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Hematological problems in the neonate
Published in Prem Puri, Newborn Surgery, 2017
Andrea M. Malone, Owen P. Smith
May–Hegglin anomaly (MHA), Fechtner syndrome, Sebastian platelet syndrome, and Epstein syndrome constitute a group of related disorders with autosomal dominant inheritance and giant platelets.19 Thrombocytopenia is mild; bleeding is infrequent and rarely life-threatening. Döhle-like inclusions within granulocytic cells are often seen on the blood smear. These disorders can also be associated with sensorineural deafness, glomerulonephritis, and cataracts. Platelet function has been reported to be normal in some and impaired in others.
Structure and function of the open canalicular system – the platelet’s specialized internal membrane network
Published in Platelets, 2018
Maria V. Selvadurai, Justin R. Hamilton
Limited information on OCS function can be gleaned from human conditions. There are a number of clinical syndromes where abnormalities in the OCS have been documented, including some conditions that involve bleeding or thrombotic sequelae. However, platelets from patients with each of these conditions have a number of other structural abnormalities, making it difficult to ascertain the specific contribution of the OCS defect, if any, to any altered platelet function. For example, a dilated, hypertrophic OCS is seen in platelets from patients with Bernard–Soulier syndrome (BSS; Figure 3). BSS is the result of an abnormality in the gene encoding the GPIb (or occasionally GPIX) component of the GPIb/IX/V receptor complex and manifests as a bleeding disorder (46). More than 100 BSS-causing mutations in these genes have been identified, which impair either the expression of the receptor complex at the plasma membrane or the ability of the receptor to interact with von Willebrand factor (47). Yet, in addition to the OCS defect, platelets from these patients are also giant, exhibit disorganized microtubules, and have sparse or even absent granulation. A similar phenotype is observed in platelets from patients with MYH9-related disorders (e.g. May–Hegglin anomaly, Epstein syndrome, Fechtner syndrome). As with BSS, platelets from these patients exhibit not only a dilated and hypertrophic OCS, but also a pronounced macrothrombocytopenia and marked agranularity (17,48,49) (Figure 3). Intriguingly, Budd–Chiari syndrome, a rare prothrombotic condition characterized by hepatic vein or inferior vena cava thrombosis (50), also results in platelets with dilation and hypertrophy of the OCS (51). Yet, again, multiple other platelet ultrastructural defects are observed, including a general lack of organelle content (Figure 3). Finally, abnormal linkage of storage granules to the OCS has been implicated in alpha–delta platelet storage pool deficiency. In an ultrastructural study of multiple familial cases of the disease, it was found that alpha and dense granules were replaced by empty vacuolar structures in platelets from these patients, and that many of these vacuoles were connected to the OCS, suggesting that extraneous connections between the granules and OCS result in the loss of granule contents to the cell exterior in the absence of platelet activation (52). Given the lack of examples of a specific OCS defect in human platelets, direct evidence of OCS function has been limited to emerging information derived from genetically modified mouse models.