) 8/40 (20%) NS Infectious deaths 2 (10%) 7 (13%) NS GRAFT FAILURE 0 11 0.03 Tabel 2. Patient hematopoietic recovery compared to controls PATIENTS CONTROLS P value (student t-test Median (days, range) SD (days) Median (days, range) SD (days) P value equal or less than 0.05 is considered significant Leucocyte 〉1.0 × 109/L 11.5 (9–16) 2.0 14 (9–26) 4.2 0.01 Neutrophils 〉0.5 × 109/L 12 (10–17) 1.9 13 (9–27) 4.6 0.06 Platelets 〉20 × 109/L 11 (9–24) 3.8 13 (7–100) 22.3 0.11 Reticulocytes 〉20 × 109/L 12 (10–31) 5.0 23 (9–41) 10.2 0.01

Clinical Significance of Polymorphisms During Hepatopoietic Stem Cell Transplantation.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3497-3497
Author(s):  
Jae-Sook Ahn ◽  
Hee Nam Kim ◽  
Nan Young Kim ◽  
Yu– Li ◽  
Il-Kwon Lee ◽  
...  
Keyword(s):  
Dna Repair ◽  
Stem Cell ◽  
Drug Metabolism ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Clinical Significance ◽  
Gene Polymorphisms ◽  
Hematopoietic Stem ◽  
Increased Risk ◽  
Metabolism Gene

Abstract Abstract 3497 Conidtioning plays an important part in hematopoietic stem cell transplantation (HSCT) and is a major cause of early mortality. Most of conditioning regimens include the ionizing radiation and alkylating agent. The tissue damage made by chemotherapy or radiation is the major cause of acute toxicity and the development of graft versus host disease (GvHD). DNA repair and drug metabolism gene polymorphisms influence the transplantation associated mortality and GvHD by causing incomplete DNA repair and interference with metabolism of drugs. To explore whether these polymorphisms influence clinical implication and the adverse outcomes related to chemo-radiotherapy, we analyzed total 12 polymorphisms in DNA repair (ERCC1, ERCC2, XRCC1, XRCC3, XRCC4, XPC, MGMT and OGG1) and drug metabolizing pathway (GST T1, GST P1, CYP1A1 rs1048943 and CYP1A1 rs4646903). The total 175 patients were assessed from a HLA identical sibling (n=122, 69.7%) and unrelated donors (n=53, 30.3%). Patients have either acute leukemia (n=123, 70.3%), MDS (n=18, 10.3%), CML (n=15, 8.6%) or others (n=19, 10.8%). We evaluated the association between SNPs with adverse effects such as venoocclusive disease (VOD), mucositis, treatment related mortality and acute/chronic GvHD. Multivariate analysis was performed adjusting for clinical factors; recipient age, donor type, diagnosis, disease status, gender mismatch, HLA mismatch, stem cell source, conditioning regimen and GvHD prophylaxis. Three SNPs were associated with clinical significance. XRCC4 (rs1056503) was associated with increased risk of acute gut GvHD (RR:6.84, 95% CI:1.69-28.2, p=0.007), CYP1A1 (rs1048943) with mucositis (RR:3.12, 95% CI:1.22-7.96, p=0.017) and XPC (rs2228001) with VOD (RR:38.23, 95% CI:2.08-702.18, p=0.014). Our findings show that the acute adverse events after allogeneic HSCT were correlated DNA repair and drug metabolism gene polymorphisms and these findings suggest that XRCC4, CYP1A1 and XPC might provide useful information for the risk stratification of HSCT Disclosures: No relevant conflicts of interest to declare.

Platelet monitoring for PCI

2009 ◽  
Vol 29 (04) ◽  
pp. 376-380 ◽  
Author(s):  
D. Capodanno ◽  
D. J. Angiolillo
Keyword(s):  
Interindividual Variability ◽  
State Of The Art ◽  
Coronary Intervention ◽  
Functional Tests ◽  
Treatment Regimens ◽  
Advantages And Disadvantages ◽  
Coronary Syndrome ◽  
Combined Use ◽  
Increased Risk ◽  
Percutaneous Coronary

SummaryDespite the clinical benefit associated with the combined use of aspirin and clopidogrel in patients with acute coronary syndrome or those undergoing percutaneous coronary intervention, a considerable interindividual variability in response to these drugs have been consistently reported. There is a growing interest on applying platelet functional tests with the goal of identifying patients at increased risk of recurrent ischaemic events and potentially tailoring antiplatelet treatment regimens.This manuscript will review the state of the art on the most commonly available platelet functional tests, describing their advantages and disadvantages and exploring their applicability in clinical practice.

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