Hamostaseologie. 2018 Feb;38(1):33-38. doi: 10.5482/HAMO-17-03-0013. Epub 2018 Feb 26.
A 7-years-old child who developed unprovoked deep vein thrombosis (DVT) and pulmonary embolism (PE) was tested for inherited thrombophilia. Protein C (PC) antigen level (87 %) and PC coagulometric and amidolytic activities (12 % and 11 %, respectively) were consistent with a homozygous PC type IIA phenotype.The patient was carrier of two heterozygous missense mutations causing p.Arg32Cys substitution associated with a type I PC defect ("null allele", from the paternal side) and p.Gly433Ser substitution responsible for a type IIA PC defect (from the maternal side). Thus, the apparently normal PC antigen level in the proband was misleading in the interpretation of phenotype/genotype relationship of this compound PC defect. The child was also carrier of heterozygous prothrombin G20210A variant.Severe venous thromboembolism can occur in otherwise healthy children with complex inherited thrombophilia. Careful laboratory characterization of the phenotype/genotype relationship can be crucial to correctly classify PC defects and for their management with anticoagulants or replacement therapy.
一名 7 岁儿童出现自发性深静脉血栓形成 (DVT) 和肺栓塞 (PE)，对其遗传性血栓形成倾向进行了检查。蛋白 C (PC) 抗原水平 (87%) 和 PC 凝血酶和氨肽酶活性 (分别为 12%和 11%) 与纯合子 PC ⅡA型表型一致。患者为两种杂合错义突变的携带者，导致 p.Arg32Cys 取代与 I 型 PC 缺陷相关（来自父系的“无效等位基因”）和 p.Gly433Ser 取代与 IIA 型 PC 缺陷相关（来自母系）。因此，在解释这种复合 PC 缺陷的表型/基因型关系时，先证者中明显正常的 PC 抗原水平具有误导性。该儿童还携带杂合子凝血酶原 G20210A 变异。复杂遗传性血栓形成倾向的健康儿童也可能发生严重静脉血栓栓塞。仔细描述表型/基因型关系的实验室特征对于正确分类 PC 缺陷以及用抗凝剂或替代疗法进行治疗至关重要。
