P0202FIRST REAL-LIFE DATA OF PATIENTS TREATED FOR THROMBOTIC THROMBOCYTOPENIC PURPURA FROM THE FRENCH THROMBOTIC MICROANGIOPATHIES NETWORK

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Mehdi Maanaoui ◽  
Eric Maury ◽  
AUGUSTO Jean François ◽  
Jean Michel Halimi ◽  
Christelle Barbet ◽  
...  
Keyword(s):  
Platelet Count ◽  
Serum Creatinine ◽  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Clinical Practices ◽  
Thrombotic Microangiopathies ◽  
Thrombocytopenic Purpura ◽  
Multicentric Study ◽  
Count Response ◽  
Reported Data

Abstract Background and Aims Caplacizumab, a bivalent Nanobody, targets the A1 domain of von Willebrand Factor, inhibiting the interaction between ultra-large vWF and platelets in the treament of Acquired Thrombotic Thrombocytopenic Purpura (aTTP). Results of the Phase 3 HERCULES study confirm that treatment with caplacizumab reduces the time to platelet count response, resulting in faster resolution of aTTP. Treatment with caplacizumab also resulted in a highly clinically meaningful reduction in aTTP-related death, recurrence of aTTP, or a major thromboembolic event during study drug treatment. Data from clinical practice confirming the clinical trial data is still scarce. We report here the first real world evidence collected in the French thrombotic microangiopathies network. Method Patients with an acute episode of aTTP were included in an observational prospective multicentric study. The diagnosis of aTTP was done according to the French score (platelet count < 30 g/l and serum creatinine< 200µmol/l) or ADAMTS13 activity if available. Adult patients were proposed to be treated with daily plasma exchange (PE) in addition to corticosteroid and frontline rituximab plus early initiation of caplacizumab. PE was stopped after 2 days of platelet count normalization. Results Fifty patients (36 females, median age of 46 years old) were treated for aTTP. 30 patients (60%) had cerebral involvement and 13 (26%) had cardiac involvement. Cardiac troponin I was above upper normal value for 61% of patients. Before treatment, median platelet count was 16 g/l and median serum creatinine was 86 µmol/l. Three initial clinical suspicions of aTTP were finally diagnosed as HUS (2 patients) or vitamin deficiency (1 patient) resulting in the stop of treatment. A median number of 6 plasma exchanges was administered (min:3 - max:16). 375mg/m rituximab injections (3 to 4 for 35/43 patients with reported data) were mostly initiated within 3 days after the first plasma exchange. Caplacizumab treatment was initiated early (37/42 patients with reported data within 2 days after 1st plasma exchange) with a total median duration of treatment of 33 days (min:18 - max:35). The median platelet count normalization was 5 days (min:4 - max:6). 6/41 (14,6%) experienced exacerbations. No deaths and no patients refractory to therapy were reported. Eight adverse events related to caplacizumab therapy were reported, all with good outcomes. Conclusion Concomitant start of additional treatments allow to target severe ADAMTS13 deficiency and platelet aggregation which causes early mortality. The clinical French score seems useful in clinical practices.

Safety and Efficacy of Mycophenolate Mofetil in Relapsing Acquired Thrombotic Thrombocytopenic Purpura: Could It Prevent Further Relapse?.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3993-3993 ◽  
Author(s):  
Sameer A. Tulpule ◽  
Yvonne A. Francis ◽  
Deepti Radia ◽  
Claire N. Harrison ◽  
Beverely J. Hunt
Keyword(s):  
Platelet Count ◽  
Mycophenolate Mofetil ◽  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Maximum Dose ◽  
Case Series ◽  
Initial Presentation ◽  
Thrombocytopenic Purpura ◽  
Methyl Prednisolone ◽  
Threatening Condition

Abstract Introduction: Thrombotic thrombocytopenic purpura (TTP) is a life threatening condition requiring rapid diagnosis and treatment. Plasma exchange (PEX) is the mainstay of treatment. Various forms of immunosuppression (IS) have been used which include steroids, cyclosporine, cyclophosphamide, vincristine and rituximab. The percentage of patients relapsing is unclear. There is a suggestion that up to half of the patients with severe acquired deficiency of von Willebrand factor -cleaving protease (vWF-CP) activity relapse within a year. There are no reports of the use of mycophenolate mofetil (MMF) in acquired TTP. We describe three patients with acquired TTP, treated with MMF at relapse, with the intention to prevent further relapse. Methods: The 3 patients presented with acute acquired TTP. They all had at least 3 of the clinical pentad of fever, microangiopathic haemolytic anaemia, thrombocytopenia, neurological and renal impairment plus a vWF-CP level of < 2% at initial presentation. All of them underwent PEX until remission (platelet count of >150 x 109/L for at least 2 consecutive days with resolution of neurological and renal signs). MMF was introduced at remission after relapse at a dose of 500mg BD, post PEX, increasing upto a maximum dose of 750 mg BD. MMF was introduced at 4th relapse for patient A, 2nd relapse for patient B and 1st relapse for patient C. Results: All 3 patients were females. The ages at presentation were 63, 72 and 46 years. At presentation, the haemoglobin was 6.0, 8.7 and 6.7 g/dL and platelet count was 19, 36 and 21 x 109 /L respectively. Patient A relapsed eight times at day (d) 9, d20, d53, d89, d198, d209, d221 and d231. She was treated with PEX in conjunction with steroids and vincristine, cyclosporine, cyclophosphamide and rituximab for the first 3 relapses respectively. During the third relapse the patient’s condition deteriorated and she became unconcious requiring ventilation. MRI brain showed multiple small foci consistent with vascular disease. She recovered, but relapsed again despite cyclophosphamide and rituximab. After the 4th relapse on d102, MMF was started reaching a maximum dose of 750mg BD. She had regular full blood counts checked. At d187 she was found to be neutropenic and the MMF was stopped. She relapsed in 11 days and was recommenced on MMF at 500mg bd after PEX. MMF was continued at the dose of 750mg BD after the 7th and 8th relapse. Despite full dose MMF, she relapsed and was treated with PEX and a further course of rituximab was given at the 8th relapse. Patient B had received 500mg of methyl prednisolone on ITU with PEX at initial presentation. MMF (500mg BD) was commenced at remission after second relapse (d23) after undergoing plasma exchange. Patient C was commenced on MMF (500mg BD) after first relapse (d36). All 3 are in remission and continue on MMF at a follow up of 12, 2 and 4 months respectively since last relapse. MMF was tolerated very well except for transient neutropenia (patient A) and transient diarrhoea (patient C). Conclusion: MMF appears to be safe in patients with relapsed TTP who received multiple lines of treatment. Due to the small size of this case series it is unclear whether MMF is efficacious in reducing the risk of relapse in TTP; a formal longer study may be warranted.

scholarly journals Thrombotic thrombocytopenic purpura and dose of plasma exchange

Blood ◽  
1979 ◽  
Vol 54 (4) ◽  
pp. 842-849 ◽  
Author(s):  
EG Taft
Keyword(s):  
Platelet Count ◽  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Exchange Transfusion ◽  
Residual Disease ◽  
Blue Dye ◽  
Success Rates ◽  
Thrombocytopenic Purpura ◽  
Adequate Dose ◽  
Ldh Activity

Abstract Four patients with thrombotic thrombocytopenic purpura (TTP) were treated by plasma-exchange transfusion, three of whom recovered completely. Because previous reports in the literature describing exchange transfusion as treatment for TTP have demonstrated variable success rates, particular attention was given to “dose”and frequency of plasma exchange. Evans blue dye studies established a measure of “dose” under conditions of varying efficiency. Serum LDH activity was found to be diminished by plasma exchange, and the rate of return of serum LDH activity reflected residual disease activity. The magnitude of LDH activity reduction correlated with the adequacy of dose of plasma exchange and was an indicator for the need of repeated daily exchanges. Failure to obtain a spontaneous increment in platelet count also suggested the need for additional exchanges and/or larger dose of exchange. There is a need for a standard expression of dose of plasma exchange. Utilizing these markers (LDH, platelet count), it may be possible to improve the survival in TTP if adequate dose and frequency of plasma exchange are used.

Platelet transfusion and catheter insertion for plasma exchange in patients with thrombotic thrombocytopenic purpura and a low platelet count

Transfusion ◽  
2015 ◽  
Vol 55 (7) ◽  
pp. 1798-1802 ◽  
Author(s):  
Etienne Riviere ◽  
Mélanie Saint-Léger ◽  
Chloé James ◽  
Yahsou Delmas ◽  
Benjamin Clouzeau ◽  
...  
Keyword(s):  
Platelet Count ◽  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Platelet Transfusion ◽  
Catheter Insertion ◽  
Thrombocytopenic Purpura ◽  
Low Platelet Count

scholarly journals Acquired Deficiency of von Willebrand Factor-Cleaving Protease in a Patient With Thrombotic Thrombocytopenic Purpura

Blood ◽  
1998 ◽  
Vol 91 (8) ◽  
pp. 2839-2846 ◽  
Author(s):  
Miha Furlan ◽  
Rodolfo Robles ◽  
Max Solenthaler ◽  
Bernhard Lämmle
Keyword(s):  
Platelet Count ◽  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Von Willebrand Factor ◽  
Protease Activity ◽  
Temporary Increase ◽  
Severe Thrombocytopenia ◽  
Thrombocytopenic Purpura ◽  
Von Willebrand ◽  
Willebrand Factor

Plasma of patients with thrombotic thrombocytopenic purpura (TTP) has been shown to contain unusually large von Willebrand factor (vWF) multimers that may cause platelet agglutination in vivo. Fresh frozen plasma infusions and plasma exchange represent the most efficient therapy of acute TTP. A specific protease responsible for cleavage of vWF multimers has been recently isolated from normal human plasma and was found to be deficient in four patients with chronic relapsing TTP. We examined the activity of the vWF-cleaving protease in plasma samples collected over a period of 400 days from a further patient with recurrent episodes of TTP who was treated by plasma exchange, plasma infusion, vincristine, corticosteroid therapy, and splenectomy. Complete deficiency of the vWF-cleaving protease was established during the first episode of TTP. The ensuing normalization of the platelet count was associated with the appearance of the protease activity. Three months after remission from the initial TTP event, the vWF-cleaving protease again disappeared and the platelet count gradually decreased. Relapses of severe thrombocytopenia occurred 7 and 11 months after the first acute episode of TTP. Deficient protease activity was associated with the presence in the patient plasma of an inhibitor that was found to be an IgG. Plasma exchange/infusion was followed by a temporary increase in the antibody titer, whereas treatment with vincristine led to a recovery of the platelet count without affecting the inhibitor concentration. Splenectomy and corticosteroid treatment resulted in disappearance of the autoantibody and normalization of the protease activity and of the platelet count. Our data suggest that the thrombocytopenia in this patient with TTP was associated with a lack of the vWF-cleaving protease activity depleted by an autoimmune mechanism. This case, together with our previously reported patients, leads us to conclude that acquired as well as constitutional deficiency of the vWF-cleaving protease may predispose to TTP.

Thrombotic Thrombocytopenic Purpura in a Patient with Sickle Cell Crisis.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3963-3963
Author(s):  
Jumana S. Chatiwala ◽  
Gunwant Guron ◽  
Ibrahim Sidhom
Keyword(s):  
Platelet Count ◽  
Sickle Cell Disease ◽  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Hemolytic Anemia ◽  
Sickle Cell ◽  
Microangiopathic Hemolytic Anemia ◽  
Cell Disease ◽  
Thrombocytopenic Purpura ◽  
Sickle Cell Crisis

Abstract Thrombotic thrombocytopenic purpura (TTP) in association with sickle cell crisis is rare. We present a case of sickle cell crisis and TTP. This is 48 years old Nigerian male with history of mild sickle cell anemia since childhood presented with sickle cell crisis and mental state changes. On admission labs are hematocrit of 20 and platelet count of 212,000. He was treated for sickle cell crisis but developed acute dysuria and progressively worsening anemia (Hct-13.7) and thrombocytopenia (Plt-9000) with sickle cell and fragmented RBCs on peripheral smear with LDH of 8772. This picture was consistent with TTP. Patient was immediately started on plasma exchange. Patient received a course of plasma exchange as well as hemodialysis and his condition improved, with return of platelet count to normal (232), LDH to baseline (276). Patient was discharged with mild renal insufficiency (serum creatinine-2.3) off dialysis and plasma exchange. Conclusion: TTP is a micro vascular occlusive disorder characterized by systemic or intrarenal aggregation of platelets, thrombocytopenia, and mechanical injury to erythrocytes. It is associated with pentard of signs and symptoms: thrombocytopenia, microangiopathic hemolytic anemia (schistocytes on peripheral blood smear), neurological abnormalities, renal failure and fever. In practice thrombocytopenia, microangiopathic hemolytic anemia and elevated lactate dehydrogenase levels are often sufficient for the diagnosis. Our patient with sickle cell crisis was a diagnostic challenge and it is our belief that TTP evolved during inpatient therapy for painful crisis. We believe his hemolysis was due to sickle cell disease and TTP. The syndrome was reversed with prompt and aggressive treatment with plasmapharesis. (1, H. E. Lee, V. J. Marder, L. J. Logan, S. Friedman, B. J. Miller, Life-threatening thrombotic thrombocytopenic purpura (TTP) in a patient with sickle cell-hemoglobin C disease. Ann Hematol. 2003 Nov 82(11): 702–4. 2, Epub 2003 Aug 16. Chehal A, Taher A, Shamseddine A, Sicklemia with multi-organ failure syndrome and thrombotic thrombocytopenic purpura. Hemoglobin. 2002 Nov; 26(4): 345–51. 3, J. Bolanos-Meade, Y. K. Keung, C. Lopez-Arvizu, R. Florendo, E. Cobos, Thrombotic thrombocytopenic purpura in a patient with sickle cell crisis. Ann Hematol. 1999 Dec 78(12): 558–9. 4, Geigel EJ, Francis CW, Reversal of multiorgan system dysfunction in sickle cell disease with plasma exchange. Acta Anaesthesiol Scand. 1997 May; 41(5): 647–50.)

Disseminated Malignancy Misdiagnosed as Thrombotic Thrombocytopenic Purpura: A Report of 10 Patients and a Systematic Review of Published Cases.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1062-1062
Author(s):  
Kristin K. Francis ◽  
Nalini Kalyanam ◽  
Deirdra R. Terrell ◽  
Sara K. Vesely ◽  
James N. George
Keyword(s):  
Systematic Review ◽  
Bone Marrow ◽  
Platelet Count ◽  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Bone Marrow Biopsy ◽  
Thrombocytopenic Purpura ◽  
History Of ◽  
History Of Cancer ◽  
Systemic Malignancy

Abstract Patients with disseminated malignancy who present with microangiopathic hemolytic anemia and thrombocytopenia may be misdiagnosed as thrombotic thrombocytopenic purpura (TTP), resulting in inappropriate plasma exchange treatment, a procedure with major risk, and delay of appropriate chemotherapy. We report the 17 year experience of The Oklahoma TTP-HUS Registry, 1989–2005, and a systematic review of previously published case reports. Ten of 335 consecutive patients in the Oklahoma Registry who were initially diagnosed with their first episode TTP and treated with plasma exchange were subsequently discovered to have disseminated malignancy; only one had a history of cancer. These 10 patients were compared to the 133 concurrent patients with idiopathic TTP. Disseminated malignancy (n=10) Idiopathic TTP (n=133) P Data are median values. P-value for neurologic symptoms compares distribution of abnormalities. Number of patients who had ADAMTS13 measured is in parentheses. 8 idiopathic TTP patients never had plasma exchange (PE). Age (years) 56 47 0.106 Sex (% female) 30% 73% 0.008 Duration of sx (days) 21 8 0.005 Presenting sx Weakness 70% 53% 0.347 cough, dyspnea 70% 26% 0.007 Fever 50% 31% 0.292 abdominal pain 40% 35% 0.745 Nausea/vomiting 20% 53% 0.052 Neurologic abnormalities Severe 20% 47% 0.128 Minor 60% 29% None 20% 24% Laboratory data hematocrit (%) 21 22 0.868 platelet count (103/ml) 21,000 13,000 0.328 creatinine (mg/dL) 2.4 2.0 0.761 LDH (U/L) 2894 1260 0.045 ADAMTS13 Median activity (%) 50(8) 23 (81) 0.167 <5% activity (% of pts) 0 30% 0.102 Response to PE 10% 82% (125) <0.001 Death (within 30 days) 90% 20% <0.001 Patients with disseminated malignancy had a longer duration of symptoms, were more often men, had more frequent presence of respiratory symptoms, higher LDH levels, more often failed to respond to plasma exchange treatment, and had a higher mortality. Neurologic abnormalities, hematocrit, platelet count, and serum creatinine were not different between the two groups. Diagnosis of malignancy was made by bone marrow biopsy in 6 patients but not until autopsy in 2 patients. A systematic review identified 19 additional patients, reported from 1965 to 2005, in whom TTP or HUS was initially suspected and systemic malignancy subsequently discovered. Only 5 patients had a history of cancer. Malignancy was not diagnosed until autopsy in 6 patients. Fourteen different malignant disorders were diagnosed in these 29 patients. CONCLUSIONS: Disseminated malignancy may be occult and may mimic TTP. A search for systemic malignancy, including a bone marrow biopsy, is appropriate when patients diagnosed with TTP have atypical clinical features or fail to respond to plasma exchange.

scholarly journals Heparin-induced thrombocytopenia as a cause of prolonged low platelet count in patient with thrombotic thrombocytopenic purpura treated with plasmapheresis

2017 ◽  
Vol 64 (2) ◽  
Author(s):  
Agata Winiarska ◽  
Norbert Kwella ◽  
Tomasz Stompór
Keyword(s):  
Platelet Count ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Low Molecular Weight Heparin ◽  
Careful Analysis ◽  
Low Molecular Weight ◽  
Thrombotic Microangiopathies ◽  
Thrombocytopenic Purpura ◽  
Heparin Induced Thrombocytopenia ◽  
Low Platelet Count ◽  
Functional Deficiency

Thrombotic thrombocytopenic purpura (TTP) is a rare disorder belonging to thrombotic microangiopathies (TMA) and is caused by functional deficiency of metalloproteinase ADAMTS-13. Plasma exchange (PE) remains the treatment of choice in this disease. Here were describe the case of patient who apparently recovered from TTP following multiple sessions of PE, but remained thrombocytopenic. Careful analysis revealed the development of heparin-induced thrombocytopenia (HIT) that precluded platelet count (PLT) normalization. Full normalization of PLT followed discontinuation of PE and low-molecular weight heparin.

scholarly journals Plasma exchange in thrombotic microangiopathies (TMAs) other than thrombotic thrombocytopenic purpura (TTP)

Hematology ◽  
2017 ◽  
Vol 2017 (1) ◽  
pp. 632-638 ◽  
Author(s):  
Jeffrey L. Winters
Keyword(s):  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Marked Improvement ◽  
Case Reports ◽  
Case Series ◽  
Controlled Trials ◽  
Complement Pathway ◽  
Thrombotic Microangiopathies ◽  
Thrombocytopenic Purpura ◽  
Randomized Controlled

Abstract Thrombotic microangiopathies (TMAs) are a diverse group of disorders that are characterized by common clinical and laboratory features. The most commonly thought-of TMA is thrombotic thrombocytopenic purpura (TTP). Because of the marked improvement in patient mortality associated with the use of therapeutic plasma exchange (TPE) in TTP, this therapy has been applied to all of the TMAs. The issue, however, is that the pathophysiology varies and in many instances may represent a disorder of the endothelium and not the blood; in some cases, the pathophysiology is unknown. The use of TPE is further obscured by a lack of strong supporting literature on its use, with most consisting of case series and case reports; controlled or randomized controlled trials are lacking. Evidence supporting the use of TPE in the treatment of TMAs (other than TTP and TMA–complement mediated) is lacking, and therefore its role is uncertain. With the greater availability of genetic testing for mutations involving complement regulatory genes and complement pathway components, there seems to be a percentage of TMA cases, other than TMA–complement mediated, in which complement pathway mutations are involved in some patients. The ability of TPE to remove abnormal complement pathway components and replace them with normal components may support its use in some patients with TMAs other than TTP and TMA–complement mediated.

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