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The sticky platelet syndrome
Abstract
The sticky platelets syndrome (SPS) is a procoagulant condition based on either arterial, venous, or capillary thrombi caused by hyperesponsive and hyperaggregable platelets. This is a frequent disease, which often remains clinically inapparent, until stressful events or combination with other factors increase the risk of developing SPS. The condition is due to a congenital platelet defect with autosomal dominant characteristics, leading to the increased platelet aggregability when they are challenged with epinephrine and adenosine diphosphate. Nowadays classification of this disorder is based on platelet reactivity to both ADP and epinephrine (SPS type 1), epinephrine alone (SPS type 2), and ADP alone (SPS type 3). The diagnoses of the syndrome depend on the functional aggregometer assay. This condition should be taken into account whenever a patient with thrombophilia is considered.
... According to the study, the platelet aggregation response to ADP and epinephrine in patients with the SPS phenotype was reverted after the administration of antiplatelet drugs. This strongly suggests that therapy with ASA or other antiplatelet agents is efficient, not only in the treatment of thrombotic events in patients with SPS but also in the prevention of these phenomena (36)(37)(38). Kubisz et al. proposed that this treatment was only pertinent when SPS was the only identified abnormality and did not coexist with other prothrombotic conditions. On the other hand, combined abnormality cases may require different therapeutic measures (39). ...
Holiday described the sticky platelet syndrome (SPS) and since then, reports from different parts of the world have become available. Initial data on SPS was acquired from studies conducted on Caucasian populations, however, it is imperative to note that further investigations have been undertaken on diverse ethnic groups, such as the Mexican population, which have revealed the existence of certain variations and disparities in the manifestation and characteristics of this syndrome. The Mexican population is defined as "mestizo" and encompasses individuals born in Mexico but with Amerindian and white ancestors. The Mexican Genome Diversity Project (MGDP) showed that the genetic diversity generated by the "mestizaje" is most relevant for some pathologies, including autoimmune disease among others. In Mexico, SPS is the second most common hereditary thrombophilic condition and that most frequently associated with arterial thrombosis, followed by the antiphospholipid syndrome. The preferred therapeutic intervention for patients diagnosed with SPS lies in the administration of antiplatelet medications, as this particular course of action effectively rectifies the phenomenon of platelet hyperaggregability in approximately 75% of afflicted individuals, thus resulting in a notable reduction in the likelihood of rethrombosis to a rate that falls below the 4% threshold. In the last two decades, SPS has become the second most common cause of primary thrombophilia in the Mexican mestizo population, and it is manifested as an autosomal dominant disease, very frequently combined with other coagulopathies. The medical community needs to recognize SPS as a frequent cause of thrombophilia since once identified, its treatment is inexpensive and effective. We herein present data accrued over 32 years, on SPS in Mexico.
... Sticky platelet syndrome (SPS) is an inherited thrombophilic condition that causes an abnormal increase in platelet aggregation and favors both arterial and venous thrombotic events [1][2][3][4] . Between January 2020 and August 2023, 11 persons with SPS were diagnosed and treated at the Center for Hematology and Internal Medicine of Puebla (Centro de Hematología y Medicina Interna de Puebla), Mexico. ...
... Since the first description of Sticky Platelet Syndrome, it has been within our uttermost interest to contribute to the study of the genetic factors, clinical management, and diagnosis of the disease; especially given that it seems to be the second most common cause of thrombophilia in our country. SPS does not usually lead to thrombosis on its own, but rather needs association with another thrombophilia-causing condition to manifest itself, such as estrogen use, mutations, other alterations in blood coagulation, and in most recent times, COVID-19 [25,26]. In some patients, SPS can be so insidious that clinicians often mislabel thrombotic events as idiopathic. ...
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.
... (3,(5)(6)(7) La hiperagregación plaquetaria puede llevar a oclusiones vasculares transitorias o permanentes, sean arteriales, capilares o venosas, debido a esto el SPS se ha posicionado como un factor favorecedor de infarto agudo al miocardio (IAM), accidente isquémico transitorio (AIT), neuropatía óptica isquémica, trombosis venosa, entre otros. (3,8,9) Es por esto que dicha entidad debe ser considerada en pacientes con trombosis de origen desconocido. (10) Sokol y otros. ...
... En el contexto clínico del desarrollo de eventos trombóticos, el SPP se encuentra asociado con liberación de catecolaminas debido a que favorecen la agregación plaquetaria, aunque se desconoce el mecanismo exacto. Clínicamente se presenta con episodios de trombosis venosa y arterial en pacientes jóvenes y niños, donde se han descrito casos de eventos isquémicos en miocardio, cerebro y sistema vascular periférico [6][7][8] . ...
Sticky platelet syndrome (SPS) is an autosomal dominant platelet disorder, representing a poorly known and studied cause of both arterial and venous thrombotic events. Its pathogenic mechanism is unknown; its presence can be determined with platelet aggregation and adhesion tests. SPS is responsible for 23% of unexplained arterial and 14% of venous thromboses, in which it is impossible to identify a cause. We describe the case of a 35-year-old woman who presented with acute and progressive hemiparesis of the upper and lower right limbs, with a final diagnosis of SPS. RESUMEN El síndrome de las plaquetas pegajosas (SPP) es un trastorno plaquetario autosómico dominante, causa poco cono-cida y estudiada de eventos trombóticos tanto arteriales como venosos. Su mecanismo patogénico no se conoce; su existencia puede determinarse con pruebas de agregación y adhesión plaquetarias. Es responsable del 23% de las trombosis arteriales inexplicables y del 14% de las venosas, en las que no es posible identificar una causa. Se describe el caso de una paciente de 35 años edad que presentó de forma aguda y progresiva hemiparesia en extremi-dades superior e inferior derechas, con diagnóstico final de SPP. Palabras clave: Síndrome de plaquetas pegajosas. Trombofilia primaria. Trombosis arterial. Trombosis venosa.
... En el contexto clínico del desarrollo de eventos trombóticos, el SPP se encuentra asociado con liberación de catecolaminas debido a que favorecen la agregación plaquetaria, aunque se desconoce el mecanismo exacto. Clínicamente se presenta con episodios de trombosis venosa y arterial en pacientes jóvenes y niños, donde se han descrito casos de eventos isquémicos en miocardio, cerebro y sistema vascular periférico [6][7][8] . ...
Sticky platelet syndrome (SPS) is an autosomal dominant platelet disorder, representing a poorly known and studied cause of both arterial and venous thrombotic events. Its pathogenic mechanism is unknown; its presence can be determined with platelet aggregation and adhesion tests. SPS is responsible for 23% of unexplained arterial and 14% of venous thromboses, in which it is impossible to identify a cause. We describe the case of a 35-year-old woman who presented with acute and progressive hemiparesis of the upper and lower right limbs, with a final diagnosis of SPS.
... En el contexto clínico del desarrollo de eventos trombóticos, el SPP se encuentra asociado con liberación de catecolaminas debido a que favorecen la agregación plaquetaria, aunque se desconoce el mecanismo exacto. Clínicamente se presenta con episodios de trombosis venosa y arterial en pacientes jóvenes y niños, donde se han descrito casos de eventos isquémicos en miocardio, cerebro y sistema vascular periférico [6][7][8] . ...
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Hypercoagulable disorders (HCDs) can be inherited or acquired. An HCD of either etiology increases the chance of venous thromboembolic events (VTEs).
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Patients with an HCD often have the condition discovered only after surgical complications.
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We recommend that patients with a concern for or a known HCD be referred to the appropriate hematological specialist for workup and treatment.
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Tourniquet use in the orthopaedic patient with an HCD is understudied and controversial. We recommend that tourniquets be avoided in the surgical management of patients with an HCD, if possible. When tourniquets are applied to patients with unknown HCD status, close follow-up and vigilant postoperative examinations should be undertaken.
RESUMEN Antecedentes: el síndrome de las plaquetas pegajosas es la segunda trombofilia identificada en México, sólo superada por la mutación 677 C->T en el gen 5,10 –metien-tetrahidrofolato-reductasa. Aproximadamente el 50% de los mestizos mexicanos con un marcador clínico de trombofilia hereditaria tienen el fenotipo del síndrome de las plaquetas pegajosas, frecuentemente asociado con otras trombofilias Objetivo: presentar cinco casos de pacientes con fenotipo de las plaquetas pegajosas en varios miembros de dos generaciones. Material y métodos: se estudiaron los propositii porque tuvieron marcadores clínicos de un estado trombofílico primario y, además, habían padecido un episodio vaso-oclusivo. Resultados: el fenotipo MSF se estudió prospectivamente en dos generaciones en estos cinco propositii, en algunos casos asociados con otras enfermedades proclives a la trombosis. Conclusiones: los estudios de la familia sugieren que el síndrome de las plaquetas pegajosas puede tener un origen genético y heredarse como un rasgo autosómico dominante. Palabras clave: síndrome de plaquetas pegajosas, trombofilia, México, hereditaria. ABSTRACT Background: The sticky platelet syndrome (SPS) phenotype is the second most frequent thrombophilic condition identified in Mexican mestizos with a clinical marker of thrombophilia, only surpassed by the 677 C->T mutation in the 5,10-methylen-tetrahydrofolate-reductase gene; approximately 50% of Mexican mestizo patients with a clinical maker of thrombophilia display the SPS phenotype, frequently as-sociated with other thrombophilic conditions. Objective: To present five kindreds of persons in whom the SPS phenotype presented in several family members. Material and methods: The kindreds were studied because proposition in each one had clinical markers of thrombophilia and had suf-fered a vaso-occlusive episode. Results: The SPS phenotype was prospectively found in two generations in these five kindreds, in some instances associated with other thrombosis-prone conditions.
SUMMARY Objective: Over a 70-month period, 100 consecutive Mexican mestizo individuals with a clinical marker associated with a primary hypercoagulable state were studied. Methods: We prospectively assessed: the sticky platelet syndrome (SPS), the activated protein C resistance (aPCR) phenotype, coagulation protein C activity and antigen, coagulation protein S, antithrombin III, plasminogen, IgG and IgM isotypes of antiphospholipid antibodies, homocysteine levels, the factor V gene Leiden, Cambridge, Hong Kong, and Liverpool mutations, the 677 C—>T mutation in the 5,10-methylenetetrahydrofolatereductase (MTHFR), and the G20210A polymorphism in the 3'-untranslated region of the prothrombin gene. Results: Of the 100 consecutive patients prospectively accrued in the study, only 29% were males. In only 6 individuals could we not record any abnormality, whereas in most individuals (81%), two to five co-existing abnormalities were identified. In a multivariate analysis of the association of all these assesments, the only significant association was found between the factor V Leiden mutation and the aPCR phenotype (r = .495; p < 0.001). Conclusions: These results confirm previous observations on thrombophilia in Mexico underlining that it is a multifactorial disease. They also suggest that the abnormalities detected are not associated to each other.
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.
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.
Leiden and Cambridge factor V coagulation mutations and activated protein C resistance (RaPC) are alterations related with vein and artery thrombosis. In this study we aimed to determine whether RaPC is associated with the presence of Leiden and Cambridge mutation and the frequency of these mutations in the racially mestizo Mexican population.
We included 150 Mexican patients with primary thrombophilia and 100 healthy subjects in this study. RaPC was determined using commercial methods and genotypes FV Leiden and FV Cambridge with PCR-RFLPs.
RaPC was positive in four patients and in one control individual; however, there was no presence of Leiden or Cambridge mutation in the studied group; thus, RaPC was not correlated with the presence of any of the studied mutations.
These results indicate that there are other primary or secondary causes different from those studied, which condition the presence of RaPC. Furthermore, the frequency obtained for RaPC in our thrombophilic population of racially mixed Mexicans is lower compared to that obtained in the Caucasian population, most probably because they are genetically different populations.
The aim of this study was to detect the prevalence of the polymorphisms of growth arrest-specific gene 6 (Gas6; Gas6 c. 834 + 7G > A) in patients with sticky platelet syndrome (SPS). Sticky platelet syndrome is a hereditary, autosomal dominant thrombophilia characterized by platelet hyperaggregation after low concentrations of platelet inducers-adenosine diphosphate (ADP) and epinephrine (EPI). The cause of SPS still remains unknown, but in recent years it was suggested that Gas6 protein may have a potential role in the pathogenesis of SPS. To assess the Gas6 polymorphisms (Gas6 c. 834 + 7G > A), 128 patients with SPS were included in the study and examined by polymerase chain reaction (PCR) method. GG genotype was detected in 63 (49.2%) patients, GA genotype in 53 (41.4%) patients, and AA genotype in 12 (9.4%) patients. The results in controls did not differ significantly compared to patients with SPS. Our findings did not prove allele A to be less associated with thrombosis and that ''prothrombotic'' allele G may be associated with higher risk of thrombosis. We cannot support the idea that Gas6 protein and Gas6 polymorphisms may be associated with thrombosis in SPS.
Sticky platelet syndrome is an autosomal-dominant thrombophilia characterized by platelet hyperaggregability in the presence of adenosine diphosphate or epinephrine. The result clinically can be widespread thromboses, often arterial, in patients without apparent risk factors for thrombotic disease. Limited data exist regarding its role in adverse pregnancy outcomes.
A gravid woman with two previous first-trimester miscarriages presented at 11 weeks of gestation with a deep venous thrombosis. Despite anticoagulation, she developed extensive and progressive arterial and venous thromboses and suffered a fetal demise. A thrombophilia panel was unremarkable, but platelet aggregometry demonstrated hyperactive platelets in the presence of adenosine diphosphate and epinephrine consistent with sticky platelet syndrome.
Sticky platelet syndrome causes arterial thromboses and may be an underappreciated etiology for adverse pregnancy outcomes.
A 48-year-old woman presented with bilateral lower extremity critical limb ischemia. In addition to this, her work-up revealed multiple other thromboembolic insults including cerebral and visceral emboli. Initial laboratory findings were significant for an indeterminate platelet count, secondary to platelet clumping. After appropriate emergent surgical treatment including bilateral lower extremity embolectomy, the patient was empirically anticoagulated with a direct thrombin inhibitor. Further embolic work-up discovered bilateral renal and splenic infarctions as well as a large mobile mitral vegetation. Finally, an upper extremity duplex revealed left axillary, left subclavian, and right internal jugular acute deep vein thromboses. Mitral valve replacement was performed to remove the septic source. A series of hypercoagulability studies was done, and results were positive for lupus anticoagulants. Months after her recovery, the patient was tested and found to be positive for sticky platelet syndrome.
We report a case of a patient who developed clinical symptoms of sticky platelet syndrome (SPS) during free microvascular flap transplantation, following resection of an oral tumor. Multiple arterial thromboses of two free tissue transfers occurred as a probable result of SPS. Diagnosis and treatment of the various forms of SPS are described.