How is thrombotic thrombocytopenic purpura (TTP) treated?

Updated: May 25, 2021
  • Author: Theodore Wun, MD, FACP; Chief Editor: Srikanth Nagalla, MD, MS, FACP  more...
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Therapy should be initiated if the diagnosis of thrombotic thrombocytopenic purpura (TTP) is seriously considered. [15] Only a minority of patients (20-30%) present with the classic pentad of microangiopathic hemolytic anemia, thrombocytopenic purpura, neurologic abnormalities, fever, and renal disease. Consequently, the presence of microangiopathic hemolytic anemia (schistocytes, elevated lactate dehydrogenase [LDH] level, and indirect hyperbilirubinemia) and thrombocytopenia in the absence of other obvious causes (eg, disseminated intravascular coagulation, malignant hypertension) is justification to begin total plasma exchange—preferably within 4–8 hours, according to British TTP guidelines. [16]

Shah et al have described the use of ADAMTS13 (thrombospondin type 1 motif, member 13) measurement to guide the use of plasma exchange in patients with TTP. In their study, plasma exchange was initiated only in patients with ADAMTS13 activity < 10%. Not initiating plasma exchange in patients without severe ADAMTS13 deficiency—or discontinuing plasma exchange after a short course, when baseline ADAMTS13 levels became available and were found to be >11%—proved to be a safe approach, with no increase in mortality. [17]

Because TTP is a medical emergency, long turnaround times for ADAMTS13 activity assay results preclude the use of this test in the decision whether to start plasma exchange. Connell et al reported a significant reduction in plasma utilization for patients with suspected TTP, with no increase in mortality, with the implementation of an assay with a rapid turnaround time. [18]

Plasma exchange with fresh frozen plasma is the therapy of choice for TTP. Octaplas is a pooled plasma (human) that has been treated with a solvent detergent process. This blood product provides a viable alternative to single-donor fresh-frozen plasma, with a reduced risk of certain viral transmissions. Replacement with normal saline and albumin is not adequate. When immediate plasma exchange is not available, simple plasma infusion can be performed until the patient can be transferred to a facility that performs plasma exchange. [19]

In 2019 the FDA approved caplacizumab (Cablivi) for adults with acquired TTP (aTTP), in combination with plasma exchange and immunosuppressive therapy. It is an antibody fragment that targets the A1-domain of von Willebrand factor (vWF), and inhibits the interaction between vWF and platelets, thereby reducing both vWF-mediated platelet adhesion and platelet consumption. 

Approval was based on results from the phase 3 HERCULES trial (n = 145). When caplacizumab was added to plasma exchange and immunosuppression, a significantly shorter time to platelet count response was observed compared with plasma exchange and immunosuppression alone (hazard ratio [HR] 1.55; 95% CI, 1.1-2.2; P = 0.01). Additionally, a significant reduction of aTTP-related death, recurrence of aTTP, or a major thromboembolic event was reduced with the addition of caplacizumab compared with plasma exchange and immunosuppression alone (12.7% vs 49.3%; P < 0.0001). There was also a lower recurrence of aTTP in the caplacizumab treated patients (13% vs 38%; P < 0.001). [5]

Usually, at least five plasma exchanges are performed in the first 10 days. The authors' routine is to exchange 1.5 plasma volumes with each exchange for 5 consecutive days, although some physicians exchange 1 predicted plasma volume. If the first course of exchanges produces no response, a second course of five exchanges can be performed. Others have used a course of at least seven exchanges during the first 9 days of therapy. In the author's cohort, the vast majority of responses were seen within the first 10 plasma exchanges. However, a few patients took up to 15 exchanges to respond.

Plasma exchange generally is well tolerated, although some patients do have intravenous access problems, hypotension, and reactions to plasma. Hypotension can result from the necessary extracorporeal volume in the apheresis device. For small patients, this may represent a considerable fraction of their total blood volume. Using a smaller bowl and/or priming the machine with colloid can circumvent this problem. In addition, the patient can be given a small colloid bolus prior to beginning the procedure.

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