Thrombotic thrombocytopenic purpura (TTP) is the common name for adults with microangiopathic hemolytic anemia, thrombocytopenia, with or without neurologic or renal abnormalities, and without another etiology for thrombotic microangiopathy (TMA).
In 10 years before, we believed that the classic clinical features of TTP which was called “classic pentad” were thrombocytopenia, microangiopathic hemolytic anemia, neurologic abnormalities, renal function abnormalities, and fever. I gave these symptoms a abbreviation name that is “TMNRF”. However now the “classic pentad” is not considered to be the classic clinical features of TTP anymore. In a study of 58 TTP patients, only 5% (3) of TTP patient had the old “classic pentad” symptoms, in whom two were subsequently discovered to have systemic infections as the cause of their clinical features; one had a previously established diagnosis of systemic lupus erythematosus (SLE).
Now the characteristic of all TTP is TMA which is called thrombotic microangiopathy. TTP is the name used for adults with microangiopathic hemolytic anemia and thrombocytopenia, with or without renal failure or neurologic abnormalities, and without another cause for TMA. These were the inclusion criteria for the randomized clinical trial that documented the benefit of plasma exchange treatment, and they have become the definition and diagnostic criteria for TTP.
Before the plasma exchange era, survival of patients with TTP was only 10%. When plasma exchange was reported to increase survival to 78%, compared with 51% survival for patients treated with plasma infusion.
VWF-Cleaving Protease (ADAMTS13)
Platelets in flowing blood adhere transiently to exposed, immobilized VWF. Transient adhesion is followed by the engagement of other adhesive and signaling receptors, which causes platelet activation, immobilization, and spreading. This platelets surface can recruit more VWF and more platelets by the same mechanism. Under the influence of fluid shear stress, the VWF is recognized by ADAMTS13, which cleaves VWF multimers, releases the platelets, and limits the growth of the thrombus. Without ADAMTS13, this feedback inhibitory mechanism fails, and microvascular thrombi continue to grow, causing tissue ischemia and infarction.
However, measurements of ADAMTS13 activity are not required and may not be appropriate for the critical initial management decision to begin or not begin plasma exchange. But severe acquired ADAMTS13 deficiency dose define a subgroup of patients who appear to benefit from treatment with corticosteroids and other immunosuppressive agents in addition to plasma exchange but who have a high risk for relapse.
Management of TTP
For acute episodes of TTP, plasma replacement is essential;replacement with one plasma volume is appropriate;all plasma products (fresh-frozen plasma, 24-hour plasma, cryoprecipitate-poor plasma) appear to have equivalent efficacy. Plasma infusion can provide temporary benefit until plasma exchange can be begun.
The assumption that plasma exchange may work by replacing ADAMTS13 and removing autoantibodies that inhibit its activity may not apply to all patients because response to plasma exchange may be the same in patients without a severe deficiency of ADAMTS13.
The complications of plasma exchange treatment are list in the table below, including central venous catheter-related sepsis, hemorrhage caused by catheter insertion, and cardiac arrest with pulseless electrical activity, which can cause fatal consequence.
For patients with severe ADAMTS13 deficiency, corticosteroids treatment may be valuable because their suppression effects on autoantibodies that inhibit ADAMTS13 activity. Patients who are unlikely to have severe ADAMTS13 deficiency are not treated with corticosteroids.
The response to plasma exchange, with or without corticosteroids, is judged by the platelet count. Once the platelet transfusions in patients with TTP is dangerous several decades ago. Now a systematic review of published case reports and case series did not document a risk from platelet transfusions. In most patients with severe thrombocytopenia and anemia, the platelet transfusion were given as part of common initial care. And no adverse events were identified.
After a remission occurs, patients need gradually fewer routine blood counts over several months;after this, they need only routine care from their primary physician. A platelet count is absolutely necessary when symptoms of any illness occur, to immediately diagnose a possible recurrence of TTP.
Many patients have persistent or intermittent ADAMTS13 deficiency after recovery. Among 41 patients who initially had severe ADAMTS13 deficiency and who have had one to 4 measurements of ADAMTS13 activity during remission, 7 (17%) have had ADAMTS13 activity less than 50% and 19 (46%) have had ADAMTS13 less than 50% at some time during their remissions;9 (22%) have had an ADAMTS13 inhibitor. However, severe ADAMTS13 deficiency during remission was not associated with clinical signs of TTP, and its clinical importance related to risk for relapse is uncertain.
Risk for relapse
The estimated risk for relapse is 41% at 7.5 years;relapses are most common during the first year after recovery. Relapse rarely occurs in patients without severe ADAMTS13 deficiency.