Red blood cell distribution width (RDW) is a routine laboratory parameter that shows variation in red blood cell size on a standard hemogram and is often used in assessing blood diseases. Higher RDW has been associated with worse outcome in the elderly, in patients with heart failure or ischemic heart disease and in those undergoing percutaneous coronary revascularization, irrespective of baseline hematocrit.1–9 An association with a higher adverse event rate in patients with acute coronary syndrome (ACS) has also been reported in the literature.3,10

The aim of this study was to assess the relationship between RDW values and risk for bleeding events in patients with non-ST elevation ACS (NSTE-ACS).

Mean RDW was 15.1%±1.6% (median 14.9%). Of the 76.6% of patients presenting with NSTEMI, 83% underwent coronary angiography, all via femoral access. Patients with higher RDW values were older and were more often previously medicated with aspirin and beta-blockers, and more had a history of coronary revascularization. Those in the third tertile more frequently had ST-segment depression, higher HR and lower Hb at admission. There were no significant differences between the three groups in antithrombotic therapy begun during hospitalization, or in the number of patients undergoing angioplasty. Those in the third tertile had higher Crusade bleeding scores. The other variables assessed are compared in Table 1.

The rate of major bleeding was 7% (36 events). Of these patients, 32 (89%) had undergone coronary angiography. In 44% of cases (n=16), the bleeding was associated with the arterial puncture site (14 groin hematomas and two cases of retroperitoneal bleeding). The site of bleeding was not identified in 33% of patients (n=12). There was also one case of alveolar hemorrhage, one of subarachnoid hemorrhage, two cases of genitourinary bleeding, three of gastrointestinal bleeding and one associated with recent orthopedic surgery. On univariate analysis (Table 2), bleeding was associated with older age, higher SBP and renal dysfunction. These patients were more often medicated with glycoprotein (Gp) IIb/IIIa inhibitors and more had undergone coronary angioplasty.

Higher RDW values were associated with a higher Crusade score and a higher percentage of in-hospital bleeding, death and combined in-hospital death and major bleeding (Figure 1). The c-statistic for the Crusade bleeding score in our population was 0.597.

Figure 1.

Adverse event rate according to tertile of red blood cell distribution width.

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Independent predictors of bleeding events were use of Gp IIb/IIIa inhibitors, more than one pain episode, SBP >142mmHg, creatinine clearance <43ml/min, and RDW >15.7% (Table 3).

The association between RDW and increased ischemic events in patients with cardiovascular disease is well known, but there have been few studies on its relation to bleeding events. In our study population, RDW was an independent predictor of major bleeding in patients with NSTEMI.

As reported in other studies, patients in the highest tertile of RDW presented characteristics associated with more severe coronary artery disease, particularly older age and a greater frequency of previous myocardial revascularization.2,3 They more frequently presented higher HR, ST-segment depression, anemia and renal dysfunction at admission. However, this patient group was treated more conservatively, less often undergoing coronary angiography. As in other populations with acute coronary syndrome, high RDW values were associated with worse outcome and greater in-hospital mortality in our study.2,3,5–7,10

As in the literature, the Crusade score showed poor discriminatory ability to predict bleeding events in our population.12,13 It is thus important to identify new risk factors that will lead to better stratification of risk for major bleeding in patients with NSTE-ACS.

The presence of renal failure and use of Gp IIb/IIIa inhibitors were also independent predictors of bleeding, as noted in previous studies.11 However, no correlation was found in our population with other conventional risk factors, such as female gender or heart failure. Bleeding was associated with the arterial puncture site in a significant proportion of cases, which highlights the importance of using radial access to reduce adverse events.

Several studies have reported that increased ischemic risk is often associated with a higher bleeding event rate, which makes management of these patients more difficult. As with other factors associated with more severe cardiovascular disease and worse prognosis in patients with NSTE-ACS, RDW is also a predictor of bleeding. The fact that it is an easily available laboratory parameter in routine blood tests that does not entail additional costs may encourage its wider use in the future.

The mechanisms behind its association with worse outcome in patients with cardiovascular disease have yet to be fully clarified but are probably multifactorial. High RDW values may indicate accelerated red blood cell destruction, nutritional deficiency (folic acid or vitamin B12), a proinflammatory state, or renal dysfunction that impairs erythropoiesis and hence red blood cell maturation.1,2,5 Further studies will be required for a better understanding of the relation of RDW to increased adverse events in patients with cardiovascular disease.

In our population, higher RDW values were associated with greater in-hospital mortality and were an independent predictor of in-hospital major bleeding in patients with NSTE-ACS. The ready availability of this parameter at no additional cost may encourage its wider use in clinical practice in the future.

The authors have no conflicts of interest to declare.