Bevacizumab, a monoclonal antibody against VEGF, is known to cause thrombotic microangiopathy (TMA), while tyrosine kinase inhibitors (TKIs) that block VEGF downstream are mainly associated with minimal change disease or focal segmental glomerulosclerosis.
Direct VEGFA inhibition <i>via</i> antibody binding or VEGF trap (a soluble decoy receptor) is associated with renal-specific thrombotic microangiopathy (TMA).
To aid in the accurate diagnosis of TMA and other associated disorders, we have undertaken a review and provided a clear interpretation of some typical biomarkers including schistocytes, LDH and platelet count, coagulation profile and more specific indexes of ADAMTS13, complement profile, and the isolation of Shiga toxin-producing <i>Escherichia coli</i> (commonly referred to as STEC).
This case demonstrates that not only blockade of VEGF but also VEGFR2 antagonism may result in TMA, which is a rare but life-threatening complication of cancer treatment drug.
In the acquired form, autoantibodies against ADAMTS13 inhibit cleaving of von Willebrand factor (vWF) multimers, thereby promoting their interaction with thrombocytes, causing TMA and MAHA.
Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy (TMA) characterized by the severe deficiency of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) activity (< 10%).
Agents targeting vascular endothelial growth factor (VEGF) have increasingly been used for the treatment of advanced malignancies, and have been found to induce renal thrombotic microangiopathy (TMA) and proteinuria.
This could lead to the earlier confirmation or rapid exclusion of TTP when ADAMTS13 testing is not avalilable, facilitating a more suitable therapy based on the aetiology of the TMA.
A deficiency in ADAMTS-13 leads to higher concentrations of ultralarge VWF multimers and pathological platelet-vessel wall interactions, in its most typical and extreme form leading to thrombocytopenic thrombotic purpura, a thrombotic microangiopathy characterized by thrombocytopenia, non-immune hemolysis, and organ dysfunction.
Accurate evaluation of ADAMTS13 activity is required for the diagnosis and clinical management of thrombotic microangiopathies, and commercial kits are available for routine laboratory use.
From 2012 to 2017, 42 patients with suspected thrombotic microangiopathies from 6 Centers were referred to Hemostasis and Thrombosis Center of "Casa Sollievo della Sofferenza" Hospital/Research Institute for ADAMTS13 testing.
The chance of complete remission increased by 10.8-fold (HR 10.8, 95% CI 1.8-65.5, p < 0.001) when ADAMTS13 inhibitor was present in SLE-associated TMA.
Patients/Methods We studied an independent cohort of 112 consecutive hospitalized patients with suspected thrombotic microangiopathy and appropriate ADAMTS-13 testing (including 21 patients with TTP diagnosis).
She had initially presented at 14 years of age with visual disturbance and acute renal failure and been diagnosed with thrombotic thrombocytopenic purpura on the basis of kidney biopsy findings of thrombotic microangiopathy and compatible ADAMTS13 (a disentegrin and metalloproteinase with a thrombospondin type 1 motif member 13).
The quantitative determination of ADAMTS13, ofADAMTS13 activity, and of the ADAMTS13 inhibitor serves to differentiate TTP fromother types of thrombotic microangiopathy.
Triggers for TMAs that can be associated with ADAMTS13 deficiency, including TTP, have been linked to events that place a burden on hemostatic regulation, such as major trauma and pregnancy.
All USS patients from the French registry for TMAs (1 January 2000 to 1 June 2017) were investigated for ADAMTS13 genotype, phenotype (activity, antigen and autoantibodies) and conformation.