Transfusion Filters Research Articles

Membrane plasma separation and the on-line treatment of plasma by membranes

The application of membranes for the separation of solids from liquids is quite common in industrial processes and has had a major impact on biomedical processes. Biomedical applications of blood processing range from the use of large-pore structures for filtration of blood for the removal of large particles (> 20 μm) (transfusion filters) to membranes for the dialysis of blood for the removal of low molecular weight solutes in the treatment of renal failure. Within the past decade membranes have been applied in the separation of plasma from whole blood. Compared to centrifugal plasma separation membrane plasma separation is preferred when used with on-line plasma fractionation since the plasma is free of cells. Also, membranes have been applied in the on-line treatment of the plasma for the selective removal of macromolecules in selected disease states obviating the need for plasma replacement products. The membranes for plasma separation and fractionation may be distinguished from conventional dialysis membranes and high-flux membranes used in hemofiltration by their very high or select passage of plasma proteins. Membrane techniques are simple and safe to apply and can be competitive to other separation technologies. Studies of membranes in the separation of components from the complex mixture of blood and their use in the separation of macromolecules in plasma are particularly useful in extending the applications of membranes in bioseparations.

In vitro effect of a microfibrillar collagen hemostat on platelets.

Microscopic particles of microfibrillar collagen hemostat (MCH) have been shown to pass through a 40-micron blood transfusion filter. This study indicates that MCH passing through the filter retains a significant portion of its ability to aggregate platelets in vitro and the aggregating ability is dose related. The extent of platelet aggregation in the presence of the MCH filtrate or an ADP standard was measured photometrically and log dose-response curves constructed from the data. An ED50 of 3.6 micrograms protein/ml platelet-rich plasma (PRP) was calculated at a protein concentration of 7.6 mg/ml in the MCH filtrate and an ED50 of 5.9 micrograms protein/ml PRP at 12 mg/ml protein in the MCH filtrate. The platelet aggregating ability of the MCH filtrates corresponded to 18.8 and 39.6% of the maximum response produced by adenosine-5'-diphosphate. These findings support the view that blood contaminated with MCH should not be returned to a patient's circulation.

Fibrin generation during production of freeze dried antihaemophilic cryoprecipitate

Thrombin activity during separation and cryoprecipitation of CPD-blood was monitored by fibrinopeptide A (FPA) determinations. After pooling and lyophilization of cryoprecipitate, the total amount of contaminating fibrin was estimated by N-terminal amino acid analyses. In addition, retention of fibrin in standard transfusion filters (170 μm) was examined by gamma counting of 125I des-AA fibrin monomer enriched cryoprecipitate prior and subsequent to filtration. Prior to pooling of cryoprecipitate, thrombin activity, as estimated by FPA levels, was most pronounced during collection of blood from the blood donors and during cryoprecipitation and thawing of the plasma bags. Comparison of these FPA concentrations to the total amount of fibrin in pooled, freeze dried cryoprecipitate, as estimated by N-terminal analyses, revealed a considerable generation of fibrin during the process of lyophilization. In freeze dried cryoprecipitate, 5.3 per cent (range 3.0–7.5 per cent) of the fibrinogen had been converted to fibrin, implying a fibrin content of 20.3–60.3 mg per bottle of 500 U factor VIII. The amount of fibrin in two bottles of a commercially available factor VIII concentrate, also containing 500 U of factor VIII, was 1115.1 and 19.8 mg, respectively. Sham transfusions of 125I des-AA fibrin monomer enriched cryoprecipitate revealed that only 1.0 per cent (range 0–2.5 per cent) of the fibrin was retained in the standard'transfusion filters. Thus, substantial amounts of fibrin may be transfused to patients upon treatment with freeze dried cryoprecipitate.

Contaminating fibrin in CPD-blood: Solubility in plasma and distribution in blood components following separation

In order to estimate the solubility of contaminating fibrin in CPD-blood, thrombin induced fibrin polymerzation in CPD-plasma was examined by light scattering and fibrinopeptide A (FPA) determinations. In addition, I 125 fibrin monomer enriched CPD-blood was used to investigate fibrin monomer retention in blood bags and transfusion filters (170 μm) and fibrin distribution in blood components derived from CPD-blood. Initial fibrin polymerization in CPD-blood occurred after conversion of 15 per cent of the fibrinogen to fibrin, implying that substantial amounts of fibrin maybe kept solubilized in CPD-blood bags. Only minor amounts of I 125 fibrin monomers were retained in blood bags (2.4 per cent) and in transfusion filters (2.9 per cent) after sham transfusions. After separating I 125 fibrin monomer enriched CPD-blood into its constituent components, the major part of fibrin (75.0 per cent) could be traced in the cryoprecipitate.

Observations on the removal of microaggregates from stored blood by centrifugation and filtration through a standard 170 micron transfusion filter.

The effect of centrifugation (5 minutes, 6900 X g) on the amount and particle size of blood microaggregates was studied in order to assess whether centrifugation and filtration by a standard (170 micron) transfusion set filter could be used for aggregate removal instead of microfiltration. Aggregates were quantitated using a method based on nylon screens with graded pore sizes. At the beginning of storage, centrifugation increased the particle size of aggregates only slightly. In 7-day-old blood, aggregates capable of passing a 160 micron screen amounted to 308 +/- 107 (SD) mg of debris protein per liter of blood before and 55 +/- 26 (SD) mg of protein (n = 10) after centrifugation. In 14-day-old blood centrifugation increased the size of aggregates even more effectively: 311 +/- 81 (SD) before and 29 +/- 14 (SD) mg of protein following centrifugation. Microaggregates can thus be removed effectively by the centrifugation and filtration method from blood stored for more than 1 week. A standard transfusion set filter can be used instead of a micropore filter.

Activation of Complement by Blood Transfusion Filters

Fresh blood, stored blood and granulocyte concentrates were passed through 170-µm and microaggregate blood filters to determine the degree of complement activation that occurs during transfusion of citrated blood products. Complement activation was assessed by measurement of C3 conversion using crossed immunoelectrophoresis and by assessment of C5a using a leukocyte aggregation functional assay. Prefiltration, fresh or stored blood products showed 0-1% C3 activation. Postfiltration, the degree of C3 conversion did not change for fresh blood or granulocyte concentrates. For stored whole blood, the degree of C3 conversion increased slightly to 2-3%. Prefiltration results for all samples showed a low level of C5a which did not change after passage through any filter. Serum incubated with filter material at 37°C showed 2-10% C3 conversion. In contrast, results with citrated plasma showed less than 3% conversion of C3. We conclude that although some filter materials may activate complement in serum, filtration of citrated blood products through microaggregate blood filters induces little complement activation.

新型polyester micropore blood transfusion filter (NS filter)の基礎的検討

新型polyester micropore blood transfusion filter (NS filter)の基礎的検討

Cardiopulmonary function following transfusion of three red blood cell products in elective abdominal aortic aneurysmectomy.

In order to evaluate the importance of red cell O(2) affinity of transfused blood on cardiac performance and adverse effects of transfusion on lung function, a prospective double-blind protocol was used in 27 patients undergoing abdominal aortic aneurysmectomy. Three types of blood were administered: packed red cells (PC), washed red cells (WC) and high 2,3 DPG red cells (2,3 DPG). An average of 4.5 units of blood was used per patient. Transfusion of 2,3 DPG blood resulted in maintenance of in vivo P(50) during surgery and an increase to 31.2 torr after operation (p < 0.001). An intraoperative fall in in vivo P(50) to 23.2 +/- 2.0 torr was observed in patients who were transfused with PC (p < 0.001) and to 25.1 +/- 2.6 torr with WC (p < 0.005). A fall in body temperature averaging 2.2 C intraoperatively was noticed in all three groups. After operation, in vitro P(50) decreased in patients transfused with PC (p < 0.005) and WC (p < 0.005) while it remained unchanged in the high 2,3 DPG group. This was consistent with the decrease of red cell 2,3 DPG in the PC (p < 0.001) and WC groups (p < 0.01) and maintenance in the 2,3 DPG group. Left ventricular stroke work and volume loading Starling type myocardial performance curves were similar for the three groups. Microaggregates measured by Coulter counting and screen filtration pressure were the same for all three products in samples drawn on both sides of the 40 microm transfusion filter. There was no relationship of transfusion volumes or type of blood product to changes in lung function (physiologic shunting, dynamic compliance and pulmonary arterial pressure) in the three groups of patients. The false negative, beta, error of missing a true 25% difference was less than 10%. It is concluded that 2,3 DPG enriched red cells improved oxygen availability, but that a 4.5 unit transfusion of any of the three blood products did not influence lung function or myocardial performance following aneurysmectomy.

Studies on the ultrastructure of blood cells and the microaggregate fraction in stored human blood.

Electron microscopy of citrate-phosphate-dextrose (CPD) buffered bank blood performed over 21 days shows that the normal architecture of erythrocytes, platelets and leucocytes disappears and that deformed organelles, leucocyte "ghosts", cell fragments and microaggregates accumulate. Leucocytes and platelets emerge as the most sensitive indicators of blood deterioration showing profound morphological changes from the first day. Microaggregates which passed through a 20-micrometer high capacity transfusion filter were identified as platelet conglomerates, leucocyte "ghost" and platelet-leucocyte "ghost" coaggregates with diameters of 6--20, 20--30 and 30--40 micrometers respectively. Of these aggregates present in the filtrate, 62% fell into the size range of 20--40 micrometers. The composition of microaggregates varies with storage time, the platelet conglomerates appear first during or after Day 1, leucocyte "ghosts" after Day 5 followed by platelet-leucocyte "ghost" coaggregate formation. At this stage the number of intact leucocytes and platelets is reduced and the filtrate shows an abundance of leucocyte debris. Microfiltration would thus appear to reduce but not eliminate the danger of microembolism and damage to capillary endothelium.

Particulate emboli retained by a screen and a depth transfusion filter: A sem study

Microembolization by platelet leukocyte aggregates is a threat to the pulmonary microvasculature when blood is transfused to patients. Those aggregates can be removed by filters (either depth filter or screen filter); their efficiency, as shown by SFP measurements is not questionable, however they are working in different ways as observed by SEM: mechanical retention and adsorption.

Filtration Characteristics of the Polyester Fiber Micropore Blood Transfusion Filter

The filtration characteristics of a new polyester fiber (Fenwal II) micropore blood transfusion filter were investigated. Filtration of stored human whole blood and packed cells resulted in return of screen filtration pressure (SFP) of the blood to normal. Increased filter weights verified removal of large amounts of debris and microaggregates from the blood. Filtration of large quantities of blood accomplished at very high flow rates did not adversely affect the composition of the filtered blood. We conclude that the polyester fiber (Fenwal II) micropore blood transfusion filter is effective in removing microaggregates from stored whole blood and packed cells. It has a high volume capacity, allows rapid flow, and is reliable during pressure transfusion.

Particulate emboli retained by the intersept (R) transfusion filter; a sem study

The Intersept (R) transfusion filter is the transfusion filter developed by Johnson and Johnson. Filtration is performed by both adsorption and mechanical retention. Not only microaggregates, but damaged and injured cells are likely to be trapped and/or adsorbed. Such a filter is not injurious to the blood components, but thrombotic material accumulation can occur with fresh blood.

Respiratory Distress Syndrome

To the Editor .—The respiratory distress syndrome, as manifested by increased pulmonary venous admixture, continues to be an important challenge in the management of multiply transfused patients. The study presented in theArchives(113:947-950, 1978), addresses the efficacy of Swank micropore transfusion filters in preventing increased pulmonary arterial venous shunting in surgical patients. They present a considerable increase in shunting as well as alveolar-arterial oxygen difference in patients transfused over 20% of blood volume through standard transfusion filters, but no difference in the same parameters in patients who were transfused through Dacron wool filters. In evaluating their preoperative data, it is apparent that the groups were noticeably different before surgery and that both groups had identical shunts and alveolar-arterial oxygen differences postoperatively. In addition, if the single patient with substantially elevated preoperative shunting were excluded from consideration, postoperative shunting would actually be less in patients with standard transfusion filters. Although

Filtration characteristics of the dual-mode (Johnson and Johnson) micropore blood transfusion filter.

Stored human whole blood and red blood cells of varying age were passed through dual mode microscope blood transfusion filters. Passage through the filters resulted in markedly decreased screen filtration pressure (SFP) of the blood and increased filter weights. Numerous microaggregates were removed and SFP returned to normal. Filtration resulted in reduced platelet and white cell counts but other blood components were not adversely affected. On the basis of this research, we conclude that this micropore blood transfusion filter is effective in removing microaggregates from stored whole blood and red blood cells. It has a high capacity and rapid flow rate and is reliable during pressure transfusion.

Increased pulmonary arteriovenous shunting in humans following blood transfusion. Relation to screen filtration pressure of transfused blood and prevention by Dacron wool (Swank) filtration.

Transfusion through standard filters to dogs of stored blood containing microaggregates results in an increase in pulmonary arteriovenous shunting (Qs/Qt) and a decreased diffusion capacity of the lung for O2. These effects are due to microemboli that pass the filters and are prevented by use of Dacron wool (Swank) micropore transfusion filters. It was the purpose of this study to determine whether alterations in pulmonary shunting occur in humans following transfusions of stored blood through standard transfusion filters. In eight patients transfused over 20% of blood volumes through standard filters, Qs/Qt and alveolar-arterial O2 tension differences increased significantly. These changes did not occur in patients transfused comparable amounts of blood through Dacron wool (Swank) filters or in patients transfused less than 20% of blood volumes. A direct correlation was found between the absolute percent change in Qs/Qt and the quantity of microaggregates passing the filter and present in the transfused blood. It is concluded that removal from stored blood of microaggregates by administration of the blood through effective micropore transfusion filters prevents an increase in Qs/Qt caused by administration of such material.

Evaluation of the Swank IL-201 transfusion filter.

The effects of a new transfusion filter (Swank IL-20U) on stored, whole blood have been examined. Six filters were preloaded by passage of two units of outdated, type-specific bank blood, and the effects of filtration on a third unit of 21-day-old blood flowing under 150 mm Hg pressure were measured. Filtration did not significantly alter erythrocyte or leukocyte count, total or plasma hemoglobin, red-cell fragility, and plasma sodium, potassium, albumin, or globulin. Platelet counts were reduced by 33%. Removal of microaggregates, assessed by Coulter counting, screen filtration pressure, total screen protein, wet and dry weight of material retained, and scanning electron microscopy, was shown to be effective over the entire range of particle size. In comparison with other transfusion filters previously examined in this laboratory, the Swank IL-201 filter combines the features of efficient microaggregate removal with moderate blood-flow rate. Compared to its predecessor, the Swank IL-200, this new filter design has improved flow characteristics without loss of microaggregate removal efficiency. In view of the similarity of performance demonstrated for several of the available filters, it seems likely that relative cost will constitute an important determinant of filter selection.

Effects of Fenwal 4C2423 transfusion microfilter on microaggregates and other constituents of stored blood.

The effects of a new micropore transfusion filter (Fenwal 4C2423) on stored whole blood have been examined. Five filters were preloaded by passage of two units of outdated type specific bank blood, and the effects of filtration on a third unit, consisting of 21-day-old blood, flowing under 150 mmHg pressure, were measured. Filtration did not significantly alter red blood cell count, total hemoglobin, red blood cell fragility, plasma sodium, potassium, albumin, or globulin. Some platelets and white blood cells were removed and a small amount of hemolygis of erythrocytes (less than 0.1%) was observed. Removal of microaggregates, assessed by Coulter counting, screen filtration pressure, total screen porteins, wet and dry weights of material retained, and scanning electron microscopy, was shown to be excellent over the entire range of particle size. Comparison of the Bentley PFS-127, Fenwal 4C2417, Johnson & Johnson Intersept, Pall Ultipore, and Swank IL200 filters led to the conclusion that the Fenwal 4C2423 was both a significant improvement over the previous Fenwal design and comparable to the most efficient of these filters for both the removal of microaggregates during massive blood transfusion and for the blood flow rates obtained.

PROGRESSION AND RESOLUTION OF CHANGES IN PULMONARY FUNCTION AND STRUCTURE DUE TO PULMONARY MICROEMBOLISM AND BLOOD TRANSFUSION

It was the purpose of this research to define the progression over several days of changes in pulmonary function and structure and to document the phases of recovery following transfusions to dogs of sublethal quantities of stored blood containing microaggregates. Ten dogs underwent partial exchange transfusions averaging 60% of blood volume through standard blood transfusion filters. Average screen filtration pressure (SFP) of the blood was 85 mm Hg. Pulmonary hypertension did not develop, but there were striking decreases in O2 consumption, increases in Qs/Qt and decreases in Do2. Changes became progressively more marked over the first 48 to 72 hours after the transfusions. Pulmonary function of surviving animals returned nearly to normal by the sixth day after transfusions. Pathologic examinations of the lungs of animals sequentially sacrificed over 6 days showed intravascular microemboli, alveolar cell hyperplasia and interstitial and alveolar pulmonary edema. Progressive recovery was associated with progressive resolution of all detrimental changes. In 6 animals exchange transfused 100% of their blood volumes through dacron wool (Swank) filters and in three control animals that were not transfused, there were no significant changes in pulmonary function or structure. These experiments define the progression of deterioration and recovery over 6 days of pulmonary function in dogs after sublethal pulmonary microembolism occurring during blood transfusion.

An evaluation of several blood transfusion filters.

Several blood transfusion filters designed to remove microemboli were evaluated for filtration and flow characteristics, as well as for hemolysis and for release of particulate debris from the filter. The Dacron wool filter, a depth filter, was superior at removing microemboli measured with an electronic particle size analyzer. A 25 micrometer pore mesh filter was least effective at removing microemboli from stored blood, but demonstrated the most favorable flow rates and induced no apparent red blood cell destruction during filtration. In general, filter efficiency and filter induced hemolysis correlated inversely with flow rate. No filter tested released significant quantities of particulate debris when compared with unfiltered isotonic saline.

Polyurethane foam (Bentley) micropore blood transfusion filter: filtration characteristics.

Stored human blood of varying age was passed through polyurethane foam (Bentley) micropore blood transfusion filters. Passage through these filters resulted in decreased screen filtration pressure (SFP) of the blood and increased filter weights. Numerous microaggregates were removed and SFP returned to normal after filtration. Occlusion of the filter occurred after passage of only 2 units of whole blood. On the basis of this research, we conclude that polyurethane foam (Bentley) micropore blood transfusion filters are effective in removal of microaggregates from stored human blood. Because the filtering capacity is not great, it is recommended that when these filters are used during transfusion a new filter be used for each unit of blood administered.