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Thrombotic Microangiopathies (TMAs) result from various pathogenic mechanisms (immune, infectious, complement dysfunction, toxins, shear stress), sharing a common final phenotype, the damage of endothelial cells leading to microcirculation thrombosis. They are clinically characterized by microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and ischemic damage to multiple organs.
Malignant Arterial Hypertension (MAH) is characterized by markedly elevated blood pressure (often exceeding 200/130 mmHg) associated with Grade III retinopathy, with or without papilledema, and multiorgan involvement due to diffuse arteriolar damage. Renal involvement varies and may manifest as severe renal failure associated with TMA. The pathogenic mechanism is linked to an increase in angiotensin II and a decrease in nitric oxide, resulting in vasoconstriction and platelet aggregation.
Treatment strategies vary depending on the etiology. The differential diagnosis is essential from the beginning, sometimes the diagnosis is made by rule out as we share in this case.
A 47-year-old male with a history of untreated hypertension presented at the ER with headache and blurred vision. His blood pressure was 180/100 mmHg, and he exhibited psychomotor excitement, with a brain CT scan showing no abnormalities. Laboratory results revealed anemia (Hb 10.5 g/dl), thrombocytopenia (86000/mm³), and renal insufficiency (Urea 130 mg/dl, Cr 3.4 mg/dl). Urinalysis indicated findings compatible with ATN, and proteinuria 2.1 g/day. Peripheral blood smear showed schistocytes (4 per field), elevated LDH, and a negative direct Coombs test. The diagnosis of AKI KDIGO III due to TMA was made. Test fo rruling out rheumatological and infectious causes were negative. ADAMTS13 activity was requested, and treatment with plasma exchange and corticosteroids was initiated. This resulted in the disappearance of schistocytes on the peripheral blood smear and correction of thrombocytopenia, but no improvement in renal function.
The patient developed hypertensive encephalopathy (Grade IV retinopathy, brain MRI showingfindingsconsistentwithhypertension-relatedmicroangiopathy). He required titratable antihypertensive medications, leading to improved blood pressure and neurological status. Secondary causes of hypertension were ruled out. Renal biopsy revealed mesangial expansion, mesangiolysis, double contour formation in glomeruli, 35% interstitial atrophy and fibrosis, and arterioles with muscular hyperplasia resembling "onion skin." Immunofluorescence was negative, and electron microscopy showed no deposits. The ADAMTS13 activity was normal. Exome sequencing directed toward atypical hemolytic uremic syndrome was negative for clinically significant variants, leading to the interpretation of TMA secondary to MAH.
With the advent of antihypertensive therapies, the incidence of severe renal involvement in MAH has been decreasing in the last decades. The diagnosis of these patients is a real challenge, because TMAs from various causes can be associated with severe hypertension. It is essential to have complete diagnostic study from the beginning to adequate the management strategies. In our case, based on all the studies conducted, we can conclude that the TMAs were secondary to MAH because we could not find another factor associated.