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Biomedical subjects

G A Rock

Publications and source records attributed to G A Rock.

33 records · Page 2Linked to original sources
PubMed1983

Analysis of contaminants in factor VIII preparations administered to patients with hemophilia.

Cryoprecipitate and the more purified factor VIII concentrates are all heterogeneous preparations that contain not only a high concentration of factor VIII but also various other materials, some of which might be injurious, causing liver damage after long-term exposure. The efficiency of three standard cryoprecipitate filters, two microaggregate filters and the appropriate factor VIII concentrate filters in reducing the amount of particulate matter delivered to the patient was assessed. Filtration of cryoprecipitate through the standard filters removed less than 20% of the contaminating microaggregates and very few of the large number of intact platelets, although the total dose of factor VIII was delivered. Microaggregate filters were no better in reducing the platelet contamination, although the total number of particles delivered was halved. However, 25% of the factor VIII was retained in the bed volume of the filter. The concentrate preparations also contained significant amounts of particulate matter that was unrelated to factor VIII and was not removed following filtration through the designated filter. These findings indicate that a new filter should be developed for administration of factor VIII concentrate that would remove the particulate matter while delivering all of the factor VIII to the patient.

Diethylhexyl Phthalate↗
PubMed1982

The functional molecular weights of factor VIII activities in whole plasma as determined by electron irradiation.

Activities of the various components of the human factor VIII complex in citrated and heparinized human plasma have been determined following radiation inactivation of the plasma in a high energy electron beam at -135 degrees C in order to determine the molecular size of the functional units. In citrated and in heparinized plasma the functional size of VIII:C was 120,000 +/- 9,700 and 140,000 +/- 10,000, respectively. Taken together with previously published data, these results suggest that VIII:C exists in plasma as a dimer of noncovalently bonded functional subunits. The size of the functional unit of the ristocetin cofactor of the factor VIII complex was determined as being approximately 330,000 in both citrated and heparinized samples. Immunological assays for VIII:C (inhibitor neutralization assay), the VIII:C antigen, and the VIII:vWF-related antigen suggest that these may not be reliable under conditions favoring the activation and inactivation of factor VIII components by thrombin or other proteases.

Electrons↗
PubMed1979

Improved yields of factor VIII from heparinized plasma.

The Factor VIII procoagulant activity in plasma, cryoprecipitate, and their polyethylene glycol (PEG) precipitates is markedly increased if blood is collected into heparin rather than into citrate phosphate dextrose (CPD). There is a 34% increase in the initial level of the Factor VIII activity in the heparinized plasma with 78% of this initial activity (184 U) recovered in the cryoprecipitated. As well, the stability of the Factor VIII activity is improved: after 24 h of incubation at 22 degrees C, 99% of the initial activity is retained in heparinized plasma whereas only 64% remains in CPD plasma. The cryoprecipitate prepared from heparinized plasma is equally stable after 24 h. The PEG concentrate prepared from the cryoprecipitate of heparinized plasma is increased to 128 U compared to only 54 U from CPD plasma. Relative recoveries were 531 U/l for heparinized plasma versus 215 U/l for CPD plasma. This represents a 147% increase in yield.

Anticoagulants↗
PubMedDate not supplied

The effects of temperature variations on cryoprecipitate.

The effect of temperature on Factor VIII levels in blood and cryoprecipitate was assessed. Freshw collected units of blood required several hours to reach 4 C, but this delay seemed of little importance since equal amounts of cryoprecipitated Factor VIII were recovered from blood stored either at 22 C or at 4 C. Freezing at -80, -60, or -40 C produced identical yields of Factor VIII, whereas freezing at -20 C resulted in significantly lower recoveries. This might be expected if one considers the physiochemical changes that occur during the freezing process.

Blood Preservation↗
PubMedDate not supplied

Storage of platelets collected by apheresis.

Increasingly, platelets obtained by apheresis must be shipped some distance prior to infusion. We have studied the effect of storage and the size of the storage container on in vitro platelet function over a 48-hour period. Five donors each donated twice at 2-week intervals with one donation of 200 ml taken into a 300-ml bag and the other into a 2000-ml bag. The platelets collected into the 2000-ml bag maintained pH well over 48 hours. The PO2 stayed at a high level, and the PCO2 decreased by 48 hours. The lactate accumulation was 38 mg per dl, and the aggregation and hypotonic shock response were maintained well. In comparison, platelets stored in the 300-ml bag had a rapid decrease in pH accompanied by a marked rise in PCO2. Lactate accumulation was also high at 124 mg per dl at 48 hours. Aggregation, 14C-serotonin uptake, hypotonic shock response, and platelet recovery were reduced. Exposure to a high concentration of the plasticizer, di-2-ethylhexyl phthalate, equivalent to that which occurs in the 2000-ml bag did not affect platelet function. Storage of the apheresis platelets in a double volume of plasma in the 2000-ml bag likewise had little effect. The data indicate that, as measured by in vitro response, apheresis platelets can be maintained for up to 48 hours if stored in a 2000-ml bag.

Blood Platelets↗
PubMedDate not supplied

Intensive plasma exchange therapy in ten patients with idiopathic thrombocytopenic purpura.

Intensive plasma exchange therapy with fresh-frozen plasma as the replacement fluid was used to manage ten patients, five with acute and five with chronic immune thrombocytopenic purpura (ITP). Therapy was started because of severe hemorrhage (1 case), failure to respond to steroid therapy (6 cases), or steroid dependence (3 cases). After a median of four exchanges over 6 days (median total volume removed, 11.7 liters), initial responses, defined as a platelet count greater than 100,000 per microliter at the end of the exchange series, were observed in 80 percent of the patients treated. Two adolescents, ages 16 and 17 years, with chronic ITP failed to respond to plasma exchange therapy and subsequently responded to splenectomy. Prolonged remissions of 9 months and greater than 2 years were observed in two patients with acute ITP; in patients with chronic ITP, no prolonged remissions occurred. Neither pre-exchange levels of platelet-associated immunoglobulin G (PAIgG) nor circulating immune complexes predicted the response to plasma exchange, although serially determined PAIgG levels correlated with the severity of ITP and response, or lack of response, to plasma exchange. We conclude that intensive plasma exchange merits further study in patients with acute ITP unresponsive to steroid therapy to determine if the need for splenectomy is reduced. In selected patients with chronic ITP, exchange therapy may provide short-term adjunctive benefit.

Adolescent↗
PubMedDate not supplied

Interaction between fenofibrate and warfarin.

OBJECTIVE: To determine whether the potentiation of warfarin's anticoagulation effect, which occurred in two patients, was due to an interaction with fenofibrate. CASE SUMMARY: Two patients developed significant potentiation of the anticoagulant effect of warfarin while receiving fenofibrate. In one patient we followed published guidelines to test the potential interaction, including rechallenge twice, and measurements of factors II, V, and VII and liver enzymes to ensure the authenticity of the interaction. We confirmed the interaction by noting that the international normalized ratio (INR) increased with rechallenge, the clotting factor concentrations decreased in concert with the INR, and no other laboratory or clinical factors accounted for this potentiation of the oral anticoagulant affect. DISCUSSION: We previously developed criteria specifically for determining the strength of inferred causation in reports of drug interactions with oral anticoagulants; these criteria were adapted from previously described principles of causality assessment. Our observations in two patients suggest a "highly probable" potentiating interaction between fenofibrate and warfarin. Our data do not allow us to draw definitive conclusions on a mechanism of interaction, but fenofibrate is an oral antilipemic agent, similar to clofibrate, that has been described as potentiating oral anticoagulants by affecting coagulation factor synthesis, likely by altering receptor synthesis. Our finding of lower concentrations of coagulation factors suggests a similar mechanism for fenofibrate. Recent data suggest that lipid lowering is effective for primary and secondary prevention of cardiac events. One might therefore expect to see an increase in the use of the various lipid-lowering agents in patients who receive long-term anticoagulation. Our results indicate that the potential for an exaggerated anticoagulant effect occurs within 5-10 days in patients treated with fenofibrate who are receiving long-term anticoagulation with warfarin. CONCLUSIONS: Fenofibrate potentiates the effect of warfarin. Serial monitoring of the INR, at least three times per week, is therefore strongly recommended when initiating fenofibrate therapy in patients receiving warfarin.

Anticoagulants↗