The pertinent issue in this case is whether this serial hemolysis is "real" (in vivo hemolysis) or "artificially made" (in vitro hemolysis). It is difficult to determine the cause of hemolysis in this case, whether in vivo or in vitro, due to the fact that the laboratory results demonstrated an elevated total bilirubin, although direct bilirubin and haptoglobin levels were unfortunately not ordered. In cases of intravascular hemolysis, one would expect indirect bilirubin levels to be markedly elevated and haptoglobin levels to be decreased. The possibility of in vitro hemolysis secondary to hemodialysis (if you call it in vitro, it would suggest that the hemolysis took place in the lab and it is not real, but it IS real in this case) is likely to be the cause of hemolysis in this case given the clinical scenario, although other causes cannot be ruled out. The timing and the spontaneous resolution of the hemolysis after the dialysis episode are consistent with this speculation. Moreover, these blood samples were all drawn by phlebotomists, further reducing the possibility of inappropriate sample handling.
The differential diagnosis of hemolysis is quite extensive and includes both intravascular and extravascular hemolytic anemias (e.g. autoimmune, hemoglobinopathies, red cell membrane disorders, pathogens, toxins) including mechanical injury secondary to hemodialysis. Hemodialysis-related hemolysis is a rare complication that may be caused by contamination, extreme temperatures, high flow rates or shear injury due to occluded lines.
This issue emphasizes the necessity of proper sample handling and result reporting Samples that are extensively hemolyzed either should be rejected along with requesting a new specimen or analyze the sample and report the results for potassium concentration with a comment regarding the extent of hemolysis and possible inaccuracies.
Although the patient did not complain of symptoms associated with acute coronary syndrome including dyspnea, chest pain or tightness and left arm numbness, electrocardiogram studies revealed a non-ST segment elevation myocardial infarction (NSTEMI) which was confirmed by elevated serial cardiac troponin (cTnI) and total creatine phosphokinase (CPK) levels. The American College of Cardiology defines myocardial infarction as any amount of myocardial necrosis as indicated by an elevation of troponin in the setting of clinical ischemia. The majority of troponins (>95%) are cytoskeletal proteins bound to tropomyosin, while the remaining proteins are found unbound in the cytoplasm. In acute coronary syndrome, cardiac troponins are released into the serum in a biphasic manner. Within the first few hours of initial myocardial injury, there is a small release of cTnT and cTnI, likely originating from the unbound cytoplasmic pool, followed by a sustained release of the bound troponins due to myocardial necrosis. Increased cTNI and cTnT levels are usually detected within 4 hours of initial symptoms of myocardial ischemia, peak in 10-24 hours and usually returns to normal within 2 weeks. The sensitivity and specificity of cardiac troponins for the detection of myocardial injury is usually superior to LDH, CK/CK-MB and myoglobin biomarkers; although, under certain clinical situations these older biomarkers may be useful. The relative index (RI= CK-MB/CPK, normal <4%), when elevated may be useful in differentiating between myocardial injury and skeletal muscle disease. Guidelines suggest a clinical requirement for turn-around times for cardiac biomarkers of <60 minutes from the time of test order to report of results.
Among asymptomatic patients with renal insufficiency, levels of cardiac troponins (cTnT) may be elevated in the absence of clinical evidence of myocardial ischemia. According to recent studies, decreased creatinine clearance is unlikely the cause of elevated serum troponin levels due to the fact that free (37kD) and bound (77 kD) cTnT proteins are relatively large molecules. There is also recent evidence that elevated cTnT in asymptomatic patients with end-stage renal disease may be a prognostic indicator of and increased cardiovascular risk and mortality. Current cTnI assays used in our laboratory (Beckman Access) has a coefficient of variation (CV) < 10% at the 99th percentile of the reference population with an upper reference limit 0.04 mg/L.
Contributed by Richard Freij, MD