ADAMTS13 deficiency, an important cause of thrombocytopenia during pregnancy

Kato, Ryohei; Shinohara, Atsuko; Sato, Jussara Leiko

doi:10.1016/j.ijoa.2008.07.009

Cited by 12 publications

(17 citation statements)

References 11 publications

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“…At the age of 36, USS-M4 became pregnant for a fourth time. With extensive FFP infusions, she continued her pregnancy until 36 weeks of gestation and delivered a healthy baby (2506 g BW) by natural birth with a skin incision [44].…”

Section: Brief Clinical Datamentioning

confidence: 99%

Natural history of Upshaw–Schulman syndrome based on ADAMTS13 gene analysis in Japan

Fujimura

Matsumoto

Isonishi

et al. 2011

Journal of Thrombosis and Haemostasis

183

228

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Summary. Upshaw–Schulman syndrome (USS) is an extremely rare hereditary deficiency of ADAMTS13 activity, termed congenital TTP. The clinical signs are usually mild during childhood, often with isolated thrombocytopenia. But their symptoms become more evident when patients have infections or get pregnant. We identified 43 USS‐patients in Japan, who ranged in age from early childhood to 79 years of age. Analysing the natural history of these USS patients based on ADAMTS13 gene mutations may help characterise their clinical phenotypes. Severe neonatal jaundice that requires exchange blood transfusion, a hallmark of USS, was found in 18 of 43 patients (42%). During childhood, 25 of 43 patients were correctly diagnosed with USS without gender disparity. These 25 patients were categorised as having ‘the early‐onset phenotype’. Between 15 and 45 years of age, 15 were correctly diagnosed, and, interestingly, they were all female. The remaining three patients were male and were diagnosed when they were older than 45 years of age, suggesting that they were ‘the late‐onset phenotype’. Two of these three males developed sudden overt TTP when they were 55 and 63 years old, respectively. These two men had two different homozygous ADAMTS13 gene mutations, p.R193W/p.R193W and p.C1024R/p.C1024R, respectively. Both of which were not discovered in the US or Western countries. In vitro expression studies showed that these two proteins were consistently secreted into the culture medium but to a lesser extent and with reduced activity compared to the wild‐type protein. Our results indicate that ‘the late‐onset phenotype’ of USS is formed with ethnic specificity.

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Section: Brief Clinical Datamentioning

confidence: 99%

Natural history of Upshaw–Schulman syndrome based on ADAMTS13 gene analysis in Japan

Fujimura

Matsumoto

Isonishi

et al. 2011

Journal of Thrombosis and Haemostasis

183

228

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“…The characteristics of these patients and babies are shown in Table 1, and for some of them the detailed clinical course during pregnancy was previously reported. 7,9,[17][18][19][20][21] Each mother's cTTP code corresponded to those in our previous reports. 3,7,9,11,22 We classified these 38 pregnancies into two groups.…”

Section: Study Design and Enrollmentmentioning

confidence: 79%

Success and limitations of plasma treatment in pregnant women with congenital thrombotic thrombocytopenic purpura

Sakai

Fujimura

Nagata

et al. 2020

Journal of Thrombosis and Haemostasis

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Background: Congenital thrombotic thrombocytopenic purpura (cTTP), otherwise known as Upshaw-Schulman syndrome, is an extremely rare hereditary disease. Pregnancy is identified as a trigger for TTP episodes in patients with cTTP. Objectives: To investigate the ideal management of pregnant patients with cTTP. Patients/Methods: We identified 21 patients with a reproductive history (38 pregnancies) in a Japanese cTTP registry. Fetal outcomes were compared between two groups: group 1 (n = 12), pregnancy after diagnosis of confirmed cTTP by ADAMTS13 gene analysis; and group 2 (n = 26), pregnancy before diagnosis of confirmed cTTP. Results: In group 1, ADAMTS13 activity was closely monitored until delivery in most cases. Among 10 pregnancies in group 1, prophylactic fresh frozen plasma (FFP) infusions during pregnancy were performed to replenish ADAMTS13. In group 2, prophylactic FFP infusions were not administrated in 23 pregnancies and FFP test infusions were performed in only three pregnancies. The live birth rate of group 1 was significantly higher than that of group 2 (91.7% vs 50.0%, respectively, P = .027).

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“…In our USS registry, one patient with USS (USS-L2) successfully gave birth to 4 babies (including twins) with taking low-dose aspirin during pregnancy [5]. Another patient successfully treated with FFP infusion and low-dose aspirin was reported by another group from our registry in Japan [6]. Antiplatelet agents such as aspirin, dipyridamole and ticlopidine, have been used in the acute treatment of acquired TTP.…”

Section: Discussionmentioning

confidence: 99%

“…These pregnancies often result in premature delivery or fetal loss. Recent papers have reported successful delivery with FFP infusion therapy in patients with USS diagnosed prior to pregnancy [6,7]. However, a detailed therapeutic protocol including FFP infusions for pregnant women with USS has not yet been established.…”

Section: Introductionmentioning

confidence: 99%

A Unique Case Involving a Female Patient with Upshaw-Schulman Syndrome: Low Titers of Antibodies against ADAMTS13 prior to Pregnancy Disappeared after Successful Delivery

Ogawa

Matsumoto

Sadakata

et al. 2015

Transfus Med Hemother

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Background: Upshaw-Schulman syndrome (USS) is usually suspected based on severe deficiency of ADAMTS13 activity without ADAMTS13 antibody, but the definitive diagnosis is made by ADAMTS13 gene analysis. We present a unique case of USS with low titers of ADAMTS13 antibodies before pregnancy. Interestingly, titers of ADAMTS13 antibodies decreased to almost undetectable levels after delivery. Case Report: In patient LL4, the diagnosis of USS was confirmed at age 27 by ADAMTS13 gene analysis. She became pregnant at age 30. During the pregnancy, she received regular fresh frozen plasma (FFP) infusion. Plasma von Willebrand factor levels increase as pregnancy progresses. To prevent platelet thrombi, much more ADAMTS13 supplementation is necessary during late gestation in patients with USS. Therefore, we shortened the interval between and increased the volume of FFP infusions as pregnancy progressed. At 39 weeks, she delivered a healthy baby girl. Before pregnancy, she had low titers of both neutralizing and binding anti-ADAMTS13 antibodies. Despite frequent FFP infusions, titers of the antibodies did not increase, but rather decreased to almost undetectable levels during pregnancy. Conclusion: Both the neutralizing and binding antibodies against ADAMTS13 decreased to almost undetectable levels after delivery in this patient, which can be caused by an immunological reset.

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ADAMTS13 deficiency, an important cause of thrombocytopenia during pregnancy

Cited by 12 publications

References 11 publications

Natural history of Upshaw–Schulman syndrome based on ADAMTS13 gene analysis in Japan

Natural history of Upshaw–Schulman syndrome based on ADAMTS13 gene analysis in Japan

Success and limitations of plasma treatment in pregnant women with congenital thrombotic thrombocytopenic purpura

A Unique Case Involving a Female Patient with Upshaw-Schulman Syndrome: Low Titers of Antibodies against ADAMTS13 prior to Pregnancy Disappeared after Successful Delivery

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