Reduced volume of red blood cell priming is safe for pediatric patients undergoing therapeutic plasma exchange

RationalTherapeutic Plasma Exchange (TPE) procedures in pediatric patients are challenging due to the large extracorporeal volume of the cell separators, which were designed for adults. Red blood cell (RBC) priming is an alternative for overpassing the risks of hypovolemia, but data referring to the volume of packed RBCs to be infused are yet incomplete. Restricting the volume of RBC priming may potentially be associated with less transfusion reactions.GoalTo determine the safety of administering a reduced volume of RBC priming for pediatric patients undergoing TPE, in comparison to the standard volume recommended by the cell separators’ manufacturers.MethodsThis was a case-control study which enrolled 15 pediatric patients undergoing TPE and weighting more than 10Kg. The TPE procedures (n = 406) were divided in two groups: 1) Group1: TPE with ≤150 mL of packed RBC priming and 2) Group2: TPE with 150-250 mL of RBC priming. Groups were compared in terms of hemoglobin / hematocrit and occurrence of adverse reactions.ResultsGroup1 and Group2 did not differ significantly in relation to pre- and post-TPE hemoglobin (Hb) levels (p = 0.19 and p = 0.18, respectively). The Δ Hb (Hb pre-TPE – Hb post-TPE) was also not statistically different between the groups. The number of adverse reactions was significantly higher in Group 2 in relation to Group 1 (p = 0.01). The number of allergic reactions was also higher in Group 2 (p = 0.06).ConclusionsRestricting the volume of RBC priming to less than 150 mL is safe for pediatric patients weighting more than 10Kg and associated with lower rates of transfusion-related adverse reactions.     

Role of kidney in the catabolic clearance of human platelet antiheparin proteins from rat circulation

Stimulated platelets release at least two antiheparin proteins: platelet factor 4 (PF4) and low affinity platelet factor 4 (LA-PF4) from which beta-thromboglobulin (beta TG) is derived. We have found previously marked elevation of LA-PF4/beta TG antigen in platelet poor plasma of patients with chronic renal failure, whereas levels of PF4 remained normal. Therefore, we examined the role of the kidneys in the metabolic clearance of LA-PF4/beta TG and PF4. The supernates of aggregates of thrombin-stimulated human platelets were injected into sham operated control rats, nephrectomized rats, and into rats with acute ureteral ligation. The disappearance of human LA-PF4/beta TG antigen and PF4 in rat plasma determined by specific radioimmunoassays followed biphasic exponential curves. The half-lives (t1/2) for the fast and slow components of LA-PF4 in control rats were 6.4 and 68.4 min. Nephrectomy significantly increased these times to 9.7 and 144 min, while ureteral ligation resulted in no significant change. Comparison of the level of LA-PF4/beta TG antigen and of creatinine in aorta and in renal vein showed 25%-30% extraction of these compounds by the kidney. Less than 0.1% of the total LA-PF4 antigen injected was recovered in the urine of control rats. In contrast to these results, the clearance of PF4 was not affected by nephrectomy. In conclusion: (1) functional renal tissue is necessary for normal clearance of LA- PF4/beta TG, but renal excretion does not play a major role in its elimination suggesting that the protein is catabolized by the kidney; and (2) catabolic clearance of PF4 does not depend on functioning kidney tissue.     

Immunoglobulin G from patients with heparin-induced thrombocytopenia binds to a complex of heparin and platelet factor 4

Heparin-induced thrombocytopenia (HIT) is an important complication of heparin therapy. Although there is general agreement that platelet activation in vitro by the HIT IgG is mediated by the platelet Fc receptor, the interaction among the antibody, heparin, and platelet membrane components is uncertain and debated. In this report, we describe studies designed to address these interactions. We found, as others have noted, that a variety of other sulfated polysaccharides could substitute for heparin in the reaction. Using polysaccharides selected for both size and charge, we found that reactivity depended on two independent factors: a certain minimum degree of sulfation per saccharide unit and a certain minimum size. Hence, highly sulfated but small (< 1,000 daltons) polysaccharides were not reactive nor were large but poorly sulfated polysaccharides. The ability of HIT IgG to recognize heparin by itself was tested by Ouchterlony gel diffusion, ammonium sulfate and polyethylene glycol precipitation, and equilibrium dialysis. No technique demonstrated reactivity. However, when platelet releasate was added to heparin and HIT IgG, a 50-fold increase in binding of radio-labeled heparin to HIT IgG was observed. The releasate was then depleted of proteins capable of binding to heparin by immunoaffinity chromatography. Only platelet factor 4-immunodepleted releasate lost its reactivity with HIT IgG and heparin. Finally, to determine whether the reaction occurred on the surface of platelets or in the fluid phase, washed platelets were incubated with HIT IgG or heparin and after a wash step, heparin or HIT IgG was added, respectively. Reactivity was only noted when platelets were preincubated with heparin. Consistent with these observations was the demonstration of the presence of PF4 on platelets using flow cytometry. These studies indicate that heparin and other large, highly sulfated polysaccharides bind to PF4 to form a reactive antigen on the platelet surface. HIT IgG then binds to this complex with activation of platelets through the platelet Fc receptors.     

Inferior Vena Caval and Right Atrial Thrombosis Complicating an Amebic Hepatic Abscess

We describe a 50-yr-old black laborer who presented with right lower chest pain, weight loss, and pedal edema. Ultrasonography and computed tomograms showed a large abscess cavity in the right lobe of the liver which extended very close to the inferior vena cava. The lumen of the adjacent inferior vena cava was partially occluded by thrombus, which could be traced up into the cavity of the right atrium. The hepatic veins were normally patent. Sterile blood-stained pus was aspirated from the abscess. Antibodies against Entamoeba histolytica were present in high titer in the patient's serum. Although propagation of hepatocellular carcinoma into the inferior vena cava and even up into the right atrium is well recognized, inferior vena caval thrombosis extending up into the right atrium has not hitherto been reported as a complication of amebic hepatic abscess.     

Effect of supporting substrate on the failure behavior of a polymer-infiltrated ceramic network material

Statement of problemRestorative materials are cemented on different types of substrates, such as dentin, metal, and glass-fiber posts with composite resin cores.PurposeThe purpose of this in vitro study was to evaluate the failure behavior after cycling fatigue of a polymer-infiltrated ceramic network material (PICN; VITA ENAMIC) cemented on different supporting substrates.Material and methodsPICN plates (N=80) were obtained from computer-assisted design and computer-assisted manufacturing (CAD-CAM) blocks and cemented with a resin cement to 4 different supporting substrates (n=20): (1) human dentin (PICNDen); (2) dentin analog (PICNDenAn); (3) nickel-chromium alloy (PICNNiCr); and (4) composite resin plus fiberglass post (PICNRc). For comparison, the fracture behavior of a feldspathic ceramic (FelDenAn; VITABLOCS Mark II) and an indirect composite resin (ResDenAn; Opallis LAB Resin) cemented to the DenAn substrate was investigated (n=20). Thus, specimens were composed of the restorative material layer (1-mm thick) resin cemented (0.1-mm-thick layer) to a 2-mm-thick supporting substrate. All specimens were subjected to mechanical cycling (MC) using a pneumatic cycling machine (500 000 cycles, 2 Hz, 50 N). Specimens that did not fracture during cycling were tested under compression using a universal testing machine at a cross-head speed of 0.5 mm/min until the sound of the first crack was detected using an acoustic system. Failure data were statistically evaluated using Weibull distribution. Failures were classified as radial crack, cone crack, combined, and catastrophic fracture.ResultsAll FelDenAn specimens were fractured during MC. Only 4 PICNRc specimens survived MC, so their fracture load data were not statistically analyzed. PICNNiCr showed the greatest characteristic load (L₀) value, followed by ResDenAn. Groups PICNDenAn and PICNDen showed lower and similar L₀ but statistically different Weibull modulus (m). There was a significant relationship between experimental group and failure mode (P<.001). FelDenAn and PICNRc had a higher frequency of radial cracks, whereas PICNNiCr failed from cone cracking.ConclusionsThe supporting substrate influenced the failure behavior of PICN. When the substrate had a higher elastic modulus than the restorative material, better mechanical behavior was observed.     

Simultaneous occurrence of biphenotypic T cell/myeloid lesions involving t(12;13)(p13;q14) in a pediatric patient

This paper chronicles a 2-year-old girl who presented with acute leukemia/lymphoma syndrome of the T cell immunophenotype. At this time, the cytogenetic analysis of her bone marrow cells showed a reciprocal translocation between the short arm of chromosome 12 and the long arm of chromosome 13, t(12;13)(p13;q14). The immunophenotyping of bone marrow blast cells by flow cytometry revealed a population of cells positive for CD56, CD117, CD45, partial CD33, partial HLA-DR, CD13, CD7, CD2 and CD5. Therefore, a diagnosis of acute leukemia with a mixed T cell/myeloid phenotype was made. The patient had a poor response to classic T cell acute lymphocytic leukemia/lymphoma therapy; thus, her treatment was changed to a myeloid leukemia protocol, which produced a good response. She underwent a successful cord blood transplantation from an unrelated HLA partially matched donor. The coexistence of these two phenotypes prompts questions about the existence of clonal instability, which might influence the choice of therapy. The rarity of the t(12;13)(p13;q14) and the coexistence of T cell/myeloid markers suggest a nonrandom association. To the best of our knowledge, this is the first reported case in which a cell clone bearing a t(12;13)(p13;q14) translocation in a mixed T cell/myeloid lesion was detected.     

Primary myelofibrosis: risk stratification by IPSS identifies patients with poor clinical outcome

OBJECTIVES:

To evaluate whether risk scores used to classify patients with primary myelofibrosis and JAK-2 V617F mutation status can predict clinical outcome.

METHODS:

A review of clinical and laboratory data from 74 patients with primary myelofibrosis diagnosed between 1992 and 2011. The IPSS and Lille scores were calculated for risk stratification and correlated with overall survival.

RESULTS:

A V617F JAK2 mutation was detected in 32 cases (47%), with no significant correlation with overall survival. The patients were classified according to the scores: Lille - low, 53 (73.%); intermediate, 13 (18%); and high, 5 (7%); and IPSS – low, 15 (26%); intermediate-1, 23 (32%); intermediate-2, 19 (26%); and high, 15 (31%). Those patients presenting a higher risk according to the IPSS (high and intermediate-2) had a significantly shorter overall survival relative to the low risk groups (intermediate-1 and low) (p = 0.02).

CONCLUSIONS:

These results emphasize the importance of the IPSS prognostic score for risk assessment in predicting the clinical outcome of primary myelofibrosis patients.