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Clara Lo, MD

  • Clara Y. Lo

Specialties

Hematology-Oncology

Work and Education

Professional Education

New York Medical College Registrar, Valhalla, NY, 06/01/2005

Residency

UCI at Children's Hospital Orange County Pediatric Residency, Orange, CA, 06/30/2008

Fellowship

Stanford University Pediatric Hematology Oncology Fellowship, Palo Alto, CA, 06/30/2011

Board Certifications

Pediatric Hematology-Oncology, American Board of Pediatrics

Pediatrics, American Board of Pediatrics

Conditions Treated

Hemophilia

Platelet Disorders

All Publications

Abnormal platelet aggregation in pediatric pulmonary hypertension PULMONARY CIRCULATION Handler, S. S., Jin, J., Ogawa, M. T., Feinstein, J. A., Lo, C. 2022; 12 (3): e12104

Abstract

Endogenous prostacyclin stimulates pulmonary vasodilation and inhibits platelet aggregation. For the synthetic analog treprostinil, used in the treatment of pulmonary hypertension (PH), conflicting, anecdotal evidence exists regarding its effects on clinically relevant platelet function. This study investigated whether treprostinil therapy results in inhibition of platelet aggregation in pediatric PH patients. This is a single institution, prospective, cohort study. Pediatric patients 18 years of age on medical therapy for PH underwent platelet function testing by light transmission aggregometry with U-46619-a stable analog of endoperoxide prostaglandin H2, exhibiting properties similar to thromboxane A2 (TXA2). Results were compared for those on continuous treprostinil therapy (TRE) versus those on other, non-prostacyclin therapies (non-TRE). Thirty-five patients were enrolled: 18 in theTRE groupand 17 in thenon-TRE group. There was no difference in platelet aggregation abnormalities between the two groups: 44% (n=8) in theTRE group and 41% (n=7) in thenon-TRE group were abnormal. Furthermore, subgroup analysis showed no difference based on treprostinil dosing. This study demonstrated similar, moderately high rates of abnormal platelet aggregation in pediatric PH patients on continuous treprostinil therapy compared to those on other, non-prostacyclin therapies. The high rate of abnormal platelet aggregation in the entire cohort, however, warrants follow-up study to identify a potential inherent risk in this population.

View details for DOI 10.1002/pul2.12104

View details for Web of Science ID 000826721400001

View details for PubMedID 35864911

View details for PubMedCentralID PMC9294293

Effect of Anticoagulant Therapy for 6 Weeks vs 3 Months on Recurrence and Bleeding Events in Patients Younger Than 21 Years of Age With Provoked Venous Thromboembolism: The Kids-DOTT Randomized Clinical Trial. JAMA Goldenberg, N. A., Kittelson, J. M., Abshire, T. C., Bonaca, M., Casella, J. F., Dale, R. A., Halperin, J. L., Hamblin, F., Kessler, C. M., Manco-Johnson, M. J., Sidonio, R. F., Spyropoulos, A. C., Steg, P. G., Turpie, A. G., Schulman, S. 2022; 327 (2): 129-137

Abstract

Among patients younger than 21 years of age, the optimal duration of anticoagulant therapy for venous thromboembolism is unknown.To test the hypothesis that a 6-week duration of anticoagulant therapy for provoked venous thromboembolism is noninferior to a conventional 3-month therapy duration in patients younger than 21 years of age.Randomized clinical trial involving 417 patients younger than 21 years of age with acute, provoked venous thromboembolism enrolled at 42 centers in 5 countries from 2008-2021. The main exclusions were severe anticoagulant deficiencies or prior venous thromboembolism. Patients without persistent antiphospholipid antibodies and whose thrombi were resolved or not completely occlusive upon repeat imaging at 6 weeks after diagnosis underwent randomization. The final visit for the primary end points occurred in January 2021.Total duration for anticoagulant therapy of 6 weeks (n=207) vs 3 months (n=210) for provoked venous thromboembolism.The primary efficacy and safety end points were centrally adjudicated symptomatic recurrent venous thromboembolism and clinically relevant bleeding events within 1 year blinded to treatment group. The primary analysis was noninferiority in the per-protocol population. The noninferiority boundary incorporated a bivariate trade-off that included an absolute increase of 0% in symptomatic recurrent venous thromboembolism with an absolute risk reduction of 4% in clinically relevant bleeding events (1 of 3 points on the bivariate noninferiority boundary curve).Among 417 randomized patients, 297 (median age, 8.3 [range, 0.04-20.9] years; 49% female) met criteria for the primary per-protocol population analysis. The Kaplan-Meier estimate for the 1-year cumulative incidence of the primary efficacy outcome was 0.66% (95% CI, 0%-1.95%) in the 6-week anticoagulant therapy group and 0.70% (95% CI, 0%-2.07%) in the 3-month anticoagulant therapy group, and for the primary safety outcome, the incidence was 0.65% (95% CI, 0%-1.91%) and 0.70% (95% CI, 0%-2.06%). Based on absolute risk differences in recurrent venous thromboembolism and clinically relevant bleeding events between groups, noninferiority was demonstrated. Adverse events occurred in 26% of patients in the 6-week anticoagulant therapy group and in 32% of patients in the 3-month anticoagulant therapy group; the most common adverse event was fever (1.9% and 3.4%, respectively).Among patients younger than 21 years of age with provoked venous thromboembolism, anticoagulant therapy for 6 weeks compared with 3 months met noninferiority criteria based on the trade-off between recurrent venous thromboembolism risk and bleeding risk.ClinicalTrials.gov Identifier: NCT00687882.

View details for DOI 10.1001/jama.2021.23182

View details for PubMedID 35015038

A case of acquired von Willebrand disease in severe pediatric pulmonary hypertension contributing to bleeding following reverse Potts shunt. Pulmonary circulation Sullivan, R. T., Lo, C., Martin, E., Kameny, R. J., Hopper, R. K. 2022; 12 (1): e12042

Abstract

The reverse Potts shunt is increasingly used as a palliative measure for end-stage pulmonary arterial hypertension (PAH) as a means to offload the right ventricle and improve functional status. This case report describes a child who developed significant hemothorax after reverse Potts shunt that required surgical exploration, blood product administration, and prolonged intensive care hospitalization. Despite lack of preoperative bleeding symptoms, testing revealed acquired von Willebrand disease (aVWD), with subsequent resolution of bleeding. Alterations in von Willebrand factor, including aVWD, have been reported in children with severe PAH but have not previously been associated with bleeding after reverse Potts shunt procedure. As bleeding is a recognized postoperative morbidity in PAH patients undergoing reverse Potts shunt, we highlight a potential role for preoperative testing for aVWD as perioperative factor replacement therapy may improve postoperative outcomes.

View details for DOI 10.1002/pul2.12042

View details for PubMedID 35506098

View details for PubMedCentralID PMC9052962

Pediatric acquired factor VIII deficiency presenting as hemarthrosis. Pediatric blood & cancer Daigh, L. H., Chien, M. C., Lo, C. Y. 1800: e29530

View details for DOI 10.1002/pbc.29530

View details for PubMedID 34913591

Next Generation Sequencing-Based Characterization of T Cell Receptor Repertoire of Patients with Immune Thrombocytopenia Han, P., You, X., Lo, C., Xu, L., Zhang, H., Zehnder, J. L., Zhang, B. AMER SOC HEMATOLOGY. 2019
Usefulness of anti-platelet therapy testing in children supported with a ventricular assist device. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation May, L. J., Liu, X., Tesoro, T., Yang, J., Lo, C., Chen, S., Murray, J., Rosenthal, D. N., Michelson, A. D., Almond, C. S. 2019

View details for PubMedID 31006520

Dietary Iron Deficiency Anemia in Children NUTRITIONAL ANEMIA: SCIENTIFIC PRINCIPLES, CLINICAL PRACTICE, AND PUBLIC HEALTH Lo, C., Jeng, M., Means, R. T. 2019: 96102
Platelet Characteristics and Bleeding Patterns in Children with Jacobsen Syndrome: A Single Center Report Gilbert, M., Lo, C., Andrews, J., Ohgami, R., Jeng, M. WILEY. 2017: S86
Case Report: Clinical Variation in Children With Thrombopoietin Receptor (C-MPL) Mutations: Report of 2 Cases. Journal of pediatric hematology/oncology Lo, C. n., Alvarez, E. n., Ohgami, R. S., Jeng, M. n. 2017

Abstract

Congenital amegakaryocytic thrombocytopenia (CAMT, MIM# 604498) is a rare congenital bone marrow failure syndrome which presents early in life with abnormal bleeding because of thrombocytopenia. Classically, megakaryocytes are decreased to absent in the bone marrow. The development of aplastic anemia early in childhood has led to the recommendation for early stem cell transplantation. Quantitative or loss-of-function mutations in the myeloproliferative leukemia gene (c-mpl), whose gene product functions as the thrombopoietin receptor, have been identified as causative for CAMT. Approximately 100 cases of CAMT are published in the medical literature. We describe 2 cases of CAMT who demonstrate disparate clinical courses, thereby highlighting phenotypic differences and increasing awareness of this clinical entity.

View details for PubMedID 28859041

Major Causes of Stroke in Children With Congenital and Acquired Heart Disease. Elbers, J., Lee, E., Yarlagadda, V. V., Lo, C., Hanisch, D., Lin, A., Almond, C. S., Shin, A. Y. LIPPINCOTT WILLIAMS & WILKINS. 2016
Updated analysis: central venous access device infection rates in an expanded cohort of paediatric patients with severe haemophilia receiving prophylactic recombinant tissue plasminogen activator. Haemophilia McCarthy, C. E., O'Brien, M., Andrews, J., Zoland, J. M., Macasiray, E., Wong, W., Lo, C., Glader, B., TAMARESIS, J., Jeng, M. 2016; 22 (1): 81-86

Abstract

Central venous access devices (CVADs) are used in the care of paediatric haemophilic patients with difficult peripheral access, but their use is limited by complications such as infection. We previously published our experience with monthly recombinant tissue plasminogen activator (r-tPA) administration to CVADs of haemophilic patients as an intervention for infection prophylaxis, which suggested a 10-fold decrease in infection rate compared to published rates without r-tPA.This study was conducted to assess the CVAD infection rate in an expanded haemophilia cohort receiving r-tPA over an extended period.A retrospective review was performed on patients with haemophilia who received monthly r-tPA to CVADs, with data collected from January 1, 2008 to December 31, 2012. The data were merged with the previously reported data set (collected from June 1, 1998 to December 31, 2007).Over the entire observation period, there were 46 350 CVAD days among 32 patients [26 severe factor VIII (FVIII) deficiency, six severe FIX deficiency]. Eight patients received immune tolerance therapy for inhibitors and 24 patients received prophylactic factor administration. No patients were HIV positive. Three infections were observed, with an overall infection rate of 0.06 infections per 1000 CVAD days.A low CVAD infection rate, similar to that observed in our previous study (0.04 per 1000 CVAD days), was observed in this expanded haemophilia cohort treated with prophylactic r-tPA, supporting the use of monthly r-tPA as CVAD infection prophylaxis in haemophilia patients.

View details for DOI 10.1111/hae.12772

View details for PubMedID 26248602

Neonatal Thrombocytopenia Neonatology: Clinical Practice and Procedures Lo, C., Glader, B., Wong, W. 2015

View details for DOI 10.4172/TYOA.1000105

Female Gender and Hispanic Ethnicity are Associated with Increased Risk of Subacute Methotrexate Encephalopathy Toxicology: Open Access Lo, C. Y., Campen, C., Luna-Fineman, S., Lacayo, N. J., Fisher, P. G., Dahl, G. V. 2015

Abstract

Immune thrombocytopenia (ITP) in children less than one year of age is less well characterized compared to ITP in toddlers and school-age children. We performed a 10-year retrospective review of ITP patients in this age-cohort at our institution. Diagnosis and classification were made according to the 2009 International Working Group criteria. Fourteen infants were identified. Their bleeding scores were Grades 1 to 2 (79%), Grade 3 (22%), Grades 4 to 5 (0%). Eight patients received treatment with a 75% response rate. Three patients (21%) developed chronic ITP. These observations suggest that ITP in very young patients is similar to typical childhood ITP.

View details for DOI 10.1097/MPH.0b013e3182580ab4

View details for PubMedID 22767132

Polycythemia Neonatology: Clinical Practice and Procedures Lo, C., Wong, W. 2015
Bone marrow failure Rodacks Hematology: Clinical Principles and Applications Lo, C., Glader, B., Sakamoto, K. 2015
Immune Thrombocytopenia in Children Less Than 1 Year of Age: A Single-institution 10-year Experience. Journal of pediatric hematology/oncology Lo, C., Wong, W., Glader, B., Jeng, M. 2013; 35 (5): 406-408
The Role of Oxidative Stress in Pediatric Immune Thrombocytopenia 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) Lo, C., Zhang, B., Cusmano-Ozog, K., Wong, W., Jeng, M., Cowan, T., Zehnder, J. L. AMER SOC HEMATOLOGY. 2012
The Role of Oxidative Stress in Pediatric Immune Thrombocytopenia Lo, C., Zhang, B., Cusmano-Ozog, K., Wong, W., Jeng, M., Cowan, T., Zehnder, J. L. AMER SOC HEMATOLOGY. 2012

Abstract

Pediatric immune thrombocytopenia (ITP) is usually self-limited. However, approximately 20% of children develop chronic ITP, which can be associated with significant morbidity because of long-term immunosuppression and splenectomy in refractory cases. To explore the molecular mechanism of chronic ITP compared with acute ITP, we studied 63 pediatric patients with ITP. Gene expression analysis of whole blood revealed distinct signatures for acute and chronic ITP. Oxidative stress-related pathways were among the most significant chronic ITP-associated pathways. Overexpression of VNN1, an oxidative stress sensor in epithelial cells, was most strongly associated with progression to chronic ITP. Studies of normal persons demonstrated VNN1 expression in a variety of blood cells. Exposure of blood mononuclear cells to oxidative stress inducers elicited dramatic up-regulation of VNN1 and down-regulation of PPAR, indicating a role for VNN1 as a peripheral blood oxidative stress sensor. Assessment of redox state by tandem mass spectrometry demonstrated statistically significant lower glutathione ratios in patients with ITP versus healthy controls; lower glutathione ratios were also seen in untreated patients with ITP compared with recently treated patients. Our work demonstrates distinct patterns of gene expression in acute and chronic ITP and implicates oxidative stress pathways in the pathogenesis of chronic pediatric ITP.

View details for DOI 10.1182/blood-2010-09-304931

View details for PubMedID 21325602

CLINICAL PRESENTATION AND MANAGEMENT OF SUBACUTE METHOTREXATE-INDUCED ENCEPHALOPATHY IN PATIENTS WITH PEDIATRIC MALIGNANCIES Lo, C., Campen, C., Lacayo, N., Dahl, G. WILEY-BLACKWELL. 2012: 105051

Abstract

Bovine topical thrombin is commonly used for local hemostasis in pediatric surgery. Acquired inhibitors to coagulation factors, particularly to factor V and bovine thrombin, have been infrequently reported in the pediatric population. We report a 3-year-old male who developed a coagulopathy and clinical bleeding after cardiothoracic surgery, during which bovine topical thrombin was used for local hemostasis. Laboratory tests revealed elevated prothrombin, partial thromboplastin, and thrombin times, and a low factor V activity level. He was found to have both human-thrombin and factor V inhibitors, among the first reported cases of these combined inhibitors secondary to bovine topical thrombin. He was treated with intravenous immunoglobulin and steroids with a rapid and durable response.

View details for DOI 10.1002/pbc.22699

View details for PubMedID 20979176

Chronic Oxidative Stress and Endothelial Dysfunction in Sickle Cell Disease Sickle Cell Disease: A New Vision for an Old Problem Lo, C., Morris, C. 2012
IMMUNE-MEDIATED THROMBOCYTOPENIA IN CHILDREN LESS THAN 1 YEAR OF AGE: A SINGLE-INSTITUTION 10-YEAR EXPERIENCE Lo, C., Newman, A., Wong, W., Glader, B., Jeng, M. WILEY-BLACKWELL. 2011: 91515
The role of vanin-1 and oxidative stress-related pathways in distinguishing acute and chronic pediatric ITP BLOOD Zhang, B., Lo, C., Shen, L., Sood, R., Jones, C., Cusmano-Ozog, K., Park-Snyder, S., Wong, W., Jeng, M., Cowan, T., Engleman, E. G., Zehnder, J. L. 2011; 117 (17): 4569-4579
Development of Antibodies to Human Thrombin and Factor V in a Patient Exposed to Topical Bovine Thrombin PEDIATRIC BLOOD & CANCER Lo, C. Y., Jones, C., Glader, B., Zehnder, J. L. 2010; 55 (6): 1195-1197