The centre back, 26, has been diagnosed with deep vein thrombosis, after he had previously sat out with a calf problem since the beginning of August.
MacDonald has played 16 times for the Championship side since his January switch from Barnsley, will now be on medication for the issue for the next four months.
In an interview with the media, MacDonald confirmed the diagnosis, and said: "It was a big shock to find I have a blood clot in my calf, which will keep me out for a while."
He continued: ""The gaffer [Nigel Adkins], coaching staff and medical team have been brilliant in finding out the problem and getting to the bottom of it, as it could have been a lot worse."
It is not the first time that MacDonald has suffered from this particular diagnosis, having already endured treatment for a blood clot on the lung at the age of 15. Thankfully in that instance, the player was able to make a full recovery.
MacDonald's next appearance may not be until Hull City host Birmingham City at the KC Stadium on 3rd March next year.
November 8, 2018