eMedicine Specialties > Hematology > Coagulation, Hemostasis, and Disorders

Thrombotic Thrombocytopenic Purpura: Treatment & Medication

Author: Theodore Wun, MD, FACP, Professor of Medicine, Professor of Pathology and Laboratory Medicine, University of California Davis School of Medicine; Chief of Hematology/Oncology, Program Director, Veterans Affairs Northern California Health Care System; Medical Director, University of California Davis CCRC
Coauthor(s): Wadie F Bahou, MD, Chief, Division of Hematology, Hematology/Oncology Fellowship Director, Professor, Department of Internal Medicine, State University of New York at Stony Brook
Contributor Information and Disclosures

Updated: Aug 27, 2009

Treatment

Medical Care

Therapy should be initiated if the diagnosis of thrombotic thrombocytopenic purpura (TTP) is seriously considered. Only the minority of patients (20-30%) present with the classic pentad. The presence of microangiopathic hemolytic anemia (schistocytes, elevated LDH, and indirect hyperbilirubinemia) and thrombocytopenia in the absence of other obvious causes (DIC, malignant hypertension) is justification to begin total plasma exchange.

• The therapy of choice for TTP is plasma exchange with fresh frozen plasma. Replacement with normal saline and albumin is not adequate. When immediate plasma exchange is not available, simple plasma infusion can be performed until transfer to a facility that performs plasma exchange.
  • Patients with HUS (usually children) often require dialysis. Plasma exchange is reserved for refractory cases.
  • Some large series have reported resolution of HUS with dialysis alone or with steroid therapy.
• Usually, at least 5 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 no response to exchange is observed, a second course of 5 exchanges can be performed. Others have used a course of at least 7 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. If the person is small, then this may represent a considerable fraction of the 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.
• Complete response criteria differ depending on the investigator, but they generally include the following:
  • Disappearance of neurologic symptoms
  • Normalization of hemoglobin, platelet count, LDH, and bilirubin
  • Normalization of creatinine
• Adequate initial response is fulfilled if neurologic signs and symptoms disappear, the platelet count climbs to greater than 50,000/microliter, and the LDH declines.
• In patients who respond to plasma exchange, the mean time to resolution of neurologic changes is approximately 3 days, to a normal LDH is 5 days, to a normal platelet count is 10 days, and to normal renal function is 15 days.
• The total number of exchanges necessary for sustained response is not established. Anecdotally, the rate of relapse is increased if plasma exchange is stopped abruptly, although no prospective, or even retrospective, study has shown this to be true. Regardless, many apheresis services taper the exchanges from 3 per week to 1 per week before stopping therapy. In the author's experience, a direct correlation existed between the number of exchanges required to reach a platelet count of 150,000 per microliter and the risk of relapse.
• Marn Pernat et al reported their 11-year experience with membrane plasma exchange for the treatment of TTP.⁴ Therapy was immediately initiated in 56 patients, then once or twice daily until the platelet counts were normalized, with an average number of 19 +/- 17 plasma exchanges per patient. Nearly 1100 plasma exchange procedures were performed, in which 1-1.5 plasma volumes (3606 +/- 991 mL) were replaced with fresh frozen plasma, with an average duration of 23 +/- 17 days.⁴ Although renal impairment was found in 36% of patients, 93% (52/56) had an excellent response to the therapy, of whom 86% (48 patients) reached complete remission (platelet count > 100 × 10⁹/L).⁴ There were 4 deaths soon after plasma exchange therapy was initiated (post 1-3 procedures), and in the follow-up period, of 6 patients who had achieved complete remission and subsequently had 1-5 relapses each year, 1 died of acute hemolytic reaction during tapering of the therapy. Additional splenectomy was performed on 3 patients.⁴ Overall, Marn Pernat et al did not find serious side effects with plasma exchange therapy in their cohort of 1066 patients.
• In those patients refractory to plasma exchange, using cryopoor plasma (or cryosupernatant) has sometimes led to a response. This is fresh frozen plasma that has had the cryoprecipitate removed and is thus depleted of high-molecular weight von Willebrand multimers, which have a pathogenic role in TTP. Whether cryosupernatant is superior to regular fresh frozen plasma is unknown and is the subject of a randomized trial.
• Corticosteroids are commonly given to patients with TTP, and responses to this alone have been documented. The use of aspirin and dipyridamole, although part of standard therapy in the past, has fallen out of favor. Vincristine, a vinca alkaloid generally used as chemotherapy, also has been shown to be useful in refractory patients. Complete response has been reported in one patient with TTP treated with vincristine alone. Finally, reports have shown patients improving with therapy using a staphylococcal protein A column (Prosorba), which presumably acts by removing immune complexes.
• Platelet transfusions should be avoided unless life-threatening (usually CNS) bleeding is present. Anecdotal reports have documented myocardial infarction and stroke following platelet transfusion in patients with TTP.

Surgical Care

• Surgical colleagues may be consulted for placement of a central venous access device adequate for apheresis and splenectomy, which has been used in refractory cases of TTP.

Consultations

• Hematologist
• Apheresis service, if different from the hematologist
• Nephrologist, if renal impairment warrants dialysis

Diet

• Other than a renal diet if the patient is azotemic or uremic, no diet is indicated for this condition.

Activity

• Activity should be restricted if the patient has altered mental status or bleeding.

Medication

Generally, drug therapy is reserved for refractory patients. Some hematologists routinely treat patients with steroids, and given the data that acquired TTP may be an autoimmune disorder with an inhibitory antibody to vWF-cleaving protease, this practice has appeal. The chemotherapeutic agent vincristine has been used as an adjunct to plasma exchange in patients with refractory disease, but its routine use has not been validated. Recent case reports have suggested that cyclosporin may be beneficial in patients with refractory disease even though this drug has been incriminated as a potential etiology of TTP.⁵ Although used in the past, aspirin and dipyridamole are no longer used in treating TTP. The anti-CD20 monoclonal antibody rituximab has also been reported to have activity in patients' refractory to plasma exchange.

Chemotherapy agents

These agents are used as an adjunct to plasma exchange.

Vincristine (Oncovin, Vincasar)

Mechanism of action uncertain. May involve a decrease in reticuloendothelial cell function or increase in platelet production. However, neither of these mechanisms fully explains the effect in TTP and HUS.

Corticosteroids

These agents are used to treat idiopathic and acquired autoimmune disorders. They are also used as an adjunct to plasma exchange.

Prednisone (Sterapred)

May work by decreasing activity of reticuloendothelial system. In light of the evidence that patients with acquired TTP have an inhibitor to vWF-cleaving protease, steroids may decrease production of autoantibody.

Monoclonal antibody

These agents have shown efficacy in the treatment of autoimmune disorders.

Rituximab (Rituxan)

Anti-CD20 chimeric monoclonal antibody initially approved for therapy of follicular lymphoma. Has been shown to have activity in several autoimmune disorders such as immune thrombocytopenia, systemic lupus erythematosus, autoimmune hemolytic anemia, and rheumatoid arthritis.

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