Lakshmi V. Srivaths

Oral Tranexamic Acid versus Combined Oral Contraceptives for Adolescent Heavy Menstrual Bleeding: A Pilot Study

STUDY OBJECTIVE To compare the efficacy of oral tranexamic acid (TA) with combined oral contraceptives (COC) in reducing menstrual blood loss (MBL) and improving quality of life in adolescent heavy menstrual bleeding (HMB). DESIGN, SETTING, AND PARTICIPANTS A prospective randomized crossover trial with 17 postmenarchal girls aged 21 years and younger with HMB who were seen at our institution. INTERVENTIONS Patients were randomized to group A (TA arm) or group B (COC arm), each for 3 cycles, with crossover to the second arm after 1-month washout. MAIN OUTCOME MEASURES The primary end points were difference in improvement in MBL and QOL, from baseline to end of each therapy. RESULTS Seventeen patients were enrolled (mean age 14.2 years, range 11.7 to 16.8 years). Nine patients completed both arms; 8 patients withdrew from the study due to adverse events or noncompliance. Compared with baseline, significant improvement (P < .05) was demonstrated by TA and COC in MBL (mean Pictorial Blood Assessment Chart score decrease: TA, 536.4; COC, 430.6) and quality of life (mean Pediatric Quality of Life Inventory(TM) version 4.0 Generic Scales score increase: TA, 15.6; COC, 16.75), but no significant difference was noted between TA and COC (P > .05). There was statistically significant reduction in the length of menstrual cycle for COC only (mean reduction 5.3 days; P = .04) and not for TA (P = .18). Ten patients (58%) experienced adverse events that were possibly drug related (TA: n = 3, 30%; COCP: n = 7, 64%). CONCLUSION In this pilot study, oral TA appeared as efficacious as COC in the management of adolescent HMB by reducing MBL and improving quality of life.

Risk factors and co-morbidities in adolescent thromboembolism are different than those in younger children

INTRODUCTION In adolescent thromboembolism (TE), multiple risk factors (RFs) and co-morbidities (CMs) are reported, though overall prevalence has not been evaluated. We hypothesized that the spectrum of RFs/CMs in adolescent TE differs from children overall and sought to review Texas Childrens Hospitals experience. PATIENTS/METHODS Medical records of adolescents aged 12-21years, diagnosed with arterial or venous TE (AT/DVT) from 2004 to 2014, were retrospectively reviewed and analyzed with IRB approval. RESULTS Sixty-four adolescents (median age 16, range 12-20years) met study criteria. Fifty-seven (89%) had DVT and six (9%) had AT. Associated RFs/CMs included obesity (47%), CVC (27%), infection (27%), surgery (27%), autoimmune disease (19%), immobility (22%), anatomical abnormality (20%), cancer (8%), estrogen therapy (6%), tobacco use (6%), trauma (3%), inherited thrombophilia (19%), and other medical conditions (11%). Fifty-two (81%) had ≥2 RFs/CMs. Therapy included anticoagulants, antiplatelet agents, and interventional therapy. Of those with follow-up imaging, 49 had complete or partial resolution, 5 had no change and 4 had progression. Fourteen (22%) had recurrent TE. The majority with recurrent TE (79%) had ≥2 RFs at initial diagnosis. Mean time to recurrence was 4.80years; time to recurrence was shorter for occlusive TE (p=0.026). CONCLUSION Adolescent TE is often multi-factorial with the majority having ≥2 RFs at diagnosis, suggesting the need for detailed evaluation for RFs in this population, which may enable optimal management including thromboprophylaxis, and institution of RF-modifying strategies to prevent occurrence/recurrence.

Platelet function defects in adolescents with heavy menstrual bleeding

Platelet function defects (PFD) are reported to occur frequently in adult women with heavy menstrual bleeding (HMB). Few studies on adolescent HMB report varying incidence rates (2–44%) for PFD. We reviewed our institutional experience in detecting and managing PFD in adolescent HMB. Postmenarchial girls and adolescents with HMB seen at our institution undergo a comprehensive bleeding disorder work‐up by paediatric haematology and paediatric gynaecology providers. Whole blood platelet aggregometry (WBPA) is performed as a second tier test after excluding thrombocytopaenia, coagulation factor deficiencies and Von Willebrand disease (VWD). We retrospectively reviewed the medical records of adolescents with HMB seen between June 2009 and November 2010, as approved by the Institutional Review Board. Patient demographics, clinical features, laboratory results, therapy details and patient outcome information were analysed. Overall, 114 postmenarchial girls and adolescents with HMB were evaluated; 68 patients (59%) had WBPA study performed. Nineteen patients (28%) had at least one aggregation or secretion defect; 12 (18%) had two or more such defects. Treatment included hormonal therapy (13/19; 68%), antifibrinolytic agents (8/19; 42%) and intra‐nasal DDAVP (3/19; 16%). Thirteen patients (81%) had improved outcome (median follow‐up – 15.6 months; range of 1–66 months). In this study, PFD were identified in nearly one‐third of girls with HMB, with the majority of these having two or more defects as identified by WBPA. Further prospective studies are needed to better define the prevalence and address appropriate management of HMB and other bleeding complications of PFD in adolescents.

Co-inheritance of mild hemophilia A and heterozygosity for type 2N von Willebrand disease: A diagnostic and therapeutic challenge

Hemophilia A and von Willebrand disease are the two most common inherited bleeding disorders. Despite their frequency, however, there are very few reports of co‐inheritance of the two disorders. We present the first report of a patient with mild hemophilia A and heterozygosity for type 2N von Willebrand disease (VWD). We discuss the patients phenotype and highlight the diagnostic and therapeutic challenges caused by this co‐inheritance. Pediatr Blood Cancer 2014; 61:1888–1890.

Haemophilia B acquired from liver transplantation: a case report and literature review

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Pediatric Acquired von Willebrand Syndrome in Cardiopulmonary Disorders: Do Laboratory Abnormalities Predict Bleeding Risk?

There are conflicting reports on whether or not laboratory abnormalities in pediatric acquired von Willebrand syndrome (AVWS) predict bleeding manifestations in patients with cardiopulmonary disorders (CPD). We retrospectively reviewed charts of patients with AVWS and CPD (n=16) seen at Texas Children’s Hospital from 2003 to 2012. The most common CPD were valve stenoses, ventricular septal defects, and pulmonary hypertension. All patients had loss of high molecular weight multimers. Fifteen (94%) patients presented with bleeding symptoms, with menorrhagia and epistaxis being the most common. Von Willebrand ristocetin cofactor activity (VWF:RCo), as well as the use of anticoagulant or antiplatelet medication, did not predict bleeding manifestations (P=0.70 and 0.84, respectively). VWF:RCo/VWF antigen (Ag) ratio of <0.7 was significantly associated with presence of bleeding symptoms. All patients who had complete repair of their cardiac defect experienced normalization of VWF multimers and VWF:RCo/Ag ratio, as well as bleeding symptom resolution. We conclude that increased bleeding risk is associated with low VWF:RCo/Ag ratio in pediatric AVWS due to CPD. However, other laboratory abnormalities such as VWF:RCo level and qualitative multimer analysis, do not appear to predict bleeding. Future studies exploring quantification of multimer loss may be helpful in further assessing bleeding risk associations.

Differences in bleeding phenotype and provider interventions in postmenarchal adolescents when compared to adult women with bleeding disorders and heavy menstrual bleeding

Due to lack of patient/health care provider awareness causing delayed diagnosis, the bleeding phenotype and provider interventions in adolescents with heavy menstrual bleeding (HMB) and bleeding disorders (BD) may be different when compared to adults.

Heavy Menstrual Bleeding

Heavy menstrual bleeding (HMB), a common complaint in adolescent and adult women, can be due to a variety of causes ranging from anovulatory bleeding, bleeding disorders, endocrine abnormalities, infectious etiology, pregnancy/miscarriage, and anatomic abnormalities of the reproductive organs. Comprehensive evaluation of the patient by the gynecologist and hematologist working in conjunction will enable prompt detection of the underlying cause and timely institution of therapy. In general, HMB can be managed with hormonal therapy and general hemostatic therapy; in patients with bleeding disorders, specific hemostatic therapy directed toward the underlying disorder can be given as primary or supplemental therapy. Appropriate medical or interventional therapy for other etiologies and management of hematologic and gynecologic complications of HMB will help to improve the patient’s overall quality of life. Patient-centered efforts and use of innovative technology for HMB can enhance patient awareness and education and promote participation in their care.

Secondary Bone Marrow Fibrosis in Children And Young Adults: An Institutional Experience.

Secondary bone marrow fibrosis (BMF) is associated with many disease conditions in children, but its prevalence and characteristics have not been well elucidated. We present our experience with pediatric secondary BMF, in an attempt to characterize it in terms of underlying diagnoses, severity, and outcome. A retrospective chart review of patients diagnosed with secondary BMF by bone marrow aspirate and biopsy between January 1984 and April 2011 showed a total of 214 patients, the majority (67.1%) of whom had an underlying oncologic disease. At diagnosis, 87 patients (39.7%) had mild, 51 (23.3%) had moderate, and 33 (15.1%) had marked BMF; it was not quantified in 48 (21.9%) patients. An underlying oncologic disease was more frequently associated with marked fibrosis compared with hematologic and miscellaneous diagnoses. Follow-up posttreatment bone marrow aspirate assessments were available for 117 patients. The outcome ranges from worsening of fibrosis to complete resolution. A majority of these children (N=70/117, 60%) showed complete resolution of fibrosis. Of note, 27 patients had marked fibrosis at initial diagnosis and 16 (60%) of them showed complete resolution. These findings underscore the importance of appropriate treatment of the underlying disorder in reversing secondary BMF. Ours is the largest series of pediatric secondary BMF reported.

Prothrombotic Risk Factors and Preventive Strategies in Adolescent Venous Thromboembolism.

Venous thromboembolism (VTE) in adolescents is a serious condition that requires prompt recognition and optimal management to prevent mortality and long-term morbidity. Adolescents account for a large proportion of cases of VTE in children. As teenagers transition from childhood to adulthood, they are at risk of developing medical conditions and exposure to risky habits that predispose them to VTE. This review focuses on the variety of risk factors and comorbidities seen in adolescent VTE and takes a quick look into risk-based preventive strategies for primary and secondary prevention.