Guía diagnóstica y terapéutica de las microangiopatías trombóticas del Grupo Español de Aféresis

Abstract

Thrombotic microangiopathies (TMA) are disorders defined by the presence of a microangiopathic hemolytic anemia (with the characteristic hallmark of schistocytes in the peripheral blood smear), thrombocytopenia and organ malfunction of variable intensity. Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome are the most important forms of TMA and, without the adequate treatment, they are associated with high morbimortality. In recent years, significant advances in the knowledge of the pathophysiology of TMA have occurred. Those advances have allowed us to move from a syndromic diagnosis with a similar treatment to all entities to the search of etiologic diagnosis which would lead to a specific treatment, finally leading to a better outcome of the patient. This document pretends to summarize the current status of knowledge of the pathophysiology of TMA and the therapeutic options available, and to offer a diagnostic and therapeutic practical tool to the professionals caring for the patients.

Hemolytic uremic syndrome in adults: A case report

“…The most common schedule is the replacement of 1.5 plasma volemia/day until stabilization of clinical parameters, when it is reduced to 1 plasma volemia/d; in cases of vital risk it is possible the replacement of 2 plasma volemia. Plasma exchange can be done with unmodified fresh frozen plasma (FFP), inactivated plasma or cryoprecipitated supernatant[2]. Corticosteroids may be given to patients presumed to have TTP at a dose of prednisone 1 mg/kg per day, 1 to 2 mg/kg of methylprednisolone per day or 1 g of methylprednisolone initially for several days, and tapered once the patient goes into remission.…”

“…It has been demonstrated that 50%-60% of patients carry mutations in genes that control the synthesis of regulatory proteins of complement activation (FHC, PCM, FIC, THBD, FBC y C3) or exhibit immunological disorders with antiFHC antibody development. Anomalous regulation of the alternative pathway of the complement occurs with activation of the coagulation cascade and secondary formation of platelet microthrombi at the level of renal capillaries[2,4]. This fact also explain the characteristics low serum levels of C3 and C4 complement found in this disorder.…”

“…After penetrating intestinal mucosa, the toxin is transported through the blood to renal tissue damaging endothelium of glomerular capillaries, mesangial cells and tubular cells of kidneys. Endothelium cells damage promotes a prothrombotic state with increase of platelet adhesion and micro-thrombi formation[1,2,7]. Shiga-toxin also induces secretion of abnormal multimers of FvW increasing platelet adhesion.…”

“…With a low incidence[2], they are characterized by microangiopathic hemolytic anemia and thrombocytopenia, with different grades of other organ injury (mainly acute renal failure, neurological and cardiac involvement). Primary TMA syndromes include thrombotic thrombocytopenic purpura (TTP) in their congenital (Upshaw-Schulman syndrome) and acquired varieties, the haemolytic-uremic syndrome (HUS) associated to infections caused by Shiga toxin-producing pathogens and the atypical HUS, associated to uncontrolled activation of the alternative pathways of complement activation[2]. Secondary TMA are associated to HELLP Syndrome and severe preeclampsia in pregnants, or induced by autoimmune disorders, drugs, systemic infections (HIV, H1N1) and organ transplantations[2].…”

Adjustment of Eculizumab Dosage Pattern in Patients with Atypical Hemolytic Uremic Syndrome with Suboptimal Response to Standard Treatment Pattern

“…Similarly, the determination of the functional alternative complement pathway using a APH50 assay has also been used in the assessment of the response to eculizumab in patients with aHUS [38]. However, it must be taken into account that CH50, which measures the functional activity of the classical complement pathway, is a nonspecific indirect way of measuring the activity of eculizumab and its usefulness in the clinical setting remains controversial [39]. Currently, not all the Spanish centers have included in their aHUS protocols the determination of CH50 or APH50, and the clinical evolution of the patient continues to be a key factor for the assessment of the response to eculizumab and the modification of the treatment pattern.…”