The treatment of thrombotic thrombocytopenic purpura: plasma infusion or exchange?

SUMMARY. Classic thrombotic thrombocytopenic purpura has substantial mortality and, because the pathogenesis is uncertain, multiple therapies are often used. These include corticosteroids and antiplatelet drugs, with plasma infusion or exchange most dramatically influencing outcome. To compare the relative efficacy of these latter two options, the records of 20 patients were retrospectively analysed. The groups were well matched for size and disease severity and received equivalent volumes of plasma. No significant difference in response rate or survival was demonstrated, although plasmapheresis may be preferable in the presence of impaired renal function with fluid overload.     

High-dose intravenous gamma-immunoglobulin infusion in the treatment of thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura has been treated with plasmapheresis, exchange transfusion, splenectomy, antiplatelet compounds, glucocorticoids, and vincristine sulfate infusion. We describe a patient with thrombotic thrombocytopenic purpura who has failed on treatment with plasmapheresis, antiplatelet compounds, glucocorticoids, and vincristine, was successfully treated with high-dose gamma-immunoglobulin infusion, and has been maintained in prolonged remission without further immunoglobulin infusion for more than 14 months at the time of this report.     

Cryosupernatant as replacement fluid for plasma exchange in thrombotic thrombocytopenic purpura

The current established treatment of thrombotic thrombocytopenic purpura (TTP) is plasma exchange with fresh frozen plasma (FFP). With this treatment, there is a 49% response after seven exchanges and a 78% survival at 1 month. Although the exact cause of TTP is unknown, the presence of von Willebrand factor (VWF) multimers has been implicated in the disease. Accordingly, it has been suggested that cryosupernatant (plasma from which cryoprecipitate has been removed), which is relatively deficient in VWF multimers, might be an effective replacement fluid during plasma exchange.
Patients from six centres were treated by plasma exchange with cryosupernatant. 18 patients who had failed a first course (average 7.7 exchanges) of plasma exchange with FFP, received a further seven exchanges with cryosupernatant. Subsequently, 40 previously untreated patients were exchanged with cryosupernatant.
Of the 18 previously treated patients, 11 responded (defined as an increase in platelet count to >150 × 10⁹/l and no neurological events) after seven exchanges and 15 (83%) of the patients were alive at 1 month. The response rate in the 40 previously untreated patients was 75% at the end of seven exchanges and 95% of the patients were alive at 1 month. These values are significantly different ( P <0.05) from those reported in our earlier study and in other patients concurrently treated at the same centres with FFP when cryosupernatant was not available.
Some patients who have failed to respond to plasma exchange with FFP replacement will respond to further exchange with cryosupernatant. Cryosupernatant replacement may be more effective as first-line treatment of TTP than FFP.     

Twice daily plasma exchange in refractory thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura (TTP) usually responds to daily single total plasma exchange (TPE) or to plasma infusion. However, some cases are refractory to total plasma exchange, and additional efficacious treatment may not be available. A 34-year-old white male diagnosed with TTP was found to be refractory to single TPE. Steroids and twice daily TPE, in addition to splenectomy and vincristine, worked well to prevent further clinical deterioration. Laboratory values were normalized at the completion of treatment protocol. Cases of TTP refractory to single TPE/day may benefit from early treatment of twice-daily TPE in addition to a combination therapy of steroids, splenectomy, and vincristine.     

Inefficacy of intravenous immunoglobulin in patients with low-risk thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome.

OBJECTIVE: To assess the efficacy of intravenous immunoglobulin (IVIG), in comparison with plasma exchange (PE), in the treatment of patients with thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome (TTP/HUS). DESIGN: Prospective, nonrandomized comparative study. SETTING: Hematology department in a general hospital. PATIENTS: 17 consecutive adult patients, six of them pregnant, with diagnosis of TTP/HUS. Three had a severity score at diagnosis less than or equal to 4 and were treated with IVIG and 14 had a severity score of greater than or equal to 5 and/or were pregnant and received PE. The response was evaluated after 5 days of therapy. RESULTS: Complete remission was obtained in 0/3 cases treated with IVIG and 10/14 (71%) with PE (Fisher's exact test P = 0.05). Three patients died for widespread TTP-HUS, and four had persistent disease. In three of the four resistant patients, complete remission was obtained by further PE but not by further IVIG. The overall remission rate was 76% (13/17). CONCLUSIONS: Our study does not confirm the utility of IVIG in the management of TTP-HUS, as suggested by earlier single case reports.     

Plasma exchange with solvent/detergent-treated plasma of resistant thrombotic thrombocytopenic purpura

A patient with unremitting thrombotic thrombocytopenic purpura (TTP), with circulating von Willebrand factor (VWF) multimers of unusually high molecular weight, and refractory to standard plasma exchange therapy, was treated with solvent detergent (S/D) plasma. The patient achieved a sustained clinical and haematological remission, with normal VWF multimeric profile. Spontaneous remission of this patient's condition could not be excluded but would appear unlikely. S/D plasma was efficacious and potentially safe for repeated large-volume plasma exchange with respect to viral safety and reduction of anaphylactoid reactions. We have assayed coagulation factors and physiological inhibitors of haemostasis in S/D plasma, which were comparable to normal plasma except in the distribution of VWF multimers.
The use of S/D plasma, previously reported in paediatric chronic relapsing TTP, should be assessed in further cases of adult TTP in the context of a clinical trial.     

Intravenous immunoglobulin as an adjunct to plasma exchange for the treatment of chronic thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease. Therapeutic plasma exchange (TPE) is the most effective therapy; however, despite TPE, about one-third of TTP patients will relapse. A subset of patients with TTP has antibodies to ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) and may become resistant to conventional treatments. We describe a patient with TTP and high-titre anti-ADAMTS13 antibodies who developed a chronic, relapsing course of TTP despite frequent TPE. Once adjuvant treatment with intravenous immunoglobulin (IVIG) was added, remission was achieved. Even during remission, anti-ADAMTS13 antibodies remained elevated. We conclude that IVIG may sustain remission in some patients with chronic, relapsing TTP.     

Solvent/detergent fresh frozen plasma as primary treatment of acute thrombotic thrombocytopenic purpura

Three patients with acute thrombotic thrombocytopenic purpura (TTP) (one associated with E. coli infection) received as primary treatment pooled fresh frozen plasma (FFP) virus inactivated by the solvent/detergent (SD) method, plus prednisolone. All three patients attained platelet counts of > 50 × 10⁹/l by days 7, 3 and 10, respectively. Serum creatinine became corrected in parallel. Neurological features were slow to resolve in one patient, and developed de novo during plasma infusion in another with rapid reversal once intensive plasma exchange with SDFFP was instituted. All patients are in stable remission > 1 years later. SDFFP was well tolerated with no febrile or other reactions, and all patients remained negative for markers of infection with HIV, hepatitis B and hepatitis C viruses. One patient was positive for antibodies for hepatitis A virus and parvovirus B19 prior to treatment. The other two patients remained antibody negative at the end of therapy.     

Anti-CD20 antibody in thrombotic thrombocytopenic purpura refractory to plasma exchange

Thrombotic thrombocytopenic purpura is a rare condition characterized by microangiopathic haemolytic anaemia, thrombocytopenia, altered neurology, renal impairment and fever. While plasma exchange has reduced mortality from more than 90% to between 10 and 30%, a proportion of cases fail to respond. Rituximab may be efficacious in the management of refractory cases of thrombotic thrombocytopenic purpura. We present two cases in which rituximab was used with successful outcomes. Treatment resulted in resolution of severe clinical and haematological abnormalities in both patients. There has been no relapse after 16 months follow up. Our experience supports the use of rituximab in difficult cases of TTP. Ongoing evaluation of its use is in progress at our institution.     

Methylene blue-photoinactivated plasma vs. fresh-frozen plasma as replacement fluid for plasma exchange in thrombotic thrombocytopenic purpura

BACKGROUND AND OBJECTIVES: Plasma exchange with fresh-frozen plasma (FFP) is the treatment of choice in thrombotic thrombocytopenic purpura (TTP). Methylene blue-photoinactivated plasma (MBPIP) has been proposed as a safer alternative to FFP, but its effectiveness in the treatment of TTP is not well established. The purpose of this study was to investigate whether MBPIP is as effective as FFP in the treatment of TTP by plasma exchange. MATERIALS AND METHODS: A retrospective analysis was carried out of 56 TTP episodes, occurring between 1990 and 2003, which had been treated by plasma exchange. MBPIP was used for fluid replacement in 27 episodes and FFP in 29. The effect of plasma (MBPIP or FFP) on treatment outcomes was analysed by multivariate logistic regression. RESULTS: Compared to patients treated with FFP, those receiving MBPIP had an increased risk of dying from progressive TTP [adjusted odds ratio (OR) = 31; 95% confidence interval (CI): 1.2 to > 100], a greater number of recurrences while on plasma exchange therapy (OR = 4.6; 95% CI: 1.2-17), and a lower probability of attaining a sustained remission within 9 days of starting plasma exchange (OR = 5.2; 95% CI: 1.3-20). CONCLUSIONS: MBPIP seems to be less effective than FFP in the treatment of TTP. It is therefore prudent to avoid MBPIP until therapeutic equivalency to FFP has been established by randomized, controlled trials.     

Solvent/detergent fresh frozen plasma as primary treatment of acute thrombotic thrombocytopenic purpura.

Three patients with acute thrombotic thrombocytopenic purpura (TTP) (one associated with E. coli infection) received as primary treatment pooled fresh frozen plasma (FFP) virus inactivated by the solvent/detergent (SD) method, plus prednisolone. All three patients attained platelet counts of > 50 x 10(9)/l by days 7, 3 and 10, respectively. Serum creatinine became corrected in parallel. Neurological features were slow to resolve in one patient, and developed de novo during plasma infusion in another with rapid reversal once intensive plasma exchange with SDFFP was instituted. All patients are in stable remission > 1 years later. SDFFP was well tolerated with no febrile or other reactions, and all patients remained negative for markers of infection with HIV, hepatitis B and hepatitis C viruses. One patient was positive for antibodies for hepatitis A virus and parvovirus B19 prior to treatment. The other two patients remained antibody negative at the end of therapy.     

Successful delivery following treatment with plasma exchange in a female patient with thrombotic thrombocytopenic purpura

We report here on a case of a 27-year-old woman in her first pregnancy. She was diagnosed with idiopathic thrombocytopenic purpura (ITP) at the age of 14 years. At 36 weeks of gestation, she was admitted to our hospital due to thrombocytopenia. We initially suspected ITP exacerbated by pregnancy. Laboratory results revealed mild anemia, thrombocytopenia (5.0×10(9)/l), and slightly elevated liver enzymes and lactate dehydrogenase. The next day, hemoglobin fell to 6.6 g/dl. Thrombotic thrombocytopenic purpura (TTP) was suspected on the basis of hemolytic anemia with schistocytes and a negative Coombs' test. Plasma exchange and methylprednisolone were initiated immediately. ADAMTS13 analysis showed a severe deficiency in ADAMTS13 activity but no inhibitors. At Day 6, the platelet count rose to 223×10(9)/l and she delivered a live baby by cesarean section. Currently, the patient receives fresh frozen plasma infusions every 2 weeks due to suspected Upshaw-Schulman syndrome.