Monday, November 27, 2006

Blood clots, eh?

ABO groups and thrombosis

or Blood clots, eh? Big grin

The title is a Canuck's mnemonic to recall that thrombosis occurs more in group A than group O individuals.

When teaching, one of the tactics that I regularly used to increase student interest was to include sex or anything unusual into the discussion. One of the topics in the latter category was whether blood groups served biological functions.

The most famous association is between the Duffy blood group system and malaria, in which the FyFy genotype confers resistance to Plasmodium vivax.

ABO was a favorite system for investigating blood group and disease associations probably because it was the first system discovered and because ABH carbohydrates are expressed on many human tissues, including red cells, platelets, vascular endothelium, and epithelium. Speculation was fueled by studies such as those which showed that group A persons were more susceptible to gastric cancer than group O persons, whereas group O individuals were more susceptible to duodenal ulcers than group A persons.

Some associations made sense, e.g., the worldwide distribution of ABO blood groups being influenced by pandemics. For example, the low frequency of A and high frequency of O blood group genes in various parts of the world could have resulted from a selective disadvantage of groups A during severe smallpox epidemics since the smallpox virus has A-like antigens. Group O individuals would have better survival rates since they have pre-existing anti-A that would destroy the virus. These and similar studies suggested that epidemics such as smallpox, plague, and cholera may have been responsible for the major differences in ABO blood group frequency observed around the globe.

But other associations were clearly without meaning, such as one showing higher intelligence in group A2 individuals. Students loved these kooky associations, which also made it possible to discuss statistical associations in general and what they actually meant.

A recent paper made me recall these earlier fun discussions:

A statistical association between ABO blood groups and risk of thrombosis has been recognized for many years. Specifically, group A, B, and AB people have demonstrated an increased incidence of thrombotic disease compared to group O individuals, presumably because ABO influences plasma levels of von Willebrand factor (vWF). vWF levels are 25% higher in non-O compared to group O individuals, but the mechanism by which ABO group determines plasma vWF levels has not been determined.

The review in Transfusion focuses on the carbohydrate structures of vWF and recent studies suggesting that differences in ABH antigen expression - which are expressed on the N-linked glycan chains of circulating plasma vWF - may have clinically significant effects on vWF proteolysis and clearance.

For more, see blood groups and disease associations (PubMed search)

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