- Transfusion Medicine
Clinical Associate Professor, Anesthesiology, Perioperative and Pain Medicine
Clinical Associate Professor (By courtesy), Pathology
Medical Director, Stanford Anesthesiology Perioperative Anemia Management Clinic (2018 - Present)
Boards, Advisory Committees, Professional Organizations
ASA Representative, Perioperative Standards Committee, AABB (2021 - Present)
Delegate, District 3, California Society of Anesthesiologists (2021 - Present)
Member, Committee on Patient Blood Management, American Society of Anesthesiologists (2018 - Present)
Board Certification: American Board of Pathology, Blood Banking/Transfusion Medicine (2017)
Board Certification: American Board of Anesthesiology, Anesthesia (2017)
Fellowship, Stanford University Medical Center, CA, Transfusion Medicine (2016)
Residency, Stanford University Medical Center, CA, Anesthesiology (2015)
Internship, University of Pennsylvania Health System, PA (2012)
MD, University of Pennsylvania School of Medicine, PA (2011)
PhD, University of Pennsylvania School of Medicine, PA (2009)
Rapid Blood Transfusion: The Importance of Hemodilution and Needleless Connectors.
2021; 13 (3): e13999
Large-bore cannulas are critical to administering IV fluids and blood products during resuscitation and treatment of hemorrhage. Although catheter flow rates for crystalloid solutions are well defined, rapid administration of blood products is poorly characterized. In this in vitro study, we examined the effects of hemodilution and needleless connectors on red blood cell (RBC) flow rates. To determine RBC flow rates through large-bore cannulae, a crystalloid solution (Normosol®, Hospira, Lake Forest, IL) or RBC units were warmed and delivered under pressure (360 mmHg) using a Level 1 H-1200 Fast Flow Fluid Warmer (Smiths Medical, St. Paul, MN). Flow rates for crystalloid, packed RBCs and diluted RBCs were determined using a stopwatch. Additionally, the effect of the MaxPlus® clear needleless connector (CareFusion, San Diego, CA) was measured in all three infusion groups. Flow rates for undiluted RBC units were 53% slower than crystalloid solution (220 mL/min vs. 463 mL/min; p=0.0003), however, when RBC units were diluted to a hematocrit of ~30% flow rate improved to 369 mL/min (p=0.005). The addition of the MaxPlus® needleless connector reduced flow of crystalloid solution by 47% (245 mL/min; p=0.0001), undiluted RBCs by 64% (78 mL/min; p=0.01), and diluted RBCs by 51% (180 mL/min; p=0.00003). Compared to undiluted RBC units, hemodilution increased RBC delivery rate through a MaxPlus® connector by 130% (p=0.004) and by 68% (p=0.02) when the catheter was directly connected to the Level 1 tubing (MaxPlus® excluded). In settings requiring rapid transfusion of RBC units, needleless connectors should not be used and hemodilution should be considered in order to decrease the time required to deliver an equivalent red cell mass.
View details for DOI 10.7759/cureus.13999
View details for PubMedID 33880314
View details for PubMedCentralID PMC8053387
- Massive Transfusion and Resuscitation Manual of Clinical Anesthesiology Wolters Kluwer. 2020; 2: 327-34
- Alternatives to Blood Product Replacement Manual of Clinical Anesthesiology Wolters Kluwer. 2020; 2: 321-26
- Blood Component Therapy Manual of Clinical Anesthesiology Wolters Kluwer. 2020; 2: 315-20
Reducing Length of Stay and Red Blood Cell Transfusion by Implementing an Anesthesia Anemia Management Clinic
LIPPINCOTT WILLIAMS & WILKINS. 2019: 10
View details for Web of Science ID 000509554600006
- Patient Blood Management: Coagulation Miller's Anesthesia Elsevier. 2019; 9: 1579–1601
Transfusion Management of Conjoined Twins Undergoing Surgical Separation: A Single Center Experience with Three Sets of Thoraco-Omphalopagus Twins over Ten Years
WILEY. 2018: 122A–123A
View details for Web of Science ID 000444475900280
Rapid Blood Administration Via Small Bore Catheters Does Not Increase Potassium Concentration
WILEY. 2017: 126A
View details for Web of Science ID 000409065000308
Blood Transfusion Therapy.
Medical clinics of North America
2017; 101 (2): 431-447
Transfusion of red blood cells (RBCs) is a balance between providing benefit for patients while avoiding risks of transfusion. Randomized, controlled trials of restrictive RBC transfusion practices have shown equivalent patient outcomes compared with liberal transfusion practices, and meta-analyses have shown improved in-hospital mortality, reduced cardiac events, and reduced bacterial infections. This body of level 1 evidence has led to substantial, improved blood utilization and reduction of inappropriate blood transfusions with implementation of clinical decision support via electronic medical records, along with accompanying educational initiatives.
View details for DOI 10.1016/j.mcna.2016.09.012
View details for PubMedID 28189180
A Standardized Approach for Transfusion Medicine Support in Patients With Morbidly Adherent Placenta.
Anesthesia and analgesia
The incidence of placenta accreta (PA) has increased from 0.8 to 3.0 in 1000 pregnancies, driven by increased rates of cesarean deliveries (32.2% in 2014) of births in the United States. The average blood loss for a delivery complicated by PA ranges from 2000 to 5000 mL, frequently requiring substantial transfusion medicine support. We report our own institutional multidisciplinary approach for managing such patients, along with transfusion medicine outcomes, in this setting over a 5-year period.We reviewed records for patients referred to our program in placental disorders from July 1, 2009, to July 1, 2014. A placental disorders preoperative checklist was implemented to ensure optimal management of patients with peripartum hemorrhage.Of 136 patients whose placentas were reviewed postpartum, 21 had PA, 39 had microscopic PA, 17 had increta, 17 had percreta, and 42 had no accreta (of which 11 had placenta previa). For each subtype, the percentage of patients receiving blood products were 71% (PA), 28% (microscopic PA), 82% (increta), 82% (percreta), and 19% (no accreta). Among patients with PA or variants, 89% of patients with PA or variants underwent postpartum hysterectomy, compared to only 5% of patients with no or microscopic PA.Based on our experience and on the findings of our retrospective analysis, patients presenting with either antepartum radiological evidence or clinical suspicion of morbidly adherent placenta will benefit from a standardized protocol for clinical management, including transfusion medicine support. We found that massive hemorrhage is predictable when abnormal placentation is identified predelivery and that blood product support is substantial regardless of the degree of placental invasiveness. The protocol at our institution provides immediate access to sufficient volumes and types of blood products at delivery for patients at highest risk for life-threatening obstetric hemorrhage. Therefore, for patients with a diagnosis of morbidly adherent placenta scheduled for planned cesarean delivery with possible hysterectomy, a programmatic checklist that mobilizes a multidisciplinary team, including proactive transfusion medicine support, represents best practices.
View details for PubMedID 28640786
- Intraoperative Coagulopathies Anesthesiology: Clinical Case Reviews 2017
Estimating Blood Loss.
Anesthesia and analgesia
2017; 125 (1): 13–14
View details for PubMedID 28628574
- Study to investigate the association between placenta accreta subtype and red blood cell transfusion MOSBY-ELSEVIER. 2016: S380–S381
Altered BCR and TLR signals promote enhanced positive selection of autoreactive transitional B cells in Wiskott-Aldrich syndrome
JOURNAL OF EXPERIMENTAL MEDICINE
2015; 212 (10): 1663-1677
Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency disorder frequently associated with systemic autoimmunity, including autoantibody-mediated cytopenias. WAS protein (WASp)-deficient B cells have increased B cell receptor (BCR) and Toll-like receptor (TLR) signaling, suggesting that these pathways might impact establishment of the mature, naive BCR repertoire. To directly investigate this possibility, we evaluated naive B cell specificity and composition in WASp-deficient mice and WAS subjects (n = 12). High-throughput sequencing and single-cell cloning analysis of the BCR repertoire revealed altered heavy chain usage and enrichment for low-affinity self-reactive specificities in murine marginal zone and human naive B cells. Although negative selection mechanisms including deletion, anergy, and receptor editing were relatively unperturbed, WASp-deficient transitional B cells showed enhanced proliferation in vivo mediated by antigen- and Myd88-dependent signals. Finally, using both BCR sequencing and cell surface analysis with a monoclonal antibody recognizing an intrinsically autoreactive heavy chain, we show enrichment in self-reactive cells specifically at the transitional to naive mature B cell stage in WAS subjects. Our combined data support a model wherein modest alterations in B cell-intrinsic, BCR, and TLR signals in WAS, and likely other autoimmune disorders, are sufficient to alter B cell tolerance via positive selection of self-reactive transitional B cells.
View details for DOI 10.1084/jem.20150585
View details for Web of Science ID 000365135200015
View details for PubMedID 26371186
Coordination and Processing of DNA Ends During Double-Strand Break Repair: The Role of the Bacteriophage T4 Mre11/Rad50 (MR) Complex
2013; 195 (3): 739-755
The in vivo functions of the bacteriophage T4 Mre11/Rad50 (MR) complex (gp46/47) in double-strand-end processing, double-strand break repair, and recombination-dependent replication were investigated. The complex is essential for T4 growth, but we wanted to investigate the in vivo function during productive infections. We therefore generated a suppressed triple amber mutant in the Rad50 subunit to substantially reduce the level of complex and thereby reduce phage growth. Growth-limiting amounts of the complex caused a concordant decrease in phage genomic recombination-dependent replication. However, the efficiencies of double-strand break repair and of plasmid-based recombination-dependent replication remained relatively normal. Genetic analyses of linked markers indicated that double-strand ends were less protected from nuclease erosion in the depleted infection and also that end coordination during repair was compromised. We discuss models for why phage genomic recombination-dependent replication is more dependent on Mre11/Rad50 levels when compared to plasmid recombination-dependent replication. We also tested the importance of the conserved histidine residue in nuclease motif I of the T4 Mre11 protein. Substitution with multiple different amino acids (including serine) failed to support phage growth, completely blocked plasmid recombination-dependent replication, and led to the stabilization of double-strand ends. We also constructed and expressed an Mre11 mutant protein with the conserved histidine changed to serine. The mutant protein was found to be completely defective for nuclease activities, but retained the ability to bind the Rad50 subunit and double-stranded DNA. These results indicate that the nuclease activity of Mre11 is critical for phage growth and recombination-dependent replication during T4 infections.
View details for DOI 10.1534/genetics.113.154872
View details for Web of Science ID 000329874100009
View details for PubMedID 23979587
Altered B Cell Homeostasis Is Associated with Type I Diabetes and Carriers of the PTPN22 Allelic Variant
JOURNAL OF IMMUNOLOGY
2012; 188 (1): 487-496
The PTPN22 genetic variant 1858T, encoding Lyp620W, is associated with multiple autoimmune disorders for which the production of autoantibodies is a common feature, suggesting a loss of B cell tolerance. Lyp620W results in blunted BCR signaling in memory B cells. Because BCR signal strength is tightly coupled to central and peripheral tolerance, we examined whether Lyp620W impacts peripheral B cell homeostasis in healthy individuals heterozygous for the PTPN221858T variant. We found that these subjects display alterations in the composition of the B cell pool that include specific expansion of the transitional and anergic IgD(+)IgM(-)CD27(-) B cell subsets. The PTPN22 1858T variant was further associated with significantly diminished BCR signaling and a resistance to apoptosis in both transitional and naive B cells. Strikingly, parallel changes in both BCR signaling and composition of B cell compartment were observed in type 1 diabetic subjects, irrespective of PTPN22 genotype, revealing a novel immune phenotype and likely shared mechanisms leading to a loss of B cell tolerance. Our combined findings suggest that Lyp620W-mediated effects, due in part to the altered BCR signaling threshold, contribute to breakdown of peripheral tolerance and the entry of autoreactive B cells into the naive B cell compartment.
View details for DOI 10.4049/jimmunol.1102176
View details for Web of Science ID 000298628400056
View details for PubMedID 22105996
Developmental Acquisition of the Lyn-CD22-SHP-1 Inhibitory Pathway Promotes B Cell Tolerance
JOURNAL OF IMMUNOLOGY
2009; 182 (9): 5382-5392
To better understand whether autoimmunity in Lyn-deficient mice arises from compromised central or peripheral B cell tolerance, we examined BCR signaling properties of wild-type and Lyn-deficient B cells at different stages of development. Wild-type mature follicular B cells were less sensitive to BCR stimulation than were immature transitional stage 1 B cells with regard to BCR-induced calcium elevation and ERK MAPK activation. In the absence of Lyn, mature B cell signaling was greatly enhanced, whereas immature B cell signaling was minimally affected. Correspondingly, Lyn deficiency substantially enhanced the sensitivity of mature B cells to activation via the BCR, but minimally affected events associated with tolerance induction at the immature stage. The effects of CD22 deficiency on BCR signaling were very similar in B cells at different stages of maturation. These results indicate that the Lyn-CD22-Src homology region 2 domain-containing phosphatase-1 inhibitory pathway largely becomes operational as B cell mature, and sets a threshold for activation that appears to be critical for the maintenance of tolerance in the B cell compartment.
View details for DOI 10.4049/jimmunol.0803941
View details for Web of Science ID 000275119200032
View details for PubMedID 19380785
RS rearrangement frequency as a marker of receptor editing in lupus and type 1 diabetes
JOURNAL OF EXPERIMENTAL MEDICINE
2008; 205 (13): 2985-2994
Continued antibody gene rearrangement, termed receptor editing, is an important mechanism of central B cell tolerance that may be defective in some autoimmune individuals. We describe a quantitative assay for recombining sequence (RS) rearrangement that we use to estimate levels of antibody light chain receptor editing in various B cell populations. RS rearrangement is a recombination of a noncoding gene segment in the kappa antibody light chain locus. RS rearrangement levels are highest in the most highly edited B cells, and are inappropriately low in autoimmune mouse models of systemic lupus erythematosus (SLE) and type 1 diabetes (T1D), including those without overt disease. Low RS rearrangement levels are also observed in human subjects with SLE or T1D.
View details for DOI 10.1084/jem.20082053
View details for Web of Science ID 000266428700006
View details for PubMedID 19075293
Editing and escape-from editing in anti-DNA B cells
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2008; 105 (10): 3861-3866
Tolerance to dsDNA is achieved through editing of Ig receptors that react with dsDNA. Nevertheless, some B cells with anti-dsDNA receptors escape editing and migrate to the spleen. Certain anti-dsDNA B cells that are recovered as hybridomas from the spleens of anti-dsDNA H chain transgenic mice also bind an additional, Golgi-associated antigen. B cells that bind this antigen accumulate intracellular IgM. The intracellular accumulation of IgM is incomplete, because IgM clusters are observed at the cell surface. In the spleen, B cells that express the heavy and light chains encoding this IgM are surface IgM-bright and acquire the CD21-high/CD23-low phenotype of marginal zone B cells. Our data imply that expression of an Ig that binds dsDNA and an additional antigen expressed in the secretory compartment renders B cells resistant to central tolerance. In the periphery, these B cells may be sequestered in the splenic marginal zone.
View details for DOI 10.1073/pnas.0800025105
View details for Web of Science ID 000253930600038
View details for PubMedID 18310318