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.