Evaluation of bleeding symptoms and laboratory parameters in sisters of patients with hemophilia A and B

Intraduction and purpose: Hemophilia is an X chromosome linked hereditary bleeding disorder, inherited recessively, caused by deficiency of factor 8 or factor 9 and mostly men are affected. However, mothers and sisters of affected men are heterozygous carriers of hemophilia. Hemophilia is a well known bleeding disorder in men, but it is seldom recognized in female carriers of hemophilia. Whereas female carriers might not only have an increased tendency of bleeding , but bleeding symptoms may be frequent and severe. The aim of this study is evaluation of clotting factor levels and determination tendency of bleeding in sisters and engage attention of phsysicians and families to prevent prolonged bleeding especially before medical interventions and implementation of prophylactic therapy. Materials and Methods: This study is designed to determine labrotory and clinical tendency of bleeding in sisters. Forty six female who have menstural cycles and have at least one hemophilia A or B patients in their family were included in the study. Forty three female who were healthy and have no hemophilia A and B patients in their family were choosen for control group. For these purpose laboratory parameters aPTT, complete blood count , vwf, bleeding time and factor 8 were studied in sisters of patients with hemophilia A patients , factor 9 for sisters of patients with hemophilia B were analyzed and compared with control group. Demographic features of sisters of patients with hemophilia, characteristics and severity of the disease in the affected family and number of children obligatory carriers have , spontaneous and induced prolonged bleeding tendency interrogated by a detailed questionnaire. This interrogation was also applyed to control group. Results: Forty six sisters of patients with hemophilia were included the study. Thirty nine (%84,8) of them were sisters of patients with hemophilia A and 7 (%15,2) of them were sisters of patients with hemophilia B. Six (%13) of them have a mild hemophilia, 4 (%8,7) of them have moderate hemophilia and 36 (%78,3) of them have severe hemophilia in their family. Laboratory results of sisters of a hemophilia patient were compared with the control group. The mean clotting factor levels were significantly decreased in sisters of patients with hemophilia ( 60,13±37,91%, 80,04±23,35 % respectively , p:0,004). Factor 8 levels were significantly decreased ( 53,77±32,07 %,75 and ,06±20,55 % respectively , p:0,001) in sisters of patients with hemophilia compared with control group. There was no significant difference between two group of factor 9 levels (respectively 90,36±50,41%, 110,71±15,02%, p:0,361). aPTT was found significantly prolonged in sisters of patients with hemophilia compared with control group. (respectively 30,5±4,08 sn, 27,2±3,13 sn, p: 0,000). Spontaneous nose bleedings were defined in 13 (%28,3) sisters of patients with hemophilia and in 7 (%16,3) of controle group. Spontaneous cutaneous bruising was defined in 13 (%28,3) of sisters of patients with hemophilia and 8 (%18,6) of controle group. Prolonged bleeding longer than 10 minutes after minor traumas was stated by 7 (% 15,2) of sisters of patients with hemophilia versus none of controle group . Requirement of additional medical treatment for prolonged bleeding after tooth extraction was noted in 12 (% 44,4) of sisters of patients with hemophilia who have experienced tooth extraction compared with 2 (%6,5) of 31 who have experienced tooth extraction of controle group. Requirement of additional medical treatment for prolonged bleeding after surgery was encountered in 6 (%35,1) of 17 sisters of patients with hemophilia who have experienced surgery compared with 2 (%9,1) of 22 who have experienced surgery of controle group. Postpartum bleeding longer than 6 weeks was stated by 3 (% 25) of 12 who gave birth of sisters of patients with hemophilia. Menorrhagia longer than 7 days was reported by 15 (%32,6) of sisters of a hemophilia patient whereas one of controle group. Clotting factor levels was measured between % 5-40 in 21 (% 45,7) , % 41-60 of 7 and above % 61 in 18 of 46 sisters of patients with hemophilia. There was significant correlation between clotting factor levels and spontaneous nose bleeding, oral mucosal bleeding and gum bleeding (p<0.05) . Sisters of patients with hemophilia experienced more bleeding after minor traumas, requirement of additional medical treatment for prolonged bleeding after tooth extraction, menorrhagia and prolonged postpartum bleeding with respect to controle group independent from level of clotting factor (p<0.05). Spontaneous nose bleeding (p:0,176), cutaneous bruising ( p:0,284) and prolonged bleeding after surgery (p:0,260 ) was found no significance between two groups. Association between severity of hemophilia in the family and clotting factor levels was found no significance (p:0,398). There were no relationship between severity of hemophilia in the family and bleeding tendency except spontaneous nose bleeding. In the conclusion ; clotting factor levels were decreased in the sisters of patients with hemophilia and they experience more frequently prolonged bleeding after minor traumas and requirement of additional medical treatment for prolonged bleeding after tooth extraction menorragia and prolonged postpartum bleeding .Therefore measurement of clotting factor levels and implementation of medical interventions is considarable to prevent prolonged bleeding for obligate and possible carriers of hemophilia . Key words; Hemophilia, sisters of patients with hemophilia, clotting factor, bleeding tendency, severity of hemophilia in the family