[Changes in oxidative stress and hemostatic parameters in the course of thrombolytic therapy of pulmonary embolism].
Acute pulmonary embolism is the third most common cause of cardiovascular mortality. Thrombolytic treatment of massive pulmonary embolism can be complicated with haemorrhage, re-thrombosis and oxidative stress.


OBJECTIVE
The purpose of this study was to evaluate the changes in platelet aggregation, haemostatic, leukocyte function parameters and oxidative stress in patients with acute pulmonary embolism treated with thrombolytics.


METHODS
Fifteen patients undergoing thrombolysis with ultra-high dose streptokinase ( n = 8), or alteplase ( n = 7) treatment were studied. Arterial blood samples were taken before (baseline) and after thrombolysis between the 4th and 24th hour at every four hours, on the second day twice a day and daily on the 3rd, 4th, 5th and 30th day. Platelet aggregation was examined as spontaneous and induced aggregation with adrenaline, collagen and adenosine diphosphate. D-dimer and fibrinogen were measured 8 hourly on the first day and later at the same time intervals as above. To analyse oxidative stress, blood samples were collected prior to thrombolysis, and then 8 hours, 1, 3, 5 and 30 days after treatment. Malondialdehyde, reduced glutathion, plasma sulphydryl groups levels, superoxide dismutase and myeloperoxidase enzyme activities were measured in plasma or whole blood for monitoring of the oxidative stress markers. Production of reactive oxygen species in whole blood was measured by luminol dependent chemiluminescence. Flow cytometry was used to determine CD11a, CD18, and CD97 surface antigen expression on leukocytes.


RESULTS
In streptokinase group, adrenaline induced platelet aggregation decreased at the 4th and 8th hour ( p < 0.03) and was significantly lower than in the alteplase group at the 36th hour and on the 3rd day. Platelet aggregation induced by adenosine diphosphate was lower at the 4th hour than at baseline in streptokinase group ( p < 0.05). Collagen induced platelet aggregation was lower at the 4th and 8th hour than at baseline ( p < 0.05) in streptokinase group. Compared to baseline, fibrinogen levels decreased in both groups after thrombolysis. D-dimer levels elevated significantly in both therapeutic groups at the 8th hour. Spontaneous platelet aggregation was not detectable and major bleeding or re-embolism was not documented. The elevated malondialdehyde, reactive oxygen species and myeloperoxidase, decreased reduced glutathion and plasma sulphydryl levels indicated the presence of oxidative stress in patients with pulmonary embolism. Malondialdehyde significantly increased, reduced glutathion significantly decreased following thrombolysis. Reactive oxygen species production peaked on the 3rd and 5th days. Thrombolysis was accompanied by significant decrease in granulocyte and monocyte CD11a and CD18 as well as in granulocyte CD97 expression ( p < 0.05).


CONCLUSIONS
Massive/submassive pulmonary embolism and thrombolysis injures inducible platelet aggregation. The changes in fibrinogen levels correlate significantly with the improvement of pulmonary perfusion which shows the effect of thrombolysis. Pulmonary embolism induced oxidative stress was detected on patients before thrombolysis. Thrombolytic treatment of pulmonary embolism augmented the increase of oxidative stress response and leukocyte activation following reperfusion, and these parameters normalised only on the 30th day.
Mühl
Diana
D
Pécsi Tudományegyetem, Altalános Orvostudományi Kar Klinikai Központ, Aneszteziológiai és Intenzív Terápiás Intézet Pécs Ifjúság u. 13. 7624. diana.muhl@aok.pte.hu
D000208:Acute Disease; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000097:blood; D015415:Biomarkers / Q000097:blood; D040881:CD11a Antigen / Q000097:blood; D018821:CD18 Antigens / Q000097:blood; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D005978:Glutathione / Q000097:blood; D006454:Hemoglobins / Q000378:metabolism; D006487:Hemostasis / Q000187:drug effects; D006801:Humans; D007962:Leukocytes / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008562:Membrane Glycoproteins / Q000097:blood; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D018579:Patient Selection; D009195:Peroxidase / Q000097:blood; D010974:Platelet Aggregation / Q000187:drug effects*; D011655:Pulmonary Embolism / Q000097:blood* / Q000188:drug therapy* / Q000201:enzymology; D017382:Reactive Oxygen Species / Q000097:blood; D043562:Receptors, G-Protein-Coupled; D013300:Streptokinase / Q000008:administration & dosage*; D013482:Superoxide Dismutase / Q000097:blood; D015912:Thrombolytic Therapy / Q000379:methods; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage*
C095004:ADGRE5 protein, human; D015703:Antigens, CD; D015415:Biomarkers; D040881:CD11a Antigen; D018821:CD18 Antigens; D005338:Fibrin Fibrinogen Degradation Products; D006454:Hemoglobins; D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; D043562:Receptors, G-Protein-Coupled; C036309:fibrin fragment D; D008315:Malondialdehyde; D005340:Fibrinogen; D009195:Peroxidase; D013482:Superoxide Dismutase; D013300:Streptokinase; D010959:Tissue Plasminogen Activator; D005978:Glutathione