Background: Legg–Calvé–Perthes disease (LCPD) is a pediatric disorder that occurs due to the avascular necrosis of the femoral head and affects the range of motion of the hip in various degrees. Its etiology is still unknown, although it has been associated with coagulation abnormalities, however, the lack of reproducibility in the results in various studies has created a controversy as to whether hemostasis disorders are related to LCPD. On the other hand, there is little information on laboratory studies that could facilitate the diagnosis and treatment of LCPD. Methods: Blood and plasma samples were tested from 25 patients with LCPD and 50 healthy controls, matched by sex and age. Cellular markers were evaluated through complete blood count, as well as coagulation times, coagulation factors activity, antithrombotic proteins, and homocysteine concentration. Results: After assessing activity value frequencies in each group, the results showed more significant activity in some of the biological risk markers of thrombophilia, presenting a substantial difference in prothrombin time↘, FV↗, FVIII↗, FIX↗, and Hcy↗. These values imply that there may be hypercoagulable states in patients, which can cause thrombotic events. Conclusions: Diminished prothrombin time and increase in FV activity, FVIII, FIX, and Hcy concentration support the hypothesis that microthrombi formation in small-caliber vessels could be causing avascularity and femoral necrosis, which are traits of LCPD. In addition, based on our results, we believe that the laboratory studies carried out are very useful in the diagnosis and treatment of LCPD.

Background: Legg–Calvé–Perthes disease (LCPD) is a rare avascular osteonecrosis of the proximal femoral epiphysis and typically occurs during the childhood growth phase. LCPD is a complex illness of unknown origin, which is considered the main difficulty in the study of this disease. Various theories on LCPD etiology have been proposed; however, no consensus has been reached about its origin. Our research objective was to evaluate the polymorphisms FVL rs6025, FVIII rs5987061, FIX Malmö rs6048, PAI-1 rs1799889, eNOS rs17899983/rs2070744, IL-23R rs1569922/rs154655686/7539625, and TNF-α rs180062, and their relationship with LCPD. Methods: A blood sample was taken from each study participant. Complete blood count, coagulation times and factors, antithrombotic proteins, and homocysteine (Hcy) were determined using a coagulometric method. DNA was obtained and genotyped using real-time PCR with TaqMan probes. Genotypic and allelic distributions were analyzed using comparative analysis, the Hardy–Weinberg equilibrium, and OR. Results: This study included 46 children: 23 with LCPD (cases) and 23 without (controls). Statistically significant differences were found in Prothrombin Time, Factor V, and Factor IX activity, as well as Hcy concentration; these values suggest the presence of hypercoagulable states in patients, which can cause thrombotic events. On the other hand, significant differences were also found in the neutrophil–lymphocyte ratio and systemic immune-inflammation index, showing major inflammation states in the patient group. Moreover, statistically significant differences were found in the IL-23R rs1569922 polymorphism; it was found that carriers of the T/T and C/T genotypes have an increased risk of developing LCPD. Conclusions: Our results show greater hemostatic activity and inflammation in the group of patients included in this study, supporting various theories previously proposed. Therefore, we believe that LCPD is a multifactorial condition in which hemostatic, inflammatory, and genetic factors play a central and triggering role in the disease.

Legg–Calvé–Perthes disease (LCPD) is a rare disease caused by avascular necrosis of the femoral head. Although its etiology is still not fully understood, evidence suggests that heritable prothrombotic and inflammatory factors, as well as environmental factors, may be implicated in its onset and progress. The objective of this study is to describe the genetic, biochemical, and environmental factors that may be associated with the etiology of LCPD. This study was conducted in three families and included seven related patients with an LCPD diagnosis. We evaluated the following gene alterations using real-time PCR: MTHFR, CBS, COL1A1, COL2A1, PT, FVL, FVIII, FIX, PAI-1, eNOS, IL-23R, TNF-α, RANNK, RANNK-L, OPG and IL-6. Additionally, we assessed fourteen thrombophilia-associated biochemical markers, as well as environmental factors that may be associated with the etiology of LCPD in family cases. The results show different hemostatic alterations in every individual analyzed, presenting out-of-range values in one or more parameters. Concentrations of hemoglobin and fibrinogen and the FIX activity percentage showed statistically significant differences (p < 0.001) when compared with healthy controls. All patients presented at least one mutated allele for the MTFHR (rs1801133), IL-23R (rs1569922) and OPG (rs2073618) polymorphisms, as well as isolated cases with other genetic variants. Our results show environmental elements from every family, and hemostatic and inflammatory disorders, may be involved in the development of LCPD. Furthermore, genetic variants could contribute to the onset of the disease. This study highlights the multifactorial nature of this pathology, involving various environmental, genetic, inflammatory, and prothrombotic factors in three families that included seven patients diagnosed with LCPD.

Background: The diagnosis of bleeding disorders through the Clinical Chemistry Laboratory requires specific tests. In Mexico, there are few reports on reference values (RVs) for coagulation factors (CFs). The prevalence and RVs in adults and older Mexican adults have already been described. However, it remains unknown whether these parameters differ among minors (MI), young adults (YA), and older adults (OA). The aim of this study was to determine CF levels in a group of healthy MI, YA, and OA in Mexico. Methods: CFs were determined on a coagulation analyzer using commercial kits for the CFs: I, II, V, VII, VIII, IX, X, XI, and XII. The effect size was determined using Glass's rank biserial correlation coefficient. Comparisons between groups were performed using Dunn-Bonferroni post hoc tests following a significant Kruskal-Wallis test, and the epsilon-squared coefficient was used to estimate effect magnitude. Results: 347 participants, stratified by age group and sex, were studied. Variability in CF activity was observed. Age was found to be an important factor influencing the activity of all CFs, particularly factors II, V, VIII, IX, X, and XII, with factors V and XII proposed as biomarkers of aging. Conclusions: CF levels observed in OA differ from those in YA and MI, as well as from the RVs proposed in commercial kits. It is important to integrate these results into established diagnostic algorithms, as well as into an evidence-based practical guide that clinical personnel can use to support a comprehensive and accurate diagnosis of patients with hemostatic disorders.

Background: Legg-Calvé-Perthes Disease (LCPD) is a condition caused by avascular necrosis of the femoral head. Although its etiology is still not fully understood, evidence suggests heritable thrombotic and inflammatory disorders and other factors may be implicated in its onset and progress. Our objective is to describe, in the three enrolled families, the genetic, biochemical, and environmental factors that may be associated with the etiology and development of LCPD. Methods: We evaluated the following gene alterations: MTHFR, CBS, PT, FVL, FVIII, FIX, PAI-1, eNOS, IL-23R, and TNF-α, and their relationship with LCPD. Additionally, we assessed thrombophilia-associated markers (FI, FII, FV, FVII, FVIII, FIX, FX, FXI, FXII, FvW, PC, PS, AT, and homocysteine) using coagulometry methods. Results: Seven patients with LCPD and 14 healthy volunteers were enrolled. Concentrations in hemoglobin (p ≤ 0.05), fibrinogen (p ≤ 0.05), homocysteine (p =<0.05), FVIII (p≤0.05), and factor IX activity percentage (p ≤ 0.05) showed statistically significant differences. Our results show that all participants of this study present at least one mutated allele for the MTFHR (rs1801133) and IL-23R (rs1569922) polymorphisms, as well as isolated cases with other genetic variants.Conclusions: Our results show environmental elements from every family and hemostatic and inflammatory disorders may be involved in suffering and developing LCPD. Also, heritable factors could contribute to the onset of the disease. Environmental, genetic, inflammatory, and prothrombotic factors are involved in this pathology.

Legg–Calvé–Perthes disease (LCPD) is a rare pediatric disorder characterized by avascular osteonecrosis of the femoral head. Its pathogenesis is multifactorial, and genetic, epigenetic, vascular, and inflammatory mechanisms may contribute to disease susceptibility and progression. To map and characterize the available evidence on genetic and epigenetic factors and molecular pathways associated with LCPD, with particular emphasis on potential interactions and convergence across biological pathways. A scoping review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR, PRISMA 2020 for Abstracts checklist). PubMed/MEDLINE was searched for studies published between March 2006 and March 2026. Relevant genetic, epigenetic, and molecular findings were extracted and synthesized according to biological pathways. See the PRISMA 2020 for Abstracts checklist. Seventeen genes and 25 single-nucleotide variants (SNVs), as reported in the included literature, were identified and grouped into three major biological axes: hypercoagulability, inflammation, and bone metabolism and remodeling. Associations with LCPD were reported in at least one study for F5 rs6025, MTHFR rs1801133, IL6 rs1800795, IL23R rs1569922, NOS3 rs1799983 and rs2070744, and OPG rs2073618. Epigenetic mechanisms, including DNA methylation and microRNA dysregulation, were also reported. Interpretation was limited by methodological heterogeneity, small study populations, limited functional validation, and a predominance of observational studies. Accumulating evidence suggests that thrombotic, inflammatory, bone remodeling, and epigenetic mechanisms contribute to LCPD susceptibility and pathogenesis. Our findings point to a potential biological convergence among these pathways; however, whether this convergence stems from a shared genetic architecture remains to be fully elucidated. LCPD pathogenesis involves a complex interplay of coagulation, inflammation, bone remodeling, and epigenetic pathways. While these mechanisms suggest biological convergence, their precise shared genetic architecture remains uncertain. Consequently, future studies utilizing independent replication and functional validation are critically needed.