Genesis of Antibiotic Resistance LIII: “Virchow’s Triad” of Capillary (Vascular) Leak Syndrome (CLS) tethered Adverse Pressure Gradient exacerbated mortality rate in NCT01663701: A critical appraisal
Authors: Mendoza Jonathan , Soto Elsa , Cerrillo Veronica , Barrientos April , Botello Cynthia , Kannan Subburaj 
Published: April 2020

Based on adverse effects of biosimilar(s), for oncological treatment modalities (radiation/chemotherapy), posted in FAERS and VigiBase, an effort has been made to derive a temporal correlation between CLS and hemodynamic (Fluid dynamic/mechanics properties) dysregulation lead exacerbated mortality rate in NCT01663701. Idiopathic (unknown etiology) systemic capillary leak syndrome (SCLS) or Capillary leak syndrome (CLS), also known as vascular leak syndrome (VLS), with clinical features such as leakage of the plasma (reversible plasma extravasation with fluid resuscitation), vascular collapse accompanied by a classic triad of hypoalbuminemia, hemoconcentration, and hypotension in the absence of secondary causes of shock with edema. Fluid management is an effective clinical management strategy for an improved prognosis (verbatim in part and modified from J Clin Med. 2018; seven (11); J Clin Med. 2019; 8(2)). The clinical presentation of CLS with a corollary of Virchow’s triad (
https://www.ncbi.nlm.nih.gov/books/NBK539697/) and the critical
events for a laminar to turbulence transition ( ELTT) is systematically correlated. Virchow’s triad I ‐ Endothelial damage:ELTT 1. Region of instability of small wavy disturbances called Tollmien‐Schlichting wave ELTT 2. Periodicity accompanied by the appearance of vortices ELTT 3. Peak‐Valley development in vortices, ELTT 4. Vorticity concentration and shear layer development with inflectional profile appearance and disappearance in Tollmien‐Schlichting wave pattern, Virchow’s triad II ‐ Venous stasis: ELTT 5. Breakdown: evolution of a staggered vortex pattern twice the wavelength of Tollmien‐Schlichting waves ( a high frequency fluctuations of hairpin eddies ‐ eddy currents, disrupts the laminar flow of blood, bringing platelets in close contact with the vascular wallVirchow’s triad III ‐ Hypercoagulability: ELTT 6. Cascading of vortices and turbulent‐spot development, (spots of thrombus lead to increased turbulence thus reduction in blood flow. Infarction and ischemia Thrombi often result in reduced blood flow to tissue (ischemia) or complete obstruction (absolute irreversible stasis NFP=0 mmHG, ?) of blood flow leading to cell death(infarction) with concurrent impairment of global net filtration pressure (NFP) in mark transition of laminar to turbulent flow pattern. Taken together, herewith it is suggested that a better understanding of the components of multifactorial mode of turbulence modelling in particular on time scale, blood viscosity, velocity profile, NFP gradient, and structural integrity of blood vessels (endothelial damage) of the capillary bed in the context of thromboembolic events [DDx: ischemic stroke(CVA), disseminated intravascular coagulation (DIC), deep vein thrombosis (DVT), pulmonary embolism and CLS], would enable better stratification of clinical risk factors, precision in clinical decision making amalgamating differential diagnosis for an accurate prognosis in early resuscitation protocol on sepsis such as NCT01663701.Support or Funding InformationSupported by professional development funds by SWTJC to Subburaj Kannan