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Biomedical subjects

B C McLeod

Publications and source records attributed to B C McLeod.

At least 37 records · Page 2Linked to original sources
PubMed1991

The technique of therapeutic apheresis. Removal of abnormal blood elements may succeed when all else fails.

Therapeutic apheresis is a generic term that refers to removal of abnormal blood cells and plasma constituents. The terms "plasmapheresis," "leukapheresis," and "erythrocytapheresis" describe the specific blood element that is removed. Apheresis therapies can be performed in the ICU to manage a number of neurologic, hematologic, and autoimmune disorders, including myasthenia gravis, Guillain-Barré syndrome, sickle-cell disease, and Goodpasture's syndrome. Apheresis procedures generally require two points of contact with the circulation--one for blood withdrawal and one for return; the withdrawal site should sustain a flow rate of at least 50 mL/min. Although apheresis is generally quite safe, hemodynamic instability, hypocalcemia, and dilutional coagulopathy can occur.

Autoimmune Diseases↗
PubMed1990

Computerization of plateletpheresis quality control records with a commercially available spreadsheet program.

Many apheresis units lack the resources to acquire customized computer software for record keeping. We have adapted a commercially available "spreadsheet" program (Lotus 1-2-3) to aid in quality control activities for plateletpheresis. Data are entered in a grid pattern wherein each donation occupies one row and successive columns contain numerical data derived from the donation. The last two columns contain formulas that calculate yield and collection efficiency from values entered in preceding columns. The program runs on an IBM PC or equivalent with 512 K RAM; the combined cost of a computer and software is currently under $2,000.00. Data entry requires fewer keystrokes per record than computation of yield and efficiency with a calculator, and creates an inclusive permanent record for future analysis. Data sorting and statistical functions allow rapid identification of incomplete records, and derivation of average platelet yield and/or collection efficiency for any time period of interest. The program also facilitates determining the proportion of donations that fall below any chosen cutoff. Performance characteristics of a particular instrument or operator can be assessed easily by isolating the pertinent records and analyzing them separately. The system will thus accomplish a variety of quality control activities, including those mandated by licensing agencies. It can be implemented by apheresis personnel with limited "computer literacy" and is superior to manual tabulation of quality control data in both ease of data entry and facility of analysis.

Data Interpretation, Statistical↗
PubMed1990

Alloimmunization to RhD by platelet transfusions in autologous bone marrow transplant recipients.

Platelet transfusions from RhD-positive (D-positive) donors are often given to RhD-negative (D-negative) cancer patients. The low observed rate of alloimmunization has been attributed to disease and therapy-related immunosuppression. We have studied the occurrence of alloimmunization in 16 D-negative patients who did not have detectable anti-D prior to autologous bone marrow transplantation for malignant disease. All received D-positive platelets, but no other D-positive blood product. Three patients (19%) developed anti-D at 13, 24 and 83 days, respectively, after first receiving D-positive platelets, and after a total dose of 53, 65 and 119 D-positive platelet unit equivalents, respectively. Two of them also developed anti-C. The 13 patients in whom anti-D was not detected were also heavily transfused with D-positive platelets (mean +/- SD = 136 +/- 82 platelet unit equivalents). In 6 of them, the last recorded antibody screen was less than 3 months after the first D-positive platelets, and may not exclude a primary immune response. Thus, despite profound immunosuppression associated with autologous marrow transplantation, alloimmune responses to D-positive red cells in platelet concentrates can occur in some D-negative recipients.

Adolescent↗
PubMed1990

Plasma exchange donation of cryoprecipitate after DDAVP stimulation: an alternative source of factor VIII.

The last few paragraphs will summarize pertinent characteristics of this material in relation to other current sources of factor VIII. First, at a time when safety is the paramount concern in hemophilia therapy, plasma exchange donation offers a product with a very low intrinsic risk of blood borne infection; in many cases, this risk can be equivalent to a single unit of blood. This is much lower than previous versions of commercial factor VIII and much lower than the intrinsic risk of the starting material for current products. We believe this risk is low enough to justify its use without viral inactivation, although certain additional measures, such as the 6-month quarantine devised by Dr. Noel, could increase the margin of safety even further. Note that the principle of limitation of donor exposure is a proven one, which should be effective against any infectious agents, including those unknown to us at this time. Second, at a time when efforts to improve the safety of commercial factor VIII have led to extraordinary increases in cost, factor VIII from plasma exchange donation promises to be relatively inexpensive. Our data indicate that most blood centers could produce factor VIII in this way at 25-50% of the price of the newest commercial products. Finally, there is the matter of supply. At present, commercial factor VIII is in short supply. It may be that worldwide demand for other plasma derivatives, combined with the reduced yield of factor VIII associated with viral inactivation measures, will dictate chronic shortages for the forseeable future. In this unsettled milieu, plasma exchange donation offers a new source of factor VIII, which need not be tied to the supply of, or demand for any other plasma products. Instead, it depends on local initiatives in blood banks and hemophilia centers, and donor activity that can be tailored specifically to the needs of hemophilia patients. Thus, in spite of the impressive advances in the safety of commercial factor VIII which have recently been implemented, we believe there is a place for single donor cryoprecipitate from plasma exchange donation in the treatment of hemophilia and other bleeding disorders in the 1990's. Its use should be more widely and more extensively investigated.

Blood Donors↗
PubMed1989

Treatment of von Willebrand's disease and hypofibrinogenemia with single donor cryoprecipitate from plasma exchange donation.

Conventional replacement therapy for hypofibrinogenemia and von Willebrand's disease requires multiple donor exposures and a correspondingly high risk of blood-borne infection. We describe the collection and successful use of cryoprecipitate derived from a single donor by plasma exchange donation to support such patients through major hemostatic stresses. The father of an epileptic patient with von Willebrand's disease produced cryoprecipitate containing 23,546 units of von Willebrand factor (vWF) in nine desmopressin-stimulated donations; this provided total factor replacement for neurosurgery to remove a seizure focus. The average yield was 2,616 units per donation and the average VWF concentration in cryoprecipitate was 17.7 units/ml. The husband of a hypofibrinogenemic patient with a history of postpartum hemorrhage provided cryoprecipitate containing 13.4 g of fibrinogen in five donations; this supported his wife through parturition without recourse to other blood products. The average yield was 2.7 g per donation, and the average fibrinogen concentration was 15.3 g/liter. Plasma exchange donation is a practical alternative source for cryoprecipitate. It can provide vWF and fibrinogen that carry a reduced risk of infectious disease transmission.

Adult↗
PubMed1989

Simultaneous collection of platelets and cryoprecipitate by plasma-exchange donation.

To increase cost efficiency, the simultaneous collection of platelets during plasma-exchange donation of cryoprecipitate was investigated. Sixteen desmopressin (DDAVP)-stimulated donors underwent 90 simultaneous donations. Permanent donor plasma loss for each donation averaged 150 ml in cryoprecipitate and 151 ml in platelet concentrates. Mean factor VIII (FVIII) yield was 4699 +/- 2754 IU per donation. The mean yield in the platelet products was 4.63 X 10(11) platelets; aggregation properties and posttransfusion increments were satisfactory. White cell contamination averaged 4.05 X 10(9) but could be lowered by a secondary centrifugation. The direct cost for a single-donor platelet transfusion produced in this way is estimated at $102.19 and that for FVIII at $0.055 per IU. Simultaneous donation is technically feasible and safe for donors, and it provides functional products that are more cost-effective than apheresis platelets or cryoprecipitate donated separately.

Blood Donors↗
PubMed1987

A high-potency, single-donor cryoprecipitate of known factor VIII content dispensed in vials.

Current factor VIII products expose recipients to many donors and hence to a high risk of acquiring blood-borne infections. Plasma-exchange donation of cryoprecipitate can reduce donor exposure by repeatedly obtaining large yields of factor VIII from individual donors. In this study, donor factor VIII levels were stimulated with desmopressin before donation. Mean yield per donation increased from 1399 +/- 425 IU in controls to 3818 +/- 1350 IU in stimulated donations (p less than 0.001), and mean factor VIII concentration in the cryoprecipitate increased from 8.2 +/- 3 IU/mL to 24 +/- 12 IU/mL (p less than 0.001). A new packaging system dispenses assayed aliquots of stimulated cryoprecipitate in plastic vials. The direct cost of production for this material is $.065 per unit. The cryoprecipitate is hemostatically active and convenient to use, and the aggregate yields from sequential donations by stimulated persons are high enough to allow long-term, single-donor support of many adults with hemophilia.

Blood Component Removal↗
PubMed1984

Use of 'single donor' factor VIII from plasma exchange donation.

We investigated the advantages of using "single donor" factor VIII derived from a new cyclic apheresis donation (plasma exchange donation) to treat hemophiliac children. By selecting donors with high factor VIII levels and using thaw-siphon isolation of cryoprecipitate, we achieved a mean yield of 1,360 units of factor VIII per weekly donation. The half-life, posttransfusion increments, and clinical efficacy of factor VIII in this material are comparable with those of factor VIII from other sources. A single donor has provided total support for seven months for one patient with severe hemophilia, and another for 24 months for a patient with mild hemophilia. Other patients have been supported through major surgery or CNS hemorrhage by a single donor. This approach to factor VIII replacement is hemostatically effective and can substantially decrease donor exposure for both major and minor bleeding episodes. The reduction in donor exposure should result in a reduced risk of acquiring hepatitis and perhaps the acquired immune deficiency syndrome in patients with hemophilia A.

Blood Donors↗
PubMed1984

'Hypocryoglobulins'. Enhanced cryoprecipitation from hypotonic serum in patients with vasculitis.

Three patients with cutaneous vasculitis and one patient with digital gangrene had a negative or equivocal test for cryoglobulins but a positive result in a modified assay for cryoproteins ( hypocryoglobulins [ HGs ]) in which serum is rendered hypotonic by dilution with an equal volume of distilled water before incubation in the cold. Each cryoprecipitate contained a mixture of immunoglobulins, and in two instances, a monoclonal component was demonstrated. Rheumatoid factor activity was found in two precipitates. All four patients improved with plasmapheresis, and two subsequently responded to alkylating agents. Seven patients with conventional cryoglobulins had precipitation from diluted serum as well, but none had a substantial increase in precipitation in the HG assay. Only two of five patients with seropositive rheumatoid arthritis had abnormal levels of HG. Hypocryoglobulins are a new category of abnormally insoluble serum proteins, probably closely related to conventional cryoglobulins, which are readily detected in a simple precipitation assay.

Aged↗
PubMed1984

Analysis of serum free light chains by crossed immunoelectrophoresis: comparison with urinary light chains in light chain disease.

We investigated the relationship between serum free light chain levels measured by crossed immunoelectrophoresis in ten patients with light chain disease and traditional 24-hour urinary light chains in the same patients. The crossed immunoelectrophoresis test requires only a venipuncture for specimen acquisition, can be completed within 24 hours, and has a reproducibility (+/- 14%) comparable with that of other immunoprecipitin techniques. Twenty-eight serum-urine pairs, representing 18 discrete intervals, were analyzed. There was a close relationship between changes in serum and urine light chain levels, with a correlation coefficient of .77 or .93, depending on the method of calculation. This suggests that serum light chain levels measured by crossed immunoelectrophoresis would be equivalent to urinary light chain levels as indicators of tumor burden. Monitoring serum levels would have the advantage of greatly simplified specimen acquisition. In patients with renal failure, serum light chain levels should be a superior indicator of light chain synthesis.

Blood Protein Electrophoresis↗
PubMed1983

Serum-free light chain analysis by crossed immunoelectrophoresis: correlation with plasmapheresis in light chain disease nephropathy.

The technique of crossed immunoelectrophoresis (X-IEP) has been used to quantify free monoclonal light chains (LC) directly in the serum of patients with light chain disease, without preliminary gel or membrane filtration of serum to separate whole immunoglobulin. LC concentration is proportional to the area under an immunoprecipitin peak formed by LC in the patient's serum and an anti-LC antibody of appropriate specificity. Light chains of beta electrophoretic mobility can be processed in the standard X-IEP technique at pH 8.6. Light chains of gamma mobility must be processed in a modified technique using a pH of 5.0 and a carbamylated antiserum in the second dimension gel. Dose response curves obtained from the method in serial dilution experiments with sera from 18 patients gave correlation coefficients greater than or equal to 0.99. Replicate measurements of absolute LC concentration on the same specimens were within +/- 10%. The method can also detect polymerized light chains. Serum light chain levels were measured during the course of plasmapheresis therapy in three patients with light chain disease and renal failure. Light chain levels were shown to fall after plasmapheresis and to rise rather rapidly in the interval between treatments.

Acute Kidney Injury↗
PubMed1983

Partial plasma protein replacement in therapeutic plasma exchange.

We wished to determine whether subtotal replacement of protein in plasma removed at plasma exchange would be adequate to prevent hypovolemia and hypoproteinemia. Seven well nourished outpatients with chronic progressive multiple sclerosis underwent 60 plasma exchanges in which two liters of plasma were replaced with 750 ml saline followed by 1250 ml of a 5% albumin solution (62.5% albumin replacement). Total serum protein, protein electrophoresis, and immunoglobulin levels were measured before and after each exchange. Clinically, the exchanges were well tolerated. Total serum protein dropped by a mean of only 18% during the study and mean preexchange serum albumin levels were unchanged, even though immunoglobulins decreased by 57-72%. We conclude that in well nourished patients, partial albumin replacement of this magnitude is an adequate substitute for plasma removed in a plasma exchange.

Adult↗
PubMed1983

Gas-like radiolucencies in a popliteal cyst.

A 71-year-old man with rheumatoid arthritis complained of pain and swelling in the left calf. X-ray examination of the calf disclosed radiolucencies suggestive of soft tissue gas; however, subsequent investigation revealed no evidence of infection and an arthrogram showed a dissected popliteal cyst in the area of the gas. Gas-like radiolucencies in a popliteal cyst are an unusual finding which has not been previously reported.

Aged↗
PubMed1983

Complement metabolism during membrane plasma separation.

Because it has been found that some plasma separator membranes can activate complement in serum, this study focuses on the behavior of complement during actual membrane plasmapheresis. Complement metabolism in subjects undergoing membrane plasma separation with three different prototypic devices was studied. Complement activation was judged by crossed immunoelectrophoretic analysis of C3 in plasma. A cellulose acetate separator employed with heparin as the anticoagulant caused extensive C3 conversion (up to 50%) in separated plasma. A polysulfone separator used with citrate, and a polyvinylchloride derivative separator employed with heparin plus citrate, caused only small amounts of C3 conversion (0-10%) in separated plasma. C3 conversion in the cellulose acetate separator was reduced when citrate was included in the anticoagulant regimen, whereas C3 conversion in the polyvinylchloride derivative separator was increased when citrate was omitted. Activation of complement by the membrane material may occur during membrane plasma separation. Selection of membranes judged weakly activating by in vitro screening and the use of citrate anticoagulation would appear to minimize complement activation in membrane plasma separators.

Cellulose↗
PubMed1982

Haemolytic transfusion reaction due to ABO incompatible plasma in a platelet concentrate.

A patients of blood type A1 developed brisk, but transient haemolysis after receiving a platelet transfusion derived from 4 group 0 donors. Anti-A was detected on his red cells and in his plasma. 2 of the platelet donor were found to have very high titers (1:10240) of anti-A and positive haemolysin tests. Thus, a haemolytic reaction can result from transfusion of incompatible plasma in a platelet concentrate.

Blood Group Antigens↗
PubMed1982

Plasmapheresis decreases neuroelectric blocking activity in multiple sclerosis.

Serum neuroelectric blocking factor activity diminished after plasmapheresis in five of seven patients with MS but returned to baseline levels in 2 to 3 weeks. In the other two patients changes were insignificant. All patients studied had progressing symptoms. Five plasma exchanges of 2 liters were performed in 10 days. Two patients improved clinically, whereas five did not. There was no correlation between the level of neuroelectric blocking activity and changes in clinical status.

Adult↗