Title : Discrepancies of prothrombin time with low FVII activity could be a rare case of Factor VII Padua
Abstract:
Introduction/background: Any discrepancies of Factor VII (FVII) activity levels using different thromboplastin in a prolonged Prothrombin Time (PT), suspect FVII Padua. This case presented with PT discrepancies using different thromboplastins, FVII Padua is highly suspected.
Methods: This is a case report of a 2-year-old male with a history of recurrent tonsillitis who presents for tonsillectomy. There is no known history of bleeding. Workups revealed prolonged PT and eventually referred for Hematology evaluation. PMH, family, and environmental history were unremarkable. Normal physical exam except for tonsillar enlargement. Other labs were all normal.
Results: There were six different time points of testing for PT in four laboratories using either human recombinant or rabbit cerebral thromboplastin. There is an intermediate prolongation of PT using human recombinant while marked PT prolongation with a low level of FVII activity (7%) using a rabbit cerebral thromboplastin.
Discussion: FVII deficiency is a hereditary autosomal recessive disease and on rare occasions, it is acquired. Acquired FVII deficiency is common in tumors, antiphospholipid antibodies, sepsis, aplastic anemia, and hematopoietic stem cell transplantation. Congenital FVII deficiency has two forms: type I and type II. Type I is deficient in FVII activity and antigen. Type II always has low FVII activity, and FVII antigen is normal or reduced. FVII Padua defect ARG304Gln mutation in exon8. FVII Padua revealed very-low results of FVII (4-10% of normal) using rabbit brain thromboplastin, whereas thromboplastin of human origin like placenta or recombinant human thromboplastin has low intermediate levels of FVII (30-40% of normal), and a normal level of FVII (105% of normal) when using ox-brain thromboplastin. FVII antigens are always normal. Girolami, et al (2011) explained that using thromboplastin from the ox-brain is very sensitive to activated FVII could be due to abnormally high circulating levels of activated FVII in FVII Padua. Increased levels of activated FVII in FVII Padua were postulated to be associated with an increased risk for thrombosis.
Conclusion: It is essential to repeat testing of PT and Factor VII assay using a different thromboplastin in a prolonged PT with a low FVII activity. Asymptomatic patients with discrepancies in PT and FVII, highly consider FVII Padua before any Factor VII replacement therapy.
Audience Takeaway:
- To recognize this rare case of FVII Padua in clinical practice.
- To understand the different PT/FVII levels using different coagulation thromboplastin reagents.
- To be aware of the risk if FVII Padua when treated with factor VII.
