Puberty menorrhagia secondary to inherited bleeding disorders

Abstract

The first patient, an 18-year-old girl suffering from Fechtner syndrome with macrothrombocytopenia, deafness and end-stage renal failure, required peritoneal dialysis and long-term steroid therapy. Her platelet count remained below 50 × 109/L despite splenectomy. She developed irregular and prolonged menstrual bleeding 1 year after her menarche, which was initially controlled with combined oral contraceptives (COC). At age 16, her periods became heavy and prolonged, resulting in severe anemia despite repeated transfusion. As her condition could not be controlled, total abdominal hysterectomy was eventually performed. The operation was complicated by subrectus hematoma, which subsided spontaneously. The second patient was a 14-year-old girl who developed prolonged and heavy menstrual flow 2 years after menarche. She had intracranial hemorrhage secondary to factor VII deficiency soon after birth, resulting in right hemiparesis, complex partial seizures and mild mental deficiency. She had severe bleeding from the mucous membrane requiring frequent and repeated hospitalization, plasma transfusion and recombinant factor VIIa infusion. Her menstruation was very heavy and difficult to control, and a 6-month course of subcutaneous injection of gonadotropin-releasing hormone analog (GnRH-a) had to be given to suppress menstruation. Her subsequent menstruation was still uncontrollable despite repeated intravenous injection of conjugated estrogen and transfusion of clotting factors. She finally underwent a hysterectomy and the operation was uneventful. Both Fechtner syndrome and factor VII deficiency are rare types of inherited coagulation disorders with intractable spontaneous mucous membrane type of bleeding. Fechtner syndrome is characterized by macrothrombocytopenia while factor VII deficiency is paradoxically associated with thrombosis. There is no effective curative treatment and the control of bleeding requires the replenishment of the deficient coagulation factors. These factors have a very short half-life, requiring repeated and frequent infusion. Bleeding disorder is a relatively common cause of menorrhagia in adolescent girls and management is difficult as the underlying coagulation problem can only be temporarily and partially corrected (1,2). Medical treatment is unlikely to work unless long-term amenorrhea can be achieved. Although amenorrhea can be achieved with continuous COC, breakthrough bleeding is common and can be heavy. The presence of epilepsy and the increased risk of thrombosis in the second patient further complicated its use. Depo-Provera should not be used as it requires intramuscular injection. Danazol carries significant androgenic side-effects, and is not tolerated by adolescent girls. GnRH-a therapy is effective in producing amenorrhea. However, suppression of sex hormone production hinders secondary sexual development and causes exaggerated osteoporosis in adolescent girls. Although “add-back” therapy may minimize the risk of osteoporosis, its effect on secondary sexual development is unknown, especially when the ideal dosage for adolescents has not been delineated (3). Although the levonorgestrel intrauterine system (LNG-IUS) can induce amenorrhea, the initial prolonged breakthrough bleeding can be heavy in patients with coagulation disorder. The relatively large size of the device also makes it inappropriate for the small uterus in adolescents. Its use is not advisable in patients on long-term steroid therapy as in our first patient. Endometrial ablation is also not an ideal treatment option as complete amenorrhea occurs in only 60% of cases, and the rate tends to decrease with time and recurrence rate is high in young girls (4). Moreover, pregnancy is contraindicated after the procedure and is associated with significant risk of postabortal or postpartum hemorrhage. Despite the immediate surgical risk, hysterectomy appears to be the only effective treatment of choice in this situation. Increased risk of bleeding is the major concern (5), but this can be minimized by perioperative transfusion of platelet concentrates, fresh frozen plasma and clotting factor as indicated. The operation should be performed by experienced surgeons with meticulous control of bleeding. Although laparoscopic surgery is reported to be associated with minimal bleeding, it is not clear whether the use of electrosurgery can control bleeding adequately in a patient with coagulation defect. We chose to perform the operation by the conventional method as it allows suture ligation to ensure adequate hemostasis. The management of severe menorrhagia in adolescents secondary to coagulation disorder carries a therapeutic dilemma. Both clinicians and patients are reluctant to resort to hysterectomy at this young age despite the lack of effective long-term treatment. When curative therapy for the underlying disorder is unavailable, hysterectomy should be considered early to avoid the risk of bleeding and to improve the quality of life.