The growth factor content as an indicator of platelet counts in platelet-rich plasma.

BACKGROUND: Platelet contains growth factors that enhance tissue repair mechanisms, including epidermal growth factor (EGF), platelet-derived growth factor (PDGF-AA and -AB), and transforming growth factor (TGF)-ß. Autologous platelet-rich plasma (PRP) has been shown to significantly improve the treatment of tendon injuries compared with hyaluronic acid and placebo. The topic of agreement between platelet concentrations and growth factors has been covered in some previous studies, but growth factor levels did not correlate well with platelet concentrations. METHOD: In this study, autologous PRP was prepared by concentrating platelets through a J6-MI centrifuge. The automatic hematology analyzer Sysmex XN-20 was used to analyze the platelet concentration in PRP, and the PRP growth factors were determined by ELISA, including PDGF, transforming growth factor- ß1 (TGF-ß1), and EGF. Statistical analysis was conducted on data from 107 patients who received autologous PRP using Pearson correlation analysis. RESULTS: Pearson correlation analysis revealed PDGF, TGF, and EGF had a strong positive correlation with the platelet concentration of the final PRP product (r = 0.697, p < 0.0001; r = 0.488, p < 0.0001; r = 0.572, p < 0.0001, respectively) CONCLUSIONS: There was a strong positive correlation between the concentration of platelets in the final PRP product and the levels of PDGF-AB, TGF-ß, and EGF. These results suggested straightforward and cost-effective growth factor tests can provide valuable information about platelet content in PRP.

[Platelet-specific Rictor knockout inhibits platelet production and activation and reduces thrombosis in mice].

OBJECTIVE: To investigate the effects of platelet-specific Rictor knockout on platelet activation and thrombus formation in mice. METHODS: PF4-Cre and Rictorfl/fl transgenic mice were crossed to obtain platelet-specific Rictor knockout (Rictor-KO) mice and wild-type mice (n=65), whose expression levels of Rictor, protein kinase B (AKT) and p-AKT were detected using Western blotting. Platelet counts of the mice were determined using routine blood tests, and hemostatic function was assessed by tail vein hemorrhage test. Venous thrombosis models were established in the mice to evaluate the effect of Rictor knockout on thrombosis. Platelet aggregation induced by ADP and thrombin was observed in Rictor-KO and wild-type mice, and flow cytometry was used to analyze the expression levels of integrin αIIbß3 and CD62P in resting and activated platelets. Plasma PF4 levels were determined with ELISA. Megakaryocytes from Rictor-KO and wild-type mice were incubated by vWF immunohistochemical antibody and APC-CD41 antibody to detect the number and ploidy of megakaryocytes, respectively. Platelet elongation on collagen surface was observed with scanning electron microscopy. RESULTS: Compared with the wild-type mice, Rictor-KO mice showed significantly decreased AKT phosphorylation, decreased platelet production, reduced thrombosis, and decreased platelet activation in response to ADP and thrombin stimulation. The Rictor-KO mice also showed lowered expression level of P-selectin protein and activation of integrin αIIbß3 with suppression of platelet extension, reduced plasma PF4 level and decreased number of megakaryocytes in the bone marrow. The ploidy of megakaryocytes and the mean area of proplatelets were both significantly decreased in Rictor-KO mice. CONCLUSION: Platelet-specific Rictor knockout inhibits platelet generation and activation to result in decreased thrombus formation in mice, suggesting the potential of mTORC2 activity inhibition as an efficient antithrombotic strategy.

Prevalence of Thrombocytopenia in Pregnant Women with COVID-19: A Systematic Review and Meta-Analysis.

Background/Objectives: Although articles and reviews have been published on the effect of SARS-CoV-2 infection on pregnancy outcomes, they show mixed results with different hypotheses, and no work has focused specifically on the prevalence of thrombocytopenia. The objective of this systematic review and meta-analysis was to synthesize previous evidence and estimate the prevalence of thrombocytopenia in pregnant women with COVID-19. Methods: This systematic review was conducted according to the PRISMA-2020 and MOOSE guidelines. The Medline and Web of Science databases were searched in February 2024, and a meta-analysis of the overall prevalence of thrombocytopenia in pregnant women with COVID-19 was performed. The risk of bias was assessed using the Joanna Briggs Institute checklists. A leave-1-out sensitivity analysis was performed to test for disproportionate effect. Publication bias was assessed by visual inspection of funnel plots and Egger's test. Results: A total of 23 studies met the inclusion criteria, of which 8 were included in the meta-analysis. There was significant (Q = 101.04) and substantial heterogeneity among the studies (I2 = 93.07%). There were no quality-based exclusions from the review of eligible studies. The combined effect of the studies showed a prevalence of thrombocytopenia of 22.9% (95%CI 4.8-41.0%). Subgroup analysis revealed no statistically significant difference in the pooled prevalence of thrombocytopenia ([16.5%; 30.3%]; p = 0.375. Egger's test for bias was not significant, indicating that smaller studies did not report larger estimates of prevalence (t = 1.01, p = 0.353). Moreover, no potential publication bias was found. Our results are consistent with those obtained in pregnant women without COVID-19 infection and extend those of previous reviews of the effect of COVID-19 infection on pregnancy outcomes. Conclusions: Infection during pregnancy does not seem to be an additional risk factor for platelet count, although monitoring platelet count in pregnant women with COVID-19 may be of great importance to determine possible therapeutic strategies, especially in emergency cases.

The platelet-mitochondria nexus in autoimmune and musculoskeletal diseases.

Platelets are crucial for thrombosis and hemostasis. Importantly, they contain mitochondria that are responsible for energy generation and therefore vital for platelet survival and activation. Activated platelets can release mitochondria that may be free or encapsulated in platelet extracellular vesicles (EVs). Extruded mitochondria are a well-known source of mitochondrial DNA, and mitochondrial antigens that can be targeted by autoantibodies forming immune complexes (IC). Interaction of IC with the platelet cell surface FcγRIIA receptor results in platelet activation and release of platelet granule components. In this review, we summarize how platelets and mitochondria may contribute to the pathogenesis of different autoimmune and musculoskeletal diseases. Targeting key drivers of mitochondrial extrusion may ultimately lead to urgently needed targeted pharmacological interventions for treating inflammation and thrombotic diathesis, and halting organ damage in some of these rheumatological conditions.

Blood bank quality control: pH assessment methods in platelet concentrates.

Platelet concentrates undergo progressive changes during storage, such as a decrease in pH. Additionally, pH and lactate production showed the strongest correlation with platelet survival in posttransfusion viability studies. pH measurement is a straightforward method for evaluating the quality control of blood components in blood bank practice. Our aim was to compare three pH assessment methods for canine platelet concentrates. The pH values of the canine platelet concentrates were assessed on the first day of storage using a calibrated pH meter, a portable gas analyzer and pH-indicator strips. The results from the pH meter and portable gas analyzer measurements were similar. The pH indicator strips presented higher average values compared to the other more reliable methods evaluated, which could result in the use of inadequate blood components. In conclusion, it is recommended to implement pH measurements using a pH meter for quality control in veterinary blood banks.

Measurement of changes in serum-based inflammatory indicators to monitor response to nivolumab monotherapy in advanced gastric cancer: a multicenter retrospective study.

BACKGROUND: Nonresectable gastric cancer develops rapidly; thus, monitoring disease progression especially in patients receiving nivolumab as late-line therapy is important. Biomarkers may facilitate the evaluation of nivolumab treatment response. Herein, we assessed the utility of serum-based inflammatory indicators for evaluating tumor response to nivolumab. METHODS: This multicenter retrospective cohort study included 111 patients treated with nivolumab monotherapy for nonresectable advanced or recurrent gastric cancer from October 2017 to October 2021. We measured changes in the C-reactive protein (CRP)-to-albumin ratio (CAR), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR) in serum from baseline to after the fourth administration of nivolumab. Furthermore, we calculated the area under the receiver operating characteristic curves (AUC ROCs) for CAR, PLR, and NLR to identify the optimal cutoff values for treatment response. We also investigated the relationship between clinicopathologic factors and disease control (complete response, partial response, and stable disease) using the chi-squared test. RESULTS: The overall response rate (complete and partial response) was 11.7%, and the disease control rate was 44.1%. The median overall survival (OS) was 14.0 (95% CI 10.7‒19.2) months, and the median progression-free survival (PFS) was 4.1 (95% CI 3.0‒5.9) months. The AUC ROCs for CAR, PLR, and NLR before nivolumab monotherapy for patients with progressive disease (PD) were 0.574 (95% CI, 0.461‒0.687), 0.528 (95% CI, 0.418‒0.637), and 0.511 (95% CI, 0.401‒0.620), respectively. The values for changes in CAR, PLR, and NLR were 0.766 (95% CI, 0.666‒0.865), 0.707 (95% CI, 0.607‒0.807), and 0.660 (95% CI 0.556‒0.765), respectively. The cutoff values for the treatment response were 3.0, 1.3, and 1.4 for CAR, PLR, and NLR, respectively. The PFS and OS were significantly longer when the treatment response values for changes in CAR, PLR, and NLR were below these cutoff values (CAR: OS, p < 0.0001 and PFS, p < 0.0001; PLR: OS, p = 0.0289 and PFS, p = 0.0302; and NLR: OS, p = 0.0077 and PFS, p = 0.0044). CONCLUSIONS: Measurement of the changes in CAR, PLR, and NLR could provide a simple, prompt, noninvasive method to evaluate response to nivolumab monotherapy. TRIAL REGISTRATION: This study is registered with number K2023006.

Somatic RAP1B gain-of-function variant underlies isolated thrombocytopenia and immunodeficiency.

The ubiquitously expressed small GTPase Ras-related protein 1B (RAP1B) acts as a molecular switch that regulates cell signaling, cytoskeletal remodeling, and cell trafficking and activates integrins in platelets and lymphocytes. The residue G12 in the P-loop is required for the RAP1B-GTPase conformational switch. Heterozygous germline RAP1B variants have been described in patients with syndromic thrombocytopenia. However, the causality and pathophysiological impact remained unexplored. We report a boy with neonatal thrombocytopenia, combined immunodeficiency, neutropenia, and monocytopenia caused by a heterozygous de novo single nucleotide substitution, c.35G>A (p.G12E) in RAP1B. We demonstrate that G12E and the previously described G12V and G60R were gain-of-function variants that increased RAP1B activation, talin recruitment, and integrin activation, thereby modifying late responses such as platelet activation, T cell proliferation, and migration. We show that in our patient, G12E was a somatic variant whose allele frequency decreased over time in the peripheral immune compartment, but remained stable in bone marrow cells, suggesting a differential effect in distinct cell populations. Allogeneic hematopoietic stem cell transplantation fully restored the patient's hemato-immunological phenotype. Our findings define monoallelic RAP1B gain-of-function variants as a cause for constitutive immunodeficiency and thrombocytopenia. The phenotypic spectrum ranged from isolated hematological manifestations in our patient with somatic mosaicism to complex syndromic features in patients with reported germline RAP1B variants.

Antibodies and complement are key drivers of thrombosis.

Venous thromboembolism (VTE) is a common, deadly disease with an increasing incidence despite preventive efforts. Clinical observations have associated elevated antibody concentrations or antibody-based therapies with thrombotic events. However, how antibodies contribute to thrombosis is unknown. Here, we show that reduced blood flow enabled immunoglobulin M (IgM) to bind to FcµR and the polymeric immunoglobulin receptor (pIgR), initiating endothelial activation and platelet recruitment. Subsequently, the procoagulant surface of activated platelets accommodated antigen- and FcγR-independent IgG deposition. This leads to classical complement activation, setting in motion a prothrombotic vicious circle. Key elements of this mechanism were present in humans in the setting of venous stasis as well as in the dysregulated immunothrombosis of COVID-19. This antibody-driven thrombosis can be prevented by pharmacologically targeting complement. Hence, our results uncover antibodies as previously unrecognized central regulators of thrombosis. These findings carry relevance for therapeutic application of antibodies and open innovative avenues to target thrombosis without compromising hemostasis.

Phenotypic and genotypic evaluation of bleeding diagnostic dilemmas: Two case studies.

Inherited platelet disorders (IPDs) are a heterogeneous group of conditions that present significant challenges in diagnosis and management. Here, we report two cases of patients presenting with clinically significant bleeding but with unclear etiologies by conventional clinical laboratory testing. Further evaluation, utilizing a combination of high-dimensional multiplexed mass cytometry and genetic sequencing, revealed the underlying causes of bleeding in both cases, leading to definitive diagnoses. These cases underscore the potential utility of combined multimodal approaches in evaluating patients with bleeding disorders. Moreover, these high-parameter methods can offer substantial mechanistic insights and can enhance our understanding of the molecular pathogenesis of IPDs. Future studies involving larger patient cohorts are needed to further validate this strategy, directly comparing its diagnostic yield and accuracy with current clinical laboratory testing approaches, which can ultimately improve patient care.

Development of a large diameter in vitro flow loop thrombogenicity test system.

BACKGROUND: To accommodate a wider range of medical device sizes, a larger in vitro flow loop thrombogenicity test system using 9.5 -mm inner diameter (ID) tubing was developed and evaluated based on our previously established 6.4 -mm ID tubing system. METHODS: Four cardiopulmonary bypass roller pumps were used concurrently to drive four flow loops during testing. To ensure that each pump produced a consistent thrombogenic response for the same material under the same test conditions, a novel dynamic roller occlusion setting method was applied. Five materials with varying thrombogenic potentials were tested: polytetrafluoroethylene (PTFE), silicone, 3D-printed nylon, latex, and nitrile rubber (BUNA). Day-old bovine blood was heparinized to a donor-specific concentration and recirculated through the flow loops containing test materials at 20 rpm for 1 h at room temperature. Material thrombogenicity was characterized by measuring the thrombus surface coverage, thrombus weight, and platelet (PLT) count reduction. RESULTS: The larger tubing system can differentiate thrombogenic materials (latex, BUNA) from the thromboresistant PTFE material. Additionally, silicone and the 3D-printed nylon exhibited an intermediate thrombogenic response with significantly less thrombus surface coverage and PLT count reduction than latex and BUNA but more thrombus surface coverage than PTFE (p < 0.05). CONCLUSION: The 9.5 -mm ID test system can effectively differentiate materials of varying thrombogenic potentials when appropriate pump occlusion settings and donor-specific anticoagulation are used. This system is being assessed in an interlaboratory study to develop standardized best practices for performing in vitro dynamic thrombogenicity testing of medical devices and materials.

Key role of activated platelets in the enhanced adhesion of circulating leucocyte-platelet aggregates to the dysfunctional endothelium in early-stage COPD.

Background: Chronic obstructive pulmonary disease (COPD), usually caused by long-term tobacco smoking, is independently associated with systemic inflammation. However, little is known about the systemic inflammatory status of patients with early-stage COPD (classified as GOLD 1) and long-term smokers with normal lung function (LF). Here, we characterised the early changes in the associated inflammatory state in patients with GOLD 1 and in long-term smokers with normal LF. Methods: Fresh blood samples from 27 patients with GOLD 1, 27 long-term smokers and 14 non-smokers were analysed. Results: Ex vivo blood analysis revealed greater leucocyte-platelet adhesion to TNFα-stimulated pulmonary endothelium in patients with GOLD 1 than in smokers and non-smokers. In addition, platelet reactivity (platelet count and activation, and fibrinogen levels) and the frequency of leucocyte-platelet aggregates were higher in the GOLD 1 group than in the other groups. Some of these findings correlated with the severity of lung dysfunction, while platelet hyperactivity correlated positively with leucocyte-platelet adhesion. The GOLD 1 group also had a higher Th17/Treg ratio and higher circulating levels of IL-17C and C-reactive protein than the other groups. However, long-term smokers also had higher leucocyte counts and activation, and higher plasma levels of TNFα and IL-6 than non-smokers. Conclusion: Our data suggest that the altered inflammatory parameters in long-term smokers may represent early biomarkers of COPD. Accordingly, peripheral immune monitoring based on the above parameters may be useful to prevent disease progression in long-term smokers with normal LF and early COPD.

EASIX (endothelial activation and stress index) predicts mortality in patients with coronary artery disease.

BACKGROUND: Coronary interventions reduce morbidity and mortality in patients with acute coronary syndrome. However, the risk of mortality for patients with coronary artery disease (CAD) additionally depends on their systemic endothelial health status. The 'Endothelial Activation and Stress Index' (EASIX) predicts endothelial complications and survival in diverse clinical settings. OBJECTIVE: We hypothesized that EASIX may predict mortality in patients with CAD. METHODS: In 1283 patients undergoing coronary catheterization (CC) and having a diagnosis of CAD, EASIX was measured within 52 days (range - 1 year to - 14 days) before CC and correlated with overall survival. In an independent validation cohort of 1934 patients, EASIXval was measured within 174 days (+ 28 days to + 11 years) after CC. RESULTS: EASIX predicted the risk of mortality after CC (per log2: hazard ratio (HR) 1.29, 95% confidence interval: [1.18-1.41], p < 0.001) in multivariable Cox regression analyses adjusting for age, sex, a high-grade coronary stenosis ≥ 90%, left ventricular ejection fraction, arterial hypertension and diabetes. In the independent cohort, EASIX correlated with EASIXval with rho = 0.7. The long-term predictive value of EASIXval was confirmed (per log2: HR 1.53, [1.42-1.64], p < 0.001) and could be validated by integrated Brier score and concordance index. Pre-established cut-offs (0.88-2.32) associated with increased mortality (cut-off 0.88: HR training: 1.63; HR validation: 1.67, p < 0.0001 and cut-off 2.32: HR training: 3.57; HR validation: 4.65, p < 0.0001). CONCLUSIONS: We validated EASIX as a potential biomarker to predict death of CAD patients, irrespective of the timing either before or after catheterization.

An evaluation of diethylhexyl phthalate free top & bottom in-line blood collection set with a new soft housing filter.

BACKGROUND AND OBJECTIVES: Di (2-ethylhexyl) phthalate (DEHP) plasticizer must be removed from polyvinylchloride (PVC) medical devices due to toxicity. DEHP/PVC blood bags were shown to provide stable quality under blood component production and to create good storage conditions for red blood cells concentrate (RBC). It is important that substitution of the DEHP maintains the RBC quality during storage, which should be achieved with Di (isononyl) cyclohexane-1,2-dicarboxylate (DINCH), although substitution of the plasticizer has been challenging. MATERIALS AND METHODS: A DEHP-free Top & Bottom in-line RBC set was validated in a tertiary hospital blood bank facility. Volunteer blood donors were randomly allocated for blood collection into DINCH/PVC or DEHP/PVC set. The groups were additionally divided according to additive solution/filter combination: PAGGS-M + DINCH/PVC filter (only with DINCH/PVC set), and SAG-M + DINCH/PVC filter and SAG-M + DEHP/PVC filter (only with DEHP/PVC set). Processing and storage effects were assessed in all components. RESULTS: RBC concentrates, platelet concentrates and plasma that was processed and stored in DEHP-free set fulfilled European requirements for quality. The cells stored in PAGGS-M after filtration through DEHP-free PVC filter showed the same low haemolysis compared with conventional set at 49 days of storage. Platelets stored in DINCH/PVC bag provided a sufficient quality of platelets after 7 days of storage. Plasma maintained the coagulation factors during 12 months of storage. CONCLUSION: A new DINCH/PVC set allows production of blood components of satisfactory quality in DEHP-free environment.

Circulating microRNAs targeting coagulation and fibrinolysis in patients with severe COVID-19.

BACKGROUND: Coronavirus-19 disease (COVID-19) frequently causes coagulation disturbances. Data remains limited on the effects of microRNAs (miRNAs) on coagulation during COVID-19 infection. We aimed to analyze the comprehensive miRNA profile as well as coagulation markers and blood count in hospitalized COVID-19 patients. METHODS: Citrated plasma samples from 40 patients (24 men and 16 women) hospitalized for COVID-19 were analyzed. Basic coagulation tests, von Willebrand factor (VWF), ADAMTS13, blood count, C-reactive protein, and 27 miRNAs known to associate with thrombosis or platelet activation were analyzed. MiRNAs were analyzed using quantitative reverse transcription polymerase chain reaction (RT qPCR), with 10 healthy controls serving as a comparator. RESULTS: Among the patients, 15/36 (41%) had platelet count of over 360 × 109/L and 10/36 (28%) had low hemoglobin of < 100 g/L, while 26/37 (72%) had high VWF of over 200 IU/dL. Patients had higher levels of the miRNAs miR-27b-3p, miR-320a-3p, miR-320b-3p, and miR-424-5p, whereas levels of miR-103a-3p and miR-145-5p were lower than those in healthy controls. In total, 11 miRNAs were associated with platelet count. Let-7b-3p was associated with low hemoglobin levels of < 100 g/L. miR-24-3p, miR-27b-3p, miR-126-3p, miR-145-5p and miR-338-5p associated with high VWF. CONCLUSION: COVID-19 patients differentially express miRNAs with target genes involved in fibrinolysis inhibition, coagulation activity, and increased inflammatory response. These findings support the notion that COVID-19 widely affects hemostasis, including platelets, coagulation and fibrinolysis.

The impact of donor-specific antibodies' presence on the outcome post-allogeneic hematopoietic stem cell transplantation: a survey from a single center.

Introduction: Donor-specific antibodies (DSAs) correspond to anti-HLA antibodies of the recipient that are specifically directed to a mismatched antigen of the donor. In the setting of solid organ transplantation DSAs are associated with rejection. Their role is still debated in allogeneic cell transplantation. International guidelines recommend testing patients for DSA before transplant, and if possible, choosing a donor with negative screening. Methods: We collected clinical data of 236 recipients of alloSCT, performed at our institution from March 2019 to October 2023, to evaluate their impact on engraftment. Serum from all patients was tested for DSA. Results: 186 patients (79%) achieved sustained myeloid engraftment within day 30 post alloSCT. Thirty-two out 236 (13%) patients engrafted after day 30 post alloSCT. The median times to neutrophil engraftment and platelet engraftment were respectively 21 days (range 11-121 days) and 19 days (range 10-203 days). Fourteen out 236 patients (6%) experienced PrGF. .Twenty-nine patients (12 %) were DSA-positive. Among 29 patients with DSA positivity, 17 had a haploidentical donor and 12 had a UD donor. DSA positivity directly correlates respectively with neutrophil and platelets engraftment failure at 30 days after alloSCT (p=0.01 and p= 0.0004). Univariate Cox analysis showed that factors, including DSAs positivity, disease type, disease status, donor type, conditioning regimen, patient's age, and CD34+ were correlated with neutrophil and platelet engraftment failure at 30 days after alloSCT. Younger patients with DSA negativity, with acute leukemia, in complete response at the time of transplant, who received a higher dose of CD34+ cells from a sibling donor after a myeloablative conditioning regimen, have a reduced risk of neutrophil and platelet engraftment failure at day +30 post alloSCT.Multivariate analysis confirmed the impact of the presence of DSA only for platelet engraftment, confirming the role of type and status disease, donor type, recipient age, and CD34+ cells infused on engraftment. DSA presence has no impact on TRM, DFS, and OS. Discussion: PrGF has a multifactorial pathogenesis, where DSA is not the only player, but its impact could vary depending on the transplant platform. Thus patient screening may be helpful to choose the best donor and transplant strategy.

Liquid biopsy: paving a new avenue for cancer research.

The current constraints associated with cancer diagnosis and molecular profiling, which rely on invasive tissue biopsies or clinical imaging, have spurred the emergence of the liquid biopsy field. Liquid biopsy involves the extraction of circulating tumor cells (CTCs), circulating free or circulating tumor DNA (cfDNA or ctDNA), circulating cell-free RNA (cfRNA), extracellular vesicles (EVs), and tumor-educated platelets (TEPs) from bodily fluid samples. Subsequently, these components undergo molecular characterization to identify biomarkers that are critical for early cancer detection, prognosis, therapeutic assessment, and post-treatment monitoring. These innovative biosources exhibit characteristics analogous to those of the primary tumor from which they originate or interact. This review comprehensively explores the diverse technologies and methodologies employed for processing these biosources, along with their principal clinical applications.

[Biology of von Willebrand factor and pathogenesis of von Willebrand disease].

Von Willebrand disease (VWD) is an inherited bleeding disorder caused by quantitative and qualitative abnormalities of von Willebrand factor (VWF), a multimeric glycoprotein that is the largest of its kind in plasma and is also found in platelet alpha granules and Weibel-Palade bodies of endothelial cells. VWF plays two roles in hemostasis: (1) primary hemostasis via adhesion of platelet GPIb to subendothelial connective tissue and (2) stabilization of coagulation factor VIII. The pathological classification proposed by the International Society of Thrombosis and Haemostasis (ISTH) in 1994 divided VWF into three major categories based on the results of VWF:RCo, VWF:Ag, and multimer analysis. Recent genetic analysis and molecular and cellular analysis of abnormal VWF have revealed a molecular basis for the dominant inheritance form of VWD.

Platelet changes and bleeding symptoms in children, adolescents, and adults with 22q11.2 deletion syndrome.

BACKGROUND: The deletion region of 22q11.2 deletion syndrome (22q11.2DS) contains a gene encoding glycoprotein Ibß (GPIbß), which is required to express the GPIb/IX/V complex on the platelet surface. Therefore, patients with 22q11.2DS may have congenital platelet disorders. However, information is limited on platelets and bleeding symptoms. In this study, we investigated clinical information, including bleeding symptoms, platelet counts, and GPIb expression levels in children and adolescents/adults with 22q11.2DS. PROCEDURE: Thirty-two patients with 22q11.2DS were enrolled in a prospective cohort study between 2022 and 2023 at outpatient clinics within our institute. RESULTS: The median platelet counts in adolescents/adults with 22q11.2DS were significantly lower than those in children (p < .0001). A gradual decrease was found along with increasing age (p = .0006). Values of median GPIb expression on platelet surfaces (66% in children and 70% in adolescents/adults) were significantly lower than those in healthy controls (p < .0001 and p = .0002). Bleeding symptoms included surgery-related bleeding (52%), purpura (31%), and epistaxis (22%); most of them were minor. The median International Society on Thrombosis and Hemostasis bleeding assessment tool score was not significantly different between children and adolescents/adults (p = .2311). CONCLUSION: Although there was an age-related decrease in platelet count and a disease-related decrease in GPIb expression, no difference in bleeding symptoms was found between children and adolescents/adults. 22q11.2DS overall had minor bleeding symptoms in daily life, and the disease had little effect on spontaneous bleeding. However, some patients had major bleeding events; further accumulation of data on hemostasis during surgery and trauma is required.

[Effect of blue range light-emitting diode radiation on platelets and blood coagulation factors in patients with chronic ischemia of lower limbs]. / Vliyanie svetodiodnogo izlucheniya sinego diapazona na trombotsity i faktory svertyvaniya krovi u bol'nykh s khronicheskoi ishemiei nizhnikh konechnostei.

Chronic arterial insufficiency of lower limbs (CAILL) is a common cardiovascular disease that affects 200 million subjects worldwide: from 4 to 12% of people aged 55-70 years and 20% - over 70 years. The cause of blood circulation disorder in this disease is usually a complex of pathological changes including abnormality of vessel walls' anatomical structure or integrity, disorder of blood rheological properties and alterations of its thrombotic potential. Thus, the therapy of patients with CAILL aiming at hemostasis and, in particular, platelets' aggregation is one of the most urgent problems of medicine. OBJECTIVE: To study the effectiveness of blue range visible radiation combined with basic therapy to improve hemostasis in patients with CAILL. MATERIAL AND METHODS: The number of male patients with CAILL equal 63 aged 43-57 years was examined. Blood flow parameters on a fixed part of femoral artery outside the occlusion area were registered based on subjective criteria, number of painless steps and ultrasound doppler flowmetry according to the Fontaine-Pokrovsky classification. The second degree of ischemia was diagnosed in 38 patients, the third degree - in 25 patients. All patients received basic pharmacotherapy. Patients were divided into 2 groups by simple randomization method: control group included 18 patients with II degree of ischemia and 12 patients with III degree of ischemia who received basic pharmacotherapy combined with photohemotherapy (PHT). A set of commonly used laboratory methods for examination of blood coagulation system was applied to assess the effectiveness of PHT. The number of apparently healthy people equal 26 was examined to evaluate normal value of hemostasiological parameters. RESULTS: Basic pharmacological treatment had a certain positive effect on studied hemostasis parameters and its thrombotic component. However, they did not differ statistically significantly from similar parameters before treatment on the 14th day after treatment. As a result of comprehensive therapy the changes in hemostasis system had identical and statistically significant in percentage terms changes compared to norm and baseline in patients' subgroups of study group with II and III degrees of ischemia. In addition, most hemostasis parameters in patients with II degree of ischemia were close to those of apparently healthy volunteers. Hemostasis parameters in patients with III degree of ischemia decreased to the levels of patients with II degree of ischemia before treatment. CONCLUSION: The use of basic pharmacological therapy with optical exposure to blood by blue light allows to correct hemostasis and its thrombotic component in patients with CAILL.