The Japanese experience with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome

A total of 290 Japanese patients with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) were analyzed with respect to ADAMTS-13 activity and its inhibitor. Twenty-one patients (17 families) had Upshaw-Schulman syndrome, and 12 patients (six families) had familial HUS of undetermined etiology. The number of patients with acquired HUS and TTP was 44 and 213, respectively. In acquired TTP, patients with severe deficiency of ADAMTS-13 activity secondary to the presence of an inhibitor were high responders to plasma exchange, but others were low responders to plasma exchange. The former patients were associated with "idiopathic" TTP, drugs, and pregnancy, and the latter patients with malignancy and stem cell transplantation. Patients with autoimmune disease-associated TTP fit into both groups.     

Quinine-associated thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: frequency, clinical features, and long-term outcomes.

BACKGROUND: Quinine-associated thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) is thought to be uncommon and to have a good prognosis. OBJECTIVE: To describe the frequency, clinical features, and long-term outcomes of quinine-associated TTP-HUS. DESIGN: Case series. SETTING: Hospitals in central-western Oklahoma. PATIENTS: 225 consecutive patients with TTP-HUS, 1989-2000. MEASUREMENTS: Presenting features and clinical outcomes. RESULTS: Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome was associated with quinine in 17 patients. Four patients died, and 7 survivors currently have chronic renal failure. Since 1 July 1995, 132 patients with clinically suspected TTP-HUS were explicitly asked about drug exposure. Fourteen (11%) had taken quinine, and 7 had taken other drugs associated with TTP-HUS. Neurologic abnormalities were as severe in patients with quinine-associated TTP-HUS as in the 118 patients who had not taken quinine. CONCLUSIONS: Quinine is a common cause of drug-associated TTP-HUS and can cause death and chronic renal failure. When the disorder is described as TTP-HUS rather than only as HUS, the severity of neurologic abnormalities and the occasional absence of renal failure are emphasized. If recurrent disease is to be prevented, clinicians must recognize quinine as a possible cause.     

Sporadic bloody diarrhoea-associated thrombotic thrombocytopenic purpura-haemolytic uraemic syndrome: an adult and paediatric comparison

Although diarrhoea-associated haemolytic uremic syndrome (HUS) in children is well described, the clinical features of bloody diarrhoea-associated thrombotic thrombocytopenic purpura (TTP)-HUS in adults are not documented. Twenty-one adults, 6.5% of the 322 adults in The Oklahoma TTP-HUS Registry, 1989-2006, have presented with bloody diarrhoea. There were no case clusters. Escherichia coli O157:H7 was identified in five patients, but many patients did not have appropriate studies. The annual incidence was 0.68/10(6), 10-fold less than the incidence of diarrhoea-associated HUS in children in Oklahoma. Two (13%) of 16 patients in whom ADAMTS13 (A Disintegrin And Metalloproteinase with a ThromboSpondin type 1 motif, member 13) was measured had <10% activity. Severe neurological abnormalities (67%) and renal failure (62%) were common; seven patients (33%) died; no survivors have relapsed. Compared to the 38 other Oklahoma Registry patients with ADAMTS13 <10%, frequency of severe neurological abnormalities and death was not different; frequency of renal failure was greater; frequency of relapse was less. Compared to 5999 children with sporadic diarrhoea-associated HUS in published reports, frequency of renal failure and relapse was not different; frequency of severe neurological abnormalities and death was greater (P < 0.05 for all differences). Awareness of the continuous occurrence of sporadic bloody diarrhoea-associated TTP-HUS in adults is important for prompt diagnosis and appropriate management.     

How I treat patients with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome

Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) are, in adults, clinically and pathologically indistinguishable except for the severity of renal failure. They are best described as a single disorder, TTP-HUS, because the diagnostic evaluation and initial management are the same. Treatment with plasma exchange, available for more than 20 years, has dramatically altered the course of disease in adults with TTP-HUS. Plasma exchange has improved survival rates from 10% to between 75% and 92%, creating urgency for the initiation of treatment. This has resulted in decreased stringency of diagnostic criteria, which in turn has resulted in a broader spectrum of disorders for which the diagnosis of TTP-HUS is considered. Long-term follow-up has revealed increasing frequencies of relapse and of chronic renal failure. Although the increased survival rate is dramatic and recent advances in understanding the pathogenesis of these syndromes are remarkable, clinical decisions remain empirical. Therefore, the management decisions for patients with suspected TTP-HUS rely on individual experience and opinion, resulting in many different practice patterns. Multipractice clinical trials are required to define optimal management. (Blood. 2000;96:1223-1229)     

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.     

von Willebrand factor-cleaving protease (ADAMTS-13) activity determination in the diagnosis of thrombotic microangiopathies: the Swiss experience

Severe deficiency of von Willebrand factor (VWF)-cleaving protease (ADAMTS-13) activity (<5% of normal) is a specific finding for acute idiopathic thrombotic thrombocytopenic purpura (TTP), a disorder that presents as thrombocytopenia, microangiopathic hemolytic anemia, and often organ dysfunction such as neurological disturbances or renal failure, and fever. Between January 2001 and July 2003, ADAMTS-13 activity was determined in plasma samples of 396 consecutive patients referred to our laboratory for diagnostic purposes. Plasma samples with ADAMTS-13 activity less than 5% were in addition tested for the presence of inhibitory antibodies. Patients were assigned to 10 predefined clinical categories according to information provided by the referring clinician: thrombotic microangiopathy (TMA) not further specified; neoplasia- or chemotherapy-associated TMA; TMA following hematopoietic stem cell transplantation; TMA with additional/alternative disorder; idiopathic TTP; hemolytic-uremic syndrome (HUS) not specified; HUS with diarrhea prodrome (D+HUS); atypical HUS; other hematological disorder; and no clinical information available. Severe ADAMTS-13 deficiency was found in 69 (17%) patients, including 42 with acquired idiopathic TTP, either at initial presentation or at relapse, 14 with confirmed or suspected hereditary TTP, 10 with TMA not further specified, two with neoplasia- or chemotherapy-associated TMA, and one in continued clinical remission 3.4 years after splenectomy for plasma-refractory TTP. Forty-three (62%) patients with ADAMTS-13 activity less than 5% displayed inhibitory antibodies. Severe ADAMTS-13 deficiency was found in 60% of patients diagnosed with acute idiopathic TTP, but in none of 130 patients diagnosed with HUS or in any of the 14 patients with hematopoietic stem cell transplantation-associated TMA. Thus, plasma ADAMTS-13 activity less than 5% does not identify all patients clinically diagnosed with TTP, and severe ADAMTS-13 deficiency is not invariably associated with clinical manifestations of microvascular platelet clumping.     

Treating TTP/HUS with plasma exchange: a single centre's 25-year experience

Thrombotic thrombocytopenic purpura/Haemolytic uremic syndrome (TTP/HUS) is a thrombotic microangiopathy with a 6-month mortality rate of 16-29%. The present study described the clinical features, treatment regime and 6-month all-cause mortality rate of TTP/HUS patients at the London Health Sciences Centre (LHSC), Canada. Data for this retrospective cohort study were obtained from inpatient and outpatient records for all patients referred for plasma exchange therapy at LHSC, Canada between 1981 and 2006. Patients (n = 110) were categorized as: idiopathic primary (38%) or relapsed (16%), and secondary responsive (30%) or non-responsive (16%). Mortality data were available for all but three patients. The all-cause 6-month mortality rate was 19% overall and was 12% and 26% among idiopathic and secondary TTP/HUS patients, respectively. No mortality events occurred among the 17 idiopathic patients who relapsed. Relapsed patients had the least severe presenting characteristics, the fastest response time, and experienced significant improvement in the severity of clinical features between the first and final presentation. These findings suggest an excellent outcome for relapsed TTP/HUS patients. Patient education, surveillance, and aggressive plasma exchange therapy are hypothesized to improve the likelihood of survival: these hypotheses should be tested in a randomized controlled trial.     

Successful Treatment of Hemolytic Uremic Syndrome and Thrombotic Thrombocytopenic Purpura with Fresh Frozen Plasma and Plasma Exchange

ABSTRACT. Four patients with hemolytic uremic syndrome (HUS) and seven with thrombotic thrombocytopenic purpura (TTP) were treated with infusions of fresh frozen plasma (FFP). In one patient with HUS and Ave patients with TTP this treatment was combined with plasma exchange (PE). The additional treatment varied; corticosteroids, antiplatelet drugs, heparin and blood exchange. All but one patient recovered completely in spite of severe illness with uremia, oliguria and/or cerebral symptoms during the acute phase. The results were surprisingly good in comparison with other published series. The success must in the first place be attributed to early diagnosis and to the infusions of FFP. PE seemed to potentiate the effect of FFP.     

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.     

ADAMTS13 activity in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: relation to presenting features and clinical outcomes in a prospective cohort of 142 patients

Initial management of patients with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) is difficult because of lack of specific diagnostic criteria, high mortality without plasma exchange treatment, and risks of plasma exchange. Although severe ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type 1 repeats) deficiency may be specific for TTP, the role of ADAMTS13 activity measurements for initial management decisions is unknown. ADAMTS13 was measured before beginning plasma exchange treatment in 142 (88%) of 161 consecutive patients with clinically diagnosed TTP-HUS with assignment to 1 of 4 categories: less than 5% (severe deficiency), 5% to 9%, 10% to 25%, and more than 25%. Eighteen (13%) of 142 patients had severe ADAMTS13 deficiency. Among 6 predefined clinical categories (stem cell transplantation, pregnant/postpartum, drug association, bloody diarrhea, additional/alternative disorder, idiopathic), severe deficiency occurred only among pregnant/postpartum (2 of 10) and idiopathic (16 of 48) patients. The presenting features and clinical outcomes of the 16 patients with idiopathic TTP-HUS who had severe ADAMTS13 deficiency were variable and not distinct from the 32 patients with idiopathic TTPHUS who did not have severe ADAMTS13 deficiency. Many patients in all ADAMTS13 activity categories apparently responded to plasma exchange treatment. Therefore, severe ADAMTS13 deficiency does not detect all patients who may be appropriately diagnosed with TTP-HUS and who may respond to plasma exchange treatment.     

von Willebrand factor cleaving protease (ADAMTS13) is deficient in recurrent and familial thrombotic thrombocytopenic purpura and hemolytic uremic syndrome

Whether measurement of ADAMTS13 activity may enable physicians to distinguish thrombotic thrombocytopenic purpura (TTP) from hemolytic uremic syndrome (HUS) is still a controversial issue. Our aim was to clarify whether patients with normal or deficient ADAMTS13 activity could be distinguished in terms of disease manifestations and multimeric patterns of plasma von Willebrand factor (VWF). ADAMTS13 activity, VWF antigen, and multimeric pattern were evaluated in patients with recurrent and familial TTP (n = 20) and HUS (n = 29). Results of the collagen-binding assay of ADAMTS13 activity were confirmed in selected samples by testing the capacity of plasma to cleave recombinant VWF A1-A2-A3. Most patients with TTP had complete or partial deficiency of ADAMTS13 activity during the acute phase, and in some the defect persisted at remission. However, complete ADAMTS13 deficiency was also found in 5 of 9 patients with HUS during the acute phase and in 5 patients during remission. HUS patients with ADAMTS13 deficiency could not be distinguished clinically from those with normal ADAMTS13. In a subgroup of patients with TTP or HUS, the ADAMTS13 defect was inherited, as documented by half-normal levels of ADAMTS13 in their asymptomatic parents, consistent with the heterozygous carrier state. In patients with TTP and HUS there was indirect evidence of increased VWF fragmentation, and this occurred also in patients with ADAMTS13 deficiency. In conclusion, deficient ADAMTS13 activity does not distinguish TTP from HUS, at least in the recurrent and familial forms, and it is not the only determinant of VWF abnormalities in these conditions.     

Systemic infections mimicking thrombotic thrombocytopenic purpura

The absence of specific diagnostic criteria, the urgency to begin plasma exchange treatment, and the risk for complications from plasma exchange make the initial evaluation of patients with suspected thrombotic thrombocytopenic purpura (TTP) difficult. Systemic infections may mimic the presenting clinical features of TTP. In the Oklahoma TTP-HUS (hemolytic-uremic syndrome) Registry, 1989-2010, 415 consecutive patients have been clinically diagnosed with their first episode of TTP; in 31 (7%) the presenting clinical features were subsequently attributed to a systemic infection. All 31 patients had diagnostic criteria for TTP; 16 (52%) had the complete "pentad" of microangiopathic hemolytic anemia, thrombocytopenia, neurologic abnormalities, renal failure, and fever. Four (16%) of 25 patients who had ADAMTS13 measurements had <10% activity; three patients had a demonstrable ADAMTS13 inhibitor. Compared with 62 patients with severe ADAMTS13 deficiency (<10%) who had no recognized alternative disorders, patients with systemic infections had more frequent fever, coma, renal failure, and the complete "pentad" of clinical features. Seventeen different infectious etiologies were documented. A systematic literature review identified 67 additional patients with a diagnosis of TTP or HUS and also a systemic infection. Among all 98 patients, infections with 41 different bacteria, viruses, and fungi were documented, suggesting that many different systemic infections may mimic the presenting clinical features of TTP. Initial plasma exchange treatment is appropriate in critically ill patients with diagnostic features of TTP, even if a systemic infection is suspected. Continuing evaluation to document a systemic infection is essential to determine the appropriateness of continued plasma exchange.     

Delayed postpartum hemorrhage--a rare clinical presentation of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: a case report

Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) are rare and closely related disorders characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal failure. Many risk factors have been reported including infection, cancer, pregnancy, a variety of drugs (e.g. anticancer drugs), and autoimmune diseases. The incidence of TTP-HUS is higher in females than in males, especially during pregnancy and the immediate postpartum period. Review of the literature reveals that delayed postpartum hemorrhage is a rare clinical presentation of TTP-HUS. We report a case of TTP-HUS with recurrent delayed postpartum hemorrhage and dismal outcome.     

Increased fragmentation of von Willebrand factor, due to abnormal cleavage of the subunit, parallels disease activity in recurrent hemolytic uremic syndrome and thrombotic thrombocytopenic purpura and discloses predisposition in families. The Italian Registry of Familial and Recurrent HUS/TTP.

We investigated here the changes in von Willebrand factor (vWF) multimers in recurrent, sporadic and familial forms of hemolytic uremic syndrome (HUS)/thrombotic thrombocytopenic purpura (TTP) to see whether they are actually proteolyzed in vivo in these patients. Molecular determinants of fragments in vWF were also characterized to identify possible sites of cleavage of the subunit. Unusually large vWF multimers were found in blood of 8 of 10 patients with recurrent HUS/TTP, both in the acute phase and in remission, but never in familial and sporadic cases. Instead, all of the groups showed evidence of enhanced fragmentation of vWF multimers during the acute phase. Increased fragmentation was also shown by decrease in native 225-kD vWF subunit. In recurrent and sporadic HUS/TTP, enhanced fragmentation normalized at remission, but the abnormality persisted in familial HUS/TTP patients. The latter findings suggest that patients with familial HUS/TTP may have a congenital abnormality in vWF processing. Analysis with specific monoclonal antibodies showed the presence of the normal vWF fragments with apparent molecular mass of 189, 176, and 140 kD in all patients; however, in 6 recurrent and in 5 familial cases, novel fragments that differed in size from normal ones were found. The size of these abnormal fragments differed from one patient to another and none of them was ever found in normal plasma. These results documented, for the first time in HUS/TTP, an abnormal cleavage of the vWF subunit that might account for the increased fragmentation observed in these patients.     

Cancer‐associated microangiopathic hemolytic anemia with thrombocytopenia: an important diagnostic consideration

Background: Early initiation of plasma exchange (PE) allows more than 80% of patients with idiopathic thrombotic thrombocytopenic purpura (TTP), most commonly because of severe ADAMTS13 deficiency, to achieve remission and mandates urgency in diagnosis and therapy. Metastatic cancer may present with a microangiopathic hemolytic anemia with thrombocytopenia that is clinically similar to TTP but does not respond to PE. ADAMTS13 activity can be diagnostic but usually not immediately available. Recognition of cancer‐associated microangiopathic hemolytic anemia with thrombocytopenia (CA‐MHA) is paramount to avoid inappropriate PE therapy and delays in cancer‐specific chemotherapy. Objective: To identify distinguishing characteristics of CA‐MHA and TTP to facilitate early recognition of CA‐MHA. Methods: In a retrospective cohort study, baseline clinical and laboratory data of consecutive adult patients with CA‐MHA (n = 7) or autoimmune TTP (n = 7) from a registry of patients with clinically suspected acute TTP referred for PE were compared. Results: The frequencies of bone pain and respiratory symptoms were significantly greater among patients with CA‐MHA compared to patients with TTP; other baseline clinical and laboratory characteristics did not differ significantly between the two groups. Response to PE and mortality at day 30 were significantly worse for CA‐MHA (14% and 71%, respectively) compared to patients with TTP (86% and 14%, respectively). Conclusions: Baseline clinical and laboratory characteristics largely do not distinguish acute CA‐MHA from autoimmune acute TTP. While all suspected acute patients TTP should receive urgent PE, bone pain, respiratory symptoms, or inadequate PE response should prompt an early search for CA‐MHA.     

Laparoscopic splenectomy for the treatment of refractory thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura (TTP) is a serious hematologic disorder with a high rate of morbidity and mortality. We report here on the surgical and homological outcomes of laparoscopic splenectomy (LS) in a patient with refractory TTP. A 69-year-old Japanese woman was referred to our hospital because of purpura in the lower extremities. In addition to the marked thrombocytopenia, hemolytic anemia and progressive mental disorder were noted. The ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 motif 13) activity was undetectable and ADAMTS13 inhibitor was extremely increased. The diagnosis of TTP was made based on the clinical features and laboratory abnormalities. She received steroid-pulse therapy for 3 days, low-dose methylprednisolone continuous infusion and plasma exchange (PE) daily for 14 days. However, the patient was found to be refractory TTP to PE. The LS was performed at 15 days after diagnosis. The ADAMTS13 inhibitor was not detected after LS, and in addition, the platelet count had increased to over 100,000/mm³ on postoperative day 17. The patient remains in remission 24 months after surgery. The results of our case demonstrate that LS is a safe and reasonable treatment option for patients with TTP refractory to PE.     

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.     

The utility of ADAMTS13 in differentiating TTP from other acute thrombotic microangiopathies: results from the UK TTP Registry

Thrombotic microangiopathies (TMAs) are frequently difficult to differentiate clinically, and measurement of ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) remains vital in thrombotic thrombocytopenic purpura (TTP) diagnosis. We retrospectively reviewed cases referred for ADAMTS13 testing, using UK TTP Registry screening data. Of a total 810 cases, 350 were confirmed as TTP. The 460 non‐TTP cases comprised secondary TMAs (24·57%) and haemolytic uraemic syndrome (HUS) (27·17% aHUS, 2·83% Shiga‐like toxin‐producing E. coli [STEC]‐HUS); the remainder were TMAs with no clear association, not TMAs, or had no confirmed diagnosis. ADAMTS13 levels were significantly lower in TTP than STEC‐HUS, aHUS and other TMAs. TTP patients had significantly lower platelet count (15 × 10⁹/l; range 0–96) than aHUS (57 × 10⁹/l; range 13–145, P < 0·0001) or STEC‐HUS (35 × 10⁹/l; range 14–106, P < 0·0001); they also had lower creatinine levels (92 μmol/l; range 43–374) than aHUS (255 μmol/l; range 23–941, P < 0·0001) and STEC‐HUS (324 μmol/l; range 117–639, P < 0·0001). However, 12/34 (35·3%) aHUS patients had a platelet count <30 × 10⁹/l and 26/150 (17·3%) of TTP patients had a platelet count >30 × 10⁹/l; 23/150 (15·3%) of TTP patients had a creatinine level >150 μmol/l. This study highlights the wide variety of TMA presentations, and confirms the utility of ADAMTS13 testing in TTP diagnosis.     

Response to plasma exchange and steroids as combined therapy for patients with thrombotic thrombocytopenic purpura.

We describe our experience in the management of 11 consecutive patients with thrombotic thrombocytopenic purpura (TTP) treated with a combined therapy of plasma exchange (PE) and steroids. Nine patients (82%) achieved complete remission (CR) after a median of 6 rounds of PE (range 2-22). There were 3 early relapses managed in the same way as the initial episode. One patient relapsed 23 months after diagnosis achieving CR with standard therapy; another patient suffered several relapses, and splenectomy was performed after the last one. Three patients died, 2 of them with resistant disease 9 and 38 days after diagnosis, and the remaining one died due to AIDS-related complications while he was in CR. Eight patients are alive in CR with a median follow-up of 38 months (range 8-74). The combination of PE and steroids is a well-tolerated and effective treatment of TTP, but improvements in therapy are needed to manage refractory patients.     

Outcomes in the treatment of thrombotic thrombocytopenic purpura with splenectomy: a retrospective cohort study

The mainstay of treatment for thrombotic thrombocytopenic purpura (TTP) is plasma exchange (PE), but the role of splenectomy is still undefined. The records of all patients with TTP at a single center over a 20-year period were retrospectively reviewed. Response to plasma exchange was determined. The outcome of patients treated with splenectomy in the setting of TTP was evaluated. Sixty-one patients had been treated for TTP. Thirty-nine patients (64%) achieved complete remission (CR) with PE, nineteen (31%) of these achieving sustained CR and seventeen (28%) with relapsed TTP. Twenty patients (33%) had PE refractory TTP and two patients (3%) had PE dependent TTP. During this time period, 10 patients (16%) underwent splenectomy, four patients (7%) for PE dependent TTP, three (5%) for relapsed TTP, and three (5%) for refractory TTP. All of the patients achieved CR after splenectomy. Two patients who had undergone splenectomy had subsequent relapses, both with previously relapsed TTP. In relapsed patients the relapse rate after splenectomy was 0.27 events per patient year compared to 0.6 events per patient year before splenectomy. Median follow-up after splenectomy was 19 months (range 0.13-90 months). In conclusion, relapses in TTP can be managed successfully with additional PE or with splenectomy. PE dependent or refractory TTP can be successfully treated with splenectomy.