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Biomedical subjects

G Rock

Publications and source records attributed to G Rock.

At least 55 records · Page 3Linked to original sources
PubMed1998

Reduction of plasma volume after storage of platelets in CP2D.

BACKGROUND: There has been concern that further deterioration might occur if stored platelets are centrifuged to reduce their volume. Although such centrifugation appears to have minimal effect on platelets in CPDA-1 (osmolarity, 470 mOsm) there is no information on the situation with CP2D (580 mOsm). STUDY DESIGN AND METHODS: Platelet concentrates from CP2D packs were sampled at 1 and 5 days and after centrifugation was used to reduce the plasma volume to 10 mL. The aggregation, hypotonic shock response, morphology, pH, and lactate, glucose, pCO2 and pO2 levels were assessed, and values were compared to those seen with CPDA-1. In addition, blood was collected from the same donors into both CP2D and standard sodium citrate anticoagulant in an anticoagulant-to-blood ratio of 1:8 and the aggregation response of the fresh platelets was measured. RESULTS: Collection of blood into CP2D results in an immediate reduction of the platelet aggregation response when compared to that found after collection of blood into sodium citrate or CPDA-1. Aggregation is further decreased after storage; however, these changes and those for hypotonic shock, pH, lactate, glucose, and pCO2 are similar to those seen for CPDA-1. Additional centrifugation did not cause further change. CONCLUSION: Platelets stored in CP2D have reduced in vitro function after 5 days of storage, but subsequent centrifugation to reduce the plasma volume does not further alter these platelets.

Anticoagulants↗
PubMed1998

The use of plasma as a replacement fluid in plasma exchange. Canadian Apheresis Group.

BACKGROUND: The Canadian Apheresis Group has maintained a national registry of apheresis activities for the past 16 years. Since 1991, the use of plasma as a replacement fluid in plasma exchange has been recorded. STUDY DESIGN AND METHODS: Six years of data from the registry on the use of plasma as a replacement fluid were analyzed. RESULTS: Plasma was used in more than 25 percent of all plasma exchange procedures. Of 41,519 plasma exchange procedures reported, 11,970 used plasma alone or in combination with albumin. In 1991, 1026 (78%) of these procedures used plasma appropriately for either thrombotic thrombocytopenic purpura (TTP) or adult hemolytic uremic syndrome (HUS); between 1992 and 1996, these numbers were 1043 (81%), 1570 (86%), 1171 (87%), 2192 (92%), and 2741 (90%), respectively. In the remaining procedures, frozen or cryosupernatant plasma was administered to 326 patients for a total of 40 diseases other than TTP or HUS. CONCLUSIONS: In those diseases for which plasma was administered as the sole replacement fluid, no disease appears to justify such treatment without the existence of an associated condition requiring specific replenishment of some plasma component. Further evaluation of the specific indications for the use of plasma as a replacement fluid in plasma exchange is required for diseases other than TTP or HUS.

Adult↗
PubMed1997

Pentastarch instead of albumin as replacement fluid for therapeutic plasma exchange. The Canadian Apheresis Group.

BACKGROUND: Human albumin is commonly used as a replacement fluid in therapeutic plasma exchange (PE). In order to determine whether Pentaspan (PES), a synthetic low molecular weight starch solution, might be an effective substitute, we compared albumin with PES in 12 patients with myasthenia gravis or Guillain-Barré syndrome. STUDY DESIGN AND METHODS: Six patients were randomly assigned to receive PES and six to receive albumin as replacement fluid during their course of PE, which consisted of two to five treatments delivered over a maximum of 10 days. All patients were hospitalized and observed closely. Blood pressures were recorded every 4 hours and daily measurements were made of hematologic, coagulation, and immunoglobulin parameters. RESULTS: Individual exchange volumes were similar in each group (37 ml/kg--range 6-62--in patients receiving albumin vs. 41 ml/kg--range 6-41--in those receiving PES). Changes in immunoglobulin levels and coagulation parameters were similar but mild, transient thrombocytopenia was observed in three subjects given PES. Total serum protein and albumin levels decreased significantly in patients replaced with PES. Clinically, PES was well tolerated. Hypotension occurred in one patient who developed septic shock due to an infected femoral catheter; in another patient, a pre-existing pleural effusion was thought to increase slightly. CONCLUSIONS: PES appears to be a safe replacement fluid for PE, but larger clinical studies are required to confirm these findings.

Adult↗
PubMed1997

Coagulation factor changes following endurance exercise.

OBJECTIVE: To compare preexercise with immediate and 24 h postvalues of coagulation parameters in experienced athletes following a single, 42-km marathon run. DESIGN: Blood samples were taken 18 h before, immediately after, and 24 h after a marathon race from 14 well-trained individuals, and coagulation factors were measured. SETTING: The setting was a 42-km race on a cloudy day in May with an ambient temperature of 22 degrees C. SUBJECTS: The subjects were fourteen normal healthy individuals (12 men and 2 women) who regularly participated in runs of at least 20 km each week. INTERVENTION: The subjects all undertook a 42-km marathon run followed by a 24-h rest period and a repeat assessment. MAIN OUTCOME MEASURES: Coagulation factors including factor VIII (FVIII) and von Willebrand factor (vWF) were measured, as was the platelet response to aggregating agents. These responses are all considered as primary outcome measures of hypercoagulability and reflect the prethrombotic state. RESULTS: The hematocrit was not altered immediately after the race, but the platelet count (mean +/- SD) was significantly elevated (p < 0.05) to 322 +/- 54 x 10(9)/L from 256 +/- 70 x 10(9)/L, and the mean platelet size increased by 24 h (p < 0.05). Platelet aggregation in response to epinephrine, adenosine diphosphate, and collagen was decreased by 40%, 15%, and 60%, respectively, at 24 h; the response to ristocetin was only slightly (10%) altered. There was a significant elevation of beta-thromboglobulin in the plasma at the end of the race, and this elevation persisted for 24 h, indicating considerable release from the platelet alpha granules. The effect on platelet function was further demonstrated by a decrease in the quantity of glycoprotein Ib at 24 h, but not immediately after the race. There was an approximately 300% increase in the levels of FVIII, vWF antigen (vWF:Ag), and ristocetin cofactor activity. In addition, the normal vWF:Ag multimer pattern was changed in the samples taken immediately after the race. CONCLUSIONS: The data support the evidence of significant alteration of certain factors that are involved in coagulation following endurance exercise. Increases in FVIII and vWF are also noted in some prethrombotic conditions. The decreased platelet aggregation suggests early activation during the period of exercise.

Adult↗
PubMed1997

New concepts in coagulation.

The process of blood coagulation is a complex and incompletely understood process. In the last decade or so critical steps have been taken toward better understanding this process. It is now widely agreed that the principal initiating pathway of coagulation is the so-called extrinsic pathway due to the action of tissue factor and Factor VII. Concomitant with this appreciation has come an understanding and elucidation of the roles of tissue factor pathway inhibitor. Although the "intrinsic pathway" is no longer felt to be the initiator of coagulation, recent evidence suggests that Factor XIa may constitute an important amplification pathway of the coagulation system in vivo. Refinement of flow cytometry has enabled the detection of novel platelet antigens on activated platelet surfaces. It is hoped that detection and characterization of these antigens, including adhesion molecules such as P-selectin, will enable further understanding of the platelet's role in pathological coagulation and inflammation. The endothelium is also intricately involved and recent work has determined the importance of endothelial produced factors such as endothelium-derived relaxation factor, endothelin, and thrombomodulin. Finally, with the meteoric rise in molecular genetic technology, specific genetic abnormalities in a number of plasma proteins has been elucidated, with marked implications on the understanding of the coagulation process. For example, the mutation on the gene for Factor V, leading to Arg506 replacement with Gln, produces activated protein C resistance with a concomitant increased risk of venous thrombosis. Thus, significant advances in knowledge of the endothelium, platelets, and plasma factors involved in coagulation have been made and now the challenge of the future is to better elucidate the interactions of these components.

Anticoagulants↗
PubMed1996

Acquired von Willebrand factor deficiency during high-dose infusion of recombinant factor VIII.

Constant infusion of factor VIII (FVIII) into patients with haemophilia A after major surgery has been recommended as optimal treatment to avoid peaks and valleys in the circulating levels of FVIII and to allow the use of much lower doses of FVIII than are historically required. One of our young patients with severe (< 0.01 U/ml FVIII) haemophilia suffered a subdural haematoma for which he received treatment with 815190 recombinant FVIII (rFVIII) units over a period of 52d. 2 weeks after admission, because of low FVIII levels and the presence of FVIII inhibitors, the infusion rate was increased to > 100 U/kg/h for 14d. During this time the FVIII level fluctuated between 0.6 and 4.2 U/ml. For some period it was not possible to detect ristocetin co-factor activity in this patient's plasma and the von Willebrand factor (VWF) level and VWF multimer pattern resembled those of a patient with von Willebrand's disease. Subsequently, when the rFVIII dose was increased 2-fold, this was not reflected by the plasma level of FVIII although antibodies were not detected. The data suggest that the prolonged infusion of very high levels of rFVIII which is deficient in von Willebrand factor can result in depletion of VWF from existing stores, producing a laboratory picture which is consistent with the diagnosis of von Willebrand's disease. Further, in the absence of complexing with VWF, FVIII appears to be cleared from the circulation at an increased rate. This is expensive and potentially compromising. Therefore, when administering very high doses of FVIII concentrates devoid of VWF for prolonged periods of time, ristocetin cofactor and VWF levels should be monitored.

Factor VIII↗
PubMed1996

Cryosupernatant as replacement fluid for plasma exchange in thrombotic thrombocytopenic purpura. Members of the Canadian Apheresis Group.

The current established treatment of thrombotic thrombocytopenic purpura (TTP) is plasma exchange with fresh frozen plasma (FEP). With this treatment, there is a 49% response after seven exchanges and a 78% survival at 1 month. Although the exact cause of TTP is unknown, the presence of von Willebrand factor (VWF) multimers has been implicated in the disease. Accordingly, it has been suggested that cryosupernatant (plasma from which cryoprecipitate has been removed), which is relatively deficient in VWF multimers, might be an effective replacement fluid during plasma exchange. Patients from six centers were treated by plasma exchange with cryosupernatant. 18 patients who had failed a first course (average 7.7 exchanges) of plasma exchange with FFP. received a further seven exchanges with cryosupernatant. Subsequently, 40 previously untreated patients were exchanged with cryosupernatant. Of the 18 previously treated patients, 11 responded (defined as an increase in platelet count to > 150 x 10(9) /1 and no neurological events) after seven exchanges and 15 (83%) of the patients were alive at 1 month. The response rate in the 40 previously untreated patients was 75% at the end of seven exchanges and 95% of the patients were alive at 1 month. These values are significantly different (P < 0.05) from those reported in our earlier study and in other patients concurrently treated at the same centres with FFP when cryosupernatant was not available. Some patients who have failed to respond to plasma exchange with FFP replacement will respond to further exchange with cryosupernatant. Cryosupernatant replacement may be more effective as first-line treatment of TTP than FFP.

Adult↗
PubMed1996

Therapeutic plasmapheresis.

Considerable work has been carried out over the past 25 years to define the conditions for application of plasmapheresis or plasma exchange. The use of plasma exchange in neurologic disorders such as Guillain-Barré syndrome has seen widespread application including the combination of plasma exchange with the use of intravenous immunoglobulin. Investigators have assessed the use of each therapy alone and in combination and, although both are advantageous, the relative benefits of each are still somewhat unclear. Other forms of neuropathies also seem to benefit from plasma exchange, as do some vasculitides. The use of cryosupernatant rather than frozen plasma to treat thrombotic thrombocytopenic purpura has improved outcome, but the cumulative data from many trials indicate that the mortality rate, if anything, persists at an even higher level than it did decades ago. Hemolysis, elevated liver enzymes, and low platelets syndrome, which has some characteristics similar to those of thrombotic thrombocytopenic purpura, has been shown to have variable response to plasma exchange. Plasma exchange has also been assessed as a treatment in organ failure and transplant rejection. Liver failure has shown variable response even when bioartificial livers are used. Of particular interest is the emerging use of photopheresis as an immune modulatory therapy. This is one of the newer innovative modifications of standard plasma exchange that will undoubtedly lead to interesting future therapeutic opportunities. The field continues to evolve.

Humans↗
PubMed1994

Anti-CD36 antibodies in thrombotic thrombocytopenic purpura.

The membrane glycoprotein CD36 (GPIV, M(r) 88,000) is found on platelets, monocytes and endothelial cells of the microvasculature. In the present study, anti CD36 antibodies have been identified as occurring with high frequency in patients with thrombotic thrombocytopenic purpura. The presence of anti CD36 antibodies in 15 TTP plasma samples thought to contain them on the basis of an initial screening by protein blots was confirmed by re-screening against a standard of purified CD36, by immunoprecipitation from 125I-labelled control platelets and by dot blots against purified CD36. In a further 28 random samples examined, 23/27 (85%) were CD36-positive by immunoprecipitation, 21/28 (75%) by protein blotting, and 17/28 (60%) by dot blots against purified CD36. On protein blots following SDS-PAGE, immunoprecipitates produced from normal platelets by TTP plasma gave positive reactions with the anti CD36 monoclonal antibody 125I-Mo91. One half of the total TTP samples examined (21/42) caused approximately 70% release in control platelets loaded with 14C-serotonin. Of samples causing release > or = 70%, one-half (8/15) failed to cause release from Naka-negative platelets which constitutively lack CD36 showing that CD36 was the sole target for platelet activation in these TTP samples. These studies demonstrate that antibodies directed against CD36 occur frequently in TTP patients and could cause thrombotic complications and vascular damage by reacting with the parent antigen present in platelets and endothelial cells.

Antigens, CD↗
PubMed1994

Anti-CD36 antibodies in patients with lupus anticoagulant and thrombotic complications.

Six patients with lupus anticoagulant with thrombotic complications, but not exhibiting systemic lupus erythematosus, demonstrated the presence in their plasma of antibodies directed against platelet antigens which were not detectable in two patients presenting with lupus anticoagulant but without thrombotic complications. Protein blotting of separated normal platelet proteins against patient plasma gave up to 18 bands of varying intensity indicative of multiple antiplatelet antibodies; one of these antibodies recognized a component with a mobility identical with CD36 (GPIV; m.w. 88,000) in 4/6 cases. Antibodies to CD36 and one or two other components were identified in 5/6 cases by immunoprecipitation from 125I-labelled control platelets and 6/6 by dot blots against purified CD36. These results suggest that antiplatelet antibodies and, specifically, anti CD36 antibodies, occur frequently in the plasma of patients presenting with lupus anticoagulant and thrombotic complications.

Adult↗
PubMed1993

Characterization of factors affecting the stability of frozen heparinized plasma.

The use of heparin rather than citrate as primary anticoagulant has been shown to significantly improve the initial activity, stability and recovery of factor VIII:C from human plasma, cryoprecipitates or factor VIII concentrates if the plasma was initially frozen at -80 degrees C and subsequently stored at this temperature. If frozen and stored at progressively warmer temperatures however, increasing amounts of insoluble protein aggregates, termed storage precipitates (SPs), were recovered in the thawed plasma and cryoprecipitate fractions. Plasma recovery by centrifugation at 7,000 g for 7 min [Method I (MI)], 2 x 10 min (MII) or 15 min (MIII) had little effect on SP formation after 1 month at any storage temperature. After 4 months at -20 degrees C, more SP was recovered from MIII plasma whereas at -40 degrees C, more SP was recovered from MI plasma. Also, the preparation method had little or no effect on factor VIII:C activity at equivalent storage times or temperatures. A trend towards improved factor VIII recoveries was noted at lower freezing and storage temperatures however. SP formation was associated with reduced fibrinogen levels in the recovered plasma without loss of antithrombin-III or increased fibrinopeptide-A. Western blots showed polymerization of A alpha or gamma-chains of fibrinogen. SP formation was reduced or eliminated with factor XIII inhibitors, antibody to the active factor XIII a subunit or adjustment of heparinized plasma to 5-10 mM sodium citrate before initial freezing and storage. Although plasma factor VIII:C recoveries were only slightly affected at these citrate concentrations under most conditions, its recovery in cryoprecipitates was substantially improved owing to the reduction or absence of SPs.

Blood Preservation↗
PubMed1992

Thrombotic thrombocytopenic purpura: outcome in 24 patients with renal impairment treated with plasma exchange. Canadian Apheresis Study Group.

The Canadian Apheresis Study Group recently completed a randomized clinical trial involving 102 patients with thrombotic thrombocytopenic purpura (TTP), in which treatment with plasma infusion and treatment with plasma exchange were compared. Thirty-three other patients were ineligible or refused to be randomly assigned in the trial. Of the 33 patients, 24 were assessed as ineligible because they would be unable to tolerate the fluid input that would occur if they were randomly assigned to receive plasma infusion. All 24 patients had oliguria and elevated creatinine and/or blood urea nitrogen level. These 24 patients were treated with acetylsalicyclic acid, dipyridamole, and plasma exchange according to the standardized protocol defined in the trial. Blood for tests of factors possibly involved in the pathogenesis of TTP was drawn before exchange and at intervals during and after exchange. The mean platelet count before exchange was 35.5 x 10(9) per L. In 12 of the 24 patients, the platelet count reached 150 x 10(9) per L or greater by 7 days after the initiation of plasma exchange. Three patients responded partially, in that their platelet count increased to at least twice that at presentation, but remained below 150 x 10(9) per L. One patient died during the first week. Of the eight other patients who experienced treatment failure at the 7-day assessment point, six subsequently responded, four while continuing to receive plasma exchange and two after plasma exchange had been discontinued. Of the 15 patients who either responded fully or responded partially by the end of the first cycle, all survived.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Repeat plateletpheresis: the effects on the donor and the yield.

Requirements for HLA ot otherwise matched single-donor platelets may sometimes require repeat plateletpheresis of an individual donor. AABB standards permit the repeat collection of platelets by plateletpheresis of a single donor at 48-hour intervals, whereas recent recommendations from England state that a donor should not donate platelets more often than 12 times a year. To assess the effects of repeat plateletpheresis on the donor, we have studied the hematological indices and the product yields following every other day plateletpheresis of 13 normal donors who gave a total of 10 times during 22 days. The platelet count decreased in every case, with the lowest values reached at the third donation (day 5). The pre-donation count averaged 225 +/- 53 x 10(9)/l decreasing to 174 +/- 27 x 10(9)/l at the time of the 3rd donation then increasing by the 6th donation to 198 +/- 46 x 10(9)/l. The yield in the product decreased from 3.2 +/- 1.3 x 10(11) on day 1 to 2.6 +/- 0.8 x 10(11) for the third donation, returning thereafter to higher values. In spite of the expected and apparent stimulation of platelet production through feedback, the counts did not rebound above starting levels indicating a basic homeostatic mechanism. The donor WBC showed minimal changes during the study period, however there was a significant increase in the total number of lymphocytes by the 3rd procedure; this was corrected by the fifth procedure. The absolute number and ratio of T4 (helper) and T8 (suppressor) lymphocytes did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Donors↗
PubMed1992

Target antigens of anti-platelet antibodies in patients with steroid-resistant ITP of recent onset. Canadian Apheresis Study Group.

Recent application of Western blotting procedures in the detection of anti-platelet antibodies has permitted more refined definition of reactivity. We report on the results of anti-platelet antibody assays in a series of 19 patients with recently diagnosed (less than 6 months duration) steroid-resistant, idiopathic thrombocytopenia purpura (ITP). At presentation, six of the 19 patients had a positive test for platelet-associated IgG (PAIgG) as measured by the direct radial-immunodiffusion (RID) assay, whereas three of the 19 were positive with the direct-platelet-suspension-immunofluorescence test (DPSIFT). The indirect-platelet-suspension-immunofluorescence test (IPSIFT) demonstrated antibodies in seven of the sera. Following Western blot (WB) analysis, the serum of 7/19 patients (only three of which were positive in the IPSIFT) could be shown to react with platelet antigens. Two patterns were seen: in four cases there were bands of apparent molecular weights of 60,000, 55,000 and 50,000; in the other three samples, a single band near 90,000 was demonstrated. Unlike the situation reported for chronic ITP, no reactivity was seen against higher molecular weight antigens other than the 'non-specific' binding at apparent molecular weight 200,000 which is also seen with normal sera. The data suggest that antibodies reacting against specific platelet antigens are present in the serum of some patients with recent onset ITP.

Adult↗
PubMed1991

Storage of platelets in balanced salt solutions: a simple platelet storage medium.

When a commercially available intravenous solution, plasmalyte-A, was added to platelet pellets as a platelet storage medium (PSM) after more than 85 percent of the plasma had been expressed, the platelets functioned equally well, after 5 days of storage, in platelet aggregation, release reaction, and serotonin uptake as did platelets stored in plasma. The level of fibrinopeptide A was significantly different in the PSM. Similarly, lower levels of kallikrein and complement components in the PSM-stored platelets indicated reduced activation of plasma enzyme systems. Morphology scores showed better shape maintenance in PSM, with values of 255 versus values of 185 in plasma (time zero, 280); electron microscopy also showed somewhat better structural maintenance in PSM. Glucose consumption, lactate and ammonia production, and fatty acid oxidation were also reduced in PSM. No significant differences in pH, white cell count, pO2, pCO2, or lactic dehydrogenase were observed after 5 days of storage in plasma or PSM; however, platelet counts were reduced after 5 days in plasma but remained constant in PSM. The beta-thromboglobulin release was significantly lower in the PSM-stored platelets after 5 days. The volume of platelet membrane glycoprotein lb (which is responsible for platelet adhesion) decreased 15 percent in plasma following storage, whereas a decrease of only 5 percent was noted in PSM. There was less leaching of plasticizers in PSM than in plasma. Survival and recovery using 51Cr-labeled autologous platelets showed that, after 5 days of storage, the recovery of PSM-stored platelets was 63 percent and the survival was 7.7 +/- 0.8 days (multiple hit model).(ABSTRACT TRUNCATED AT 250 WORDS)

Ammonia↗
PubMed1990

Development of a heat-treated factor VIII/von Willebrand factor concentrate prepared from heparinized plasma.

A high yield, intermediate purity factor VIII concentrate derived from heparinized plasma has been developed which can be heat-treated at 60 degrees C, 68 degrees C or 80 degrees C/72 h to permit inactivation of viral contaminants which may be present. After cold reprecipitation of the heparinized cryoprecipitate (CRC), the resolubilized CRC precipitate was adjusted to 25-30 mg/ml protein and pH 6.35 +/- 0.1 and incubated for 1 h at 8 degrees C. After centrifugation to remove the precipitated fibrinogen and fibronectin, a factor VIII-rich supernatant can be recovered which contains greater than 500 units of VIII:C per liter of starting plasma (Method I product) at a purity of 1.5 U/mg protein. Adjusted to 50 mM glycine and pH 6.8, the product can be lyophilized and heat-treated at 60 degrees C/72 h without a significant loss of VIII:C activity. However, at 68 degrees C or 80 degrees C/72 h, temperatures now reported to be more effective in viral inactivation, the recoveries were reduced to 68 and 33% respectively. Significantly improved recoveries after heat-treatment (HT) at 68 degrees C or 80 degrees C/72 h were achieved if the 8 degrees C supernatant product was prepared by a modified procedure (Method II). This further reduces the fibrinogen content of the product while maintaining VIII:C yields greater than 500 U/l at a purity of 1.9 U/mg. When adjusted to 50 mM glycine and 1-2% (w/v) sucrose (pH 6.8), lyophilized and heat treated at 60 degrees C, 68 degrees C or 80 degrees C/72 h, the VIII:C recoveries of Method II product were 88-100%, 79-84% and 80-83% of pre-HT levels respectively. The yield of VIII:C was greater than 400 U/l at a purity of 1.6-1.4 U/mg at 1-2% (w/v) sucrose even after the severe heat-treatment at 80 degrees C. In addition, the von Willebrand factor multimers are similar in size and triplet pattern to those observed in routine cryoprecipitate preparations.

Chemical Precipitation↗