Creatine Kinase (CK) Isoenzymes, Serum
      
CPT
  82550; 82552
Synonyms
  CK Fractionation; CK Isoenzymes; CPK Isoenzymes; Creatine Phosphokinase Isoenzymes
Test Includes
  Total CK and relative percentage of BB (CK-1), MB (CK-2), and MM (CK-3)
Special Instructions
  State sex of patient on the test request form.
Specimen
  Serum
Volume
  1 mL
Minimum Volume
  0.2 mL
Container
  Red-stopper tube or serum gel separator tube
Storage Instructions
  Refrigerate up to 48 hours. Freeze (-20 degrees C) up to 2 weeks.
Patient Preparation
  CK is most commonly elevated in acute myocardial infarction (AMI) in which it has its greatest usefulness. Collection of specimen at onset of symptoms to establish baseline values is needed. A patient at onset of AMI will have normal results, but some patients reach medical attention at or beyond CK peak. To support the diagnosis of AMI, three CK isoenzyme determinations have classically been recommended, one on admission, a second 12 hours after admission, a third 24 hours after admission. Another at 48 hours may be needed. CK-MB usually peaks between 15 and 20 hours after the onset of a myocardial infarction. Pappas summarizes current literature regarding timing as follows. In non-Q wave, incomplete occlusion, nontransmural MI, CK- MB peaks on the average 15 hours from onset. In Q wave (complete occlusion) (transmural) infarction, CK-MB average peak is 17 to 20 hours after onset of symptoms. He emphasizes the importance of a sample for CK-MB drawn 16 hours after onset.1 When increased CK-MB values have returned to normal, CK isoenzyme determinations are usually no longer required.
Causes for Rejection
  Moderate or excessive hemolysis
Reference Interval
  Total CK: male: 24-204 U/L, female: 24-173 U/L; CK-MM: 97% to 100%; CK-MB: 0% to 3%; CK-BB: 0%
Use
  Diagnose myocardial infarction (MI). Three fractions normally may be found, each an isoenzyme:
  • MM is found in normal serum.
  • MB is the myocardial fraction associated with MI and occurs in certain other states. MB can be used in estimation of infarct size.

MB increases have been reported with entities which cause damage to the myocardium, such as myocarditis, some instances of cardiomyopathy, and with extensive rhabdomyolysis, Duchenne muscular dystrophy, malignant hyperthermia, polymyositis, dermatomyositis, mixed connective tissue disease, myoglobinemia, Rocky Mountain spotted fever, Reye syndrome and rarely in rheumatoid arthritis with high titer RF.2 CK-MB does not generally abruptly rise and fall in such nonacute MI settings, as it does in acute myocardial infarct (AMI).

BB is rarely present. BB has been described as a marker for adenocarcinoma of the prostate, breast, ovary, colon, adenocarcinomas of gastrointestinal tract, and for small cell anaplastic carcinoma of lung. BB has been reported with severe shock and/or hypothermia, infarction of bowel,3 brain injury, stroke, as a genetic marker in some families with malignant pyrexia, and with MB in alcoholic myopathy.

Limitations
  Exercise, intramuscular injections, myxedema, grand mal seizures, prior trauma or surgery and acute MI very early or late lead to the combination of increased total CK but usually normal CK-MB. Increased CK-MB has been described in marathon runners without MI.4 CK isoenzyme analysis is not usually practical when the total CK is very low, although in elderly people with low muscle mass, the use of sensitive mass concentration assays may be useful. A single CK isoenzyme examination may be misleading. One should look for a pattern in serial CK isoenzyme analyses and seek confirmation with the isoenzymes of LD (LDH), ideally beginning with onset to establish the baseline. LD isoenzyme 1:2 flip is most consistently found about two days after onset of acute infarction of myocardium. The diagnosis of myocardial injury should not be based solely on MB isoenzyme, but rather should be supported by clinical findings, ECG, and often other laboratory parameters (ie, confirmation by LD isoenzymes).1
Methodology
  Total-Kinetic; Isoenzymes-Agarose gel electrophoresis with densitometry
Additional Information
  CK-MB is found in much higher concentrations in cardiac muscle than in ordinary skeletal muscle.

CK-MB is usually not elevated in exercise (total CK elevated); myxedema (total CK elevated in about half of cases); injections into muscle (total CK elevated); strokes, CVA, and other brain disorders in which total CK may be increased; pericarditis; pneumonias or other lung diseases; pulmonary embolus; seizures (CK may be very high but no great MB increase, if any). Although CK-MB is not usually increased in angina, some CK-MB elevations are recognized in angina patients, depending partly on laboratory methodology.

Atypical forms of CK occur. Macro-CK migrates between MM and MB and is composed of immunoglobulin complexes of normal isoenzymes. This is found mainly in elderly women and is of no clinical significance. Mitochondrial-CK migrates cathodal to MM and is found in seriously ill patients, especially those with metastatic carcinoma. Its presence is a poor prognostic sign.