Clinical Case
A 41-year-old female patient, Maria, of asthenic build, consulted a general practitioner presenting with decreased performance over the past two months. Self-measured hemoglobin was 11.7 g/dL, which formally corresponds to anemia. Such complaints are among the most common in primary care, making it essential to master a systematic algorithm for clarifying them.
Anamnesis collection
When clarifying a complaint, it is necessary to assess its duration, qualitative and quantitative characteristics, as well as factors that aggravate or alleviate the symptom (triggers and alleviating factors). For example, worsening of dyspnea upon contact with flowers may indicate asthma, while worsening of cough in the supine position points to heart failure.
In this patient, symptoms included decreased performance, dyspnea upon climbing two flights of stairs, and rapid fatigue. The symptoms emerged after a viral illness, showed no clear trend of improvement or worsening, and no history of chronic diseases was identified. A burdened family history was noted: the patient's father was diagnosed with cancer of the cecum.
Special attention is paid to screening for signs of chronic non-traumatic blood loss. For this purpose, the following are clarified:
- Gynecological history: presence and heaviness of menstruation, as further diagnostic strategy depends on this;
- Hemorrhagic history: presence of blood in stool or urine, hemoptysis, epistaxis, gum bleeding;
- Association of symptom onset with a prior viral infection — this may indicate either rare post-viral asthenia (chronic fatigue syndrome) or bone marrow disorders and other conditions starting after a viral infection.
Physical Examination
When anemia is suspected, in addition to standard examination, it is advisable to palpate the liver and spleen to assess the likelihood of a hemolytic process. Specific signs of decreased hemoglobin include pallor of the skin, nail plates, and palms.
An informative yet rarely discussed sign is also highlighted: pallor of the lower eyelid conjunctiva. Both the upper and lower margins of the lower eyelid conjunctiva are assessed: normally, the upper margin is noticeably brighter and redder than the lower due to a rich capillary network. In anemia, the upper margin becomes indistinguishable from the lower. This sign exhibits high sensitivity and specificity.
Laboratory Diagnostics of Anemia
For further diagnostics, in addition to hemoglobin, a complete blood count with erythrocyte indices is required. Ferritin is uninformative at the initial stage since it is an acute-phase protein and increases during inflammation.
The patient's complete blood count revealed elevated platelets (also a marker of inflammation) and signs of an inflammatory process. Hemoglobin and hematocrit reflect the severity of anemia—in this case, a mild degree not requiring emergency measures (blood transfusion).
The key parameter for subsequent strategy is mean corpuscular volume (MCV), according to which anemias are classified into:
- Normocytic — MCV 80–100 fL;
- Microcytic — MCV below 80 fL;
- Macrocytic — MCV above 100 fL.
This classification simplifies the diagnostic search by dividing the general algorithm into three narrower directions.
Diagnostic Algorithm for Normocytic Anemia
In normocytic anemia, hemolysis is first ruled out by counting reticulocytes: an elevated count indicates active bone marrow function and compensatory erythrocyte replenishment, while a decreased count indicates inadequate production.
The next step is assessing C-reactive protein and the erythrocyte sedimentation rate, which point to anemia of chronic disease. Next, the levels of iron, vitamin B12, and folic acid are investigated to rule out deficiency anemias. If all listed causes are ruled out, rarer options are considered—decreased erythrocyte production due to liver, thyroid, or kidney pathology; if these data are uninformative, bone marrow microscopy and, if necessary, trephine biopsy are indicated.
In the patient, reticulocytes were 1%, ferritin was 237 ng/mL (norm up to 30), and vitamin B12 and folic acid were within the reference range. Thus, normocytic anemia of chronic disease associated with inflammation was identified.
Pathogenesis of Anemia of Chronic Disease and Final Diagnosis
Anemia of chronic disease develops against the background of systemic inflammation: the body perceives the situation as a bacterial infection and limits iron availability to pathogens. Under the influence of cytokines, the liver produces the protein hepcidin, which reduces intestinal iron absorption and blocks its release from macrophages. As a result, the level of available iron drops, and erythrocyte production slows down despite normal body iron stores.
Treatment aims to eliminate the underlying disease; iron supplements are contraindicated in bacterial inflammation as they may aggravate the infectious process. Blood transfusion is indicated only for severe anemia, which is rare.
Additional examination revealed extremely low TSH with significantly elevated T4 and T3 in the patient, which is characteristic of thyrotoxicosis. Since TSH is inversely related to thyroxine levels, its decrease alongside high T4/T3 indicates thyroid hyperfunction rather than hypothyroidism. Ultimately, subacute thyroiditis was diagnosed, which frequently develops after a viral infection. Following treatment, the patient's blood parameters normalized within a month.
Key points
- When evaluating a complaint of fatigue, it is essential to clarify the duration, dynamics, triggers, and alleviating factors of the symptom.
- In menstruating women with anemia, gynecological and hemorrhagic history must be evaluated to rule out chronic blood loss.
- Pallor of the upper margin of the lower eyelid conjunctiva is a highly sensitive and specific sign of anemia.
- Mean corpuscular volume (MCV) determines the direction of diagnostic search: normocytic, microcytic, or macrocytic anemia.
- In normocytic anemia, diagnostics begin with reticulocytes to rule out hemolysis, followed by assessing CRP and ESR.
- Anemia of chronic disease is associated with elevated hepcidin, which blocks iron absorption and release during inflammation.
- Low TSH with high T4 and T3 indicates thyrotoxicosis rather than hypothyroidism.
- Subacute thyroiditis frequently develops after a viral infection and can mimic the clinical picture of anemia of chronic disease.