scholarly journals Atypical Presentation of Thrombotic Thrombocytopenic Purpura without Hematological Features

2020 ◽  
Author(s):  
Balraj Singh ◽  
Kok Hoe Chan ◽  
Parminder Kaur ◽  
Varun Modi ◽  
Michael Maroules
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Neurological Dysfunction ◽  
Thrombotic Complication ◽  
Atypical Presentation ◽  
Thrombocytopenic Purpura ◽  
Severe Deficiency ◽  
Life Threatening ◽  
Neurological Features ◽  
High Index Of Suspicion ◽  
Von Willebrand

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease, usually diagnosed with high index of suspicion. The pathophysiology of TTP is due to severe deficiency of von Willebrand factor cleaving protease, known as ADAMTS 13. Early diagnosis is crucial as without treatment TTP is associated with high mortality rate. Plasma exchange is currently the mainstay of treatment. Nonetheless, the classical pentad of microangiopathic hemolytic anemia (MAHA), thrombocytopenia, neurological dysfunction, kidney dysfunction and fever are seen only in 40 percent of the patients. MAHA and thrombocytopenia are the common presenting features. Presentation with thrombotic complication without hematological features (MAHA and thrombocytopenia) is rare and makes the diagnosis difficult. Herein, we report an unusual presentation of a 53-year-old male, who was initially presented in 2014 with classical features of TTP, however had an atypical presentation of TTP in 2016 with only neurological features without hematological features.

scholarly journals How I treat thrombotic thrombocytopenic purpura in pregnancy

Blood ◽  
2020 ◽  
Vol 136 (19) ◽  
pp. 2125-2132
Author(s):  
Barbara Ferrari ◽  
Flora Peyvandi
Keyword(s):  
Differential Diagnosis ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Current Knowledge ◽  
Fetal Outcome ◽  
Subsequent Pregnancy ◽  
Thrombocytopenic Purpura ◽  
Severe Deficiency ◽  
Life Threatening ◽  
High Index Of Suspicion ◽  
In Pregnancy

Abstract Thrombotic thrombocytopenic purpura (TTP) is an acute, life-threatening thrombotic microangiopathy (TMA) caused by acquired or congenital severe deficiency of ADAMTS13. Pregnancy is a recognized risk factor for precipitating acute (first or recurrent) episodes of TTP. Differential diagnosis with other TMAs is particularly difficult when the first TTP event occurs during pregnancy; a high index of suspicion and prompt recognition of TTP are essential for achieving a good maternal and fetal outcome. An accurate distinction between congenital and acquired cases of pregnancy-related TTP is mandatory for safe subsequent pregnancy planning. In this article, we summarize the current knowledge on pregnancy-associated TTP and describe how we manage TTP during pregnancy in our clinical practice.

scholarly journals THROMBOTIC THROMBOCYTOPENIC PURPURA (TTP) AND MODERN APPROACH TO ITS INVESTIGATION AND TREATMENT

2019 ◽  
pp. 12-13
Author(s):  
K. Ukleba ◽  
L. Gvetadze
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Severe Thrombocytopenia ◽  
Thrombocytopenic Purpura ◽  
Modern Approach ◽  
Severe Deficiency ◽  
Life Threatening ◽  
Adamts13 Deficiency ◽  
Von Willebrand ◽  
Willebrand Factor

Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening thrombotic microangiopathy characterized by microangiopathic hemolytic anemia, severe thrombocytopenia, and organ ischemia linked to disseminated microvascular platelet rich-thrombi. TTP is specifically related to a severe deficiency in ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13), the specific von Willebrand factor-cleaving protease. ADAMTS13 deficiency is most frequently acquired via ADAMTS13 autoantibodies, but rarely, it is inherited via mutations of the ADAMTS13 gane. The first acute episode of TTP usually occurs during adulthood, with a predominant anti – ADAMTS13 autoimmune etiology. In rare cases, however, TTP begins as soon as childhood, with frequent inherited forms. TTP is 2 – fold more frequent in women, and its outcome is characterized by a relapsing tendency.

FRETS-VWF73 rather than CBA assay reflects ADAMTS13 proteolytic activity in acquired thrombotic thrombocytopenic purpura patients

2014 ◽  
Vol 112 (08) ◽  
pp. 297-303 ◽  
Author(s):  
Ilaria Mancini ◽  
Carla Valsecchi ◽  
Luca Lotta ◽  
Louis Deforche ◽  
Silvia Pontiggia ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Proteolytic Activity ◽  
Binding Activity ◽  
Adamts13 Activity ◽  
Flow Conditions ◽  
Thrombocytopenic Purpura ◽  
Severe Deficiency ◽  
Adamts13 Deficiency ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryCollagen-binding activity (CBA) and FRETS-VWF73 assays are widely adopted methods for the measurement of the plasmatic activity of ADAMTS13, the von Willebrand factor (VWF) cleaving-protease. Accurately assessing the severe deficiency of ADAMTS13 is important in the management of thrombotic thrombocytopenic purpura (TTP). However, non-concordant results between the two assays have been reported in a small but relevant percentage of TTP cases. We investigated whether CBA or FRETS-VWF73 assay reflects ADAMTS13 proteolytic activity in acquired TTP patients with non-concordant measurements. Twenty plasma samples with non-concordant ADAMTS13 activity results, <10% using FRETS-VWF73 and ≥20% using CBA, and 11 samples with concordant results, <10% using either FRETS-VWF73 and CBA assays, were analysed. FRETS-VWF73 was performed in the presence of 1.5 M urea. ADAMTS13 activities were also measured under flow conditions and the VWF multimer pattern was defined in order to verify the presence of ultra-large VWF due to ADAMTS13 deficiency. In FRETS-VWF73 assay with 1.5 M urea, ADAMTS13 activity significantly increased in roughly 50% of the samples with non-concordant results, whereas it remained undetectable in all samples with concordant measurements. Under flow conditions, all tested samples showed reduced ADAMTS13 activity. Finally, samples with non-concordant results showed a ratio of high molecular weight VWF multimers higher than normal. Our results support the use of FRETS-VWF73 over CBA assay for the assessment of ADAMTS13 severe deficiency and indicate urea as one cause of the observed differences.

scholarly journals A case of severe ADAMTS 13 deficiency presenting as thrombotic thrombocytopenic purpura in pregnancy

2012 ◽  
Vol 65 (9-10) ◽  
pp. 436-439 ◽  
Author(s):  
Marinos Nikolaou ◽  
Marina Karakantza ◽  
George Adonakis ◽  
George Theodorou ◽  
Nikolaos Zoumbos ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Prophylactic Treatment ◽  
Thrombocytopenic Purpura ◽  
Treatment And Prevention ◽  
Severe Deficiency ◽  
History Of ◽  
Adamts13 Deficiency ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Plasma Infusions

Introduction. Thrombotic thrombocytopenic purpura is a rare lifethreatening disorder characterized by thrombocytopenia and microangiopathic hemolytic anemia. It is caused by the absent or severe deficiency of the von Willebrand Factor-cleaving protease named ADAMTS13. Pregnancy is a well recognized factor precipitating the appearance of the disease both in women that had reduced levels of ADAMTS13 activity prior to gestation and in those with other inherited or acquired thrombophilic syndromes. Case Report. We report a 25-year old woman with severe ADAMTS13 deficiency presented early in her 1st pregnancy and relapsed in two subsequent gestations. This presentation is uncommon for thrombotic thrombocytopenic purpura is associated with pregnancy (ADAMTS13 deficiency <5%, without an inhibitor). In the first pregnancy she started with daily plasma exchange 1.5xvolume, corticosteroids and IV immunoglobulin and finally entered remission after 23 sessions and termination of pregnancy. In the second pregnancy she did not receive prophylactic treatment and relapsed in the 3rd trimester. Prophylactic treatment during the third pregnancy with plasma infusions proved also ineffective to prevent relapse. Discussion. Many issues regarding treatment and prevention of thrombotic thrombocytopenic purpura relapses in subsequent pregnancies are unclear. Proposed guidelines recommend that the same treatment should be performed on pregnant and non pregnant patients without modification of plasma replacement dose according to ADAMTS13 levels. In addition, many authors suggest that pregnant patients with history of thrombotic thrombocytopenic purpura and severe deficiency of ADAMTS13 levels should received prophylactic treatment for prevention of relapses in the subsequent pregnancies. Conclusion. Severe ADAMTS 13 deficiency may present as thrombotic thrombocytopenic purpura of pregnancy. Pregnant women with thrombotic thrombocytopenic purpura and especially with severe deficiency of ADAMTS13 levels require specific consideration regarding treatment and prophylaxis in subsequent pregnancies.

scholarly journals Case Report: Two Cases of Pediatric Thrombotic Thrombocytopenic Purpura Treated With Combined Therapy

2021 ◽  
Vol 9 ◽  
Author(s):  
Costanza Tripiciano ◽  
Paola Zangari ◽  
Mauro Montanari ◽  
Giovanna Leone ◽  
Laura Massella ◽  
...  
Keyword(s):  
Platelet Count ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Combined Therapy ◽  
Laboratory Data ◽  
Adamts13 Activity ◽  
Laboratory Findings ◽  
Thrombocytopenic Purpura ◽  
Life Threatening ◽  
Successful Clinical Outcome ◽  
Von Willebrand

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy caused by a severely reduced activity of the von Willebrand factor-cleaving protease ADAMTS13. Over 95% of TTPs are acquired, due to autoantibody inhibitors. In children, acquired TTP is a very rare, life-threatening disease. To date, no consensus exists on the treatment strategy of pediatric TTP. We report the cases of two pediatric patients with a diagnosis of TTP, successfully treated with a combination of various therapeutic approaches. Although the patients complained of different sets of symptoms, laboratory data showed Coombs negative hemolytic anemia, renal impairment, and low platelet count in both cases. The diagnosis of acquired TTP was supported by the PLASMIC score and confirmed by the reduction of the ADAMTS13 activity and the presence of anti-ADAMTS13 antibodies. Intravenous immunoglobulin, corticosteroids, and plasma exchange (PEX) were performed without delay. As soon as available, caplacizumab was added to the therapy, with a prompt normalization of platelet count. Nevertheless, ADAMTS13 activity was persistently low, and anti-ADAMTS13 antibodies level was high; thus, a course of rituximab was administered, with persistent normalization of laboratory findings. No adverse events were observed during the treatment. In our experience, the combined use of PEX, caplacizumab, and immunosuppressive therapy during the acute phase of the disease is safe and may have a significant impact on the prognosis with successful clinical outcome and decrease in life-threatening events.

Congenital thrombotic thrombocytopenic purpura in association with a mutation in the second CUB domain of ADAMTS13

Blood ◽  
2004 ◽  
Vol 103 (2) ◽  
pp. 627-629 ◽  
Author(s):  
John E. Pimanda ◽  
Akiko Maekawa ◽  
Troels Wind ◽  
Julian Paxton ◽  
Colin N. Chesterman ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Proteinase Activity ◽  
Wild Type ◽  
Wild Type Enzyme ◽  
Thrombocytopenic Purpura ◽  
Severe Deficiency ◽  
Cub Domain ◽  
Congenital Thrombotic Thrombocytopenic Purpura ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Severe deficiency of the von Willebrand Factor (VWF)–cleaving proteinase, ADAMTS13, is associated with the development of thrombotic thrombocytopenic purpura (TTP). Several mutations spread across the ADAMTS13 gene have been identified in association with a deficiency of VWF-cleaving proteinase activity in patients with congenital TTP. The spread of these dysfunctional mutations and the domain structure of ADAMTS13 are suggestive of a complex interaction between the enzyme and its substrate. We have studied a patient with congenital TTP who is a compound heterozygote for the Thr196Ile mutation in the metalloproteinase domain and a frameshift mutation (4143-4144insA) in the second CUB domain that results in loss of the last 49 amino acids of the protein. The VWF-cleaving proteinase activity of the truncated enzyme was comparable to that of the wild-type enzyme but its secretion from transfected COS-7 cells was about 14% of the wild type.

scholarly journals Unexpected frequency of Upshaw-Schulman syndrome in pregnancy-onset thrombotic thrombocytopenic purpura

Blood ◽  
2012 ◽  
Vol 119 (24) ◽  
pp. 5888-5897 ◽  
Author(s):  
Marie Moatti-Cohen ◽  
Céline Garrec ◽  
Martine Wolf ◽  
Pierre Boisseau ◽  
Lionel Galicier ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
National Registry ◽  
Cross Sectional ◽  
Thrombocytopenic Purpura ◽  
Severe Deficiency ◽  
Specific Subgroup ◽  
Life Threatening ◽  
Adamts13 Deficiency ◽  
Sectional Analysis

Abstract Pregnancy may be complicated by a rare but life-threatening disease called thrombotic thrombocytopenic purpura (TTP). Most cases of TTP are due to an acquired autoimmune or hereditary (Upshaw-Schulman syndrome [USS]) severe deficiency of a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13 (ADAMTS13). In the present study, we performed a cross-sectional analysis of the national registry of the French Reference Center for Thrombotic Microangiopathies from 2000-2010 to identify all women who were pregnant at their initial TTP presentation. Among 592 adulthood-onset TTP patients with a severe ADAMTS13 deficiency, 42 patients with a pregnancy-onset TTP were included. Surprisingly, the proportion of USS patients (n = 10 of 42 patients [24%]; confidence interval, 13%-39%) with pregnancy-onset TTP was much higher than that in adulthood-onset TTP in general (less than 5%) and was mostly related to a cluster of ADAMTS13 variants. In the present study, subsequent pregnancies in USS patients not given prophylaxis were associated with very high TTP relapse and abortion rates, whereas prophylactic plasmatherapy was beneficial for both the mother and the baby. Pregnancy-onset TTP defines a specific subgroup of patients with a strong genetic background. This study was registered at www.clinicaltrials.gov as number NCT00426686 and at the Health Authority, French Ministry of Health, as number P051064.

scholarly journals Efficacy and Safety of Rituximab for Refractory and Relapsing Thrombotic Thrombocytopenic Purpura: A Cohort of 10 Cases

2015 ◽  
Vol 8 ◽  
pp. CMBD.S25326 ◽  
Author(s):  
Halima El Omri ◽  
Ruba Y. Taha ◽  
Amna Gamil ◽  
Firyal Ibrahim ◽  
Hisham Al Sabah ◽  
...  
Keyword(s):  
Complete Remission ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Dose Range ◽  
Thrombocytopenic Purpura ◽  
Clinical Criteria ◽  
Severe Deficiency ◽  
Life Threatening ◽  
Multiple Relapses

Objective Idiopathic thrombotic thrombocytopenic purpura (TTP) is a life-threatening disorder mediated by autoantibodies directed against ADAMTS13. This provides a rationale for the use of rituximab in this disorder. We report our experience and the outcome of 10 cases of TTP (9 refractory and 1 relapsing) successfully treated with rituximab in combination with plasma exchange (PE) and other immunosuppressive treatments. Methods The diagnosis of TTP was based on clinical criteria and supported by severe deficiency of ADAMTS13 activity and presence of inhibitors in seven cases. Rituximab was started after a median of 18.6 sessions of PE (range: 5-35) at the dose of 375 mg/m2/week for 4-8 weeks. Results Complete remission was achieved in all patients after a median time of 14.4 days of the first dose (range: 6-30). After a median follow-up of 30 months (range: 8-78), eight patients were still in remission and two developed multiple relapses, treated again with the same therapy, and achieved complete responses; they are alive, and in complete remission after a follow-up of 12 and 16 months. Conclusion Rituximab appears to be a safe and effective therapy for refractory and relapsing TTP. However, longer follow-up is recommended to assess relapse and detect possible long-term side effects of this therapy.

scholarly journals Thrombotic thrombocytopenic purpura: An unusual presentation with intracranial bleed

2021 ◽  
pp. 436-438
Author(s):  
Shaik Mohammad Tahaseen ◽  
Ravi Kirti ◽  
Subhash Kumar
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Peripheral Blood Smear ◽  
Severe Thrombocytopenia ◽  
Provisional Diagnosis ◽  
Thrombocytopenic Purpura ◽  
Intracranial Bleed ◽  
Life Threatening ◽  
High Index Of Suspicion ◽  
The Brain ◽  
Tomography Scan

Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening thrombotic microangiopathy characterized by microangiopathic hemolytic anemia, severe thrombocytopenia, and organ ischemia linked to disseminated microvascular platelet-rich thrombi. We present the case of a 44-year-old lady who presented with severe thrombocytopenia and anemia that did not respond to repeated transfusions and steroids. Non-contrast computed tomography scan of the brain revealed an intracranial bleed. Schistocytes were seen on the peripheral blood smear. A provisional diagnosis of TTP was made. Plasmapheresis could not be done due to her deteriorating hemodynamic status. She succumbed to her illness in spite of the best possible efforts. This case highlights the need for keeping a high index of suspicion for TTP as early diagnosis and prompt initiation of plasmapheresis are crucial for preventing death.

Nonneutralizing IgM and IgG antibodies to von Willebrand factor–cleaving protease (ADAMTS-13) in a patient with thrombotic thrombocytopenic purpura

Blood ◽  
2003 ◽  
Vol 102 (9) ◽  
pp. 3241-3243 ◽  
Author(s):  
Friedrich Scheiflinger ◽  
Paul Knöbl ◽  
Bettina Trattner ◽  
Barbara Plaimauer ◽  
Gabriele Mohr ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Fluid Phase ◽  
Future Research ◽  
Enzyme Linked Immunosorbent Assay ◽  
Igg Antibodies ◽  
Thrombocytopenic Purpura ◽  
Endothelial Cell Surface ◽  
Severe Deficiency ◽  
Von Willebrand

Abstract Acquired thrombotic thrombocytopenic purpura (TTP) has been linked to severe deficiency of ADAMTS-13 activity caused by autoantibodies inhibitory to ADAMTS-13. We report data on a patient with confirmed TTP who had severely reduced ADAMTS-13 activity but showed no ADAMTS-13 inhibition in a widely used fluid phase activity assay. With a newly developed enzyme-linked immunosorbent assay, using immobilized recombinant ADAMTS-13, we found high titers of IgM and IgG antibodies that bound to ADAMTS-13, but did not neutralize protease activity. These autoantibodies probably influenced the half-life of ADAMTS-13 or its binding to the endothelial cell surface, thereby compromising ADAMTS-13 activity in vivo. Given that ADAMTS-13 may interact physiologically with various receptors or ligands, the occurrence, distribution, and the epitope mapping of nonneutralizing antibodies will be an important area for future research.

Sign in / Sign up

Export Citation Format

Share Document