Ever found yourself chugging iron supplements like your life depended on it, only to have your anemia shrug and proffer the equivalent of “Yeah, not today, mate.”? Worry not – you're not alone. In fact, you've just been formally invited to the unglamorous club of non-responders – an exclusive group of iron-deficiency anaemics who find their allotted doses of iron supplements less fruitful than a desert cactus.

Now, before you resign yourself to a lifetime of seeking solace in perpetual tiredness, you should know – this could very well be science’s equivalent of a twisted plotline. You may not lack iron at all – your condition could be a masquerading thalassemia, a hereditary blood disorder that's as notorious as it is elusive.

Iron absorption tests are usually the go-to sleuths in this detective story. Suppose your iron levels spike post-administration. In that case, it's a pretty solid sign that your body is on board with absorbing that much-needed red-cell fodder. But if the levels are throwing a fit worse than a spoiled kid on a candy-deprived afternoon, your physician may likely recommend a classier alternative - iron infusions via intravenous.

However, this is where things get mighty interesting – cue in Thalassemia. This condition embodies a downright rebellion against hemoglobin, the protein responsible for turning your red blood cells into efficient oxygen-carriers. When your body morphs into a less-than-adequate hemoglobin factory, you're bestowed with a brand of anemia known as hemolytic anemia.

Diagnosis of thalassemia is a lot like deciphering a coded message. The pencil pushers in the lab look at certain tell-tale signs. For instance, your red blood cells could be unusually pint-sized (think teacup chihuahua), a condition scientifically dubbed microcytosis. While it packs a dense-sounding name, it's just a label to categorize your red blood cells based on their hemoglobin content and size.

There are two key characters to keep an eye on in this plot – the alpha and beta globin, the proverbial nuts and bolts of hemoglobin. Depending on whether you carry alpha thalassemia or beta thalassemia, your body either skimps on alpha globin or beta globin. Unfortunately, at first glance, your lab results might mimic that of regular iron deficiency anemia, leading to misdiagnoses and a treatment detour.

Testing for iron deficiency can feel like navigating through a dietary minefield. Your iron levels yo-yo based on meals. So if you strut into the lab first thing in the morning without breakfast, your iron levels might just drop the mic on you. Alternatively, ferritin level tests reveal the amounts of iron you have in storage, offering a clearer picture.

Thalassemia also has its own signature red flags. One simple math blunder is the giveaway - an anomaly in the red blood cell count. Ideally, a low count implies iron deficiency anemia. On the other hand, with thalassemia, the count ranges from standard to ‘party in the blood cells’.

Lastly, a more rigorous test, the hemoglobin electrophoresis or hemoglobinopathy evaluation, keeps score of the different varieties of hemoglobin in your blood. For adults, the guest list should ideally feature hemoglobin A and A2. If you come across A2 and/or F (fetal), put your detective hat on – beta thalassemia trait might be the culprit.

All said and done, it’s crucial to unravel this iron yarn – not just to prevent years of fruitless treatment, but also to preempt the risk of inheriting thalassemia, which can escalate to a severe form of anemia that requires monthly blood transfusions. So next time your iron supplementation seems to be as ineffective as a screen door on a submarine, it may be time to consider – could it be Thalassemia?