Analysis of Platelet Factor 3 in Platelet Concentrates
Stored for Transfusion

Bode, Arthur P.; Miller, D.

doi:10.1159/000461513

Cited by 16 publications

(21 citation statements)

References 17 publications

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“…In the light of evidence of thrombin activity, plasmin activity, and the limited activation of the complement sys tem in the plasma of standard platelet concentrates during storage [12][13][14], the protease inhibitors Thromstop and aprotinin were added along with PGE! and theophylline in the present study of the artificial medium in case plasma carryover was significant.…”

Section: Addition Of Protease Inhibitorsmentioning

confidence: 99%

Extended Storage of Platelets in an Artificial Medium with the Platelet Activation Inhibitors Prostaglandin E(1) and Theophylline

Bode¹,

Holme²,

Heaton³

et al. 1991

Vox Sanguinis

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The addition of platelet activation inhibitors to the anticoagulant and the replacement of plasma with a fortified electrolyte medium have been shown separately in previous work to improve the storage of platelets during a 2-week period. In the present study, we have combined these strategies to investigate whether a synergistic improvement could be obtained. A total of 85 concentrates was studied with 300nM prostaglandin E(1) (PGE(1)) and 1.9mM theophylline added to the whole blood, platelet-rich plasma (PRP), and/or the storage medium during the preparation of platelet concentrates. In vitro markers of platelet aggregation, respiration, and cell integrity were measured over a 20-day storage period and evaluated in an analysis of variance. We found that a single-step addition of PGE(1) and theophylline to the PRP prior to centrifugation was not sufficient in terms of preventing a rapid fall in pH, rise in pO(2), fall in pCO(2), loss of hypotonic shock response, and loss of aggregation response, compared to the addition of the inhibitors to the storage medium used to resuspend the platelet pellet. Factorial analysis showed that a reduction in the surface-to-volume ratio of the storage container further improved the maintenance of platelet respiration and, for three in vitro markers (hypotonic shock response, released lactic dehydrogenase, and surface glycoprotein lb levels) displayed an interactive effect with the inhibitors. The addition of protease inhibitors to the formulation of PGE(1) and theophylline showed further improvement in several markers. These findings demonstrate the possibility of preserving platelets for 15-20 days with the synergistic effects of activation inhibitors and an electrolyte storage medium fortified with citrate, buffers, and dextrose. In addition, these data suggest that platelet agonists generated in plasma accelerate the in vitro aging process of stored platelets.

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Section: Addition Of Protease Inhibitorsmentioning

confidence: 99%

Extended Storage of Platelets in an Artificial Medium with the Platelet Activation Inhibitors Prostaglandin E(1) and Theophylline

Bode¹,

Holme²,

Heaton³

et al. 1991

Vox Sanguinis

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“…This is in agreement with results of Prodouz [ 161 who described intracellular calcium-dependant calpain protease during platelet aging. Extracellular proteolysis of GPIb was also described [17] without inhibition by the addition of any known protease inhibitors in the storage medium [18].…”

Section: Discussionmentioning

confidence: 99%

“…The loss of platelet integrity during storage is closely correlated with an intracellular decrease in cAMP [24]. Prostaglandin-El-induced conversion of ATP to cAMP did not increase in vitro platelet viability, contrary to what occurs when theophyllin inhibits the degradation of CAMP into AMP [18]. A decrease in ATP during storage due to exhaustion of the energetic substrates or to a change from aerobic to anaerobic catabolism was probably responsible for the intracellular CAMP decrease.…”

Section: Discussionmentioning

confidence: 99%

Loss of phospholipid asymmetry in human platelet plasma membrane after 1–12 days of storage

Gaffet¹,

Bassé²,

Bienvenüe³

1994

European Journal of Biochemistry

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We used paramagnetic analogs of endogenous phospholipids to study modification of phospholipid distribution in platelet plasma membranes during aging. Asymmetrical distributions and translocation kinetics were very different for spin-labeled phosphatidylserine and spin-labeled phosphatidylcholine in fresh platelet plasma membranes. In freshly prepared platelets and up to day 7, spin-labeled phosphatidylserine very rapidly penetrated to the inner leaflet of the platelet plasma membrane. However, spin-labeled phosphatidylcholine was mainly retained on the external leaflet. From day 7 to day 9, the two translocation kinetics became identical with symmetrical distribution of both spin-labeled phospholipids at equilibrium. Inhibition of translocase activity and modification of membrane stability accounted for these transformations. The rapid re-exposition of spin-labeled phosphatidylserine after stimulation by the calcium ionophore A231 87, measured in fresh platelet concentrates, persisted up to day 9 but disappeared between day 10 and day 12. From day 7 to day 9, a strong cytoskeleton proteolysis and marked decrease in intracellular ATP were observed. Moreover, complete suppression of P-N-acetyl glucosaminidase secretion and vesicle formation after A23187 stimulation of aged platelets indicated that platelets could no longer be activated beyond day 9. Taken together, these results showed that during in vitro aging there are metabolic and membrane modifications in platelet similar to those described for platelet activation. In addition, all of the observed events occurred simultaneously between day 7 and day 9. These results highlight the importance of maintaining plasma membrane asymmetry to increase the hemostatic effectiveness of transfused platelet concentrates.The coagulation cascade begins after vascular injury to maintain hemostasis in the circulatory blood system. Briefly, the coagulation process starts when blood platelets interact with the tissue factor released by subendothelium cells, inducing platelet activation close to the lesion [l]. These activated platelets undergo several transformations such as skeleton proteolysis, granule secretion, vesicle shedding, shape change and lose their transmembrane phospholipid asymmetry to acquire a surface rich in phosphatidylserine (PtdSer) and phosphatidylethanolamine (PtdEtn) [2-41. All coagulation events then occur and result in formation of the hemostatic plug.Storage lesion, a phenomenon very similar to platelet activation transformation, was observed during in vitro aging of blood bank platelet concentrates. In fact, skeleton proteolysis, degranulation, shape change and vesicle formation have been described during in vitro platelet aging, whereas phos- The aim of this study was to investigate modifications in PL distribution in the plasma membrane during in vitro platelet aging. The study was carried out using paramagnetic phospholipids that were previously described to be good reporters for endogenous PL movements [7, 81. Cytoskeleton proteolysis and intrace...

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“…Thrombin generation has been observed during blood collection [13] and could be responsible for, and supported by, the expression of plate let factor 3 activity by activated platelets [3,14,15], Activation of platelets through the binding of thrombin to the 40-kilodalton platelet protein is a slow process at 21 °C and takes about 5 min to reach steady state [16]. In addition we have found that in PC prepared from blood collected into CPD-adenine, the aggregation response to low doses of collagen is lowered relative to that in PC from blood collected simply into CPD [Solberg MS, in prepa ration], Platelet aggregation and release are inhibited by cAMP [16] and exposure of platelets to physical stimuli such as centrifugation has been reported to diminish cAMP levels [17], Furthermore, during the first centrifu gation the platelets are centrifuged together with the red cells at a ratio of 1:20.…”

Section: Platelet Countmentioning

confidence: 99%

Effect of Centrifugation on the Storage Properties of Platelets

Solberg¹,

Moen²,

Little³

1988

Vox Sanguinis

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Some of the recommended centrifugation methods for the preparation of platelet concentrates may cause accelerated deterioration of platelets stored in second-generation containers. The deterioration is characterized by increasing pH, pO(2) and decreasing pCO(2), a high discharge of lactate dehydrogenase (LDH) and increasing amounts of small particles which have recently been shown to have platelet factor 3 activity [Solberg, C; Østerud, B.; Little, C.: Thrombosis Res. 48: 559-565, 1987], A short first centrifugation (3,270 g, 2 min 15 s) yielded platelets with better storage properties than platelet-rich plasma prepared with longer centrifugation times (2,200 g, 4 min 30 s and 1,100 g, 6 min). By using multivariate data analysis the effect of different platelet concentrations and metabolic parameters can be used to predict the discharge of LDH or the change in morphology.

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Analysis of Platelet Factor 3 in Platelet Concentrates Stored for Transfusion

Cited by 16 publications

References 17 publications

Extended Storage of Platelets in an Artificial Medium with the Platelet Activation Inhibitors Prostaglandin E(1) and Theophylline

Extended Storage of Platelets in an Artificial Medium with the Platelet Activation Inhibitors Prostaglandin E(1) and Theophylline

Loss of phospholipid asymmetry in human platelet plasma membrane after 1–12 days of storage

Effect of Centrifugation on the Storage Properties of Platelets

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