Today, a patient had a macrocytic anaemia, low platelets and an oddly low neutrophil count despite having clear signs and a chest xray suggestive of a lobar pneumonia. To my on-the-ball consultant, this was explained by chronic alcohol abuse.

Pretty much all doctors, nurses and even orthopaedic surgeons know that alcohol abuse can cause a macrocytosis of the red blood cells. But why? And what else does it do to the blood?  Are there any blood tests that highlight alcohol abuse?

I’m not quite sure what audience this review about alcohol and the blood is aimed at, but it’s very readable whilst explaining things from first principles. Alcohol basically has a bone marrow suppressing effect, potentially leading to:

1. a macrocytic anaemia

2. a suppressed white cell count, especially neutrophils

3. a much reduced platelet count.

Paradoxically, the patient is at increased risk of both bleeds (e.g. intracranial bleeds) and clots. The bleeding risk is because of a decrease in the effectiveness of the platelets, as well as reduced platelet numbers. The patient could also have alcoholic liver disease and its associated clotting factor production failure. The clotting risk is more complex. Fibrinolysis (i.e. getting rid of unwanted clots) is a balance between tissue plasminogen activator (tPA), which wants to make plasmin and so lead to fibrinolysis, and plasminogen activator inhibitor (PAI-1), which stops plasmin production. At moderate levels of alcohol consumption, tPA is stimulated. This may explain the protective effect of moderate alcohol intake against myocardial infarctions. At higher levels, PAI-1 is also stimulated, which would increase the risk of inappropriate clots not being mopped up.

There are multiple reasons for alcohol to affect the red blood cells, which can be split into:

1. Vacuoles messing with the membrane – these generally disappear after 3-7 days of abstinence. These are found in most alcohol abusers. Anything that messes with the red cell membrane can lead to macrocytosis. Cell membrane failure is in fact the mechanism behind macrocytosis in liver disease (cholesterol metabolism is impaired, leading to increased cholesterol and phospholipids deposition in the red cell membrane).

2. Sideroblastic anaemia – one third of alcoholics have some form of sideroblastic anaemia. This is because alcohol screws up an enzyme in the haem sysnthesis pathway, leading to iron (in the form of ferritin) wandering around with nothing better to do than form ferritin rings called sideroblasts in the cell. This prevents the cell from maturing further (and is usually a microcytic anaemia).

3. Co-existing B12/folate deficiency – alcoholics don’t eat proper food.

4. Don’t know – this is the most common explanation I found for the cause of macrocytosis in alcohol. It takes a good month or two from abstinence for the cells to recover to normal size, so it is likely to affect RBCs early in their development.

Are there ways of detecting alcohol abuse in the blood? Again, medical students, doctors and most orthopaedic surgeons would know something about gamma GT. I have heard many people give their own opinion on it being incredibly useful or totally worthless, so I decided to look into the relationship between gamma GT and alcohol.

Gamma GT is a membrane bound enzyme. It is raised in most liver diseases, especially ones that feature biliary obstruction. A WHO/ISBRA study found that 52% of chronic alcohol users had an elevation in the level of gamma GT. In other words, 48% did not. The test was more sensitive for alcohol abuse in men.

The real problem with this test is the lack of specificity. If you are  presented with a set of LFTs and asked to comment on the gamma GT, the trick is to look at the AST:ALT ratio. The greater the AST relative to the ALT, the more likely  it is to be an alcoholic issue (AST:ALT > 2 as a guide). The greater the ALT relative to the AST, the more we think about viral hepatitis, NASH and Wilson’s (which has an ALT:AST >4). Many chronic liver diseases have roughly equal levels of AST and ALT. An elevated gamma GT in a patient with nothing to suggest biliary obstruction, combined with an elevated AST:ALT and a FBC suggestive of alcohol abuse as discussed earlier would make me more confident of alcohol abuse than an elevated gamma GT in a patient with obstructive jaundice and an elevated ALT compared to AST.

I also learnt that it takes about 2-3 weeks for gamma GT to come back down following abstinence. To me, gamma GT when applied to alcohol abuse seems more like a tumour marker in how we should use it. Combined with a clinical history and having thought about other causes of it being raised, we can use it to monitor progression in a patient diagnosed with the condition. We need to avoid using it in isolation to make a diagnosis.

Socially, physically, mentally. There aren’t many more ways in which a drug can be damaging. It amazes me how alcohol abuse is tolerated as a way of life in this country. If I were in charge, tobacco would be illegal, alcohol abuse necessitating police or health action punishable with a fine and psilocybin/cannabis would be used under controlled conditions with carefully selected patients for the medical benefits. Just my thoughts.

Edit 16/5/2013: Professor Nutt has been doing plenty of interesting research on psilocybin as a potential antidepressant.