Diurnal variation in platelet inhibition by clopidogrel.

Morning increase in the occurrence of myocardial infarction, stroke and sudden cardiac death is a well-recognized phenomenon, which is in line with a morning enhancement of platelet aggregation. We investigated whether platelet inhibition during clopidogrel and aspirin therapy varies during the day. Fifty-nine consecutive patients (45 men and 14 women) with first ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary interventions (pPCI) on dual antiplatelet therapy were prospectively enrolled into the study. Blood samples were collected 4 days after start of clopidogrel treatment at 6.00 a.m., 10.00 a.m., 2.00 p.m. and 7.00 p.m. Arachidonic acid and adenosine diphosphate (ADP)-induced platelet aggregation were assessed by impedance aggregometry. Platelet inhibition by clopidogrel was lowest in the midmorning: median ADP-induced platelet aggregation was 55%, 17% and 27% higher at 10.00 a.m. compared to 6.00 a.m., 2.00 p.m. and 7.00 p.m., respectively (p < 0.002). Nonresponsiveness to clopidogrel defined according to the device manufacturer was 2.4-fold more frequent in the midmorning than in the early morning. We observed a more pronounced midmorning increase in ADP-induced platelet aggregation in diabetic patients when compared to non-diabetics. In contrast, no diurnal variation in the antiplatelet effect of aspirin was observed. In conclusion, in patients presenting with STEMI undergoing pPCI, platelet inhibition by clopidogrel is less strong in the midmorning hours. This periodicity in platelet aggregation in patients on dual antiplatelet therapy should be taken into consideration when assessing platelet function in clinical studies.

[Haemostatic disturbances in essential thrombocythosis]. / Zaburzenia hemostazy w nadplytkowosci samoistnej.

Essential thrombocythemia (ET) is one of the chronic myeloproliferative disorders which is characterized by megakaryocytic metaplasia. The most common complications of ET are thrombohemorrhagic events. The overall incidence of thrombosis is 70% and hemorrhagic events about 10-15%. We investigated 21 patients with ET. Median age was 51.0 (range 41-61 years). 29 healthy controls were similar in aspects of sex and age. Patients had examined whole blood count, blood smear, platelet counts, prothrombin time (PT), activated partial thromboplastin time (aPTT), euglobulin lysis time (ELT), fibrin degradation products (FDP), thrombin-antithrombin III complexes (TAT), plasmin-alpha2-antiplasmin complexes (PAP), antigen of tissue and urokinase plasimogen activators (t-PA:Ag, u-PA:Ag), antigen of tissue plasminogen activator inhibitor types 1 and 2 (PAI-1:Ag, PAI-2:Ag), fibrinogen, antitrombin (AT) and alpha2-antiplasmin (alpha2-AP) activity. TAT concentraction (26.83 ng/ml) was significantly higher in ET group than in controls (3.41 ng/ml). We also showed in patients with ET significantly prolonged aPTT (50.12 s) and elevated platelet count (859.5 G/l). Fibrinolytic parameters PAI-1:Ag (56.2 ng/ml) and PAP (662.5 ng/ml) were significantly higher in patients with ET. High TAT concentration means enhanced thrombinogenesis and prolonged aPTT-disturbances in coagulation activation process. A cause of increased plasminogenesis is increased concentration of PAP.

[Hemostatic disturbances in chronic myeloid leukemia]. / Zaburzenia hemostazy w przewleklej bialaczce szpikowej.

UNLABELLED: Chronic myeloid leukemia (CML) is one of the chronic myeloproliferative disorders. Haemostatic disturbances and infections are the main causes of death in CML. MATERIAL AND METHODS: We investigated 22 patients with CML aged 38-55 years (median 45.0). Twenty nine healthy controls were sex and age-matched. Patients underwent following examination: whole blood count, blood smear, platelets count, prothrombin time (PT), activated partial thromboplastin time (aPTT), euglobulin lysis time (ELT), fibrin degradation products (FDP), thrombin-antithrombin complexes (TAT), plasmin-alpha2-antiplasmin complexes (PAP), antigen and urokinase plasminogen activators (t-PA:Ag, u-PA:Ag), antigen of tissue plasminogen activator inhibitors type 1 and 2 (PAI-1:Ag, PAI-2:Ag), fibrinogen concentrations, antitrombin (AT) and alpha2-antiplasmin (alpha2-AP) activity. RESULTS: TAT concentration (35.46 ng/ml) was significantly higher in examined group than in controls (3.41 ng/ml). Significantly higher fibrinogen concentration (3.31 g/l) and elevated platelet count (611.0 G/1) was observed in patients with CML. We also showed significantly higher concentrations of u-PA:Ag (0.67 ng/ml), PAI-1:Ag (34.8 ng/ml), PAP complexes (473.10 ng/ml) and FDP (17.10 microg/ml) in patients with CML. CONCLUSION: High TAT, fibrinogen concentrations and elevated platelet count in patients with CML are the evidences of an activation of coagulation. On the other hand fibrinolysis activation is proved by higher concentrations of u-PA:Ag, PAI-1:Ag, complexes PAP and FDP.

Risk of venous thromboembolic disease in postmenopausal women taking oral or transdermal hormone replacement therapy.

OBJECTIVE: The influence of hormone replacement therapy (HRT) on hemostasis processes depends on the type of hormone, the combination of doses, the time of taking HRT, and the route of administration (oral, transdermal, implanted). The aim of the current study was to assess some parameters of coagulation, especially tissue factor pathway inhibitor (TFPI) and tissue factor (TF) in postmenopausal women using oral or transdermal HRT. METHODS: The study was conducted on 76 healthy women, including 46 women aged 44-58 years who were taking oral (26) or transdermal (20) HRT, and 30 women aged 44-54 years who did not take HRT as the control group. Plasma concentrations of TF, TFPI, thrombin-antithrombin complex (TAT), and D-dimer were performed by enzyme-linked immunosorbent assay (ELISA). Moreover, the concentration of fibrinogen and activity of protein C were measured by chromogenic and chronometric methods. RESULTS: We observed a significantly higher concentration of TF and a significantly lower concentration of TFPI in women taking oral and transdermal HRT in comparison with the control group. We also found a significantly lower concentration of fibrinogen in women taking oral HRT vs. the control group. Moreover, no statistically significant changes in concentrations of TAT and D-dimer, or activity of protein C were noted. CONCLUSIONS: In this study, the occurrence of an increased TF concentration simultaneously with a decreased concentration of TFPI in women taking HRT indicates hypercoagulability. No significant modification of TAT or D-dimer occurred, and thus there may not be increased risk of thrombosis.

Pantoprazole may enhance antiplatelet effect of enteric-coated aspirin in patients with acute coronary syndrome.

BACKGROUND: Antiplatelet therapy has proven beneficial in the treatment of cardiovascular disease. Proton pump inhibitors (PPIs) are commonly used for gastroprotection in patients receiving antiplatelet therapy. Several trials have been carried out to establish interactions between PPIs, clopidogrel and soluble formulations of aspirin, but no studies with PPIs and enteric-coated (EC) forms of aspirin have been conducted. The aim of this study was to assess if concomitant pantoprazole usage influences antiplatelet effect of EC aspirin in patients with acute coronary syndrome treated with percutaneous coronary intervention (PCI) and dual antiplatelet therapy. METHODS: Thirty-one consecutive patients were prospectively enrolled in the randomized, crossover, open-labelled designed study. The first 16 patients were given orally 40 mg of pantoprazole for the first four days while the next 15 subjects were treated with pantoprazole from the fifth to the eighth day of hospitalisation. Blood samples were collected at 6.00 a.m., 10.00 a.m., 2.00 p.m., and 7.00 p.m. on the fourth and eighth day of hospitalization. Aggregation in response to arachidonic acid was assessed in the whole blood on a new generation impedance aggregometer. RESULTS: Lower overall platelet aggregation in patients treated with pantoprazole (p < 0.03) was observed. When aggregation of platelets was analyzed separately at different times, the differences reached statistical significance six hours after the administration of pantoprazole and antiplatelet agents. The highest absolute difference in arachidonic acid-dependent aggregation was observed two hours after drug ingestion. CONCLUSIONS: Co-administration of pantoprazole may enhance the antiplatelet effect of enteric-coated aspirin in patients with acute coronary syndrome undergoing PCI.

Increased morning ADP-dependent platelet aggregation persists despite dual antiplatelet therapy in patients with first ST-segment elevation myocardial infarction: Preliminary report.

BACKGROUND: Numerous trials have reported on the morning increase in the occurrence of myocardial infarction, stroke and sudden cardiac death. Similarly, enhanced morning platelet aggregation has been observed in healthy individuals and in subjects with coronary artery disease without adequate antiplatelet treatment. The purpose of the study was to assess circadian variation in platelet aggregation in patients with first ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary interventions (pPCI) and dual antiplatelet therapy. METHODS: Fifteen consecutive patients (12 men and 3 women) were prospectively recruited into the study. Blood samples were collected at 6.00 a.m., 10.00 a.m., 2.00 p.m. and 7.00 p.m. on the third day of hospitalization. Aggregation in response to arachidonic acid and adenosine diphosphate (ADP) was assessed in the whole blood on a new generation impedance aggregometer. RESULTS: A morning increase of 75% in ADP-dependent platelet aggregation was noted in the study population (p < 0.04). In contrast, we failed to show any significant diurnal variation in arachidonic acid-mediated platelet aggregation. The magnitude of the morning surge in platelet aggregation after ADP stimulation did not correlate with its baseline level. CONCLUSIONS: Increased morning ADP-dependent platelet aggregation persists despite dual antiplatelet therapy in patients with first STEMI undergoing pPCI. The clinical significance of this finding remains to be demonstrated.