A Retrospective Analysis of Clinical and Laboratory Data of Patients with Factor VII Deficiency: A Single Centre Experience

Abstract

Bleeding phenotype in patients with congenital factor VII (FVII) deficiency is highly variable. No direct correlation between FVII activity and bleeding tendency is noted. The aim of this study was to analyse clinical and laboratory phenotype of patients with FVII deficiency treated in one haemophilia treatment centre in Little Poland. Clinical and laboratory data of 106 patients were collected retrospectively. Bleeding symptoms were evaluated according to the Bleeding Assessment Tool. The mean FVII activity was 19.5% (range: 1.0–49.2) and the mean prothrombin time (PT) was 29.7 seconds (range: 13.2–64.8), comparable in both sexes. Activity was lower than 1% in 6.6% of individuals. The average age at diagnosis (31.2 years; range: 1–76) did not correlate with FVII activity. Half of the patients were diagnosed incidentally, mostly due to routine PT measurement. The most frequently reported symptoms were gum, nose and tooth extraction bleeds. A total of 22.6% of patients remained asymptomatic and 60.4% never required replacement therapy. Thrombotic episodes were diagnosed in five women (4.7%). In conclusion, the clinical picture of the analysed group is similar to the previously described. It should be stressed that a significant risk of bleeds, including joint haemorrhages, can be expected in patients with mildest FVII deficiency (>26%) as well. The rate of thrombosis (4.7%) was similar to other reports, with all affected patients having strong prothrombotic risk factors or being intensively treated with FVII concentrate.

Zusammenfassung

Die klinische Ausprägung des angeborenen Faktor-VII-Mangels ist variabel. Die Blutungsneigung korreliert nur wenig mit der Faktor-VII-Aktivität. Ziel dieser Arbeit ist die Darstellung der klinischen und diagnostischen Charakteristika von Patienten mit Hypoprokonvertinämie, betreut im Hämophiliezentrum (Kleinpolen). Die retrospektive Klinik- und Labordaten von 106 Patienten waren analysiert. Blutungsneigung wurde evaluiert anhand des standardisierten Fragebogens (Bleeding Assessment Tool). Durchschnittliche Faktor-VII-Aktivität betrug 19.5% (1.0–49.2) und durchschnittliche Prothrombinzeit 29.7 second (13.2–64.8), vergleichbar bei beiden Geschlechtern. Faktor-VII-Aktivität war niedriger als 1% bei 6.6% der Patienten. Durchschnittlicher Alter zum Zeitpunkt der Diagnose (31.2 Jahre; 1–76) korrelierte nicht mit der Faktor-VII-Aktivität. Bei der Hälfte der Patienten wurde die Krankheit zufällig entdeckt, meistens infolge routinemäßiger Prothrombinzeit Messung. Die am häufigsten gemeldeten Symptome waren Zahnfleischbluten, Nasenbluten und Blutungen nach der Zahnextraktion. Bei 22.6% der Patienten trafen keine Symptome auf und 60.4% der Patienten erhalten niemals Ersatztherapie. Thrombose tritt auf in 5 Frauen (4.7%). Das klinische Bild dieser Blutungsneigung in unserer Patientengruppe ist vereinbar mit anderen Literaturberichten. Zu unterstreichen ist, dass ein signifikantes Risiko der Blutungen (auch Gelenkblutungen) besteht auch bei Patienten mit dem höchsten Faktor-VII-Spiegel (>26%). Häufigkeit der Thrombose (4.7%) war ähnlich wie in früheren Studien. Alle Patienten erwiesen dabei starke Risikofaktoren für die Thrombose oder waren intensiv mit Faktor-VII-Konzentrat behandelt.

Keywords

congenital FVII deficiency - bleeding symptoms - diagnosis - replacement therapy - thrombosis

Schlüsselwörter

angeborener Faktor-VII-Mangel - Blutungsneigung - Ersatztherapie - Thrombose

• References

• 1 Mariani G, Herrmann FH, Dolce A. , et al; International Factor VII Deficiency Study Group. Clinical phenotypes and factor VII genotype in congenital factor VII deficiency. Thromb Haemost 2005; 93 (03) 481-487
• 2 Di Minno MN, Dolce A, Mariani G. ; STER Study Group. Bleeding symptoms at disease presentation and prediction of ensuing bleeding in inherited FVII deficiency. Thromb Haemost 2013; 109 (06) 1051-1059
• 3 de Moerloose P, Schved JF, Nugent D. Rare coagulation disorders: fibrinogen, factor VII and factor XIII. Haemophilia 2016; 22 (Suppl. 05) 61-65
• 4 Zawilska K, Chojnowski K, Klukowska A. , et al. Polskie zalecenia postępowania w rzadkich niedoborach osoczowych czynników krzepnięcia. Hematologia. 2011; 2 (04) 303-310
• 5 Napolitano M, Siragusa S, Mariani G. Factor VII deficiency: clinical phenotype, genotype and therapy. J Clin Med 2017; 6 (04) 38
• 6 Sevenet PO, Kaczor DA, Depasse F. Factor VII deficiency: from basic to clinical laboratory diagnosis and patient management. Clin Appl Thromb Hemost 2017; 23 (07) 703-710
• 7 Clinical and Laboratory Standard Institute. Determination of Coagulation Factor Activities Using the One-Stage Clotting Assay; CLSI document H48. 2nd ed. Wayne, PA: Clinical and Laboratory Institute; 2016
• 8 Mariani G, Bernardi F. Factor VII deficiency. Semin Thromb Hemost 2009; 35 (04) 400-406
• 9 Rodeghiero F, Tosetto A, Abshire T. , et al; ISTH/SSC joint VWF and Perinatal/Pediatric Hemostasis Subcommittees Working Group. ISTH/SSC bleeding assessment tool: a standardized questionnaire and a proposal for a new bleeding score for inherited bleeding disorders. J Thromb Haemost 2010; 8 (09) 2063-2065
• 10 Quintavalle G, Riccardi F, Rivolta GF. , et al; Ad-Hoc Study Group. F7 gene variants modulate protein levels in a large cohort of patients with factor VII deficiency. Results from a genotype-phenotype study. Thromb Haemost 2017; 117 (08) 1455-1464
• 11 Peyvandi F, Di Michele D, Bolton-Maggs PHB, Lee CA, Tripodi A, Srivastava A. ; Project on Consensus Definitions in Rare Bleeeding Disorders of the Factor VIII/Factor IX Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. Classification of rare bleeding disorders (RBDs) based on the association between coagulant factor activity and clinical bleeding severity. J Thromb Haemost 2012; 10 (09) 1938-1943
• 12 Jain S, Donkin J, Frey MJ, Peltier S, Gunawardena S, Cooper DL. Phenotypical variability in congenital FVII deficiency follows the ISTH-SSC severity classification guidelines: a review with illustrative examples from the clinic. J Blood Med 2018; 9: 211-218
• 13 Girolami A, Cosi E, Ferrari S, Girolami B, Lombardi AM. Bleeding manifestations in heterozygotes with congenital FVII deficiency: a comparison with unaffected family members during a long observation period. Hematology 2017; 22 (06) 375-379
• 14 Dorgalaleh A, Alavi SE, Tabibian S. , et al. Diagnosis, clinical manifestations and management of rare bleeding disorders in Iran. Hematology 2017; 22 (04) 224-230
• 15 Napolitano M, Di Minno MN, Batorova A. , et al. Women with congenital factor VII deficiency: clinical phenotype and treatment options from two international studies. Haemophilia 2016; 22 (05) 752-759
• 16 Herrmann FH, Wulff K, Auerswald G. , et al; Greifswald Factor FVII Deficiency Study Group. Factor VII deficiency: clinical manifestation of 717 subjects from Europe and Latin America with mutations in the factor 7 gene. Haemophilia 2009; 15 (01) 267-280
• 17 Baumann Kreuziger LM, Morton CT, Reding MT. Is prophylaxis required for delivery in women with factor VII deficiency?. Haemophilia 2013; 19 (06) 827-832
• 18 Mariani G, Napolitano M, Dolce A. , et al; Seven Treatment Evaluation Registry; International Factor VII Deficiency Study Group. Replacement therapy for bleeding episodes in factor VII deficiency. A prospective evaluation. Thromb Haemost 2013; 109 (02) 238-247
• 19 Mariani G, Herrmann FH, Schulman S. , et al; International Factor VII Deficiency Study Group. Thrombosis in inherited factor VII deficiency. J Thromb Haemost 2003; 1 (10) 2153-2158
• 20 Girolami A, Tezza F, Scandellari R, Vettore S, Girolami B. Associated prothrombotic conditions are probably responsible for the occurrence of thrombosis in almost all patients with congenital FVII deficiency. Critical review of the literature. J Thromb Thrombolysis 2010; 30 (02) 172-178
• 21 Giansily-Blaizot M, Marty S, Chen SW, Pellequer JL, Schved JF. Is the coexistence of thromboembolic events and Factor VII deficiency fortuitous?. Thromb Res 2012; 130 (Suppl. 01) S47-S49
• 22 Napolitano M, Siragusa S. Coronary artery stenosis treatment in aging patients with inherited factor VII deficiency: where do we stand?. Transfus Apheresis Sci 2017; 56 (06) 867-869
• 23 Napolitano M, Dolce A, Batorova A. , et al. Replacement therapy in inherited factor VII deficiency: occurrence of adverse events and relation with surgery. Haemophilia 2015; 21 (06) e513-e517
• 24 Batorova A, Mariani G, Kavakli K. , et al; STER Study Group. Inhibitors to factor VII in congenital factor VII deficiency. Haemophilia 2014; 20 (02) e188-e191