scholarly journals Heparin-induced thrombocytopenia: further evidence for a unique immune response

Blood ◽  
2012 ◽  
Vol 120 (20) ◽  
pp. 4238-4245 ◽  
Author(s):  
Christian Pötschke ◽  
Sixten Selleng ◽  
Barbara M. Bröker ◽  
Andreas Greinacher

AbstractCardiopulmonary bypass surgery (CPB) is associated with a high incidence of IgG Abs against platelet factor 4/heparin (PF4/H) complexes by day 6 after surgery. These Abs are associated with an immune-mediated adverse drug reaction, heparin-induced thrombocytopenia. Although the early onset of the anti-PF4/H IgG response is compatible with a secondary immune response, the rapid decline of Ab titers thereafter is not. To shed light on the origin of these Abs, in the present study, we prospectively compared the kinetics of these Abs with that of Abs against 2 recall Ags and to that of autoantibodies in 166 CPB patients over 4 months. Surgery induced strong inflammation, as shown by an increase in mean C-reactive protein levels. Consistent with previous studies, anti-PF4/H IgG optical density transiently increased between baseline and day 10 (P < .001; not associated with C-reactive protein levels), followed by a decrease over the next months. In contrast, concentrations of antidiphtheria toxin IgG and antitetanus toxin IgG increased constantly over the 4 months after surgery by 25%-30%. IgG autoantibodies did not change. Therefore, the transient kinetics of the anti-PF4/H IgG response resembled neither that of recall Abs nor that of IgG autoantibodies, but rather showed a unique profile.

2010 ◽  
Vol 67 (11) ◽  
pp. 893-897 ◽  
Author(s):  
Zeljko Lausevic ◽  
Goran Vukovic ◽  
Biljana Stojimirovic ◽  
Jasna Trbojevic-Stankovic ◽  
Vladimir Resanovic ◽  
...  

Background/Aim. Injury-induced anergy is one of the key factors contributing to trauma victims' high susceptibility to sepsis. This group of patients is mostly of young age and it is therefore essential to be able to predict as accurately as possible the development of septic complications, so appropriate treatment could be provided. The aim of this study was to assess kinetics of interleukin (IL) -6 and -10, phospholipase A2- II and C-reactive protein (CRP) in severely traumatized patients and explore the possibilities for early detection of potentially septic patients. Methods. This prospective study included 65 traumatized patients with injury severity score (ISS) > 18, requiring treatment at surgical intensive care units, divided into two groups: 24 patients without sepsis and 41 patients with sepsis. C-reactive protein, IL-6 and -10 and phospholipase A2 group II, were determined within the first 24 hours, and on the second, third and seventh day of hospitalization. Results. Mean values of IL-6 and phospholipase A2-II in the patients with and without sepsis did not show a statistically significant difference on any assessed time points. In the septic patients with ISS 29-35 and > 35 on the days two and seven a statistically significantly lower level of IL-10 was found, compared with those without sepsis and with the same ISS. C-reactive protein levels were significantly higher in septic patients with ISS 18-28 on the first day. On the second, third and seventh day CRP levels were significantly lower in the groups of septic patients with ISS 29-35 and > 35, than in those with the same ISS but without sepsis. Conclusion. Mean levels of CRP on the first day after the injury may be useful predictor of sepsis development in traumatized patients with ISS score 18-28. Mean levels of CRP on the days two, three and seven after the injury may be a useful predictor of sepsis development in traumatized patients with ISS score more than 28. Mean levels of IL-10 on the second and seventh day after the injury may be a useful predictor of sepsis development in traumatized patients with ISS score > 28.


2012 ◽  
Vol 107 (04) ◽  
pp. 717-725 ◽  
Author(s):  
Manali V. Joglekar ◽  
Pedro M. Diez ◽  
Stephen Marcus ◽  
Rui Qi ◽  
Benjamin Espinasse ◽  
...  

SummaryRecent studies have shown that ultra-large complexes (ULCs) of platelet factor 4 (PF4) and heparin (H) play an essential role in the pathogenesis of heparin-induced thrombocytopenia (HIT), an immune-mediated disorder caused by PF4/H antibodies. Because antigenic PF4/H ULCs assemble through non-specific electrostatic interactions, we reasoned that disruption of charge-based interactions can modulate the immune response to antigen. We tested a minimally anticoagulant compound (2-O, 3-O desulfated heparin, ODSH) with preserved charge to disrupt PF4/H complex formation and immunogenicity. We show that ODSH disrupts complexes when added to pre-formed PF4/H ULCs and prevents ULC formation when incubated simultaneously with PF4 and UFH. In other studies, we show that excess ODSH reduces HIT antibody (Ab) binding in immunoassays and that PF4/ODSH complexes do not cross-react with HIT Abs. When ODSH and unfractionated heparin (UFH) are mixed at equimolar concentrations, we show that there is a negligible effect on amount of protamine required for heparin neutralisation and reduced immunogenicity of PF4/UFH in the presence of ODSH. Taken together, these studies suggest that ODSH can be used concurrently with UFH to disrupt PF4/H charge interactions and provides a novel strategy to reduce antibody mediated complications in HIT.Presented in part at the 52nd American Society of Hematology Annual Meeting and Exposition, December 6th, 2010, Orlando, Florida, USA.


2021 ◽  
Author(s):  
N Veyrenche ◽  
A Pisoni ◽  
S Debiesse ◽  
K Bollore ◽  
AS Bedin ◽  
...  

ABSTRACTIntroductionSARS-CoV-2 nucleocapsid antigen (N-Ag) can be detected in the blood of patients with Covid-19. In this study, we used a highly sensitive and specific nucleocapsid-Ag assay to explore the presence of N-Ag in urine during the course of Covid-19, and explore its relationship with the severity of the disease.Material and MethodsUrine and blood samples were collected from 82 patients with a SARS-CoV-2 infection proven by PCR and included in the COVIDotheque. We explored the presence of N-Ag in urine and blood using the AAZ N-Ag test, studied the kinetics of the marker according to the time since the onset of symptoms and evaluated the association between N-Ag levels, clinical severity and inflammation.ResultsIn the first and second weeks of Covid-19, hospitalized patients tested positive for urinary N-Ag (81.25% and 71.79%, respectively) and blood N-Ag (93.75% and 94.87%, respectively). N-Ag levels in urine and blood were moderately correlated with the number of days after the onset of symptoms (r=-0.43, p<0.0001; r=-0.55 p<0.0001, respectively). The follow up of seven SARS-CoV-2 infected patients confirmed the waning of N-Ag in urine and blood over the course of the disease. High urinary N-Ag levels were associated with the absence of SARS-CoV-2 nucleocapsid-IgG (N-IgG), admission in intensive care units, high C-reactive protein levels, lymphopenia, eosinopenia, and high lactate dehydrogenase (LDH).ConclusionOur study demonstrate that N-Ag is present in the urine of patients hospitalized in the early phase of Covid-19. As a direct marker of SARS-CoV-2, urinary N-Ag reflects the dissemination of viral compounds in the body. Urine N-Ag is a promising marker to predict adverse evolution of SARS-CoV-2 infections.


2021 ◽  
Vol 334 ◽  
pp. 109339
Author(s):  
Sergey D. Varfolomeev ◽  
Alexander A. Panin ◽  
Valeriy I. Bykov ◽  
Svetlana B. Tsybenova ◽  
Sergey V. Zhuravel ◽  
...  

2021 ◽  
Vol 496 (1) ◽  
pp. 44-47
Author(s):  
S. D. Varfolomeev ◽  
S. V. Zhuravel ◽  
A. A. Panin ◽  
L. V. Shogenova ◽  
V. I. Bykov ◽  
...  

VASA ◽  
2015 ◽  
Vol 44 (3) ◽  
pp. 0187-0194 ◽  
Author(s):  
Xiaoni Chang ◽  
Jun Feng ◽  
Litao Ruan ◽  
Jing Shang ◽  
Yanqiu Yang ◽  
...  

Background: Neovascularization is one of the most important risk factors for unstable plaque. This study was designed to correlate plaque thickness, artery stenosis and levels of serum C-reactive protein with the degree of intraplaque enhancement determined by contrast-enhanced ultrasound. Patients and methods: Contrast-enhanced ultrasound was performed on 72 carotid atherosclerotic plaques in 48 patients. Contrast enhancement within the plaque was categorized as grade 1, 2 or 3. Maximum plaque thickness was measured in short-axis view. Carotid artery stenosis was categorized as mild, moderate or severe. Results: Plaque contrast enhancement was not associated with the degree of artery stenosis or with plaque thickness. Serum C-reactive protein levels were positively correlated with the number of new vessels in the plaque. C-reactive protein levels increased in the three groups(Grade 1: 3.72±1.79mg/L; Grade 2: 7.88±4.24 mg/L; Grade 3: 11.02±3.52 mg/L), with significant differences among them (F=10.14, P<0.01), and significant differences between each two groups (P<0.05). Spearman’s rank correlation analysis showed that serum C-reactive protein levels were positively correlated with the degree of carotid plaque enhancement (Rs =0.69, P<0.01). Conclusions: The combination of C-reactive protein levels and intraplaque neovascularization detected by contrast-enhanced ultrasound may allow more accurate evaluation of plaque stability.


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