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NDT Advance Access originally published online on March 30, 2006
Nephrology Dialysis Transplantation 2006 21(6):1549-1554; doi:10.1093/ndt/gfl127
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© The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Original Articles: Clinical Nephrology

Acute myocardial infarction in thrombotic microangiopathies—clinical characteristics, risk factors and outcome

Daniel Patschan1, Oliver Witzke1, Ulrich Dührsen2, Raimund Erbel3, Thomas Philipp1 and Stefan Herget-Rosenthal1

1 Department of Nephrology, 2 Department of Haematology and 3 Department of Cardiology, University Hospital, Essen, University of Duisburg-Essen, Germany

Correspondence and offprint requests to: Stefan Herget-Rosenthal, MD, Klinik für Nieren- und Hochdruckkrankheiten, Universitätsklinikum Essen, Hufelandstr. 55, D-45122 Essen, Germany. Email: stefan.herget-rosenthal{at}uni-essen.de



   Abstract
Top
 Abstract
Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Background. Acute myocardial infarction (AMI) has been reported and is associated with poor outcome in the course of thrombotic microangiopathies (TMA). However, data are very limited in regard to the clinical characteristics, risk factors and outcome of AMI during TMA. Furthermore, current AMI definitions based on troponins are more sensitive and specific to detect myocardial injury.

Methods. We retrospectively analysed 74 consecutive patients with 78 TMA episodes. TMA was defined as platelets below 150 x 109/l, haemolytic anaemia, elevated lactate dehydrogenase (LDH) and increased red cell fragmentation, and AMI as serum troponin I above 1 ng/ml with symptoms of myocardial ischaemia and/or appropriate electrocardiography (ECG) alterations.

Results. AMI occurred in 14 TMA episodes (18%) (9 non- and 5 ST-segment elevation AMI). AMI occurred 5±3 days after TMA diagnosis, predominately in clinically suspected thrombotic thrombocytopenic purpura (TTP) as TMA subtype. Independent risk factors for subsequent AMI were TTP (RR 2.2; 95% CI 1.1–5.6), and serum LDH above 1000 U/l (RR 2.7; 95% CI 1.3–7.2) as well as serum troponin I above 0.20 ng/ml at TMA presentation (RR 13.5; 95% CI 2.6–86.8). LDH above 1000 U/l together with troponin I above 0.20 ng/ml had a sensitivity of 86% (95% CI 60–96%) and a specificity of 95% (95% CI 86–98%) to predict AMI in the later course of TMA. AMI contributed substantially to morbidity causing left ventricular dysfunction in three of eight survivors and potentially accounted for the death in five of six non-survivors.

Conclusions. AMI is an early, frequent and severe complication during TMA. AMI occurs especially in TTP, and serum LDH above 1000 U/l in combination with serum troponin I above 0.20 ng/ml at TMA presentation are excellent predictors of subsequent AMI.

Keywords: myocardial infarction; prediction; thrombotic microangiopathy; thrombotic thrombocytopenic purpura; troponin



   Introduction
Top
 Abstract
 Introduction
Subjects and methods
 Results
 Discussion
 References
 
Despite therapeutic advances, thrombotic microangiopathies (TMA) are still associated with high mortalities [1–10]. Post-mortem studies observed extensive myocardial microthrombi in TMA, predominately in thrombotic thrombocytopenic purpura (TTP), resulting in acute myocardial infarction (AMI) and potentially contributing to the high mortality of these patients [11–15]. Although smaller clinical reports demonstrate that AMI may be common in TTP [16,17], data from larger studies do not provide adequate information regarding AMI during TMA [1–10]. Furthermore, definitions of AMI have substantially changed within the last years and current definitions of AMI are based on serum troponins as the most sensitive and specific markers of myocardial injury [18]. Our aim was to systematically assess the frequency of AMI in TMA by the current definition, to characterize the clinical course and outcome, and to identify potential risk factors of AMI during TMA.



   Subjects and methods
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 Abstract
 Introduction
 Subjects and methods
Results
 Discussion
 References
 
In this retrospective cohort study, we included all consecutive patients at the age of 18 years or above with an initial or recurrent, acute episode of TMA who reported to the Department of Nephrology, a tertiary referral centre, for potential plasma exchange (PE) from 1999 to 2004. This department is the largest of five PE providers in the metropolitan Ruhr area of Germany and also serves a large cancer centre. TMA was defined as platelets below 150 x 109/l, Coombs negative haemolytic anaemia, elevated lactate dehydrogenase (LDH; upper reference value 240 U/l) and red cell fragmentation. As quantification of fragmented red cells is difficult to reproduce, counts in our centre were consistently performed by the same experienced laboratory technician. TMA classification was adapted from recent proposals [19]. TTP was clinically suspected (i) by the presence of TMA, (ii) in the absence of other conditions associated with TMA, such as malignant hypertension, pregnancy, specific medication, systemic autoimmune disease, transplantation and others, and (iii) in the absence of features suggestive of classical haemolytic uraemic syndrome (HUS), such as diarrhoea in the preceding 2 weeks, oliguria and serum creatinine above 130 µmol/l. We omitted von Willebrand factor-cleaving protease (ADAMTS13) activity or inhibitor level as diagnostic indicators of TTP, as these were only available in 12 patients. Classical HUS was clinically suspected by TMA in the presence of the aforesaid features and a documented Escherichia coli O157:H7 infection [19]. The remaining patients were classified as ‘non-classical HUS/other TMA types’ [19]. Non-cardiac involvement by TMA was defined as new hepatic, intestinal, neurological and renal dysfunction in temporal association with the occurrence of TMA, and counted as the total number of organs involved. Clinical and laboratory data were obtained from patients’ records, and values at presentation were the measurements closest to the time of diagnosis of TMA. Diabetes (fasting plasma glucose ≥7.0 mmol/l and/or the use of hypoglycaemic agents or insulin), hypertension (blood pressure ≥140/90 mmHg and/or the use of antihypertensive agents), and hypercholesterolaemia [total cholesterol>5 mmol/l, low-density lipoprotein (LDL)-cholesterol>3 mmol/l and/or the use of cholesterol-lowering drugs] were recorded [20]. Our standard TMA treatment has been intermittent PE with fresh frozen plasma (4 l per treatment) using the COBE Spectra continuous flow centrifugal apheresis system (Gambro BCT, Martinsried, Germany), initiated within 12 h after the diagnosis of TMA, and then PE for three consecutive days and thereafter in cycles of five treatments within 8 days until remission, defined as a platelet count above 150 x 109/l for 2 days [1]. Our policy has been not to conduct PE in TMA patients with extended malignancy under palliative treatment and in other TMA subtypes unlikely to respond to PE. Venous access was obtained by placing double-lumen central venous catheters in the jugular veins. As adjunctive therapy, all TMA patients received 2–4 mg/kg methylprednisolone prior to PE (median dose methylprednisolone of 250 mg). We do not transfuse platelets unless there is a life-threatening haemorrhage. The LDH ratio, a marker of response to PE in TMA, was calculated as serum LDH prior to the third PE divided by the serum LDH prior to the first PE [21]. Antiplatelet agents were not administered. In all patients, laboratory testing at presentation included serum troponin I, creatine kinase, and creatine kinase-MB in the case of elevated creatine kinase (>174 U/l). Thereafter, these markers as well as ECGs were only serially measured or performed in patients displaying clinical manifestations attributable to AMI. AMI was diagnosed when (i) serum troponin I increased above 1 ng/ml with at least one further criterion, (ii) symptoms of myocardial ischaemia as acute chest or epigastric pain for more than 20 min, or acute dyspnea, (iii) ST-segment elevation or depression, or (iv) T-wave inversion [18,22] was observed. Data are presented as mean±SD. Continuous data were compared by Student's t- or rank-sum test, and categorical data by the chi square or Fisher's exact test. The following cut-off values at admission were used for further analysis: 30 x 109/l for platelets, 5% for fragmented red cells, 1000 U/l for LDH and 0.20 ng/ml for serum troponin I. A cut-off value of 0.6 was applied for the LDH ratio [21]. Potential risk factors for AMI during TTP were coded as present or absent. Variables with P ≤ 0.20 by univariate analysis were included in the multivariate, stepwise logistic regression analysis. After logarithmic transformation, serum creatinine and troponin I values at presentation of TMA were correlated by the Spearman test. All tests were two-tailed and P<0.05 was considered significant. Sensitivity and specificity were calculated according to the cut-off values described above. The local institutional review board approved the protocol prior to data collection. Patient consent was not required and the study is in accordance with the Helsinki Declaration of 1975 as revised in 1996.



   Results
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 Abstract
 Introduction
 Subjects and methods
 Results
Discussion
 References
 
Seventy-four TMA patients were identified and classified as follows: clinically suspected TTP (n = 32), classical HUS (n = 7), and non-classical HUS/other TMA types (n = 35). A total of 78 TMA episodes were studied (35 TTP, seven classical HUS and 36 non-classical HUS/other TMA-episodes), as TMA reoccurred in four patients of which three had TTP. Patients studied were 43±14 years old (range 22–70 years) and predominately female (55%). AMI occurred in 14 TMA episodes (18%), 5±3 days after presentation with TMA (range 2–11 days). All AMI developed during the initial TMA episodes. Eight AMI patients (57%) presented with symptoms typical of myocardial ischaemia. In two sedated and mechanically ventilated patients and in four patients with non-typical symptoms, AMI was detected by elevated troponine I and ECG changes. No patient presenting with typical symptoms of myocardial ischaemia who was found not to have AMI. There were nine non- and five ST-segment elevation AMI, and the maximum troponin I was 6.8±4.6 ng/ml. Maximum serum creatine kinase levels of 379±152 U/l were reached 24 h after the AMI, and creatine kinase normalized after 3 days. As shown in Table 1, no patients with and very few patients without AMI had a history or symptoms of coronary artery disease prior to the TMA episode. Patients who developed AMI did not differ in respect to risk factors of myocardial infarction from patients without AMI (Table 1). In TMA episodes with subsequent AMI, TTP was more frequently suspected as the underlying type of TMA (Table 1). TMA episodes with AMI also caused higher numbers of dysfunctional non-cardiac organs. During more TMA episodes with than without AMI, platelets were transfused prior to the diagnosis of TMA. During one episode of TMA each with and without AMI, platelets were transfused after diagnosis. At presentation, significantly higher numbers of fragmented red cells, serum LDH and troponin I levels as well as lower platelet values were present in TMA episodes with subsequent AMI compared with TMA episodes without AMI (Table 2). PE was performed in 69 TMA episodes (88%), more often in TMA episodes with than without AMI (Table 1). Furthermore, the LDH ratio was higher in TMA episodes with AMI. The separate analysis of TTP episodes with and without AMI confirmed the findings in the entire cohort (Table 3). TTP episodes with AMI were also associated with a significantly higher LDH, troponin I and LDH ratio than TTP episodes without AMI. Multivariate analysis identified clinically suspected TTP, and serum LDH above 1000 U/l and serum troponin I above 0.20 ng/ml at presentation as independent factors associated with AMI (Table 4). Values at presentation for serum LDH above 1000 U/l together with serum troponin I above 0.20 ng/ml had a sensitivity of 86% (95% CI 60–96%) and a specificity of 95% (95% CI 86–98%) to predict AMI in the later course of TMA. Correlation of serum creatinine and serum troponin I values at presentation of TMA was weak, with the correlation coefficient R = –0.04 (P = 0.75).


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  		Table 1. Clinical characteristics of TMA episodes with and without AMI

 

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  		Table 2. Laboratory values of TMA episodes with and without AMI

 

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  		Table 3. Clinical characteristics and laboratory values of TMA episodes with and without AMI caused by suspected TTP

 

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  		Table 4. Multivariate analysis of factors associated with AMI in the course of TMA

 
Coronary angiography was performed only in three patients immediately after AMI. It demonstrated complete occlusion of the left anterior descending coronary artery in one patient and mild atherosclerotic alterations without occlusions or significant stenosis of the coronary vessels in the other two. Neither percutaneous coronary interventions nor thrombolysis was performed in any of the TMA patients with AMI. In five of the six TMA patients with AMI who died in hospital during admission for TMA, death may have been caused by AMI (cardiac shock, n = 3; ventricular fibrillation, n = 2). Autopsy in four patients revealed myocardial necrosis (n = 4), cardiac microvascular thrombosis (n = 4) and myocardial haemorrhage (n = 2). The remaining patient died of respiratory failure due to diffuse pulmonary haemorrhage. Three of the eight survivors showed a left ventricular ejection fraction below 40% in transthoracic echocardiography in the first 12 months after TMA remission. No patient developed chronic TMA. Eleven patients with clinically suspected classical HUS, or non-classical HUS/other TMA types developed chronic kidney disease, and five required chronic dialysis.



   Discussion
Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
References
 
Our findings indicate that AMI is an early, frequent and severe complication during TMA. Patients with clinically suspected TTP, substantial serum LDH and marginal troponin I elevations at presentation of TMA are at a high risk to develop AMI. Although the high incidence and severity of AMI during TMA was previously suggested, these reports were predominantly derived from autopsies and smaller case series but not from larger studies of consecutive patients with TMA [11–17]. In sharp contrast, data on AMI are scarce in the larger studies on TMA over the last 15 years [1–10]. Apparently, clinicians unlike pathologists may have underestimated ischaemic myocardial injury caused by TMA, leading to infrequent use of diagnostic tests to detect AMI [11–15]. In recent years, the measurement of troponins has become a standard clinical practice and troponins permit a more sensitive and specific diagnosis of AMI [18,22]. Thus, the current AMI definition based on troponin I allowed us to diagnose AMI in TMA more often and accurately in these patients and to detect its full clinical impact which had not been done before. The most important implication of our study is that moderately elevated serum troponin I in combination with substantially increased serum LDH at diagnosis may accurately predict the development of AMI.

Our data suggest that TMA episodes with consecutive AMI were characterized by more severe disease and higher disease activity. Thus, TMA possibly also impaired myocardial perfusion. Indices of TMA severity and activity such as fragmented red cells, LDH, platelet count and number of impaired organs associated with TMA were more extensively altered in episodes with AMI. In addition, during many TMA episodes, the AMI platelets were transfused prior to the diagnosis of TMA and this may have further aggravated TMA activity [23]. However, it may also be argued that a higher requirement of platelet transfusion could merely be a surrogate of more pronounced thrombocytopenia and, thus, TMA severity. Finally, elevated LDH ratio in TMA patients with AMI suggested a limited response to PE as the standard treatment in these patients [21]. Further note, TTP was identified as an independent factor associated with AMI in TMA. Interestingly, a recent paper reported a low incidence of acute myocardial injury in classical HUS, which indirectly supports our finding stated earlier [24]. Enhanced platelet activation seems characteristic of TTP, and microthrombi in TTP are characterized by large amounts of von Willebrand factor which was reported as distinctly different from fibrin-rich microthrombi in HUS [13,15]. Although speculative, massive platelet aggregation due to high TTP activity could be the key factor in the development of AMI in TMA, and this was supported by previous and our autopsy findings [11,12,14,15]. In contrast, we could not explain AMI in TMA patients by an increased rate of risk factors for myocardial infarction or pre-existing coronary artery disease.

Another potential implication of our findings is that performing daily cardiac monitoring with troponins and ECG in TMA patients, especially those with clinically suspected TTP, who present with LDH above 1000 U/l and troponin I above 0.20 ng/ml could be beneficial. Presumably, not all TTP require intensified cardiac monitoring, and the LDH and troponin I cut-off values mentioned earlier seem also well suited to distinguish between TTP with and without subsequent AMI. A further implication is that the use of antiplatelet agents in TMA patients at risk for AMI early in the course of TMA may be profitable. Our standard treatment of TMA did not include antiplatelet agents as we feared serious bleeding complications without proven therapeutic benefit, although this is not undisputed [1,25,26]. Likewise, thrombolysis or percutaneous coronary interventions with stenting were not applied due to the potentially high rate of serious adverse events and the undesirable but necessary medium-term treatment with antiplatelet agents after stenting. Waiving these effective therapies of AMI is presumably one reason for the high morbidity and mortality rate, as we observed. The recently introduced glycoprotein IIb/IIIa antagonists eptifibatide and tirofiban may offer advantages over other antiplatelet agents in AMI during TMA. Both inhibit platelet aggregation more effectively with shorter half-lives than other antiplatelet agents [27]. Thus, in the case of bleeding, their administration would be discontinued and platelet function restored within a few hours. However, prospective, randomized studies will be necessary to establish the benefit of these antiplatelet agents in TMA. Although speculative, we would propose an early invasive strategy with coronary angiography and subsequent angioplasty and stenting for those patients at high risk of developing an AMI with a continuing increase of troponin and signs of regional myocardial wall-motion abnormalities, as visible by echocardiography. This subgroup of patients with a higher likelihood of macrovascular coronary artery disease as the cause of AMI may profit more from coronary angiography and subsequent angioplasty and stenting than those TMA patients with diffuse microvascular coronary artery disease. The early invasive strategy may further be limited to those with minor bleeding which permits the peri- and postinterventional use of heparin and antiplatelet agents. Furthermore, the potential harm from long-term, intensified antiplatelet treatment after angioplasty and stenting in the course of TMA has to be individually balanced with advantages of percutaneous coronary intervention. Thus, these proposals are only partially consistent with current guidelines for AMI [18,22].

This study is limited by its observational and retrospective design and may have been affected by a selection bias. As our department is a tertiary referral centre, we studied patients with particularly severe disease and subsequent negative outcomes, as demonstrated by our higher mortality rate compared with others [1,2,4–7,9,10]. Nonetheless, severe TMA is likely to have a high impact on morbidity and mortality, and these patients in particular may profit from early detection of AMI and therapeutic interventions. Yet, our findings may not apply to all TMA patients. Our TMA classification, especially the criteria for TTP may be challenged. However, there are currently no consensus definitions for TMA and its subtypes available. Recent data suggest that the TTP definition will be based upon the deficiency of ADAMTS13 or the presence of ADAMTS13 inhibitors [19]. Complete data on ADAMTS13 were not available to be included in our study, but a recent study suggested that clinical features like those applied by us may be sensitive to identify TTP [28]. Since we measured total LDH and not isoenzymes, attributable to, for example, erythrocytes or myocardium, we cannot differentiate between these tissues as LDH sources. Due to moderate elevations of troponin I in chronic kidney disease patients without myocardial injury, this marker has been questioned in this setting [29]. However, further studies did not observe non-specific, false-positive serum troponin I in renal insufficiency in the absence of AMI [30–32]. Additionally, in our study impaired glomerular filtration rates did not affect troponin I levels. Thus, it appears that troponin I is an accurate marker to predict or detect AMI in TMA patients who may have some degree of renal insufficiency. Finally, as in any single-centre study, our findings require validation by a large multicentre study.

In conclusion, our data suggest that AMI is an early, frequent and severe complication during TMA. AMI occurs especially in clinically suspected TTP, and serum LDH above 1000 U/l in combination with serum troponin I above 0.20 ng/ml at presentation of TMA may predict subsequent AMI.

Conflict of interest statement. None declared.

(See related article by Basic-Jukic et al. NDT Advance Access publication January 18, 2006. doi:10.1093/ndt/gfk091.)



   References
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 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 

  1. Rock GA, Shumak KH, Buskard NA et al. Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura. N Engl J Med 1991; 325: 393–397[Abstract]
  2. Bell WR, Braine HG, Ness PM et al. Improved outcome in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Clinical experience in 108 patients. N Engl J Med 1991; 325: 398–403[Abstract]
  3. Pene F, Vigneau C, Auburtin M et al. Outcome of severe adult thrombotic microangiopathies in the intensive care unit. Intensive Care Med 2005; 31: 71–78[CrossRef][Medline]
  4. Zheng XL, Kaufman RM, Goodnough LT et al. Effect of plasma exchange on plasma ADAMTS13 metalloprotease activity, inhibitor level, and clinical outcome in patients with idiopathic and nonideopathic thrombotic thrombocytopenic purpura. Blood 2004; 103: 4043–4049[Abstract/Free Full Text]
  5. Hollenbeck M, Kuthuhn B, Aul C et al. Haemolytic-uraemic syndrome and thrombotic-thrombocytopenic purpura in adults: linical findings and prognostic factors for death and end-stage renal disease. Nephrol Dial Transplant 1998; 13: 76–81[Abstract/Free Full Text]
  6. Dervenoulas J, Tsirigotis P, Bollas G et al. Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS): treatment outcome, relapses prognostic factors. Ann Hematol 2000; 79: 66–72[CrossRef][Web of Science][Medline]
  7. Lara PN, Coe TL, Zhou H et al. Improved survival with plasma exchange in patients with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Am J Med 1999; 107: 573–579[CrossRef][Web of Science][Medline]
  8. Coppo P, Bussel A, Charrier S et al. High-dose plasma infusion versus plasma exchange as early treatment of thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome. Medicine 2003; 82: 27–38[CrossRef][Medline]
  9. George JN, Gilcher RO, Smith JW et al. Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: diagnosis and management. J Clin Apheresis 1998; 13: 120–125[CrossRef][Web of Science][Medline]
  10. Bandarenko N, Brecher ME. United States Thrombotic Thrombocytopenic Purpura Apheresis Study Group (US TTP ASG): multicenter survey and retrospective analysis of current efficacy of therapeutic plasma exchange. J Clin Apheresis 1998; 13: 133–141[CrossRef][Web of Science][Medline]
  11. Ridolfi RL, Hutchins GM, Bell WR. The heart and cardiac conduction system in thrombotic thrombocytopenic purpura. Ann Intern Med 1979; 91: 357–363[Abstract/Free Full Text]
  12. Bell MD, Barnhart JS, Martin JM. Thrombotic thrombocytopenic purpura causing sudden, unexpected death – a series of eight patients. J Forensic Sci 1990; 35: 601–613[Web of Science][Medline]
  13. James TN, Alperin JB. Apoptotic myocardial degeneration in thrombotic thrombocytopenic purpura. Apoptosis 1997; 2: 384–394[CrossRef][Medline]
  14. Podolsky SH, Zembowicz A, Schoen FJ et al. Massive myocardial necrosis in thrombotic thrombopenic purpura. Arch Pathol Lab Med 1999; 123: 937–940[Medline]
  15. Hosler GA, Cusumano AM, Hutchins GM. Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome are distinct pathological entities. Arch Pathol Lab Med 2003; 127: 834–839[Web of Science][Medline]
  16. McCarthy LJ, Danielson CF, Skipworth EM et al. Myocardial infarction/injury is relatively common at presentation of acute thrombotic thrombocytopenic purpura: the Indiana University experience. Ther Apher 2002; 6: 2–4[CrossRef][Medline]
  17. Brandenburg VM, Gaertner S, Lindemann-Docter K et al. Underestimated complications in thrombotic thrombocytopenic purpura – haemolytic uraemic syndrome. Nephrol Dial Transplant 2004; 19: 2142–2146[Free Full Text]
  18. Van de Werf F, Ardissino D, Betriu A et al. The Task Force on the Management of Acute Coronary Syndromes of the European Society of Cardiology. Management of acute coronary syndromes in patients presenting with ST-segment elevation. Eur Heart J 2003; 24: 28–66[Free Full Text]
  19. Tsia HM. Advances in the pathogenesis, diagnosis, and treatment of thrombotic thrombocytopenic purpura. J Am Soc Nephrol 2003; 14: 1072–1081[Abstract/Free Full Text]
  20. De Backer G, Ambrosioni E, Broch-Johnsen K et al. European guidelines on cardiovascular disease prevention in clinical practice. Eur J Cardiovasc Prev Rehabil 2003; 10 [Suppl 1]: S1–S78
  21. Haas M, Leko-Mohr Z, Lang T et al. The LDH ratio as a marker for response to plasma exchange in HUS/TTP of the adult. Clin Nephrol 2002; 57: 414–420[Medline]
  22. Bertrand ME, Simoons ML, Fox KA et al. The Task Force on the Management of Acute Coronary Syndromes of the European Society of Cardiology. Management of acute coronary syndromes in patients presenting without ST-segment elevation. Eur Heart J 2002; 23: 1809–1840[Free Full Text]
  23. McCarthy LJ, Danielson CF, Miraglia C et al. Platelet transfusion and thrombotic thrombocytopenic purpura. Transfusion 2003; 43: 829[Medline]
  24. Thayu M, Chandler WL, Jelcic S, Gordon CA, Rosenthal GL, Tarr PI. Cardiac ischemia during hemolytic uremic syndrome. Pediatr Nephrol 2003; 18: 286–289[Web of Science][Medline]
  25. Rosove MH, Ho WG, Goldfinger D. Ineffectiveness of aspirin and dipyridamole in the treatment of thrombotic thrombocytopenic purpura. Ann Intern Med 1982; 96: 27–33[Abstract/Free Full Text]
  26. Bobbio-Pallavicini E, Gugliotta L, Centurioni R et al. Antiplatelet agents in thrombotic thrombocytopenic purpura. Results of a randomized multicenter trial by the Italian cooperative group for TTP. Haematologica 1997; 82: 429–435[Abstract/Free Full Text]
  27. Schror K, Weber AA. Comparative pharmacology of GP IIb/IIIa antagonists. J Thromb Thrombolysis 2003; 15: 71–80[CrossRef][Web of Science][Medline]
  28. Veyradier A, Obert B, Houllier A, Meyer D, Girma JP. Specific von Willebrand factor-cleaving protease in thrombotic microangiopathies: a study of 111 cases. Blood 2001; 98: 1765–1772[Abstract/Free Full Text]
  29. Mockel M, Schindler R, Knorr L et al. Prognostic value of cardiac troponin T and I elevations in renal disease patients without acute coronary syndromes: a 9-month outcome analysis. Nephrol Dial Transplant 1999; 14: 1489–1495[Abstract/Free Full Text]
  30. McCullough PA, Nowak RM, Foreback C et al. Performance of multiple cardiac biomarkers measured in the emergency department in patients with chronic kidney disease and chest pain. Acad Emerg Med 2002; 9: 1389–1396[CrossRef][Web of Science][Medline]
  31. Nakai K, Nakai K, Nagane Y et al. Serum levels of cardiac troponin I and other marker proteins in patients with chronic renal failure. Clin Exp Nephrol 2004; 8: 43–47[Medline]
  32. Needham DM, Shufelt KA, Tomlinson G, Scholey JW, Newton GE. Troponin I and T levels in renal failure patients without acute coronary syndrome: a systematic review of the literature. Can J Cardiol 2004; 20: 1212–1218[Web of Science][Medline]
Received for publication: 22. 2.06
Accepted in revised form: 28. 2.06


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