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Since March 2021, cases with unusual clots, particularly cerebral venous sinus thrombosis and splanchnic vein thrombosis, have been reported worldwide following adenoviral vector-based coronavirus disease 2019 (COVID-19) vaccination. This entity has been termed vaccine-induced thrombotic thrombocytopenia (VITT). We report a 23-year-old healthy female who developed seizures, altered sensorium, and left hemiparesis, 20 days after receiving the first dose of adenoviral vector-based COVID-19 vaccine "Covishield™." The patient had transient thrombocytopenia. The D-dimer level was 2460 ng/mL. Magnetic resonance imaging (MRI) demonstrated occlusion of M2 segment of the middle cerebral artery and cerebral infarction. Platelet factor-4 antibodies level was normal. Treatment with aspirin and antiepileptic drugs resulted in a remarkable recovery. This is the first Indian case report of ischemic stroke and transient thrombocytopenia following SARS-CoV-2 ChAdOx1 nCoV-19 vaccination. Our case had clinical features consistent with the diagnosis of probable VITT. Familiarity with VITT is crucial because timely treatment with non-heparin anticoagulants and intravenous immunoglobulin improves the outcome., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Family Medicine and Primary Care.)

Objectives: The goal of this exploratory study is to determine if urine:serum fractional excretion ratios can outperform the corresponding urinary biomarker proteins in identifying active renal disease in systemic lupus erythematosus (SLE)., Methods: Thirty-six adult SLE patients and twelve healthy controls were examined for serum and urine levels of 8 protein markers, namely ALCAM, calpastatin, hemopexin, peroxiredoxin 6 (PRDX6), platelet factor 4 (PF4), properdin, TFPI and VCAM-1, by ELISA. Fractional excretion of analyzed biomarkers was calculated after normalizing both the urine and serum biomarker levels against creatinine. A further validation cohort of fifty SLE patients was included to validate the initial findings., Results: The FE ratios of all 8 proteins interrogated outperformed conventional disease activity markers such as anti-dsDNA, C3 and C4 in identifying renal disease activity. All but VCAM-1 FE were superior to the corresponding urine biomarkers levels in differentiating LN activity, exhibiting positive correlation with renal SLEDAI. ALCAM FE , PF4 FE and properdin FE ratios exhibited the highest accuracy (AUC>0.9) in distinguishing active LN from inactive SLE. Four of the FE ratios exhibited perfect sensitivity (calpastatin, PRDX6, PF4 and properdin), while ALCAM FE , PF4 FE and properdin FE exhibited the highest specificity values for active LN. In addition, several of these novel biomarkers were associated with higher renal pathology activity indices. In the validation cohort ALCAM FE , PF4 FE and properdin FE once again exhibited higher accuracy metrics, surpassing corresponding urine and serum biomarkers levels, with ALCAM FE exhibiting 95% accuracy in distinguishing active LN from inactive SLE., Conclusions: With most of the tested proteins, urine:serum fractional excretion ratios outperformed corresponding urine and serum protein measurements in identifying active renal involvement in SLE. Hence, this novel class of biomarkers in SLE ought to be systemically evaluated in larger independent cohorts for their diagnostic utility in LN assessment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Soliman, Stanley, Vanarsa, Ismail, Mok and Mohan.)

In the new science emanating from the COVID-19 pandemic, effective vaccine development has made a huge difference and saved countless lives. Vaccine roll-out led to the identification of rare cases of severe thrombotic and thrombocytopenic problems in some recipients. This apparent coupling of thrombosis with haemorrhagic potentiation might seem baffling but the ensuing clinical investigation rapidly shed important light on its molecular mechanism. This review outlines the current understanding on the role of adenovirus-based platforms, the immunogenic triggers and the immunothrombotic response underlying vaccine-induced immune thrombotic thrombocytopenia., (© Royal College of Physicians 2022. All rights reserved.)

The coronavirus disease 2019 (COVID-19), a deadly pandemic that has affected millions of people worldwide, is associated with cardiovascular complications, including venous and arterial thromboembolic events. Viral spike proteins, in fact, may promote the release of prothrombotic and inflammatory mediators. Vaccines, coding for the spike protein, are the primary means for preventing COVID-19. However, some unexpected thrombotic events at unusual sites, most frequently located in the cerebral venous sinus but also splanchnic, with associated thrombocytopenia, have emerged in subjects who received adenovirus-based vaccines, especially in fertile women. This clinical entity was soon recognized as a new syndrome, named vaccine-induced immune thrombotic thrombocytopenia, probably caused by cross-reacting anti-platelet factor-4 antibodies activating platelets. For this reason, the regulatory agencies of various countries restricted the use of adenovirus-based vaccines to some age groups. The prevailing opinion of most experts, however, is that the risk of developing COVID-19, including thrombotic complications, clearly outweighs this potential risk. This point-of-view aims at providing a narrative review of epidemiological issues, clinical data, and pathogenetic hypotheses of thrombosis linked to both COVID-19 and its vaccines, helping medical practitioners to offer up-to-date and evidence-based counseling to their often-alarmed patients with acute or chronic cardiovascular thrombotic events.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible and pathogenic coronavirus responsible for the pandemic coronavirus disease 19 (COVID-19). It has significant impact on human health and public safety along with negative social and economic consequences. Vaccination against SARS-CoV-2 is likely the most effective approach to sustainably control the global COVID-19 pandemic. Vaccination is highly effective in reducing the risk of severe COVID-19 disease. Mass-scale vaccination will help us in attaining herd immunity and will lessen the negative impact of the disease on public health, social and economic conditions. The present pandemic stimulated the development of several effective vaccines based on different platforms. Although the vaccine is safe and efficacious, rare cases of thrombosis and thrombocytopenia following the use of vaccination with the ChAdOx1 CoV-19 vaccine (AstraZeneca, University of Oxford, and Serum Institute of India) or the Ad26.COV2.S vaccine (Janssen/Johnson & Johnson) have been reported globally. This review focussed on the definition, epidemiology, pathogenesis, clinical features, diagnosis, and management of vaccine associated thrombosis., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Annals of Thoracic Medicine.)

Angiogenesis is the process of new vascular formation, which is derived from various factors. For suppressing cancer cell growth, targeting angiogenesis is one of the therapeutic approaches. Vascular endothelial growth factor family receptors, including Flt-1, Flk-1 and Flt-4, have been found to play an essential role in regulating angiogenesis. Rapamycin is a macrolide compound with anti-proliferative properties, while platelet factor-4 (PF-4) is an antiangiogenic ELR-negative chemokine. Rapamycin inhibits mTOR ligands activation, thus suppressing cell proliferation, while PF-4 inhibits cell proliferation through several mechanisms. In the present study, we evaluated the effects of rapamycin and platelet factor-4 toward breast carcinoma at the proteomic and genomic levels. A total of 60 N-Methyl-N-Nitrosourea-induced rat breast carcinomas were treated with rapamycin, platelet factor-4 and rapamycin+platelet factor-4. The tumours were subsequently subjected to immunohistochemical protein analysis and polymerase chain reaction gene analysis. Protein analysis was performed using a semiquantitative scoring method, while the mRNA expression levels were analysed based on the relative expression ratio. There was a significant difference in the protein and mRNA expression levels for the selected markers. In the rapamycin+platelet factor-4-treated group, the Flt-4 marker was downregulated, whereas there were no differences in the expression levels of other markers, such as Flt-1 and Flk-1. On the other hand, platelet factor-4 did not exhibit a superior angiogenic inhibiting ability in this study. Rapamycin is a potent antiangiogenic drug; however, platelet factor-4 proved to be a less effective drug of anti-angiogenesis on rat breast carcinoma model.

Background: Heparin induced thrombocytopenia (HIT) is reported at a variable rate in extracorporeal membrane oxygenation (ECMO) patients. A critical factor impacting platelet factor-4 (PF4)-heparin antibody formation is plasma PF4 concentration. We hypothesized that PF4 concentration would be increased during veno-arterial (VA) ECMO., Methods: Plasma PF4 concentration was measured during the first 5 ECMO days in 20 VA ECMO patients and 10 control plasma samples. PF4-heparin ratios were estimated using an assumed heparin concentration of 0.4 IU/mL. This correlates with an activated partial thromboplastin time of 60 to 80 seconds, which is the anticoagulation target in our center., Results: Twenty VA ECMO patients were enrolled, 10 of which had pulmonary embolism. Median PF4 concentration was 0.03 µg/mL [0.01, 0.13] in control plasma. Median PF4 concentration was 0.21 µg/mL [0.12, 0.34] on ECMO day 1 or 2, 0.16 µg/mL [0.09, 0.25] on ECMO day 3, and 0.12 µg/mL [0.09, 0.22] on ECMO day 5. Estimated median PF4-heparin ratios were 0.04, 0.03, and 0.02 respectively. Two patients (10%) developed HIT that was confirmed by serotonin release assay. PF4 concentration did not differ significantly in these patients compared to non-HIT patients (p = 0.37). No patient had an estimated PF4-heparin ratio between 0.7 and 1.4, which is the reported optimal range for PF4-heparin antibody formation., Conclusion: Our data suggest that PF4 concentration is mildly elevated during VA ECMO compared to control plasma. Estimated PF4-heparin ratios were not optimal for HIT antibody formation. These data support epidemiologic studies where HIT incidence is low during VA ECMO.

Introduction: The role of platelet activation in allergic inflammation is receiving increasing attention. Sublingual immunotherapy for allergic rhinitis can modify the immunological process to an allergen, rather than simply treating symptoms., Objective: The aim of this study was to explore the role of platelet activation during sublingual immunotherapy in children with allergic rhinitis., Methods: Forty-two House Dust Mite - sensitized children with allergic rhinitis were enrolled and received House Dust Mite allergen extract for sublingual immunotherapy or placebo. Serum of different time points during treatment was collected and used for detection of Platelet Factor-4 and Beta-Thromboglobulin concentration by Enzyme-Linked Immuno Sorbent Assay., Results: Our data showed decreased expression of Platelet Factor-4 and Beta-Thromboglobulin protein after one year's sublingual immunotherapy. In addition, the decrease of symptom scores and serum Platelet Factor-4 and Beta-Thromboglobulin protein concentrations was positively related., Conclusion: During sublingual immunotherapy, platelet activation was inhibited significantly. Our results might indicate that inhibition of platelet activation within the systemic circulation is an important mechanism during sublingual immunotherapy., (Copyright © 2016. Published by Elsevier Editora Ltda.)

Paraneoplastic thrombocytosis has been reported in different types of solid tumors, including ovarian epithelial cancer, and found to be associated with a worse outcome. Although the effect of cancer on increasing platelet counts is well documented, the effect of cancer on platelet functions is not well known. We compared in vitro aggregation response of platelets isolated from 34 patients with ovarian cancer to those of platelets from 19 patients with benign ovarian tumors. Aggregation studies were conducted in a light transmission aggregometer, using both a high and a low dose of ADP and collagen. We evaluated platelet preactivation by measuring the plasma concentration of β-thromboglobulin (β-TG) and platelet factor-4 (PF-4) as markers of platelet α granule secretion, using ELISA. We found that ovarian cancer is not associated with an enhanced aggregation response of platelets to ADP or collagen, and plasma concentration of β-TG and PF-4 is not higher in patients with ovarian cancer compared to those in patients with benign ovarian tumors., Competing Interests: Declaration of interest The authors report no conflicts of interest.

Platelet activation and thrombin generation are crucial steps in primary and secondary haemostasis. However, both also play major roles in intravascular thrombus formation and therefore in the development of adverse cardiovascular events. In the current study, we first sought to investigate the associations of the platelet biomarkers platelet factor (PF)-4, thrombospondin (TSP)-1, soluble CD40 ligand (sCD40L), and soluble P-selectin (sP-selectin) with each other and with monocyte-platelet aggregate (MPA) formation in 316 patients undergoing angioplasty and stenting. To better understand the interplay between platelet activation and thrombin generation, we subsequently investigated the associations of the platelet biomarkers with thrombin generation potential. The mostly platelet-specific markers PF-4, TSP-1 and sCD40L correlated strongly with each other (all p < 0.001), and the best correlation was observed between PF-4 and TSP-1 (r=0.91). In contrast, sP-selectin, which derives from platelets and endothelial cells, correlated rather poorly with TSP-1 (r=0.12, p=0.04), and did not correlate with PF-4 and sCD40L. While PF-4, TSP-1 and sP-selectin correlated significantly with in vivo MPA formation (all p< 0.001), no such association was found between sCD40L and MPA formation. PF-4, TSP-1 and sCD40L correlated strongly with peak thrombin generation (all p< 0.001) with the best correlation between PF-4 and peak thrombin generation (r=0.55), whereas sP-selectin did not correlate with peak thrombin generation. Likewise, PF-4, TSP-1 and sCD40L correlated significantly with the area under the thrombin generation curve (AUC; all p< 0.01), whereas sP-selectin did not correlate with the AUC. In conclusion, platelet-specific markers are associated with MPA formation and thrombin generation potential in patients with advanced atherosclerosis.

Background/aims: Kidneys from uncontrolled non heart-beating donors achieve a good level of renal function after transplantation. However, a number of them will never function in the recipient. Our aim was to determine if serum biomarkers associated with platelet activity, inflammation and the nitric oxide system in uncontrolled non heart-beating donors may help to predict no renal function recovery after renal transplantation., Methods: Serum levels of interleukin (IL)-6, IL-10, intercellular cell adhesion molecule-1 (ICAM-1), cyclic guanosine monophosphate (cGMP), nitrite + nitrate and platelet factor-4 (PF4) were measured using enzyme-linked immunosorbent assay (ELISA) kits in 88 uncontrolled non heart-beating donors divided according to the renal functionality achieved in the recipients into functional (n = 76) and non functional (n = 12)., Results: Kidneys from donors with higher IL-6 levels (>900 pg/ml) were functional after transplantation. Serum cGMP levels below 372.3 fmol/l were also associated with kidneys that recovered the renal function. However, serum levels of PF4 showed the best correlation with recovery of renal functional in the recipients since they were significantly lower in the donors whose kidneys functioned after transplantation., Conclusions: Serum PF4 levels in uncontrolled non heart-beating donors may be a good predictor for kidneys that never will reach functional recovery. Some serum cGMP, IL-6 and IL-10 levels may simply help identify kidneys that will function after transplantation.