Angiotensin (1-7) prevents platelet activation and vascular endothelial damage by binding to MAS receptors on the endothelium and increasing the production of nitric oxide and prostacyclin. Through oxidative stress and various pathways, including overexpression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), cyclooxygenase-2 (COX-2), and vascular endothelial growth factor (VEGF), impaired RAAS regulation can cause endothelial damage and thus predispose the arteries to thrombotic events (3). In addition, endothelial damage or dysfunction contributes to the generation and activation of thrombin via the release of procoagulant factor VIII, (7-9). Upon endothelial damage, sub-endothelial VWF is released and acts as a molecular adhesive, binds platelets to sub-endothelial collagen, and activates platelet aggregation and thrombosis . In severe cases, dysregulated innate immune response and widespread release of proinflammatory cytokines (cytokine storm) are involved in the pathogenesis of the disease and lead to the activation of various “immunothrombotic” pathways and blood coagulation. Complement overactivation is also observed in response to dysregulated innate immune response in COVID-19 infection. Following an infection, neutrophils prevent the spread of microorganisms into the blood by releasing neutrophil extracellular traps (NETs) (3). A study found the excessive NETs formation (NETosis) to be involved in various human pathologies including sepsis, vasculitis, and thrombosis (10). dysregulated RAAS due to ACE-2 inhibition in COVID-19 can also activate mitogen-activated protein kinases (ERK, p38, and JNK), that are early activated in the innate immune response, and thus increase the risk of thrombosis (3). a combination of underlying medical conditions, hospitalization, bedridden status, and COVID-19 infection may increase the hypercoagulopathy in patients. One of the organs affected by coagulation due to COVID-19 infection is the kidney (11). RVT may lead to complete or partial blockage of the renal veins. It often begins in the small intrarenal veins and subsequently spreads through the larger interlobar veins to the main renal veins and even to the IVC, causing pulmonary embolism. The condition rarely occurs in healthy adults and is often unilateral. About 15%-20% of patients with nephrotic syndrome may develop RVT. RVT is associated with abdominal surgery such as laparoscopic cholecystectomy, trauma, tumor invasion, or invasion of the renal vein by primary retroperitoneal diseases. The Causes and mechanisms of RVT are not different from venous thrombosis in other parts of the body and involve a combination of three related factors including endothelial damage, stasis, and hypercoagulability. The clinical manifestations of RVT in adults depend on the rate, extent, and degree of venous occlusion formation. Patients may be asymptomatic or have minor nonspecific symptoms such as nausea and weakness. Sometimes, due to the presence of more nonspecific major symptoms, such as upper abdominal pain, acute flank pain, and hematuria, the condition might be mistaken with renal colic caused by renal and ureteric calculi, especially in young and healthy patients. Lack of clinical manifestations makes RVT undiagnosed and therefore less reported. However, the diagnosis of RVT is necessary considering its possible consequences, including pulmonary embolism and progressive renal failure associated with vascular compromise and the risks of potentially harmful treatment (including anticoagulation or thrombolysis) (12).

The case reported in this study had a previous history of extensive DVT and a positive family history of DVT despite the negative results of hereditary thrombophilia tests. In this case, COVID-19 could be considered as the most important risk factor for thrombotic events, including RVT, especially after the arbitrarily discontinuation of prescribed warfarin tablets.