Monitoring intravenous UFH infusions with the anti-Xa HA, compared to the aPTT, achieves therapeutic anticoagulation more rapidly, maintains the values within the goal range for a longer time, and requires fewer adjustments in dosage and repeated tests.
Primary hemostasis begins with endothelial injury. VWF, produced by endothelial cells, binds to platelets and links them to subendothelial collagen. Platelet-derived ADP and thromboxane activate non-adhered platelets via their GPIIb/IIIa receptors, allowing these platelets to participate in platelet aggregation. Secondary hemostasis is initiated with the binding of factor VII to extravascular tissue factor (TF). Factors II, VII, IX and X are vitamin K-dependent factors. The role of vitamin K is to assist in the addition of gamma carboxylate groups to glutamic acids in the "GLA" domains of these factors.In vitro the intrinsic pathway is initiated when fresh whole blood is placed in a glass tube. The negative charge of the glass initiates the "contact pathway" where FXII is activated and then FXIa cleaves FIX to FIXa. The extrinsic pathway is triggered when tissue factor, phospholipid and calcium are added to plasma anticoagulated with citrate. In vitro, FVII is activated to FVIIa, and TF-FVIIa preferentially converts FX to FXa activating the common pathway.The prothrombin time is commonly used to monitor warfarin anticoagulant therapy. To correct for differences in reagent and instrument, the international normalized ratio was developed to improve standardization of PT reporting globally. The activated partial thromboplastin time (aPTT) is used to evaluate the intrinsic and common pathways of coagulation. The aPTT is useful clinically as a screening test for inherited and acquired factor deficiencies as well as to monitor unfractionated heparin therapy although the anti-Xa assay is now the preferred measure of the effects of unfractionated heparin. The Clauss assay is the most commonly performed fibrinogen assay and uses diluted plasma where clotting is initiated with a high concentration of reagent thrombin.The mixing study assists in the assessment of an abnormally prolonged PT or aPTT. An equal volume of citrated patient plasma is mixed with normal pooled plasma and the PT or aPTT are repeated on the 1:1 mix. Factor activity assays are most commonly performed as a one-stage assay. The patient's citrated plasma is diluted and mixed 1-to-1 with a single factor-deficient substrate plasma. A PT or aPTT is performed on the above mix, depending on the factor being tested.Factor inhibitors are antibodies that are most commonly diagnosed in male patients with severe hemophilia A (FVIII deficiency) where they are induced by factor replacement therapy.Factor inhibitors can also appear in the form of spontaneous autoantibodies in both male and female individuals who were previously well. This is an autoimmune condition called "acquired hemophilia."Most coagulation laboratories can measure the plasma concentration of VWF protein (VWF antigen) by an immunoturbidimetric technique. Testing the functional activity of VWF, utilizes the drug ristocetin.The state of multimerization of VWF is important and is assessed by electrophoresis on agarose gels. Type 2a and 2b VWD are associated with the lack of intermediate- and high mole...
Iron is one of the most important nonorganic substances that make life possible. Iron plays major roles in oxygen transport (eg, hemoglobin; -67% of total body iron [TBI]), short-term oxygen storage (eg, myoglobin; -3.5% of TBI), and energy generation (eg, cytochromes; -3% of TBI). Iron also serves vital roles in various nonheme-containing enzymes (-2% of TBI). Figure 1 lists heme-containing and nonheme iron-containing proteins. TBI is controlled by the rate of iron absorption; there are no physiologic mechanisms to excrete excess iron. Iron deficiency has many adverse consequences, including anemia, and in children, behavioral and learning disorders. Iron excess is toxic to the body, harming the heart, liver, skin, pancreatic islet beta cells, bones, joints, and pituitary gland. Maintaining proper iron balance is essential for maintaining homeostasis and health. TBI in adults normally ranges between 3.5 and 5.0 g. A total of 75% of TBI is functional, and 25% is stored within cells as ferritin or hemosiderin. Ferritin contains 24 subunits of light chains (L chains; 19.7 kDa) and heavy chains (H chains; 21.1 kDa). The L chains are encoded on chromosome 19q13.33 and are 175 amino acids long. The H chains are encoded on chromosome 11q1 and are 183 amino acids long. Each ferritin molecule can contain as many as approximately 4500 ferric ions. Because the major role of iron is in hemoglobin synthesis, this review will focus on iron, iron transport, and hematopoiesis.
The ADVIA 2120 Hematology System was recently released by Bayer HealthCare, Diagnostics Division, as a bench-top analyzer designed for medium- to large-volume laboratories. This flow cytometry-based system uses light scatter, differential white blood cell (WBC) lysis, and myeloperoxidase and oxazine 750 staining to provide a complete blood cell count, a WBC differential, and a reticulocyte count. A cyanide-free method is used to measure hemoglobin colorimetrically. The system is automation ready; in addition to its capability for analyzing peripheral blood specimens, the analyzer is also equipped to analyze cerebrospinal fluid samples. In this article we explain the underlying technology of the ADVIA 2120, provide linearity ranges, method-specific reference ranges, and stability data, and describe novel parameters and applications that are unique to the methodology used by this instrument. Finally, we discuss research applications and future directions, such as the use of this hematology analyzer in the determination of fetal lung maturity.
Automated cell counters are widely used in modern clinical laboratories to provide reliable, fast, and cost-effective complete blood counts (CBCs), white blood cell differentials, and reticulocyte measurements. In addition, some advanced instruments provide novel parameters, such as the hemoglobin content of reticulocytes or the percentage of hypochromic cells, and are capable of analysis of a variety of body fluids. Bayer recently introduced the ADVIA 2120 system as an automation-ready cell counter for mid- to high-volume testing in the clinical laboratory. This instrument, which builds on the established technology of the ADVIA 120 system, operates with a cyanide-free method for hemoglobin measurement, has a new user interface, and can routinely analyze biological fluid samples in addition to blood. We used 749 samples from 6 worldwide trial sites to evaluate the clinical performance of this new device. Accuracy of the ADVIA 2120 system versus its predecessor model, the ADVIA 120 system, was excellent for all CBC and white cell differential parameters and reticulocyte counts (all correlation coefficients except for basophils >0.9). Correlation of the white cell differential with the standard manual method and within-run precision of the ADVIA 2120 system also was very good. Use of the novel cyanide-free method for hemoglobin measurement had no clinically significant impact on hemoglobin results, even in patients with hemoglobinopathies. We concluded that the ADVIA 2120 system has clinically equivalent performance to the ADVIA 120 system.
The diagnosis of type 1 diabetes versus other forms of diabetes such as type 2 diabetes is paramount to guiding proper therapy. Several islet autoantibodies have been identified that serve to diagnose immune-mediated, type 1a diabetes in clinically ambiguous cases. These autoantibodies also serve to predict type 1 diabetes in nondiabetic individuals. The most useful islet autoantibodies include islet cell cytoplasmic autoantibodies, insulin autoantibodies, glutamic acid decarboxylase autoantibodies, and insulinoma-associated-2 autoantibodies. Once type 1 diabetes can be safely and reliably prevented, large-scale islet autoantibody screening programs of the general pediatric population may be warranted. It is controversial whether islet autoantibodies influence the course of type 1 diabetes following diagnosis.
Continuous infusion unfractionated heparin (UH) has traditionally been monitored using the activated partial thromboplastin time (aPTT). The use of this test to monitor heparin therapy is not based on randomized controlled clinical trials, and the test is associated with significant intra- and inter-patient variability that is not related to circulating blood heparin activity. Due to these and other limitations, the use of aPTT alone to monitor UF has been questioned. Many laboratories are now transitioning to monitoring actual heparin activity (by anti-factor Xa analysis). In this review, we discuss the limitations of using the aPTT to monitor UH therapy and additionally the limitations of solely using heparin activity to monitor therapy. We also include a discussion of the challenges with monitoring heparin therapy in the pediatric population.
BackgroundThe recommendations of the American Board of Internal Medicine Foundation’s “Choosing Wisely®” initiative recognize the importance of improving the appropriateness of testing behavior and reducing the number of duplicate laboratory tests.ObjectiveTo assess the effectiveness of an electronic medical record Best Practice Alert (BPA or “pop up”) intervention aimed at reducing duplicate laboratory tests and hospital costs.DesignComparison of the number of duplicated laboratory tests performed on inpatients before and after the intervention.SettingUniversity of Florida Health Shands Hospital, Gainesville, FL, USA, during 2014–2017.InterventionThe electronic medical record intervention was a BPA pop-up alert that informed the ordering physician if a recent identical order already existed along with the “ordering time”, “collecting time”, “resulting time”, and the result itself.Main outcome measuresPercentage change in the number of inpatient duplicate orders of selected clinical biochemistry tests and cost savings from reduction of the duplicates. Student’s t-test and beta-binomial models were used to analyze the data.ResultsResults from the beta-binomial model indicated that the intervention reduced the overall duplicates by 18% (OR=0.82, standard error=0.016, P-value<0.000). Percent reductions in 9 of the 17 tests were statistically significant: serum hemoglobin A1C level, vitamin B12, serum erythrocyte sedimentation rate, serum folate, serum iron, lipid panel, respiratory viral panel, serum thyroid stimulating hormone level, and Vitamin D. Additionally, important cost savings were realized from the reduction of duplicates for each lab test (with the exception of CRP) with an estimated overall savings of $72,543 over 17 months in the post-intervention period.ConclusionsThe present study included all hospital inpatients and covered 17 clinical laboratory tests. This rather simple and low-cost intervention resulted in significant reductions in percentage duplicates of several tests and resulted in cost savings. The study also highlights the role of hospitalists in quality improvement.
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