Pregnancy-associated thrombotic thrombocytopenic purpura

2009 ◽  
Vol 101 (02) ◽  
pp. 248-251 ◽  
Author(s):  
Jens Gerth ◽  
Ekkehard Schleussner ◽  
Karim Kentouche ◽  
Martin Busch ◽  
Mandy Seifert ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Normal Values ◽  
Successful Outcome ◽  
Severe Thrombocytopenia ◽  
Management Problem ◽  
Thrombocytopenic Purpura ◽  
Close Cooperation ◽  
Male Neonate ◽  
Plasma Infusions ◽  
In Pregnancy

SummaryThrombocytopenia during pregnancy is a common diagnostic and management problem. Several differential diagnosis must be considered including manifestations of thrombotic thrombocytopenic purpura (TTP). We report here on a case of a 21-year-old pregnant woman who presented initially severe thrombocytopenia (8 Gpt/l) in the 20th+1 week of gestation. The patient had an antibody against ADAMTS13, and enzyme activity was <5%. Immediate plasmapheresis treatment was initiated, followed by plasma infusions, and again plasmapheresis. A male neonate was delivered by caesarean section in the 32nd week of gestation. The child had an uncomplicated postnatal development. After delivery, the mother’s platelet count and ADAMTS13 activity increased to normal values. This case shows interesting aspects of TTP in pregnancy and a close cooperation between obstetricians, nephrologists and pediatricians is necessary for a successful outcome of the pregnancy.

scholarly journals Diagnostic dilemma: Severe thrombotic microangiopathy in pregnancy

2017 ◽  
Vol 18 (4) ◽  
pp. 348-351 ◽  
Author(s):  
Sarah Birkhoelzer ◽  
Alexandra Belcher ◽  
Helen Peet
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Haemolytic Anaemia ◽  
Thrombotic Microangiopathy ◽  
Interdisciplinary Approach ◽  
Severe Thrombocytopenia ◽  
Diagnostic Dilemma ◽  
Thrombocytopenic Purpura ◽  
Microangiopathic Haemolytic Anaemia ◽  
Elevated Liver Enzymes ◽  
In Pregnancy

A diagnostic dilemma occurred when thrombotic microangiopathy developed during pregnancy. The diagnostic criteria of thrombotic microangiopathy include thrombocytopenia (platelets <100) and microangiopathic haemolytic anaemia (including thrombotic thrombocytopenic purpura and haemolytic-uraemic syndrome). An urgent interdisciplinary approach is required to treat thrombotic microangiopathy in pregnancy to differentiate between thrombotic microangiopathy and HELLP syndrome (haemolysis, elevated liver enzymes, low platelets).1 This case presented with the pentad of thrombotic thrombocytopenic purpura: severe thrombocytopenia (platelets 9 × 109/L), microangiopathic haemolytic anaemia (reticular count 245 × 109/L (20–110)), LDH >5000 U/L (<425)), neurological abnormalities (Glasgow Coma Scale 10/15), renal failure (creatinine 140 µmol/L (<97)), fever (37.7℃). A Disintegrin And Metalloproteinase with a Thrombospondin type 1 motif, member 13 (ADAMTS13) activity of less than 5% and anti-ADAMTS13 antibodies retrospectively confirmed the diagnosis of acquired idiopathic thrombotic thrombocytopenic purpura in pregnancy. The immediate management in the Emergency Department with an interdisciplinary team of Consultant Nephrologists, Intensivists, Haematologists and Obstetricians facilitated prompt diagnosis resulting in immediate plasma exchange (PEX) and coordination of semi-elective delivery of the foetus.

scholarly journals Thrombotic Thrombocytopenic Purpura: Pathophysiology, Diagnosis, and Management

2021 ◽  
Vol 10 (3) ◽  
pp. 536
Author(s):  
Senthil Sukumar ◽  
Bernhard Lämmle ◽  
Spero R. Cataland
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Initial Therapy ◽  
Fresh Frozen Plasma ◽  
Organ Injury ◽  
Severe Thrombocytopenia ◽  
Front Line ◽  
Thrombocytopenic Purpura ◽  
Fresh Frozen ◽  
Biallelic Mutations ◽  
Line Setting

Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy characterized by microangiopathic hemolytic anemia, severe thrombocytopenia, and ischemic end organ injury due to microvascular platelet-rich thrombi. TTP results from a severe deficiency of the specific von Willebrand factor (VWF)-cleaving protease, ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13). ADAMTS13 deficiency is most commonly acquired due to anti-ADAMTS13 autoantibodies. It can also be inherited in the congenital form as a result of biallelic mutations in the ADAMTS13 gene. In adults, the condition is most often immune-mediated (iTTP) whereas congenital TTP (cTTP) is often detected in childhood or during pregnancy. iTTP occurs more often in women and is potentially lethal without prompt recognition and treatment. Front-line therapy includes daily plasma exchange with fresh frozen plasma replacement and immunosuppression with corticosteroids. Immunosuppression targeting ADAMTS13 autoantibodies with the humanized anti-CD20 monoclonal antibody rituximab is frequently added to the initial therapy. If available, anti-VWF therapy with caplacizumab is also added to the front-line setting. While it is hypothesized that refractory TTP will be less common in the era of caplacizumab, in relapsed or refractory cases cyclosporine A, N-acetylcysteine, bortezomib, cyclophosphamide, vincristine, or splenectomy can be considered. Novel agents, such as recombinant ADAMTS13, are also currently under investigation and show promise for the treatment of TTP. Long-term follow-up after the acute episode is critical to monitor for relapse and to diagnose and manage chronic sequelae of this disease.

Thrombotic thrombocytopenic purpura in pregnancy

1982 ◽  
Vol 89 (6) ◽  
pp. 476-479 ◽  
Author(s):  
M. ATLAS ◽  
G. BARKAI ◽  
J. MENCZER ◽  
N. HOULU ◽  
P. LIEBERMAN
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Thrombocytopenic Purpura ◽  
In Pregnancy

The occurrence of thrombotic thrombocytopenic purpura during treatment of HCV with direct-acting antiviral agents

2018 ◽  
Vol 1 (1) ◽  
pp. 1-9
Author(s):  
Amr Hanafy ◽  
◽  
Waseem Seleem ◽  
Salem Mohamed ◽  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Hemolytic Anemia ◽  
Peripheral Blood Smear ◽  
Hcv Infection ◽  
Severe Thrombocytopenia ◽  
Direct Acting Antivirals ◽  
Thrombocytopenic Purpura ◽  
Direct Acting Antiviral ◽  
Chronic Hcv ◽  
Direct Acting

Background and aim Experts have reported thrombocytopenia linked to chronic liver disease in up to 70% in patients with advanced fibrosis and portal hypertension. Thrombotic thrombocytopenic purpura (TTP) occurrence with HCV infection is a rare and life-threatening event. We aimed to investigate the cause of disturbed conscious level, acute hemolytic anemia, and severe thrombocytopenia in a male patient with chronic HCV and under treatment with direct-acting antivirals. Case report: Development of severe thrombocytopenia, acute hemolytic anemia, neurological symptoms in the form of fits and coma in a 32- year- old man with chronic HCV infection after one week of treatment with direct-acting antivirals (sofosbuvir 400mg PO daily, and daclatasvir 60 mg PO daily). Brain CT was normal, with a negative Coombs test and the presence of schistocytes in the peripheral blood smear. The patient presentation was suggestive of thrombotic thrombocytopenic purpura (TTP). Conclusion: This is a case of TTP after one week of direct-acting antiviral drugs despite the safety profile of these medications. Studying the pathophysiology of TTP after DAAs needs more clarifications.

scholarly journals Insights from the Hereditary Thrombotic Thrombocytopenic Purpura Registry: Discussion of Key Findings Based on Individual Cases from Switzerland

2020 ◽  
Vol 40 (S 01) ◽  
pp. S5-S14
Author(s):  
Johanna A. Kremer Hovinga ◽  
Thomas R. Braschler ◽  
Florian Buchkremer ◽  
Stefan Farese ◽  
Heinz Hengartner ◽  
...  
Keyword(s):  
Cohort Study ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Disease Onset ◽  
Myocardial Infarctions ◽  
Thrombocytopenic Purpura ◽  
Blood Disorder ◽  
A Disintegrin And Metalloproteinase ◽  
Systematic Collection ◽  
Plasma Infusions

AbstractThe Hereditary TTP Registry is an international cohort study for patients with a confirmed or suspected diagnosis of hereditary thrombotic thrombocytopenic purpura (hTTP) and their family members. Hereditary TTP is an ultra-rare blood disorder (prevalence of ∼1–2 cases per million), the result of autosomal-recessively inherited congenital ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) deficiency (ADAMTS13 activity <10% of the normal), and associated with yet many unanswered questions. Until December 2017, the Hereditary TTP Registry had enrolled 123 confirmed hTTP patients. Their median age at disease onset was 4.5 years (range: 0–70) and at clinical diagnosis 16.7 years (range: 0–69), a difference that highlights the existing awareness gap in recognizing hTTP. The systematic collection of clinical data of individual patients revealed their substantial baseline comorbidities, as a consequence of recurring TTP episodes in the past. Most notable was the high proportion of patients having suffered from premature arterial thrombotic events, mainly transient ischemic attacks, ischemic strokes, and to a lesser extent myocardial infarctions. At 40 to 50 years of age and above, more than 50% of patients had suffered from at least one such event, and many had experienced arterial thrombotic events despite regular plasma infusions every 2 to 3 weeks that supplements the missing plasma ADAMTS13. The article by van Dorland et al. (Haematologica 2019;104(10):2107–2115) and the ongoing Hereditary TTP Registry cohort study were recognized with the Günter Landbeck Excellence Award at the 50th Hemophilia Symposium in Hamburg in November 2019, the reason to present the Hereditary TTP Registry in more detail here.

scholarly journals Exome Sequencing Identifies Glycosylation Defects As a Probable Cause of Immune Thrombotic Thrombocytopenic Purpura

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 217-217
Author(s):  
Felipe Massicano ◽  
Elizabeth M. Staley ◽  
Konstantine Halkidis ◽  
Nicole K. Kocher ◽  
Lance A. Williams ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Potential Contribution ◽  
Severe Thrombocytopenia ◽  
Adamts13 Activity ◽  
Genomic Alterations ◽  
Autoantibody Production ◽  
Thrombocytopenic Purpura ◽  
Long Term Outcome ◽  
Clinical Presentations

Background: Immune thrombotic thrombocytopenic purpura (iTTP) is a potentially fatal syndrome, resulting primarily from autoantibodies against ADAMTS13. However, the mechanism underlying the autoantibody formation and the contribution of other genomic alterations to the pathogenesis of iTTP are largely unknown. Methods: Whole exome sequencing (WES) and bioinformatic analyses were performed to determine the genetic variations in 40 patients with iTTP who had ADAMTS13 activity &lt;10 IU/dL and a positive inhibitor or an elevated anti-ADAMTS13 IgG in concordance with clinical presentations of severe thrombocytopenia and microangiopathic hemolytic anemia with various degrees of organ injury. WES was also performed at the same time in fifteen age-, gender-, and ethnicity- matched individuals who did not have a history of iTTP or other hematological disorders as controls. Results: WES identified variants or mutations in the genes involving in glycosylation, including O-linked glycosylation, to be the major pathway affected in patients with iTTP. We propose that the altered glycosylation may be responsible for the development of autoantibodies against ADAMTS13 which impair the proteolytic cleavage of von Willebrand factor, accelerate the clearance of ADAMTS13 from circulation, and result in severe thrombocytopenia platelets in patients with iTTP. We also identified defects in ankyrin repeat containing protein ANKRD36C, a protein with hitherto unknown function, as the most statistically significant genomic alterations associated with iTTP (p &lt; 10-5). Moreover, candidate gene analysis revealed that various genes involving in hemostasis, complement activation, platelet function and signaling pathway, and inflammation were all affected in patients with iTTP, which may contribute to the onset, progress, severity, and long-term outcome of iTTP. Finally, we also identified two patient subgroups where the disease mechanism might be different. Conclusion: Our findings provide novel insight into the pathogenic mechanism underlying ADAMTS13 autoantibody production and the potential contribution of other genetic abnormalities in modifying the iTTP clinical presentations in the individuals with severe deficiency of plasma ADAMTS13 activity. Disclosures Zheng: Alexion: Speakers Bureau; Ablynx/Sanofi: Consultancy, Speakers Bureau; Shire/Takeda: Research Funding; Clotsolution: Other: Co-Founder.

scholarly journals Annual Incidence and Severity of Acute Episodes in Hereditary Thrombotic Thrombocytopenic Purpura

Blood ◽  
2021 ◽  
Author(s):  
Erika Tarasco ◽  
Lukas Bütikofer ◽  
Kenneth D. Friedman ◽  
James N George ◽  
Ingrid V Hrachovinova ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Disease Onset ◽  
Premature Death ◽  
Annual Incidence ◽  
Prospective Data ◽  
Thrombocytopenic Purpura ◽  
Adamts13 Deficiency ◽  
Survival Frequency ◽  
Overt Disease ◽  
Plasma Infusions

Hereditary thrombotic thrombocytopenic purpura (hTTP) is a rare thrombotic microangiopathy characterized by severe congenital ADAMTS13 deficiency and recurring acute episodes causing morbidity and premature death. Information on the annual incidence and severity of acute episodes in hTTP patients is largely lacking. This study reports prospective data of 87 patients from the Hereditary TTP Registry (ClinicalTrials.gov NCT01257269) for survival, frequency and severity of acute episodes from enrollment until December 2019. The 87 patients, followed for median 4.2 years (range 0.01-15), had a median age at overt disease onset and at clinical diagnosis of 4.6 years and of 18 years (range 0.0-70 for both), respectively. Forty-three patients received regular plasma prophylaxis, while 22 did not, and treatment changed over time or was unknown in the remaining 22. Forty-three patients experienced 131 acute episodes of which 91 (69%) occurred in patients on regular prophylaxis. This resulted in an annual incidence of acute episodes of 0.36 (95%CI 0.29-0.44) with and of 0.41 (95%CI 0.30-0.56) without regular plasma treatment. More than one third of acute episodes (n=51) were documented in children &lt;10 years of age at enrollment and were often triggered by infections. Their annual incidence of acute episodes was significantly higher than in patients &gt;40 years of age (1.18 [95% CI 0.88-1.55] vs. 0.14 [95% CI 0.08-0.23]). Prophylactic plasma infusion regimens used were insufficient to prevent acute episodes in many patients. Such regimens are burdensome, caregivers, patients and their guardians are reluctant to start regular plasma infusions, from which particularly children would benefit.

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