An ADAMTS13 mutation that causes hereditary thrombotic thrombocytopenic purpura: a case report and literature review

Background Neonatal‐onset hereditary thrombotic thrombocytopenia purpura (hTTP) is often misdiagnosed due to its rarity. It begins with jaundice, similar to infants with ABO incompatibility. Objective To explore early indicators of neonatal‐onset hTTP. Methods This study was a retrospective case series of newborns with hTTP and ABO incompatibility. We compared the clinical characteristics and laboratory test results in these two groups. Results This study included four hTTP patients and 20 ABO‐incompatible newborns. All patients manifested disease during the neonatal period. There were equal numbers of males and females in each group. hTTP newborns showed earlier (median difference, 57.0 h; 95% confidence interval [CI], 24.0–65.0) and more severe hyperbilirubinemia (mean difference, 8.0 mg/dl; 95% CI, 3.8–12.1) than ABO‐incompatible newborns. In hTTP newborns, anemia was more common within 7 days after birth than in ABO‐incompatible newborns (odds ratio, 25.4; 95% CI, 1.2–551.6), and platelet counts were lower than in ABO‐incompatible newborns (17 ± 12 × 10 9 /L vs. 291 ± 76 × 10 9 /L). The levels of serum creatinine (median difference, 51.8 μmol/L; 95% CI, 16.0–109.4) and blood urea nitrogen (median difference, 5.7 mmol/L; 95% CI, 2.8–38.7) were higher in hTTP newborns than in ABO‐incompatible newborns. There were no significant differences in white blood cell counts, C‐reactive protein, alanine aminotransferase, or albumin levels. Conclusions Severe jaundice soon after birth, early anemia, and severe thrombocytopenia were more common in newborns with hTTP than ABO incompatibility. These are distinguishing early features of hTTP.

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“…Of the eight ADAMTS‐13 gene mutations, c.330+1G>A and c.1335delC had been reported previously. 1 , 14 …”

Section: Resultsmentioning

confidence: 99%

“…Genetic test resultsshowed compound heterozygous ADAMTS-13 gene mutations (Table2). Of the eight ADAMTS-13 gene mutations, c.330+1G>A and c.1335delC had been reported previously 1,14.…”

mentioning

confidence: 99%

Early indicators of neonatal‐onset hereditary thrombotic thrombocytopenia purpura

Liu

Zhang

et al. 2022

Research and Practice in Thrombosis and Haemostasis

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“…The diagnosis was supported by the genetic results. We reviewed nine published studies of newbornonset patients (all were diagnosed by ADAMTS13 activity, in seven cases gene mutation analysis was performed) and compared them with our three cases for clinical symptoms and laboratory testing (Table 1) (7)(8)(9)(10)(11)(12)(13). In our literature review, all infants showed jaundice and thrombocytopenia after birth to varying degrees, accompanied by other different symptoms (e.g., fever and hematuria) (7,8).…”

Section: Discussionmentioning

confidence: 99%

Novel ADAMTS13 mutation in a family with three recurrent neonatal deaths: a case report and literature review

Yang¹,

Li²,

Zhu³

et al. 2022

Transl Pediatr

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Background: Upshaw-Schulman syndrome (USS) is rare, autosomal recessive, hereditary thrombotic thrombocytopenic purpura (TTP) caused by variants in a disintegrin-like and metalloprotease with thrombospondin type 1 motif (ADAMTS13). USS has a heterogeneous clinical course, and most symptoms overlap with other diseases. Early diagnosis may have important implications for the patients. We found novel ADAMTS13 mutation and explored the clinical features and prognosis of newborn-onset USS to increase awareness of the disease.Case Description: The same, non-consanguineous couple had three unexplained neonatal deaths. The symptoms of the three infants were mainly severe jaundice, anemia and thrombocytopenia after birth, which was consistent with the reported USS symptoms of neonates and died rapidly suddenly in the during rescue efforts. By using whole-exome sequencing (WES) for the study family, we found a novel heterozygous compound in ADAMTS13 (c.1187 (exon10) G>A (p.C396Y)/c.1595 (exon14) G>T (p.C532F)) that was carried by the three newborns originating from father and mother respectively. We reviewed nine published studies of newborn-onset USS and compared our cases for clinical symptoms and laboratory testing. All nine published cases were diagnosed by ADAMTS13 activity; in seven cases gene mutation analysis was performed and eight cases were still alive at the time of publication. Conclusions:The case has added clinicians' awareness of the diagnosis and treatment of USS. A novel rare mutation in ADAMTS13 broadens the spectrum of genetic causes of this rare disorder and expands the phenotypic spectrum.

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“…ADAMTS13 deficiency leads to a buildup of vWF multimers, which bind platelets and occlude microcirculation leading to thrombocytopenia, MAHA, and end-organ damage 19. Of note, there is an autosomal recessive inherited ADAMTS13 deficiency associated with relapsing TTP called Upshaw-Schulman syndrome 21. Typical HUS (associated with gastroenteritis) is associated with Escherichia coli (O157:H7) production of Shiga-like toxins 22.…”

Section: Thrombotic Thrombocytopenic Purpura and Hemolytic Uremic Syn...mentioning

confidence: 99%

“…19 Of note, there is an autosomal recessive inherited ADAMTS13 deficiency associated with relapsing TTP called Upshaw-Schulman syndrome. 21 Typical HUS (associated with gastroenteritis) is associated with Escherichia coli (O157:H7) production of Shiga-like toxins. 22 Atypical HUS occurs as a result of uncontrolled activation of the complement system, a component of our innate 102 CRITICAL CARE NURSING QUARTERLY/JANUARY-MARCH 2023 immune system.…”

Section: Thrombotic Thrombocytopenic Purpura and Hemolytic Uremic Syn...mentioning

confidence: 99%

Hematologic and Oncologic Emergencies

Holden

Rao

White

et al. 2023

Critical Care Nursing Quarterly

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This article reviews both hematologic and oncologic emergencies that may be seen in the intensive care setting. Hematologic emergencies, including autoimmune hemolytic anemia, thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, and disseminated intravascular coagulation, as well as oncologic emergencies including tumor lysis syndrome, superior vena cava syndrome, and cardiac tamponade secondary to metastatic disease, are discussed in detail. This review focuses on the pathophysiology, clinical features, diagnosis, and treatment of each entity.

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An ADAMTS13 mutation that causes hereditary thrombotic thrombocytopenic purpura: a case report and literature review

Cited by 6 publications

References 25 publications

Early indicators of neonatal‐onset hereditary thrombotic thrombocytopenia purpura

Early indicators of neonatal‐onset hereditary thrombotic thrombocytopenia purpura

Novel ADAMTS13 mutation in a family with three recurrent neonatal deaths: a case report and literature review

Hematologic and Oncologic Emergencies

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