Acquired dysfunction due to the circulation of “exhausted” platelets

Pareti, F. I.; Capitanio, A; Mannucci, L.; Ponticelli, Claudio; Pm, Mannucci

doi:10.1016/0002-9343(80)90383-6

Cited by 185 publications

(89 citation statements)

References 17 publications

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“…27 It is characterized by defective platelet aggregation, reduced levels of adenine nucleotides and serotonin, and an abnormal uptake and storage of amines. This defect is thought to be related to the presence in the circulation of exhausted platelets following their in vivo exposure to inducers of the release reaction, such as damaged endothelium, thrombin and immune complexes.…”

Section: Discussionmentioning

confidence: 99%

Hypoaggregability of washed platelets from stroke-prone spontaneously hypertensive rats (SHRSP).

Tomita¹,

Umegaki²,

Hayashi³

1984

Stroke

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SUMMARY The aggregation properties of washed SHRSP platelets were investigated in comparison with normotensive WKY platelets at prehypertensive (4 weeks), early hypertensive (11 weeks) and late hypertensive (17 weeks) ages in the absence of plasma factors. The number of platelets in SHRSP was markedly lower with the development of hypertension than that in WKY. The thrombin-and collagen-induced aggregation was markedly reduced in the platelets from 11 and 17 week old SHRSP compared with that of age-matched WKY, whereas the degree of platelet aggregation in 4 week old SHRSP showed a tendency to be even greater than that in WKY. The changes in blood pressure and platelet aggregability were correlated inversely. ADP did not induce aggregation in the same system used for thrombin and collagen stimulation but in another system it aggregated washed rat platelets. Aggregation responses to ADP and ionophore A23187 were also significantly lower in 14 week old SHRSP platelets than age-matched WKY platelets. Together with other evidence, these results suggest that defective Ca 2+ function, rather than the presence of exhausted platelets, is responsible for hypoaggregability in SHRSP platelets.Stroke Vol 15, No I, 1984 PLATELET ADHESIVENESS and ADP-induced platelet aggregation has been reported to have increased in patients with hypertension regardless of the aethiology and severity of the disease.1 " 4 It is well known that the leading causes of death in patients with hypertension are thrombosis of coronary and cerebral arteries. SHRSP, a substrain of SHR, which was established in 1974 by Okamoto et al 5 develops more severe hypertension spontaneously than SHR, and dies of massive cerebral hemorrhage or infarction between 100 and 500 days after birth. Using these strains of spontaneous hypertension which are considered to represent the closest model to human hypertension, we have been able to show the changes in some aortic enzyme activities due to hypertension. As hypertension is assumed to be one of the important factors in thrombotic diseases, it seems of interest to investigate platelet functions in SHRSP. Using platelet-rich plasma Yamazaki et al 7 demonstrated that platelet aggregability and thrombogenic tendency in response to ADP were lower in SHR compared to WKY. Yamori et al 8 reported similar observation with SHRSP. There is evidence that the insoluble collagen of the aorta from SHRSP induced a greater aggregation response than that from WKY, 9 and that the fibrinolytic system in SHRSP and SHR was impaired. 10Platelet-rich plasma contains various humoral factors influencing platelet functions such as PGI 2 , PGD 2 , PGE 2 , catecholamines and angiotensins, most of which were shown to deviate in these hypertensive rats."" 16 Thus in this study, washed platelets were prepared from SHRSP at prehypertensive, early hypertensive and late hypertensive ages, and platelet responses to thrombin, collagen, ADP and ionophore A23187 in the absence of humoral factors were investigated in comparison with age-matched normote...

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Section: Discussionmentioning

confidence: 99%

Hypoaggregability of washed platelets from stroke-prone spontaneously hypertensive rats (SHRSP).

Tomita¹,

Umegaki²,

Hayashi³

1984

Stroke

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“…The specific mechanism is unknown but may involve "platelet exhaustion," where platelets become activated en masse and are refractory to further stimulation for up to 24 hours afterward. 52,53 However, because the minimally injured patients above 49 had little evidence of bleeding (2% mortality and minimal transfusion requirements [Babak Sarani, George Washington University, electronic communication, May 17, 2016]) despite inhibition of platelet function on TEG-PM, the contribution of such platelet dysfunction to TIC is ambiguous. A recent study by Stalker et al investigating location-dependent differential platelet activation and organization may shine some light on this question.…”

Section: Platelet Dysfunctionmentioning

confidence: 99%

Advances in the understanding of trauma-induced coagulopathy

Chang

Cardenas

Wade

et al. 2016

Blood

246

225

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Ten percent of deaths worldwide are due to trauma, and it is the third most common cause of death in the United States. Despite a profound upregulation in procoagulant mechanisms, one-quarter of trauma patients present with laboratory-based evidence of trauma-induced coagulopathy (TIC), which is associated with poorer outcomes including increased mortality. The most common causes of death after trauma are hemorrhage and traumatic brain injury (TBI). The management of TIC has significant implications in both because many hemorrhagic deaths could be preventable, and TIC is associated with progression of intracranial injury after TBI. This review covers the most recent evidence and advances in our understanding of TIC, including the role of platelet dysfunction, endothelial activation, and fibrinolysis. Trauma induces a plethora of biochemical and physiologic changes, and despite numerous studies reporting differences in coagulation parameters between trauma patients and uninjured controls, it is unclear whether some of these differences may be “normal” after trauma. Comparisons between trauma patients with differing outcomes and use of animal studies have shed some light on this issue, but much of the data continue to be correlative with causative links lacking. In particular, there are little data linking the laboratory-based abnormalities with true clinically evident coagulopathic bleeding. For these reasons, TIC continues to be a significant diagnostic and therapeutic challenge.

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“…An altered functionality is manifested as heightened platelet activation in vivo, while platelets from the same allergic patients are found to be refractory to a variety of stimuli ex vivo, possibly resulting from platelet 'exhaustion', due to the inability of platelets to replenish many released mediators that require de novo synthesis because platelets lack a nucleus (Harker et al, 1980;Pareti et al, 1980). Platelet 'exhaustion' has been reported as an inability of noradrenaline and adenosine di-phosphate (ADP) to induce full aggregation of platelets, with no secondphase aggregation, an occurrence that has been correlated with increased serum immunoglobulin E (IgE) in asthmatic patients (Maccia et al, 1977;Palma-Carlos et al, 1991).…”

Section: Platelet Activation In Asthma and Rhinitismentioning

confidence: 99%

Novel uses for anti‐platelet agents as anti‐inflammatory drugs

Pitchford

2007

British J Pharmacology

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An alteration in the character and function of platelets is manifested in patients with inflammatory diseases, and these alterations have been dissociated from the well‐characterized involvement of platelets in thrombosis and haemostasis. Recent evidence reveals platelet activation is sometimes critical in the development of inflammation. The mechanisms by which platelets participate in inflammation are diverse, and offer numerous opportunities for future drug intervention. There is now acceptance that platelets act as innate inflammatory cells in immune responses, with roles as sentinel cells undergoing surveillance, responding to microbial invasion, orchestrating leukocyte recruitment, and migrating through tissue, causing damage and influencing repair processes in chronic disease. Some of these processes are targeted by drugs that are being developed to target platelet participation in atherosclerosis. The actions of platelets therefore influence the pathogenesis of diverse inflammatory diseases in various body compartments, encompassing parasitic and bacterial infection, allergic inflammation (especially asthma and rhinitis), and non‐atopic inflammatory conditions, for example, chronic obstructive pulmonary disease (COPD), rheumatoid arthritis (RA), inflammatory bowel disease (IBD) and atherosclerosis. This review will first discuss the evidence for platelet activation in these various inflammatory diseases, and secondly discuss the mechanisms by which this pathogenesis occurs and the various anti‐platelet agents which have been developed to combat platelet activation in atherosclerosis and their potential future use for the treatment of other inflammatory diseases.British Journal of Pharmacology (2007) 152, 987–1002; doi:10.1038/sj.bjp.0707364; published online 2 July 2007

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Acquired dysfunction due to the circulation of “exhausted” platelets

Cited by 185 publications

References 17 publications

Hypoaggregability of washed platelets from stroke-prone spontaneously hypertensive rats (SHRSP).

Hypoaggregability of washed platelets from stroke-prone spontaneously hypertensive rats (SHRSP).

Advances in the understanding of trauma-induced coagulopathy

Novel uses for anti‐platelet agents as anti‐inflammatory drugs

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