Frequent recurrence of pregnancy-triggered congenital thrombotic thrombocytopenic purpura: A rare case report

2020 ◽  
pp. 1-6
Author(s):  
Jialiang Xu ◽  
Sijian Yu ◽  
Fuhua Zhang
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Novel Mutation ◽  
Immunosuppressive Agents ◽  
Acute Attack ◽  
Genetic Mutation ◽  
Plasma Therapy ◽  
Thrombocytopenic Purpura ◽  
Rare Case Report ◽  
Congenital Thrombotic Thrombocytopenic Purpura ◽  
Von Willebrand

Thrombotic thrombocytopenic purpura (TTP) in adults is rare thrombotic microangiopathy (TMA), which is closely related to the lack of specific proteases of von Willebrand factor (vWF) multimers. It is currently believed that both congenital TTP (cTTP) and acquired TTP (aTTP) can induce acute attack through pregnancy. We report a case of a 24-year-old woman who was diagnosed as TTP during early pregnancy. A novel mutation was detected: c.3667G>T (p.E1223*). She responded well to plasma therapy during pregnancy and had a child by cesarean section at 32 weeks. TTP is still recurrent in postpartum patients. The plasma transfusion was effective, but caused a severe transfusion reaction. Cyclosporine was administered with the consent of the patient. This case showed cyclosporine-A (CSA) had a positive effect on ADAMTS13 activity. At 11-months follow-up, the patient’s blood cells and LDH status were stable and no symptom was seen. Our case suggests that the patient had an unreported genetic mutation that causes TTP, immune factors may be involved in the onset of cTTP during pregnancy, and the use of immunosuppressive agents is effective in preventing recurrence.

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.

Investigation of Side Effects of Plasmaexchange In the Treatment of Thrombotic Thrombocytopenic Purpura

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4661-4661
Author(s):  
Sarah Steinemann ◽  
Tanja Falter ◽  
Mirjeta Qorraj ◽  
Thomas Vigh ◽  
Inge Scharrer
Keyword(s):  
Side Effects ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Side Effect ◽  
Conflicts Of Interest ◽  
Allergic Reactions ◽  
Adamts13 Activity ◽  
Plasma Therapy ◽  
Thrombocytopenic Purpura ◽  
Wide Range ◽  
Von Willebrand

Abstract Abstract 4661 Introduction: Thrombotic thrombocytopenic purpura (TTP) is characterized by thrombocytopenia, hemolytic anemia and microthrombi. A deficiency of the metalloprotease ADAMTS 13, which cleaves a Tys1605-Met1606 bond in the A2 subunit of von Willebrand factor (VWF), leads to formation of ultra large von Willebrand multimers (UL-VWF) and can cause platelet aggregation and mircovascular thrombosis. Treatment of choice is the substitution of plasma with plasmaexchange. There are two different plasma types available: Fresh Frozen Plasma (FFP) and solvent/detergent (s/d) treated plasma. This treatment may carry significant risks and side effects for the patients. Therefore we investigated the side effects of the therapy and furthermore the ADAMTS13 activity of the two plasma types. Methods: A questionnaire was send to 66 TTP patients of the Department of Hematology to evaluate different side effects of the therapy. 20 batches of FFP and 4 batches of s/d plasma of all blood groups were investigated on ADAMTS13 activity. The ADAMTS13 activity was detected with BCS-Method according to Böhm and two commercial FRET assays. Results: So far 34 patients were inquired about age, weight and suspected trigger situations that might have caused their TTP manifestation. The mean age of the patients was 34 years with a mean weight of 70kg. A previous infection caused TTP manifestation in 42% of the patients; drug therapy (22%) and pregnancy (17%) were other mentioned triggers. 94% of the patients suffered from an acquired TTP and only 6% had a hereditary TTP. The patients had 2.88 relapses and were treated with 16.27 plasmaexchanges. 56% had an additional therapy with Rituximab to achieve a faster remission of the disease. These patients needed less plasmaexchanges for recovery, which proofed to be significant at 2% level in a one sided t-test. Tingling (64.7%) and shivering (51%) were the most often mentioned side effects and simultaneously described as the strongest. Shivering was significantly correlated to tachycardia (p<0.01). Headaches were significantly correlated to hot flushes, tingling and collapse (p< 0.05). Side effects and allergic reactions occurred in the therapy with FFP as well as with s/d plasma. Another side effect was the complication that came along with infection of the venous access. Most patients had a central venous catheter (72%) and described infections and pruritus (60%), 50% of them mentioned this complication more than once. We found in usual FFP slightly higher ADAMTS13 activity levels (696.97 ng/ml) than in s/d virus inactivated plasma (643.86 ng/ml). The ADAMTS13 activity varied between the different assays (normal range: 666 ± 135ng/ml). Conclusion: Our investigation demonstrated that plasmaexchange therapy is still associated with a wide range of side effects. Side effects of plasmaexchange that were most frequently described by patients were tingling and shivering. Headaches also occurred in various cases. Patients suffered generally from more than one side effect at the same time during the treatment. Allergic reactions to the plasma therapy were mentioned by 65% of the patients. Disclosures: No relevant conflicts of interest to declare.

Von Willebrand Factor in Thrombotic Thrombocytopenic Purpura

1999 ◽  
Vol 82 (08) ◽  
pp. 592-600 ◽  
Author(s):  
Bernhard Lämmle ◽  
Miha Furlan
Keyword(s):  
Bone Marrow ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Complete Recovery ◽  
The United States ◽  
Severe Thrombocytopenia ◽  
Plasma Therapy ◽  
Thrombocytopenic Purpura ◽  
Platelet Aggregates ◽  
Patients Experience ◽  
Von Willebrand

IntroductionThrombotic thrombocytopenic purpura (TTP), a disseminated form of thrombotic microangiopathy, was initially described by Moschcowitz in 1924.1 TTP is defined by a pentad of findings, including severe thrombocytopenia, intravascular hemolysis with erythrocyte fragmentation, neurologic deficit, renal dysfunction, and fever.2–4 The thrombocytopenia occurs in the presence of normal or even increased numbers of megakaryocytes in the bone marrow, suggesting increased consumption. Platelet aggregates, found in the microcirculation, contain little if any fibrin polymers, indicating that activation of coagulation and fibrin formation may be secondary and limited in extent.About one-third of patients experience recurrent acute episodes at irregular and unpredictable intervals, whereas the majority of patients who recover from an acute TTP event experience no relapse and no persistent organ failure. TTP is usually classified as relapsing if complete remissions occurred between acute events and as chronic if complete recovery did not occur between bouts.Genetic predisposition to TTP has been shown in several siblings suffering from recurrent TTP.5 Thus, cases of TTP can be further divided according to whether the disease has a familial or genetic component or is not heritable. Acute episodes of TTP may be triggered by viral or bacterial infection, autoimmune disorders, bone marrow transplantation, drug therapy, cancer, chemotherapy, and pregnancy.3,4 The incidence of TTP is estimated to be two to eight cases per million people per year.3,6 Until four decades ago, the mortality rate was virtually 100% but has since decreased to less than 20% after introduction of plasma therapy. Still, there were more than 4,500 TTP-associated deaths recorded in the United States between 1968 and 1991.6

Three Novel ADAMTS-13 Gene Mutations in Thrombotic Thrombocytopenic Purpura (TTP).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3965-3965
Author(s):  
Nam Keun Kim ◽  
Moon Ju Jang ◽  
Sun Kim ◽  
Sun Ju Lee ◽  
Hye Won Park ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Thrombus Formation ◽  
Gene Mutations ◽  
Missense Mutations ◽  
Thrombocytopenic Purpura ◽  
Congenital Thrombotic Thrombocytopenic Purpura ◽  
Platelet Thrombus ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Splicing Site

Abstract ADAMTS-13 is an enzyme which cleave von Willebrand factor (VWF) to prevent excessive platelet thrombus formation. Mutation of ADAMTS-13 is associated with congenital thrombotic thrombocytopenic purpura (TTP). In this study, we report three novel missense mutations of ADAMTS-13 gene in TTP families. Genetic analysis of ADAMTS-13 gene was performed in 6 TTP families. Three novel ADAMTS-13 gene mutations (2708C>T [S903L], 3650T>C [I1217T] and 3941C>T [S1314L]) detected in 3 families. They were all found with heterozygous genotype in exon 21, 26 and 28, respectively. The 3650T>C mutation was found at exon 26 in the patient and his mother. A heterozygous guanine to adenine substitution was found at 5′ splicing site of intron 3(IVS+ 1) in the patient, his brother and his father. The plasma ADAMTS-13 activities of the patient, father, mother, and brother were less than 3%, 56%, 55% and 62% respectively. ADAMTS-13 inhibitors were not detected in all family members. 3941C>T was found at exon 28 in the patient and her father. The plasma ADAMTS-13 activities of the patient, father, and mother were 96%, 83%, and 83% respectively.

Recovery and Half-Life of von Willebrand Factor-Cleaving Protease after Plasma Therapy in Patients with Thrombotic Thrombocytopenic Purpura

1999 ◽  
Vol 81 (01) ◽  
pp. 8-13 ◽  
Author(s):  
Rodolfo Robles ◽  
Beat Morselli ◽  
Pierre Sandoz ◽  
Bernhard Lämmle ◽  
Miha Furlan
Keyword(s):  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Von Willebrand Factor ◽  
Half Life ◽  
Protease Activity ◽  
Plasma Therapy ◽  
Thrombocytopenic Purpura ◽  
Plasma Infusion ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryPlasma exchange using fresh-frozen plasma (FFP) for replacement was given to two brothers during a relapse of thrombotic thrombocytopenic purpura (TTP). A constitutional deficiency of von Willebrand factor(vWF)-cleaving protease had been previously established in both patients. No inhibitor of vWF-cleaving protease was present in patients’ plasmas. They received plasma exchange for four and three consecutive days, respectively. In both patients, the activity of vWF-cleaving protease after the first plasmapheresis session was evaluated and was found to be virtually identical to anticipated activity calculated from predicted patient plasma volume and volume of exchanged plasma. Pathologic platelet counts and lactate dehydrogenase levels were normalized in both patients within 4-6 days. The biologic half-life of vWF-cleaving protease was determined in these patients following the last plasma exchange. The respective half-lives of 3.3 and 2.1 days represent the lowest known clearance rates of proteases in circulating human plasma.Another patient with relapsing TTP was treated with plasma exchange and/or plasma infusion for 10 consecutive days during the first relapse, 221-231 days after the initial TTP event. Pharmacokinetic studies of vWF-cleaving protease were performed after plasma exchange on day 221 and after plasma infusion on day 231. High level of an IgG in patient plasma, capable of completely inhibiting protease activity in an equal volume of normal plasma, had been established prior to first plasmapheresis. There was no measurable protease activity at any time during plasma therapy. Following plasma exchange, the level of the inhibitor was transiently slightly depressed. After 10 days of plasma therapy, the concentration of the inhibitor in patient plasma was increased about 5-fold. We suggest that, in contrast to protease deficient patients without circulating inhibitor, complementary therapy including immunosuppressive treatment, vincristine and/or splenectomy is indicated in patients with acquired inhibitors of vWF-cleaving protease. Testing for vWF-cleaving protease inhibitor may be useful in predicting the response to plasma exchange in patients with TTP.

scholarly journals Congenital thrombotic thrombocytopenic purpura related to a novel mutation in ADAMTS13 gene and management during pregnancy

2016 ◽  
Vol 91 (6) ◽  
pp. 644-646 ◽  
Author(s):  
Narendranath Epperla ◽  
Kathleen Hemauer ◽  
Kenneth D. Friedman ◽  
James N. George ◽  
Patrick Foy
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Novel Mutation ◽  
Thrombocytopenic Purpura ◽  
Congenital Thrombotic Thrombocytopenic Purpura

scholarly journals Characterization of Two Cases of Congenital Thrombotic Thrombocytopenic Purpura (TTP)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5005-5005
Author(s):  
Xia Bai ◽  
JIan Su ◽  
Lijuan Cao ◽  
Changgeng Ruan
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Binding Assay ◽  
Conflicts Of Interest ◽  
Hek293 Cells ◽  
Novel Mutations ◽  
Thrombocytopenic Purpura ◽  
Congenital Thrombotic Thrombocytopenic Purpura ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Introduction: Congenital thrombotic thrombocytopenic purpura (TTP) is characterized by disseminated thrombus due to the mutations of ADAMTS13, which cleaves its substrate von Willebrand factor(VWF) in shear-induced unfolding condition. Most of the congenital TTP we found is woman with pregnancy. Here, we characterize two children suspected with congenital TTP. Methods:ADAMTS13 activities were analyzed by residual collagen binding assay (R-CBA) plus FRET-VWF substrate. And the inhibitors of ADAMTS13 were analyzed by 9:1 mixture of patient and pooled normal plasma followed by R-CBA. The secretion of recombinant ADAMTS13 mutants was studied. Results: Two children, one aged four months and the other aged three years old, were diagnosed with congenital TTP because their ADAMTS13 activities were less than 5% (both FRET-VWF and R-CBA), and there are short of ADAMTS13 inhibitors. The following mutations were found: Q1385P, Y177C, C522R. In addition to the previously reported mutation of Y177C, the two novel mutations (Q1385P and C522R) failed to secrete from the HEK293 cells. Conclusion: Two children with congenital TTP were determined thanks to screening of ADAMTS13 activity and its corresponding inhibitor assays, and it seems that congenital TTP could occur in different ages although most of congenital TTP we found were women with pregnancy. Disclosures No relevant conflicts of interest to declare.

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.

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