Acrocyanosis and digital necrosis are associated with poor prognosis in COVID‐19

Abstract

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Case Report: Extensive Gangrene: A Rare Presentation of Multisystem Inflammatory Syndrome in Children

“…It has been observed that the presence of skin acrocyanosis and digital necrosis may suggest disease severity, as the thrombosis can be seen in multiple organs and may predict poor outcomes. 11,12 To the best of our knowledge, only one report of two children with MIS-C with acral gangrene has been reported as of the time of this publication. 13 Both of these children had hemodynamic instability, required intensive care, and developed gangrenous changes during the second week of illness.…”

COVID-19 Sepsis: Pathogenesis and Endothelial Molecular Mechanisms Based on “Two-Path Unifying Theory” of Hemostasis and Endotheliopathy-Associated Vascular Microthrombotic Disease, and Proposed Therapeutic Approach with Antimicrothrombotic Therapy

“…49,50,[58][59][60][61][62] The simple fact is the vascular events (e.g., surgery, accesses, procedures, devices and ventilators) may cause local vascular wall damage which releases ULVWF and TF and initiate thrombogenesis, leading to macrothrombosis at the injury site and spreading to other sites. In addition, distinguished from this macrothrombosis, inexplicable macrothrombotic disorder in COVID-19 characterized by "multiple" small macrothromboses mixed with microthrombotic disorder was observed in the lungs in the same patient, 52,53,63,64 and also occurred in the digits with gangrene [12][13][14] For personal use only.…”

“…This inexplicable thrombotic syndrome has rarely occurred but commonly been reported in the COVID-19 literature because of its oddity. 14,[70][71][72][73][74][75][76] However, this gangrene had been described enough in sepsis of the non-COVID-19 literature 22,[77][78][79][80] because of its mysterious nature and serious consequences with high morbidity and sometimes death. The diagnosis of combined micro-macrothrombotic syndrome is affirmed logically from two facts in every patient: 1) underlying disseminated microthrombosis (i.e., EA-VMTD); and 2) gangrene formation which never occurs without macrothrombosis.…”

“…This interaction between COVID-19 septic endotheliopathy and vascular access-induced injury explain the unique "combined micro-macrothrombotic syndrome." 22 Symmetrical peripheral gangrene, 79 peripheral digit ischemic syndrome, 77 limb hemorrhagic gangrene, 70 limb ischemia, 71 acrocyanosis, 14 purpura fulminans, 73,75,76,80 and perhaps coumadin-induced gangrene and diabetic leg gangrene have been associated with sepsis-associated microthrombosis, sometimes with underlying thrombophilia. These gangrene syndromes represent variable phenotypes of combined micro-macrothrombotic syndrome observed in COVID-19.…”

“…Later, complex hemostatic phenotypes of micro and macrothrombotic disorders and multiorgan dysfunction syndrome (MODS) had become apparent, including inexplicable gangrene involving the extremities, and digits in particular. [10][11][12][13][14] Like other pathogens, severe COVID-19 sepsis was found to be associated with complement activation, [15][16][17] endotheliopathy, 18,19 microvascular injury and thrombosis, 16 and pathologic hemostasis. 20,21 Previously, these mechanisms were affirmed to be involved in other pathogen-induced sepsis and identified as the pathogenesis causing ARDS, MODS, thrombotic disease and coagulopathy via endotheliopathy-associated vascular microthrombotic disease (EA-VMTD).…”