Thrombotic microangiopathies in the 1980s: clinical features, response to treatment, and the impact of the human immunodeficiency virus epidemic

Abstract

We reviewed the medical records of 44 adults with 50 consecutive episodes of thrombotic thrombocytopenia purpura (TTP) or hemolytic uremic syndrome (HUS) seen at the University of California, San Francisco affiliated hospitals during the past decade. Patients were treated according to a uniform plan in which initial therapy included daily large volume plasmapheresis using fresh frozen plasma. Patients not responding completely to initial therapy were treated with a salvage regimen including splenectomy, dextran, and corticosteroids. At the time of diagnosis, the lactate dehydrogenase (LDH) was elevated in 98% of cases, with a median value of 1,208 U/L. Other clinical features were present inconsistently, and only 34% of “TTP” episodes involved the classic pentad of hemolytic anemia, thrombocytopenia, neurologic disorders, noninfectious fever, and renal impairment. Primary treatment with plasma exchange produced complete remission in 56% (27 of 48) of the episodes. Previously splenectomized patients uniformly responded to plasma therapy (12 of 12). In patients not responding completely to primary therapy, salvage splenectomy produced complete responses in 81% (13 of 16) of the cases. The pattern of clinical response to therapy was consistent, with initial resolution of neurologic dysfunction (median, 3 days) followed by normalization of LDH levels (5 days) and platelet count (7 days). Normalization of renal function occurred significantly later (15 days). Although short-term responses to plasma therapy in human immunodeficiency virus (HIV)-seropositive patients did not differ from other patients, no HIV-positive patient survived more than 2 years from diagnosis of thrombotic microangiopathy (TMA). We conclude that the diagnosis of TMA requires a high degree of clinical suspicion and that the diagnostic criteria should consist of microangiopathic hemolytic anemia, thrombocytopenia, and an elevated LDH. Initial therapy with plasma exchange leads to disease control in the majority of cases, but an optimal treatment strategy requires the use of alternative methods if initial remission is transient or not achieved. Salvage therapy with splenectomy, steroids, and dextran is highly effective in this setting.

Human Immunodeficiency Virus‐Associated Thrombotic Microangiopathies: Clinical Characteristics and Outcome According to ADAMTS13 Activity

“…intensive and possibly prolonged plasmatherapy with TPE [25][26][27][28]. By contrast, TMA in more advanced HIV infection with AIDS-related complications usually display a poor response to plasmatherapy [18,[29][30][31][32][33][34][35][36][37], which should question the consideration of prolonged TPE in those patients.…”

Diagnosis of thrombotic thrombocytopenic purpura based on modulation by patient plasma of normal platelet adhesion under flow condition

“…In spite of the significant progression in diagnostic methods, the differential diagnosis of TTP is not easy because various diseases, such as haemolytic uraemic syndrome (HUS), haemolysis, elevated liver enzymes, low platelet syndrome (HELLP) and acute fatty liver of pregnancy (AFLP), share similar clinical features (Thompson et al, 1992;Saphier & Repke, 1998;Cines et al, 2000). Moreover, ultra-large VWF multimers have been found in different clinical situations and in healthy newborns (Mannucci et al, 2001).…”

Usefulness of automatic detection of fragmented red cells using a hematology analyzer for diagnosis of thrombotic microangiopathy

“…Three patients were followed. All had the pentad of thrombocytopenia, anemia, renal dysfunction, fever, and neurologic deficit (Thompson et al, 1992) (Table 1). Case 1 was diagnosed as having hemorrhagic colitis-related TTP and recovered after several plasma exchange (PE) procedures.…”