Elevated platelet count, C-reactive protein and thromboxane analog-induced platelet aggregation in patients with Gulf War veterans’ illnesses

Abstract

A previous study of Gulf War veteran's illnesses (GWVI) observed evidence of platelet activation in a majority of patients with GWVI. To further characterize platelet function, we studied 43 patients (40 men) with GWVI (GWVI+) and 21 veterans who served concurrently in the Gulf War but who lacked criteria for GWVI (GWVI-). All participants were free of infection and known inflammatory diseases. Studies performed included platelet count, immature platelet fraction (IPF), plasma thrombopoietin (TPO), C-reactive protein (CRP), platelet aggregation and ATP secretion in response to six agonists, and spontaneous aggregation. Platelet counts and CRP were significantly elevated in GWVI+ compared to GWVI- patients without elevation in IPF or TPO. Platelet aggregation did not differ between GWVI+ and GWVI- patients except for spontaneous aggregation that was significantly greater in GWVI+ patients. Platelet ATP secretion was similar in the two groups, except the response to 50 μmol/l thrombin receptor agonist peptide 6 (TRAP 6) was significantly greater in GWVI+ patients. When platelet aggregation was analyzed in relation to CRP, the response to 0.5 μmol/l U46619 was significantly greater in patients whose CRP was at least 2 μg/ml. Therefore, GWVI+ patients had elevated platelet counts, spontaneous aggregation, TRAP 6-induced secretion, and CRP, but no impairment of platelet function. The increased platelet counts and U46619-induced aggregation appear to be consequences of an underlying inflammatory state in GWVI.

Reduced Human Leukocyte Antigen (HLA) Protection in Gulf War Illness (GWI)

“…All the evidence from this study points to an enhanced vulnerability (or lack of protection) of the GWI veterans and, conversely, a reduced vulnerability (or additional protection) of the healthy veterans who served in the Gulf War but did not suffer from GWI. Collectively, our findings are in keeping with other evidence for an immune dysfunction in GWI ( Broderick et al, 2012 , 2013; Craddock et al, 2015 , Hotopf et al, 2000 , Israeli, 2012 , Moss, 2013 , Toubi, 2012 , Whistler et al, 2009 ), in addition to other factors, including inflammatory components ( Broderick et al, 2012 , 2013; Johnson et al, 2013 ), mitochondria dysfunction ( Koslik et al, 2014 ) and genetic variants regarding butyrylcholinesterase enzyme activity ( Steele et al, 2015 ). In fact, our findings provide a genetic susceptibility framework within which environmental triggers (e.g.…”

“…The results of our study simply add a genetic susceptibility framework within which the effects of the factors above could be interpreted and investigated in future work. The nature of this postulated protection is likely to relate to autoimmune as well as inflammatory processes, since HLA has been implicated in both ( Trowsdale and Knight, 2013 , Johnson et al, 2013 , Blackwell et al, 2009 ). In addition, HLA genetic underpinnings in immune responses to vaccines have been well established ( Ovsyannikova et al, 2006 , Ovsyannikova and Poland, 2011 , Poland et al, 2007 , Poland et al, 2008a , Poland et al, 2008b ).…”

Gulf war illness-related chemicals increase CD11b/c+ monocyte infiltration into the liver and aggravate hepatic cholestasis in a rodent model

“…Several clinical studies reported elevated markers of inflammation in veterans with GWI symptoms. Thus, elevated platelet count, C-reactive protein and thromboxane analog-induced platelet aggregation suggested increased vascular inflammation in veterans suffering from GWI 29 even though the results of this pilot study were not fully confirmed in a larger study 16 . A study that measured the levels of several cytokines in GWI-affected subjects found TNFα to be among the most significant cytokines associated with Gulf War syndrome 15 .…”

Blood Biomarkers of Chronic Inflammation in Gulf War Illness

“…Kelsall, et al [ 20 ] reported evidence of inflammation (elevated erythrocyte sedimentation rate, C-reactive protein, or leucocyte count) in Australian Veterans of the Gulf War who had multisymptom illness, but only pooled biomarker data was published. A previous study carried out in our laboratory also found higher blood CRP, plus elevated platelet counts and thromboxane analog-stimulated platelet aggregation, in deployed veterans with GWI compared to deployed veterans without GWI [ 21 ]. The results of this study stimulated evaluation of a larger cohort of Gulf War Veterans to determine if significant blood biomarker differences exist between veterans with GWI and without GWI as defined by accepted symptomatic criteria [ 22 ].…”