1495 22Nd Ave Apt #4
San Francisco CA 94122
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The whole is greater than the sum of its parts: hemostatic profiles of whole blood variants. - The journal of trauma and acute care surgery
Mounting evidence highlighting the benefits of hemostatic resuscitation has led to a renewed interest in whole blood (WB) and reconstituted WB (RWB). However, few data exist to characterize the clotting profiles of these variants. This study characterizes banked WB variants and RWB in standard 1:1:1 and 2:1:1 transfusion ratios of packed red blood cells, fresh frozen plasma, and platelets (PLTs). We hypothesized that the global hemostatic profile of 1:1:1 RWB is superior to 2:1:1 RWB and that PLT-modified WB (MWB) is superior to 1:1:1 RWB.Twenty-three units of packed red blood cells, fresh frozen plasma, and PLTs were obtained from the regional blood collection center and mixed to create 23 1:1:1 and 23 2:1:1 RWB units. Freshly donated WB units were obtained and used to create 11 of each nonmodified WB (NMWB) (room temperature and cooled) and MWB (room temperature and cooled) variants. International normalized ratio (INR)/partial thromboplastin time (PTT), complete blood cell count, functional studies, and an extensive panel of procoagulant and anticoagulant factor assays were performed on all products.The 1:1:1 RWB had significantly lower INR and PTT (1.31 vs. 1.55, p = 0.0029; 42 seconds vs. 50 seconds, p = 0.0008) and higher activity of factors II, V, VII, VIII, IX, and X; antithrombin III, as well as protein C and higher fibrinogen levels than did 2:1:1 RWB (factor IX, 86% vs. 70%, p = 0.0313; fibrinogen, 242 mg/dL vs. 202 mg/dL, p = 0.0385). There were no differences in INR/PTT or factor activity between MWB and NMWB. However, MWB had greater maximum clot firmness (MCF) by rotational thromboelastometry tissue factor-activated extrinsic clotting cascade measures than did NMWB (MCF, 61 mm vs. 50 mm, p = 0.0031). MWB also had greater MCF by rotational thromboelastometry tissue factor-activated extrinsic clotting cascade measures than did 1:1:1 RWB (MCF, 61 mm vs. 45 mm, p = 0.0005).Although 1:1:1 RWB had a superior clotting profile relative to 2:1:1 RWB, MWB exhibited even better global hemostasis than did 1:1:1 RWB. Characterization of factor-level and functional clotting differences between WB variants is imperative for understanding the clinical benefits of hemostatic resuscitation.
Two septic transfusion reactions presenting as transfusion-related acute lung injury from a split plateletpheresis unit. - Critical care medicine
We report two simultaneous cases of Staphylococcus aureus sepsis initially consistent with and diagnosed as transfusion-related acute lung injury. The sepsis in both cases resulted from transfusion of two split products from a single contaminated plateletpheresis unit. In each case, the platelets were given along with numerous other blood products during posterior spine surgery. The discussion includes presentation, clinical course, diagnosis, and similarities between sepsis and transfusion-related acute lung injury. The cases and discussion highlight the importance of considering sepsis as part of the differential for any patient believed to have transfusion-related acute lung injury with clinical features of sepsis.Data were collected from the patients' electronic medical records and the hospital laboratory medicine database.Our cases highlight the importance of vigilant investigation in patients suspected of transfusion-related acute lung injury, as septic transfusions are easily missed and may mimic or coexist with transfusion-related acute lung injury. Sepsis should be strongly considered whenever clinical features such as hypotension, leucopenia, and fever are noted in patients with suspected transfusion-related acute lung injury. In comparison to patients receiving red blood cells or plasma, platelet transfusion recipients are at a greater risk for sepsis from a contaminated unit. Patients developing sepsis from a contaminated blood product may meet the clinical definition of transfusion-related acute lung injury. In such cases, if the clinical syndrome is attributed solely to transfusion-related acute lung injury and bacterial sepsis is not suspected, the correct diagnosis may be missed or delayed. Consequently, appropriate treatment for sepsis would also be delayed or not provided and likely result in increased morbidity and mortality.
Adverse effects of plasma transfusion. - Transfusion
Plasma utilization has increased over the past two decades, and there is a growing concern that many plasma transfusions are inappropriate. Plasma transfusion is not without risk, and certain complications are more likely with plasma than other blood components. Clinical and laboratory investigations of the patients suffering reactions after infusion of fresh-frozen plasma (FFP) define the etiology and pathogenesis of the panoply of adverse effects. We review here the pathogenesis, diagnosis, and management of the risks associated with plasma transfusion. Risks commonly associated with FFP include: 1) transfusion-related acute lung injury, 2) transfusion-associated circulatory overload, and 3) allergic and/or anaphylactic reactions. Other less common risks include 1) transmission of infections, 2) febrile nonhemolytic transfusion reactions, 3) red blood cell alloimmunization, and 4) hemolytic transfusion reactions. The effects of pathogen inactivation or reduction methods on these risks are also discussed. Fortunately, a majority of the adverse effects are not lethal and are adequately treated in clinical practice.Â© 2012 American Association of Blood Banks.
A mild acute hemolytic transfusion reaction in a patient with alloanti-Ge3: a case report and review of the literature. - Transfusion
The clinical significance of the Gerbich antibodies has been described as variable and there are no well-documented reports of hemolytic transfusion reactions (HTRs).We present the case of a woman with a long history of documented anti-Ge3 alloantibody who received multiple units of Ge+ red blood cells (RBCs) uneventfully. During the first admission to our hospital she was transfused 8 units of Ge+ RBCs and had a negative monocyte monolayer assay (MMA) before receiving the units. Within 2 weeks of the transfusions, the anti-Ge3 became significantly stronger by indirect antiglobulin test, and the MMA increased from 2.2 to 79.5% reactivity. She returned 4.5 years later with an emergent need for blood and was transfused with 2 units of Ge+ RBCs after premedication with steroids and intravenous immunoglobulin.The first unit was transfused without incident; however, she developed clinical and laboratory signs consistent with an acute HTR with the second unit.After a comprehensive review of the literature, we believe this to be the first well-documented case of acute HTR due to anti-Gerbich alloantibodies.Â© 2011 American Association of Blood Banks.
Establishing assay cutoffs for HLA antibody screening of apheresis donors. - Transfusion
Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related deaths. Donor HLA antibodies have been implicated in TRALI cases. Blood centers are implementing TRALI risk reduction strategies based on HLA antibody screening of some subpopulations of ever-pregnant apheresis platelet (PLT) donors. However, if screening assay cutoffs are too sensitive, donation loss may adversely impact blood availability.Pregnancy history and HLA antibody screening and single-antigen bead data from blood donors in the Retrovirus Epidemiology Donor Study-II Leukocyte Antibody Prevalence Study were evaluated for correlations between assay screening values, HLA antibody titer, and number of HLA antigen specificities. The probabilities of matching a cognate antigen in a recipient were calculated and examined in association with total number of specificities observed and screening values. The relative impact of imposing various screening assay cutoffs or pregnancy stratification was examined in relation to detection of HLA antibody-reactive donations and loss of donors and donations.We provide evidence that higher HLA antibody screening assay values are associated with maintaining higher screening signals upon dilution and an increased breadth of specificities compared with lower screening values; the latter correlated with an increased risk of a cognate antigen match in potential recipients. Depending on the TRALI risk reduction strategy used, the potential loss of donations ranged between 0.9 and 6.0%.This analysis should enable blood centers to decide upon a TRALI risk reduction strategy for apheresis PLTs that is consistent with how much donation loss the blood center can tolerate.Â© 2011 American Association of Blood Banks.
Agreement among HLA antibody detection assays is higher in ever-pregnant donors and improved using a consensus cutoff. - Transfusion
HLA antibodies might contribute to the pathogenesis of transfusion-related acute lung injury (TRALI). HLA antibody detection methods include ELISA, flow cytometry, and multiplex bead-based assays, as well as the older lymphocytotoxicity assay, and it is not obvious how to compare results across platforms.Five hundred twenty-five serum samples were selected from 7841 donors in the Leukocyte Antibody Prevalence Study (LAPS) repository based on risk for the development of HLA antibodies, using the number of pregnancies as the risk factor. Subjects included 81 males and females with 0 (n = 187), 1 (n = 67), or 2+ pregnancies (n = 190). Replicate frozen serum aliquots were sent blinded to four different HLA antibody assay manufacturers for detection using five different assays.The flow cytometry and multiplex bead based-assays typically resulted in a larger proportion of HLA antibody positive samples compared with ELISA based assays. Latent variable analysis was used to derive a new set of consensus cutoffs, which yielded similar sensitivities across test platforms and increased concordance amongst assays. Assay agreement was higher in ever pregnant females than in males and never-pregnant females.Different assays resulted in varied positivity rates when the manufacturer's suggested cutoffs were used, demonstrating that care needs to be taken when comparing clinical outcomes data generated using different HLA antibody assays and testing platforms. The method used here, involving latent variable analysis, presents one possible approach to calculating comparable cutoffs that result in broad agreement across assays with respect to positivity designation.Â© 2010 American Association of Blood Banks.
CD57 defines a functionally distinct population of mature NK cells in the human CD56dimCD16+ NK-cell subset. - Blood
Natural killer (NK) cells are innate immune lymphocytes that express a heterogeneous repertoire of germline-encoded receptors and undergo a distinct pattern of maturation. CD57 is a marker of terminal differentiation on human CD8(+) T cells. Very few newborn or fetal NK cells express CD57; however, the frequency of CD57-bearing NK cells increases with age. We assessed the transcriptional, phenotypic, and functional differences between CD57(+) and CD57(-) NK cells within the CD56(dim) mature NK subset. CD57(+) NK cells express a repertoire of NK-cell receptors, suggestive of a more mature phenotype, and proliferate less when stimulated with target cells and/or cytokines. By contrast, a higher frequency of CD57(+) NK cells produced interferon-Î³ and demonstrated more potent lytic activity when these cells were stimulated through the activating receptor CD16; however, they are less responsive to stimulation by interleukin-12 and interleukin-18. Finally, CD57 expression is induced on CD57(-)CD56(dim) NK cells after activation by interleukin-2. A combination of a mature phenotype, a higher cytotoxic capacity, a higher sensitivity to stimulation via CD16, with a decreased responsiveness to cytokines, and a decreased capacity to proliferate suggest that CD57(+) NK cells are highly mature and might be terminally differentiated.
Measurement of microalbuminuria using protein chip electrophoresis. - American journal of clinical pathology
Microalbuminuria reflects the progression of nephropathy and cardiovascular disease in diabetic and hypertensive patients. Most commercially available tests currently used to measure microalbuminuria are immunoassays. We developed a microfluidics-based assay using the P200 protein chip (Caliper Life Sciences, Mountain View, CA, and Agilent Technologies, Santa Clara, CA) and 2100 Bioanalyzer (Agilent Technologies) to detect microalbuminuria. The method integrates and automates the electrophoretic separation and fluorescent detection of proteins from 14 to 200 kd. The assay was linear up to 750 mg/L and demonstrated good sensitivity with a lower detection limit of 7.5 mg/L. Intrachip and interchip coefficients of variation ranged from 0% to 4% and 4.9% to 13.5%, respectively. When albumin was measured by chip and immunoturbidimetry in diabetic urine samples, the chip consistently showed higher albumin concentrations. The discrepancy may be due to the chip's ability to detect immunounreactive albumin. Overall, this simple, cost-effective assay offers a sensitive and accurate measurement of microalbuminuria that can be easily implemented in a clinical laboratory.
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1495 22Nd Ave Apt #4 San Francisco, CA 94122
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