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Immune-mediated thrombotic thrombocytopenic purpura (TTP) is a life-threatening disorder caused by antibodies against ADAMTS13. From the United Kingdom TTP registry, we undertook a prospective study investigating the impact of the presenting anti-ADAMTS13 IgG antibody and ADAMTS13 antigen on mortality. A total of 312 episodes involving 292 patients over 87 months were included; 68% were female, median age 46 (range, 11-88 years), and median presenting ADAMTS13 of 77%) had a mortality of 16.9% compared with 5.0% for the lowest quartile (antibody 11%) (P = .005). The synergistic effect of anti-ADAMTS13 IgG antibody in the upper quartile and ADAMTS13 antigen in the lowest quartile had the highest mortality of 27.3%. We conclude that both anti-ADAMTS13 IgG antibody and ADAMTS13 antigen levels correlate with outcome in TTP with increased cardiac and neurological involvement and increased mortality.

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 × 10(9) /l; range 0-96) than aHUS (57 × 10(9) /l; range 13-145, P0·0001) or STEC-HUS (35 × 10(9) /l; range 14-106, P0·0001); they also had lower creatinine levels (92 μmol/l; range 43-374) than aHUS (255 μmol/l; range 23-941, P0·0001) and STEC-HUS (324 μmol/l; range 117-639, P0·0001). However, 12/34 (35·3%) aHUS patients had a platelet count30 × 10(9) /l and 26/150 (17·3%) of TTP patients had a platelet count30 × 10(9) /l; 23/150 (15·3%) of TTP patients had a creatinine level150 μmol/l. This study highlights the wide variety of TMA presentations, and confirms the utility of ADAMTS13 testing in TTP diagnosis.

Acute antibody-mediated thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy with high morbidity and mortality. Rituximab is highly effective as prophylaxis in patients at risk of acute TTP relapse, but the ideal dosing regimen is unknown. A multicenter retrospective cohort study evaluated outcomes of patients given rituximab prophylaxis to prevent TTP relapse. Rituximab was given in 76 episodes to 45 patients (34 women and 11 men). Four once-per-week infusions of standard- (375 mg/m2 [24 episodes]), reduced- (200 mg [19 episodes]), and intermediate- (500 mg [17 episodes]) dose rituximab were given; in the remaining 16 episodes, patients received 100 to 1000 mg rituximab in 1 to 5 doses. Patients were deemed at high risk of TTP relapse on the basis of ADAMTS13 activity dropping to ≤15% from the normal range. Preprophylaxis median ADAMTS13 level was 5% (range

related to the subsections of this guideline. The writing group produced the draft guideline, which was subsequently revised by consensus by members of the Haemostasis and Thrombosis Task Force of the BCSH. The guideline was then reviewed by a sounding board of British haematologists, the BCSH and the British Society for Haematology Committee and comments incorporated where appropriate. The ‘GRADE’ system was used to quote levels and grades of evidence, details of which can be found at http://www.bcshguidelines.com. The objective of this guideline is to provide healthcare professionals with clear, up-to-date, and practical guidance on the management of TTP and related thrombotic microangiopathies, defined by thrombocytopenia, microangiopathic haemolytic anaemia (MAHA) and small vessel thrombosis.

Thrombotic thrombocytopenic purpura (TTP) is an acute prothrombotic disorder. Human immunodeficiency virus (HIV) is an identified precipitant. This study reviewed 30 episodes of HIV-associated TTP in 24 patients from the South-East England Apheresis units, over the last 10 years. All patients were heterosexual Black Africans. First presentation of TTP revealed a new diagnosis of HIV in eight patients. TTP relapse occurred on six occasions (in four patients) as a result of non-adherence to highly active antiretroviral therapy (HAART). Prompt initiation/re-initiation of HAART in parallel with plasma exchange (PEX)±steroid led to prompt remission. Adjunct immunomodulatory agents (e.g. Rituximab) were required in 10% of cases. Once-daily HAART regimens are recommended, being compatible with PEX requirement, maximizing drug exposure between PEX. High viral loads (>500,000 copies/ml) require more PEX to remission. ADAMTS13 activity was reduced (

Thrombotic thrombocytopenic purpura (TTP) may be idiopathic or secondary. We report seven TTP cases precipitated by pancreatitis. The patients were admitted with acute pancreatitis and at that time had no clinical or laboratory features of TTP. The median time to develop TTP after pancreatitis was 3 d. The patients had moderately reduced ADAMTS13 activity (mean activity 49%; normal range 66-126%) with no evidence of anti-ADAMTS13 inhibitory autoantibodies. The median number of plasma exchanges to remission was 10 (range 7-14) and no additional treatment with immunosuppression was required to maintain remission. There have been no relapses to date.

Venous thromboembolism (VTE) is not a feature of thrombotic thrombocytopenic purpura (TTP), but there has been a recent report of VTE in association with plasma exchange (PEX) treatment for TTP using the solvent detergent (SD) plasma, PLAS+SD. We reviewed the occurrence of VTE in 68 consecutive patients with TTP (25 men, 43 women). Eight documented VTE events [six deep venous thromboses (DVTs), three pulmonary emboli] were identified in seven patients (all female) during PEX therapy. All six DVTs were associated with central lines at the site of thrombosis. Other known precipitating factors included pregnancy, immobility, obesity and factor V Leiden heterozygosity. VTE occurred at a mean of 53 d following the first PEX. The European SD plasma, Octaplas was the last plasma to be used in PEX prior to the VTE in 7/8 events. This is the first report of VTE following Octaplas infusion. VTE is a multifactorial disease and, although several known precipitating factors were present in all patients in this study, the use of large volumes of SD plasma in PEX may be an additional risk factor. We recommend prevention of VTE with graduated elastic compression stockings (class I) at diagnosis and prophylactic low-molecular-weight heparin once the platelet count rises above 50 x 10(9)/l.

Background aims There is real and sustained interest in preparing T-regulatory cells from leukapheresis collections for cellular therapy through the use of simple, effective and reliable methods conforming to Good Manufacturing Practice (GMP). We describe a GMP-ready isolation procedure for CD25 + products with the use of a sterile docking device, pigtail sampling, a laminar flow hood and the CliniMACS system that uses leukapheresis collections made by two apheresis machines. Methods We used CD8/CD19 depletion followed by CD25-positive selection. The median number of CD4 + cells recovered was 72.5 ± 32.6 × 10 6 , of which 60.5% ± 17.8% were CD25 + FOXP3 + cells. Suppression of autologous CD25 − cell proliferation by the cryopreserved CD25 + products was 51.3% ± 4.4%, 49.0% ± 3.7% and 39.0% ± 3.6% at CD25 + :CD25 − ratios of 1:1, 1:2 and 1:4 ( n = 6), respectively, comparable to suppression by fresh CD25 + products (53% ± 6.2%, 51% ± 3.3% and 39% ± 7.1%). Results We found Leukapheresis collections by Cobe Spectra contained more lymphocytes and platelets than collections by Spectra Optia apheresis machine (median, 9.2 × 10 9 versus 6.7 × 10 9 ; P = 0.04) and platelets (median, 610 × 10 9 versus 170 × 10 9 ; P = 0.04). The frequency of CD4 + CD25 + FOXP3 + was significantly higher in the leukapheresis (4.85%; 95% confidence interval, 1.95% to 5.38%) than in peripheral blood (3.9%; 95% confidence interval, 2.63% to 6.45%) ( P = 0.02). The CD8- and CD19-negative depletion step was associated with significant loss of total CD4 + T cells ( P = 0.001). Conclusions Results suggest that functional CD25 + products can be isolated with a GMP-ready method, and good recovery can be obtained with the use of an optimized cryopreservation protocol. These data and methods show the potential, possibilities and future work needed to isolate target cell populations in a reproducible, time-efficient and cost-efficient manner for clinical applications.

Approaches to the management of adolescents and young adults with acute leukaemia were investigated by sending a questionnaire to hospitals identified as having diagnosed or treated patients aged 15-29 years. The responses demonstrated the types of hospital treating these patients, the haematologists' perceived practice for entry of patients to Medical Research Council (MRC) leukaemia trials and reasons for non-entry. Data were linked to MRC trials data to determine the proportion of patients aged 15-29 years at diagnosis in responding hospitals actually treated in MRC leukaemia trials in the 5 years preceding the questionnaire. Eighty-two per cent of haematologists stated that they entered patients 'always' or 'whenever possible' for acute myeloid leukaemia (AML) and 76% for acute lymphoblastic leukaemia (ALL), but actual entry rates from the study hospitals were 46% of 239 AML patients and 36% of 182 ALL patients. The reasons most commonly reported for not entering eligible patients to national leukaemia trials were clinician preference for one arm of an MRC trial, a regional study or non-trial protocol, and concern about workload and ethical approval.

Thrombotic thrombocytopenic purpura (TTP) is an acute, rare, life-threatening disorder. This report presents the South East (SE) England registry for TTP, from April 2002 to December 2006, which included 176 patients and 236 acute episodes; 75% of patients were female and 25% were male, overall median age at presentation was 42 years. Mortality was 8.5%, most cases died before treatment was instigated. The main ethnic groups were Caucasian (64%) and Afro Caribbean (27%). Seventy-seven percent of cases were idiopathic, 5% were congenital and the remaining cases had a defined precipitant. Neurological features were the most prevalent, but cardiac involvement accounted for 42% of presenting features. The overall median number of plasma exchanges (PEXs) to remission was 15; between April 2002 and December 2003, the median number of PEXs was 19 and it was 12 between January 2004 and December 2006 (P < 0.0001). In the latter period, adjuvant therapies were reduced, but Rituximab was increased. ADAMTS 13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity was

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disorder and plasma exchange (PEX) remains the primary treatment modality. Twenty-five patients with acute refractory/relapsing idiopathic TTP received rituximab in conjunction with PEX because of progressive clinical disease or deterioration in laboratory parameters, despite intensive standard therapy. In relapsing TTP, rituximab was started if antibody to ADAMTS-13 (a disintegrin and metalloproteinase with thrombospondin motif-13) was demonstrated during previous episodes. All 25 patients attained complete clinical and laboratory remission in a median of 11 d after initiating rituximab. In 21 cases, ADAMTS-13 activity was within the normal range following rituximab. Inhibitors were detected in 24/25 patients by mixing studies and/or immunoglobulin G (IgG) antibodies to ADAMTS-13 pre-rituximab. There was no evidence of inhibitors and/or IgG activity

Thrombotic thrombocytopenic purpura (TTP) is an acute, rare, life threatening disorder. We present data from the South East (SE) England registry for TTP, from April 2002–December 2005. Included are 156 patients and 179 acute episodes. Seventy four percent of cases were female and 26% males, median age at presentation, 41 and 47.5 years respectively. Mortality to December 2003 was 12%, and from January 2004 to December 2005 was 5%; 5/12 died before treatment was instigated. The main ethnic groups were Caucasian (63%), Afro Caribbean (22%) and Asian (12%). In 61%, this was their first TTP episode; 39% represented with acute relapse. Precipitating events (n=123); idiopathic (56%), a defined infection (11%), pregnancy (6%), HIV disease (7%), congenital (5%) and associated autoimmune disease (6%). Features at presentation include: neurological disease (39%), temperature (15%), abdominal symptoms (12%), renal impairment (10%), symptomatic cardiac disease (7%), symptoms related to low platelets (17%) and no symptoms (2%). From April 2002–December 2003, the median number of plasma exchanges until complete remission (CR) recorded in 36 patients was 20 (5–79). One patient received plasma infusion (PI) in conjunction with PEX. 33 patients received 3 doses of pulsed intravenous methylprednisolone (IV MP) and 9 orally. Other therapies used were Rituximab (1), defibrotide (5), cyclosporine (9) and vincristine (15). In the second cohort (January 2004–December 2005), the median number of PEX to CR in 88 episodes was 8 (3–80). PI was used in 5 cases, 48 patients received 3 doses of pulsed IV MP on admission and 6 patients oral prednisolone. Other therapies used were Rituximab (26), defibrotide (2), cyclosporine (3), vincristine (5) and BPL 8Y (9). The latter is an intermediate purity Factor VIII concentrate used in congenital TTP. The median Haemoglobin (Hb) was 9.9g/dL at presentation and platelet count 18 ×109/L. The 2002–2003 group had 48% cases with platelet counts 66% in 7% at presentation. Antibody to ADAMTS 13 (determined by mixing studies using CBA and/or anti-ADAMTS 13 IgG antibodies) was present in 61% of all cases. In those patients with acute idiopathic TTP, 93% had associated antibody. In conclusion: Improved recognition and prompt diagnosis of TTP may be associated with reduction in mortality and changes in treatment protocols reduced the number of PEX to achieve CR. Acute idiopathic TTP is the most common presentation, but improved identification of subgroups such as HIV and congenital TTP have resulted in appropriate tailoring of therapy.

Thrombotic thrombocytopenic purpura (TTP) is a life threatening disorder characterised by thrombocytopenia and microangiopathic haemolytic anaemia associated with a deficiency in ADAMTS 13. Plasma exchange (PEX) remains the primary treatment modality in acute TTP, with various immunosuppressive agents (e.g. methylprednisolone, vincristine, ciclosporin (CSA)) and other disease modifying agents(e.g. defibrotide), added in refractory cases. However, mortality remains at 15–20%. Rituximab is a monoclonal CD 20 antibody, which acts specifically to clear peripheral B lymphocytes involved with antibody production. We have treated 15 patients with acute refractory TTP; 12 female and 3 male, with 2–8 weekly Rituximab infusions, 375mg/m2. Fourteen had neurological features and 3 had cardiac TTP at presentation. Patients received Rituximab because of progressive clinical disease or deterioration of laboratory parameters despite intensive therapy. On admission, median haemoglobin was 8.2 (range 5.1–12) g/dl, platelet count 14 (range 3–70) X 109/L, lactate dehydrogenase (LDH) 1620 (range 411–>2832) IU/L. All patients attained normal laboratory parameters and clinical remission within 22 days of starting Rituximab therapy. Three patients proceeded to further Rituximab based on ADAMTS 13 activity following 4 treatments. Twelve patients had initial ADAMTS 13 activities