Platelet function in mitochondriopathy with stroke and stroke-like episodes.
Stroke and stroke-like episodes are frequent complications in mitochondriopathy, particularly in MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke like episodes) which is a disorder of the mitochondrial oxidative metabolism in diverse cell types. To clarify a possible pathological aspect of stroke in these patients, we investigated platelet function before and after physical exercise. Ten patients with mitochondriopathy and stroke and ten healthy sex and age matched controls were investigated in an analyst blinded, prospective cross-sectional trial. Exercise decreased intraplatelet adenosine triphosphate (ATP) concentrations by -22% from baseline in patients with mitochondriopathy (p<0.01 between groups) while exercise increased ATP-levels by 28% healthy controls (p=0.01 vs baseline). Thrombin receptor activating peptide (TRAP) stimulated P-selectin expression increased up to 50% (p<0.05) in healthy subjects following exercise compared to 39% (p>0.05) in patients with mitochondriopathy. Exercise trendwise decreased platelet plug formation under shear stress by 24% in patients as measured by the platelet function analyzer PFA-100(R). Tromboelastography showed firm thrombus formation and delayed lysis in patients following exercise. In conclusion, this trial has shown that ATP depletion during and after exercise probably accounts for a defective oxidative metabolism in platelets of patients with mitochondriopathy and stroke. This might induce decreased platelet function in these patients but fails to explain the increased stroke rate. Therefore other mechanisms seem to be etiologically involved in the pathogenesis of stroke in patients with mitochondriopathy.
Department of Clinical Pharmacology-TARGET, Vienna University School of Medicine, Währinger Gürtel 18-20, A-1090, Vienna, Austria. nicole.hergovich@univie.ac.at
Nicole
N
Kotzailias
Josef
J
Finsterer
Maria
M
Zellner
Claudia
C
Marsik
Tanja
T
Dukic
Bernd
B
Jilma
D000255:Adenosine Triphosphate / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D017304:Annexin A5 / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism* / Q000502:physiology; D016022:Case-Control Studies; D003094:Collagen / Q000378:metabolism; D004396:Coloring Agents / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism; D004837:Epinephrine / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D017241:MELAS Syndrome / Q000097:blood*; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000473:pathology*; D019007:P-Selectin / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D015539:Platelet Activation; D010979:Platelet Function Tests; D011485:Protein Binding; D020521:Stroke / Q000097:blood* / Q000473:pathology; D013997:Time Factors
D017304:Annexin A5; D004396:Coloring Agents; D019007:P-Selectin; D010446:Peptide Fragments; C086309:thrombin receptor peptide SFLLRNP; D000255:Adenosine Triphosphate; D003094:Collagen; D004837:Epinephrine