“… 47 , 57 However, mild to moderate deficiency of plasma ADAMTS‐13 activity or relative deficiency is common in patients with several acute and chronic disorders including myocardial infarction, 29 , 31 , 32 cerebral ischemia, 38 , 58 , 59 preeclampsia, 35 , 60 , 61 , 62 and sepsis, 63 , 64 , 65 as well as severe SARS‐CoV‐2 infection. 39 , 40 , 41 , 66 , 67 Consistent with such a notion, low plasma ADAMTS‐13 activity or reduced ratio of ADAMTS‐13 activity to VWF antigen or activity is prevalent in our patients with suspected HIT; this may be primarily caused by congestive heart failure, pulmonary embolism, and sepsis, resulting in reduced synthesis and increased consumption of ADAMTS‐13. In some cases, low ADAMTS‐13 activity may be the result of IgG autoantibodies against ADAMTS‐13 that binds ADAMTS‐13 and accelerates clearance of immune complexes from circulation.…”
Section: Discussionsupporting
confidence: 80%
“… 28 Relative deficiency of plasma ADAMTS‐13 has been observed in patients with acute cerebral infarction, 29 , 30 myocardial infarction, 31 , 32 malignant malaria, 33 , 34 preeclampsia, 35 , 36 acute traumatic brain injury, or multiple site injury, 37 , 38 as well as in patients with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. 39 , 40 , 41 However, the role of ADAMTS‐13 in pathogenesis, disease progression, and outcome in patients with suspected HIT has not been systematically determined. The present study aims to determine the associations among plasma levels of ADAMTS‐13 activity, VWF antigen, VWF activity, and other clinical factors or laboratory parameters, and in particular the role of ADAMTS‐13 and VWF in predicting in‐hospital mortality in patients with suspected HIT.…”
Background
Heparin‐induced thrombocytopenia (HIT) is a life‐threatening thrombotic complication after heparin exposure. However, the role of ADAMTS‐13 and von Willebrand factor (VWF) in the disease process and outcomes of HIT is not known.
Objective
To determine the potential role of ADAMTS‐13 and VWF in hospitalized patients suspected with HIT.
Methods
Associations of the HIT tests, ADAMTS‐13 activity, and VWF antigen or activity with other clinical parameters and outcomes in the patients suspected with HIT were determined.
Results
Of 261 patients, 87 (33.3%) were positive and 174 (66.7%) were negative for a HIT antibody determined by an enzyme immunoassay (EIA). Of these 87 EIA+ patients, 31 (35.6%) were also positive but 56 (64.4%) were negative for serotonin‐releasing assay (SRA). There was no statistically significant difference among all three groups (i.e., EIA–, EIA+/SRA+, and EIA+/SRA–) as to their demographic features, reasons for admission to the hospital, type of procedures performed, and in‐hospital mortality. Compared to those in the healthy controls, plasma ADAMTS‐13 activity in patients suspected with HIT was significantly lower but plasma VWF antigen (VWFAg) and activity (VWFAc) in these patients were significantly higher. While there was no statistically significant difference among all three groups regarding plasma levels of ADAMTS‐13 activity, VWFAg, and VWFAc, plasma levels of ADAMTS‐13 activity <50% or the low ratios of ADAMTS‐13 activity to VWFAg (or VWFAc) are highly predictive for a 90‐day mortality rate, particularly in the EIA+SRA+ group.
Conclusions
These results demonstrate that relative deficiency of plasma ADAMTS‐13 activity in hospitalized patients suspected with HIT is common, which may contribute at least in part to the adverse outcomes in this patient population, particularly in those with true HIT.
“… 47 , 57 However, mild to moderate deficiency of plasma ADAMTS‐13 activity or relative deficiency is common in patients with several acute and chronic disorders including myocardial infarction, 29 , 31 , 32 cerebral ischemia, 38 , 58 , 59 preeclampsia, 35 , 60 , 61 , 62 and sepsis, 63 , 64 , 65 as well as severe SARS‐CoV‐2 infection. 39 , 40 , 41 , 66 , 67 Consistent with such a notion, low plasma ADAMTS‐13 activity or reduced ratio of ADAMTS‐13 activity to VWF antigen or activity is prevalent in our patients with suspected HIT; this may be primarily caused by congestive heart failure, pulmonary embolism, and sepsis, resulting in reduced synthesis and increased consumption of ADAMTS‐13. In some cases, low ADAMTS‐13 activity may be the result of IgG autoantibodies against ADAMTS‐13 that binds ADAMTS‐13 and accelerates clearance of immune complexes from circulation.…”
Section: Discussionsupporting
confidence: 80%
“… 28 Relative deficiency of plasma ADAMTS‐13 has been observed in patients with acute cerebral infarction, 29 , 30 myocardial infarction, 31 , 32 malignant malaria, 33 , 34 preeclampsia, 35 , 36 acute traumatic brain injury, or multiple site injury, 37 , 38 as well as in patients with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. 39 , 40 , 41 However, the role of ADAMTS‐13 in pathogenesis, disease progression, and outcome in patients with suspected HIT has not been systematically determined. The present study aims to determine the associations among plasma levels of ADAMTS‐13 activity, VWF antigen, VWF activity, and other clinical factors or laboratory parameters, and in particular the role of ADAMTS‐13 and VWF in predicting in‐hospital mortality in patients with suspected HIT.…”
Background
Heparin‐induced thrombocytopenia (HIT) is a life‐threatening thrombotic complication after heparin exposure. However, the role of ADAMTS‐13 and von Willebrand factor (VWF) in the disease process and outcomes of HIT is not known.
Objective
To determine the potential role of ADAMTS‐13 and VWF in hospitalized patients suspected with HIT.
Methods
Associations of the HIT tests, ADAMTS‐13 activity, and VWF antigen or activity with other clinical parameters and outcomes in the patients suspected with HIT were determined.
Results
Of 261 patients, 87 (33.3%) were positive and 174 (66.7%) were negative for a HIT antibody determined by an enzyme immunoassay (EIA). Of these 87 EIA+ patients, 31 (35.6%) were also positive but 56 (64.4%) were negative for serotonin‐releasing assay (SRA). There was no statistically significant difference among all three groups (i.e., EIA–, EIA+/SRA+, and EIA+/SRA–) as to their demographic features, reasons for admission to the hospital, type of procedures performed, and in‐hospital mortality. Compared to those in the healthy controls, plasma ADAMTS‐13 activity in patients suspected with HIT was significantly lower but plasma VWF antigen (VWFAg) and activity (VWFAc) in these patients were significantly higher. While there was no statistically significant difference among all three groups regarding plasma levels of ADAMTS‐13 activity, VWFAg, and VWFAc, plasma levels of ADAMTS‐13 activity <50% or the low ratios of ADAMTS‐13 activity to VWFAg (or VWFAc) are highly predictive for a 90‐day mortality rate, particularly in the EIA+SRA+ group.
Conclusions
These results demonstrate that relative deficiency of plasma ADAMTS‐13 activity in hospitalized patients suspected with HIT is common, which may contribute at least in part to the adverse outcomes in this patient population, particularly in those with true HIT.
“…There are 10 studies comprising of 996 patients included in this systematic review and meta-analysis [ Figure 1 ]. ( Cugno et al, 2021 ; Goshua et al, 2020 ; De Jongh et al, 2021 ; Mancini et al, 2021b ; von Meijenfeldt et al, 2021 ; Philippe et al, 2021 ; Rauch et al, 2020 ; Rodríguez Rodríguez et al, 2021 ; Sweeney et al, 2021 ; Vassiliou et al, 2021 ) The baseline characteristics of the included studies were presented in Table 1 . Figure 1 PRISMA Flowchart …”
Background: In this systematic review and meta-analysis, we aimed to compare the level of von Willebrand Factor (vWF) antigen in patients with poor outcome compared to those without. Additionally, we also explored factors that may affect the difference in terms of vWF antigen between the two groups.
Methods: A comprehensive literature search was performed using the PubMed, Embase, and Scopus databases from inception up until 7 April 2021. The main outcome was poor outcome, which is a composite of mortality and severe COVID-19.
Results: There are 10 studies comprising of 996 patients included in this systematic review and meta-analysis. vWF antigen was higher in patients with poor outcome (standardized mean difference [SMD] 0.84 [0.45, 1.23], p<0.001; I
2
: 87.3, p<0.001). Subgroup analysis on vWF antigen that uses percentage as unit (mean difference 121.6 [53.7, 189.4], p<0.001; I
2
: 92.0, p<0.001). Meta-regression showed that the SMD between poor outcome and good outcome was affected by platelets (coefficient: 0.0061, p=0.001), d-dimer (coefficient: 0.0007, p=0.026), and factor VIII level (coefficient: 0.0057, p=0.031), but not by age (coefficient: -0.0610, p=0.440), gender (coefficient: 0.0135, p=0.698), obesity (coefficient: 0.0282, p=0.666), hypertension (coefficient: 0.0273, p=0.423), diabetes (coefficient: 0.0317, p=0.398), malignancy (coefficient: 0.0487, p=0.608).
Conclusion: This meta-analysis showed that the level of vWF antigen was significantly higher in patients with poor outcome, signaling a marked endotheliopathy. Meta-regression showed that differences became larger as the number of platelets, d-dimer levels, and factor VIII levels increases.
“…The few studies investigating this connection have discovered a positive correlation between an imbalance of VWF/ADAMTS13 activity levels and COVID-19 severity and mortality. Several studies have observed elevated levels and activity of VWF and decreased activity of ADAMTS13 in patients with COVID-19 ( 10 – 12 , 23 , 47 – 52 ). In addition, a retrospective study examining 3,672 plasma samples identified a correlation between elevated levels of VWF and markers of coagulation ( 53 ).…”
Section: A Possible Connection Between Covid-19 Coagulopathy and Vwf/adamts13 Imbalancementioning
The 2019 coronavirus disease (COVID-19) is the disease caused by SARS-CoV-2 infection. While this infection has been shown to affect the respiratory system, a high incidence of thrombotic events has been observed in severe cases of COVID-19 and in a significant portion of COVID-19 non-survivors. While prior literature has reported on both the coagulopathy and hypercoagulability of COVID-19, the specifics of coagulation have not been fully investigated. Observations of microthrombosis in COVID-19 patients have brought attention to potential inflammatory endothelial injury. Von Willebrand factor (VWF) and its protease, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13), play an important homeostatic role in responding to endothelial injury. This report provides an overview of the literature investigating the role the VWF/ADAMTS13 axis may have in COVID-19 thrombotic events and suggests potential therapeutic strategies to prevent the progression of coagulopathy in COVID-19 patients.
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