Vaginal Bleeding and Hemorrhagic Prepatellar Bursitis in a Preadolescent Girl,Possibly Related to Fluoxetine

To The Editor:

In recent years, the use of psychiatric drugs such as serotonin reuptake inhibitors (SSRIs) has increased among children and adolescents (Whittington et al. 2004). SSRIs are preferred as the first-line treatment for depression and anxiety disorders in children and adolescents, and are thought to be reliable drugs compared with other psychotropic drugs. In addition to their common side effects such as nausea, vomiting, diarrhea, agitation, headache, insomnia, somnolence, anxiety, and sexual dysfunction, SSRIs have also been associated with bleeding complications (Goldberg 1999). Case reports have described adult and adolescent patients with various bleeding disorders (e.g., ecchymoses, purpura, epistaxis, gastrointestinal bleeding, intracranial bleeding, bleeding during surgery), whereas in a child, bleeding is a rare condition related to SSRI treatment (Weinrieb et al. 2005). Here, we present a preadolescent girl who developed vaginal bleeding and hemorrhagic prepatellar bursitis after treatment with fluoxetine for her anxiety problems.

Case Report

This patient was referred to our outpatient unit at the age of 11 years for treatment of some anxiety symptoms. Her psychiatric examination revealed obsessive-compulsive disorder (OCD) and social anxiety disorders. Fluoxetine was administered at 10 mg/day. This dose was well tolerated, and was increased to 20 mg/day after 1 week. Three weeks later, the patient was sent to our Department of Child and Adolescent Psychiatry from the Department of Physical Medicine and Rehabilitation for spontaneous bruises on her arms and legs, hemorrhagic prepatellar bursitis, and vaginal bleeding of 10 days' duration. This patient had no personal or family history of a bleeding disorder, trauma, or self-injurious behavior. She had not had any bleeding suggesting the start of her menstrual cycling. Her developmental history and psychometric assessment were within normal limits. Her complete hepatic function tests, blood cell count, prothrombin time, bleeding time, partial prothrombin time, activated partial prothrombin time, international normalized ratio (INR), clotting time, and fibrinogen level were within the normal limits. A genital ultrasound revealed no abnormality, and showed normal flow on color Doppler. Physical examination revealed no abnormality other than vaginal bleeding, edema, and erythema on the anterior of the right knee, and the patient's gynecological examination revealed that the bleeding was not menstrual bleeding. The patient also was unable to flex her knee beyond 50 degrees because of pain. Other possible causative factors were excluded; therefore, her symptoms were considered to be related to fluoxetine. She did not take any other medication. Her symptoms completely disappeared after fluoxetine discontinuation and did not reoccur during the next 6 months of clomipramine treatment at 50 mg/day.

Discussion

The accepted mechanism underlying these adverse effects is that SSRIs limit uptake of blood serotonin by platelets. Because platelets are unable to synthesize serotonin, this leads to a lower concentration of serotonin within the platelets, and because one of the functions of serotonin within the platelets is to promote platelet aggregation, a decreased amount of serotonin in the platelets may increase the risk of abnormal bleeding. SSRIs also appear to modify the formation of platelet plugs, as well as the responsiveness of peptide-induced activation of platelets through stimulation of the thrombin receptor (Hergovich et al. 2000). Several other mechanisms for SSRI-related bleeding diathesis are blockade of calcium mobilization, inhibition of nitric oxide synthase, and drug-induced immune thrombocytopenia (Skop and Brown 1996; Meijer et al. 2004). Van Walraven et al. found that higher doses of SSRIs treatment are related to more bleeding problems (van Walraven et al. 2001). We could not find any abnormal standard laboratory results in our case, which is consistent with previous reports of SSRI-induced bleeding. There are several case reports about SSRI-related vaginal bleeding and other bleeding problems in adolescent or adult subjects (Smith and Robinson 2002; Boricević Marsanić and Kusmić 2010). For example, Dalton et al. found in a large cohort study an increased in risk of upper gastrointestinal bleeding in patients using SSRIs (Dalton et al. 2003). Another recent retrospective study in orthopedic patients undergoing surgery reported an association between the use of serotonergic antidepressants and an increased risk of bleeding and subsequent need for blood transfusion during orthopedic surgery, and attributed this increased risk to inhibition of serotonin-mediated platelet activation (Movig et al. 2003).

To our knowledge, there is no report of vaginal bleeding and hemorrhagic prepatellar bursitis caused by treatment with fluoxetine in children or preadolescent girls. Our patient was a preadolescent girl whose menstrual bleeding had not begun yet. In addition, ıt is not clear why bleeding did not reemerge with clomipramine. Long-term consequences of abnormal bleeding associated with SSRIs is unknown. SSRIs should be used with caution by clinicians in children and adolescents, because of adverse effects.