Diagnostic challenge of the newborn patients with heritable protein C deficiency

Abstract

AbstarctObjectiveThe diagnosis of neonatal-onset protein C (PC) deficiency is challenging. This study aimed to establish the neonatal screening of heritable PC deficiency in Japan.Study designWe determined the changes in plasma activity levels of PC and protein S (PS) in healthy neonates, and studied newborn patients with PROC mutation in the Japanese registry.ResultPhysiological PC and PS levels increased with wide range. The PC/PS-activity ratios converged after birth. The PC/PS-activity ratios of 19 patients with biallelic mutations, but not, 9 with monoallelic mutation, were lower than those of 13 without mutation. The logistic regression analyses established a formula including two significant variables of PC activity (cut-off < 10%, odds ratio = 30.0) and PC/PS-activity ratio (cut-off < 0.35, odds ratio = 22.7), with 93% sensitivity and 44% specificity for determining patients with mutation(s).ConclusionThe PC/PS-activity ratio is an effective parameter for the genetic screening of neonatal-onset PC-deficiency in Japanese population.

Congenital heterozygous protein C deficiency with portal vein thrombosis

“…The PC/PS activity ratio (cut-off <0.35) is reported useful for screening neonatal PC deficiency. 4 The PC/PS activity ratio in our case was as low as 0.157, effectively suggesting PC deficiency.…”

“…It is difficult to diagnose PC deficiency based only on the absolute value of PC activity. The PC/PS activity ratio (cut‐off <0.35) is reported useful for screening neonatal PC deficiency 4 . The PC/PS activity ratio in our case was as low as 0.157, effectively suggesting PC deficiency.…”

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

“…For these patients, the PC/PS activity ratio may provide a basis for suspecting PROC variants. 14 Genetic testing based on these parameters can be used to perform a highly cost-effectiveness screening for EOT. There may be variants that cannot be detected by the current Sanger sequencing.…”

“…The anticoagulant activities of PC, PS, and AT were determined using the Staclot PC kit, Staclot PS kit (Diagnostica Stago), and Chromostrate ATIII kit (Hitachi), respectively. 2,14 Genetic testing was performed for patients whose PC, PS, or AT activity was lower than the lower limit of the reference range (RR) for each age group, [15][16][17] those who had recurrent thromboses, or those who had first-or second-degree relatives with low anticoagulant activity or EOT. Repeated measurements of anticoagulant activities until genetic testing were performed in patients who showed borderline activities at the first assessment.…”

Hot topics in coagulation testing: Important considerations for testing children for bleeding/thrombotic disorders

“…There remains a scarcity of evidence proving clinical relevance of out‐of‐normal‐range results in the paediatric setting. While there are some haemostatic disorders for which clinical phenotype and management may be predicted by a specific out‐of‐range result (eg severe haemophilia 19,20 ), the significance of other abnormal results (eg low protein C levels in premature infants 21‐23 and normal vWF concentration at birth) may be less clear. For instance, despite a family history a diagnosis of type I von Willebrand disease may not be possible at birth due to physiological increase in vWF concentration.…”