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Biomedical subjects

P Tittley

Publications and source records attributed to P Tittley.

At least 19 recordsLinked to original sources
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↗
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

Rearrangement of BCR genes in malignant lymphoma.

The Philadelphia chromosome, originally thought to be associated solely with chronic myelogenous leukemia (CML), has since been identified in acute leukemias and in some cases of lymphoma. The Philadelphia chromosome results from reciprocal translocation of genetic material between chromosome 9 and 22 involving the c-abl and BCR genes respectively. Southern blot analysis of the BCR genes was carried out on biopsy specimens from 49 patients presenting with malignant lymphoma without a previously documented CML phase. In two patients, BCR gene rearrangements were detected in the malignant lymph nodes but not in the bone marrow samples. A third patient showed BCR gene rearrangements in the bone marrow but not in the lymph node. From this limited study, it seems that the overall incidence of BCR gene rearrangement in malignant lymphoma is similar to that observed in adult AML.

Blotting, Southern↗
PubMed1990

A comparison of results obtained by two different chromium-51 methods of determining platelet survival and recovery.

A number of different methods exist that use chromium-51 to determine platelet survival and recovery. A 1986 article in TRANSFUSION described the recommended methods for conducting such studies in the hope of standardizing methodology and permitting interlaboratory comparison of results. The results obtained with the recommended method have been compared with those of our previous method. With the new method, recovery of fresh random-donor platelets prepared in polyolefin bags was 76 +/- 6 percent with a survival of 9.3 +/- 2.8 days (n = 4). After 5 days of storage, these values were 67 +/- 8 percent and 7.8 +/- 1.9 days. Similar values were obtained for fresh and stored platelets collected on automated cell separators. However, when our previous (pre-1986) method of evaluation was used, recovery of fresh platelets in the polyolefin bags was 56 +/- 11 percent, and survival was 8.6 +/- 1.3 days. The 5-day values were 36 +/- 5 percent and 6.9 +/- 2.7 days. These values are significantly lower (p less than 0.05) than those obtained with the newer method, but they are in agreement with those previously reported for other techniques. Thus, the new method consistently gives higher values, possibly as a result of a less harmful labeling procedure.

Blood Platelets↗
PubMed1989

Studies on the prolonged bleeding time in von Willebrand's disease.

Ten studies of the effect of cryoprecipitate infusion in four patients with von Willebrand's Disease (vWD) are reported. The doses studied (4, 8 and in one case 10 bags of cryoprecipitate) were based on previous reports of correction of the bleeding time (BT) with such doses. A modest shortening of the BT was observed in only 2 studies and complete correction of the BT at 1 and 4 hours was observed in only one study. This latter result could not be reproduced in a subsequent study of the same patient. In all cases, the von Willebrand factor antigen (vWF:Ag) multimer patterns were normal in the infused cryoprecipitate and in the recipients' plasma post infusion with the presence of high molecular weight multimers demonstrated in all samples. These results contradict earlier reports of the effect on the BT of similar doses of cryoprecipitate and suggest that the presence of the high molecular weight forms of vWF:Ag does not necessarily correlate with the presence of the factor which corrects the bleeding time.

Adult↗
PubMed1989

Epinephrine and dDAVP administration in patients with congenital nephrogenic diabetes insipidus. Evidence for a pre-cyclic AMP V2 receptor defective mechanism.

We recently showed that the administration of the antidiuretic V2 specific agonist, 1-desamino[8-D-arginine]vasopressin (dDAVP), to seven male patients with congenital nephrogenic diabetes insipidus (CNDI) did not cause a decrease in blood pressure nor an increase in plasma renin activity or factor VIIIc or von Willebrand factor release. In normal subjects, plasma renin activity, coagulation factors and plasma cyclic AMP are stimulated not only by dDAVP but also by the administration of epinephrine. In the present study, we measured tissue plasminogen activator (activity and antigenicity), von Willebrand factor multimers, plasma and urinary cyclic AMP concentrations following dDAVP or epinephrine administration. We infused epinephrine into three male patients with CNDI. Factor VIIIc and tissue plasminogen activator augmented by 75 to 100% and von Willebrand Factor multimers were increased; plasma renin activity and plasma cyclic AMP concentration increased by 200%. None of these values changed when the same subjects as well as eleven other male patients with CNDI received dDAVP. Furthermore, dDAVP administration increased plasma cyclic AMP concentrations in normal subjects, but not in 14 male patients with CNDI. These results demonstrate the specificity of the extrarenal V2 receptor defect expressed in our patients. The lack of a plasma cyclic AMP response to the administration of dDAVP would suggest an altered pre-cyclic AMP stimulation mechanism.

Adult↗
PubMed1989

Formation of a cryogel during processing of cell-free plasma.

Automated plasmapheresis devices are being integrated into many modern plasma procurement programs. Owing to the use of a different concentration and type of anticoagulant, the recovered plasma differs in pH and citrate levels from that obtained by manual plasmapheresis or whole blood donation. Recently, fractionators noted the recovery of a sticky, gelatinous fraction (cryogel) during thawing of cell-free (CF) plasma, along with reduced recovery of factor VIII:C (FVIII:C) in the cryoprecipitate fraction. Following their manufacturing procedures, it was established that the cryogel fraction of CF plasma is enriched in FVIII:C, fibrinogen, and fibronectin, as compared to cryoprecipitate from CPDA-1 plasma. Cryogel formation was not significantly affected by pH or citrate adjustment of the recovered plasma, by the use of polycarbonate or nylon filter membranes, or by the filter wetting agent polyvinylpyrrolidone (PVP). Furthermore, passage of CPDA-1 plasma through the polycarbonate filter did not alter cryoprecipitate quality. However, cryogel formation from CF plasma was reduced significantly by 1) slow thawing at 4 degrees C rather than quick thawing at 20 and 0 or 20 and 4 degrees C, 2) the use of 1:16.6 sodium citrate rather than 1:12.5 ACD-A, or 3) the addition of intact platelets, platelet lysate, membranes, or cytosol to CF plasma before freezing. The data suggest an important and, indeed, essential role of platelet constituents in the formation of both cryoprecipitate and cryogel during the low-temperature purification of plasma proteins.

Blood Platelets↗
PubMed1989

5-day storage of single-donor platelets obtained using a blood cell separator.

Platelets were collected from normal donors via a blood cell separator (Fenwal CS-3000). Platelets were stored initially in two separate 1000-ml bags (average count per bag, 2.3 +/- 0.5 x 10(11)) in 100 ml of autologous plasma for 5 days. Little change in platelet count was noted after 5 days of storage; however, the white cell count fell from 5.1 +/- 1.7 x 10(9) at Time 0 to 3.4 +/- 2.3 x 10(9) per l at Day five. The initial lactate values were 32 +/- 11 mg per dl and rose to 165 +/- 28 mg per/dl by 5 days. Platelet aggregation was impaired both by the collection procedure and during storage: whereas the response to ADP of the donors' platelets before the procedure was 100 percent, samples taken from the product immediately after collection had only a 45 percent response, which fell to 12 percent by Day 5. Aggregation using epinephrine was similarly affected, with a 75 percent response after collection and 0 percent response by Day 5. The plasma beta-thromboglobulin (beta-TG) level was high, both after collection (5.0 micrograms/ml at Time 0) and after storage (11.0 micrograms/ml), indicating a considerable effect of collection on platelet alpha granule release. In vivo recovery of these platelets was very good at 67 +/- 6 percent, with an average survival of 7.3 +/- 1.4 days (multiple hit; n = 4).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Component Removal↗
PubMed1989

5-day storage of platelets collected on a blood cell separator.

One of the earliest devices available for plateletpheresis is the Haemonetics system; this machine has been updated recently to permit the use of software in a closed system and thus storage of the collected platelets beyond 24 hours. The authors examined the in vitro and in vivo function of platelets collected on the Haemonetics AutoSurge machine and stored for 5 days in two separate 1000-mL CLX bags. The average count per bag was 1.8 +/- 0.4 x 10(11) in approximately 200 mL of plasma. Immediately following collection, the platelet response to ADP and epinephrine represented 78 and 35 percent, respectively, of the preapheresis values. Aggregation to single stimuli subsequently decreased to 29 and 0 percent, respectively by Day 5. This response is equal to or better than the response reported with the Fenwal CS-3000, the only other plateletpheresis device routinely used for long-term storage. The pH of the preparations was well maintained throughout storage, and there was little alteration in hypotonic shock response or serotonin uptake. Serotonin release decreased consistently. The morphology scores indicated good maintenance of shape immediately following collection; this subsequently decreased after 5 days of storage. Bacterial cultures were negative in all instances. The 51Cr in vivo survival and recovery was good with 65.5 +/- 7.1 percent recovery and an average survival of 7.3 +/- 1.3 days (multiple hit; n = 5). The data indicate that storage of the Haemonetics plateletpheresis product is feasible and that the product is as good as others currently available.

Blood Component Removal↗
PubMed1988

Abnormal platelet von Willebrand factor interaction in patients with TTP.

Thrombotic thrombocytopenic purpura (TTP) is associated with abnormal platelet function and disturbances in coagulation; however, a specific causative factor is not defined. Plasma infusion or plasma exchange (PE) are thought to be of benefit in replacing a deficient plasma component or removing some toxic compound. In three patients with TTP, samples taken prior to initiation of PE showed high levels of vWF:Ag in the plasma (208, 264, and 321 U/dl), whereas the VIII:C levels were normal. The vWF:Ag multimer patterns of the plasma demonstrated a decrease in the amount of high molecular weight (HMW) forms. Analysis of the platelets from one patient also showed an increase in the HMW multimers. Platelets from all three patients showed a decreased ability to absorb vWF:Ag, with little or no absorption of the HMW forms. Following extensive PE and resolution of disease, the platelets regained their ability to absorb vWF:Ag in the one patient examined.

Adult↗
PubMed1988

An antibody to platelet membrane antigen associated with thrombotic events in essential thrombocythemia.

A 71-year-old man with essential thrombocythemia presented with acute onset of thrombosis in his fingers. The platelet count at presentation was 752 x 10(9)/liter, and his PTT was within the normal range. Platelet aggregation was normal in response to ADP, decreased to epinephrine, and absent to collagen, with the patient receiving 1.2 g aspirin/day. Plasma vWF:Ag was 158 U/dl, VIII:C was 150 U/dl, and the vWF:Ag multimer pattern was normal. HLA antibodies were not detected in his serum, and the platelet-associated IgG was normal at 3.9 fg/platelet. Incubation of normal, unactivated platelets with the patient's plasma did not result in agglutination of the platelets. However, a serum antibody reacting against a platelet antigen with an apparent molecular weight of 45,000 could be demonstrated by Western blotting. This antibody also reacted with endothelial cells. The reactive pattern was similar to that of commercially obtained actin; the serum antibody could be removed by preincubation with actin. Platelet-plasmapheresis was carried out daily for 10 days, after which the serum still reacted weakly with the platelet antigen. By day 20, the band could still be identified on the electroblot, but 2 weeks later no band could be seen. Similar assay of sera from six other patients with myeloproliferative disorders and comparable thrombocytosis but without thrombotic manifestations did not show any such reactions. The data suggest a correlation between the presence of an antibody possibly directed against platelet and/or endothelial cell actin and the vascular events in this patient with essential thrombocythemia.

Aged↗
PubMed1988

Effectiveness, specificity and safety of intranasal 1-deamino-8-D-arginine vasopressin treatment of normal blood donors.

A study of the absorption of 300 micrograms of 1-deamino-8-D-arginine vasopressin (DDAVP) given intranasally to normal blood donors was carried out to determine (a) the correlation between plasma levels of DDAVP and the percent rise of factor VIII procoagulant activity (VIII:C) and (b) the efficacy, specificity and safety of this treatment in increasing the recovery of factor VIII:C in donated blood. The maximum drug concentration was highly correlated to the maximum percent rise of VIII:C (r = 0.858, p less than 0.01). A differentiated effect of DDAVP on increases of VIII:C, VIII:Ag, vWF:Ag and vWF multimers was observed. A transient rise of fibrinopeptide A from 5 to 16 ng/ml, 30 min post-DDAVP, was not accompanied by changes in fibrinogen levels or generation of detectable factor Xa or thrombin. DDAVP had no effect on the factor XII-dependent pathway of plasminogen activation, or on the donor's vital signs and hematological parameters. Side effects were minor and of short duration. Intranasal DDAVP treatment of blood donors is considered to be a practical means of improving the recovery of VIII:C from normal donors.

Administration, Intranasal↗
PubMed1987

Electroblotting and immunohistochemical staining for identification of platelet antibodies.

The Western blot procedure has been adapted for use with a biotinylated antiglobulin reagent and a horseradish peroxidase complex (Vectastain ABC) to determine specific sites of antigen binding and permit discrimination between various types of platelet antibodies. Monospecific anti-PlA1 antisera or sera containing mixtures of multispecific HLA and unidentified platelet specific antibodies were tested with PlA1 phenotyped platelets. Using monospecific anti-PlA1, one intense band with relative molecular weight (Mr) of 88,000 and corresponding to glycoprotein IIIa was seen with the PlA1+ platelets. With mixtures of antibodies, reactions were seen with platelet specific antibodies without interference from the HLA antibodies; with one serum a band of Mr approximately 135,000 was identified with Baka+, but not Baka- platelets, indicating the presence of an anti-Baka in the serum. The location of the Baka antigen corresponded to the area for GP IIb. With another serum, a band of Mr 88,000 was revealed with PlA1- and some PlA1+ platelets suggesting the presence of an anti-PlA2. Two additional bands of Mr 160,000 and 200,000 were present on all preparations including autologous controls, probably due to the presence of non-specific IgG. Thus, immunohistochemical staining is readily adaptable to the Western blot technique, and antibodies to platelet-specific antigens can be easily differentiated from HLA antibodies.

Antibodies↗