Thrombocytopenia and Severe Hyperbilirubinemia in the Neonatal Period Secondary to Congenital Thrombotic Thrombocytopenic Purpura and ADAMTS13 Deficiency

2004 ◽  
Vol 26 (8) ◽  
pp. 535-538 ◽  
Author(s):  
Deborah E Schiff ◽  
William D Roberts ◽  
Jennifer Willert ◽  
Han-Mou Tsai
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Neonatal Period ◽  
Thrombocytopenic Purpura ◽  
Congenital Thrombotic Thrombocytopenic Purpura ◽  
Adamts13 Deficiency ◽  
Severe Hyperbilirubinemia

Fatal congenital thrombotic thrombocytopenic purpura with apparent ADAMTS13 inhibitor: in vitro inhibition of ADAMTS13 activity by hemoglobin

Blood ◽  
2005 ◽  
Vol 105 (2) ◽  
pp. 542-544 ◽  
Author(s):  
Jan-Dirk Studt ◽  
Johanna A. Kremer Hovinga ◽  
Gerhard Antoine ◽  
Martin Hermann ◽  
Manfred Rieger ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Pediatric Patient ◽  
Inhibitory Effect ◽  
Adamts13 Activity ◽  
Thrombocytopenic Purpura ◽  
Normal Plasma ◽  
Congenital Thrombotic Thrombocytopenic Purpura ◽  
Adamts13 Deficiency ◽  
In Vitro Inhibition

AbstractSevere ADAMTS13 deficiency in thrombotic thrombocytopenic purpura (TTP) is either constitutional and caused by ADAMTS13 mutations, or acquired and most often due to ADAMTS13 inhibitory autoantibodies. In strongly hemolytic serum of a pediatric patient, diagnosed with TTP postmortem, ADAMTS13 activity was less than 3%. Both parents had an ADAMTS13 activity of approximately 50%. Sequencing of the ADAMTS13 gene revealed an intronic 687-2A>G substitution affecting exon 7, homozygous in the propositus and heterozygous in both parents, confirming constitutional ADAMTS13 deficiency. ADAMTS13 activity of normal plasma was inhibited by incubation with the propositus' serum, suggesting alloantibody formation to ADAMTS13. However, immunoglobulin purified from serum had no ADAMTS13 inhibitory effect, whereas the immunoglobulin-depleted hemolytic serum inhibited ADAMTS13 activity of normal plasma, suggesting an inhibitory effect of hemolysis products. Incubation of hemoglobin, recombinant and from lysed erythrocytes, with normal plasma revealed an ADAMTS13 inhibitory effect at hemoglobin concentrations of 2 g/L or higher.

ADAMTS13 Helps Distinguish Thrombotic Thrombocytopenic Purpura From Other Microangiopathies and Guide Necessity of Plasma Exchange Therapy

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2328-2328
Author(s):  
Neil Shah ◽  
Karen Matevosyan ◽  
James Burner ◽  
Ravindra Sarode
Keyword(s):  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Conflicts Of Interest ◽  
Genetic Mutations ◽  
Thrombocytopenic Purpura ◽  
Plasma Exchange Therapy ◽  
Severe Deficiency ◽  
Congenital Thrombotic Thrombocytopenic Purpura ◽  
Adamts13 Deficiency ◽  
Clinical Conditions

Abstract Abstract 2328 Introduction: Congenital thrombotic thrombocytopenic purpura (TTP) is caused by genetic mutations in ADAMTS13, a metalloproteinase that cleaves ultra-large VWF multimers to generate normal sized multimers present in circulation. However, acquired deficiency of ADAMTS13 due to auto-antibodies is not universally accepted as diagnostic of idiopathic TTP. Distinguishing idiopathic TTP from other thrombotic microangiopatheis (TMA) is important in guiding treatment as plasma exchange (PE) is only beneficial in TTP and select cases of other microangiopathies such as atypical HUS. Since January 2006 we routinely obtain ADAMTS13 activity performed by FRET assay from The Blood Center of Wisconsin in all patients with TMA. We report the diagnostic utility of ADAMTS13 to distinguish TTP from other forms of TMAs. Methods: A retrospective analysis was performed on consecutive patients with TMA who had ADAMTS13 assayed from January 2006 to October 2010. Demographics, presenting clinical and laboratory features are given in the Table. Responses to therapeutic plasma exchange (TPE), diagnoses at discharge, and other underlying clinical conditions were also recorded. Relevant statistical analysis was performed using unpaired t-test to compare means and Fisher's exact method for contingency tables. Results: We divided our cases based on severe ADAMTS13 deficiency (<10%) as TTP and non-severe deficiency (>20%) as TMA. TMA causes included quinine induced HUS (1), gemcitabine related HUS (1), malignant hypertension/pre-eclampsia/HEELP (3), sepsis (2), MCTD (5), malignancy (3), ITP (1), HIV/opportunistic infection (5), drugs (1), and multiple (5). Conclusions: In our experience severe ADAMTS13 deficiency appears to distinguish TTP from TMA. TMA had better mortality despite either not initiating or discontinuing PE based on ADAMTS13 levels. However, if we had continued PE in TMA then these patients would have been considered as NON-ADAMTS13 deficient TTP who responded well to PE. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Characterization and treatment of congenital thrombotic thrombocytopenic purpura

Blood ◽  
2019 ◽  
Vol 133 (15) ◽  
pp. 1644-1651 ◽  
Author(s):  
Ferras Alwan ◽  
Chiara Vendramin ◽  
Ri Liesner ◽  
Amanda Clark ◽  
William Lester ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Age Of Onset ◽  
Organ Damage ◽  
Compound Heterozygous ◽  
Prophylactic Therapy ◽  
Thrombocytopenic Purpura ◽  
Stroke Incidence ◽  
End Organ Damage ◽  
Congenital Thrombotic Thrombocytopenic Purpura ◽  
Diagnosis Age

Abstract Congenital thrombotic thrombocytopenic purpura (cTTP) is an ultra-rare thrombomicroangiopathy caused by an inherited deficiency of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13). There are limited data on genotype-phenotype correlation; there is no consensus on treatment. We reviewed the largest cohort of cTTP cases, diagnosed in the United Kingdom, over the past 15 years. Seventy-three cases of cTTP were diagnosed, confirmed by genetic analysis. Ninety-three percent were alive at the time of review. Thirty-six percent had homozygous mutations; 64% had compound heterozygous mutations. Two presentation peaks were seen: childhood (median diagnosis age, 3.5 years) and adulthood, typically related to pregnancy (median diagnosis age, 31 years). Genetic mutations differed by age of onset with prespacer mutations more likely to be associated with childhood onset (P = .0011). Sixty-nine percent of adult presentations were associated with pregnancy. Fresh-frozen plasma (FFP) and intermediate purity factor VIII concentrate were used as treatment. Eighty-eight percent of patients with normal blood counts, but with headaches, lethargy, or abdominal pain, reported symptom resolution with prophylactic therapy. The most common currently used regimen of 3-weekly FFP proved insufficient for 70% of patients and weekly or fortnightly infusions were required. Stroke incidence was significantly reduced in patients receiving prophylactic therapy (2% vs 17%; P = .04). Long-term, there is a risk of end-organ damage, seen in 75% of patients with late diagnosis of cTTP. In conclusion, prespacer mutations are associated with earlier development of cTTP symptoms. Prophylactic ADAMTS13 replacement decreases the risk of end-organ damage such as ischemic stroke and resolved previously unrecognized symptoms in patients with nonovert disease.

scholarly journals Pregnancy onset congenital thrombotic thrombocytopenic purpura (Upshaw-Schulman syndrome) mimicking HELLP syndrome: a case report

2021 ◽  
Vol 29 (3) ◽  
pp. 270-273
Author(s):  
Başak Ergin ◽  
Berna Buse Kobal ◽  
Zeynep Yazıcı ◽  
Ali Hakan Kaya ◽  
Sezin Canbek ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Hellp Syndrome ◽  
Epigastric Pain ◽  
Novel Mutation ◽  
Adamts13 Activity ◽  
Thrombotic Microangiopathies ◽  
Thrombocytopenic Purpura ◽  
Uremic Syndrome ◽  
Congenital Thrombotic Thrombocytopenic Purpura ◽  
Low Platelet Count

Objective Thrombotic thrombocytopenic purpura is a thrombotic microangiopathic condition characterized by hemolytic anemia, thrombocytopenia, neurologic abnormalities, fever and renal dysfunction. Thrombotic microangiopathies such as preeclampsia and HELLP syndrome are pregnancy-specific, whereas others such as thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome are not. In this report, we present a case at which we identified a novel mutation which led to a significant reduction of ADAMTS13 activity. Case(s) A nulliparous pregnant woman of 32-year-old presenting with epigastric pain, hypertension and low platelet count was first suspected of HELLP syndrome, but was diagnosed with congenital TTP after delivery. Conclusion HELLP syndrome co-existed with undiagnosed TTP in this case. We strive to have sufficient awareness in order to distinguish these two pathologies from each other on an antenatal basis, because the causes of the managements are entirely different.

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.

Thrombotic Thrombocytopenic Purpura Associated with von Willebrand Factor-Cleaving Protease (ADAMTS13) Deficiency in Children

2006 ◽  
Vol 32 (2) ◽  
pp. 090-097 ◽  
Author(s):  
Chantal Loirat ◽  
Agnès Veyradier ◽  
Jean-Pierre Girma ◽  
Anne-Sophie Ribba ◽  
Dominique Meyer
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Von Willebrand Factor ◽  
Thrombocytopenic Purpura ◽  
Adamts13 Deficiency ◽  
Von Willebrand ◽  
Willebrand Factor

Thrombotic thrombocytopenic purpura related to severe ADAMTS13 deficiency in children

2009 ◽  
Vol 24 (1) ◽  
pp. 19-29 ◽  
Author(s):  
Chantal Loirat ◽  
Jean-Pierre Girma ◽  
Céline Desconclois ◽  
Paul Coppo ◽  
Agnès Veyradier
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Thrombocytopenic Purpura ◽  
Adamts13 Deficiency
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