Alkaline Phosphatase (ALP)

Diagnostic Use

Although plasma alkaline phosphatase (ALP) test is normally classified under the ‘liver function” test panel, it actually measures the combined enzyme activities contributed by different circulating ALP isoenzymes. Liver and bone specific ALP are the 2 dominant contributors, with almost equal contribution in adult until around 50+ years. During puberty (male and female) and in post-menopausal state there is a relative bone ALP dominance. During pregnancy, placental ALP (another isoenzyme) accounts for total ALP rise from latter part of the 2nd trimester onwards.

ALP can be increased in cholestatic liver conditions including hepatitis, cirrhosis, tumours, liver abscess, some drugs or toxins. It is not common for ALP to be raised without GGT rise in cholestatic conditions (see GGT entry for more info).

ALP as a bone formation marker can be increased in bone conditions like rickets, osteomalacia, secondary hyperparathyroidism, healing fractures, Paget’s disease or bone metastases. P1NP (procollagen-1 N-terminal propeptide) is another bone formation marker which is more specific for bone.

Isolated, mild and persistently raised ALP can be found in 2 benign conditions:

Benign familial hyperphosphatasemia (BFH) : an asymptomatic benign familial variant. Family members may also have a raised ALP (believed to be of autosomal dominant inheritance) .
Macro-ALP: ALP binds to immunoglobulins, forming a high molecular weight complex which has reduced clearance
Transient hyperphosphatasaemia of infancy and early children is another benign condition which is most commonly found in children less than 5 years of age though can occur in adults. ALP can be up in the thousands range and it normally returns to baseline within about 4 months. The pathophysiology of this condition is not very clear but thought relate to increase ALP sialylation in both liver and bone isozyme.

Low ALP: can be found in oxalate or EDTA contamination of heparin/serum collects and post cardiopulmonary bypass surgery. It can also be encountered in conditions like Zn deficiency, Mg deficiency, malnutrition, severe anaemia, hypothyroidism or Wilson’s disease presented with acute hepatic failure. If persistent and otherwise unexplained, may consider the diagnosis of Hypophosphatasia – loss of function mutation of the ALPL gene causing low to absent production of tissue-nonspecific ALP enzyme. Its wide clinical spectrum can range from perinatal death, to symptomatic (mineralization defects) including bone related abnormalities, early dental loss and non-traumatic fractures, to totally asymptomatic. Consider discussion with endocrine service if this condition is suspected.

ALP isoenzyme electrophoresis test (available at LabPLUS) aids differentiation of origin of ALP rise in relation to pathological or benign conditions especially when other biomarkers (e.g. GGT or P1NP) are not considered helpful.ALP should be >200 U/L, see the LabPLUS test guide for more information.

Placental ALP test (available at LabPLUS) is a quantitative test making use of the unique heat stable nature of Placental or Placental-like ALP to distinguish it from other less heat stable iso-enzymes. See the LabPLUS test guide for more information.