Plasma exchange for COVID‐19 thrombo‐inflammatory disease

Arulkumaran, Nishkantha; Thomas, Mari; Brealey, David; Alwan, Ferras; Singh, Deepak; Lunn, Michael P.; Welch, Anna; Clark, Sandra; Raith, Eamon; Reddy, Ugan; Low, Ryan; Leverett, David; Singer, Mervyn; Scully, Marie

doi:10.1002/jha2.140

Cited by 28 publications

(53 citation statements)

References 12 publications

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“…[60][61][62] Similar promising results have been reported with plasma exchange. 38 These findings all suggest that secondary thrombotic microangiopathy may be a major driver of outcomes in SARS-CoV-2 infection, such that its attenuation by therapies already used in the treatment of thrombotic microangiopathy would appear a reasonable strategy.…”

Section: Discussionmentioning

confidence: 93%

“…They were treated with plasma exchange, a treatment commonly applied in TTP, and patients improved clinically and gradually recovered neurologically (after 27-32 days). Another interesting case series was presented by Arulkumaran et al, 38 who utilized plasma exchange in seven severely critical COVID-19 patients with acute respiratory distress syndrome (ARDS) versus seven matched controls, and who not only showed improvement in patients after plasma exchange but also noted that five of seven controls developed AKI, whereas AKI was developed in none of the seven plasma-exchangetreated patients. The reported ADAMTS-13 levels in this case series were normal (median, 73 [IQR, 65-89] U/dL), but the median VWF/ADAMTS-13 ratio was high (4.0 [IQR, 2.8-5.7]).…”

Section: Discussionmentioning

confidence: 99%

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Increased VWF and Decreased ADAMTS-13 in COVID-19: Creating a Milieu for (Micro)Thrombosis

Favaloro

Henry

Lippi

2021

Semin Thromb Hemost

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Abstractvon Willebrand factor (VWF) is a large adhesive multimeric protein involved in hemostasis. The larger the size (or number of VWF multimers), the greater the functionality of the protein. A deficiency or defect of VWF can lead to von Willebrand disease (VWD) and cause bleeding. Conversely, an increase in VWF may create an environment that promotes thrombosis. ADAMS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), sometimes called VWF-cleaving protease, is primarily responsible for controlling the size of VWF. The most severe deficiency (<10% of normal levels) of ADAMTS-13 arises in thrombotic thrombocytopenic purpura, a condition characterized by the presence of ultralarge VWF and clinically resulting in enhanced risk of thrombosis. However, ADAMTS-13 deficiency may result from other pathological processes. Of relevance is the recent finding that COVID-19 (coronavirus disease 2019) is associated with both increased levels and activity of VWF as well as generally decreased (or occasionally normal) activity levels of ADAMTS-13. Thus, in COVID-19 there is an alteration in the VWF/ADAMTS-13 axis, most often described by increased VWF/ADAMTS-13 ratio (or reduced ADAMTS-13/VWF ratio). COVID-19 is also associated with high prothrombotic risk. Thus, the imbalance of VWF and ADAMTS-13 in COVID-19 may be providing a milieu that promotes (micro)thrombosis, in a clinical picture resembling a secondary thrombotic microangiopathy in some patients. This review therefore assesses the literature on VWF, ADAMTS-13, and COVID-19. Whenever reported in COVID-19, VWF has always been identified as raised (compared with normal reference ranges or control populations). Reports have included VWF level (i.e., VWF antigen) and in some cases one or more VWF “activity” (e.g., collagen binding; platelet glycoprotein Ib [GPIb] binding, using ristocetin cofactor or more modern versions including VWF:GPIbR [recombinant] and VWF:GPIbM [mutant]). Whenever reported, ADAMTS-13 has been reported as “normal” or reduced; however, it should be recognized that “normal” levels may still identify a relative reduction in individual cases. Some reports also discuss the raised VWF/ADAMTS-13 (or reduced ADAMTS-13/VWF) ratio, but very few provide actual numerical data.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Increased VWF and Decreased ADAMTS-13 in COVID-19: Creating a Milieu for (Micro)Thrombosis

Favaloro

Henry

Lippi

2021

Semin Thromb Hemost

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“…Although dexamethasone and remdesivir have been reported to be useful in the treatment of COVID‐19 [4,7], it is still reported that even with multidisciplinary treatment, there is a high risk of the condition being fatal in men older than 65 years, and in patients with diabetes, hypertension, and heart disease [8]. So far, numerous reports on the efficacy of PE for severe COVID‐19 have been published, including case reports and case series [9–13].…”

Section: Discussionmentioning

confidence: 99%

Combination therapy with plasma exchange and glucocorticoid may be effective for severe COVID‐19 infection: A retrospective observational study

et al. 2021

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We retrospectively analyzed the characteristics and outcomes of five patients with COVID‐19 who were received glucocorticoid (with or without pulse therapy) and therapeutic plasma exchange. The efficacy of the treatment was determined by whether the patient was able to be transferred from the COVID‐19 exclusive ICU to the general ward. In comparing patients who received prednisolone pulse therapy (three cases) with those who did not (two cases), 2/3 (66%) and 0/2 (0%) patients could be discharged from the COVID‐19 dedicated ICU, respectively. Among five patients who was performed plasma exchange, two elderly male patients who underwent plasma exchange as early as within 8 days of disease exacerbation survived and were able to be transferred to the general ward. This observational study indicates that plasma exchange in conjunction with methylprednisolone pulse therapy at the appropriate time may be an effective treatment for elderly patients with severe COVID‐19.

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“…Further studies on evaluating such treatment modalities-N-acetyl cysteine [22,23] (cleaves disulphide bonds linking VWF dimers), fresh frozen plasma/ cryo-supernatant infusion (provides VWF cleaving enzyme called a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 [ADAMTS13]) [24] and therapeutic plasma exchange (VWF-pheresis as well as provides ADAMTS13 supplementation) [25,26], can be considered. Recent studies have explored the role of therapeutic plasma exchange in tackling thrombo-inflammation in COVID-19 patients [27].…”

Section: Discussionmentioning

confidence: 99%

Plasma Von Willebrand Factor Levels Predict Survival in COVID-19 Patients Across the Entire Spectrum of Disease Severity

Thomas

Kumar

Alexander

et al. 2021

Indian J Hematol Blood Transfus

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Background: Characterization of reticulo-endothelial activation in COVID-19 may guide treatment. Objectives: To assess reticulo-endothelial activation and its correlation with disease severity and death in patients across the entire spectrum of COVID-19 severity. Methods: Consecutive hospitalized COVID-19 patients were studied, with similar number of patients in each disease severity category. Baseline serum ferritin, sCD163 (macrophage activation markers) and plasma von Willebrand factor (VWF) antigen (endothelial activation marker) levels were studied. Clinical parameters and plasma D-dimer levels were also studied. The study parameters were correlated with COVID-19 severity and survival. Results: The 143 patients (104 males [80%], age 54 [42 – 65] years, median [inter-quartile range]) presented 4 (3—7) days after symptom onset. Thirty-four patients had mild disease, 36 had moderate disease, 36 had severe disease and 37 had critical disease at baseline. With increasing COVID-19 severity, ferritin, sCD163, VWF and D-dimer levels significantly increased at baseline, however, 139 patients had normal sCD163 levels. Of the reticulo-endothelial markers, VWF level independently correlated with COVID-19 severity and with survival. VWF level > 332.6 units/dl correlated with COVID-19 severity (odds ratio [OR]: 2.77 [95% confidence interval (C.I): 1.1 – 6.99], p value: 0.031) and in-hospital death (OR [95% CI]: 29.28 [5.2 – 165], p value < 0.001). Conclusions: Reticulo-endothelial activation markers increased incrementally with worsening COVID-19 severity. Baseline endothelial activation marker (VWF), and not macrophage activation markers, independently correlated with COVID-19 severity and death.

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Plasma exchange for COVID‐19 thrombo‐inflammatory disease

Cited by 28 publications

References 12 publications

Increased VWF and Decreased ADAMTS-13 in COVID-19: Creating a Milieu for (Micro)Thrombosis

Increased VWF and Decreased ADAMTS-13 in COVID-19: Creating a Milieu for (Micro)Thrombosis

Combination therapy with plasma exchange and glucocorticoid may be effective for severe COVID‐19 infection: A retrospective observational study

Plasma Von Willebrand Factor Levels Predict Survival in COVID-19 Patients Across the Entire Spectrum of Disease Severity

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