From the Guidelines
Elevated alkaline phosphatase (ALP) in the context of platelet destruction, also known as thrombocytopenia, is most likely caused by liver disease, particularly cholestatic liver disease, as indicated by the recent study 1. The study published in the Journal of the American College of Radiology in 2023 1 highlights that ALP is produced mainly in the liver and is present in the canalicular membrane of the hepatocyte. Key points to consider in this context include:
- ALP elevation is nonspecific and can occur in various conditions affecting the liver, such as cirrhosis, chronic hepatitis, and viral hepatitis 1.
- Pathologically increased levels of ALP may occur in cholestatic liver disease, such as primary biliary cholangitis, primary sclerosing cholangitis, intrahepatic or extrahepatic bile duct obstruction, and drug-induced cholestasis 1.
- Measurements of gamma-glutamyl transpeptidase (GGT) can help determine whether elevated ALP is of hepatic or nonhepatic origin, as GGT is found in the liver but not in bone 1. Given the complexity of diagnosing the cause of elevated ALP in thrombocytopenia, a comprehensive approach including liver function tests, bone markers, and possibly bone marrow examination is necessary to identify the underlying cause. Treatment should be tailored to the specific diagnosis, and monitoring both ALP and platelet counts regularly is crucial to track treatment response 1.
From the Research
Causes of Elevated Alkaline Phosphatase (ALP)
- Elevated ALP levels can be caused by various factors, including sepsis, malignant obstruction, and AIDS, as well as bone involvement from malignancy or Paget's disease 2.
- Liver disease, such as alcohol-induced hepatitis, can also lead to elevated ALP levels, even in patients with hypophosphatasia, a rare inherited disorder characterized by low serum ALP 3.
- In patients with liver diseases, the main source of elevated serum ALP activity is the liver isoenzyme, and an abnormally large proportion of this isoenzyme can be found in the serum alkaline phosphatase isoenzymogram 4.
- Elevated ALP levels have been associated with higher mortality in patients on peritoneal dialysis, with the highest ALP quartile being significantly associated with a hazard ratio for all-cause mortality and cardiovascular mortality 5.
- Marked elevations of serum ALP have been observed in patients with AIDS, with 17% of consecutive patients with AIDS having elevations in excess of 1,000 IU/L, although the causes of these elevations are not always clear 6.
Relationship to Thrombocytopenia
- There is no direct evidence in the provided studies to suggest a link between elevated ALP and thrombocytopenia (platelet destruction).
- However, some of the underlying conditions that cause elevated ALP, such as sepsis or liver disease, may also be associated with thrombocytopenia, although this is not explicitly stated in the provided studies.