Caregiver Knowledge of and Attitudes Toward the Levonorgestrel-Containing Intrauterine Device for the Treatment of Heavy Menstrual Bleeding in Adolescents and Young Adults.

STUDY OBJECTIVE: We evaluated caretaker knowledge of and attitudes toward the levonorgestrel-containing intrauterine device (L-IUD) as a treatment option for adolescents and young adults with heavy menstrual bleeding. DESIGN: A survey assessed demographic characteristics, menstrual history, perception of the L-IUD, and knowledge of the indications, risks, and benefits of the L-IUD. SETTING: Participant recruitment occurred in the offices of a pediatric gynecologist, pediatric hematologist, and adolescent medicine physician in a hospital-based practice in New York. PARTICIPANTS: English-speaking caretakers of patients with a chief concern of heavy menstrual bleeding (<21 years old) were invited to participate. INTERVENTIONS: Electronic and paper surveys were administered prior to seeing the physician. MAIN OUTCOME MEASURES: The primary outcome was participant willingness to allow their daughter to use the L-IUD for heavy menstrual bleeding. Additional outcomes were explored by calculating a mean knowledge score and conducting a descriptive analysis of the perception questions. RESULTS: Forty surveys were included. Seventy percent of participants said they would allow their daughter to use birth control pills for heavy menstrual bleeding, whereas only 10% said the same of the L-IUD. The mean knowledge score was 73.3% (±15.7). Sixty-five percent of participants expressed the need for additional information on the L-IUD. CONCLUSION: Caretaker acceptance of the L-IUD as treatment for their daughter with heavy menstrual bleeding is limited. Although baseline knowledge was high, many indicated needing additional information. Because heavy menstrual bleeding can negatively impact quality of life, potential caretaker bias must be addressed to ensure full access to this highly effective treatment option.

Use of global assays to understand clinical phenotype in congenital factor VII deficiency.

Congenital factor VII (FVII) deficiency is characterized by genotypic variability and phenotypic heterogeneity. Traditional screening and factor assays are unable to reliably predict clinical bleeding phenotype and guide haemorrhage prevention strategy. Global assays of coagulation and fibrinolysis may better characterize overall haemostatic balance and aid in haemorrhagic risk assessment. We evaluated the ability of novel global assays to better understand clinical bleeding severity in congenital FVII deficiency. Subjects underwent central determination of factor VII activity (FVII:C) as well as clot formation and lysis (CloFAL) and simultaneous thrombin and plasmin generation (STP) global assay analysis. A bleeding score was assigned to each subject through medical chart review. Global assay parameters were analysed with respect to bleeding score and FVII:C. Subgroup analyses were performed on paediatric subjects and subjects with FVII ≥ 1 IU dL(-1). CloFAL fibrinolytic index (FI2 ) inversely correlated with FVII:C while CloFAL maximum amplitude (MA) and STP maximum velocity of thrombin generation (VT max) varied directly with FVII:C. CloFAL FI2 directly correlated with bleeding score among subjects in both the total cohort and paediatric subcohort, but not among subjects with FVII ≥ 1 IU dL(-1) . Among subjects with FVII ≥ 1 IU dL(-1), STP time to maximum velocity of thrombin generation and time to maximum velocity of plasmin generation inversely correlated with bleeding score. These preliminary findings suggest a novel potential link between a hyperfibrinolytic state in bleeding severity and congenital FVII deficiency, an observation that should be further explored.

Heavy menstrual bleeding in adolescents: hormonal or hematologic?

Adolescence in girls is marked by a host of physical and psychological changes including those associated with menstruation. Heavy menstrual bleeding is one of the most commonly encountered medical problems during transition from childhood to adulthood. Although common, it is likely underreported given that the definition is dependent upon personal experience and influenced by their perception of "normal". Anovulatory cycles related to an immaturity of the hypothalamic pituitary ovarian axis seems to be common, however bleeding disorders such as coagulation factor deficiencies including von Willebrand disease, and quantitative and qualitative abnormalities of platelets must be ruled out. Other medical conditions such as endocrinopathies including diabetes mellitus, Cushing syndrome, polycystic ovarian syndrome, hypothyroidism, chronic hepatic and renal disease, anatomical uterine anomalies, pregnancy, obesity, medications causing hyperprolactinemia must also be considered. Management is based on the presence of hemodynamic instability and acuity of presentation. Treatment options include the use of combined oral contraceptive pills and antifibrinolytic agents; levonorgesterel impregnated intrauterine devices and or treatment of the specific underling bleeding disorder or endocrinopathy. Ongoing management needs to be accomplished through a multi disciplinary team approach in a comprehensive care setting with an adolescent gynecologist, hematologist, pediatrician, and nutritionist involved in the program for a better outcome of this problem.

Power Doppler sonography in the diagnosis of hemophilic synovitis--a promising tool.

BACKGROUND: Recurrent hemarthroses in hemophilia results in synovitis and joint arthropathy. Primary prophylaxis when universally instituted at current doses can prevent joint deterioration but is expensive. Alternatively, the selective implementation of prophylaxis would require a more sensitive tool for detecting synovitis than possible with clinical surveillance or plain radiographs. Magnetic resonance imaging (MRI) is such a tool and is utilized for the evaluation of hemophilic joint disease (HJD). However, it is expensive, and requires sedation in younger children precluding its utility for monitoring of synovitis. Ultrasonography (USG) with power Doppler (USG-PDS) has been utilized to detect and quantitate synovial vascularity in other arthritides and could provide an equally effective but less costly tool for HJD, particularly in children who would not require sedation. OBJECTIVES: To determine whether USG-PDS is comparable to MRI in the evaluation of hemophilic synovitis. PATIENTS: A prospective cohort of 31 subjects including 33 joints (knees, elbows, ankles) underwent dynamic contrast enhanced (DCE)-MRI and USG-PDS. RESULTS: USG-PDS measurements of synovial thickness(r = 0.70, P < 0.0001) and synovial vascularity (r = 0.73, P < 0.0001) correlated strongly with those obtained with DCE-MRI. A cutoff of PDS intensity of 1.3 decibels (dB) per mm(2) was found to yield a sensitivity of 100% and a specificity of 94.1% in 17 joints with/without a history of hemarthroses. Pettersson radiographic scores correlated significantly with synovial thickness in adults but not children. CONCLUSIONS: Our data suggest that USG-PDS may be an inexpensive and easily implemented imaging tool for detecting hemophilic synovitis and could be useful in tailoring effective prophylaxis.

Rare inherited disorders of fibrinogen.

Fibrinogen, a hexameric glycoprotein encoded by three genes - FGA, FGB, FGG - clustered on chromosome 4q is involved in the final steps of coagulation as a precursor of fibrin monomers required for the formation of the haemostatic plug. Inherited disorders of fibrinogen abnormalities are rare and not as well clinically characterized as some other inherited bleeding disorders. To characterize the clinical manifestations, molecular defects and treatment modalities of these rare disorders, a Medline search from January 1966 to September 2007 for these disorders reported in large studies and registries was undertaken. Inherited fibrinogen disorders can manifest as quantitative defects (afibrinogenemia and hypofibrinogenemia) or qualitative defects (dysfibrinogenemia). Quantitative fibrinogen deficiencies may result from mutations affecting fibrinogen synthesis, or processing while qualitative defects are caused by mutations causing abnormal polymerization, defective cross-linking or defective assembly of the fibrinolytic system. Clinical manifestations vary from being asymptomatic to developing catastrophic life-threatening bleeds or thromboembolic events. Management of bleeds includes use of purified plasma-derived concentrates, cryoprecipitate or fresh frozen plasma. Use of some of these products carries risks of viral transmission, antibody development and thromboembolic events. Establishment of registries in Iran, Italy and North America has fostered a better understanding of these disorders with an attempt to explore molecular defects. Rare Bleeding Disorder Registries developed through the United States and international efforts hopefully will encourage development and licensure of safer, effective products.

Exemestane: a milestone against breast cancer.

Rapid advances in the treatment of breast cancer, especially in the form of hormone therapy have truly increased the hope of longer and better disease-free survival for these patients. Exemestane, a third generation aromatase inhibitor has been extensively evaluated in metastatic as well as adjuvant therapy of breast cancer. It has also been evaluated for its safety profile, especially on bone and lipids. Exemestane provides hope to the patients with breast cancer both in early and metastatic disease. This review analyzes all the aspects of exemestane therapy.

Rare Bleeding Disorder Registry: deficiencies of factors II, V, VII, X, XIII, fibrinogen and dysfibrinogenemias.

A North American registry for rare bleeding disorders [factor (F)II, factor (F)VII, factor (F)X, factor (F)V, factor (F)XIII, fibrinogen deficiencies and dysfibrinogenemias] was established to gather information about disease prevalence, genotyping frequency, diagnostic events, clinical manifestations, treatment and prophylaxis strategies, as well as disease- and treatment-related complications. Questionnaires were sent to 225 hemophilia treatment centers in the USA and Canada. Among 26% of responding centers, 294 individuals [4.4% of the registered children (200/4583) and 2.4% of adults (94/3809)] were diagnosed with one or more of the rare bleeding disorders (RBDs) included in this survey. The ethnic distribution for each disorder paralleled that of the general US population with the exception of the disproportionately large number of Latinos with FII deficiency. Only 5.4% of affected individuals were genotyped. An abnormal preoperative bleeding screen most often led to diagnosis. The most common coagulopathy was FVII deficiency; however, 40% of homozygous patients were asymptomatic. FX and FXIII deficiencies caused the most severe bleeding manifestations. Among all RBDs, the most common sites of bleeding were skin and mucus membranes. Multiple products were used to treat hemorrhage; however, half of the bleeding episodes required no therapy. The majority of patients suffered no long-term complications from hemorrhage. Treatment-related complications included viral seroconversion, anemia, allergic reactions and venous access device-related events. This registry provides the most comprehensive information to date about North American individuals with RBDs and could serve as an important resource for both basic scientist and clinician.

A case of orthodeoxia caused by an atrial septal aneurysm.

Platypnea-orthodeoxia is an uncommon syndrome that may occur due to the postpneumonectomy state, cirrhosis of the liver, recurrent pulmonary embolism, and intracardiac shunting. We describe a patient who was found to have a positional change in desaturation after being admitted for dehydration. Workup revealed an atrial septal defect with aneurysm. Following surgical repair, the orthodeoxia resolved. Different mechanisms explain positional desaturation, such as atriovenous malformations at the lung base of cirrhotic patients. In an atrial septal defect, the increased shunting of blood across a malformed septum in an upright position may cause orthodeoxia. This case highlights the necessity of heightened awareness of this syndrome and the need for documenting orthostatic changes in cases of severe hypoxemia.

Annexin II and regulation of cell surface fibrinolysis.

The regulated function of the fibrinolytic system is fundamental to the solubilization of fibrin-containing thrombi and to a number of other biologic processes. In recent years, several receptors, which serve to localize proteolytic activity on the cell surface, have been identified on endothelial cells, blood cells, neuronal cells, and tumor cells. One such receptor is annexin II, a calcium- and phospholipid-binding protein that serves as a profibrinolytic co-receptor for tissue plasminogen activator and plasminogen on endothelial cells. Accumulating evidence suggests that impaired cell surface fibrinolytic assembly could lead to progressive atherothrombotic disease. In addition, dysregulation of annexin II expression in acute promyelocytic leukemia is an important mechanism for the bleeding diathesis associated with this malignancy.