Clinical and genetic features of Chinese pediatric patients with severe congenital protein C deficiency who first presented with purpura fulminans: A case series study and literature review

Tang, Xue; Zhang, Zhiyong; Yang, Hui; Xiao, Jianwen; Wen, Xiaohong; Yu, Dou; Yu, Jie; Hu, Yanni

doi:10.1016/j.thromres.2021.12.026

Cited by 7 publications

(3 citation statements)

References 33 publications

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“…Moreover, prenatal‐onset ICTH and/or OB have been found in PC‐deficient neonates with biallelic variants. Considering that ocular lesions were detected in two (29%) of seven PROC ‐biallelic neonatal cases in China, 45 the incidence in Japan (4/29, 14%) may recall the limit of postnatal intervention for severe neonatal PC deficiency. In Japan, APC is the sole licensed agent for acute treatment; however, it does not prevent thrombosis in heritable PC‐deficient patients.…”

Section: Discussionmentioning

confidence: 99%

The clinical and genetic landscape of early‐onset thrombophilia in Japan

Egami,

Ishimura,

Ochiai

et al. 2023

Pediatric Blood & Cancer

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ObjectivesTo determine the optimal management for early‐onset thrombophilia (EOT), the genetic and clinical features of protein C (PC)‐, protein S (PS)‐, or antithrombin (AT)‐deficient patients of ≤20 years of age were studied in Japan.Methods/resultsClinical and genetic information of all genetically diagnosed cases was collected through the prospective, retrospective study, and literature review. One‐hundred‐one patients had PC (n = 55), PS (n = 29), or AT deficiency (n = 18). One overlapping case had PC‐ and PS‐monoallelic variant. Fifty‐five PC‐deficient patients (54%) had 26 monoallelic or 29 biallelic variant(s), and 29 (29%) PS‐deficient patients had 20 monoallelic or nine biallelic variant(s). None of the patients had AT‐biallelic variants. The frequent low‐risk allele p.K193del (PC‐Tottori) was found in five patients with monoallelic (19%) but not 29 with biallelic variant(s). The most common low‐risk allele p.K196E (PS‐Tokushima) was found in five with monoallelic (25%) and six with biallelic variant(s) (67%). One exceptional de novo PC variant was found in 32 families with EOT. Only five parents had a history of thromboembolism. Thrombosis concurrently developed in three mother–newborn pairs (two PC deficiency and one AT deficiency). The prospective cohort revealed the outcomes of 35 patients: three deaths with PC deficiency and 20 complication‐free survivors. Neurological complications were more frequently found in patients with PC‐biallelic variants than those with PC‐, PS‐, or AT‐monoallelic variants (73% vs. 24%, p = .019).ConclusionsWe demonstrate the need for elective screening for EOT targeting PC deficiency in Japan. Early prenatal diagnosis of PC deficiency in mother–infant pairs may prevent perinatal thrombosis in them.

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Section: Discussionmentioning

confidence: 99%

The clinical and genetic landscape of early‐onset thrombophilia in Japan

Egami,

Ishimura,

Ochiai

et al. 2023

Pediatric Blood & Cancer

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“…Individuals heterozygous for PROC are predisposed to thrombosis when infected or distressed [7]. A case series of 12 Chinese infants revealed that all the cases with neonatal PF, except one, had a protein C level of less than 10% [8]. Heterozygous protein C deficiency is associated with less severe symptoms and is unlikely to present with arterial thrombosis [9].…”

Section: Table 1: Blood Workup At Admissionmentioning

confidence: 99%

Neonatal Purpura Fulminans in a Patient With Arterial Thrombosis and Congenital Renal Agenesis

Abbaker,

Edupuganti,

Elmukashfi

et al. 2024

Cureus

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Neonatal purpura fulminans (PF) is an uncommon skin disorder characterized by acute disseminated intravascular coagulation, tissue necrosis, and small vessel thrombosis. Here, we present a case of a sevenday-old male who was admitted to the Neonatal Intensive Care (NICU) Unit at Gaafar Ibn Auf Tertiary Hospital, in January 2023. He presented with black bullous lesions on the plantar surface of the left foot, deep bluish discoloration over the right buttock and right lower abdomen, and gangrenous changes in the right foot with clear demarcation. Birth history was not significant other than mild pallor and icterus. His blood workup was consistent with severe anemia, thrombocytopenia, elevated prothrombin time, and partial thromboplastin time with decreased protein C and S levels; blood culture yielded no growth. A Doppler ultrasound scan of lower extremities confirmed distal occlusion of the right dorsalis pedis artery. The abdominal ultrasound revealed a free left renal bed and left-sided renal agenesis. We came to a diagnosis of neonatal PF and started administering blood and fresh frozen plasma and subcutaneous heparin injections, but unfortunately, the patient eventually passed away. Hence, we decided to report this case to emphasize the significance of the clinical picture in assisting with early diagnosis, despite limited access to genetic testing. We also want to highlight the importance of a "high index of suspicion" that might be mandatory for better outcomes.

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“…Further, the possibility of obtaining a PC + PS concentrate from unused plasma fractionation intermediates rather than from plasma fractions earmarked for other products would significantly reduce manufacturing costs, favourably impacting prices for patients and National Health Systems. The clinical importance of PC and its cofactor PS has been deduced from the finding of reduced plasma levels of PC or PS in patients with congenital thrombotic disease [12,13] and in NPF where the deficiency can be caused by a lack of PC but also of PS [14].…”

Section: Introductionmentioning

confidence: 99%

New plasma protein C and protein S concentrate: A synergy for therapeutic purposes

Mori,

Angelini,

Farina

2023

Vox Sanguinis

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Background and ObjectivesDeficiencies of protein C (PC) or protein S (PS) are rare diseases, characterized by mutations in the PC or PS genes, which encode plasma serine proteases with anti‐coagulant activity. Severe PC or PS deficiencies manifest in early life as neonatal purpura fulminans, a life‐threatening heamorrhagic condition requiring immediate treatment. First‐line treatment involves replacement therapy, followed by maintenance with anti‐coagulants. Replacement therapy with specific protein concentrates is currently only limited to PC, and therefore, a PC + PS concentrate represents a useful addition to therapeutic options, particularly for severe PS deficiency. Further, the production of a PC + PS concentrate from unused plasma fractionation intermediates would impact favourably on manufacturing costs, and consequently therapy prices for patients and health systems.Materials and MethodsSeveral chromatographic runs were performed on the same unused plasma fractionation intermediates using different supports to obtain a PC/PS concentrate. The best chromatographic mediums were chosen, in terms of specific activity and recovery. A full process of purification including virus inactivation/removal and lyophilization steps was set up.ResultsThe final freeze‐dried product had a mean PC concentration of 47.75 IU/mL with 11% of PS, and a mean specific activity of 202.5 IU/mg protein, corresponding to over 12,000‐fold purification from plasma.ConclusionThe development of a novel concentrated PC/PS mixture obtained from a waste fraction of other commercial products could be used for its potential therapeutic role in the management of neonatal purpura fulminans pathology.

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Clinical and genetic features of Chinese pediatric patients with severe congenital protein C deficiency who first presented with purpura fulminans: A case series study and literature review

Cited by 7 publications

References 33 publications

The clinical and genetic landscape of early‐onset thrombophilia in Japan

The clinical and genetic landscape of early‐onset thrombophilia in Japan

Neonatal Purpura Fulminans in a Patient With Arterial Thrombosis and Congenital Renal Agenesis

New plasma protein C and protein S concentrate: A synergy for therapeutic purposes

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