Rituximab for treatment of refractory/relapsing thrombotic thrombocytopenic purpura (TTP)

Plasma exchange is the standard treatment for thrombotic thrombocytopenic purpura (TTP). For patients refractory to plasma exchange, treatment options are limited and often unsuccessful. The platelet thrombi that form in acquired TTP are believed to result from the presence of procoagulant ultralarge multimers of von Willebrand factor (VWF) in the circulation due to autoantibody inhibition of VWF cleaving protease (ADAMTS-13), the enzyme that normally cleaves the ultralarge multimers. Rituximab, a chimeric monoclonal antibody against CD20, has been recognized as a useful therapy for antibody-mediated autoimmune disease. We therefore treated four patients with recurrent TTP with 2 or 4 weekly doses of rituximab in addition to corticosteroids, vincristine, plasma, or continuing plasma exchange. Three patients responded with prompt improvement in microangiopathic hemolytic anemia and thrombocytopenia, which allowed plasma exchange to be discontinued or avoided and prednisone to be rapidly discontinued. Two of the 3 responders have remained in unmaintained complete remission for 13+ months. The third patient relapsed at 13 months; a second course of rituximab and prednisone resulted in an unmaintained remission for 6+ months. All four patients were tested for ADAMTS-13 activity and its inhibitor at a point in their course when samples were available. Low ADAMTS-13 activity was noted in 3 patients tested at relapse, and the inhibitor activity was detectable in 2 patients. ADAMTS-13 activity increased during remission in one of these 2 patients although the patient had a persistence of the inhibitor. One patient tested only during remission had a normal ADAMTS-13 level. We conclude that rituximab may have a role and deserves further study in the treatment of patients with relapsing TTP.     

Rituximab for chronic recurring thrombotic thrombocytopenic purpura: a case report and review of the literature

Deficiency of von Willebrand factor (VWF) cleaving protease ADAMTS13 has been demonstrated to be the proximate cause of a subset of thrombotic microangiopathic haemolytic anaemias (MAHA) typical for thrombotic thrombocytopenic purpura (TTP). ADAMTS13 gene mutations cause the hereditary form; acquired deficiency has been attributed to presence of an autoantibody, which may represent a specific subset of MAHA best termed 'autoimmune thrombotic thrombocytopenic purpura'. We describe a patient with relapsing TTP because of ADAMTS13 inhibitors, who failed to achieve sustained remission despite therapies with plasma exchange, steroids, vincristine, staphylococcal protein A and splenectomy. The ADAMTS13 inhibitor titre remained elevated and clinical stability was only maintained by plasma exchange every 2-3 d over a period of 268 d. The patient then received rituximab therapy (eight doses of 375 mg/m2 weekly), during which she required five plasma exchanges in the first 10 d, two exchanges in the next 3 weeks, and none thereafter for 450 d and ongoing. The ADAMTS13 inhibitor titre decreased and enzyme activity increased. We compared this case with that of seven previously reported TTP cases also treated with rituximab; experience suggests that rituximab therapy deserves further investigation for patients with either refractory or relapsing TTP caused by ADAMTS13 inhibitors.     

Rituximab for acute plasma-refractory thrombotic thrombocytopenic purpura. A case report and concise review of the literature

Thrombotic thrombocytopenic purpura (TTP) is a rare disease which responds well to plasma exchange treatment in the majority of patients. We report on a patient with acute TTP caused by severe autoantibody-mediated ADAMTS-13 deficiency, in whom remission was not achieved by initial treatment consisting of plasma exchange (PE), plasma infusion and corticosteroids, followed by vincristine and splenectomy. In view of the ongoing activity of TTP, treatment was initiated with rituximab, a chimaeric monoclonal antibody directed against the CD 20 antigen present on B lymphocytes. The patient received 4 weekly infusions of 375 mg/m2, each administered after the daily PE session and withholding PE until 48 hours later. Three weeks after the last infusion of rituximab a complete clinical and laboratory remission of this first episode of acute refractory TTP was documented. A concise review of the literature on the role of rituximab in patients with a first episode of acute plasma-refractory TTP suggests that rituximab in that situation may produce clinical remission in a significant proportion of patients, result in a lowered plasma requirement and avoid the complications of salvage immunosuppressive therapy. The use of rituximab in acute refractory TTP appears to be safe, with no excess infectious complications. We conclude that rituximab should be considered in TTP patients with acquired ADAMTS-13 deficiency who fail to respond clinically after 7-14 days of standard treatment with daily PE and glucocorticoids.     

High-dose plasma infusion versus plasma exchange as early treatment of thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome

Thrombotic thrombocytopenic purpura and adult hemolytic-uremic syndrome (TTP/HUS) have a substantial mortality rate even with currently available treatments. Although therapeutic plasma exchange is the recommended treatment of TTP/HUS, this cumbersome procedure may not be available for all patients in an emergency. In this context, plasma infusion may represent an alternative first-line therapy. We compared the effectiveness of high-dose plasma infusion (25-30 mL/kg per day) and therapeutic plasma exchange as first-line treatment of adult TTP/HUS at a single center. Two groups of patients with TTP/HUS were identified according to their initial therapy, that is, high-dose plasma infusion (19 patients) and therapeutic plasma exchange (18 patients). Clinical charts and outcomes were retrospectively analyzed. Endpoints for comparison were the duration of platelet counts below 150 x 10 /L and LDH levels above normal values; the volumes of plasma administered and the duration of treatment; complete remission, relapse, and mortality rates; and treatment-related complications. Patients of the 2 groups had comparable clinical and laboratory features on admission. Sixteen patients achieved complete remission in each group. Median times to recovery of platelet counts and LDH levels were comparable between the 2 groups. Eight patients in the high-dose plasma infusion (HD-PI) group were switched to therapeutic plasma exchange because of fluid overload (6 patients), persistent biologic disturbances (1 patient), or unresponsiveness to high-dose plasma infusion treatment (1 patient). This latter patient had severe TTP/HUS that remained refractory to therapeutic plasma exchange and vincristine, and rapidly died. All 7 remaining patients achieved complete remission with therapeutic plasma exchange. Four patients in the HD-PI group and 3 patients in the therapeutic plasma exchange (TPE) group died. In the HD-PI group, 5 patients experienced a transient nephrotic-range proteinuria during treatment. Main complications in the TPE group were collapse (1 patient) and central venous catheter infection (2 patients) or thrombosis (1 patient). Three patients in each group relapsed. High-dose plasma infusion may be an efficient treatment of TTP/HUS in patients who cannot have early plasma exchange. However, the large volumes of plasma required to reach complete remission may result in fluid overload, which may necessitate subsequent therapeutic plasma exchange.     

Refractory thrombotic thrombocytopenic purpura successfully treated with a combination of rituximab and vincristine

A 26-year-old man was referred to our hospital with vomiting and high fever. He was disoriented and laboratory results showed microangiopathic hemolytic anemia (Hb 7.1 g/dl) and severe thrombocytopenia (15 x 10(3)/microl). The diagnosis of thrombotic thrombocytopenic purpura (TTP) was established. The activity of von Willebrand cleaving protease (ADAMTS13) was found to be remarkably low (<0.5%) and the high activity of the inhibitor (11.0 Bethesda U/ml) was detected, confirming the diagnosis of typical acquired TIP. Although he had been successfully treated with daily plasma exchange and methylprednisolone, he relapsed after a week. To this therapeutic strategy we added four weekly doses of rituximab (375 mg/m2) and two weekly doses of vincristine (1 mg/m2) simultaneously. The response was very rapid and complete, that is, the platelet count recovered to normal seven days after the first rituximab and vincristine treatment. The patient maintains complete remission nine months later under the administration of 17.5 mg prednisolone. Recovery of the plasma ADAMTS13 activity was clearly correlated with the decrease or disappearance of the inhibitor activity. Combination of rituximab and vincristine therapy would appear to be very effective against refractory TTP.     

Two cases of refractory thrombotic thrombocytopenic purpura associated with collagen vascular disease were significantly improved by rituximab treatment

Thrombotic thrombocytopenic purpura (TTP) is a rare disorder of small vessels. TTP is associated with deficiency of the von Willebrand factor-cleaving protease, ADAMTS13, and its inhibitor. Low ADAMTS13 activity is present in most of idiopathic TTP patients. The prognosis of TTP was improved by plasma exchange treatment, which replaces the ADAMTS13 and removes ADAMTS13 inhibitor. However, ADAMTS13 activity is normal in some TTP patients. These are found among the secondary TTP patients associated with collagen disease, hematopoietic stem cell transplantation, malignancy, or drugs. In addition, most of them do not respond to plasma exchange. On the other hand, several reports demonstrated that rituximab, which is an anti-CD20 monoclonal antibody, is effective for refractory TTP cases caused by ADAMTS13 deficiency. It is considered that the effect of rituximab is associated with disappearance of ADAMTS13 inhibitor. However, rituximab therapy was effective for the TTP patients with normal ADAMTS13 activity in our cases. We considered another mechanism of rituximab for TTP cases.     

Rituximab prevents recurrence of thrombotic thrombocytopenic purpura: a case report

Thrombotic thrombocytopenic purpura (TTP) is a rare disorder of small vessels that is associated with deficiency of the von Willebrand factor-cleaving protease, ADAMTS13. The presence of anti-ADAMTS13 autoantibodies is considered a factor predisposing to relapses. Despite close monitoring and intensive plasma treatment, in these patients acute episodes are still associated with substantial morbidity and mortality rates, and the optimal therapeutic option should be prevention of relapses. This study was conducted in a patient with recurrent TTP due to high titers of ADAMTS13 inhibitors, who used to have 2 relapses of TTP a year. The study compared the standard treatment plasma exchange with rituximab. Results documented that plasma exchange had only a small transient effect on ADAMTS13 activity and inhibitors; on the contrary, prophylaxis with rituximab was associated with disappearance of anti-ADAMTS13 antibodies, a progressive recovery of protease activity, and it allowed the patient to maintain a disease-free state during a more than 2-year follow-up.     

Thrombocytopenic purpura and cardiomyopathy in pregnancy reversed by combined plasma exchange and infusion

Thrombocytopenia and hemolytic anemia have been seen with thrombotic thrombocytopenic purpura (TTP), HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets), and hemolytic uremic syndrome (HUS). Differentiating between TTP, HUS, and HELLP syndrome is often difficult. Coexistence of TTP and HELLP is possible. Cardiomyopathy occurring in pregnancy can be idiopathic or associated with TTP. We describe a previously healthy woman who developed thrombocytopenia and hemolysis at 34 wk gestation. The patient underwent delivery after transfusion with platelets and RBCs. The suspicion of TTP was raised, and plasma exchange was begun by the third hospital day. On the seventh day of treatment, the patient developed shortness of breath, and an echocardiogram showed global hypokinesis with an ejection fraction of 25%. Plasma infusion, one unit q 4 h, was initiated in addition to the daily plasma exchange. The patient improved and her ejection fraction normalized. Plasma exchange and infusion and corticosteroids were gradually tapered off. von Willebrand factor (vWF) protease activity in the plasma upon transfer was completely deficient with the presence of inhibitor. This case illustrates that vWF protease assay and detection of inhibitor can be used for the diagnosis of TTP during pregnancy; and a severe cardiomyopathy in TTP can be reversed rapidly with combined plasma exchange and infusion.     

Rituximab induces remission of cerebral ischemia caused by thrombotic thrombocytopenic purpura

OBJECTIVE: This report describes the experience of a case of atypical thrombotic thrombocytopenic purpura (TTP) whose diagnosis was based on severe deficiency of the von Willebrand factor (vWF) cleaving metalloprotease ADAMTS13. METHODS: The level of ADAMTS13 activity, the titer of the inhibitors of this protease and the size distribution of vWF multimers in plasma samples were analysed in a patient with recurrent episodes of dizziness and blurred vision. RESULTS: In the absence of thrombocytopenia or microangiopathic hemolysis, diagnosis of TTP was established by demonstration of very low ADAMTS13 activity levels and the presence of inhibitors of this protease. After rituximab therapy decreased the inhibitor titer and increased the ADAMTS13 level, the patient has had no relapse of ischemic symptoms in the following 16 months. CONCLUSIONS: Acute neurological deficits may occur in TTP without concurrent thrombocytopenia or microangiopathic hemolysis. The role of rituximab for patients with TTP deserves further exploration.     

Efficiency of curative and prophylactic treatment with rituximab in ADAMTS13-deficient thrombotic thrombocytopenic purpura: a study of 11 cases

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease that occurs mainly in young adults. Acquired cases are usually a result of antibodies directed against ADAMTS13 (a disintegrin-like and metalloprotease [reprolysin type] with thrombospondin type 1 motif 13), a protease that cleaves the von Willebrand factor multimers. Prognosis has been improved by plasma therapy, but some acute severe forms are refractory to this treatment and achieving a sustained remission is still a challenge in chronic relapsing forms. We therefore conducted a multicentric open-label prospective trial to test the efficacy of rituximab, an anti-B-cell monoclonal antibody, as a curative and prophylactic treatment in patients with TTP as a result of anti-ADAMTS13 antibodies. Six patients were included during an acute refractory TTP episode. Five patients with severe relapsing TTP and persistent anti-ADAMTS13 antibodies were prophylactically treated during remission. All patients received 4 weekly infusions of rituximab. The target of treatment was to restore a significant ADAMTS13 plasma activity (> 10%). Treatment with rituximab led to clinical remission in all cases of acute refractory TTP. In all patients, anti-ADAMTS13 antibodies disappeared, and a significant (18%-75%) plasma ADAMTS13 activity was detected following treatment. Tolerance of rituximab was good. Rituximab is a promising first-line immunosuppressive treatment in patients with acute refractory and severe relapsing TTP related to anti-ADAMTS13 antibodies.     

Effects of fresh-frozen plasma and its cryosupernatant fraction on von Willebrand factor multimeric forms in chronic relapsing thrombotic thrombocytopenic purpura

Remission plasma samples of some patients with chronic relapsing thrombotic thrombocytopenic purpura (TTP) contain unusually large von Willebrand factor (vWF) multimers similar to those produced by normal human endothelial cells in culture. The infusion of the cryosupernatant fraction of normal plasma is as effective as normal fresh-frozen plasma (FFP) in the treatment or prevention of TTP episodes in patients with the chronic relapsing form of TTP. Three patients with chronic relapsing TTP during remission have unusually large vWF multimers present in their plasma. Two of the patients were transfused once with FFP, one of the two received cryosupernatant on three occasions, and the third patient was studied before and immediately after plasma exchange. Unusually large vWF multimers decreased or disappeared from patient plasma samples within 1/2 to 1 1/2 hours following the transfusion of FFP (on two occasions) or cryosupernatant (on two of three occasions), and immediately after plasma exchange (on one occasion). The patient who received cryosupernatant was studied serially after the infusions. Unusually large vWF multimers returned to her plasma within ten to 24 hours and persisted thereafter. Unusually large vWF multimers did not disappear from patient remission plasma samples, or from the culture medium removed from normal human endothelial cells, when these fluids were incubated in vitro with either normal FFP or cryosupernatant. We conclude that an activity in FFP, and its cryosupernatant fraction, promoted the rapid in vivo disappearance of unusually large vWF multimers from the plasma of two patients with chronic relapsing TTP in remission, and plasma exchange reversed the abnormality in a third patient who was in partial remission. Neither FFP nor cryosupernatant directly converted unusually large multimers to smaller vWF forms in vitro in the fluid phase. These results indicate that an activity in the cryosupernatant fraction of normal plasma is involved in vivo in controlling the metabolism of unusually large vWF multimers, and that this process is defective in some chronic relapsing TTP patients.     

Long-term follow-up of idiopathic thrombotic thrombocytopenic purpura treated with rituximab

Rituximab may be used to treat patients with thrombotic thrombocytopenic purpura (TTP) refractory to plasma exchange or recurrent disease. While initial response rates are reported to be high, long-term follow-up data of patients treated with rituximab are not available to date, however important to estimate the safety and benefit of this treatment. Twelve patients with non-familial idiopathic TTP refractory to plasma exchange or with recurrent disease treated with rituximab between 2000 and 2008 were reexamined. The median follow-up was 49.6 months, ranging from 11 to 97 months. All patients achieved initial complete remission after application of rituximab. During follow-up, nine patients remained disease-free and three patients suffered from recurrent disease. All patients with recurrent disease responded to subsequent rituximab therapy. No long-term side effects were noted during the follow-up period. In conclusion, rituximab represents an effective second-line treatment option in relapsing or refractory TTP. Still, patients need to be closely monitored for relapses with extended follow-up.     

Clinical presentation and management of acquired thrombotic thrombocytopenic purpura: A case series of 55 patients

The aim of this study was to explore the clinical characteristics and treatment of acquired thrombotic thrombocytopenic purpura (TTP). The clinical manifestations, laboratory findings, differential diagnoses, therapeutic methods, and prognosis of 55 patients with acquired TTP were retrospectively analyzed. Among the 55 TTP patients, 17 were males and 38 were females, with a mean age of 40 ± 15 years. Twenty‐one patients had the Triad syndrome, which included neurological syndromes, microangiopathic hemolytic anemia, and thrombocytopenia. Twenty‐three patients had the Quinary syndrome, which included fever, microangiopathic hemolytic anemia, thrombocytopenia, renal insufficiency, and neurological symptoms. Twenty‐eight patients received the measurement for a disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13 (ADAMTS13) activity and 23 patients had <10% of the normal range. ADAMTS13 inhibitor was tested in 20 patients and was positive in 18 patients. Both ADAMTS13 activity and ADAMTS13 inhibitor were examined in 20 patients and 90% of the patients showed double positive results. The treatment methods included plasma exchange, glucocorticoids, rituximab, immunosuppressants, and intravenous immunoglobulin. Thirty‐three patients survived, and 22 patients died. Plasma exchange improved the remission rate from 16.7% to 65.3% (P = .022). The combined immunosuppressive therapy based on plasma exchange and glucocorticoids raised the remission rate from 43.8% to 75.8%. Most of acquired TTP patients had the Triad syndrome or the Quinary syndrome. A high proportion of TTP patients had ADAMTS13 activity reduction and ADAMTS13 inhibitor positivity. Plasma exchange and immunosuppressive therapy may improve the prognosis of this disease.     

Rituximab for the treatment of refractory idiopathic thrombocytopenic purpura (ITP) and thrombotic thrombocytopenic purpura (TTP): report of three cases

Three patients (one with idiopathic thrombocytopenic purpura [ITP] and two with thrombotic thrombocytopenic purpura [TTP]) were treated with rituximab (anti-CD20 chimeric antibody) at a dose of 325 mg/m2 administered weekly after they failed standard therapies. The patient with ITP who did not respond to steroids and anti-D antibody administration achieved augmentation of her platelet counts up to 180 x 10(3)/microL after four doses of rituximab. Six months later, when her counts started to decrease, she received maintenance therapy with an additional course of 4 standard doses of antibody that resulted in consolidation of her platelet counts around 100 x 10(3)/microL. One patient with TTP and concurrent idiopathic nephropathy who was previously treated with plasmapheresis, steroids, and vincristine improved only after 4 weekly administrations of the antibody. Moreover, his nephrotic-range proteinuria resolved after he received rituximab. The other patient with chronic TTP who still relapsed after splenectomy received 5 doses of rituximab with concomitant plasmapheresis. His thrombocytopenia improved slowly, and his platelet count stabilized at 300 x 10(3)/microL. All three patients showed evidence of response to anti-CD20 antibody with improvement in clinical outcome as well as augmentation of platelet counts to normal levels. We conclude that rituximab is a useful immunomodulating adjunct in the treatment of refractory ITP and TTP.     

Successful management of pregnancy in women with a history of thrombotic thrombocytopaenic purpura.

Pregnancy is an initiating event for acute thrombotic thrombocytopaenic purpura (TTP). There is a high risk of relapse during pregnancy and of foetal morbidity. We describe five cases with successful maternal and foetal outcomes in patients with a history of TTP. Cases 1 and 2 presented with TTP in their first pregnancy and had second-trimester foetal losses. Case 3 had four TTP relapses and soon after achievement of clinical remission became pregnant. Case 4 presented with TTP and left-sided stroke in pregnancy. ADAMTS-13 activity was less than 5% at presentation in four patients and prior to therapy during pregnancy in cases 1-4. Case 5, who had a single acute episode of TTP and became pregnant 6 years later, had normal ADAMTS-13 activity throughout pregnancy. Only case 3 had evidence of an inhibitor on mixing studies. All five patients underwent close haematological and obstetric monitoring and continued low-dose aspirin throughout pregnancy. Patients 1-4 had regular plasma exchange and received low molecular weight heparin during pregnancy. Patient 4 also received rituximab during the third trimester with no observed maternal or neonatal toxicity. Live healthy infants were delivered in all five cases in the third trimester. These findings suggest that successful pregnancy outcome is achievable in patients with a history of TTP and that patients with severely reduced ADAMTS-13 activity at the onset of pregnancy, necessitates regular plasma exchange during pregnancy.     

Short- and long-term effects of rituximab for the treatment of thrombotic thrombocytopenic purpura: four case reports

We report four cases of thrombotic thrombocytopenic purpura (TTP) successfully treated with rituximab in combination with plasma exchange and other immunosuppressive agents. All four cases fulfilled the diagnostic criteria of TTP with severe deficiencies in ADAMTS13 activity and a detectable anti-ADAMTS13 inhibitor. Four weekly doses of 375?mg/m² rituximab were initiated on day 3?C29 of presentation as a salvage treatment for relapsing/refractory disease in three patients and as a first-line treatment in one. Resolution of clinical symptoms and hematological abnormalities occurred as early as the second dose and, after the completion of treatment, all four patients achieved complete response (CR). They are currently free from relapse and the duration of CR has been 13?C72?months. During the treatment course, the level of ADAMTS13 activity and the titer of the inhibitor correlated well with resolution or exacerbation of the disease. This report suggests that rituximab exhibits short- and long-term favorable effects for the treatment of TTP and that a severe ADAMTS13 deficiency and ADAMTS13 inhibitor positivity may support early administration of rituximab in both acute/refractory and relapsing cases.     

Rituximab in the treatment of relapsed thrombotic thrombocytopenic purpura

Several reports have defined nonfamilial thrombotic thrombocytopenic purpura (TTP) as an autoimmune disorder caused by antibodies to von Willebrands factor-cleaving protease (vWF-CP). This raises the possibility that rituximab, a monoclonal antibody against CD20 present in B-lymphoid cells, may have utility in the treatment of TTP. We report five consecutively treated patients with relapsed TTP who responded rapidly to immune suppression by rituximab at our institution. These two male and three female patients had a median age of 37 years (27–70). The median time from diagnosis to therapy was 24 months (8–60). Prior therapies included plasma exchange and corticosteroids in all cases, splenectomy (4), vincristine and aspirin (3), and azathioprine (2). The median number of plasma exchanges received prior to therapy was 59 (21–158). The cohort had a median platelet count of 48×10⁹/l (23–110), median hemoglobin of 9 g/dl (8–11), and median lactate dehydrogenase of 632 IU/l (311–945) prior to administration of rituximab. Analysis of vWF-CP activity demonstrated absent or decreased activity with detectable inhibitors in four patients. All patients attained a complete response. The median time to response after the first dose of rituximab was 5 weeks. Responses are maintained in all patients from 10 to 21 months after treatment. This report adds to the evidence that rituximab has efficacy in nonfamilial TTP and warrants further study.     

Effectiveness of cryosupernatant therapy in refractory and chronic relapsing thrombotic thrombocytopenic purpura

This report describes objective improvement in two patients with poorly responsive thrombotic thrombocytopenic purpura (TTP) syndromes (with cryosupernatant). The first had a partial response to plasma exchange with whole plasma (fresh frozen plasma; FFP) and responded dramatically when switched to plasma exchange with cryosupernatant replacement. The second had chronic TTP (three relapses in 9 months) that required prolonged courses of exchange with FFP (～ 1 month each) to achieve remission. Attempts to manage her recurrent TTP with infusion of two units of FFP had been unsuccessful. The latter patient was tried on cryosupernatant infusions (2 units daily) and responded within 4 days. Moreover, she has been in continuous remission for 12 months while receiving 2 units (one to three times per week). These results suggest that cryoprecipitate-poor plasma may offer advantages over whole plasma in the management of both acute and chronic forms of TTP. © 1993 Wiley-Liss, Inc.     

A phase‐II sequential case‐series study of all patients presenting to four plasma exchange centres with presumed relapsed/refractory thrombotic thrombocytopenic purpura treated with rituximab

The primary objective of this phase II study was to evaluate the efficacy of rituximab in the management of adult patients with physician‐diagnosed presumed thrombotic thrombocytopenic purpura (TTP); relapsed or refractory. We conducted a multicentre study in four Canadian hospital‐based apheresis units. Forty patients with presumed TTP (20 refractory and 20 relapsing) were sequentially enrolled and all received rituximab in a standardized manner. A complete response was documented in 14 of 19 refractory patients by week 8 and 15/16 were alive and in remission at 52 weeks (one patient was lost to follow‐up, one was a non‐responder, and three died). Among relapsing patients, 16/18 had a complete response at week 8 and 18/18 at week 52 (one patient lost to follow‐up and one withdrew). At 1 year, all relapsing and 85% of refractory patients survived. Of 38/40 patients who had ADMATS13 testing at study entry, 13/19 refractory and 10/19 relapsing patients had ADAMTS13 < 10% (typical TTP); whereas 6/19 refractory and 9/19 relapsing cases had ADAMTS13 > 10% (other thrombotic microangiopathy; TMA). Refractory‐typical TTP in contrast to refractory‐other TMA and all relapsing patients treated with plasma exchange and rituximab, were less likely to be responsive and more likely to die or relapse.     

Ofatumumab for acute treatment and prophylaxis of a patient with multiple relapses of acquired thrombotic thrombocytopenic purpura

Acquired thrombotic thrombocytopenic purpura (TTP) is an autoimmune disorder resulting in potentially life-threating systemic thrombotic microangiopathy due to production of antibodies directed against the von Willebrand factor-cleaving protease ADAMTS13. Typically managed with plasma exchange, glucocorticoids, and the first-generation anti-CD20 monoclonal antibody rituximab, patients with multiple relapses or refractory disease present unique management challenges. We describe a case of a young woman with multiple relapses of TTP despite standard therapy who was treated with ofatumumab, a second-generation anti-CD20 monoclonal antibody, after developing a severe hypersensitivity reaction to rituximab precluding its use. Ofatumumab was effective for the treatment of an acute relapse of TTP in combination with plasmapheresis and as a single-agent for prophylaxis. The patient has had no evidence of relapse 2 years after completion of acute treatment and 1 year after completing prophylactic therapy. Hypersensitivity to ofatumumab did not develop.