ADAMTS13 Activity and Autoantibodies Subclasses as Recurrency Risk Predictors In Acquired Thrombotic Thrombocytopenic Purpura

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2532-2532
Author(s):  
Giuseppe Bettoni ◽  
Luca A Lotta ◽  
Dario Consonni ◽  
Dino FA Motti ◽  
Roberta Palla ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Recurrent Disease ◽  
Random Effect ◽  
Acute Disease ◽  
Plasma Samples ◽  
Adamts13 Activity ◽  
Microangiopathic Hemolytic Anemia ◽  
Thrombocytopenic Purpura ◽  
Disease Remission

Abstract Abstract 2532 Background: Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening disease characterized by acute episodes of thrombocytopenia and microangiopathic hemolytic anemia due to disseminated microvascular thrombosis. Up to 40% of patients with TTP who survive the first acute disease episode develop one or more recurrent episodes. The severe deficiency of the von Willebrand factor (VWF) cleaving protease ADAMTS13 in plasma and the presence of anti-ADAMTS13 autoantibodies during both acute presentation and disease remission are associated with increased risk for recurrence. However, additional markers are needed for an accurate prediction of the risk for recurrent disease. Anti-ADAMTS13 autoantibodies of different immunoglobulin (Ig) subclass, specificity and mechanisms of action have been described in patients with the autoimmune form of TTP. We sought to determine the relationships between anti-ADAMTS13 Ig subclasses and risk for recurrence in a large cohort of TTP patients. Patients and methods: TTP was defined using commonly accepted criteria (microangiopathic hemolytic anemia, thrombocytopenia and exclusion of alternative explanation for the disease symptoms). Anti-ADAMTS13 IgM, IgA, IgG and IgG1, IgG2, IgG3 and IgG4 subclasses were measured by ELISA in plasma samples obtained from a total of 115 patients with TTP referred to the Milan TTP registry. Plasma samples had been collected during acute disease presentation (n=60), disease remission (n=92) or both (n=37). ADAMTS13 activity and inhibitor were also measured. The levels of different Ig subclasses were compared between two groups of patients with or without recurrence during follow-up. Patients with a follow-up <24 months were excluded from analysis. Statistical analysis was performed using random effect linear regression models. Results: TTP patients had a median follow-up of 64 months (range 0–399). A total of 11 patients (9.5% of all patients) were followed-up for less than 24 months and excluded from further analysis. Of patients with a follow-up >24 months, 53 (50%) developed recurrences, whereas 51 did not. Recurrences occurred at a median of 24 months (45 days to 11 years) after the first episode and were more common in the first three years (n=35, 67%). Comparison of anti-ADAMTS13 Ig subclasses measured during acute disease presentation in TTP patients with recurrence and in patients without recurrence revealed lower levels of IgA (0.017 vs 0.243, p=0.05), IgG1 (0.076 vs 0.234, p=0.01) and IgG3 (0.126 vs 0.385, p=0.002) in recurrent patients, whereas IgG4 were higher in recurrent TTP (0.712 vs 0.289, p<0.0005). Notably, levels of IgA (random effect, p=0.018), IgG1 (random effect, p=0.005) and IgG3 (random effect, p=0.006) were also associated with lower platelet counts at presentation of acute TTP and IgG3 levels were associated with the number of plasma exchange procedures performed until remission/death. In TTP patients during remission lower levels of ADAMTS13 antigen (49.3 vs 69.5 p<0.0005) and activity (41.4 vs 75.5 p<0.0005) as well as high levels of anti-ADAMTS13 total IgG (21.93 vs 5.13 p=0.007) were confirmed to be predictors of recurrent disease. Other Ig subclasses, measured during remission were not associated with a history of recurrent TTP. The logistic analysis showed an odds of relapse of 4.2 (range 1.5–12 p=0.008) at remission in patients with reduced ADAMTS13 and of 4.4 (range 1.7–11.3; p=0.002) in patients with high levels of IgG, but not in the acute phase. Conclusions: Low values of ADAMTS13 and anti-ADAMTS13 autoantibodies showed and association with a fourfold increase of recurrency risk, while the same result is not confirmed for the acute phase. Anti-ADAMTS13 IgA, IgG1, 3 and 4 subclasses, measured at acute TTP presentation, showed association with recurrent disease in a retrospective cohort study of TTP patients. Ig subclass measurement might be useful to improve recurrence risk prediction in patients with TTP. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Diagnosis of thrombotic thrombocytopenic purpura

2020 ◽  
Vol 92 (12) ◽  
pp. 207-217
Author(s):  
G. M. Galstyan ◽  
E. E. Klebanova
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Inhibitory Effect ◽  
Plasma Samples ◽  
Adamts13 Activity ◽  
Microangiopathic Hemolytic Anemia ◽  
Inhibitory Effects ◽  
Thrombocytopenic Purpura ◽  
Life Threatening ◽  
Von Willebrand ◽  
Willebrand Factor

Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening disease, disease, characterised by microangiopathic hemolytic anaemia, consumption thrombocytopenia, and organ dysfunction. The pathogenesis of TTP is attributed to the deficiency in the activity of the metalloproteinase ADAMTS13, specific von Willebrand factor cleaving protease. TTP is suspected when detecting microangiopathic hemolytic anemia, thrombocytopenia, damage to various organs. Diagnosis of TTP is confirmed by the detection of ADAMTS13 activity in plasma less than 10%. Plasma samples for the study of ADAMTS13 activity should be taken before the start of plasma transfusions or plasma exchange. In patients with severe ADAMTS-13 deficiency autoantibodies anti-ADAMTS13 and inhibitor ADAMTS13 should be investigated. Anti-ADAMTS13 antibodies belonging to IgG not always have inhibitory effects. The inhibitory effect of anti-ADAMTS13 antibodies is confirmed by mixing test. All patients with the first established diagnosis of TTP should be examined for mutations of the ADAMTS13 gene.

scholarly journals Active and Ultra-Large Von Willebrand Factor Is Significantly Elevated in Patients with Immune Thrombotic Thrombocytopenic Purpura

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 523-523
Author(s):  
Wenjing Cao ◽  
Alicia Veninga ◽  
Elizabeth M. Staley ◽  
Adam Miszta ◽  
Nicole Kocher ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Von Willebrand Factor ◽  
Plasma Levels ◽  
Acute Episode ◽  
Healthy Controls ◽  
Plasma Samples ◽  
Adamts13 Activity ◽  
Thrombocytopenic Purpura ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Background: Immune thrombotic thrombocytopenic purpura (iTTP), a potentially fatal hematological emergency, is primarily caused by acquired deficiency of ADAMTS13 activity due to autoantibodies. Immunoglobulin G (IgG)-type autoantibodies bind ADAMTS13 and inhibit its ability to cleave endothelium-derived ultra large von Willebrand factor (ULVWF). However, it remains poorly understood whether plasma VWF status can be used as a disease marker for diagnosis and monitoring therapy in patients with acute iTTP. Objective: To address this question, we determined plasma levels of VWF antigen (VWF:Ag), collagen-binding activity (VWF:CB), active forms of VWF (VWF:Ac), and VWF multimers in iTTP patients during acute episode and in early remission. Patients and Methods: From the Alabama registry, we identified 69 unique patients with a confirmed diagnosis of iTTP in whom plasma ADAMTS13 activity was <10 U/dL with positive inhibitors and elevated anti-ADAMTS13 IgGs. Of 69 patients, 21 had longitudinal plasma samples collected. Plasma samples from 56 healthy individuals, who did not have a hematological disease, cancer, and infection, were recruited as controls. Plasma levels of VWF:Ag, VWF:CB, and VWF:Ac were determined by an ELISA-based assay. Plasma VWF multimer distribution was assessed by an in-gel Western blotting assay following electrophoresis on a 1% SDS-agarose gel. Results: The mean age for our cohort iTTP patients was 43.9 ± 13.4 years. Twenty-six patients were male and 43 were female with male to female ratio of 1 to 1.7. Fifty-three patients were African American descents, 14 Caucasians, 1 Hispanic, and 1 unknown race. Plasma levels of VWF:Ag in acute iTTP patients were 289.4 ± 17.7%, significantly increased compared with those in the healthy controls (144.9 ± 7.6%) (p<0.0001); plasma levels of VWF:CB in these patients were 241 ± 17.9%, also significantly elevated compared with those in the healthy controls (149.9 ± 12.01%) (p=0.0001); additionally, plasma levels of VWF:Ac (304.6 ± 23.2%), assessed by its ability to bind anti-VWF-A1 nanobody, were more dramatically elevated compared with those in the controls (101.6 ± 5.9%) (p<0.0001). More interestingly, while the ratios of VWF:CB to VWF:Ag in patients with acute iTTP (0.8 ± 0.04) were lower than those in the healthy controls (1.0 ± 0.05) (p=0.0036), the ratios of VWF:Ac to VWF:Ag were significantly higher in patients with acute episode (1.2 ± 0.1) than those in the controls (0.8 ± 0.05) (p=0.0003). Furthermore, there was no statistically significant difference in the patient plasma levels of VWF:Ag (p=0.69) and VWF:CB (p=0.08) during acute episode and during early remission. However, the plasma levels of VWF:Ac in patients with acute disease were significantly higher than those in the early remission (p=0.002). Surprisingly, 90% (36/40) of out iTTP patients during acute episode showed the presence of ULVWF in their plasma using in-gel Western blotting, which allows the ULVWF to be detected without the transfer step to avoid any potential loss of larger VWF multimers during protein transfer. These ULVWF multimers disappeared in 3/4 iTTP patients in remission when ADAMTS13 activity recovered. In 28 healthy control samples, only one showed ULVWF. Conclusion: Our results demonstrate, for the first time in a large cohort, that active forms of VWF and ultra large VWF multimers are present in iTTP patient's plasma during the acute period, which is reduced or disappears during the early remission. Therefore, measuring active forms of VWF and ultra large VWF multimers may aid in diagnosis of iTTP and help monitoring of disease processes following therapy. Our ongoing study is to determine whether these biomarkers can be used to predict responses to treatment and long-term outcome. Disclosures Zheng: Alexion: Research Funding, Speakers Bureau.

scholarly journals Open ADAMTS13, induced by antibodies, is a biomarker for subclinical immune-mediated thrombotic thrombocytopenic purpura

Blood ◽  
2020 ◽  
Author(s):  
Elien Roose ◽  
An-Sofie Schelpe ◽  
Edwige Tellier ◽  
György Sinkovits ◽  
Bérangère S Joly ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Adamts13 Activity ◽  
Thrombocytopenic Purpura ◽  
Follow Up Study ◽  
Open Conformation ◽  
Immune Mediated ◽  
Long Term Follow Up ◽  
Donor Plasma

Recently, we showed that during the acute phase of immune-mediated thrombotic thrombocytopenic purpura (iTTP), ADAMTS13 circulates in an open conformation. Although the cause of this conformational change in acute iTTP remains elusive, ADAMTS13 is mainly closed in iTTP patients (i) in remission with an ADAMTS13 activity &gt;50% and undetectable anti-ADAMTS13 autoantibodies, and (ii) after rituximab treatment, suggesting a role for anti-ADAMTS13 autoantibodies. Therefore, IgGs from 18 acute iTTP patients were purified and added to closed ADAMTS13 in healthy donor plasma. This resulted in open ADAMTS13 in 14/18 (78%) samples, proving that indeed anti-ADAMTS13 autoantibodies can induce an open ADAMTS13 conformation. To further elucidate the conformation of ADAMTS13 in iTTP patients, we studied a novel iTTP patient cohort (n=197) that also included plasma samples of iTTP patients in remission where ADAMTS13 activity was &lt;50%. The open ADAMTS13 conformation was not only found during acute iTTP but also in patients in remission with an ADAMTS13 activity &lt;50% and in half of the patients with an ADAMTS13 activity &gt;50%, although free anti-ADAMTS13 autoantibodies were not always detected. Thus open ADAMTS13 is not only a hallmark of acute iTTP, but also a novel biomarker to detect subclinical iTTP in patients in remission. Finally, a long term follow-up study in one iTTP patient showed that the open conformation precedes a severe drop in ADAMTS13 activity. In conclusion, we have shown that anti-ADAMTS13 autoantibodies from iTTP patients induce an open ADAMTS13 conformation. Most importantly, an open ADAMTS13 conformation is a biomarker for subclinical iTTP and could become an important tool in TTP management.

Evaluation of Clotting Factor Concentrates for Treatment of Thrombotic Thrombocytopenic Purpura.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3678-3678
Author(s):  
Tanja Falter ◽  
Mirjeta Qorraj ◽  
Sarah Steinemann ◽  
Thomas Vigh ◽  
Inge Scharrer
Keyword(s):  
Human Plasma ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Blood Group ◽  
Conflicts Of Interest ◽  
Blood Groups ◽  
Clotting Factor ◽  
Plasma Samples ◽  
Adamts13 Activity ◽  
Thrombocytopenic Purpura ◽  
Clotting Factor Concentrates

Abstract Abstract 3678 Introduction: Thrombotic thrombocytopenic purpura (TTP) is characterized by microthrombi, hemolytic anemia as well as thrombocytopenia. These symptoms are caused by a decreased activity of the protease ADAMTS13 which cleaves the von Willebrand Factor (VWF), due to mutation of the ADAMTS13-gene or autoantibodies. At the moment, the only available immediate therapy is plasmapheresis with Fresh Frozen Plasma (FFP) which may induce side effects. Therefore an alternative therapy might be the treatment with clotting factor concentrates. Methods: 40 plasma samples were tested, consisting of FFP and solvent/detergent treated plasma, four batches of each blood group; VWF/VIII concentrates (Wilate®; Wilfactin®; Haemate®P; Immunate®; Kogenate®, Beriate®). In all samples ADAMTS13 activity, antigen and autoantibodies against ADAMTS13 were investigated. Additionally, the samples were tested for the presence of ultralarge VWF multimers. The BCS method according to Böhm, two ELISAs (Technozym®ADAMTS13 and Actifluor™ADAMTS13) and the electrophoresis on a SDS gel were used. Results: ADAMTS13 activity was found in all VWF)VIII concentrates, which are produced from human plasma, but only with a very low activity (Wilate® 5.6%; Wilfactin® 2.8%; Haemate®P 13%; Immunate® 3.7%). ADAMTS13 activity was not detectable in the factor VIII concentrates (Kogenate® <2%; Beriate® <2%). Usual FFP and solvent/detergent treated plasma samples, contained much higher ADAMTS13 activity and antigen values than concentrates (FFP 78.6%, solvent/detergent treated plasma 77.6%). However a difference of activity between individual blood groups was evident in FFP samples (blood group A 69.4%; B 64.9%; AB 98.1%; 0 82.0%). Ultralarge VWF multimers could be demonstrated in VWF containing concentrates, less in VIII concentrate from human plasma and not in FFP and solvent/detergent treated plasma samples. As expected recombinant-produced VIII concentrate contained no traces of ultralarge VWF. In all analyzed samples antibodies were negative. Conclusion: For therapy of TTP clotting factor concentrates cannot be used as an alternative to the usual FFP and solvent/detergent treated plasma, because their ADAMTS13 activity values are too low. In addition, the VWF/VIII concentrates contain higher quantities of ultralarge VWF multimers, which are contraindicated for TTP patients. The differences of ADAMTS13 activity in FFP samples varies between the individual blood groups and batches. Solvent/detergent treated plasma shows less variation in ADAMTS13 activity due to the manufacturing process involving plasma pooling. Disclosures: No relevant conflicts of interest to declare.

Preemptive Rituximab Infusions Efficiently Prevent Relapses In Acquired Thrombotic Thrombocytopenic Purpura. Experience Of The French Thrombotic Microangiopathies Reference Center

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 448-448
Author(s):  
Miguel HIE ◽  
Julie Gay ◽  
Lionel Galicier ◽  
Francois Provot ◽  
Sandrine Malot ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Median Number ◽  
Continuous Variables ◽  
Adamts13 Activity ◽  
Thrombocytopenic Purpura ◽  
History Of ◽  
Adamts13 Deficiency ◽  
Group 2 ◽  
Group 1

Context Acquired thrombotic thrombocytopenic purpura (TTP) results from a severe, antibody-mediated, deficiency in the von Willebrand factor-cleaving protease ADAMTS13. Rituximab is increasingly used in this indication in patients with a suboptimal response to plasma exchange. When severe acquired ADAMTS13 deficiency persists during remission, the estimated incidence rate is of 0.4/year. So far, it is still controversial whether preemptive rituximab efficiently prevents relapses in these patients. Patients and methods We defined two groups of patients with a history of acquired TTP who displayed a persistent severe ADAMTS13 deficiency during remission. Patients of group 1 were treated with preemptive infusions of rituximab. Patients of group 2 were managed in centers in which preemptive rituximab infusions were not the standard of care. The relapse incidence was evaluated and compared between both groups. Patients were treated according to National recommendations and enrolled from 12 French centers during a 12-year period. Patients were explored for ADAMTS13 activity and peripheral B-cell count every 3 months. Only patients with a > 12-month follow-up after rituximab administration are reported here. Median (25th - 75th percentile) was determined for all continuous variables. Wilcoxon’s test was used to compare continuous variables and the chi-square test or Fisher’s exact test to compare binary data. Relapse-free survival was compared between both groups using the Kaplan-Meier estimator with the corresponding 95% confidence interval. Results Forty-eight patients (20.6%) with a history of acquired TTP displayed a persistent severe ADAMTS13 deficiency on remission or experienced a subsequent severe ADAMTS13 deficiency (24 cases each) after a median follow-up of 17 months (12-29 months). Anti-ADAMTS13 antibodies concentration was 44 U/mL (24-59 U/mL). Thirty patients received preemptive infusions of rituximab (group 1), whereas 18 others had no therapeutical intervention (group 2). In group 1, 16 patients experienced a past history of TTP with a median number of 2 (1-3) episodes, corresponding to a relapse incidence of 0.22 (0-0.57)/year. Rituximab infusions were performed 14.5 months (6.5-27.4 months) after the last TTP episode. A median number of 4 (1-4) rituximab infusions were performed. The median follow-up between the first preemptive infusion of rituximab and the last ADAMTS13 evaluation is of 36 months (24-65 months). After preemptive rituximab administration, only 3 patients experienced a clinical relapse (0 [0] episode/year), corresponding to a significant reduction in the relapse incidence (P < .01). ADAMTS13 activity was 58.5% (30.5%-86.3%). Three months after the first rituximab infusion, ADAMTS13 activity was 46% (30-68); it further increased until the 12th month, and subsequently decreased. Accordingly, B-cell lymphocytes remained undetectable until the 6th month, and progressively increased at the 9th month to reach normal values at the 18th month. Nine patients (30%) required one (5 cases), two (2 cases), three (1 case) or ten (1 case) additional courses of rituximab for a further decrease or a persistent undetectable ADAMTS13 activity, which allowed to maintain a detectable ADAMTS13 activity in all but one patients. The time between two consecutive courses of rituximab was 26 months (5-59 months). At the end of follow-up, ADAMTS13 activity remained normal in 18 patients; 10 patients had a moderate ADAMTS13 deficiency, and 2 patients had a persistently undetectable ADAMTS13 activity. In four patients (13%), rituximab alone failed to increase durably ADAMTS13 activity, which required additional immunosuppressive drugs. In group 2, 14 patients relapsed after a 66-month follow-up (36-105 months), corresponding to a higher relapse incidence than in patients who received preemptive infusions of rituximab (0.23 [0.1-0.46] relapse/year, P<.01). Moreover, 2 patients died of TTP in group 2, whereas no fatal outcome was recorded in group 1. Relapse free survival over time was significantly longer in group 1 (Log-rank test: P = .049). Five patients experienced adverse effects including benign infections in 2 cases. Conclusion Rituximab efficiently prevents TTP relapses in most patients with a persistent acquired ADAMTS13 deficiency, with acceptable side effects. Disclosures: Off Label Use: Rituximab Rituximab may prevent relapses in acquired thrombotic thrombocytopenic purpura.

An enzyme immunoassay of ADAMTS13 distinguishes patients with thrombotic thrombocytopenic purpura from normal individuals and carriers of ADAMTS13 mutations

2004 ◽  
Vol 91 (04) ◽  
pp. 806-811 ◽  
Author(s):  
Wenhua Zhou ◽  
Han-Mou Tsai
Keyword(s):  
Fusion Protein ◽  
Enzyme Immunoassay ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Activity Level ◽  
Dependent Manner ◽  
Plasma Samples ◽  
Adamts13 Activity ◽  
Thrombocytopenic Purpura ◽  
Normal Plasma ◽  
Normal Individuals

SummaryRecent studies demonstrate that assay of ADAMTS13, a circulating zinc metalloprotease that cleaves von Willebrand factor (VWF) at the Y1605-M1606 bond, is an important tool in the diagnosis of thrombotic thrombocytopenic purpura (TTP). In order to develop a method that could be adapted for general use, we describe an enzyme immunoassay (EIA)-based method for measuring the activity of ADAMTS13 in patient plasma samples. A monomeric peptide consisting of the amino acid residues D1596-R1668 of VWF was produced that spanned the ADAMTS13 cleavage site and was franked by glutathione s-transferase (GST) and a 6His sequences at the amino and carboxyl termini respectively. When probed with either anti-GST or anti-6His, the VWF fragment appeared as a 38.1-kDa band. After incubation with normal plasma, the VWF fragment was replaced by a 30.4-kDa band, which was recognized by antiGST but not by anti-6His, consistent with the expected cleavage at the Y1605-M1606 bond. EDTA or plasma samples from patients with TTP inhibited this cleavage. After incubation with normal plasma, the VWF fusion protein immobilized onto antiGST coated microtiter plate wells lost its anti-6His binding activity in a timeand plasma concentration-dependent manner. By using this EIA, the ADAMTS13 activity level was less than 0.12 U/mL in patients with acquired or hereditary TTP, distinguishing these patients from normal individuals or carriers of one copy of mutant ADAMTS13 allele. These results suggest the EIA method based on the VWF fusion protein is a simple but promising alternative for measuring ADAMTS13 activity.

scholarly journals Relapse of congenital thrombotic thrombocytopenic purpura, after spontaneous remission, in a second-trimester primigravida: case report and review of the literature

2017 ◽  
Vol 135 (5) ◽  
pp. 491-496 ◽  
Author(s):  
Donavan de Souza Lúcio ◽  
Jacqueline Foelkel Pignatari ◽  
Marcelo Gil Cliquet ◽  
Henri Augusto Korkes
Keyword(s):  
Case Report ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Hemolytic Anemia ◽  
Specific Treatment ◽  
Spontaneous Remission ◽  
Adamts13 Activity ◽  
Second Trimester ◽  
Microangiopathic Hemolytic Anemia ◽  
Thrombocytopenic Purpura ◽  
Uremic Syndrome

ABSTRACT CONTEXT: Thrombotic microangiopathy syndrome or thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) describes distinct diseases sharing common pathological features: microangiopathic hemolytic anemia and thrombocytopenia, without any other apparent cause. CASE REPORT: An 18-year-old second-trimester primigravida presented with a history of fifteen days of intense weakness, followed by diarrhea over the past six days. She reported having had low platelets since childhood, but said that she had never had bleeding or menstrual abnormalities. Laboratory investigation showed anemia with schistocytes, thrombocytopenia and hypohaptoglobulinemia. Red blood cell concentrate and platelet transfusions were performed. The hypothesis of TTP or HUS was put forward and ADAMTS13 enzyme activity was investigated. The patient evolved with increasing platelet counts, even without specific treatment, and she was discharged. One month afterwards, she returned presenting weakness and swollen face and legs, which had developed one day earlier. The ADAMTS13 activity was less than 5%, without presence of autoantibodies. Regarding the two previous admissions (at 9 and 16 years of age), with similar clinical features, there was spontaneous remission on the first occasion and, on the second, the diagnosis of TTP was suspected and plasmapheresis was performed, but ADAMTS13 activity was not investigated. CONCLUSION: To date, this is the only report of congenital TTP with two spontaneous remissions in the literature This report reveals the importance of suspicion of this condition in the presence of microangiopathic hemolytic anemia and thrombocytopenia without any other apparent cause.

Thrombotic Thrombocytopenic Purpura Associated with Ticlopidine

1993 ◽  
Vol 27 (9) ◽  
pp. 1060-1061 ◽  
Author(s):  
Michael J. Kovacs ◽  
Patrick Y. Soong ◽  
Ian H. Chin-Yee
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Case Reports ◽  
Severe Thrombocytopenia ◽  
Microangiopathic Hemolytic Anemia ◽  
Thrombocytopenic Purpura ◽  
Case Summary ◽  
Aspirin Intolerance ◽  
One Year ◽  
Ischemic Attack

OBJECTIVE: To report a case of possible ticlopidine-induced thrombotic thrombocytopenic purpura (TTP). CASE SUMMARY: A 68-year-old man was started on ticlopidine therapy for transient ischemic attack because of aspirin intolerance. Three weeks after starting therapy, the patient developed TTP, manifest by severe thrombocytopenia, renal failure, microangiopathic hemolytic anemia, and neurologic symptoms. The condition reversed over three to five days coincident with the discontinuation of ticlopidine and therapy with daily plasma infusion and exchange. No evidence of relapse was found at one-year follow-up. DISCUSSION: TTP is a well-defined clinical entity with varied etiologies. Ticlopidine has been reported as causing neutropenia and isolated thrombocytopenia. Case reports have linked ticlopidine to the development of TTP. CONCLUSIONS: Including this case there are now seven patients who have been documented as developing TTP while receiving ticlopidine. In addition to monitoring for neutropenia and isolated thrombocytopenia, patients receiving ticlopidine also should be monitored for the development of TTP.

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