1,721,045 research outputs found
Inherited thrombocytopenias frequently diagnosed in adults.
No full textThe diagnosis of inherited thrombocytopenias is difficult for many reasons. First, as all rare diseases, they are little known by clinicians who, therefore, tend to suspect the most common forms. Secondly, making a definite diagnosis often requires complex laboratory techniques that are available only in a few centers. Finally, half of patients have forms that have not yet been described. As a consequence, many patients with inherited thrombocytopenias are misdiagnosed with immune thrombocytopenia and are at risk of receiving futile treatments. Misdiagnosis is particularly frequent in patients whose low platelet count is discovered in adult life, because in these cases even the inherited origin of thrombocytopenia may be missed. Making promptly the correct diagnosis is important since we recently learned that some forms of inherited thrombocytopenia predispose to other illnesses, as leukemia or kidney failure, and affected subjects therefore require close surveillance and, if necessary, prompt treatments. Moreover, medical treatment can increase platelet count in specific disorders, and affected subjects can therefore receive drugs instead of platelet transfusions when selective surgery is required. In this review we will discuss how to suspect, diagnose and manage inherited thrombocytopenias, with particular attention to the forms that frequently present in adults. Moreover, we describe four recently identified disorders that belong to this group of disorders often diagnosed in adults: MYH9-related disease, monoallelic Bernard-Soulier syndrome, ANKRD26-related thrombocytopenia and familial platelet disorder with predisposition to acute leukemia
Inherited thrombocytopenia: from gene to therapy
No full textBACKGROUND AND OBJECTIVES:
Inherited thrombocytopenias are a heterogeneous group of rare diseases characterized by a reduced number of blood platelets. Some of these diseases are exclusive to megakaryocytes and platelets, while in others the pathology extends to other cell types. Although the defective genes, coding for membrane glyoproteins, cytoskeleton components and intracellular signaling pathways, as well as transcription factors, have been identified in most cases, the pathophysiology of these disorders is often unknown. This review describes recent contributions to clinical and diagnostic aspects, biology and treatments of familial thrombocytopenias.
EVIDENCE AND INFORMATION SOURCES:
The information presented here derives from literature and the experience of the authors. The most relevant studies are critically analyzed and discussed.
STATE OF ART:
The clinical and laboratory features of most of the inherited thrombocytopenias have been reviewed. The different forms have been classified into 3 groups depending on platelet volume. Although this criterion is not completely satisfactory, it is one of the most useful in diagnostic algorithms. We report on recent advances in Wiskott-Aldrich and Bernard-Soulier syndromes, as well as in MYH9-related diseases, a new nosological entity that groups old distinct forms known as May-Hegglin anomaly, Sebastian, Fetchner, and Epstein syndromes. Other, less frequent forms are also discussed, including non-syndromic forms of mild thrombocytopenia that are genetically heterogeneous.
PERSPECTIVES:
In the past, inherited thrombocytopenias were considered exceedingly rare and the number of well-defined forms was very small. In the last few years, the widespread diffusion of electronic cell counters has allowed these conditions to be detected more frequently and several new entities have been identified through the co-ordinated efforts of physicians, biologists and geneticists. The pathogenesis of many new and old forms is being unraveled, thus providing insights on the molecular basis of platelet production and function. This knowledge will be a valuable resource for clinicians in the diagnostic approaches to such disorders
Inherited thrombocytopenia: from gene to therapy
No full textBACKGROUND AND OBJECTIVES:
Inherited thrombocytopenias are a heterogeneous group of rare diseases characterized by a reduced number of blood platelets. Some of these diseases are exclusive to megakaryocytes and platelets, while in others the pathology extends to other cell types. Although the defective genes, coding for membrane glyoproteins, cytoskeleton components and intracellular signaling pathways, as well as transcription factors, have been identified in most cases, the pathophysiology of these disorders is often unknown. This review describes recent contributions to clinical and diagnostic aspects, biology and treatments of familial thrombocytopenias.
EVIDENCE AND INFORMATION SOURCES:
The information presented here derives from literature and the experience of the authors. The most relevant studies are critically analyzed and discussed.
STATE OF ART:
The clinical and laboratory features of most of the inherited thrombocytopenias have been reviewed. The different forms have been classified into 3 groups depending on platelet volume. Although this criterion is not completely satisfactory, it is one of the most useful in diagnostic algorithms. We report on recent advances in Wiskott-Aldrich and Bernard-Soulier syndromes, as well as in MYH9-related diseases, a new nosological entity that groups old distinct forms known as May-Hegglin anomaly, Sebastian, Fetchner, and Epstein syndromes. Other, less frequent forms are also discussed, including non-syndromic forms of mild thrombocytopenia that are genetically heterogeneous.
PERSPECTIVES:
In the past, inherited thrombocytopenias were considered exceedingly rare and the number of well-defined forms was very small. In the last few years, the widespread diffusion of electronic cell counters has allowed these conditions to be detected more frequently and several new entities have been identified through the co-ordinated efforts of physicians, biologists and geneticists. The pathogenesis of many new and old forms is being unraveled, thus providing insights on the molecular basis of platelet production and function. This knowledge will be a valuable resource for clinicians in the diagnostic approaches to such disorders
Inherited thrombocytopenias: molecular mechanisms
No full textEach megakaryocyte forms 10(3) platelets and 10(11) platelets are replenished daily. The unique and amazing mechanisms that allow megakaryocytes to become giant and polyploid and to release such a large number of platelets are still poorly understood. The study of inherited thrombocytopenias offers the possibility to gain new information on these processes because several different forms, deriving from defective megakaryocytic commitment, differentiation, maturation, or platelet formation, have been identified. Moreover, in the presence of some genetic defects, megakaryocytes produce platelets with a shortened life span. In this review, we summarize what we have learned about inherited thrombocytopenias in the last few years
The role of plasma fibronectin in platelet adhesion to collagen.
No full textHuman washed platelets were eluted from columns of Sepharose 4B linked to different preparations of collagen in order to evaluate cell adhesion. Collagen preparations characterized by low and high affinity toward platelets were identified. In our experiments, fibronectin purified from human plasma modified platelet adhesiveness, though not dramatically. When washed platelets, resuspended in a buffer containing fibronectin, were filtered on a low-affinity collagen-Sepharose, a significant increase in their adhesion occurred. A similar modification could be observed when platelets were allowed to adhere to the same collagen-Sepharose preconditioned with fibronectin. The effect of fibronectin was otherwise negligible when the high-affinity collagen was used for the experiments
Why the disorder induced by GATA1 Arg216Gln mutation should be called "X-linked thrombocytopenia with thalassemia" rather than "X-linked gray platelet syndrome"
No full textno abstrac
Effect of a monoclonal antibody against GPs IIb-IIIa on platelet aggregation and ATP secretion
No full textmurine monoclonal antibody against glycoproteins IIb-IIIa of platelet membrane completely abolished platelet aggregation induced by epinephrine, arachidonic acid, and low concentration of collagen and thrombin, but it had only minor inhibitory effects on aggregation induced by ADP, higher amounts of collagen and thrombin, and these agents combined in pairs. The simultaneous studies of aggregation and ATP secretion demonstrated that aggregation plays an essential role in stimulating the platelet-release reaction, except for the thrombin-induced ATP secretion that seems to be largely dependent on fibrinogen binding to platelet surfac
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