Tag: platelets

Serological Biomarkers at Hospital Admission Are Not Related to Long-Term Post-COVID Fatigue and Dyspnea in COVID-19 Survivors

Abstract:

Objective: The aim of this study was to investigate the association between serological biomarkers at the acute phase of infection at hospital admission with the development of long-term post-COVID fatigue and dyspnea.

Methods: A cohort study including patients hospitalized due to COVID-19 in one urban hospital of Madrid (Spain) during the first wave of the outbreak (from March 20 to June 30, 2020) was conducted. Hospitalization data, clinical data, and eleven serological biomarkers were systematically collected at hospital admission. Patients were scheduled for an individual telephone interview after hospital discharge for collecting data about the presence of post-COVID fatigue and dyspnea.

Results: A total of 412 patients (age: 62 years, standard deviation: 15 years; 47.5% women) were assessed with a mean of 6.8 and 13.2 months after discharge. The prevalence of post-COVID fatigue and dyspnea was 72.8% and 17.2% at 6 months and 45.4% and 13.6% at 12 months after hospital discharge, respectively. Patients exhibiting post-COVID fatigue at 6 or 12 months exhibited a lower hemoglobin level, higher lymphocyte count, and lower neutrophil and platelets counts (all, p < 0.05), whereas those exhibiting post-COVID dyspnea at 6 or 12 months had a lower platelet count and lower alanine transaminase, aspartate transaminase, and lactate dehydrogenase (LDH) levels (all, p < 0.05) than those not developing post-COVID fatigue or dyspnea, respectively. The multivariate regression analyses revealed that a lower platelet count and lower LDH levels were associated but just explaining 4.5% of the variance, of suffering from post-COVID fatigue and dyspnea, respectively.

Conclusion: Some serological biomarkers were slightly different in patients exhibiting post-COVID fatigue or dyspnea, but they could not explain the long-COVID problems in those patients.

Source: Fernández-de-Las-Peñas C, Ryan-Murua P, Rodríguez-Jiménez J, Palacios-Ceña M, Arendt-Nielsen L, Torres-Macho J. Serological Biomarkers at Hospital Admission Are Not Related to Long-Term Post-COVID Fatigue and Dyspnea in COVID-19 Survivors. Respiration. 2022 Apr 5:1-8. doi: 10.1159/000524042. Epub ahead of print. PMID: 35381597. https://www.karger.com/Article/FullText/524042 (Full text)

Comparative Analysis of Extracellular Vesicles in Patients with Severe and Mild Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Myalgic encephalomyelitis, or chronic fatigue syndrome (ME/CFS) is a serious disease whose cause has yet to be identified. Objective markers of the disease are also not well understood and would serve as important tools in diagnosis and management.

One potential biomarker or transmitter of immune signals in ME/CFS is the extracellular vesicle (EV) compartment. These small, membrane bound particles have been shown to play a key role in intercellular signaling. Our laboratory has focused on methods of detection of EVS in clinical samples. In this study we explored whether the prevalence of EVs in the plasma of participants with mild or severe ME/CFS differed from the plasma of healthy control participants. By staining for multiple cell surface molecules, plasma EVs could be fingerprinted as to their cell of origin.

Our study revealed a significant correlation between severe ME/CSF and levels of EVs bearing the B cell marker CD19 and the platelet marker CD41a, though these changes were not significant after correction for multiple comparisons. These findings point to potential dysregulation of B cell and platelet activation or homeostasis in ME/CFS, which warrants validation in a replication cohort and further exploration of potential mechanisms underlying the association.

Source: Bonilla H, Hampton D, Marques de Menezes EG, Deng X, Montoya JG, Anderson J, Norris PJ. Comparative Analysis of Extracellular Vesicles in Patients with Severe and Mild Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Front Immunol. 2022 Mar 4;13:841910. doi: 10.3389/fimmu.2022.841910. PMID: 35309313; PMCID: PMC8931328. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8931328/ (Full text)

Platelet Storage Pool Deficiency and Elevated Inflammatory Biomarkers Are Prevalent in Postural Orthostatic Tachycardia Syndrome

Abstract:

A significant number of postural orthostatic tachycardia syndrome (POTS) patients have platelet delta granule storage pool deficiency (δ-SPD).

The etiology of POTS is unknown but a number of laboratories, including ours, have reported elevations of G-protein-coupled adrenergic receptor and muscarinic acetylcholine receptor autoantibodies in POTS patients, detected by a variety of techniques, suggesting that the disorder is an autoimmune condition. Thus, it could also be considered an inflammatory disease.

In a pilot study, we investigated a limited number of platelet-related cytokines and chemokines and discovered many that were elevated.

This case–control study validates our pilot study results that POTS patients have an activated innate immune system.

Plasma of 35 POTS patients and 35 patients with unexplained bleeding symptoms and categorized as “non-POTS” subjects was analyzed by multiplex flow cytometry to quantify 16 different innate immune system cytokines and chemokines. Electron microscopy was used to quantify platelet dense granules.

Ten of 16 biomarkers of inflammation were elevated in plasma from POTS patients compared to non-POTS subjects, with most of the differences extremely significant, with p values < 0.0001.

Of particular interest were elevations of IL-1β and IL-18 and decreased or normal levels of type 1 interferons in POTS patients, suggesting that the etiology of POTS might be autoinflammatory.

All POTS patients had δ-SPD. With a growing body of evidence that POTS is an autoimmune disease and having elevations of the innate immune system, our results suggest a potential T-cell-mediated autoimmunity in POTS characteristic of a mixed-pattern inflammatory disease similar to rheumatoid arthritis.

Source: Gunning WT, Kramer PM, Cichocki JA, Karabin BL, Khuder SA, Grubb BP. Platelet Storage Pool Deficiency and Elevated Inflammatory Biomarkers Are Prevalent in Postural Orthostatic Tachycardia Syndrome. Cells. 2022; 11(5):774. https://doi.org/10.3390/cells11050774  https://www.mdpi.com/2073-4409/11/5/774/htm (Full text)

Combined triple treatment of fibrin amyloid microclots and platelet pathology in individuals with Long COVID/ Post-Acute Sequelae of COVID-19 (PASC) can resolve their persistent symptoms

Abstract:

We recognise that fibrin(ogen) amyloid microclots and platelet hyperactivation, that we have previously observed in COVID-19 and Long COVID/Post-Acute Sequelae of COVID-19 (PASC) patients, might form a suitable set of foci for the clinical treatment of the symptoms of long COVID/PASC. We first report on the comorbidities and symptoms found in a cohort of 845 South African Long COVID/PASC patients who filled in the South African Long COVID/PASC registry, of which hypertension and high cholesterol levels (dyslipidaemia) were the most important comorbidities. The gender balance (70% female) and the most commonly reported Long COVID/PASC symptoms (fatigue, brain fog, loss of concentration and forgetfulness, shortness of breath, as well as joint and muscle pains) were comparable to those reported elsewhere. This suggests that our sample was not at all atypical. Using a previously published scoring system for fibrin amyloid microclots and platelet pathology, we analysed blood samples from 70 patients, and report the presence of significant fibrin amyloid microclots and platelet pathology in all cases; these were associated with Long COVID/PASC symptoms that persisted after the recovery from acute COVID-19.

A subset of 24 patients was treated with one month of dual antiplatelet therapy (DAPT) (Clopidogrel 75mg/Aspirin 75mg) once a day, as well as a direct oral anticoagulant (DOAC) (Apixiban) 5 mg twice a day. A proton pump inhibitor (PPI) pantoprazole 40 mg/day was also prescribed for gastric protection. Such a regime must only be followed under strict and qualified medical guidance to obviate any dangers, especially haemorrhagic bleeding, and of the therapy as a whole. Thromboelastography (TEG®) was used to assist in determining their clotting status.

Each of the 24 treated cases reported that their main symptoms were resolved and fatigue as the main symptom was relieved, and this was also reflected in a decrease of both the fibrin amyloid microclots and platelet pathology scores. Nine patients were genotyped for genetic variation in homocysteine metabolism implicated in hypertension, a common COVID-19 co-morbidity reported in both patients found to be homozygous for the risk-associated MTHFR 677 T-allele. Fibrin amyloid microclots that block capillaries and inhibit the transport of O2 to tissues, accompanied by platelet hyperactivation, provide a ready explanation for the symptoms of Long COVID/PASC. The removal and reversal of these underlying endotheliopathies provide an important treatment option that seems to be highly efficacious, and warrants controlled clinical studies.

Source: Pretorius, Etheresia & Venter, Chantelle & Laubscher, Gert & Kotze, Maritha & Moremi, Kelebogile & Oladejo, Sunday & Watson, Liam & Rajaratnam, Kanshu & Watson, Bruce & Kell, Douglas. Combined triple treatment of fibrin amyloid microclots and platelet pathology in individuals with Long COVID/ Post-Acute Sequelae of COVID-19 (PASC) can resolve their persistent symptoms. Preprint from Research Square, 28 Dec 2021 https://assets.researchsquare.com/files/rs-1205453/v1_covered.pdf?c=1640805028 (Full text)

Is chronic fatigue syndrome associated with platelet activation?

Abstract:

Chronic fatigue syndrome (CFS) is a debilitating condition that has no known aetiology or pathophysiology. Recent investigations by other workers have suggested that individuals with CFS may have a hypercoagulable state. This study investigated various aspects of platelet activation and function in 17 patients with CFS and in 16 age-matched and sex-matched healthy controls. Platelet aggregation, platelet volume and coagulation tests were performed.

Platelet aggregation was investigated by means of the photometric changes using citrated platelet-rich plasma, whole blood aggregation was calculated as the percentage fall in single platelet counts and the coagulation tests were performed on an automatic microcentrifugal analyser.A trend was observed for the patients to have lower aggregation results and a reduced mean platelet volume. However, this only reached statistical significance for one result; the rate of the aggregation slope by 1.0 microg/ml collagen [CFS patients, 18 (9-28) versus controls, 32.5 (19-36); Mann-Whitney U test, P = 0.029].

No significant differences were found for any of the measurements of coagulation. These results are in contrast to previously reported findings. However, due to the heterogeneous nature of the disease, and the resulting lifestyles of the patients, caution should be taken when comparing one group of patients with another. Nevertheless, we certainly found no evidence of increased platelet activation or of a hypercoagulable state in patients with CFS and, on the basis of these results, anti-platelet or anti-coagulant therapy is not warranted.

 

Source: Kennedy G, Norris G, Spence V, McLaren M, Belch JJ. Is chronic fatigue syndrome associated with platelet activation? Blood Coagul Fibrinolysis. 2006 Mar;17(2):89-92. https://www.ncbi.nlm.nih.gov/pubmed/16479189