Karen L. Hay

An Analysis of Platelet Activation and Aggregation Produced by Three Classes of Contrast Media

PURPOSE To evaluate the platelet activation and aggregation produced by ionic high-osmolality contrast media (HOCM) and both ionic and nonionic low-osmolality contrast media (LOCM). MATERIALS AND METHODS After each agent was mixed with heparinized blood, sequential platelet counts were used to monitor platelet aggregation, and flow cytometry was used to monitor both aggregation and activation. Aggregation was measured with CD41a-FITC (specific for glycoprotein IIb-IIIa) and activation was measured with CD62-PE (specific for P-selectin). RESULTS High concentrations of the nonionic LOCM (> 31% by volume in whole blood) induced more than 90% platelet activation within 2 minutes of exposure to freshly drawn heparinized whole blood. Aggregation followed immediately after activation and was somewhat reversible. High concentrations of the ionic HOCM (> 31%) induced prominent activation, although it occurred at a much slower rate and to a lesser degree than with the nonionic media. There was approximately 70% activation after 45 minutes of exposure. Ionic HOCM inhibited platelet aggregation, however. The ionic LOCM ioxaglate produced minimal or no platelet aggregation or activation. CONCLUSION There is likely to be an agent-related difference in the risk of platelet activation and aggregation in the catheter lumen and in the immediate environment of the catheter tip, where high concentrations of contrast media are known to exist.

Postoperative bypass bleeding: A bypass-associated dilutional (BAD) coagulopathy?☆

A number of associations with post-bypass bleeding have been described in the accompanying paper. Herein we hypothesize that dilution is an underlying cause through a malign series of bypass-associated events. Heparinized blood behaves anomalously when diluted. Clotting times first shorten somewhat, then--as the dilution of whole blood approaches 50%--rapidly lengthen to unclottability. During cardiopulmonary bypass, low blood volume patients are at a significant risk of clotting factor dilution which will always be more severe than the level of whole blood dilution. If severe enough, this dilution may lower plasma clotting factors to a critical level and may result in excess protamine administration, secondary to overestimation of heparin. The presence of un-neutralized protamine combined with critically lowered clotting factors leads to marked coagulopathy.

Factors Influencing the Activation of Platelets by Nonionic Contrast Medium

PURPOSE To determine why nonionic, low-osmolality contrast media (LOCM) at high concentrations (> 30%) induce almost immediate platelet activation and to explore preventive measures. MATERIALS AND METHODS Nonionic LOCM, when added to blood, activates platelets, raises the osmolality, and lowers the ionic strength. To clarify the mechanisms involved, platelet activation was studied in sodium chloride-sucrose solutions of varying osmolalities and varying ionic strengths. Several salts and Iloprost were evaluated as potential inhibitors of platelet activation. RESULTS Platelets are activated by both osmolality and ionic strength changes. The salts most inhibitory to platelet activation were magnesium sulfate and sodium citrate. Iloprost lowered platelet activation to control levels at 4.3 ng/mL of nonionic LOCM and completely eliminated it at 8.6 ng/mL. CONCLUSION Three-quarters of nonionic LOCM-induced platelet activation appeared to be due to increased osmolality-the remainder to the decrease in ionic strength. Magnesium sulfate and Iloprost are potent inhibitors of this type of platelet activation.

Association of plasma dilution with cardiopulmonary bypass-associated bleeding and morbidity

OBJECTIVE To investigate the relationship of cardiopulmonary bypass-associated plasma dilution with blood product transfusion and postoperative morbidity. DESIGN Retrospective chart review. SETTING Single academic medical center. PARTICIPANTS Five hundred forty adults undergoing cardiac surgery between January 4, 2005 and September 19, 2007. INTERVENTIONS Records were analyzed for demographics, blood volumes (BVs), and fluid balance. Plasma protein concentrations (% of baseline) at the end of bypass were calculated. The lowest and highest quartiles of plasma protein concentration were correlated with blood product administration and postoperative complications. MEASUREMENTS AND MAIN RESULTS At the end of bypass, calculated plasma protein concentrations ranged from a low of 10% to a high of 111% of baseline. Concentrations below 45% of baseline were associated with increased blood product administration, longer ventilator support, and longer intensive care unit stay. CONCLUSIONS Patient morbidity and likelihood of transfusion were associated with calculated plasma protein concentrations below 45% of baseline. Bleeding and administered fluids decrease both hematocrit and plasma proteins. Infusion of washed, salvaged blood or red blood cells raises hematocrit, but further dilutes clotting factors. If this dilution is excessive, coagulopathy may ensue. Patients with the smallest BVs are at greatest risk, but dilution can negatively impact patients with large BVs as well if the fluid used for cardiopulmonary bypass prime and anesthesia management represents a significant fraction of total BV.

Statistical clues to postoperative blood loss: moving averages applied to medical data.

With the advent of computerized databases, medical data has become easy to accumulate; however, effective use of this data continues to pose significant problems. In other circumstances, smoothing algorithms have been used to uncover non-obvious correlations, trends and relationships in noisy data. We have applied four such algorithms to a large dataset of postoperative blood replacement in cardiopulmonary bypass patients. When applied to this dataset, one of the algorithms proved surprisingly effective. It confirmed several previously observed correlations, and also provided an additional series of counterintuitive and apparently unrelated associations. These associations have been explored in an accompanying paper.

Crotalus atrox venom preconditioning increases plasma fibrinogen and reduces perioperative hemorrhage in a rat model of surgical brain injury

Perioperative bleeding is a potentially devastating complication in neurosurgical patients, and plasma fibrinogen concentration has been identified as a potential modifiable risk factor for perioperative bleeding. The aim of this study was to evaluate preconditioning with Crotalus atrox venom (Cv-PC) as potential preventive therapy for reducing perioperative hemorrhage in the rodent model of surgical brain injury (SBI). C. atrox venom contains snake venom metalloproteinases that cleave fibrinogen into fibrin split products without inducing clotting. Separately, fibrinogen split products induce fibrinogen production, thereby elevating plasma fibrinogen levels. Thus, the hypothesis was that preconditioning with C. atrox venom will produce fibrinogen spilt products, thereby upregulating fibrinogen levels, ultimately improving perioperative hemostasis during SBI. We observed that Cv-PC SBI animals had significantly reduced intraoperative hemorrhage and postoperative hematoma volumes compared to those of vehicle preconditioned SBI animals. Cv-PC animals were also found to have higher levels of plasma fibrinogen at the time of surgery, with unchanged prothrombin time. Cv-PC studies with fractions of C. atrox venom suggest that snake venom metalloproteinases are largely responsible for the improved hemostasis by Cv-PC. Our findings indicate that Cv-PC increases plasma fibrinogen levels and may provide a promising therapy for reducing perioperative hemorrhage in elective surgeries.

Control of analyzer slope and intercept in the measurement of packed red cell volume (PCV): part II.

A majority of packed cell volume (PCV) assays performed in the United States are performed by multichannel hematology analyzers rather than by centrifugation of blood samples in glass capillary tubes. PCV results from both analytical approaches were compared to the recently described ICSH reference method to determine the effect of assay slope on clinical utility. Though not controllable by the end user, the slope of the PCV assay versus the reference was satisfactory when performed in centrifuged glass capillaries. In the small sample of multichannel analyzers surveyed, only two of six machines functioned as well in this respect as did the glass capillaries. The worst of the unsatisfactory multichannel analyzers would have identified correctly only about half of the anemic and the polycythemic patients in the 12,623 males surveyed in the Third National Health and Nutrition Examination Survey (NHANES III). The performance on the females in this U.S. Department of Health and Human Services study would have been similarly poor. It is important that manufacturers of multichannel analyzers attend to the slopes of their PCV assays if the results are to be diagnostically useful.

An algorithm for preventing bypass-associated dilutional (BAD) coagulopathy: Theory and example ☆ ☆☆

OBJECTIVES Crystalloid administered during cardiopulmonary bypass may significantly dilute clotting factor concentrations, particularly in low blood volume patients. Should the administered fluid (pump prime plus IVs) drop the clotting factor concentrations below approximately 38%, almost all patients will bleed, heparin levels will be overestimated and excessive neutralizing protamine will be administered. This combination can render blood virtually unclottable. This paper describes algorithms that quantify dilution risk and the maximum fluid that can be safely administered. A confirmatory calculation to prevent excessive protamine administration is also described.