- Normal variation – statistically, 2.5% of the population will have levels above the ULN.
- Analytical variation – combined analytical & biochemical variation is approx 8%. Levels increase by approx 6% if sample stored for 96 hrs at room temp before analysis.
- Familial (intestinal ALP)
- Adolescent growth spurt
- Drugs (see below)
- Postprandial rise after fatty meals (occurs in people with Types B & O)
In one study, 95% of raised alkaline phosphatases proved to be of no significance.
Common drugs causing ALP rises
May act via enzyme induction or hepatic cholestasis.
- Antibiotics: penicillins, erythromycin, aminoglycosides
- Antiepileptics: carbamazepine, phenobarbital, phenytoin
- Antihypertensives: captopril, diltiazem, felodipine
- DMARDs: penicillamine, sulfas
- Psychotropics: MAOIs, chlorpromazine
Pathological causes other than liver or bone
- Acute phase reactant in extrahepatic infection
- Intestinal disease
History: Abdominal pain/swelling, bone pain, appetite/weight loss, clinical features of hepatic failure/ESRF/CCF.
Bloods: Repeat within 4 weeks, together with calcium profile, gamma-GT, U&Es, FBC, & TSH.
Any other abnormalities – follow up as appropriate.
Raised ALP + GGT – ALP assumed to be of hepatic origin. If ALP <1.5 x ULN repeat in 3/12. If >1.5 x ULN, or persistently raised, then proceed to:
- Liver USS (for cholestasis or infiltrative lesion)
- Antimitochondrial antibodies (primary biliary cirrhosis)
If tests negative and ALP persistently > 1.5 x ULN, refer to hepatologist. If tests negative and ALP < 1.5 x ULN, evaluate for symptoms in 6/12 – liver biopsy tends not to be very helpful, further Ix not cost-effective.
Raised ALP with normal GGT/other tests – ALP non-hepatic, probably bony origin. Causes include:
- Vitamin D deficiency
- Paget’s disease of bone
- Adolescent growth spurts
- Healing fractures
- Bone tumours (these and fractures should be clinically evident)
If asymptomatic, check Vitamin D levels and treat any deficiency. If Vitamin D normal and ALP <1.5 x ULN, investigate only if symptoms develop. If ALP >1.5 x ULN, possibly worth doing bone scintigraphy to identify early asymptomatic Paget’s disease (opinion divided on whether worthwhile to treat this prior to symptoms developing).