Fc-independent cross-linking of a novel platelet membrane protein by a monoclonal antibody causes platelet activation

A monoclonal antiplatelet antibody (MA-13G8E1) is described that dose- dependently induces platelet aggregation and serotonin release in an Fc- independent fashion. Whereas platelets were equally aggregated by F(ab')2 fragments of this monoclonal antibody (MoAb), its Fab fragments, on the other hand, were inactive, indicating that divalent interaction is an essential requirement to induce platelet activation by MA-13G8E1. In addition, we could show that platelet epitope cross- linking by MA-13G8E1 occurred on the same platelet. MA-13G8E1 stimulated platelet phospholipase C (PLC) and induced activation of protein kinase C (PKC), both of which were almost unaffected by aspirin pretreatment. Furthermore, PLC activation appeared to be a direct antibody-mediated effect, since intracellular Ca2+ rises were not inhibited by EGTA, cytochalasin B, or aggregation-blocking MA-16N7C2 (antiglycoprotein [anti-GP]IIb/IIa). The MA-13G8E1 antigen is constitutively expressed on resting platelets of different species (7,100 +/- 800 molecules per human platelet), but not on other cell types tested. Both immunoprecipitation and affinity isolation by MA- 13G8E1 showed two low-molecular weight proteins (45 and 36 kD), having slightly acidic isoelectric pH levels (4.5 to 5.5) and forming multimolecular complexes. In conclusion, we found an MoAb that is able to induce platelet activation in an Fc-independent fashion. The mechanism involves cross-linking of a hitherto undescribed platelet membrane protein, leading to PLC and PKC stimulation.     

The role of pancreatic venous sampling in the localization of occult insulinomas

The palpation and enucleation of occult insulinomas (less than 15 mm) can be a difficult surgical problem even with good arteriographic localization. In the authors' limited experience, confirmation of arteriographic findings by pancreatic venous sampling provided little additional localizing information. However, if arteriography is negative or equivocal, venous sampling can indicate the segment of pancreas to be "blindly" resected if the adenoma is not palpable. Venous sampling may be misleading in polyendocrine syndromes because of the frequency of multiple adenomas and variable hormone production.     

Seroprevalence of hepatitis B and C viruses in moderate and severe COVID-19 inpatients: A cross-sectional study at a referral center in Mexico

Introduction and ObjectivesThe emergence of SARS-CoV-2, which causes the coronavirus disease (COVID-19) has caused a great impact on healthcare systems worldwide, including hepatitis B and C viruses screening and elimination programs. The high number of COVID-19 hospitalizations represent a great opportunity to screen patients for hepatitis B virus (HBV) and hepatitis C virus (HCV), which was the aim of this study.Material and MethodsCross-sectional, retrospective study performed between April 2020 and 20201 at a referral center in Mexico dedicated to the care of adults with severe/critical COVID-19. We retrieved clinical, demographic, and laboratory results from each patient´s medical records, including antibodies against HCV (anti-HCV), HBV surface antigen (HBsAg), antibodies against the HBV core antigen (anti-HBcAg), and antibodies against HBsAg (anti-HBsAg).ResultsOut of 3620 patients that were admitted to the hospital, 24 (0.66%), 4 (0.11%), and 72 (1.99%) tested positive for anti-HCV, HBsAg, and anti-HBcAg, respectively. Of all seronegative patients, 954 (27%) had undetectable anti-HBsAg and 401 (12%) had anti-HBsAg at protective levels. Blood transfusion was the most relevant risk factor. Only 9.7% of the anti-HBc positive, 25% of the HBsAg positive, and 52% of the anti-HCV positive were aware of their serological status.ConclusionsIn this study we found a prevalence of anti-HCV of 0.66%, HBsAg in 0.11%, and isolated anti-HBcAg in 1.99%. We also found that HBV vaccination coverage has been suboptimal and needs to be reinforced. This study gave us a trustworthy insight of the actual seroprevalence in Mexico, which can help provide feedback to the Hepatitis National Elimination Plan.     

Produits sanguins labiles provenant de donneurs immunisés dans le système HLA. À propos d'un cas d'œdème pulmonaire lésionnel

A case of transfusion-related acute lung injury (TRALI) due to HLA antibodies present in one unit of packed red blood cells led us to discuss the screening of HLA antibodies for female donors having been pregnant, and the use of labile blood products.     

Trabecular bone architecture in female renal allograft recipients-- assessed by computed tomography

BACKGROUND: Osteopenia with decreased bone mineral density (BMD) is a frequent finding in renal allograft recipients. Data concerning the bone architecture in these patients do not exist, however. METHODS: We compared the bone architecture of 33 randomly assigned women (age 49 +/- 12 years), who had received renal allografts 5.6 +/- 5.3 years before the investigation, with 74 women (age 50 +/- 14 years) who were admitted for osteodensitometry. All patients underwent single-energy computed tomography (SEQCT) and a midvertebral high-resolution tomography with computer-assisted analysis of the trabecular vertebral body architecture. RESULTS: Progressive alteration of bone architecture was associated with increasing vertebral height loss of the vertebral body. Height reduction of a vertebral body of more than 15% was associated with a significantly lower BMD (-2.3 +/- 0.8 versus -1.1 +/- 1.1 standard deviations below normal BMD), a lower trabecular bone area (13 +/- 8% versus 42 +/- 22%) and a lower trabecular diameter (1.4 +/- 0.5 mm versus 2.2 +/- 0.8 mm) compared to recipients without height reduction. In comparison to a matched group of patients with similarly reduced BMD (1.1 +/- 1.2 versus 1.2 +/- 1.1 SD below normal BMD), renal allograft recipients showed a lower number of trabecular plates (5.6 +/- 3.1 versus 7.0 +/- 3.7) and a smaller intertrabecular surface (54 +/- 116 mm versus 75 +/- 138 mm). CONCLUSIONS: Alterations of bone architecture in renal allograft recipients were associated with progressive vertebral height loss. Despite similar bone mineral density, differences of bone architecture could be observed between renal allograft recipients and patients with osteoporosis.      

Enabling a person with multiple disabilities and minimal motor behaviour to control environmental stimulation with chin movements

Purpose: To assess whether a young man with multiple disabilities and minimal motor behaviour would learn to control environmental stimulation using chin movements and a mechanical microswitch. Method: The study was carried out according to an ABAB design in which A represented baseline and B intervention phases. The chin movements controlled the stimulation only during the intervention phases. A 2-month post-intervention check was conducted. Results: The man increased the frequency of his chin movements, thus increasing the level of environmental stimulation, during the intervention phases. This performance was maintained at the post-intervention check. Conclusion: The use of chin movements is a practical strategy for enabling individuals with minimal motor movements to control environmental stimulation. Future research should examine whether similar types of movements may enable some individuals to control voice-output communication devices.     

Quality systems and total process control in blood banking

Blood banking has dramatically changed in the past few years. Is the old business hierarchy and medical model for management still workable? How do we want to organize our work today for success in the future? Implementation of quality systems may seem overwhelmingly complex at this time to many blood banking establishments. However, by methodically adhering to the requirements of organization development described in this review, blood centers can achieve goals of quality improvement and TPC. The FDA and the pharmaceuticals and medical device industries have set the direction and provided guidance to blood establishments. The AABB, American Society for Quality Control, the American Society for Training and Development, and numerous other professional organizations can contribute information and materials. The FDA's document on quality assurance and the CFR are the basic texts guiding the approach presented in this paper. The organization's structure and processes may need to be reengineered to meet the requirements of a culture based on quality and process control.     

The heterogeneity of type IIA von Willebrand's disease: studies with protease inhibitors

The absence of large von Willebrand factor (vWF) multimers from plasma is a characteristic of Type IIA von Willebrand's disease (vWD) and is thought to contribute to the clinical expression of this disorder. Recently, three IIA patients have been reported in whom intermediate and large multimers could be restored if blood were collected in 5 mm EDTA, 6 mmol/L N-ethylmaleimide, and 1 mmol/L leupeptin. This suggested that absence of large multimers resulted from in vitro proteolysis. We have now collected blood from ten Type IIA vWD patients in these inhibitors but were not able to detect large multimers in the plasma of any of them. In addition, intermediate-sized multimers were reduced or completely absent in all. The inclusion of inhibitors in the citrate anticoagulant, as compared to citrate alone, was found to increase the relative proportion of intermediate multimers in some patients but had no effect in others, and in none did it restore large multimers to plasma. The results with platelet vWF were more varied. Four patients showed an absence or decrease of large multimers, whereas in seven patients large multimers were present. When compared with citrate anticoagulant alone, the inclusion of inhibitors in the anticoagulant had little or no effect on the platelet multimeric pattern. 1-Deamino-8- D-Arginine Vasopressin (DDAVP) was administered to six patients from five families. Two patients from one family showed complete correction and a third patient showed almost complete correction of her bleeding time. Two patients showed minimal correction and one showed no detectable correction. An increase in multimer size after DDAVP tended to be associated with correction of the bleeding time. However, in no case did the largest multimers appear in plasma even in patients with complete bleeding time correction. The presence or absence of inhibitors in the anticoagulant had little or no effect on the multimeric pattern after DDAVP. These results indicate that Type IIA vWD is a heterogeneous disorder in which absence of largest and intermediate multimers is an in vivo phenomenon.