Effect of all-trans retinoic acid on procoagulant and fibrinolytic activities of cultured blast cells from patients with acute promyelocytic leukemia

The mechanisms underlying acute promyelocytic leukemia (APL) coagulopathy and its reversal by administration of all-trans retinoic acid (ATRA) have been investigated. Bone marrow promyelocytic blasts from nine patients with APL were cultured with or without ATRA 1 mumol/L. Cultured blasts (days 0, 3, 6, and 9) were washed, resuspended in phosphate buffer, lysed by freezing and thawing, and then assayed for procoagulant activity (PCA), elastase activity, tissue factor (TF) antigen, tissue-type plasminogen activator (t-PA) antigen and urokinase- type plasminogen activator (u-PA) antigen. PCA was determined by a recalcification assay. Elastase was measured by an amidolytic assay (S- 2484). TF, t-PA, and u-PA antigens were measured by an enzyme-linked immunosorbent assay (ELISA). Malignant promyelocytes isolated from the patients had increased levels of PCA and TF as compared with the control polymorphonucleates, and low levels of elastase, t-PA, and u- PA; the patient blast PCA level was significantly related to the degree of hypofibrinogenemia. In this system, blast PCA depended on the tissue factor and was significantly correlated to the TF antigen values. In the cultures without ATRA, PCA, TF, and u-PA progressively increased, whereas elastase and t-PA levels remained essentially unchanged. In the presence of ATRA, all parameters (except u-PA) decreased during the culture time. Thus, a major role of the promyelocytic blast cell PCA in the pathogenesis of M3-related coagulopathy is suggested; the ATRA effect on coagulopathy seems mainly mediated by a downregulation of the PCA.     

Key High‐efficiency Practices of Emergency Department Providers: A Mixed‐methods Study

Objective

The objective of this study was to determine specific provider practices associated with high provider efficiency in community emergency departments (EDs).

Methods

A mixed‐methods study design was utilized to identify key behaviors associated with efficiency. Stage 1 was a convenience sample of 16 participants (ED medical directors, nurses, advanced practice providers, and physicians) identified provider efficiency behaviors during semistructured interviews. Ninety‐nine behaviors were identified and distilled by a group of three ED clinicians into 18 themes. Stage 2 was an observational study of 35 providers was performed in four (30,000‐ to 55,000‐visit) community EDs during two 4‐hour periods and recorded in minute‐by‐minute observation logs. In Stage 3, each behavior or practice from Stage 1 was assigned a score within each observation period. Behaviors were tested for association with provider efficiency (relative value units/hour) using linear univariate generalized estimating equations with an identity link, clustered on ED site.

Results

Five ED provider practices were found to be positively associated with efficiency: average patient load, using name of team member, conversations with health care team, visits to patient rooms, and running the board. Two behaviors, “inefficiency practices,” demonstrated significant negative correlations: non–work‐related tasks and documentation on patients no longer in the ED.

Conclusions

Average patient load, running the board, conversations with team member, and using names of team members are associated with enhanced provider productivity. Identification of behaviors associated with efficiency can be utilized by medical directors, clinicians, and trainees to improve personal efficiency or counsel team members.

     

Antiphospholipid antibodies before and after liver transplantation

OBJECTIVE: The aim of this study was to determine whether liver transplantation of patients with antiphospholipid antibodies (APA) is 1) adversely affected with vascular thrombosis and 2) whether such antibodies persist post transplantation. METHODS: Twelve patients with APA awaiting transplant were identified and characterized biochemically and immunologically. Each had the level of APA determined using commercially available enzyme-linked immunoassay kits before, during, and after liver transplantation. RESULTS: No patient in this series experienced a transplant-related vascular thrombosis. The titer of APA fell to levels at or below those present in normals and remained low in two of 12 or undetectable in 10 of 12 patients 1 yr after liver transplantation. CONCLUSIONS: We reached the following conclusions: 1) Antiphospholipid positivity does not identify patients at high risk for post-transplant vascular thrombosis. 2) The levels of antiphospholipid present in sera pretransplant fell during transplantation and remained low or undetectable 1 month and 1 yr post transplantation.     

Factor V Leiden and allogeneic bone marrow transplantation: chimerism as a confounding factor in genetic test interpretation

Factor V Leiden is one of the most common genetic conditions predisposing to venous thrombosis. Diagnosis is currently made by plasma activity assay for activated protein C (APC) resistance or polymerase chain reaction (PCR)-based DNA assay. The occurrence of factor V Leiden is reported in a patient affected by acute myeloid leukaemia submitted to allogeneic bone marrow transplantation from an HLA identical sister. The donor was not affected by the factor V mutation. The patient did not develop thrombosis during induction and consolidation chemotherapy and the post-transplantation course was not complicated by thrombosis or veno-occlusive disease. At engraftment, PCR analysis showed the disappearance of factor V Leiden. Genetic tests on DNA after allogeneic marrow transplantation should be carefully interpreted as a result of donor chimerism.     

Predictors and Clinical Impact of Prosthesis-Patient Mismatch After Self-Expandable TAVR in Small Annuli

ObjectivesThe aim of this study was to define predictors of prosthesis-patient mismatch (PPM) and its impact on mortality after transcatheter aortic valve replacement (TAVR) with self-expandable valves (SEVs) in patients with small annuli.BackgroundTAVR seems to reduce the risk for PPM compared with surgical aortic valve replacement, especially in patients with small aortic annuli. Nevertheless, predictors and impact of PPM in this population have not been clarified yet.MethodsPredictors of PPM and all-cause mortality were investigated using multivariable logistic regression analysis from the cohort of the TAVI-SMALL (International Multicenter Registry to Evaluate the Performance of Self-Expandable Valves in Small Aortic Annuli) registry, which included patients with severe aortic stenosis and small annuli (annular perimeter <72 mm or area <400 mm² on computed tomography) treated with transcatheter SEVs: 445 patients with (n = 129) and without (n = 316) PPM were enrolled.ResultsIntra-annular valves conferred increased risk for PPM (odds ratio [OR]: 2.36; 95% confidence interval [CI]: 1.16 to 4.81), while post-dilation (OR: 0.46; 95% CI: 0.25–0.84) and valve oversizing (OR: 0.53; 95% CI: 0.28–1.00) seemed to protect against PPM occurrence. At a median follow-up of 354 days, patients with severe PPM, but not those with moderate PPM, had a higher all-cause mortality rate compared with those without PPM (log-rank p = 0.008). Multivariable Cox regression confirmed severe PPM as an independent predictor of all-cause mortality (hazard ratio: 4.27; 95% CI: 1.34 to 13.6).ConclusionsAmong patients with aortic stenosis and small aortic annuli undergoing transcatheter SEV implantation, use of intra-annular valves yielded higher risk for PPM; conversely, post-dilation and valve oversizing protected against PPM occurrence. Severe PPM was independently associated with all-cause mortality.     

Early changes in phosphatidylcholine metabolism in human acute promyelocytic leukemia cells stimulated to differentiate by phorbol ester

The HL-60 leukemia cell line derived from a human acute promyelocytic leukemia is stimulated to differentiate into macrophages within 24-28 hr after exposure to the phorbol ester, 12-O-tetradecanoylphorbol-13- acetate (TPA). We studied early alterations (within 90 min of exposure to TPA) in phosphatidylcholine metabolism in HL-60 cells and found that phosphatidylcholine synthesis by methylation is phosphatidylethanolamine was inhibited in a dose-dependent fashion. In contrast, synthesis of phosphatidylcholine from endogenous choline was enhanced and correlated inversely with the degree of inhibition of the methylation pathway. Phorbol ester congeners of TPA caused similar alterations in phosphatidylcholine metabolism in direct relationship to their capacity to induce differentiation in HL-60 cells. Perturbation of phosphatidylcholine metabolism is an early membrane even in TPA- induced HL-60 cell differentiation.