Final Diagnosis -- Hemodialysis-related hemolysis


DIAGNOSIS:

Hemodialysis-related hemolysis

DISCUSSION:

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.

CARDIAC TROPONINS

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.

REFERENCES

  1. Behrens J. Assessing Anemia Secondary to Hemolysis in Hemodialysis Patietns. Nephrology Nursing Journal, 2001(28)2; 253-256
  2. Burns ER, Yoshikawa N. Hemolysis in serum samples drawn by emergency department personnel versus laboratory phlebotomists. Lab Med.2002; 33: 378 -380.
  3. Burtis, Carl A. PhD, Ashwood, Edward R. MD. Tietz Textbook of Clinical Chemistry, Sixth Edition. Saunders; 6th edition, November 20, 2007
  4. Carraro P, Servidio G, Plebani M. Hemolyzed specimens: a reason for rejection or a clinical challenge? Clin Chem. 2000; 46: 306-7.
  5. Mehmet Koseoglu, Aysel Hur, Aysenur Atay, Serap Cuhadar*. Effects of hemolysis interference on routine biochemistry parameters. Biochemia Medica 2011; 21(1):79-85.
  6. Trakarnvanich T et al. The efficacy of single-needle versus double-needle hemodialysis in chronic renal failure. J Med Assoc Thai 1006; 89:196-206
  7. Vermeer HJ et al. Automated Processing of Serum Indices Used for Interference Detection by the Laboratory Information System. Clinical Chemistry, 2005(15); 1:244-247

QUESTIONS

  1. Hemolysis may be caused by:
    1. May occur in vivo as a result of pathology or drug effect.
    2. May occur during the collection of blood.
    3. May occur during specimen transport.
    4. May occur during specimen processing.
    5. All of the above.

  2. Which of the following is/are true regarding specimen collection:
    1. The use of a small-bore needle, resulting in a large vacuum force applied to the blood, may cause shear stress on the red blood cells, causing them to rupture.
    2. The use of a large bore needle may result in a much faster and more forceful flow of blood through the needle, resulting in hemolysis.
    3. Reduced tourniquet time causes the interstitial fluid to leak into the tissue causing hemolysis.
    4. Both A and B.
    5. All of the above.

  3. Samples that are extensively hemolyzed should be dealt with in the following ways:
    1. Report the results
    2. Reject the specimen and request a new sample.
    3. Analyze the sample and report the results for potassium concentration with a comment regarding the. extent of hemolysis and possible inaccuracies.
    4. Either B or C.
    5. All of the above.

  4. Among asymptomatic patients with renal insufficiency, levels of cardiac troponins (cTnT) may be elevated in the absence of clinical evidence of myocardial ischemia. T/F

  5. The relative index (RI= CK-MB/CPK, normal <4%) is not be useful in differentiating between myocardial injury and skeletal muscle disease. T/F

ANSWERS

1. E
2. D
3. D
4. T
5. F

Contributed by Richard Freij, MD




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