Further Outpatient Care
The necessary outpatient follow-up for patients with thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS) who have entered a complete or partial response is not well defined. After recovery from an acute episode of immune TTP, patients are at risk of both relapse and long-term complications that include neurocognitive deficits and cardiovascular events. [39] Anecdotal reports of increased relapse rates upon abrupt cessation of plasma exchange have resulted in many apheresis services tapering off plasma exchange over the course of 2-3 weeks. However, this practice has not been validated in any prospective or retrospective analysis.
Recommendations are that the patient be seen every week for 2 weeks and, if stable, every 2 weeks for a month. During this time, weekly measurement of a complete blood count and lactate dehydrogenase (LDH) are performed. If the platelet count drops or the LDH level starts to rise, another course of five plasma exchanges is reinstituted. If the patient remains stable for a month, the frequency of the follow-up is decreased.The relapse rate is 13-36%, and recurrences as many as 9 years later have been reported.
Regular monitoring of ADAMTS13 activity is also recommended during follow‐up of patients with TTP in remission. A decrease in ADAMTS13 activity to less than 10 IU/dL is generally considered an indication for preemptive therapy to prevent clinical relapse. Rituximab is typically used for preemptive therapy; however, approximately 15% of patients experience refractoriness or intolerance to rituximab. Comparon et al report successful use of cyclosporine for preemptive therapy in such cases. [40, 15, 41]
Further Inpatient Care
Patients with TTP should remain hospitalized until at least a partial response is achieved. Criteria for discharge include the following:
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Resolution of altered mental status
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Improved platelet count
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Reduced LDH level
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Stable hemoglobin level
In some patients, intravenous access will become a concern. Large-bore dual-lumen apheresis catheters are now readily available and many are now placed by interventional radiology services. The patient and/or a caregiver can be instructed in the proper care of these catheters.
Complications
If patients recover from the acute episode of TTP or HUS, generally, no long-term complications occur. Complications can be divided into disease-related and treatment-related.
Disease-related complications are rare. Persistent neurologic abnormalities can occur after otherwise successful treatment of TTP. Abnormalities may result from actual stroke. Persistent renal impairment to the point of requiring dialysis is rare, although mild renal impairment may persist for weeks to months.
Treatment-related complications include fluid overload or allergic reactions from plasma infusion. Apheresis catheters can become thrombosed or infected. During the apheresis, hypotension can occur. Paresthesias are related to hypocalcemia from the anticoagulant acid-citrate dextrose (ACD) most commonly used in apheresis procedures; however, this is transient. Long-term complications include the small risk of a bloodborne infection.
Prognosis
The overall response rate to plasma exchange is 75-90%.The early mortality rate is 10-20%.
Long-term survival depends largely on the presence or absence of serious underlying comorbidities such as cancer, HIV infection, or solid organ transplantation. In the authors' series of 126 patients, the estimated 10-year survival rate of patients without comorbid conditions was 82%, compared with a survival rate of 50% if comorbid conditions were present.
A clinical severity score, incorporating the presence or absence of neurologic symptoms, creatinine, platelet count, and hemoglobin, was shown to be predictive of 30-day mortality in the authors' retrospective analysis. The absence of fever and a higher creatinine level was associated with a higher rate of relapse. However, upon further analysis of a larger cohort of patients (as yet unpublished), these factors are no longer predictive.
A study by Staley et al of 73 patients with immune-mediated TTP found that the following findings on admission were associated with higher mortality [42] :
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Prolonged activated partial thromboplastin time
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High fibrinogen level
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Elevated serum lactate dehydrogenase level
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Elevated complement activation marker Bb
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Elevated complement activation marker sC5b-9
Other findings predictive of higher mortality included the following [42] :
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Failure to normalize platelet counts within 7 days
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Failure to markedly reduce serum lactate dehydrogenase by day 5
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Low total serum protein or albumin
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High troponin levels prior to total plasma exchange
Shumak et al reported that more than one third of patients who survive an acute episode of TTP will have at least one relapse in the following 10 years. [43] French researchers found that patients who have had acute TTP are at increased risk for development of an autoimmune disorder—most often, systemic lupus erythematosus (SLE) or Sjögren syndrome—for as long as 12 years afterward. Risk was highest in patients who had anti–double-stranded (ds)DNA antibodies (hazard ratio [HR] 4.98) or anti-SSA antibodies (HR 9.98) at the time of TTP diagnosis. These researchers recommend prolonged follow-up to detect any autoimmune disorder early in its course. [44]
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Differential diagnosis of immune thrombocytopenia (ITP), thrombotic thrombocytopenic purpura (TTP), and disseminated intravascular coagulation (DIC).
