Manejo de la trombastenia de Glanzmann durante el embarazo: reporte de un caso y revisión de la literatura / Management of Glanzmann's thrombasthenia during pregnancy: a case report and literature review

Resumen Objetivo: Reportar el caso de una paciente con trombastenia de Glanzmann que recibe manejo con transfusión de plaquetas con factor VII activado y realizar una revisión de la literatura referente al tratamiento y el pronóstico de esta patología durante la gestación. Método: Se presenta el caso de una paciente de 27 años con trombastenia de Glanzmann y embarazo de 33 semanas, con cesárea al término sin complicaciones. Se realizó una búsqueda en las bases de datos Medline vía PubMed, Lilacs, SciELO y ScienceDirect; se incluyeron reportes de caso, series de casos y revisiones bibliográficas hasta 2021. Resultados: Se encontraron 21 artículos, con 23 casos reportados. Los embarazos se presentaron entre la tercera y la cuarta décadas de la vida, siendo la mayoría pacientes con anticuerpos frente a antígenos plaquetarios (43,4% de los casos). El principal manejo fue con transfusión plaquetaria. Conclusiones: La trombastenia de Glanzmann durante el embarazo es infrecuente y se asocia a eventos hemorrágicos. La presencia de anticuerpos frente a antígenos plaquetarios condiciona el manejo con mayor riesgo de complicaciones perinatales. No tiene un enfoque terapéutico unificado, siendo el de elección la transfusión de plaquetas y como segunda línea el factor VII activado.

Abstract Objective: To report the case of a patient with Glanzmann's thrombasthenia who receives management with platelet transfusion with activated factor VII and a literature review regarding the treatment and prognosis of this pathology during pregnancy. Method: We present the case of a 27 year old patient with Glanzmann's thrombasthenia and a 33-week pregnancy, with a cesarean section at term without complications. Medline databases were searched via PubMed, Lilacs, SciELO and ScienceDirect; case reports, case series and bibliographic reviews were included until 2021. Results: A total of 21 articles were found, with 23 reported cases; the pregnancies occurred between the third and fourth decades of life, the majority being patients with anti-platelet antigen antibodies in 43.4% of the cases. The main management was with platelet transfusion. Conclusions: Glanzmann's thrombasthenia during pregnancy is rare and is associated with hemorrhagic events. The presence of anti-platelet antigen antibodies conditions management with a higher risk of perinatal complications. It does not have a unified therapeutic approach, with platelet transfusion being the management of choice and activated factor VII as second line.

Comparison of the effects of platelet concentrates produced by high and low-speed centrifugation protocols on the healing of critical-size defects in rat calvaria: a microtomographic and histomorphometric study.

The current study evaluated the healing of critical-size defects (CSD) created in rat calvaria treated with platelet concentrates produced by high-speed (Leukocyte- and Platelet-Rich Fibrin - L-PRF) and low-speed (Advanced Platelet-Rich Fibrin - A-PRF) protocols of centrifugation. Twenty-four rats were distributed into three groups: Control, L-PRF, and A-PRF. Five mm diameter CSD were created on the animals' calvaria. The defects of the L-PRF and A-PRF groups were filled with 0.01 ml of L-PRF and A-PRF, respectively. The control group defects were filled with a blood clot only. All animals were euthanized on the 35th postoperative day. Histomorphometric and microtomographic analyses were then performed. The L-PRF and A-PRF groups had significantly higher bone volume and neoformed bone area than those of the control group and lowered bone porosity values (p < .05). No significant differences were observed between A-PRF and L-PRF groups for the analyzed parameters. Therefore, it can be concluded that i) L-PRF and A-PRF potentiated the healing of CSD in rat calvaria; ii) high and low-speed centrifugation protocols did not produce PRF matrices with different biological impacts on the amount of bone neoformation.

High-power laser for periodontal surgery in a patient with glanzmann thrombasthenia / Laser de alta potência para cirurgia periodontal em paciente com trombastenia de glanzmann

Background: Glanzmann thrombasthenia (GT) is a rare autosomal recessive disorder characterized by platelet function impairment. Considering that the oral cavity is highly vascularized and performing some local hemostatic maneuvers may be difficult, GT patients are at high risk for hemorrhage related to invasive oral procedures. This study aimed to present an alternative method for periodontal surgery in a young GT patient. Case Report: A 15-year-old female GT patient with a recent history of excessive bleeding following dental surgeries was referred to a public dental center, presenting gingival hyperplasia. The procedure was performed using a high-power laser (HPL), and except for local anesthesia with epinephrine, no further hemostatic agent was necessary. Conclusion: According to the case, the HPL seems to be an efficient tool for preventing perioperative bleeding in GT patients submitted to minor oral surgeries(AU)

Introdução: A trombastenia de Glanzmann (TG) é uma doença autossômica recessiva rara caracterizada por comprometimento da função plaquetária. Tendo em vista que a cavidade oral é altamente vascularizada e a realização de algumas manobras hemostáticas locais pode ser difícil, pacientes com TG apresentam alto risco de hemorragia relacionada a procedimentos orais invasivos. Este artigo teve como objetivo apresentar uma técnica alternativa para cirurgia periodontal em um paciente jovem com TG. Relato de Caso: Paciente com TG, sexo feminino, 15 anos, com história recente de sangramento excessivo relacionado a cirurgias odontológicas prévias, foi encaminhada a um centro odontológico público apresentando hiperplasia gengival. O procedimento de remoção foi realizado com laser de alta potência e, com exceção da anestesia local com epinefrina, nenhum outro agente hemostático foi necessário. Conclusão: De acordo com o caso, o laser de alta potência parece ser uma ferramenta eficiente na prevenção de sangramento perioperatório em pacientes com TG submetidos a pequenas cirurgias orais(AU)

Dialysis-related thrombocytopenia: a case report / Plaquetopenia relacionada à hemodiálise: relato de caso

Abstract Thrombocytopenia is frequently observed in hemodialysis patients, and its correct investigation and control remain a challenge. It is estimated that during the hemodialysis session there is a drop of up to 15% in the platelet count, with recovery after the end of treatment. This reduction in platelets is due to platelet adhesion and complement activation, regardless of the membrane material. Several studies with platelet surface markers demonstrate increased platelet activation and aggregation secondary to exposure to cardiopulmonary bypass. This case report describes a patient on hemodialysis who developed severe thrombocytopenia during hospitalization. Investigation and exclusion of the most common causes were carried out: heparin-related thrombocytopenia, adverse drug reaction, hypersplenism, and hematological diseases. Afterwards, the possibility of hemodialysis-related thrombocytopenia was raised, since the fall was accentuated during the sessions with partial recovery after the dialyzer change. Attention to the sterilization method and dialyzer reuse must be considered for correction. In the current case, reusing the dialyzer minimized the drop in platelet counts associated with hemodialysis.

Resumo Plaquetopenia é frequentemente observada em pacientes em hemodiálise, e sua correta investigação e controle permanecem um desafio. Estima-se que, durante a sessão de hemodiálise, ocorra queda de até 15% da contagem de plaquetas, com recuperação após o término do tratamento. Essa queda de plaquetas é decorrente de adesão plaquetária e ativação do complemento, independentemente do material da membrana. Vários estudos com marcadores de superfície plaquetária demonstram aumento da ativação e agregação plaquetária secundários à exposição à circulação extracorpórea. Este relato de caso mostra um paciente dialítico que evoluiu com plaquetopenia severa durante internação. Realizada investigação e exclusão de causas mais comuns: plaquetopenia relacionada à heparina, reação adversa a medicamentos, hiperesplenismo e doenças hematológicas, foi então aventada a possibilidade de plaquetopenia relacionada à hemodiálise após observação de que a queda se acentuava durante as sessões de hemodiálise com recuperação parcial após. Mudança do dialisador, atenção ao método de esterilização e realização do reuso devem ser consideradas para correção. No presente caso, a utilização do reuso minimizou a plaquetopenia associada a hemodiálise.

Concurrencia entre el síndrome de Guillain-Barré y púrpura trombocitopénica inmune posiblemente inducidos por COVID-19 prolongado / Concurrence between Guillain-Barré syndrome and immune thrombocytopenic purpura possibly induced by long COVID-19

RESUMEN Durante la infección aguda por el SARVS-CoV-2 se produce una desregulación del sistema inmune que puede durar hasta ocho meses después de controlado el cuadro agudo. Esto, sumado a otros factores, posiblemente este asociado con un aumento del riesgo de aparición y concurrencia de enfermedades autoinmunes. La aparición simultanea del síndrome de Guillain-Barré (SGB) y púrpura trombocitopénica (PTI) se ha reportado poco en la literatura, y el SGB raramente se asocia con otra enfermedad autoinmune. Presentamos el caso de un varón que luego de un mes de tener un cuadro agudo de COVID-19 moderado, presentó concurrentemente SGB y PTI con respuesta adecuada al tratamiento.

ABSTRACT During acute SARS-CoV-2 infection, there is persistent deregulation of the immune system that can last up to 8 months after the acute condition is controlled. This, added to other factors, is possibly associated with an increased risk of the appearance and concurrence of autoimmune diseases. The simultaneous occurrence of GBS and ITP has been rarely reported in the literature, and GBS is rarely associated with another autoimmune disease. We present the case of a man who, one month after his recovery from acute moderate COVID-19, presented concurrent GBS and ITP with an adequate response to treatment.

Invasive procedures in the oral cavity of individuals with Bernard-Soulier syndrome: An integrative review.

AIM: Bernard-Soulier syndrome (BSS) is an inherited bleeding disorder characterized by macroplatelets and thrombocytopenia, prolonged bleeding time, and a prevalence of less than 1 in 1,000,000. In view of the recognition of the risk of bleeding and the management of daily surgical practice in these patients, adequate strategies are necessary to provide the safest care. This article aims to perform an integrative review of the literature on the management of invasive procedures in the oral cavity of individuals with BSS. METHOD: The PubMed/Medline and LILACS databases were searched using Boolean operators related to BSS, bleeding disorders, and oral care. RESULTS: As a result, only five articles with the main theme were included: one letter to the editor and four case reports, described chronologically as to date of publication, classification of the article, and medical/odontological measures taken. CONCLUSION: We conclude with this review the need for adequate knowledge of surgeons regarding coagulation disorders and the need to discuss and plan procedures with the hematology team, as well as the importance of the notion of management of possible complications resulting from invasive treatments in the oral cavity of patients with BSS.

Síndrome de Bernard-Soulier / Bernard-Soulier síndrome

Resumen: El síndrome de Bernard-Soulier ocupa el séptimo lugar entre los trastornos de la coagulación más comunes y es una enfermedad poco frecuente de carácter genético, que se distingue por disfunción o ausencia del complejo plaquetario glicoproteína Ib-IX-V, que es el principal receptor del factor de von Willebrand, importante en la adhesión plaquetaria al subendotelio. Su incidencia puede llegar a ser de más de un caso por millón porque a menudo es mal diagnosticado si el paciente no manifiesta los datos clínicos típicos o si no hay resultados de laboratorio concluyentes. Los pacientes manifiestan macrotrombocitopenia con recuentos de plaquetas variables, además de prolongación del tiempo de coagulación. A la fecha se han descrito más de 100 mutaciones relacionadas con los componentes del complejo plaquetario, la manifestación de la enfermedad puede llegar a ser muy heterogénea incluso en pacientes que tengan una mutación idéntica.

Abstract: The Bernard-Soulier syndrome ranked seventh among the most common coagulation disorders; it is a rare genetic disease, characterized by dysfunction or absence of the glycoprotein Ib-IX-V platelet complex, which is the main receptor of von Willebrand factor, important in platelet adhesion to the subendothelium. Its incidence can be more than 1 per 1 million because it is often misdiagnosed if the patient does not present with the typical clinic or if there are no conclusive laboratory results. The syndrome presents macrothrombocytopenia with variable platelet counts as well as prolongation of the coagulation time. To date, more than 100 mutations related to the components of the platelet complex have been described, the presentation of the disease can become very heterogeneous even in patients who have an identical mutation.

Effects of leukocyte- and platelet-rich fibrin associated or not with bovine bone graft on the healing of bone defects in rats with osteoporosis induced by ovariectomy.

OBJECTIVE: To evaluate the healing of critical size defects (CSDs) in calvaria of rats with osteoporosis induced by ovariectomy and treated with leukocyte- and platelet-rich fibrin (L-PRF) associated or not with bovine bone graft (XENO). MATERIAL AND METHODS: A total of 32 rats underwent a bilateral ovariectomy procedure. After 3 months, one 5 mm in diameter CSD was created in the middle of the calvaria of each animal. In group C, defect was filled with blood clot only. In PRF, XENO, and PRF-XENO groups, defects were filled with 0.1 ml of L-PRF, 0.1 ml of XENO, and a mixture of 0.1 ml of L-PRF plus 0.1 ml of XENO, respectively. L-PRF compressed clots were used to cover the defects in PRF and PRF-XENO groups. Animals were submitted to euthanasia at 30 postoperative days. Histomorphometric, microtomographic, and immunohistochemical analyses were performed. RESULTS: PRF-XENO group presented greater amount of neoformed bone (NB) when compared with XENO group, as well as higher expression of vascular endothelial growth factor (VEGF), osteocalcin (OCN), and bone morphogenetic protein (BMP-2/4) (p < .05). PRF group presented increased amount of NB and higher expression of VEGF, OCN, BMP-2/4, and Runt-related transcription factor 2 (RUNX-2) when compared with group C (p < .05). CONCLUSIONS: (a) The isolated use of L-PRF clot can improve bone neoformation in CSDs in rats with osteoporosis induced by ovariectomy, but seems to lead to decreased amount of bone neoformation when compared to the isolated use of XENO; (b) L-PRF potentiates the healing of XENO in rats with osteoporosis induced by ovariectomy.

Trombastenia de Glanzmann: conceptos clave de la enfermedad / Glanzmann thrombasthenia: key concepts of the disease

La trombastenia de Glanzmann (TG), es un trastorno autosómico recesivo en el cual hay una reducción grave o ausencia de la agregación plaquetaria. Se debe a las alteraciones cualitativas o cuantitativas de la integrina α IIb o de integrina β 3, codificados por los genes ITGA2B e ITGB3 y relacionadas con la glicoproteína IIb/IIIa, que intervienen en la activación plaquetaria. La mayor incidencia de TG ha sido reportada en la población judía-iraquí, pero también se ha presentado en Israel, Jordania, Arabia saudita, Italia y, en menor número, en familias gitanas y pakistaníes. A pesar de ser poco frecuente, este trastorno se debe sospechar en casos de trastornos hemorrágicos graves espontáneos o inducidos por traumatismos, que varían desde hemorragias gastrointestinales y mucocutáneas, como epistaxis y hemorragias gingivales recurrentes de difícil manejo, las cuales son potencialmente mortales y en más del 75 por ciento de los casos requieren transfusión sanguínea o plaquetaria. Para realizar la confirmación del diagnóstico, los hallazgos de laboratorio se caracterizan por tiempos de sangrado prolongados, retracción del coágulo disminuida y respuestas anormales de agregación plaquetaria a estímulos fisiológicos. Aunque, actualmente no existe una cura para la enfermedad, el tratamiento adecuado con transfusiones plaquetarias y en caso de refractariedad, el uso del factor VIIa, permiten un buen pronóstico para los pacientes. Aún queda mucho por estudiar en estos casos debido a esto se están realizando nuevos estudios para la posibilidad de otros tratamientos, entre ellos la terapia génica plaquetaria(AU)

Glanzmann's thrombasthenia (GT) is an autosomal recessive disorder in which there is a severe reduction or absence of platelet aggregation. It is due to the qualitative or quantitative alterations of integrin #945; IIb or integrin #946; 3, encoded by the ITGA2B and ITGB3 genes and related to glycoprotein IIb / IIIa, which intervene in platelet activation. The highest incidence of GT has been reported in the Jewish-Iraqi population, but it has also been reported in Israel, Jordan, Saudi Arabia, Italy, and in smaller numbers in Gypsy and Pakistani families. Despite being uncommon, this disorder should be suspected in cases of severe spontaneous or trauma-induced bleeding disorders, ranging from gastrointestinal and mucocutaneous hemorrhages such as epistaxis and recurrent, difficult to manage gingival hemorrhages, which are potentially fatal and more than 75 percent of cases require blood or platelet transfusion. To confirm the diagnosis, the laboratory findings are characterized by prolonged bleeding times, decreased clot retraction and abnormal platelet aggregation responses to physiological stimuli. Although there is currently no cure for the disease, adequate treatments with platelet transfusions and in case of refractoriness, the use of factor VIIa, allow a good prognosis for patients. There is still much to study in these cases, because of this, new studies are being conducted for the possibility of other treatments, including platelet gene therapy(AU)

Sex-divided reference intervals for mean platelet volume, platelet large cell ratio and plateletcrit using the Sysmex XN-10 automated haematology analyzer in a UK population

ABSTRACT Background: This study aimed to define the sex-divided reference intervals for platelet indices (mean platelet volume (MPV), platelet distribution width (PDW), platelet large cell ratio (P-LCR) and plateletcrit (PCT)) on the Sysmex XN-10. Methods: A total of 2376 samples were assayed for full blood count on the Sysmex XN-10 haematology analyzer. After removing the outliers, reference intervals were calculated using the mean ± 2SD. The P value 0.05 was adopted to denote statistical significance. Results: There was a statistical significance (α = 0.05) between sex-divided reference intervals for MPV (p = 0.007), P-LCR (p = 0.015) and PCT (p < 0.001), thus separate reference intervals were calculated for these indices, with orientation to the sex-divisions as follows: MPV, 9.1-13.0 fL [males] and 9.2-12.8 fL [females]; P-LCR, 17.6-47.0% [males] and 17.8-47.8% [females]; and PCT, 0.16-0.35% [males] and 0.18-0.37% [females]. No significance was found between sex-divided reference intervals for the PDW (p = 0.838), therefore a reference interval for total individuals was calculated for this platelet measurement as 9.3-17.3 fL. Conclusion: This study showed comparable reference intervals, using the Sysmex XN-10, with the previous literature. It determined the need to define sex-specific reference intervals for the MPV, P-LCR and PCT, but not for the PDW. These reference intervals will allow for low and high values to be facilitated in order to do further research and guide platelet disorder management.

Sex-divided reference intervals for mean platelet volume, platelet large cell ratio and plateletcrit using the Sysmex XN-10 automated haematology analyzer in a UK population.

BACKGROUND: This study aimed to define the sex-divided reference intervals for platelet indices (mean platelet volume (MPV), platelet distribution width (PDW), platelet large cell ratio (P-LCR) and plateletcrit (PCT)) on the Sysmex XN-10. METHODS: A total of 2376 samples were assayed for full blood count on the Sysmex XN-10 haematology analyzer. After removing the outliers, reference intervals were calculated using the mean±2SD. The P value 0.05 was adopted to denote statistical significance. RESULTS: There was a statistical significance (α=0.05) between sex-divided reference intervals for MPV (p=0.007), P-LCR (p=0.015) and PCT (p<0.001), thus separate reference intervals were calculated for these indices, with orientation to the sex-divisions as follows: MPV, 9.1-13.0fL [males] and 9.2-12.8fL [females]; P-LCR, 17.6-47.0% [males] and 17.8-47.8% [females]; and PCT, 0.16-0.35% [males] and 0.18-0.37% [females]. No significance was found between sex-divided reference intervals for the PDW (p=0.838), therefore a reference interval for total individuals was calculated for this platelet measurement as 9.3-17.3fL. CONCLUSION: This study showed comparable reference intervals, using the Sysmex XN-10, with the previous literature. It determined the need to define sex-specific reference intervals for the MPV, P-LCR and PCT, but not for the PDW. These reference intervals will allow for low and high values to be facilitated in order to do further research and guide platelet disorder management.

Diagnostic challenges of inherited mild bleeding disorders: a bait for poorly explored clinical and basic research.

The best-known inherited mild bleeding disorders (MBDs), i.e. type 1 von Willebrand disease (VWD), platelet function disorders (PFDs), and mild to moderate clotting factor deficiencies, are characterized clinically by mucocutaneous bleeding, and, although they are highly prevalent, still pose difficult diagnostic problems. These include establishing the pathological nature of bleeding, and the uncertainties surrounding the clinical relevance of laboratory results. Furthermore, the high frequency of bleeding symptoms in the normal population and the subjective appraisal of symptoms by patients or parents makes elucidating the pathological nature of bleeding difficult. Standardized bleeding assessment tools and semiquantitative bleeding scores (BSs) help to discriminate normal from abnormal bleeding. However, as most MBDs have similar bleeding patterns, for example, bleeding sites, frequency, and severity, BSs are of little help for diagnosing specific diseases. Global tests of primary hemostasis (bleeding time; PFA-100/200) lack sensitivity and, like BSs, are not disease-specific. Problems with the diagnosis of type 1 VWD and PFD include assay standardization, uncertain definition of von Willebrand factor cut-off levels, and the lack of universal diagnostic criteria for PFD. Regarding clotting factor deficiencies, the bleeding thresholds of some coagulation factors, such as factor VII and FXI, are highly variable, and may lead to misinterpretation of the clinical relevance of mild to moderate deficiencies. Remarkably, a large proportion of MBDs remain undiagnosed even after comprehensive and repeated laboratory testing. These are tentatively considered to represent bleeding of undefined cause, with clinical features indistinguishable from those of classical MBD; the pathogenesis of this is probably multifactorial, and unveiling these mechanisms should constitute a fertile source of translational research.

Platelet count response to Helicobacter pylori eradication for idiopathic thrombocytopenic purpura in northeastern Brazil.

BACKGROUND: Several studies have demonstrated that platelet counts in Helicobacter pylori-positive patients with chronic idiopathic thrombocytopenic purpura improved significantly after successful eradication of the infection. However, depending of the geographical region of the study the results have been highly divergent. OBJECTIVE: The purpose of this study was to evaluate the effect of H. pylori eradication therapy on platelet count in a cohort of chronic idiopathic thrombocytopenic purpura patients from northeastern Brazil. METHOD: H. pylori status was determined in 28 chronic idiopathic thrombocytopenic purpura patients using the rapid urease test and histology. H. pylori-positive patients received standard triple therapy for one week. The effect of the eradication therapy was evaluated using the 13C-urea breath test two to three months after treatment. RESULTS: The prevalence of H. pylori infection was similar to that found in the general population. Twenty-two patients (78.5%) were H. pylori-positive. Fifteen were treated, 13 (86%) of whom successfully. At six months, 4/13 (30%) displayed increased platelet counts, which remained throughout follow-up (12 months). Platelet response was not associated to mean baseline platelet count, duration of chronic idiopathic thrombocytopenic purpura, gender, age, previous use of medication, or splenectomy. CONCLUSIONS: H. pylori eradication therapy showed relatively low platelet recovery rates, comparable with previous studies from southeastern Brazil. The effect of H. pylori eradication on platelet counts remained after one year of follow-up suggesting that treating H. pylori infection might be worthwhile in a subset of chronic idiopathic thrombocytopenic purpura patients.

Platelet count response to Helicobacter pylori eradication for idiopathic thrombocytopenic purpura in northeastern Brazil

Abstract Background: Several studies have demonstrated that platelet counts in Helicobacter pylori-positive patients with chronic idiopathic thrombocytopenic purpura improved significantly after successful eradication of the infection. However, depending of the geographical region of the study the results have been highly divergent. Objective: The purpose of this study was to evaluate the effect of H. pylori eradication therapy on platelet count in a cohort of chronic idiopathic thrombocytopenic purpura patients from northeastern Brazil. Method: H. pylori status was determined in 28 chronic idiopathic thrombocytopenic purpura patients using the rapid urease test and histology. H. pylori-positive patients received standard triple therapy for one week. The effect of the eradication therapy was evaluated using the 13C-urea breath test two to three months after treatment. Results: The prevalence of H. pylori infection was similar to that found in the general population. Twenty-two patients (78.5%) were H. pylori-positive. Fifteen were treated, 13 (86%) of whom successfully. At six months, 4/13 (30%) displayed increased platelet counts, which remained throughout follow-up (12 months). Platelet response was not associated to mean baseline platelet count, duration of chronic idiopathic thrombocytopenic purpura, gender, age, previous use of medication, or splenectomy. Conclusions: H. pylori eradication therapy showed relatively low platelet recovery rates, comparable with previous studies from southeastern Brazil. The effect of H. pylori eradication on platelet counts remained after one year of follow-up suggesting that treating H. pylori infection might be worthwhile in a subset of chronic idiopathic thrombocytopenic purpura patients.

Platelet-rich fibrin application in dentistry: a literature review.

The development of bioactive surgical additives to regulate the inflammation and increase the speed of healing process is one of the great challenges in clinical research. In this sense, platelet rich fibrin (PRF) appears as a natural and satisfactory alternative with favorable results and low risks. The following review attempts to summarize the relevant literature regarding the technique of using PRF, focusing on its preparation, advantages, and disadvantages of using it in clinical applications. PRF alone or in combination with other biomaterials seems to have several advantages and indications both for medicine and dentistry, due it is a minimally invasive technique with low risks and satisfactory clinical results.

Hyperaggregability and impaired nitric oxide production in platelets from postmenopausal women.

OBJECTIVE: Cardiovascular mortality increases after menopause in women. Nitric oxide is essential for proper platelet function inhibiting its aggregation and maintaining vascular haemostasis. Here, we investigated whether platelet function and intraplatelet l-arginine-nitric oxide pathway are impaired in postmenopausal women. STUDY DESIGN: Cross-sectional. MAIN OUTCOMES MEASURES: Blood was collected from 16 premenopausal and 12 postmenopausal women without any additional risk factor for cardiovascular disease. Platelet reactivity was measured by light transmission aggregometry. l-Arginine-nitric oxide pathway was assessed measuring transmembrane l-[(3)H]-arginine transport, nitric oxide synthase activity by the citrulline assay, and arginase activity by the conversion of l-[(14)C]arginine to l-[(14)C]-urea. The activity of antioxidant enzymes was measured by spectrophotometric assays. Protein expression was determined by Western blotting. RESULTS: Platelet aggregation was increased in postmenopausal compared to premenopausal women. Postmenopausal women demonstrated reduced plasma levels of l-arginine, a lower nitric oxide synthase activity, similar endothelial and inducible nitric oxide synthase expression, and a compensatory increase in l-arginine transmembrane transport. Arginase expression and activity did not differ between groups. In regard to oxidative stress, no differences between groups were observed NAPDH oxidase subunits expression and protein carbonylation. However, the activity of the antioxidant enzyme superoxide dismutase and catalase protein levels in platelets were higher in postmenopausal women. CONCLUSION: Postmenopausal women present increased platelet reactivity, which may be due to a reduction in intraplatelet nitric oxide synthesis. Platelet hyperaggregability is known to be associated with arterial and venous thromboembolic event; therefore, it may contribute to the heightened risk of cardiovascular adverse events in this population.

Mechanism of race-dependent platelet activation through the protease-activated receptor-4 and Gq signaling axis.

OBJECTIVE: Black individuals are at an increased risk of myocardial infarction and stroke, 2 vascular diseases with strong thrombotic components. Platelet activation is a key step in platelet clot formation leading to myocardial infarction and stroke, and recent work supports a racial difference in platelet aggregation through the thrombin protease-activated receptors (PARs). The underlying mechanism for this racial difference, however, has not been established. Determining where in the signaling cascade these racial differences emerge will aid in understanding why individuals of differing racial ancestry may possess an inherent difference in their responsiveness to antiplatelet therapies. APPROACH AND RESULTS: Washed human platelets from black volunteers were hyperaggregable in response to PAR4-mediated platelet stimulation compared with whites. Interestingly, the racial difference in PAR4-mediated platelet aggregation persisted in platelets treated ex vivo with aspirin and 2MeSAMP (2-methylthioadenosine 5'-monophosphate triethylammonium salt hydrate), suggesting that the racial difference is independent of secondary feedback. Furthermore, stimulation of platelets from black donors with PAR4-activating peptide showed a potentiated level of activation through the Gq pathway compared with platelets from white donors. Differences in signaling included increased Ca(2+) mobilization, Rap1 (Ras-related protein 1) activation, and integrin αIIbß3 activation with no observed difference in platelet protein expression between the groups tested. CONCLUSIONS: Our study is the first to demonstrate that the Gq pathway is differentially regulated by race after PAR4 stimulation in human platelets. Furthermore, the racial difference in PAR4-mediated platelet aggregation persisted in the presence of cyclooxygenase and P2Y12 receptor dual inhibition, suggesting that current antiplatelet therapy may provide less protection to blacks than whites.

Mechanisms underlying platelet function defect in a pedigree with familial platelet disorder with a predisposition to acute myelogenous leukemia: potential role for candidate RUNX1 targets.

BACKGROUND: Familial platelet disorder with a predisposition to acute myelogenous leukemia (FPD/AML) is an inherited platelet disorder caused by a germline RUNX1 mutation and characterized by thrombocytopenia, a platelet function defect, and leukemia predisposition. The mechanisms underlying FPD/AML platelet dysfunction remain incompletely clarified. We aimed to determine the contribution of platelet structural abnormalities and defective activation pathways to the platelet phenotype. In addition, by using a candidate gene approach, we sought to identify potential RUNX1-regulated genes involved in these defects. METHODS: Lumiaggregometry, α-granule and dense granule content and release, platelet ultrastructure, αIIb ß3 integrin activation and outside-in signaling were assessed in members of one FPD/AML pedigree. Expression levels of candidate genes were measured and luciferase reporter assays and chromatin immunoprecipitation were performed to study NF-E2 regulation by RUNX1. RESULTS: A severe decrease in platelet aggregation, defective αIIb ß3 integrin activation and combined αδ storage pool deficiency were found. However, whereas the number of dense granules was markedly reduced, α-granule content was heterogeneous. A trend towards decreased platelet spreading was found, and ß3 integrin phosphorylation was impaired, reflecting altered outside-in signaling. A decrease in the level of transcription factor p45 NF-E2 was shown in platelet RNA and lysates, and other deregulated genes included RAB27B and MYL9. RUNX1 was shown to bind to the NF-E2 promoter in primary megakaryocytes, and wild-type RUNX1, but not FPD/AML mutants, was able to activate NF-E2 expression. CONCLUSIONS: The FPD/AML platelet function defect represents a complex trait, and RUNX1 orchestrates platelet function by regulating diverse aspects of this process. This study highlights the RUNX1 target NF-E2 as part of the molecular network by which RUNX1 regulates platelet biogenesis and function.

Síndrome de plaqueta pegajosa / Sticky platelet síndrome

Resumen: El síndrome de plaqueta pegajosa es una trombofilia hereditaria, de carácter autosómico dominante, caracterizada por aumento in vitro de la agregación plaquetaria en respuesta a bajas concentraciones de epinefrina y/o adenosindifosfato (ADP) que se expresa como un estado protrombótico, tanto arterial como venoso. De acuerdo con el patrón de la agregometría plaquetariacon diferentes concentraciones de epinefrina y ADP, se presentan tres formas: síndrome de plaqueta pegajosa tipo I, hiperagregación plaquetaria con epinefrina y ADP; síndrome de plaqueta pegajosa tipo II, hiperagregación plaquetaria con epinefrina sola; y, síndrome de plaqueta pegajosa tipo III, hiperagregación plaquetaria con ADP solo. Las manifestaciones clínicas están relacionadas con la predisposición a trombosis arteriales o venosas, que se expresan como isquemia coronaria o cerebral, isquemia de vasos retinianos y trastornos de la microcirculación placentaria que puede asociarse con restricción del crecimiento intrauterino del feto, preeclampsia,eclampsia y pérdidas fetales, entre otras manifestaciones. El diagnóstico del síndrome de plaqueta pegajosa se establece mediante la agregación plaquetaria al demostrar la hiperagregación de las plaquetas inducida por pequeñas dosis de epinefrina y/o ADP. El tratamiento se basa en la administración de antiagregantes plaquetarios, siendo la aspirina a baja dosis la droga ideal y el clopidogrel cuando hay resistencia a la aspirina o esta está contraindicada. El objetivo de este módulo es revisar la literatura médica mundial sobre este nuevo síndrome que debe ser tenido en cuenta en el diagnóstico y manejo de la trombofilia como una nueva opción para el paciente afectado por uno de estos síntomas.

Abstract: Sticky platelet syndrome is an autosomal dominant inherited thrombophilia, characterizedby increased in vitro platelet aggregation in response to low concentrations of epinephrine or adenosine diphosphate (ADP). It is present as a prothrombotic state, both arterial and venous. According to platelet aggregation pattern, with the different ADP and epinephrine concentrations,three types of the syndrome can be identified: sticky platelet syndrome type I, platelet hyperaggregation with both reagents; sticky platelet syndrome type II, platelet hyperaggregation with epinephrine alone; and, sticky platelet syndrome type III, platelet hyperaggregation with ADP alone. The clinical manifestations are associated with predisposition to venous and arterial thrombosis, including cardiac or cerebral ischemia, retinal vein ischemia, and placental microcirculationdisorders, associated with intrauterine growth restriction, preeclampsia, eclampsia, and fetal loss, among others. Sticky platelet syndrome is diagnosed by platelet aggregation test, where is found a platelet hyperaggregation in response to low doses of epinephrine and ADP. Treatment includes the use of platelet antiaggregation agents, being low-dose aspirin therapy the best choice and clopidogrel in the cases of resistance or contradiction for aspirin. The aim of this module is to review the medical literature about this new syndrome, which it should take into account in the diagnosis and management of thrombophilia as a possible option to a patient affected by these symptoms.

An adenine insertion in exon 6 of human GP6 generates a truncated protein associated with a bleeding disorder in four Chilean families.

BACKGROUND: Glycoprotein VI (GPVI), 60-65 kDa, is a major collagen receptor on platelet membranes involved in adhesive and signaling responses. Mice lacking GPVI have impaired platelet response to collagen and defective primary adhesion and subsequent thrombus formation. Complete or partial deficiency of GPVI in humans is a rare condition presenting as a mild bleeding disorder. The defect in most of the reported patients is acquired and associated with other diseases. To date, only two patients have been characterized at the molecular level who carry different compound heterozygous mutations in the GP6 gene. OBJECTIVE: To report four unrelated patients from non-consanguineous families who presented with mucocutaneous bleeding. They had absent platelet aggregation and (14) C-5-HT secretion with collagen, convulxin and collagen-related peptide. RESULTS: Flow cytometry and immunofluorescence-confocal microscopy showed an absence of GPVI in non-permeabilized platelets. All the patients had an adenine insertion in exon 6 (c.711_712insA), changing the reading frame and generating a premature 'stop codon' in site 242 of the protein. The mutation predicts the synthesis of the truncated protein before the trans-membrane domain, corresponding to a band of ≈49 kDa observed in western blots and in permeabilized platelets by immunofluorescence. Platelet mRNA from all the patients was sequenced and contained the corresponding adenine insertion. Heterozygous relatives had no pathological bleeding, normal response to collagen and convulxin and intermediate membrane expression of GPVI. CONCLUSIONS: The identification of four unrelated homozygous patients with an identical defect suggests that inherited GPVI deficiency is more frequent than previously suspected, at least in Chile.