http://informahealthcare.com/plt ISSN: 0953-7104 (print), 1369-1635 (electronic) Platelets, 2014; 25(8): 587–591 ! 2014 Informa UK Ltd. DOI: 10.3109/09537104.2013.847176
ORIGINAL ARTICLE
Mean platelet volume levels in patients with cardiac myxoma Mehmet Emin Kalkan1, Go¨ksel Ac¸ar1, Mu¨slu¨m S¸ ahin1, Muhammed Hakan Ta¸s2, Serdar Demir1, Mehmed Yanarta¸s3, & Rezzan Deniz Acar1 1
Department of Cardiology, Kartal Kosuyolu High Specialty Education and Research Hospital, Istanbul, Turkey, 2Department of Cardiology, Faculty of Medicine, Ataturk University, Erzurum, Turkey, and 3Department of Cardiovascular Surgery, Kartal Kosuyolu High Specialty Education and Research Hospital, Istanbul, Turkey Abstract
Keywords
Thromboembolic events such as cerebrovascular stroke are common and serious complications in patients with cardiac myxomas (CMs). Previous studies have reported that a high mean platelet volume (MPV) level reflects an activated platelet function and has been proven to be an independent risk factor for thromboembolic events. The aim of this study was to evaluate the relation between MPV level and CM. We compared the MPV levels between patients with CM and control subjects, and also evaluated the differences in the MPV levels in patients with CM before and after a successful surgical treatment. Furthermore, we compared the MPV levels in patients with and without cerebrovascular embolic symptoms. Fifty-one consecutive patients (13 men, 38 women, mean age 51.1 16.9 years) who underwent excision of CM in our hospital in the last 13 years and 50 normal subjects as the control group were included in this study. The patients with CM were divided into two groups according to the presence or absence of cerebrovascular embolic symptoms. The preoperative and postoperative MPV levels of each CM patient was evaluated. MPV levels were found to be significantly higher in patients with CM than in control subjects (9.86 1.30 fL vs. 7.63 0.78 fL, p50.001). Moreover, the MPV levels significantly decreased after the surgical removal of CM (9.86 1.30 fL vs. 8.68 1.20 fL, p50.001). We also found that the MPV values were significantly higher in patients with neurological embolic events (10.55 1.29 fL vs. 9.59 0.78 fL, p ¼ 0.016). We conclude that increased MPV levels might be considered as a marker of increased thromboembolic risk in patients with CM.
Cardiac myxoma, mean platelet volume, thromboembolism, stroke
Introduction Cardiac myxomas (CMs) are the most common primary tumors of the heart, accounting for approximately half of all benign primary cardiac tumors. CM is often seen in the left atrium originating from the interatrial septum, but it may also appear in any cardiac chamber [1, 2]. Patients with CM can have various clinical conditions depending on the location, size, mobility, and fragility of the tumor [1–3]. They usually have signs and/or symptoms of intracardiac obstruction or systemic embolic manifestations [2, 3]. Systemic embolism has been reported in approximately 30–50% of patients, half of whom had cerebral infarction [4]. Because of the high risk of neurological embolic events, surgical excision of CM must be done as soon as possible after the diagnosis. Platelets are known to play an important role in the thromboembolic condition. Previous studies have reported that the mean platelet volume (MPV) level reflects the platelet function and activity. Increased MPV level has been proven to be an independent risk factor for thromboembolism, such as stroke or cardiovascular events [5–7]. In recent years, MPV has gained large attention owing to its relation with coronary heart disease, stroke, diabetes
Correspondence: Go¨ksel Ac¸ar, Department of Cardiology, Kartal Kosuyolu High Specialty Education and Research Hospital, 34846 Kartal, Istanbul, Turkey. Tel: +90 (216) 500 1500. Fax: +90 (216) 459 6321. E-mail: [email protected]
History Received 13 June 2013 Revised 16 September 2013 Accepted 17 September 2013 Published online 18 November 2013
mellitus, atherosclerosis, heart failure, and hypertension [8]. To our knowledge, there are no data on MPV levels in patients with CM. We aimed to investigate the MPV level as a simple marker of platelet activation in patients with CM. We compared the MPV levels in patients with CM and control subjects. We also evaluated the differences in the MPV levels in patients with CM before and after a successful surgical treatment. Furthermore, we compared the MPV levels in patients with and without neurological embolic events.
Methods Study population The present study was designed as a retrospective observational study that was carried out at Kartal Ko¸suyolu Cardiovascular Education and Research Hospital in Istanbul. The records of 51 consecutive patients (13 men, 38 women, mean age 51.1 16.9 years) with CM who underwent excision in our hospital between January 2000 and February 2013 were evaluated retrospectively. Patients with a history of atrial fibrillation or flutter, use of antiplatelet drugs such as acetylsalicylic acid, concomitant moderate-to-severe valvular heart disease, hematological disorder, heart failure, renal and hepatic failure, thyroid disorders, chronic obstructive pulmonary disease, and coronary artery disease were excluded. Patients who had atrial or ventricular tachyarrhythmias and cardiac failure were also excluded. In the preoperative period, routine hemogram and other laboratory tests, electrocardiograms,
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echocardiographic data, and other clinical data were checked and noted. Medical history, body mass index, diabetes mellitus, hypertension, hyperlipidemia, and current smoking were recorded. The medical records of all patients were reexamined before discharge, and the hemogram results were also noted. The 51 investigated patients were divided into two groups according to the presence or absence of neurological embolic events. The control group consisted of 50 age- and sex-matched normal subjects who were selected consecutively from subjects admitted to outpatient clinics. The controls were selected from subjects who did not fit the exclusion criteria. The patients’ routinely measured laboratory and clinical parameters were obtained from the medical records. Statistical analysis Statistical analysis was performed using the SPSS for Windows version 11.0 software (Chicago, IL). All continuous variables are expressed as mean SD, and categorical variables are expressed as numbers of patients (percentage). The Kolmogorov–Smirnov test was used to test the normality of distribution. Differences between groups were analyzed by independent sample t-test and paired sample t-test when appropriate. Categorical variables were compared using the chi-square test. Statistical significance was set as a p value of 50.05.
Results We retrospectively reviewed the medical records of 51 consecutive patients with CM who had had a tumor resection in the last 13 years. The baseline demographics, laboratory results, and conventional echocardiographic findings of the CM patients and controls are shown in Table I. The baseline clinical characteristics were similar between the two groups except for a higher heart rate in the CM group. Furthermore, there were no significant differences in the biochemical parameters, including glucose, blood urea nitrogen, and creatinine, between the groups. Left ventricular systolic and diastolic diameters, as well as the ejection fraction, were similar between the two groups, whereas the left atrial diameters were significantly larger in the CM group (p50.001). The hematologic parameters of patients with CM and controls are shown in Table II. The MPV levels were significantly higher in the CM group (9.86 1.30 fL vs. 7.63 0.78 fL, p50.001) (Table II, Figure 1). In the comparison of patients with and without neurological embolic events, the MPV values were significantly higher in those with neurological embolic events (10.55 1.29 fL vs. 9.59 0.78 fL, p ¼ 0.016) (Table III, Figure 2). Comparisons of the hematological parameters of the study population before and after surgery are shown in Table IV. MPV values significantly decreased after surgery (p50.001) (Figure 3), but increased to high levels at postoperative recordings when compared with control subjects (8.68 1.20 fL vs. 7.63 0.78 fL, p50.001). However, the platelet counts in patients did not change significantly after the surgery. The clinical symptoms or signs in all patients are presented in Table V. Forty-two patients presented with one or more signs or symptoms (dyspnea and/or orthopnea, 45%; neurological embolic events, 29%; fatigue, weight loss, or fever, 25%; palpitations, 21%; chest pain, 11.7%), whereas nine patients were asymptomatic.
Discussion This is the first study to evaluate MPV levels in patients with CM. In the present study, we demonstrated that MPV levels were significantly higher in patients with CM than in controls. We also showed that the MPV level significantly decreased after the
Platelets, 2014; 25(8): 587–591
Table I. The comparison of baseline clinical characteristics, laboratory and conventional echocardiographic findings of patients with myxoma and control group.
Variables Age [years] Gender [Female sex] Glucose, mg/dl Bun, mg/dl Creatinine, mg/dl SBP [mm Hg] DBP [mm Hg] Heart rate [bpm] LAd [mm] LVEF [%] LVDd [mm] LVSd, [mm] BSA HL DM HT Current smokers
Myxoma (n ¼ 51)
Control (n ¼ 50)
p Value
51.1 16.9 38 (75%) 95.38 12.81 29.19 11.31 1.124 0.266 113.23 17.06 67.63 10.55 88.79 18.25 40.85 7.34 63.13 7.39 46.21 2.69 29.63 2.33 1.72 0.13 6 (12 %) 4 (8 %) 11 (22 %) 10 (20 %)
48.34 14.18 33 (66%) 94.72 12.01 27.76 5.29 1.097 0.265 111.78 15.99 67.52 10.33 81.32 10.65 36.46 2.88 62.88 7.35 45.84 2.69 28.88 2.25 1.73 0.11 7 (14%) 5 (10%) 13 (26%) 12 (24%)
0.516 0.329 0.795 0.423 0.622 0.665 0.960 0.015 50.001 0.870 0.501 0.111 0.540 0.589 0.498 0.546 0.527
Results are expressed as mean SD and number of patients (percentage). SBP – Systolic Blood Pressure; DBP – Diastolic Blood Pressure; LAd – Left Atrial diameter; LVEF – Left Ventricular Ejection Fraction; LVDd – Left Ventricular end – Diastolic diamater; LVSd – Left Ventricular end-Systolic diamater; BSA – Body Surface Area; HL – Hyperlipidemia; DM – Diabetes Mellitus; HT – Hypertension
Table II. Comparison of the hematological parameters of between patients with myxoma and control group. Variables 3
3
Platelet [10 /mm ] MPV [fL] WBC [103/mL] Haemoglobin [g/dL] HTC [g/dL]
Myxoma (n ¼ 51)
Control (n ¼ 50)
p Value
241.44 72.26 9.86 1.30 7.13 1.46 12.25 1.5 36.99 4.77
271.08 58.98 7.63 0.78 6.90 1.63 13.39 1.20 39.59 3.39
0.028 50.001 0.464 50.001 0.02
MPV – Mean Platelet Volume; WBC – White Blood Cell; HTC – Haematocrit.
surgical removal of CM. Furthermore, MPV values were significantly higher in patients with cerebrovascular embolic symptoms. CMs are the most common primary tumors of the heart. The clinical manifestations of CM are defined by a classic triad that includes (1) cardiac obstructive symptoms, (2) systemic embolic events, and (3) constitutional symptoms [9, 10]. In our study, 42 patients presented with at least one symptom that represents the classic triad, whereas the condition was incidentally diagnosed in nine patients. The incidence of obstructive cardiac, embolic, and neurologic symptoms was similar to those of previous studies. Systemic embolism has been reported in approximately 50% of CM patients, and it usually occurs as cerebrovascular embolic events [4, 9–13]. Embolization can be caused by fragmentation of the CM itself or thrombus formation at the surface of the CM [2, 11]. On histological examination, about half (41%) of CMs have surface thrombi, and cerebrovascular embolic events are most likely related to the thrombus and the irregular indented surface of the myxomas [12, 13]. Similar to a previous study, we found that 29% of patients with CM presented with transient ischemic attack or cerebrovascular stroke [14]. CMs present not only the local presence of the tumor but also the release of humoral factors that have local and systemic effects. Several cytokine abnormalities have been documented to be
MPV levels in CM
DOI: 10.3109/09537104.2013.847176
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Figure 1. Comparison of the MPV levels of between patients with myxoma and controls. Table III. Haematological parameters in patients with and without neurological embolic events.
Variables
Neurological embolic events (þ) (n ¼ 15)
Neurological embolic events () (n ¼ 36)
p Value
Platelet [103/mm3] MPV [fL] WBC [103/mL] Hemoglobin [g/dL] HTC
254.53 78.66 10.55 1.29 7.25 1.29 12.47 1.73 37.67 5.3
235.48 69.61 9.59 0.78 7.06 1.55 12.13 1.38 36.64 4.57
0.403 0.016 0.693 0.458 0.495
Table IV. Comparison of the hematological parameters of patients with myxoma before and after surgical removal (n ¼ 51). Variables
MPV – Mean Platelet Volume; WBC – White Blood Cell; HTC – Haematocrit; LA – Left Atrial.
elevated in CM patients [15, 16]. Also, MPV levels reflect both proinflammatory and prothrombotic conditions, in which numerous inflammatory cytokines (e.g., interleukin [IL]-1, IL-6, and tumor necrosis factor [TNF]-a) regulate thrombopoiesis [8]. Many studies have shown that IL-6 and TNF-a levels were significantly increased in CM patients [15–18] and could stimulate the formation of larger and more reactive platelets [19, 20]. Therefore, in this study, we hypothesized that, although not directly but perhaps as a result of the inflammatory process in the CM, larger platelets and thus thrombopoiesis may be related to elevated levels of cytokines. It is known that platelets play a significant role in several thromboembolic events [5, 6, 21]. Enlarged platelets are both metabolically more active and have a higher thrombotic potential. Previous studies have reported that the MPV value reflects the thrombogenic potential of platelets [21–23]. Furthermore, increased platelet size has been proven to be an independent risk factor for thromboembolic events such as cerebrovascular emboli [3, 5–7]. However, in CM patients, there are no data concerning MPV and its relation to clinical manifestations such as cerebrovascular embolic events. We demonstrated that MPV levels were significantly higher while platelet counts were significantly lower in patients with CM when compared with the control subjects. We also found that MPV levels significantly decreased after the surgical removal of CM. We believe that the
3
3
Platelet [10 /mm ] MPV [fL] WBC [103/mL] Haemoglobin [g/dL] HTC
Preop
Postop
p Value
241.44 72.26 9.86 1.30 7.13 1.46 12.25 1.5 36.99 4.77
234.19 71.02 8.68 1.20 8.8 1.80 11.18 0.94 33.75 3.33
0.553 50.001 50.001 50.001 50.001
p Value is for comparison between parameters before and after treatment MPV – Mean Platelet Volume; WBC – White Blood Cell; HTC – Haematocrit.
increased MPV levels in patients with CM may be attributed to the effect of cytokines produced by the disease. Moreover, the indented surface of the myxomas could contribute to platelet activation by the increased interactions between myxomatous cells and platelets. Previous studies have reported that increased platelet size is often associated with decreased platelet count [21]. As shown previously, we also found that MPV levels increased while platelet counts decreased. Although there is a lack of studies about the hypercoagulability status in CM patients, some studies demonstrated that a relation exists between several conditions such as size, mobility, surface characteristics and the surface thrombi burden of CM, and serum IL-6 level and embolic manifestations in patients with CM [12, 13, 24, 25]. MPV values may be used as a practical indicator of the tendency for thrombogenicity in CM patients. The increased MPV in our patients with CM could be reflected by the increased platelet activation and the thromboembolic tendency. In this study, we found that MPV levels were higher in patients who presented with cerebrovascular embolic symptoms. We speculate that increased MPV levels may be a sign of a potential thromboembolic risk due to CM.
Limitation The present study has several limitations. Owing to the retrospective nature of the study, several limitations can be cited especially
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Platelets, 2014; 25(8): 587–591
Figure 2. Comparison of MPV levels in patients with and without neurological embolic events.
Figure 3. Comparison of MPV levels of patients with myxoma before and after surgical removal. Table V. Clinical data for 51 patients with cardiac myxomas. Clinical signs or symptoms
Frequency
Dyspnoea and/or orthopnoea Constitutional* Neurological embolic events** Palpitations Chest Pain Asymptomatic or incidental
23 (45%) 13 (25%) 15 (29%) 11 (21%) 6 (12 %) 9 (18 %)
Clinical data were available for the 51 patients in the series; 42 of 51 patients had one or more signs or symptoms. Numbers in parentheses are percentages. *Fatigue, weight loss, and/or fever. ** Syncope, transient ischemic attack, ischemic stroke
considering the long duration of patient recruitment. Multiple factors can affect MPV measurement, including the method of collection, interval from collection to analysis, and method of analysis, which were not analyzed in the present study [26–28]. The different recruitment periods between the patients and the control groups are also another limitation. Moreover, our study has a small patient population size. Finally, we found no evidence for a pathophysiological link between the MPV level and CM.
Conclusions In this study, we demonstrated that MPV levels in patients with CM were significantly higher than in control subjects, and that
DOI: 10.3109/09537104.2013.847176
these values significantly decreased after the surgical removal of the myxoma. Furthermore, MPV levels were higher in patients who presented with cerebrovascular emboli than those with other clinical situations. We conclude that increased MPV levels might be considered as a marker of higher thromboembolic risk in patients with CM. Further prospective studies of a larger scale are needed to establish the pathophysiological and clinical significance of increased MPV in CM patients.
Declaration of interest The authors report no declarations of interest. They certify that there is no conflict of interest with any financial organization regarding the material discussed in the manuscript.
References 1. Reynen K. Medical progress: Cardiac myxomas. N Eng J Med 1995; 333:1610–1617. 2. Silverman J, Olwin JS, Graettinger JS. Cardiac myxomas with systemic embolization. Review of the literature. Circulation 1962; 26:99–103. 3. Majano-Lainez RA. Cardiac tumors: A current clinical and pathological perspective. Crit Rev Oncog 1997;8:293–303. 4. Sabolek M, Bachus-Banaschak K, Bachus R, Arnold G, Storch A. Multiple cerebral aneurysms as delayed complication of left cardiac myxoma: A case report and review. Acta Neurol Scand 2005;111: 345–350. 5. Smith NM, Pathansali R, Bath PM. Platelets and stroke. Vasc Med 1999;4:165–172. 6. Martin JF, Bath PM, Burr ML. Influence of platelet size on outcome after myocardial infarction. Lancet 1991;338:1409–1411. 7. Chu SG, Becker RC, Berger PB, Bhatt DL, Eikelboom JW, Konkle B, Mohler ER, Reilly MP, Berger JS. Mean platelet volume as a predictor of cardiovascular risk: A systematic review and metaanalysis. J Thromb Haemost 2010;8:148–156. 8. Gasparyan AY, Ayvazyan L, Mikhailidis DP, Kitas GD. Mean platelet volume: A link between thrombosis and inflammation? Curr Pharm Des 2011;17:47–58. 9. Grande AM, Ragni T, Vigano M. Primary cardiac tumors: A clinical experience of 12 years. Texas Heart Inst J 1993;20:223–230. ¨ zler 10. Kaplan M, Demirta¸s MM, C¸imen S, Gerc¸ekog˘lu H, Yapıcı F, O A. Cardiac myxomas: Surgical experience with 45 cases. Turkish J Thorac Cardiovasc Surg 2002;10:11–14. 11. Tipton BK, Robertson JT, Robertson JH. Embolism to the central nervous system from cardiac myxoma. Report of two cases. J Neurosurg 1977;47:937–940. 12. Burke AP, Virmani R. Cardiac myxoma: A clinicopathologic study. Am J Clin Pathol 1993;100:671–680.
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13. Lee SJ, Kim JH, Na CY, Oh SS. Eleven years’ experience with Korean cardiac myxoma patients: focus on embolic complications. Cerebrovasc Dis 2012;33:471–479. 14. Pinede L, Duhaut P, Loire R. Clinical presentation of left atrial cardiac myxoma: A series of 112 consecutive cases. Medicine (Baltimore) 2000;80:159–172. 15. Smith M, Chaudhry MA, Lozano P, Humphrey MB. Cardiac myxoma induced paraneoplastic syndromes: A review of the literature. Eur J Intern Med 2012;23:669–673. 16. Lin JN, Lai CH, Lu LF, Lin HH. Fever of unknown origin from a left atrial myxoma: An immunologic basis and cytokine association. South Med J 2011;104:360–362. 17. Parissis JT, Mentzikof D, Georgopoulou M, Gikopoulos M, Kanapitsas A, Merkouris K, Kefalas C. Correlation of interleukin6 gene expression to immunologic features in patients with cardiac myxomas. J Interferon Cytokine Res 1996;16:589–593. 18. Colucci WS, Schoen FJ. 2001. Primary tumors of the heart. In: Braunwald E, Zipes DP, Libby P, editors. Heart disease, a textbook of cardiovascular medicine. 6th ed. Philadelphia: WB Saunders. pp 1807–1822. 19. Lotem J, Shabo Y, Sachs L. Regulation of megakaryocyte development by interleukin-6. Blood 1989;74:1545–1551. 20. Kaushansky K. Thrombopoietin: The primary regulator of platelet production. Blood 1995;86:419–431. 21. Hendra TJ, Oswald GA, Yudkin JS. Increased mean platelet volume after acute myocardial infarction relates to diabetes and to cardiac failure. Diabetes Res Clin Pract 1988;5:63–69. 22. Martin JF, Trowbridge EA, Salmon G, Plumb J. The biological significance of platelet volume: Its relationship to bleeding time, platelet thromboxane B2 production and megakaryocyte nuclear DNA concentration. Thromb Res 1983;32:443–460. 23. Thompson CB, Eaton KA, Princiotta SM, Kushkin CA, Valeri CR. Size dependent platelet subpopulations: Relationship of platelet volume to ultrastructure, enzymatic activity and function. Br J Haematol 1982;50:509–519. 24. Mendoza CE, Rosado MF, Bernal L. The role of interleukin-6 in cases of cardiac myxoma. Clinical features, immunologic abnormalities, and a possible role in recurrence. Tex Heart Inst J 2001;28: 3–7. 25. Wada A, Kanda T, Hayashi R, Imai S, Suzuki T, Murata K. Cardiac myxoma metastasized to the brain: Potential role of endogenous interleukin-6. Cardiology 1993;83:208–211. 26. Park Y, Schoene N, Harris W. Mean platelet volume as an indicator of platelet activation: Methodological issues. Platelets 2002;13: 301–306. 27. Bath PM. The routine measurement of platelet size using sodium citrate alone as the anticoagulant. Thromb Haemost 1993;70: 687–690. 28. Trowbridge EA, Reardon DM, Hutchinson D, Pickering C. The routine measurement of platelet volume: A comparison of lightscattering and aperture-impedance technologies. Clin Phys Physiol Meas 1985;6:221–238.
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ORIGINAL ARTICLE
Mean platelet volume levels in patients with cardiac myxoma Mehmet Emin Kalkan1, Go¨ksel Ac¸ar1, Mu¨slu¨m S¸ ahin1, Muhammed Hakan Ta¸s2, Serdar Demir1, Mehmed Yanarta¸s3, & Rezzan Deniz Acar1 1
Department of Cardiology, Kartal Kosuyolu High Specialty Education and Research Hospital, Istanbul, Turkey, 2Department of Cardiology, Faculty of Medicine, Ataturk University, Erzurum, Turkey, and 3Department of Cardiovascular Surgery, Kartal Kosuyolu High Specialty Education and Research Hospital, Istanbul, Turkey Abstract
Keywords
Thromboembolic events such as cerebrovascular stroke are common and serious complications in patients with cardiac myxomas (CMs). Previous studies have reported that a high mean platelet volume (MPV) level reflects an activated platelet function and has been proven to be an independent risk factor for thromboembolic events. The aim of this study was to evaluate the relation between MPV level and CM. We compared the MPV levels between patients with CM and control subjects, and also evaluated the differences in the MPV levels in patients with CM before and after a successful surgical treatment. Furthermore, we compared the MPV levels in patients with and without cerebrovascular embolic symptoms. Fifty-one consecutive patients (13 men, 38 women, mean age 51.1 16.9 years) who underwent excision of CM in our hospital in the last 13 years and 50 normal subjects as the control group were included in this study. The patients with CM were divided into two groups according to the presence or absence of cerebrovascular embolic symptoms. The preoperative and postoperative MPV levels of each CM patient was evaluated. MPV levels were found to be significantly higher in patients with CM than in control subjects (9.86 1.30 fL vs. 7.63 0.78 fL, p50.001). Moreover, the MPV levels significantly decreased after the surgical removal of CM (9.86 1.30 fL vs. 8.68 1.20 fL, p50.001). We also found that the MPV values were significantly higher in patients with neurological embolic events (10.55 1.29 fL vs. 9.59 0.78 fL, p ¼ 0.016). We conclude that increased MPV levels might be considered as a marker of increased thromboembolic risk in patients with CM.
Cardiac myxoma, mean platelet volume, thromboembolism, stroke
Introduction Cardiac myxomas (CMs) are the most common primary tumors of the heart, accounting for approximately half of all benign primary cardiac tumors. CM is often seen in the left atrium originating from the interatrial septum, but it may also appear in any cardiac chamber [1, 2]. Patients with CM can have various clinical conditions depending on the location, size, mobility, and fragility of the tumor [1–3]. They usually have signs and/or symptoms of intracardiac obstruction or systemic embolic manifestations [2, 3]. Systemic embolism has been reported in approximately 30–50% of patients, half of whom had cerebral infarction [4]. Because of the high risk of neurological embolic events, surgical excision of CM must be done as soon as possible after the diagnosis. Platelets are known to play an important role in the thromboembolic condition. Previous studies have reported that the mean platelet volume (MPV) level reflects the platelet function and activity. Increased MPV level has been proven to be an independent risk factor for thromboembolism, such as stroke or cardiovascular events [5–7]. In recent years, MPV has gained large attention owing to its relation with coronary heart disease, stroke, diabetes
Correspondence: Go¨ksel Ac¸ar, Department of Cardiology, Kartal Kosuyolu High Specialty Education and Research Hospital, 34846 Kartal, Istanbul, Turkey. Tel: +90 (216) 500 1500. Fax: +90 (216) 459 6321. E-mail: [email protected]
History Received 13 June 2013 Revised 16 September 2013 Accepted 17 September 2013 Published online 18 November 2013
mellitus, atherosclerosis, heart failure, and hypertension [8]. To our knowledge, there are no data on MPV levels in patients with CM. We aimed to investigate the MPV level as a simple marker of platelet activation in patients with CM. We compared the MPV levels in patients with CM and control subjects. We also evaluated the differences in the MPV levels in patients with CM before and after a successful surgical treatment. Furthermore, we compared the MPV levels in patients with and without neurological embolic events.
Methods Study population The present study was designed as a retrospective observational study that was carried out at Kartal Ko¸suyolu Cardiovascular Education and Research Hospital in Istanbul. The records of 51 consecutive patients (13 men, 38 women, mean age 51.1 16.9 years) with CM who underwent excision in our hospital between January 2000 and February 2013 were evaluated retrospectively. Patients with a history of atrial fibrillation or flutter, use of antiplatelet drugs such as acetylsalicylic acid, concomitant moderate-to-severe valvular heart disease, hematological disorder, heart failure, renal and hepatic failure, thyroid disorders, chronic obstructive pulmonary disease, and coronary artery disease were excluded. Patients who had atrial or ventricular tachyarrhythmias and cardiac failure were also excluded. In the preoperative period, routine hemogram and other laboratory tests, electrocardiograms,
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echocardiographic data, and other clinical data were checked and noted. Medical history, body mass index, diabetes mellitus, hypertension, hyperlipidemia, and current smoking were recorded. The medical records of all patients were reexamined before discharge, and the hemogram results were also noted. The 51 investigated patients were divided into two groups according to the presence or absence of neurological embolic events. The control group consisted of 50 age- and sex-matched normal subjects who were selected consecutively from subjects admitted to outpatient clinics. The controls were selected from subjects who did not fit the exclusion criteria. The patients’ routinely measured laboratory and clinical parameters were obtained from the medical records. Statistical analysis Statistical analysis was performed using the SPSS for Windows version 11.0 software (Chicago, IL). All continuous variables are expressed as mean SD, and categorical variables are expressed as numbers of patients (percentage). The Kolmogorov–Smirnov test was used to test the normality of distribution. Differences between groups were analyzed by independent sample t-test and paired sample t-test when appropriate. Categorical variables were compared using the chi-square test. Statistical significance was set as a p value of 50.05.
Results We retrospectively reviewed the medical records of 51 consecutive patients with CM who had had a tumor resection in the last 13 years. The baseline demographics, laboratory results, and conventional echocardiographic findings of the CM patients and controls are shown in Table I. The baseline clinical characteristics were similar between the two groups except for a higher heart rate in the CM group. Furthermore, there were no significant differences in the biochemical parameters, including glucose, blood urea nitrogen, and creatinine, between the groups. Left ventricular systolic and diastolic diameters, as well as the ejection fraction, were similar between the two groups, whereas the left atrial diameters were significantly larger in the CM group (p50.001). The hematologic parameters of patients with CM and controls are shown in Table II. The MPV levels were significantly higher in the CM group (9.86 1.30 fL vs. 7.63 0.78 fL, p50.001) (Table II, Figure 1). In the comparison of patients with and without neurological embolic events, the MPV values were significantly higher in those with neurological embolic events (10.55 1.29 fL vs. 9.59 0.78 fL, p ¼ 0.016) (Table III, Figure 2). Comparisons of the hematological parameters of the study population before and after surgery are shown in Table IV. MPV values significantly decreased after surgery (p50.001) (Figure 3), but increased to high levels at postoperative recordings when compared with control subjects (8.68 1.20 fL vs. 7.63 0.78 fL, p50.001). However, the platelet counts in patients did not change significantly after the surgery. The clinical symptoms or signs in all patients are presented in Table V. Forty-two patients presented with one or more signs or symptoms (dyspnea and/or orthopnea, 45%; neurological embolic events, 29%; fatigue, weight loss, or fever, 25%; palpitations, 21%; chest pain, 11.7%), whereas nine patients were asymptomatic.
Discussion This is the first study to evaluate MPV levels in patients with CM. In the present study, we demonstrated that MPV levels were significantly higher in patients with CM than in controls. We also showed that the MPV level significantly decreased after the
Platelets, 2014; 25(8): 587–591
Table I. The comparison of baseline clinical characteristics, laboratory and conventional echocardiographic findings of patients with myxoma and control group.
Variables Age [years] Gender [Female sex] Glucose, mg/dl Bun, mg/dl Creatinine, mg/dl SBP [mm Hg] DBP [mm Hg] Heart rate [bpm] LAd [mm] LVEF [%] LVDd [mm] LVSd, [mm] BSA HL DM HT Current smokers
Myxoma (n ¼ 51)
Control (n ¼ 50)
p Value
51.1 16.9 38 (75%) 95.38 12.81 29.19 11.31 1.124 0.266 113.23 17.06 67.63 10.55 88.79 18.25 40.85 7.34 63.13 7.39 46.21 2.69 29.63 2.33 1.72 0.13 6 (12 %) 4 (8 %) 11 (22 %) 10 (20 %)
48.34 14.18 33 (66%) 94.72 12.01 27.76 5.29 1.097 0.265 111.78 15.99 67.52 10.33 81.32 10.65 36.46 2.88 62.88 7.35 45.84 2.69 28.88 2.25 1.73 0.11 7 (14%) 5 (10%) 13 (26%) 12 (24%)
0.516 0.329 0.795 0.423 0.622 0.665 0.960 0.015 50.001 0.870 0.501 0.111 0.540 0.589 0.498 0.546 0.527
Results are expressed as mean SD and number of patients (percentage). SBP – Systolic Blood Pressure; DBP – Diastolic Blood Pressure; LAd – Left Atrial diameter; LVEF – Left Ventricular Ejection Fraction; LVDd – Left Ventricular end – Diastolic diamater; LVSd – Left Ventricular end-Systolic diamater; BSA – Body Surface Area; HL – Hyperlipidemia; DM – Diabetes Mellitus; HT – Hypertension
Table II. Comparison of the hematological parameters of between patients with myxoma and control group. Variables 3
3
Platelet [10 /mm ] MPV [fL] WBC [103/mL] Haemoglobin [g/dL] HTC [g/dL]
Myxoma (n ¼ 51)
Control (n ¼ 50)
p Value
241.44 72.26 9.86 1.30 7.13 1.46 12.25 1.5 36.99 4.77
271.08 58.98 7.63 0.78 6.90 1.63 13.39 1.20 39.59 3.39
0.028 50.001 0.464 50.001 0.02
MPV – Mean Platelet Volume; WBC – White Blood Cell; HTC – Haematocrit.
surgical removal of CM. Furthermore, MPV values were significantly higher in patients with cerebrovascular embolic symptoms. CMs are the most common primary tumors of the heart. The clinical manifestations of CM are defined by a classic triad that includes (1) cardiac obstructive symptoms, (2) systemic embolic events, and (3) constitutional symptoms [9, 10]. In our study, 42 patients presented with at least one symptom that represents the classic triad, whereas the condition was incidentally diagnosed in nine patients. The incidence of obstructive cardiac, embolic, and neurologic symptoms was similar to those of previous studies. Systemic embolism has been reported in approximately 50% of CM patients, and it usually occurs as cerebrovascular embolic events [4, 9–13]. Embolization can be caused by fragmentation of the CM itself or thrombus formation at the surface of the CM [2, 11]. On histological examination, about half (41%) of CMs have surface thrombi, and cerebrovascular embolic events are most likely related to the thrombus and the irregular indented surface of the myxomas [12, 13]. Similar to a previous study, we found that 29% of patients with CM presented with transient ischemic attack or cerebrovascular stroke [14]. CMs present not only the local presence of the tumor but also the release of humoral factors that have local and systemic effects. Several cytokine abnormalities have been documented to be
MPV levels in CM
DOI: 10.3109/09537104.2013.847176
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Figure 1. Comparison of the MPV levels of between patients with myxoma and controls. Table III. Haematological parameters in patients with and without neurological embolic events.
Variables
Neurological embolic events (þ) (n ¼ 15)
Neurological embolic events () (n ¼ 36)
p Value
Platelet [103/mm3] MPV [fL] WBC [103/mL] Hemoglobin [g/dL] HTC
254.53 78.66 10.55 1.29 7.25 1.29 12.47 1.73 37.67 5.3
235.48 69.61 9.59 0.78 7.06 1.55 12.13 1.38 36.64 4.57
0.403 0.016 0.693 0.458 0.495
Table IV. Comparison of the hematological parameters of patients with myxoma before and after surgical removal (n ¼ 51). Variables
MPV – Mean Platelet Volume; WBC – White Blood Cell; HTC – Haematocrit; LA – Left Atrial.
elevated in CM patients [15, 16]. Also, MPV levels reflect both proinflammatory and prothrombotic conditions, in which numerous inflammatory cytokines (e.g., interleukin [IL]-1, IL-6, and tumor necrosis factor [TNF]-a) regulate thrombopoiesis [8]. Many studies have shown that IL-6 and TNF-a levels were significantly increased in CM patients [15–18] and could stimulate the formation of larger and more reactive platelets [19, 20]. Therefore, in this study, we hypothesized that, although not directly but perhaps as a result of the inflammatory process in the CM, larger platelets and thus thrombopoiesis may be related to elevated levels of cytokines. It is known that platelets play a significant role in several thromboembolic events [5, 6, 21]. Enlarged platelets are both metabolically more active and have a higher thrombotic potential. Previous studies have reported that the MPV value reflects the thrombogenic potential of platelets [21–23]. Furthermore, increased platelet size has been proven to be an independent risk factor for thromboembolic events such as cerebrovascular emboli [3, 5–7]. However, in CM patients, there are no data concerning MPV and its relation to clinical manifestations such as cerebrovascular embolic events. We demonstrated that MPV levels were significantly higher while platelet counts were significantly lower in patients with CM when compared with the control subjects. We also found that MPV levels significantly decreased after the surgical removal of CM. We believe that the
3
3
Platelet [10 /mm ] MPV [fL] WBC [103/mL] Haemoglobin [g/dL] HTC
Preop
Postop
p Value
241.44 72.26 9.86 1.30 7.13 1.46 12.25 1.5 36.99 4.77
234.19 71.02 8.68 1.20 8.8 1.80 11.18 0.94 33.75 3.33
0.553 50.001 50.001 50.001 50.001
p Value is for comparison between parameters before and after treatment MPV – Mean Platelet Volume; WBC – White Blood Cell; HTC – Haematocrit.
increased MPV levels in patients with CM may be attributed to the effect of cytokines produced by the disease. Moreover, the indented surface of the myxomas could contribute to platelet activation by the increased interactions between myxomatous cells and platelets. Previous studies have reported that increased platelet size is often associated with decreased platelet count [21]. As shown previously, we also found that MPV levels increased while platelet counts decreased. Although there is a lack of studies about the hypercoagulability status in CM patients, some studies demonstrated that a relation exists between several conditions such as size, mobility, surface characteristics and the surface thrombi burden of CM, and serum IL-6 level and embolic manifestations in patients with CM [12, 13, 24, 25]. MPV values may be used as a practical indicator of the tendency for thrombogenicity in CM patients. The increased MPV in our patients with CM could be reflected by the increased platelet activation and the thromboembolic tendency. In this study, we found that MPV levels were higher in patients who presented with cerebrovascular embolic symptoms. We speculate that increased MPV levels may be a sign of a potential thromboembolic risk due to CM.
Limitation The present study has several limitations. Owing to the retrospective nature of the study, several limitations can be cited especially
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Platelets, 2014; 25(8): 587–591
Figure 2. Comparison of MPV levels in patients with and without neurological embolic events.
Figure 3. Comparison of MPV levels of patients with myxoma before and after surgical removal. Table V. Clinical data for 51 patients with cardiac myxomas. Clinical signs or symptoms
Frequency
Dyspnoea and/or orthopnoea Constitutional* Neurological embolic events** Palpitations Chest Pain Asymptomatic or incidental
23 (45%) 13 (25%) 15 (29%) 11 (21%) 6 (12 %) 9 (18 %)
Clinical data were available for the 51 patients in the series; 42 of 51 patients had one or more signs or symptoms. Numbers in parentheses are percentages. *Fatigue, weight loss, and/or fever. ** Syncope, transient ischemic attack, ischemic stroke
considering the long duration of patient recruitment. Multiple factors can affect MPV measurement, including the method of collection, interval from collection to analysis, and method of analysis, which were not analyzed in the present study [26–28]. The different recruitment periods between the patients and the control groups are also another limitation. Moreover, our study has a small patient population size. Finally, we found no evidence for a pathophysiological link between the MPV level and CM.
Conclusions In this study, we demonstrated that MPV levels in patients with CM were significantly higher than in control subjects, and that
DOI: 10.3109/09537104.2013.847176
these values significantly decreased after the surgical removal of the myxoma. Furthermore, MPV levels were higher in patients who presented with cerebrovascular emboli than those with other clinical situations. We conclude that increased MPV levels might be considered as a marker of higher thromboembolic risk in patients with CM. Further prospective studies of a larger scale are needed to establish the pathophysiological and clinical significance of increased MPV in CM patients.
Declaration of interest The authors report no declarations of interest. They certify that there is no conflict of interest with any financial organization regarding the material discussed in the manuscript.
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