ST elevasyonlu ve ST elevasyonsuz miyokard infarktüsünde ortalama trombosit hacmi

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Introduction
The biological events that occur in the coronary
artery system immediately preceding acute coronary
syndromes are still unclear. However, platelets are
definitely involved, and changes in platelet structure may be a causal factor in producing a thrombus
in the coronary artery. All regional acute myocardial
infarctions are caused by thrombosis developing on a
culprit coronary atherosclerotic plaque. Thrombosis
is also the major initiating factor in unstable angina,
particularly when rest pain is recent and increasing in
severity, frequency and duration. Platelet activation,
by favoring thrombus formation and coronary artery
occlusion, is thought to play a key pathogenetic role
in acute myocardial infarction.
It has been shown that platelet size, measured as
mean platelet volume (MPV), correlates with their
reactivity (2). Circulating platelets are heterogeneous
in size, density, and reactivity. Platelet age and size
are independent determinants of platelet function.
Mean platelet volume is positively associated with
indicators of platelet activity including expression
of glycoprotein Ib and glycoprotein IIb/IIIa receptors (3-7). Higher values of MPV characterize patients
with myocardial infarction and unstable angina as
compared to those with stable angina or noncardiac
chest pain, and elevated MPV has been recognized as
an independent risk factor for myocardial infarction
and stroke (8-11). In acute states of platelet activation, increase in platelet volume might be a result of
a change in the fragmentation pattern of megakaryocyte cytoplasm (12). An elevated MPV is associated
with poor clinical outcome among survivors of myocardial infarction (13,14).
To the best of our knowledge, this property of
MPV has only been studied in the context of comparing stable and unstable angina pectoris (USAP) as
well as USAP and acute myocardial infarction (MI).
This laboratory parameter has never been investigated in comparing ST elevation myocardial infarction
(STEMI) and non-ST elevation myocardial infarction
(NSTEMI) patients in terms of understanding the pathophysiological difference between platelets in both
clinical conditions. In this study, we aimed to investigate the MPV and platelet count for better understanding the pathophysiologic role of platelets in both
STEMI and NSTEMI patients.
Material and Methods
Fifty two consecutive patients with NSTEMI (mean
age 69±14 years, 77% of them male) and 56 consecutive patients with STEMI (mean age 66±16 years,
68% of them male), thus a total of 108 acute coronary syndrome patients (mean age 68±16 years,
75% of them male) were enrolled in this study. Age-
and gender-matched 50 healthy subjects (mean age
66±15, 74% of them male) without diabetes mellitus,
hypertension, dyslipidemia and no history of bleeding diathesis constituted the control group. None of
the subjects were smoker, under any medication, had
any known platelet diseases and abnormal routine
blood chemistry values.
Enrollment criteria required a clinical picture consistent with acute MI, with ongoing chest pain unresponsive to nitrates and lasting more than 30 minutes
and elevated serum cardiac markers such as troponins, creatinin kinase and aspartate transaminase.
Patients with cardiogenic shock, currently receiving
antithrombotic therapy, stroke within 2 years, or any
permanent residual neurologic defect were excluded.
STEMI was defined as the presence of ST-segment elevation of at least 1 mm in 2 or more contiguous leads
or new (or presumably new) left bundle branch block.
NSTEMI criteria included other electrocardiographic
patterns, such as ST-segment depression or T-wave inversion and required angiographic demonstration of
a high-grade culprit stenosis with an associated segmental wall motion abnormality before enrollment.
In all cases, venous peripheral blood samples for
the MPV measurement were drawn on admission.
Blood samples were taken into standardized tubes
containing dipotassium ethylenedinitro tetraacetic
acid (EDTA) and stored in room temperature. All measurements were performed within 30 min after blood collection. A biochemical profile was obtained by
automated analysis (R-A 1000, RA-XT autoanalyser,
Technicon, Tarrytown, NY, USA) in the Department
of Biochemistry. A Coulter MD II device (Coulter MD
II Series Analyzer, Coulter Cooperation, Miami, FL,
USA) was utilized for whole blood counts with appropriate calibration (15). The assessment of MPV was
made without clopidogrel, heparin, or tirofiban on
medication board.
In each case, coronary angiography was performed
in standard projections for different coronary arteries (Integris H5000C, Philips Company, Netherlands).
Digital angiograms were then analyzed by an experienced interventional cardiologist. All angiograms
were assessed with a respect to Thrombolysis In
Myocardial Infarction (TIMI) flow scale in infarctrelated artery (16).
All patients received 300 mg acetylsalicylic acid before intervention and unfractioned heparin during
PCI on a routine basis. Clopidogrel was given (600
mg loading dose, and subsequently 75 mg daily) to
all stent implanted cases. Glycoprotein IIb/IIIa inhibitors (tirofiban) were administered during PCI, at
the discretion of the operator. All specific drugs were
started in the cardiac intensive care unit according to
current guidelines (17,18).
In statistical analysis data were analyzed using SPSS
for Windows statistical package version 15.0 (SPSS
Inc., Chicago, IL). Quantitative data were presented as mean±standard deviation. Demographic characteristics were expressed by descriptive analysis.
Independent samples t-test or Mann-Whitney U-test
was used to compare continuous variables where appropriate. Statistical difference was defined by a p value below 0.05.
Results
There were no differences between the STEMI and
NSTEMI groups in terms of age, smoking habits,
hypertension, diabetes mellitus, blood lipid profile,
whole blood count, sedimentation and leukocyte differential counts (Table I). Only the MPV comparison
between STEMI and NSTEMI groups demonstrated a
statistical significance in favor of higher MPV values
for STEMI (p=0.001). When we compared the MPV
values of both STEMI and NSTEMI patients individually with healthy controls, only the MPV values in
the STEMI group were found to be significantly higher (8.7±1 vs 8.1±0.7, p=0.03 and 7.9±0.7 vs 8.1±0.7,
p=0.52, respectively). Comparing STEMI and NSTEMI
total platelet counts individually with those of healthy people demonstrated lower platelet counts for
both STEMI and NSTEMI groups reaching statistical significance (221.2±69.9 vs 350.1±102.8; p=0.01
and 256.5±78 vs 350.1±102.8; p<0.001, respectively).
Total platelet counts in the STEMI and NSTEMI patients did not show any statistical difference (p=0.2).
All NSTEMI patients survived, but four STEMI patients (7%) died in the early 30-day periodable I. Characteristics of the study groups
Control group
(n=50)
Non-ST elevation myocardial
infarction group (n=52)
ST elevation myocardial infarction
group (n=56)
p value*
Age (year) 67±14 69±14 66±16 0.11
Gender (male) 35 (70%) 40 (77%) 38 (68%) 0.29
Smoking 9 (18%) 9 (17%) 11 (20%) 0.75
Hypertension 11 (22%) 11 (21%) 14 (25%) 0.65
Diabetes mellitus 7 (14%) 6 (12%) 8 (14%) 0.67
Cholesterol/HDL 4.9±2.3 5.1±3.5 4.8±1.7 0.81
LDL (mg/dL) 122.1±48.6 121.8±53.8 122.3±46.8 0.90
HDL (mg/dL) 43.1±14.7 43.9±15.4 42.9±14.3 0.88
VLDL (mg/dL) 26±22 24±19 35±29 0.23
Triglyceride (mg/dL) 173±114 168.3±94 181.3±148 0.10
White blood count (10
9
/L) 8.7±4 11.4±6 11.2±4 0.93
Neutrophil (%) 58.1±19.4 73.3±20 62.8±20 0.10
Lymphocyte (%) 27.5±12 20.2±9 26.4±19 0.22
Monocyte (%) 4.8±3 5.9±3 6.1±2 0.28
Eosinophil (%) 0.3±0.1 0.3±0.1 0.4±0.1 0.44
Basophil (%) 2.5±1.6 2.7±0.1 2.5±8.7 0.36
Red blood cell (10
12
/L) 4.4±0.9 4.2±0.9 4.4±0.5 0.63
Hemoglobin (gr/dl) 14.1±2 12.6±2 13.6±1 0.28
Hematocrit (%) 42±6.8 37.1±7.7 40.4±4 0.22
Mean corpuscular volume (fl) 89.2±7 87.1±6 91.7±5 0.07
Platelet count (10
9
/L) 350.1±102.8 256.5±78 221.2±69.8 0.21
Mean platelet volume (fl) 8.1±0.7 7.9±0.7 8.7±1 <0.1Discussion
Circulating platelets are heterogeneous in size,
density, and reactivity (19,20). Changes in these variables may be causal in acute coronary syndromes
(13). Initial plaque rupture in the coronary artery and
subsequent exposure of thrombogenic components
of the vessel wall to platelets might be the precipitating event in thrombus formation. However, independent of the prothrombotic changes in the plaque,
the presence of larger, more reactive platelets is also
likely to contribute to thrombosis (21-23). Platelet
size has been shown to reflect platelet activity. MPV
can reflect changes in the level of platelet stimulation (physiology) and the rate of platelet production
(biology) (24).
Changes in the platelet size and count, on the other hand, was relatively well documented in patients
with acute coronary syndromes. P selectin and MPV,
two markers associated with platelet reactivity, were
shown to be elevated in acute coronary syndromes
(27).
Our study showed higher MPV values in STEMI
as compared to NSTEMI patients. Also, when these
results were compared with healthy controls, only
STEMI patients’ MPV results were significantly higher.
In our study, platelet counts were similar in both
NSTEMI and STEMI patients, not reaching statistical
difference, but comparison of platelet counts between healthy and NSTEMI as well as healthy and STEMI
patients demonstrated significantly lower platelet counts, consistent with the literature (2,9,26). No significant difference in MPV was reported in chronic
stable patients with ischemic disease waiting for cardiac surgery compared with healthy volunteers (28).
One might argue that only the transition from the
stable to the unstable form of coronary artery disease is accompanied by activation of thrombopoiesis
and may produce larger platelets with lower platelet
numbers, which is also consistent with our findings
comparing the healthy normal individuals with acute myocardial infarction patients (28).
Further evidence implying that an increased MPV
contributes to the prothrombotic state in acute coronary syndromes has been reported in a recent study
by Pizzulli et al performed on 981 patients (9). They
have found a significant increase in MPV in patients
with unstable angina as compared to stable angina
and noncardiac chest pain. This increase in platelet
size has been accompanied by a decrease in platelet
count, which is also consistent with our findings (9).There was no statistical difference in platelet counts between STEMI and NSTEMI patients. To the
best of our knowledge, this has not been reported in
the literature previously. When we compared MPV
for both STEMI and NSTEMI groups, we found higher
MPV values for STEMI compared to healthy controls,
which was consistent with larger and reactive platelets causing a higher prothrombotic state leading to
consumption of larger and reactive platelets (29,30).
Although not reaching statistical significance, smaller MPV values were found in NSTEMI compared to
healthy controls. Therefore, one may conclude why
STEMI is a more emergent and mortal state in the
early period of acute myocardial infarction comparing to NSTEMI rather than the late period and deserves more aggressive approach in terms of emergent
revascularization (10).
Another important finding of our study was that,
when MPV values in STEMI and NSTEMI groups were
compared with healthy individuals, larger MPV were found in STEMI, possibly leading to increased consumption of larger and reactive platelets causing a higher
prothrombotic state in STEMI rather than the NSTEMI
(10). It has also been reported that a combination of
higher MPV and lower platelet count is a major risk factor for myocardial infarction, which is again consistent
with our findings in terms of increased early mortality
only in STEMI but not in NSTEMI (31,32).
Early PCI (with or without abciximab) should be
the default mechanical reperfusion therapy in STEMI.
Although overall long-term survival is in general
excellent in non-shock patients with STEMI and
NSTEMI undergoing mechanical reperfusion therapy, close follow-up of patients with both STEMI
and NSTEMI is warranted because of their increased
rates of ischemic events one month to one year after
primary PCI because of increased prothrombotic state
in both conditions.
In conclusion MPV but not platelet count differs
between STEMI and NSTEMI patients, which deserve further clinical research in terms of understanding
the pathophysiological basis of these clinical circumstances and developing new therapeutic strategies for
this particular acute coronary syndrome.