DNA Polymorphisms in Pregnant Women with Sticky Platelet Syndrome.

Sticky platelet syndrome (SPS) is a thrombophilia caused by the increased aggregability of platelets in response to the addition of low concentrations of epinephrine (EPI) and/or adenosine diphosphate (ADP). Some of the single nucleotide polymorphisms (SNP), alleles and haplotypes of platelet glycoprotein receptors were proved to have a role in the etiology of thrombotic episodes When comparing SPS and the control group, in VEGFA rs3025039, the p value for both CC vs. TT and CT vs. TT analyses was <0.001. Interestingly, no minor TT genotype was present in the SPS group, suggesting the thrombotic pathogenesis of recurrent spontaneous abortions (RSA) in these patients. Moreover, we found a significant difference in the presence of AT containing a risky A allele and TT genotype of ALPP rs13026692 (p = 0.034) in SPS patients when compared with the controls. Additionally, we detected a decreased frequency of the GG (CC) genotype of FOXP3 rs3761548 in patients with SPS and RSA when compared with the control group (p value for the CC (GG) vs. AA (TT) 0.021). This might indicate an evolutionary protective mechanism of the A (T) allele in the SPS group against thrombotic complications in pregnancy. These results can be used for antithrombotic management in such pregnant patients.

Primary Thrombophilia XVII: A Narrative Review of Sticky Platelet Syndrome in México.

Sticky Platelet Syndrome (SPS) is a disorder characterized by platelet hyperaggregability, diagnosed by studying in vitro platelet aggregation with ADP and epinephrine. It is the second most common cause of thrombophilia in Mexican Mestizos and manifests as an autosomal dominant trait which, combined with other coagulopathies, contributes significantly to the morbidity and mortality of patients with primary thrombophilia. It is easily treatable with antiplatelet drugs; however, the methods for diagnosis are not readily available in all clinical laboratories and the disorder is often overlooked by most clinicians. Herein, we present the results of more than 20 years of Mexican experience with the study of SPS in a Mestizo population.

MicroRNA and hyperaggregability of platelets in women with sticky platelet syndrome and pregnancy complications.

AIMS: We aimed to characterize relationship between the expression profiles of platelet miR-96, miR-126 and miR-223 and platelet function examination in patients with sticky platelet syndrome (SPS) and in healthy controls. BACKGROUND: MicroRNAs (miRNA, miR) are a group of small and non-coding RNAs involved in many mechanisms as regulators of post-transcriptional protein expression in platelets. SPS is defined as platelet hyperaggregability after administration of low doses of adenosine diphosphate and/or epinephrine. Clear genetic abnormality of this syndrome is not known yet. METHODS: We examined 45 patients with SPS and 30 healthy volunteers. For functional platelet examination we used light transmission aggregometry, and qRT-PCR was used to determine the expression of the miRNAs. RESULTS: We observed no relationship of the platelet miRNA expression with functional platelet examination in the entire cohort of patients with SPS. However, in a group of patients with SPS and pregnancy complications, we found that the expression of platelet miR-96 (p = 0.009) was up-regulated. CONCLUSION: In spite of the multiple limitations of the study, it can be considered that the increased expression of platelet miR-96 found in a group of patients with SPS and pregnancy complications could be related to the hyperaggregability in these selected patients (Tab. 2, Ref. 31).

High Prevalence of Sticky Platelet Syndrome in Patients with Infertility and Pregnancy Loss.

Platelet hyperaggregability, known as sticky platelet syndrome (SPS), is a prothrombotic disorder that has been increasingly associated with pregnancy loss. In this retrospective study, we aimed to investigate the clinical and diagnostic relevance of SPS in 208 patients with infertility and unexplained pregnancy loss history. We studied 208 patients that had been referred to undergo a dose-dependent platelet aggregation response to adenosine diphosphate and epinephrine using light transmission aggregometry modified by Mammen during an 11-year period. Patients' platelet aggregation response was compared with platelet function in 29 female healthy controls of fertile age with no previous history of pregnancy loss. We found a prevalence of SPS type II (33.2%) in 208 female patients with infertility and pregnancy loss. ∆-epinephrine-induced platelet aggregation in patients with SPS was significantly decreased (median 7% and range -21 to 43%) compared to patients without SPS (median 59%, range 7-88% and p < 0.0001) and healthy controls (median 57%, range 8-106% and p < 0.0001). The optimum SPS-diagnostic cutoff value for ∆-epinephrine aggregation was ≤32% (sensitivity 95.7%, specificity 95.2%). SPS patients with low-dose acetylsalicylic acid (ASA) therapy (n = 56) showed improved pregnancy outcome (32 pregnancies; live births n = 18 (56%)) compared to SPS patients without low-dose ASA (n = 13) (3 pregnancies; live births n = 1 (33%)). Our study demonstrates the clinical and diagnostic relevance of platelet hyperaggregation in women with infertility and pregnancy loss history. Further studies should investigate the potential of SPS as a novel decisional tool with both diagnostic and clinical implications in infertility and pregnancy loss.

Primary Thrombophilia in Mexico XIII: Localization of the Thrombotic Events in Mexican Mestizos With the Sticky Platelet Syndrome.

The sticky platelet syndrome (SPS) is a common cause of both arterial and venous thrombosis, being a dominant autosomal disease with qualitative platelet alterations and familial occurrence. It is characterized by platelet hyperreactivity with increased platelet aggregability in response to low concentrations of platelet agonists: epinephrine, adenosine diphosphate, or both. The clinical manifestations involve venous or arterial thrombosis, recurrent pregnancy loss, and fetal growth retardation. To analyze the localization of the thrombotic episodes in a cohort of Mexican mestizo patients with SPS. Between 1992 and 2016, 86 Mexican mestizo patients with SPS as the single thrombophilic condition were prospectively identified; all of them had a history of thrombosis. There were 15 males and 71 females. The thrombotic episodes were arterial in 26 cases and venous in 60 (70%). Arterial thrombosis was mainly pulmonary thromboembolism, whereas venous thromboses were identified most frequently in the lower limbs. Mexican mestizo population with SPS is mainly female; the type I of the condition is the most frequent; both arterial and venous thrombosis can occur, and they are mainly pulmonary embolism and lower limbs venous thrombosis, respectively.

GP6 Haplotype of Missense Variants is Associated with Sticky Platelet Syndrome Manifested by Fetal Loss.

Disequilibrium of hemostasis is central to the pathogenesis of all thromboses, and platelets are essential for primary hemostasis. The platelet membrane glycoprotein receptor is involved in the clot formation in blood; therefore, the changes in related genes could impair platelet aggregation in patients with sticky platelet syndrome (SPS). Patients with SPS who experienced fetal loss were shown to harbor a risk haplotype at GP6 locus. The aim of the study was to examine the genetic linkage of this selected risk haplotype with single nucleotide variations (SNVs) in the coding sequence of the GP6 gene in order to identify possible functional SNVs in association with SPS and fetal loss. A total of 37 patients with SPS manifested fetal loss, and 42 healthy controls were enrolled in the study. The SPS was diagnosed with platelet aggregometry. The SNVs were determined by dideoxy sequencing and high-resolution melting analysis. The missense variations were detected in patients with risk haplotype only. The association analysis showed association of the minor alleles with the SPS manifested by fetal loss as follows-rs1671152 (odds ratio [OR]: 4.667, 95% confidence interval [CI]: 1.462-14.89, P = .006), rs2304167 (OR: 5.085, 95% CI: 1.605-16.10, P = .003), and rs1654416 (OR: 5.085, 95% CI: 1.605-16.10, P = .003). Using the Expectation-Maximization (EM) algorithm, the estimated minor haplotype with predicted protein residue PEAN was significantly associated with the given phenotype (OR: 4.746, 95% CI: 1.486-15.15, P = .005). We have shown that haplotype PEAN associated with SPS and manifested by fetal loss and suggest that the mechanism involved in the action of GPVI has significant effect on GPVI-mediated signal transduction through Syk-phosphorylation.

Sticky platelet syndrome: an important cause of life-threatening thrombotic complications.

Sticky platelet syndrome (SPS) is a prothrombotic thrombocytopathy with familial occurrence, characterized by hyperaggregability of platelets in response to adenosine diphosphate (ADP), epinephrine (EPI) or both. The syndrome has been identified in approximately 21% of unexplained arterial thrombotic episodes, regarded to be the most common thrombophilia in arterial thrombosis and 13.2% of unexplained venous thromboembolism (VTE). The relatively young age at the first manifestation, relation to fertility and pregnancy, seriousness of the symptoms, easy and effective management of the disorder indicate to the necessity to take it into account in the differential diagnosis of the underlying cause of the thrombotic event. As the various localizations of the thrombosis in SPS have been reported, its management often requires a multidisciplinary approach. This review deals with the clinical aspects of thrombophilia, its etiopathogenesis, diagnosis as well as novel advances in the treatment and outlines the challenges for the further research.

Seguimiento de gestante con síndrome de plaquetas pegajosas: primer caso comunicado en Cuba / Gestational follow-up of pregnant woman with sticky platelets syndrome: first patient reported in Cuba

El síndrome de plaquetas pegajosas es una entidad en la que se presentan hiperagregabilidad plaquetaria y manifestaciones clínicas trombóticas. Fue observada hace más de 30 años en personas jóvenes con eventos oclusivos, arteriales, venosos, miorcárdicos, cerebrales y, años más tarde, se describió en mujeres con pérdidas recurrentes de embarazos y complicaciones obstétricas. El tratamiento de elección es la aspirina, con la cual se logra revertir la hiperagregabilidad plaquetaria. Se presenta el seguimiento de una gestante con diagnóstico de síndrome de plaquetas pegajosas tipo II, con antecedentes de dos pérdidas de embarazos. Durante la gestación recibió terapia antiagregante plaquetaria y heparina de bajo peso molecular. A pesar de esta terapéutica surgieron complicaciones en el tercer trimestre de la gestación que condujeron a la interrupción temprana del embarazo. Se logró una recién nacida viva, con bajo peso, sin otras complicaciones perinatales. Actualmente la paciente se mantiene con aspirina y no ha referido eventos oclusivos. Este trabajo demuestra que la atención a estas pacientes por un equipo multidisciplinario permite obtener resultados alentadores.

Sticky platelet syndrome is an entity where patients have platelet hiperaggregability and thrombotic clinical manifestations. It was observed more than 30 years ago in young people with occlusive arterial, venous, myocardial infarctions, stroke, and later it was reported in women with recurrent pregnancy loss and obstetric complication events. The treatment of choice is aspirin which reverted platelet hyperaggregability. We present a pregnant woman diagnosed with type II sticky platelets syndrome with a history of two pregnancy loss. During this pregnancy, she received antiplatelet therapy and molecular weight heparin. Despite this therapy, complications arose in the third quarter that led to the early termination of pregnancy, but we obtained an alive underweight newborn without any perinatal complications. Currently, the patient maintains aspirin and she has no occlusive events. These results demonstrate that the care of these patients by a multidisciplinary team has successful outcome.

Seguimiento de gestante con síndrome de plaquetas pegajosas: primer caso comunicado en Cuba / Gestational follow-up of pregnant woman with sticky platelets syndrome: first patient reported in Cuba

El síndrome de plaquetas pegajosas es una entidad en la que se presentan hiperagregabilidad plaquetaria y manifestaciones clínicas trombóticas. Fue observada hace más de 30 años en personas jóvenes con eventos oclusivos, arteriales, venosos, miorcárdicos, cerebrales y, años más tarde, se describió en mujeres con pérdidas recurrentes de embarazos y complicaciones obstétricas. El tratamiento de elección es la aspirina, con la cual se logra revertir la hiperagregabilidad plaquetaria. Se presenta el seguimiento de una gestante con diagnóstico de síndrome de plaquetas pegajosas tipo II, con antecedentes de dos pérdidas de embarazos. Durante la gestación recibió terapia antiagregante plaquetaria y heparina de bajo peso molecular. A pesar de esta terapéutica surgieron complicaciones en el tercer trimestre de la gestación que condujeron a la interrupción temprana del embarazo. Se logró una recién nacida viva, con bajo peso, sin otras complicaciones perinatales. Actualmente la paciente se mantiene con aspirina y no ha referido eventos oclusivos. Este trabajo demuestra que la atención a estas pacientes por un equipo multidisciplinario permite obtener resultados alentadores(AU)

Sticky platelet syndrome is an entity where patients have platelet hiperaggregability and thrombotic clinical manifestations. It was observed more than 30 years ago in young people with occlusive arterial, venous, myocardial infarctions, stroke, and later it was reported in women with recurrent pregnancy loss and obstetric complication events. The treatment of choice is aspirin which reverted platelet hyperaggregability. We present a pregnant woman diagnosed with type II sticky platelets syndrome with a history of two pregnancy loss. During this pregnancy, she received antiplatelet therapy and molecular weight heparin. Despite this therapy, complications arose in the third quarter that led to the early termination of pregnancy, but we obtained an alive underweight newborn without any perinatal complications. Currently, the patient maintains aspirin and she has no occlusive events. These results demonstrate that the care of these patients by a multidisciplinary team has successful outcome(AU)

Síndrome de las plaquetas pegajosas como marcador importante de trombosis en los pacientes con trombofilia / The sticky platelet syndrome. Important markers of thrombosis in patient with thrombophilia

Introducción: el síndrome de las plaquetas pegajosas (SPP), es una entidad que provoca trastornos en la agregación de las plaquetas caracterizados por incremento anormal (hiperagregabilidad plaquetaria) y tendencia a la ocurrencia de trombosis, enfermedad que provoca morbilidad y mortalidad.Objetivo: caracterizar el comportamiento del síndrome de las plaquetas pegajosas como un marcador de trombogénesis en los pacientes con trombofilia y determinar la relación de este síndrome con la aparición y recurrencia de la enfermedad trombótica, asociado o no a otros marcadores de trombosis.Métodos: la muestra quedó constituida por 63 pacientes atendidos en la Consulta de Trombofilia del Hospital Hermanos Ameijeiras y 66 sujetos de ambos sexos y edades inferiores a 45 años, supuestamente sanos, del banco de sangre del hospital, en el período comprendido entre febrero de 2013 y abril de 2014. Como parte del perfil trombofílico, se estudiaron las pruebas de hiperagregación plaquetaria por método de transmisión de luz, la antitrombina, las proteínas C y S y el anticoagulante lúpico, mediante estudios cromogénicos y coagulométricos. Las alteraciones genéticas: factor V Leiden y factor II G20210 A (PG20210A) se evaluaron mediante la reacción en cadena de la polimerasa...

Introduction: the sticky platelet syndrome is an entity that causes dysfunctions in the aggregation of the platelets characterized by their abnormal increase (platelet hiperaggregability) and tendency to the thrombosis occurrence, illness that causes morbidity and mortality.Objective: to characterize the behaviour of the sticky platelet syndrome as a thrombus-genesis marker in the patients with thrombophilia and to determine the relationship of this syndrome with this illness appearance and recurrence associated or not to other thrombosis markers.Methods: the sample consisted of 63 patients treated in the thrombophilia service at Hermanos Ameijeiras Hospital and 66 subjects of both genders, younger than 45 years age, supposedly healthy, from the hospital blood bank of from February 2013 to April 2014. As part of thrombophilic profile, the hyper-aggregation platelet tests were studied by light transmission method, antithrombin, protein C and S, and the lupus anticoagulant, using chromogenic and coagulometric studies. Genetic alterations: factor V Leiden and factor II G20210A A (PG20210A) were assessed by polymerase chain reaction...

Síndrome de las plaquetas pegajosas como marcador importante de trombosis en los pacientes con trombofilia / The sticky platelet syndrome. Important markers of thrombosis in patient with thrombophilia

Introducción: el síndrome de las plaquetas pegajosas (SPP), es una entidad que provoca trastornos en la agregación de las plaquetas caracterizados por incremento anormal (hiperagregabilidad plaquetaria) y tendencia a la ocurrencia de trombosis, enfermedad que provoca morbilidad y mortalidad. Objetivo: caracterizar el comportamiento del síndrome de las plaquetas pegajosas como un marcador de trombogénesis en los pacientes con trombofilia y determinar la relación de este síndrome con la aparición y recurrencia de la enfermedad trombótica, asociado o no a otros marcadores de trombosis. Métodos: la muestra quedó constituida por 63 pacientes atendidos en la Consulta de Trombofilia del Hospital Hermanos Ameijeiras y 66 sujetos de ambos sexos y edades inferiores a 45 años, supuestamente sanos, del banco de sangre del hospital, en el período comprendido entre febrero de 2013 y abril de 2014. Como parte del perfil trombofílico, se estudiaron las pruebas de hiperagregación plaquetaria por método de transmisión de luz, la antitrombina, las proteínas C y S y el anticoagulante lúpico, mediante estudios cromogénicos y coagulométricos. Las alteraciones genéticas: factor V Leiden y factor II G20210 A (PG20210A) se evaluaron mediante la reacción en cadena de la polimerasa. Resultados: existen diferencias significativas entre uno y otro sexo a favor del masculino para la aparición de la trombosis (X²= 0,512 para p= 0,004). Predominó el color de piel blanco en el desarrollo de la enfermedad trombótica, hubo mayor número de pacientes con marcadores trombogénicos y combinaciones entre ellos para esta etnia (X²= 92,5 para p= 0,000). El marcador genético prevalente en pacientes con trombosis fue factor V Leiden. Al relacionar los diferentes marcadores trombogénicos en pacientes con trombosis y en sujetos no seleccionados se evidenció que existen diferencias significativas (X²=18,68; p=0,002) entre la presencia de marcadores biológicos y la aparición de la enfermedad trombótica. El SPP tipo I fue el más frecuente en este estudio, seguido del tipo III y el tipo II (OR= 10,5; 7,1 y 2.5). Conclusiones: existen diferencias significativas entre la presencia de marcadores biológicos y la aparición de la enfermedad trombótica. El SPP tipo I fue el más frecuente en este estudio(AU)

Introduction: the sticky platelet syndrome is an entity that causes dysfunctions in the aggregation of the platelets characterized by their abnormal increase (platelet hiperaggregability) and tendency to the thrombosis occurrence, illness that causes morbidity and mortality. Objective: to characterize the behaviour of the sticky platelet syndrome as a thrombus-genesis marker in the patients with thrombophilia and to determine the relationship of this syndrome with this illness appearance and recurrence associated or not to other thrombosis markers. Methods: the sample consisted of 63 patients treated in the thrombophilia service at Hermanos Ameijeiras Hospital and 66 subjects of both genders, younger than 45 years age, supposedly healthy, from the hospital blood bank of from February 2013 to April 2014. As part of thrombophilic profile, the hyper-aggregation platelet tests were studied by light transmission method, antithrombin, protein C and S, and the lupus anticoagulant, using chromogenic and coagulometric studies. Genetic alterations: factor V Leiden and factor II G20210A A (PG20210A) were assessed by polymerase chain reaction. Results: there are significant differences between the genders in favour of men for the occurrence of thrombosis (X²= 0.512 p = 0.004). White skin colour predominated to develop thrombotic disease, there were more patients with thrombogenic markers and combinations between them to this ethnic group (X²= 92.5; p = 0.000). The prevalent genetic marker in patients with factor V Leiden was thrombosis. Significant differences (X²= 18.68; p= 0.002) are showed between the presence of biomarkers and development of thrombotic disease when linking the different thrombogenic markers in patients with thrombosis and in unselected subjects. SPP type I was the most frequent in this study, followed by type III and type II. (OR= 10.5, 7.1 and 2.5). Conclusions: there are significant differences between the presence of biomarkers and development of thrombotic disease. The sticky platelet syndrome type I was the most frequent in this study(AU)

Genetic variations of the GP6 regulatory region in patients with sticky platelet syndrome and miscarriage.

INTRODUCTION: Thrombophilia increases the risk of venous thrombosis during pregnancy and may predispose to gestational vascular complications. OBJECTIVE: The aim of this study is to evaluate the variability of GP6 regulatory regions in a group of patients with platelet hyperaggregability manifested as miscarriage compared with control subjects. METHODS: We examined 27 female patients with platelet hyperaggregability and history of spontaneous abortion and 42 healthy women. Platelet hyperaggregability was established by light transmission aggregometry. We also assessed eight SNPs within the GP6 gene. RESULTS: We found a higher occurrence of three SNPs in patients with platelet hyperaggregability and history of miscarriage (rs1671152, rs1654433, rs1671215). The haplotype analysis showed a significant higher occurrence of two haplotypes (ACGG, CCGT). CONCLUSIONS: Our results support the idea that genetic variability of GP6 regulatory regions can be associated with platelet hyperaggregability - a possible cause of miscarriage.

Primary thrombophilia in México X: a prospective study of the treatment of the sticky platelet syndrome.

INTRODUCTION: The sticky platelet syndrome (SPS) is a common cause of thrombosis. There are no prospective studies concerning treatment. OBJECTIVE: To analyze changes in platelet hyperaggregability of patients with SPS who were given antiplatelet drugs and to assess its association with rethrombosis. METHODS: A total of 55 patients with a history of thrombosis and SPS phenotype were prospectively studied before and after treatment with aspirin and/or clopidogrel. RESULTS: Patients were followed for 1 to 129 months, median 13. Of 55 patients, 40 received aspirin, 13 received aspirin + clopidogrel, and 2 received only clopidogrel. The platelet aggregation response to adenosine diphosphate and epinephrine significantly diminished after treatment, and only 2 patients developed rethrombosis 52 and 129 months after starting therapy, with the freedom from rethrombosis rate of the patients being 96.4% at 129 months. CONCLUSION: Using antiplatelet drugs, the platelet hyperreactivity of patients with the SPS phenotype was reverted; and this translated into a substantial decrease in the rethrombosis rate.

Platelet Hyperaggregability is Highly Prevalent in Patients With Chronic Kidney Disease: An Underestimated Risk Indicator of Thromboembolic Events.

BACKGROUND: Platelet hyperaggregation is known to be associated with arterial and venous thromboembolic events. The prevalence of platelet hyperaggregation in patients with chronic kidney disease (CKD) has not been described to date. METHODS: Platelet hyperaggregation in patients with renal disease was defined by comparison of platelet aggregation patterns to non-CKD patients without thromboembolic disorders and healthy controls. RESULTS: Among the 30 hemodialysis patients and 34 renal transplant recipients, 20 (67%) and 28 (82%) showed significantly decreased median Δ-epinephrine aggregation and increased 0.5 mol/L epinephrine response (65% and 54%) compared to healthy controls and non-CKD patients. In concordance to the laboratory finding of platelet hyperaggregability, renal transplant recipients showed a high rate of thromboembolic events (normal platelet aggregation: 0 events and platelet hyperaggregation: 30 events in 13 of 28 patients). CONCLUSIONS: Patients with CKD exhibit a hitherto unappreciated high prevalence of platelet hyperaggregability indicating sticky platelet syndrome. Laboratory testing of platelet hyperaggregability may supplement the assessment of thromboembolic complications in patients with CKD.

Frecuencia del síndrome de plaquetas pegajosas en pacientes con pérdidas fetales recurrentes / Frequency of sticky platelet syndrome in patients with recurrent fetal loss

El síndrome de las plaquetas pegajosas es un trastorno plaquetario autosómico dominante considerado como una de las causas más frecuentes de eventos trombóticos. Se cree que el defecto específico puede estar localizado en los receptores de la superficie plaquetaria y está caracterizado por un incremento anormal en la agregabilidad de las plaquetas con difosfato de adenosina, epinefrina, o ambos. En estudios realizados acerca de esta entidad se ha descrito una elevada incidencia, pero esta se ha calculado en pacientes que han tenido episodios trombóticos previos (enfermedad tromboembólica, infarto agudo del miocardio y accidente cerebrovascular), antecedentes familiares o tienen factores de riesgo para este tipo de eventos, mientras que su incidencia en una población de mujeres en edad fértil, con dos o más pérdidas de embarazo y sin antecedentes es desconocida. En el presente trabajo se estudiaron un total de 126 pacientes femeninas con al menos dos pérdidas de embarazo; de ellas, 27 resultaron positivas al estudio de hipersensibilidad plaquetaria con difosfato de adenosina y epinefrina mediante pruebas de agregometría, lo que representa el 21 por ciento de positividad en la población estudiada. Es significativo que la clase de síndrome de plaqueta pegajosa predominante fue de tipo II (hipersensibilidad con epinefrina). Finalmente, destacar que el seguimiento y tratamiento oportuno durante la gestación en las pacientes incluidas en el estudio ha permitido el nacimiento de 4 niños saludables de madres con síndrome de plaquetas pegajosas...

The sticky platelet syndrome is an autosomal dominant platelet disorder considered one of the most frequent causes of thrombotic events. It is supposed that the specific fault can be localized to the platelet surface receptor and is characterized by an abnormal increase in aggregability adenosine diphosphate and/or epinephrine. In studies on this entity a high incidence has been described, but this was calculated in patients who have had previous thrombotic events (thromboembolic disease, myocardial infarction and stroke), family history or risk factors for this kind of events, while its incidence in a population of women of childbearing age with two or more pregnancy losses and no previous history is unknown.During our research a total of 126 female patients with at least two miscarriages were studied; 27 of them showed platelet hypersensitivity to adenosine diphosphate and epinephrine by testing aggregometry, which represents 21 percent positivity in the population studied. It is significant that the sticky platelet syndrome was predominantly of type II (hypersensitivity with epinephrine). In conclusion, we consider important to remark that with the monitoring and opportune treatment during pregnancy, four of the patients included in our study gave birth four healthy children despite the sticky platelet syndrome...

Frecuencia del síndrome de plaquetas pegajosas en pacientes con pérdidas fetales recurrentes / Frequency of sticky platelet syndrome in patients with recurrent fetal loss

El síndrome de las plaquetas pegajosas es un trastorno plaquetario autosómico dominante considerado como una de las causas más frecuentes de eventos trombóticos. Se cree que el defecto específico puede estar localizado en los receptores de la superficie plaquetaria y está caracterizado por un incremento anormal en la agregabilidad de las plaquetas con difosfato de adenosina, epinefrina, o ambos. En estudios realizados acerca de esta entidad se ha descrito una elevada incidencia, pero esta se ha calculado en pacientes que han tenido episodios trombóticos previos (enfermedad tromboembólica, infarto agudo del miocardio y accidente cerebrovascular), antecedentes familiares o tienen factores de riesgo para este tipo de eventos, mientras que su incidencia en una población de mujeres en edad fértil, con dos o más pérdidas de embarazo y sin antecedentes es desconocida. En el presente trabajo se estudiaron un total de 126 pacientes femeninas con al menos dos pérdidas de embarazo; de ellas, 27 resultaron positivas al estudio de hipersensibilidad plaquetaria con difosfato de adenosina y epinefrina mediante pruebas de agregometría, lo que representa el 21 por ciento de positividad en la población estudiada. Es significativo que la clase de síndrome de plaqueta pegajosa predominante fue de tipo II (hipersensibilidad con epinefrina). Finalmente, destacar que el seguimiento y tratamiento oportuno durante la gestación en las pacientes incluidas en el estudio ha permitido el nacimiento de 4 niños saludables de madres con síndrome de plaquetas pegajosas(AU)

The sticky platelet syndrome is an autosomal dominant platelet disorder considered one of the most frequent causes of thrombotic events. It is supposed that the specific fault can be localized to the platelet surface receptor and is characterized by an abnormal increase in aggregability adenosine diphosphate and/or epinephrine. In studies on this entity a high incidence has been described, but this was calculated in patients who have had previous thrombotic events (thromboembolic disease, myocardial infarction and stroke), family history or risk factors for this kind of events, while its incidence in a population of women of childbearing age with two or more pregnancy losses and no previous history is unknown.During our research a total of 126 female patients with at least two miscarriages were studied; 27 of them showed platelet hypersensitivity to adenosine diphosphate and epinephrine by testing aggregometry, which represents 21 percent positivity in the population studied. It is significant that the sticky platelet syndrome was predominantly of type II (hypersensitivity with epinephrine). In conclusion, we consider important to remark that with the monitoring and opportune treatment during pregnancy, four of the patients included in our study gave birth four healthy children despite the sticky platelet syndrome(AU)

Decreased Threshold of Aggregation to Low-Dose Epinephrine is Evidence of Platelet Hyperaggregability in Patients with Thrombosis.

Sticky platelet syndrome has been described as a hereditary thrombophilic condition. The aim of this study is to identify the presence of platelet hyperaggregability in patients who have experienced thrombosis. Light-transmittance platelet aggregometry was used to assess for spontaneous platelet aggregation, aggregation in response to full and low-dose (LD) epinephrine (Epi) and adenosine diphosphate, as well as arachidonic acid, and identify a distinct pattern of platelet hyperaggregability. Light-transmittance platelet aggregometry results were correlated with PFA-100® (Dade-Behring, Marburg, Germany) results, when available. An exaggerated response to LD Epi was found in 68% of patients with thrombosis compared to only 36% of healthy controls (P=0.034). Patients with thrombosis, either arterial or venous, demonstrated an exaggerated response to LD Epi nearly twice as frequently as healthy controls, even without significant family history of thrombophilia or other known risk factors for thrombosis. This suggests that platelet hyperaggregability may be multifactorial in nature and not necessarily hereditary.

Nine kindreds of familial sticky platelet syndrome phenotype.

INTRODUCTION: Sticky platelet syndrome (SPS) is most likely a hereditary thrombophilia characterized by platelet hyperaggregation after low concentrations of platelet inducers--adenosine diphosphate and/or epinephrine. We present 9 kindreds with SPS familial occurrence. MATERIAL AND METHODS: Familial trait of SPS was looked up in the database of the National Center of Hemostasis and Thrombosis. Families with at least 3 SPS-positive members were studied, described, and presented. RESULTS: In the group of 1093 symptomatic patients, SPS was confirmed in 240 cases. Familial occurrence with at least 3 SPS-positive relatives was found in 9 cases. CONCLUSION: The exact pathogenesis of SPS is not sufficiently explained. Our findings seem to support the idea that SPS might have an autosomal dominant hereditary fashion.

Primary thrombophilia in Mexico IX: the glycoprotein IIIa PLA1/A2 polymorphism is not associated with the sticky platelet syndrome phenotype.

INTRODUCTION: The sticky platelet syndrome (SPS) seems to be a common cause of thrombosis, although no molecular substrate to explain platelet hyperaggregability has been found. OBJECTIVE: To analyze an association between the SPS phenotype and the platelet glycoprotein (GP) IIIa PL(A1/A2) (human platelet antigen [HPA]-1a/b) gene polymorphism. METHODS: Along an 18-month period, Mexican mestizo thrombophilic patients were prospectively accrued. The SPS phenotype was assessed by aggregometry, whereas a tetra-primer amplification refractory mutation system (ARMS) polymerase chain reaction analysis was used to detect the PLA1 and PLA2 alleles. RESULTS: A total of 95 individuals with SPS and 127 healthy donors were studied; in 11 of the donors and 16 of the patients with SPS the A2 allele of the GP IIb/IIIA was found, yielding a weak and nonsignificant association (odds ratio 2.14, 95% CI 0.94-4.85). CONCLUSION: In Mexican mestizo patients, the platelet GP IIIa PL(A1/A2) gene polymorphism does not lead to the SPS phenotype.

Utilidad clínica de la agregometría plaquetaria / Clinical utility of platelet aggregometry

Resumen: La acción de las plaquetas en la hemostasia primaria comprende la adhesión a losvasos sanguíneos afectados, la activación, la secreción del contenido granular, y posteriormente,la agregación plaquetaria para la formación del tapón hemostático primario. Bajo las condicionesfisiológicas de flujo vascular, estos procesos requieren la acción sinérgica de varias proteínasy receptores plaquetarios, como también de agonistas que inducen la activación plaquetaria.Por ello, las mutaciones de los genes que codifican para moléculas y receptores de superficieimplicados en estos procesos darán origen a desórdenes hemorrágicos como la enfermedad devon Willebrand, la trombastenia de Glanzmann, el síndrome de Bernard Soulier y la deficienciade gránulos plaquetarios, entre otros. El diagnóstico de estas enfermedades se realiza medianteensayos de función plaquetaria que simulan los procesos fisiológicos de activación, adhesión,liberación del contenido granular y agregación. Una de las pruebas de función plaquetaria másutilizada es la agregometría. En este artículo de revisión se describe la utilidad de esta prueba parael diagnóstico de desórdenes hemorrágicos hereditarios y del síndrome de la plaqueta pegajosa,un desorden trombótico hereditario caracterizado por hiperagregabilidad. Adicionalmente, se revisa el fundamento de esta prueba, las condiciones preanalíticas, analíticas y posaanaliticas, analiticas y poanaliticas las indicaciones las contraindicaciones y la interpetación de los resultados.

Abstract: The role of platelets in primary hemostasis involves their adherence to sites of vessel injury, activation, secretion of platelet granule content, and finally, aggregation to form the primaryhemostatic plug. Under physiologic conditions of vascular flow, these processes require thesynergistic action of several proteins and platelet receptors, and also the action of physiologicalagonists that stimulate the activation of the platelets. As a result, hereditary mutations of genescodifying for molecules and surface receptors implied in primary hemostasis will be expressedas hemorrhagic disorders, including von Willebrand disease, Glanzmann thrombasthenia,Bernard Soulier syndrome, storage pool diseases, among others. The diagnosis of these diseases is possible through platelet function assays that resemble the physiological processesof activation, adhesion, release of granule content, and aggregation. Platelet aggregometry isone of the most frequently used tests. This review article intends to describe the utility of plateletaggregometry for the diagnosis of hereditary hemostatic disorders and sticky platelet syndrome, a hereditary thrombotic disorder characterized by increased platelet aggregability. In addition, the fundamentals of the test, the pre-analytical, analytical and post-analytical conditions, the test indications, contraindications and results interpretation are discussed.