Hermansky–Pudlak syndrome (HPS) is characterized by oculocutaneous albinism, excessive bleeding, and often additional symptoms. Variants in ten different genes have been involved in HPS. However, ...some patients lack variants in these genes. We aimed to identify new genes involved in nonsyndromic or syndromic forms of albinism.
Two hundred thirty albinism patients lacking a molecular diagnosis of albinism were screened for pathogenic variants in candidate genes with known links to pigmentation or HPS pathophysiology.
We identified two unrelated patients with distinct homozygous variants of the BLOC1S5 gene. Patients had mild oculocutaneous albinism, moderate bleeding diathesis, platelet aggregation deficit, and a dramatically decreased number of platelet dense granules, all signs compatible with HPS. Functional tests performed on platelets of one patient displayed an absence of the obligate multisubunit complex BLOC-1, showing that the variant disrupts BLOC1S5 function and impairs BLOC-1 assembly. Expression of the patient-derived BLOC1S5 deletion in nonpigmented murine Bloc1s5-/- melan-mu melanocytes failed to rescue pigmentation, the assembly of a functional BLOC-1 complex, and melanosome cargo trafficking, unlike the wild-type allele.
Mutation of BLOC1S5 is disease-causing, and we propose that BLOC1S5 is the gene for a new form of Hermansky–Pudlak syndrome, HPS-11.
The association between endometriosis and autoimmune diseases is well known, however no acquired platelet function defect has been described so far. We describe the case of two patients with ...endometriosis associated with an antiplatelet glycoprotein VI (anti-GPVI) antibody. The two women with deep pelvic endometriosis associated with secondary infertility presented a mild bleeding tendency, a deficient platelet aggregation response to collagen, convulxin or CRP and a severe GPVI deficiency. Immunoblot revealed a combined FcRγ deficiency but no indication of GPVI cleavage. In the first case, platelet count was normal and an anti-GPVI IgG was detected in plasma. A first corticosteroids administration normalized
platelet functions but further administrations were unsuccessful. Three IVF attempts failed. Conservative laparoscopic surgery was carried out after antifibrinolytic treatment without bleeding. The second case presented with a history of moderate thrombocytopenia and a weak anti-GPVI in the context of infertility and autoimmune disease, the Sjögren syndrome resolved after corticosteroids and hydroxychloroquine treatment. Acquired GPVI deficiencies are rare. It would be useful to determine whether the association with endometriosis is coincidental or not by more systematic investigations. It does not seem that in these patients, GPVI deficiency is associated with an increased risk of bleeding.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Defining hemostatic profile for preterm infants is a challenge when severe bleedings are frequent.
The aim was to define the hemostatic profile at birth of infants with spontaneous prematurity and to ...evaluate whether characteristic profiles can predict the development of intraventricular hemorrhage (IVH) in prematures.
We included 122 newborns with a median age of 31
gestational age (GA) 29
;34
and median weight of 1145 g 785;1490. Levels of fibrinogen, factor II (FII) and factor V (FV) rose with GA (p = 0.017,p = 0.009, p = 0.001). In the group of 23
- 28
GA, the 5th percentile was defined as 0.6 g/L for fibrinogen, 15 IU/dL for FII and 16 IU/dL for factor V (n = 30). In the group of 29
-32
GA, the 5th percentile was defined as 1.0 g/L for fibrinogen, 24 IU/dL for FII and 41 IU/dL for factor V (n = 46). In the group of 33
-36
GA, the 5th percentile was defined as 1.0 g/L for fibrinogen, 24 IU/dL for FII and 30 IU/dL for factor V (n = 46). Level of fibrinogen was higher in case of vaginal delivery and lower in case of IUGR. Only lower level of FV at birth was significantly associated with IVH (63.5 46.0; 76.5 vs 74.0 58.0; 89.0, p = 0.026) with an unadjusted OR per SD increase in FV of 0.57 (95%CI, 0.34 to 0.96). After adjustment for age, the association between FV level and IVH was slightly attenuated (adjusted OR, 0.70; 95%CI, 0.40 to 1.23) but remained not significant (p = 0.22).There was no correlation with FII and fibrinogen.
We can define hemostastic profile of prematures and corroborate references ranges for studied parameters. Further large studies are still called for, to correlate the grade of hemorrhage and the factor V level at birth.
Summary Background Apoptosis-related molecules may contribute to left ventricular (LV) remodeling after myocardial infarction (MI). To validate this hypothesis, we evaluated the relation between ...circulating plasma levels of soluble Fas ligand (sFas-L) and LV remodeling in patients post-MI. Methods and results This prospective multicenter study included 246 patients with a first anterior Q-wave MI. Serial echocardiographic studies were performed at hospital discharge and 3 and 12 months after MI; quantitative analysis was performed at a core echocardiography laboratory. Clinical follow-up was performed at 3 years post-MI. Blood samples to measure sFas-L were obtained at 1 month after MI. Median sFas-L level was 50.2 pg/mL. During the 1 year follow-up, LV remodeling was documented by a significant increase in LV volumes. LV end-diastolic and end-systolic volumes at baseline, 3 months, and 12 months after MI did not differ according to sFas-L levels; changes in LV volumes were not associated with sFas-L levels. By multivariate analysis, 2 variables were independently associated with LV remodeling: B-type natriuretic peptide (BNP) ( p = 0.008) and baseline ejection fraction ( p = 0.02). sFas-L levels were not associated with cardiovascular death or rehospitalization for heart failure at 3 years; conversely, high levels of BNP were associated with worse clinical outcome. Conclusions Soluble Fas-L levels are not associated with LV remodeling after MI. Further research is needed to identify apoptotic markers that may be associated with outcome post-MI.
This is the first report of an early association between elevated fibrinogen and asymptomatic unicentric Castleman's disease (CD). A 49-year-old asymptomatic female who was serving as a normal ...control in an unrelated study was incidentally found to have significantly elevated levels of plasma fibrinogen. Upon further investigation with computer tomography scans and magnetic resonance imaging, the woman was found to have a mobile mass in the abdominal region which was surgically removed. Based on histological analysis, a diagnosis of CD was made. At four-month follow-up, no additional signs of CD were present and fibrinogen levels returned to the normal range. This report, therefore, signifies the importance for physicians to consider unicentric CD in the differential diagnosis when patients present with elevated levels of plasma fibrinogen. Awareness of this diagnostic possibility may lead to increased early diagnosis of CD before symptoms become apparent, and provide a marker candidate for CD activity that may assist in monitoring treatment success. J Clin Exp Hematop 54(1): 85-88, 2014