ABSTRACT
Thrombotic thrombocytopenic purpura (TTP) is a known menace in hematology and is quite rare in practice with known triggers. Lately, in the COVID-19 pandemic, hematology has seen a new pathology amongst which TTP associated with COVID-19 messenger RNA (mRNA) vaccine is unique. We report a case of a 69-year-old male with multiple comorbidities who presented to the hospital with severe fatigue and shortness of breath. Labs were significant for thrombocytopenia, anemia, and hemolysis with schistocytes consistent with TTP with a second dose of BNT162b2 mRNA vaccine as a likely culprit been documented.
Subject(s)
COVID-19 Vaccines/adverse effects , COVID-19 , Immunization, Secondary/adverse effects , Pandemics , Purpura, Thrombotic Thrombocytopenic/etiology , SARS-CoV-2 , ADAMTS13 Protein/immunology , Aged , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines/immunology , Combined Modality Therapy , Dyspnea/etiology , Fatigue/etiology , HIV Infections/complications , Hepatitis B, Chronic/complications , Humans , Hypertension/complications , Immunosuppressive Agents/therapeutic use , Kidney Failure, Chronic/complications , Male , Plasma Exchange , Purpura, Thrombotic Thrombocytopenic/blood , Purpura, Thrombotic Thrombocytopenic/therapy , Venous Thrombosis/complicationsABSTRACT
The metalloproteinase ADAMTS13 (a disintegrin with a thrombospondin type 1 motif, member 13), also known as VWF (von Willebrand factor) protease, may be assessed in a vast array of clinical conditions. Notably, a severe deficiency of ADAMTS13 characterizes TTP (thrombotic thrombocytopenic purpura), a rare but potentially fatal disorder associated with thrombosis due to accumulation of prothrombotic ultra-large VWF multimers. Although prompt identification/exclusion of TTP can be facilitated by rapid ADAMTS13 testing, the most commonly utilized assays are based on ELISA (enzyme linked immunosorbent assay) and require long turnaround time and have relatively limited throughput. Nevertheless, several rapid ADAMTS13 assays are now available, at least in select geographies. The current mini-review discusses these issues, as well as the potential utility of ADAMTS13 testing in a range of other conditions, including coronavirus disease 2019 (COVID-19).
Subject(s)
ADAMTS13 Protein/blood , COVID-19/complications , Purpura, Thrombotic Thrombocytopenic/diagnosis , SARS-CoV-2 , ADAMTS13 Protein/deficiency , ADAMTS13 Protein/immunology , Autoantibodies/blood , Autoantibodies/immunology , COVID-19/blood , Enzyme-Linked Immunosorbent Assay , Female , Fluorescence Resonance Energy Transfer , Humans , Luminescent Measurements , Male , Multicenter Studies as Topic , Pre-Eclampsia/diagnosis , Pre-Eclampsia/enzymology , Predictive Value of Tests , Pregnancy , Purpura, Thrombotic Thrombocytopenic/blood , Purpura, Thrombotic Thrombocytopenic/enzymology , Purpura, Thrombotic Thrombocytopenic/etiology , Recombinant Proteins/metabolism , Sensitivity and Specificity , von Willebrand Diseases/diagnosis , von Willebrand Diseases/enzymology , von Willebrand Factor/metabolismABSTRACT
Both neutrophil extracellular traps (NETs) and von Willebrand factor (VWF) are essential for thrombosis and inflammation. During these processes, a complex series of events, including endothelial activation, NET formation, VWF secretion, and blood cell adhesion, aggregation and activation, occurs in an ordered manner in the vasculature. The adhesive activity of VWF multimers is regulated by a specific metalloprotease ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motifs, member 13). Increasing evidence indicates that the interaction between NETs and VWF contributes to arterial and venous thrombosis as well as inflammation. Furthermore, contents released from activated neutrophils or NETs induce the reduction of ADAMTS13 activity, which may occur in both thrombotic microangiopathies (TMAs) and acute ischemic stroke (AIS). Recently, NET is considered as a driver of endothelial damage and immunothrombosis in COVID-19. In addition, the levels of VWF and ADAMTS13 can predict the mortality of COVID-19. In this review, we summarize the biological characteristics and interactions of NETs, VWF, and ADAMTS13, and discuss their roles in TMAs, AIS, and COVID-19. Targeting the NET-VWF axis may be a novel therapeutic strategy for inflammation-associated TMAs, AIS, and COVID-19.