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Plasma volume substitution.

Blood loss up to 10-15% of the total blood volume can be substituted by mere crystalloids. A quicker and more stable volume replacement can be accomplished with colloid solutions. Combination of artificial colloids (e.g., dextran 60, dextran 70 or hydroxyethyl starches with high degree of hydroxyethylation) with crystalloids (isotonic balanced solutions) produces a long lasting volume effect. Due to dose limitation recommendations for the artificial colloids, volume substitution may be continued, at a later stage, by albumin.

Blood Volume↗

Solubility of inert gases in PFC blood substitute, blood plasma, and mixtures.

Measurements are reported of the solubility of nonreactive gases, e.g., hydrogen and xenon, in the following liquids: (a) Oxypherol (FC-43 emulsion) blood substitute, (b) blood plasma, (c) mixtures of Oxypherol and blood plasma, and (d) perfluorotributylamine. Typical results for Ostwald solubility at 25 degrees C for Xe gas in various liquids are 0.118 in H2O, 0.12 in blood plasma, and 1.51 in N(C4F9)3. Observed solubilities for the mixtures can be calculated from the relation: L(mixture) = L(emulsion)xv(emulsion) + L (plasma)xv(plasma), in which the v's are the volume fractions in the mixture. This linear relation implies that the gas dissolves independently in each liquid in the mixture. The effect of the emulsifier (Pluronic F-68, 2.6%), on gas solubility in the mixture, is small. Results for the temperature dependence of Ostwald solubility, L(T), in the range 10-37 degrees C are reported.

Blood Substitutes↗

Avoidance of blood transfusion in coronary artery surgery: a trial of hydroxyethyl starch.

Banked blood transfusion, with its attendant hazards, may be avoided in certain instances. A search for an acceptable plasma substitute was made. A randomized prospective trial of hydroxyethyl starch (HES) versus plasma for postoperative volume replacement is described. Ninety patients undergoing operations for coronary artery disease were studied over a six-month period. Ten received banked blood in the immediate postoperative period and were excluded from the study. The remaining 80 were randomized into two groups. Group 1 received plasma, and Group 2 received HES. All patients initially had autologous blood transfusion, and in 7 patients this sufficed; these patients were excluded from the study except for regression analysis. Postoperative blood loss and urine output did not differ between groups, but Group 2 patients required significantly more volume replacement (p less than 0.02). In a total of 27 patients drawn from both groups, coagulation factors and colloid osmotic pressure were investigated. There were no significant differences in fibrinogen titer and prothrombin time between groups, but return to normal values was significantly delayed in the HES group (p less than 0.01). Activated clotting time and partial thromboplastin time were unaffected. Colloid osmotic pressure was significantly higher at one week in the HES group (p less than 0.001) and was correlated with the volume of HES given (r = 0.525; p less than 0.01). There were no untoward effects attributable to HES. It is concluded that HES is a safe, cheap, and effective plasma substitute for volume replacement following cardiac surgical procedures.

Adult↗

Comparison of fresh frozen plasma with a standardized serum protein solution following therapeutic plasma exchange in patients with autoimmune disease: a prospective controlled clinical trial.

The aim of the study was the comparison of the influence of fresh frozen plasma (FFP) (Freiburg, Germany) and Biseko, Biotest Pharma GmbH (Dreieich, Germany), as a plasma substitute (a standardized, virus inactivated human serum protein solution) on the coagulation factors, inhibitors, proteins, and complement factors in the plasma of autoimmune disease patients following membrane plasma separation. Patients (n = 24) with autoimmune disease were randomized to receive either FFP or Biseko for membrane plasma separation therapy. During each plasma exchange, 100% of the plasma volume was replaced by the respective substitute. Plasma exchange volume was performed once daily for 3 days. Target test parameters of the coagulation system were fibrinogen, fibrinopeptide A, factor VIII (FVIIIC), von Willebrand factor antigen (vWFAg), partial thromboplastin time (PTT), thromboplastin time (Quick value), and antithrombin (AT III). The immunoglobulins were IgG, IgA, and IgM and C-reactive protein (CRP). The thrombocytes were platelet factor 4 (PF4), and complement factors were C3 and C4. Biseko was well tolerated with 1 mild adverse drug reaction (ADR) (n = 1) while FFP gave rise to ADR on 7 occasions (n = 4). Statistically significant differences in the 2 groups were observed for fibrinogen, PTT, Quick value, and AT III. From the clinical point of view, all fluctuations and differences in parameter levels remained clinically silent. The differences had no clinical consequences. Reflecting on a potential decrease in the risk of infections in comparison to FFP therapy and the lower rate of adverse drug reactions, it is possible to postulate an advantage of Biseko for plasma exchange therapy.

Adult↗

The effect of hydroxyethyl starch and other plasma volume substitutes on endothelial cell activation; an in vitro study.

OBJECTIVE: To study the effect of medium molecular weight hydroxyethyl starches on endothelial cell and neutrophil activation in vitro. SETTING: Laboratory analysis. METHODS: The effects of albumin and hydroxyethyl starch on the neutrophil adhesion molecule (CD11bCD18), with and without lipopolysaccharide stimulation, were studied in whole blood. E-selectin expression on human umbilical vein endothelial cells was stimulated with lipopolysaccharide alone and in the presence of either albumin or hydroxyethyl starch. The effect of albumin and hydroxyethyl starches on rapid endothelial cell activation was studied using von Willebrand factor release as a marker. MEASUREMENTS AND RESULTS: Hydroxyethyl starches but not albumin inhibited stimulated vWF release in a dose dependent manner. No effect was seen on endothelial E-selectin or neutrophil CD11bCD18 expression. CONCLUSIONS: these results suggest a possible beneficial role of hydroxyethyl starches in the inhibition of endothelial activation thus preventing neutrophil adhesion during sepsis syndrome.

Cell Adhesion↗

[Changes in the internal organs after hemodilution under hyperbaric oxygenation].

It has been shown in experiments on dogs that following blood replacement with a plasma substitute up to 0.5-2.5 g/100 ml Hb at an oxygen pressure of 3 at. abs., the morphological changes seen in the cerebral hemispheres, heart, liver, kidneys and lungs assume an adaptation character and are rapidly reversible. Microcirculatory disorders were found to play the leading part in the genesis of cellular changes recorded. The blood analysis data revealed the relationship between the degree of hemodilution and microvascular permeability and overall shifts in energy formation. To reduce the functional tension in the organ tissue systems, it is advisable to exercise the correction of the plasma substitute composition by which the permeability of the histohematic barrier could be stabilized. The hemodilution technique may be applied under hyperbaric oxygenation both in surgery and other fields of medicine with on object of replacing donor's blood by hemodynamic plasma substitutes.

Animals↗

Platelet function analysis after in vitro treatment with hemostasis-affecting components.

An overall platelet function test in whole blood, which simulates conditions under arterial pressure, is useful in measuring the effect of polymer materials on blood hemostatic function. We performed biocompatibility tests with materials or plasma substitutes by interaction of blood from healthy volunteers and then subjected these blood samples to platelet function analysis (Thrombostat). We tested also the capacity of locally applied hemostatic agents for bleeding control by direct application of these agents onto the Thrombostat measuring cell. The biocompatibility tests with materials exposed to blood appeared very discriminating between compatible and noncompatible materials. The hemostatic capacity of blood exposed to noncompatible materials (assessed by binding of active thrombin) reduced markedly after one hour incubation of the material. The plasma substitutes did not affect hemostasis significantly. However, a blood dilution of 40%, as in cardiopulmonary bypass, increased the time required for closure of the measuring cell by a platelet plug exponentially. Local hemostatic agents could be selected according to their capacity to enhance platelet plug formation. In addition, ADP mixed with the hemostatic agent was most effective in improving capacity. We conclude that platelet function analysis contributes importantly to screening of materials and plasma substitutes with regard to their interaction with primary hemostasis.

Biocompatible Materials↗

Influence of a blood component program on postoperative complication rates: a retrospective study in 372 patients.

We did a retrospective study of 372 thoracic and cardiovascular surgery patients, except open heart cases, which were treated by the same senior staff during the last year before (N = 197) and the first year after (N = 175) the introduction of a blood component program. There were no other basic changes of therapeutic policies. The two populations were comparable with respect to various basic characteristics. During the period 'before' the large majority of red cell units was 'deplasmatized' blood with a plasma deficit of 100 ml and a hematocrit of 40%. During the period 'after' it was red cell concentrates with a plasma deficit of 200 ml and a hematocrit of 70%. The usage pattern of red cell units did not change. The only statistically significant (and deliberate) quantitative difference between the transfusion regimens 'before' and 'after' was a more extensive intraoperative use of a gelatin plasma substitute to balance the plasma deficit of the red cell concentrates. As judged by various criteria, the postoperative courses of the patients 'before' and 'after' were virtually indistinguishable. We conclude that the blood component program practised at our hospital has no adverse effects on the postoperative course.

Adult↗

[Experience with a blood component program in surgical hemotherapy].

Within the component concept applied during the past 6 years at the University Hospital in Berne (Switzerland), 85% of all red cell units are transfused as concentrates with a hematocrit of 70%, and the remaining 15% as fresh whole blood. The rationale in surgical patients is to exploit the different "critical levels" of the blood volume, hematocrit, total serum protein, plasmatic coagulation factors, and platelets. A colloid plasma substitute compensating for the plasma deficit of the red cell concentrates is an integral part of the system. A carefully checked, retrospective study in 372 patients revealed no disadvantages for the postoperative course. During the first 4 1/2 years after its introduction it did not increase the demand for human plasma protein solutions. With the red cells as a pacemaker for the number of blood donations, this system can simultaneously cover a reasonable national demand for albumin and factor VIII.

Blood Transfusion↗

[Degree of substitution and volume expanding effect of various medium molecular weight hydroxyethyl starch solutions].

Hydroxyethylstarch (HES) is today one of the most frequently used artificial plasma substitutes in prehospital, as well as in clinical settings. However, there are no studies comparing the volume effect of different HES solutions. The goals of the present study therefore were to compare the volume effect of three HES solutions, which are similar with regard to mean molecular weight but different in concentration and degree of substitution. The obtained results enable guidelines for fluid resuscitation in hypovolemia to be laid down. In 30 patients fulfilling the ASA physical status classification I and II 500 ml of either 10% HES 200/0.5, 6% HES 200/0.5 or 6% HES 200/0.6-0.66 were infused within 30 min. The effect of each solution was evaluated using the mechanical oscillator technique (MOT). This technique measures precisely density changes of blood and plasma and allows-using standard formulae-calculation of blood and plasma volume changes. All 3 HES solutions showed similar effects in increasing plasma volume. Immediately after the end of infusion plasma volume was increased by about 800 ml with 10% HES and by about 650 ml with 6% HES 200/0.5. The volume expanding effect of 6% HES 200/0.6-0.66 amounted to 700 ml. The volume expanding effect of all starches decreased only slightly during the following two hours; an interesting detail observed was a second volume effect of HES (about 20% of the volume infused). We conclude that for the correlation of fluid deficits due to trauma, hemorrhage and shock HES solutions seem to be most effective artificial plasma substitutes.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Viscosity↗

Albumin, HES 120 and dextran 70 as adjuvants to red blood cell concentrates: a study on colloid osmotic pressure changes in vitro.

An in vitro model of surgical bleeding was developed to simulate continuous blood loss and replacement therapy with plasma substitutes and red cell concentrates. The model was used to determine the lowest colloid concentration in vitro for each of the plasma substitutes that sustains colloid osmotic pressure above 2.4 kPa (or 18 mmHg) when used up to the recommended maximal total dose. Plasma, supernatant separated from red cell concentrates and dextran 70, hydroxyethyl starch 120 or albumin were mixed to create dilutions imitating plasma composition in the course of clinical blood loss and replacement therapy. The relative volume of each component was calculated according to the model when the bleeding was equal to multiples of 10% of blood volume up to a blood loss of 120%. Our measurements indicate that the colloid concentrations of 5.0% for albumin, 4.0% for hydroxyethyl starch 120 and 3.5% for dextran 70 preserve colloid osmotic pressure above 2.4 kPa.

Albumins↗

On haemodilution therapy for patients with sudden loss of hearing: clinical and rheological results.

In cases of sudden loss of hearing, it must be assumed that a microcirculatory disturbance is involved, on the basis of a vasospasm of the afferent blood vessels and a "sludging phenomenon" in the region of the distal end-arteries of the cochlea. The microcirculatory disturbance results in an impairment of the O2 concentration in the perilymph, which can bring about disturbances, which are usually of short duration, and reversible changes in metabolism and structure of the hair cells. For this reason the therapeutic objective should be a reduction in the blood viscosity and flow resistance, plus a reduction in surface tension and an influence on the glycogenolytic metabolism of the erythrocytes. The therapeutic concept here is to be sought in a hypervolaemic haemodilution therapy with plasma substitutes. Care should be taken in the selection of the plasma substitute that not only parameters crucial to the macrocirculation are influenced, such as PCV and whole blood viscosity, but also those significant for the microcirculation, such as plasma viscosity and erythrocyte aggregation. A rheologically effective plasma expander would appear to have been found in the 10% hydroxyethyl starch 200/0.5, which together with naftidrofuryl would appear to be a proven agent in the combination therapy for sudden loss of hearing, due to its positive effect on plasma viscosity and erythrocyte aggregation, as shown by the significantly better mean increase in hearing on completion of therapy.

Cochlea↗

Abnormalities in the contact activation through factor XII in Fujiwara trait: a deficiency in both high and low molecular weight kininogens with low level of prekallikrein.

Fujiwara trait, the first case of kininogen deficiency in Japan previously reported which did not show any clinical symptom except the prolonged activated partial thromboplastin time was further examined. The activated partial thromboplastin time of the patient was corrected by addition of normal, Factor XII deficient or Fletcher plasma, but not corrected by Fitzgerald or Williams plasma. It was also corrected by addition of highly purified bovine or human high molecular weight (HMW) kininogen, but not by low molecular weight (LMW) kininogen. When total kininogen was measured as the amount of bradykinin released by trypsin, only a trace amount was detected in Fujiwara as well as Williams plasma. No immunoreactive protein against anti-human-HMW-kininogen nor anti-human-LMW-kininogen was found in Fujiwara plasma. Acetone-kaolin-activated plasma kallikrein was not generated by Fujiwara plasma. Substitution with normal plasma in various ratios showed the generation of various plasma kallikrein activities. Calculations with these activities of mixed plasma gave the prekallikrein content of Fujiwara trait plasma about 30% of the normal level. These results suggest that Fujiwara trait is very similar to Williams trait in that both plasmas were deficient in HMW and LMW kininogens with reduced content of prekallikrein.

Factor XII↗

[Side effects of therapeutic plasma exchange. A controlled prospective study].

Solutions of human albumin are generally used as plasma substitutes during therapeutic plasma exchanges. The safety of 2 solutions of human albumin was evaluated in a multicentre, randomized, double-blind trial. Between June, 1984 and February, 1986, 80 patients who were undergoing plasma exchanges for the first time entered the study and were randomly assigned into 2 groups according to whether they received plasma albumin (PM) or placental albumin (PC). Each patient had 6 plasma exchanges over a 2-week period. Failure was defined as the occurrence of an untoward effect during an exchange. No significant difference in the number of failures was found between the 2 albumins (PM 23/40, PC 15/40; P = 0.07). However, when the type of adverse reaction was taken into account there was a significant difference between the two treatment groups regarding the number of febrile episodes (PM 8, PC 2; P = 0.043) and shivering fits (PM 9, PC 2; P = 0.023). Thus, the nature of the albumin has no significant influence on the overall safety of plasma exchanges, but it seems that different methods of preparation may affect the type of untoward effect observed.

Adult↗

The clinical significance of alpha 1-antitrypsin-elastase (alpha 1AT-ELP) and alpha 2-antiplasmin-plasmin (alpha 2AP-PL) complexes for the differentiation of coagulation protein turnover: indications for plasma protein substitution in patients with septicaemia.

In inflammation, particularly in septicaemia, complex coagulation disorders may lead to a dangerous haemorrhagic diathesis. The conventional concept for this syndrome called DIC implicates the occurrence of active thrombin in the circulation, which may be followed by hyperfibrinolysis due to plasmin formation. In this study data are presented suggesting an important role for a third proteolytic system, granulocytic elastase. The complexes of plasmin and elastase with their specific inhibitors, alpha 2-antiplasmin-plasmin (alpha 2AP-PI) and alpha 1-antitrypsin-elastase (alpha 1AT-ELP) were determined immunologically. The alpha 1AT-ELP appears mainly in gram-negative septicaemia, particularly in meningococcal disease. The estimation of alpha 2AP-PI and alpha 1AT-ELP, together with a method for the detection of the antithrombin III--thrombin complex which remains to be established, is a suitable tool for for the differential diagnosis of the consumption of coagulation proteins. The assumption that at least three proteolytic systems participate in the development of the haemorrhagic diathesis during inflammation leads to the concept of a broad, comprehensive substitution therapy with e.g. concentrates of AT III, PPSB, or fresh frozen plasma. The aim of this treatment is to replace not only the consumed procoagulatory factors, but also the lacking inhibitors in order to control this "abnormal proteolysis syndrome".

Adult↗

Fujiwara trait: the first case of kininogen deficiency in Japan.

Asymptomatic identical twins were found to show the prolonged activated partial thromboplastin time, which was corrected by addition of normal, Hageman factor deficient or Fletcher trait plasma but not corrected by Fitzgerald or Williams plasma. The prolonged activated partial thromboplastin time was also corrected by addition of highly purified bovine high molecular weight kininogen but not by low molecular weight kininogen. When total kininogen was measured as the amount of bradykinin released by trypsin on acid treated plasma, only trace amount was detected in Fujiwara and Williams plasmas, although Fitzgerald plasma showed approximately 50% of the total kininogen of normal plasma level. Acetone-kaolin activated amidase activity of plasma kallikrein was not generated by Fujiwara plasma. Substitution with normal plasma in various ratios showed plasma kallikrein activity proportionally to the normal plasma contents. Extrapolation with the values at 120 min after activation gave the prekallikrein content of Fujiwara plasma as 30% of the normal value.

Diseases in Twins↗