Management of the Sponataneous Bleeding Episodes in Factor VII Deficiency. A Prospective Evaluation of the STER,

Abstract

Abstract 3368 IntroductionPatients with an inherited factor VII (FVII) deficiency may display a wide range of clinical phenotypes, from an asymptomatic condition to serious hemorrhagic episodes such as fatal central nervous system (CNS) or gastrointestinal (GI) bleeds (Mariani G et al. Thromb Haemost 2005; 93: 481–7). Symptomatic patients can be divided into two major categories: those with mild-to-moderate bleeding tendency and individuals with a severe bleeding tendency which may be more severe than that in hemophilia. The former group mainly experience mucosal bleeding, a clinical picture that mimics that of a platelet disorder and often does not call for treatment. In contrast, for the most severely affected patients, characterized by life- or limb-threatening hemorrhages, more aggressive Replacement Therapy (RT) as long or short-term prophylxis may be required. AimWithin the frame of the Seven Treatment Evaluation Registry we have prospectively collected large numbers of treatments for spontaneous bleeding episodes and evaluted schedules and side-effects. Clinicaltrials.gov identifier: NCT01269138. ResultsAs of May 2011, 64 evaluable spontaneous bleedings (managed in 16 haemophilia treatment centres, 11 countries), were observed in 40 FVII-deficient subjects (25 females and 15 males) with residual FVII coagulant activity (FVIIc) levels between <1% and 20% (90% of patients had FVIIc below 5% of normal). Bleeding episodes were grouped into the following categories: 1. CNS + GI (n=2+4), 2. Hemarthroses (n=23), 3. Muscle hematomas (n=6), Epistaxis (n=4), Gum bleeding (n=7), Menorrhagia (n=11), Other (n=7) (hemorrhoidal n=2, subcutaneous hematomas n=2, easy bruising n=1, hematuria n=1, hemoperitoneum n=1). Recombinant FVIIa was given to treat 47 episodes, plasma derived FVII (pdFVII) concentrates 7, Prothrombin Complex Concentrate (PCC) 3 and Fresh Frozen Plasma (FFP) 7 (Table 1). No thrombosis episodes were reported during the thirty-day follow up.Table 1Type of Bleeding, Replacement Therapy (RT) schedules and outcomeBleedsnRTRT daysn. of dosesTotal dose range (μg/Kg IU/Kg ml/Kg)OutcomeCNS & GI6rFVIIa 31–41–8rFVIIa 160-240median 160Excellent 1 P.Effective 2pdFVII 2pdFVII 15-60–P.Effective 1 Effective 1FFP 1FFP 2–Effective 1Hemarthrosis23rFVIIa 221–21–7rFVIIa 18 – 110060Excellent 19 Effective 3PCC 1PCC 38–Excellent 1Hematomas (muscle & subcut.)8rFVIIa 41–61–12rFVIIa 54- 8066Excellent 3 Effective 1pdFVII 1pdFVII 56–Excellent 1PCC 2PCC 30–Excellent 1 n.e. 1FFP 1FFP 72–Effective 1Menorrhagia11rFVII 101–61–8rFVII 20 – 12041Excellent 5 Effective 5pdFVII 1pdFVII 135Effective 1Epistaxis & Gum bleeding12rFVIIa 511–3rFVIIa 27- 18071Excellent 4 Effective 1pdFVII 4pdFVII 21-5644Excellent 3 Effective 1FFP 3FFP 1.8-122.6Effective 3Other5rFVIIa 31-111-52rFVIIa 33-1716†33Excellent 1 Effective 2pdFVII 1pdFVII 18–Excellent 1FFP 1FFP 31–P.Effective 1*patient treated for severe hemoperitoneum; P.Effective:Partly Effective; n.e.: not evaluable ConclusionTreatment schedules and outcomes depend on the clinical setting. As for the severest bleeds (CNS and GI), on demand RT is probably not the best choice and prophylaxis should be considered as first line option especially in babies and children. Hemarthroses can be successfully treated for one day only; the number of doses used vary (from 1 to 7) as variable is the total dose of rFVIIa (from 35 to 210 μg/Kg/bw, mean 73.7, median 60) but an average intermediate dose of 60 μg/Kg/bw, possibly split in two doses, seems appropriate. The same holds for muscle and subcutaneous hematomas, always with one-day treatment schedule. RT protocols for menorrhagia varied either in terms of duration or rFVIIa total dose (1 to 6 days, total rFVIIa dosing ranging from 20 to 135 μg/Kg/bw, mean 88, median 40); treatment duration, however, did not appear to influence the outcome as one day RT showed the same efficacy as multiple days schedules. Successful RT for gum bleeding and epistaxis required treatment for one day only with doses of rFVIIa ranging from 27 to 180 μg/Kg/bw (mean 87.8, median 71) and of pdFVII ranging from 21 to 56 IU/Kg/bw (mean 41.5, median 44.5). Others bleed management were reported (hemorrhoidal, hematuria, easy bruising, peritoneal bleeding) but numbers do not allow to draw any conclusion as is the case for treatments carried out with FFP and PCCs. Disclosures:Knudsen:Novonordisk: Employment.