RESUMEN

Diet is the leading predictor of health status, including all-cause mortality, in the modern world, yet is rarely measured; whereas virtually every adult in a developed country knows their approximate blood pressure, hardly any knows their objective diet quality. Leading authorities have called for the inclusion of nutrition in every electronic health record as one of the many remedial steps required to give dietary quality the routine attention it warrants. Existing tools to capture dietary intake are based on either real-time journaling or recall. Journaling, or logging, is time and labor intensive. Recall is notoriously unreliable, as humans are notably bad at remembering detail. Even allowing for the challenge of recall, these dietary intake methods are labor and time intensive, and require analysis at the n-of-1 level. We hypothesize that dietary intake assessment can be "reverse engineered"-predicating assessment on the recognition of fully formed dietary patterns-rather than endeavoring to assemble such a representation one food, meal, dish, or day at a time. This pattern recognition-based method offers potential advantages over existing methods, including speed, efficiency, cost, and applicability. We have developed and provisionally tested such a system, and the results thus far support our hypothesis. We are convinced that leveraging pattern recognition to make dietary assessment quick, user-friendly, economical, and scalable can allow for the conversion of dietary quality into a universally measured and routinely managed vital sign. In this paper, we present the supporting case.

RESUMEN

Decreased von Willebrand factor cleaving protease activity (VWFCP, ADAMTS 13) leads to persistence of unusually large multimers of von Willebrand factor that bind to platelets, causing platelet aggregates, microangiopathic hemolysis, and thrombocytopenia in patients with thrombotic thrombocytopenic purpura (TTP). The clinical value of measuring ADAMTS 13 and its inhibitor is not fully defined; the case reported here illustrates the usefulness of the assay to help confirm the clinical diagnosis in a patient with other potential causes for thrombotic microangiopathy; the assay also helped in making treatment decisions. A patient with systemic lupus erythematosis (SLE) presented with fever and abdominal pain, thrombocytopenia, and anemia. Thrombotic microangiopathy was diagnosed by the appearance of schistocytes, decreasing platelet count, and evidence of hemolysis. ADAMTS 13 was decreased and an inhibitor was demonstrated in the patient's initial blood sample within 24 hr of admission. Plasma exchange was initiated, and serial assays showed increased ADAMTS 13 activity and decreased inhibitor after each plasma exchange; there was a rebound in inhibitor and a decrease in ADAMTS 13 activity prior to the next exchange that lessened over time. Increasing levels of protease activity correlated with clinical and laboratory improvement. Measurement of ADAMTS 13 activity and its inhibitor aided in the diagnosis of this complicated case of a patient with other potential causes for microangiopathic hemolysis. Subsequent levels correlated with the clinical course, and disappearance of the inhibitor indicated that long-term plasma exchange or other immunosuppressive treatment was not needed.

Asunto(s)

Asunto(s)

Asunto(s)

RESUMEN

Control of warfarin anticoagulation during the initial phase of therapy is difficult and empirically based. Plasma and urine samples were obtained from normal controls, patients under stable anticoagulation, and patients in the initial phase of anticoagulation. Total plasma prothrombin, des-carboxy (non-adsorbable with barium chloride) prothrombin, and native (total minus non-adsorbable) prothrombin were quantitated using Echis carinatus venom activation. Functional plasma factor VII (VII) was measured using a one-stage clotting assay. Total and des-carboxy urine prothrombin F1 (F1) were measured by ELISA. All urine F1 in normals and both anticoagulated groups was adsorbed by barium chloride. Plasma des-carboxy prothrombin concentration was similar for the two anticoagulated groups and did not correlate with 1/INR. Native prothrombin correlated with 1/INR in both the stable (r = 0.76) and initial phase (r = 0.74) groups. For any given INR, the subjects on stable anticoagulation had lower native prothrombin concentrations than the initial phase patients. Functional factor VII concentration also correlated significantly with 1/INR in both the stable (r = 0.64) and initial phase (r = 0.76) patients. Unlike native prothrombin, VII concentrations did not vary between the two cohorts for any given INR. Previous studies indicate that native prothrombin is a superior predictor of both hemorrhagic and thromboembolic complications during warfarin therapy. Our findings indicate that VII, and not prothrombin, may be the predominant factor monitored by the INR. This further supports the need to reevaluate the usefulness of the INR in the monitoring of warfarin therapy during the initial phase.

Asunto(s)

RESUMEN

Five plasma preparations (11 lots) used in the treatment of von Willebrand's disease (vWD) were evaluated. The collagen binding function of von Willebrand factor (vWF) containing preparations was compared with the ristocetin cofactor activity and the vWF antigen. Some preparations have higher ratio of functional activity (ristocetin cofactor and collagen binding) relative to the antigen than is found in normal plasma. The ristocetin cofactor activity and the collagen binding activity are tightly correlated (r = .95). Ultracentrifugal (UCF) analysis was used to compare the size distribution of vWf antigen, ristocetin cofactor and collagen binding activity. The sedimentation of all of the vWF parameters in the plasma products was slower than in plasma. In plasma products the ristocetin cofactor activity sediments the most rapidly, the collagen binding activity is slower and the antigen the slowest. The collagen/antigen ratio decreases with decreasing vWF size. Assignment of potency to vWF containing preparations utilizing the collagen binding activity may be more precise and as accurate as with the traditional ristocetin cofactor assay.

Asunto(s)

RESUMEN

During the past 10 years the quality of plasma derived virus inactivated products containing von Willebrand factor (vWF) has improved and the ratios of ristocetin cofactor activity (vWF:RCo) to von Willebrand factor antigen (vWF:Ag) have increased. There are, however, considerable variations in AHF-vWF products with ranges from 0.25 to 1.4 unit of vWF:RCo for each unit of vWF:Ag, and 0.5 to 5.3 units of vWF:RCo for each factor VIIIC (FVIIIC) unit. The availability of a vWF product depleted of FVIII has allowed pharmacokinetic studies of the vWF protein. There have been no dose response studies, dosage regimens remain empirical and are still, except in rare instances, based on FVIIIC dosage. Current concentrates are as effective as cryoprecipitate in the management of patients with vWD non responsive to DDAVP. These concentrates should be preferred to cryoprecipitate which carries a risk of virus transmission.

Asunto(s)

RESUMEN

Nine patients (10 infusions) with a confirmed diagnosis of type 3 VWD were infused with von Willebrand factor (human), a preparation of von Willebrand factor (VWF) with a very low factor VIII content. Each patient was infused with one dose of approximately 50 or 100 iu ristocetin cofactor activity (VWF:RiCoF) per kg body weight. Bleeding times were performed during the 24 h period after infusion. Plasma samples were obtained over the 96 h period after infusion and were analysed for factor VIII coagulant activity (FVIIIC), VWF:RiCoF, von Willebrand factor antigen (VWF:Ag), and multimers. The FVIIIC data were analysed by non-linear least-squares analysis assuming constant FVIIIC 'synthesis' and exponential decay. The VWF data were fitted for exponential decay. The average decay rates for FVIIIC, VWF:RiCoF and VWF:Ag were 0.041, 0.061 and 0.056 respectively. The average calculated 'synthesis' rate for FVIIIC was 6.4 u/dl/h. The synthesis of FVIIIC was slightly faster and the decay slightly slower following the infusion of 100 iu VWF:RiCoF/kg than of 50 iu VWF:RiCoF/kg. Correction of the bleeding time was strongly dose dependent. At 4 h post infusion the median bleeding time was 9 min following a dose of 50 iu VWF:RiCoF/kg versus 3 min with a dose of 100 iu VWF:RiCoF/kg. There was no decrease in the bleeding time until the level of VWF:Ag or VWF:RiCoF reached > 100 u/dl.

Asunto(s)

RESUMEN

Activation of factor VIII is signaled by an increase in the 1-stage factor VIII activity and release from von Willebrand factor. Ultracentrifugation in 10-40% sucrose gradients was used to identify such activation in therapeutic concentrates. Plasma-derived factor VIII lots were examined and factor VIII sedimenting independently of von Willebrand factor was identified in some of the preparations. In addition there was slower sedimentation of factor VIII by the 1-stage assay than by the chromogenic assay. These results are consistent with a factor VIII cleaved at residue 1689, a site important for von Willebrand binding. This activated form leads to some of the assay discrepancies between the 1-stage assay and the chromogenic or the 2-stage assay. There is more rapid sedimentation of the factor VIII measured by the chromogenic assay than the von Willebrand factor in some manufacturers' samples indicating that the method of fractionation may select a low molecular weight von Willebrand factor which does not bind factor VIII. Routine comparison between the 1-stage and chromogenic assays during fractionation may be able to identify such activated preparations. Other assay discrepancies may be due to structural differences between the standards and the tested product.

Asunto(s)

RESUMEN

The coagulant content and thrombin generating potential of synovial fluid from patients with osteoarthritis were studied as a model of extravascular coagulation. The concentrations of individual coagulant proteins were partially correlated with their molecular weight. The levels of the very large coagulants factor V, factor VIII and von Willebrand factor antigen (vWF:ag) are less than 1% of the activities found in a normal pooled reference plasma while smaller coagulants including factors IX, XI and prothrombin range between 9 and 30%. The protease inhibitors antithrombin-III (AT-III) and Alpha-2 macroglobulin in synovial fluid were present at levels of 74% and 13% of plasma, higher than expected based on their molecular weights. Prothrombin was more rapidly activated by tissue thromboplastin than by aPTT reagent. The thrombin activity formed in synovial fluid decreased more rapidly than that formed in dilute plasma. The addition of recombinant factor VIII or bovine factor V to synovial fluid accelerated the thrombin production by APTT but not by tissue thromboplastin. Indicating that the low levels of factor VIII and factor V did limit the rate of thrombin production. The addition of specific antibodies to factor VIII or factor V strongly inhibited thrombin production by aPTT. These data confirm a roughly inverse relationship between the concentrations of coagulation proteins and their molecular weight in synovial fluid and indicate that thrombin can be generated in synovial fluid. The inactivation of thrombin in synovial fluid may be more dependent on antithrombin-III than in plasma because of the increased AT-III/alpha-2 macroglobulin ratio seen in synovial fluid.

Asunto(s)

RESUMEN

Six brands of normal reference plasma produced in the United States, with assigned assay values for factor VII and IX and, in four instances, ristocetin cofactor and van Willebrand antigen, were assayed in nine coagulation laboratories in academic institutions in the same country. Differences in mean assays of reference plasmas, as a percent of labelled potency, were significant and were greater than differences among laboratories. Standard methods of assigning potency to commercial reference plasmas are recommended.

Asunto(s)

RESUMEN

Plasma and therapeutic preparations of factor VIII (1 recombinant factor VIII and two monoclonally purified plasma-derived factor VIII preparations, Kogenate, and AHF-M and Monoclate, respectively) were centrifuged in a sucrose density gradient, and the fractions were analyzed for factor VIII and von Willebrand factor (vWF). The residual vWF in the monoclonally purified factor VIII preparations sediments more slowly than the vWF of plasma. In the absence of added vWF, the factor VIII in all preparations sediments more slowly than plasma factor VIII. These same preparations of factor VIII added to hemophilic plasma as a source of vWF sediment differently. The addition of either recombinant factor VIII or AHF-M results in sedimentation of the factor VIII with the plasma vFW and in a position indistinguishable from factor VIII in plasma. In contrast, when Monoclate is added to hemophilic plasma in vitro, the factor VIII sediments more slowly than the vWF of the hemophilic plasma. However, 5 min after the infusion of Monoclate into a patient with hemophilia A, the factor VIII sediments with the plasma vWF. These results indicate that the addition of recombinant factor VIII and AHF-M results in random binding to all vWF multimers of plasma, while there is little exchange between the added factor VIII in Monoclate and the plasma vWF in vitro. In contrast, when the Monoclate is infused, there is rapid binding of factor VIII to the plasma vWF.(ABSTRACT TRUNCATED AT 250 WORDS)

Asunto(s)

RESUMEN

HIV was introduced into the blood supply at least 4 years before there was any clinical illness in hemophiliacs. While viral removal and inactivation techniques of plasma products have improved, contamination with a very stable virus is still a possibility.

Asunto(s)

Asunto(s)

Asunto(s)

Asunto(s)

RESUMEN

BACKGROUND: Fibrinolytic therapy is associated with frequent rethrombosis. There is evidence of both increased coagulation and platelet activation. METHODS AND RESULTS: Platelet-rich plasma (PRP) or washed platelets were incubated with the fibrinolytic agents urokinase, recombinant tissue-type plasminogen activator (rt-PA), or plasmin at concentrations consistent with those in the plasma of patients treated for myocardial infarction. All of the fibrinolytic agents induced a more rapid generation of thrombin and decreased the clotting times of non-contact-activated PRP than in untreated PRP. This effect was not blocked by the inclusion of thrombin inhibitors during the fibrinolytic treatment. Washed platelets derived from rt-PA-treated PRP induced more rapid thrombin generation when resuspended in untreated plasma or treated plasma. Washed platelets were treated with plasmin, rt-PA, and urokinase and added to platelet-poor plasma. Platelets treated with either plasmin or rt-PA increased the ability of washed platelets to support thrombin generation, but urokinase was without significant effect. CONCLUSIONS: These results indicate not only that plasmin can cause increased platelet support of prothrombin activation but also that rt-PA in the absence of plasminogen can have a direct effect on the platelet, which increases thrombin generation.

Asunto(s)

Asunto(s)

Asunto(s)

Asunto(s)