Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: pathophysiology and management. Myers L. Nephrology Nursing Journal 2002;29(2):171-180.

ABSTRACT:

Pathogenic mechanisms of renal injury by thrombotic microangiopathies present a challenge to the multidisciplinary team caring for a patient with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS). First recognized 77 years ago as a rare disorder characterized by reversible platelet aggregation in the microcirculation causing ischemia in various organs, the prognosis was always fatal. In the past 20 years, due to effective treatment with plasma exchange therapy, there has been a decline in the mortality rate to 10-20%. The classic pentad of symptoms of TTP-HUS includes thrombocytopenia, microangiopathic hemolytic anemia, neurologic abnormalities, fever, and renal impairment. Frequency of TTP-HUS appears to be increasing. Due to the urgent need for a diagnosis, sufficient diagnostic criteria for TTP-HUS are currently thrombocytopenia and microangiopathic hemolytic anemia in the absence of another apparent cause. Exchange transfusions of fresh frozen plasma (FFP) or cryo-poor plasma (CPP) remain the cornerstone of treatment for classic TTP-HUS. A multiinstitutional study comparing initial therapy of TTP using either treatment type demonstrated that the efficacy is the same in both FFP and CPP. Therapeutic plasma exchange (TPE) is effective in treating this illness because it not only allows for the replacement of the metalloproteinase by means of replacement plasma, but also removes other elements from the plasma that contribute to TTP. A plasma product that has recently been developed and used successfully in patients who are refractory to standard TPE therapy is solvent detergent treated plasma (SDP). Use of SDP can prevent exposure of patients to the plasma from very large numbers of donors. Further clinical trials are needed to determine if SDP is as effective as CPP or whether the alterations in the SDP have any impact on the disease. TPE is not without risks, such as infection. Patients may need to be medicated with corticosteroids, antihistamines, or epinephrine due to a 50% rate of hypersensitivity reactions with FFP. Glucocorticoids, such as prednisone, are standard therapy for all TTP patients. Vincristine is a chemotherapeutic agent, which can be effective in patients refractory to plasma exchange, platelet inhibitor drugs, or corticosteroids. Survival may be increased to as much as 88% with vincristine. These advances in therapy have opened the door for new therapies in what still remains a life-threatening condition for some patients. There is a need for further multicenter studies to address treatment issues and for long-term follow-up with quality of life surveys.