Anemia: medical history, symptoms and physical examination

Article written and reviewed by Dr Luca Moretti

An accurate clinical assessment of the anemic patient is the essential starting point for correctly guiding diagnostic suspicion. Although anemia is a frequent finding in medical practice, it may be the manifestation of highly heterogeneous diseases, some of which are potentially severe or rapidly progressive. In this context, a detailed medical history and a complete physical examination are indispensable tools not only for identifying the presence and characteristics of anemia, but also for laying the foundations for a targeted and timely diagnostic pathway.

Medical history

A properly conducted medical history should aim to reconstruct the temporal and qualitative profile of anemia, with particular attention to:

• Onset and temporal course: the rapidity with which symptoms appear helps distinguish acute forms (hemorrhage, acute hemolysis) from chronic forms (systemic diseases, nutritional deficiencies).
• Characteristics and extent of blood loss: it is essential to investigate both evident losses (menorrhagia, epistaxis, gastrointestinal bleeding) and occult losses, which may be insidious and unrecognized for a long time.
• Any associated systemic symptoms: fever, weight loss, night sweats, arthralgia, bone pain or abdominal pain may suggest underlying hematologic, inflammatory or neoplastic diseases.
• Previous transfusions or surgical procedures: a history of recurrent blood transfusions, major surgery or postoperative hemorrhage may point toward chronic diseases or coagulation defects.
• Use of drugs and substances: in addition to myelotoxic drugs, alcohol intake, substances of abuse, herbal products or supplements that may interfere with absorption or erythroid production should also be investigated.
• Lifestyle, dietary habits and any dietary restrictions: vegetarian or vegan diets, extreme diets or conditions that reduce micronutrient intake must be explored, especially when documented deficiencies are present.
• Specific physiologic conditions: pregnancy, puerperium, pediatric age and older age are situations in which the balance between erythrocyte production and consumption can be easily altered.
• Family history of hematologic or metabolic diseases: collecting information on cases of anemia, jaundice, splenomegaly or sudden deaths in the family is essential for orienting the diagnosis toward inherited forms.

A complete environmental and occupational history must include assessment of exposure to industrial toxic agents, ionizing radiation, organic solvents, lead and other agents that can cause aplastic, sideroblastic or hemolytic anemia.

Symptoms

The symptoms of anemia derive mainly from tissue hypoxia and the activation of compensatory responses by various organs and systems. The clinical picture is often subtle, and the correlation between the severity of anemia and the intensity of symptoms is not linear, especially in patients with comorbidities or in older adults. In clinical practice, it is essential to assess not only the symptoms reported by the patient, but also those detected through the clinical interview and careful observation.

The most common manifestations include:

• Fatigue, weakness and progressive asthenia, sometimes unrecognized in older patients or wrongly attributed to physiologic aging or depression.
• Dyspnea, which may initially occur only on exertion and subsequently at rest, especially in the presence of heart disease or chronic pulmonary disease.
• Palpitations, tachycardia, a sensation of “the heart pounding in the throat”, reflecting the adrenergic response and the need to increase cardiac output.
• Dizziness, vertigo, presyncope or syncope, especially when blood pressure is low or cerebral perfusion is impaired.
• Cognitive changes in frail individuals, with the onset of confusion, psychomotor slowing, worsening attentional abilities or acute delirium.
• Chest pain in patients with known coronary artery disease, sometimes the only sign of clinically significant anemia.

Manifestations such as glossitis, cheilosis, nail fragility and alopecia may accompany specific nutritional deficiencies; paresthesias and ataxia point mainly to vitamin B12 deficiency. The presence of jaundice, dark urine, splenomegaly or bleeding signs points toward hemolytic disorders, hematologic diseases or pancytopenias.

Physical examination

The physical examination of an anemic patient must always be systematic and meticulous, taking into account that physical signs vary with the severity and speed of onset of anemia and with individual patient characteristics. Careful examination may suggest the underlying cause, but it does not confirm anemia: diagnosis requires measurement of hemoglobin.

The most common physical findings include:

• Cutaneous and mucosal pallor: this should be sought particularly at conjunctival level, in the oral mucosae, on the palms of the hands and in the nail beds. In patients with dark skin, pallor may be less evident and greater reliance should be placed on mucosae and nail beds.
• Tachycardia, weak or thready pulse, orthostatic hypotension: especially in acute or rapidly progressive forms.
• “Innocent” systolic murmurs, reflecting increased flow through the cardiac valves in the absence of structural lesions.
• Signs of peripheral hypoperfusion: cold extremities, delayed capillary refill.
• Signs of heart failure: dependent edema, jugular venous distension, congestive hepatomegaly in patients with reduced cardiac reserve.

The physical examination must include a systematic assessment of the hematopoietic organs (lymph nodes, spleen and liver), the skin (petechiae, ecchymoses, ulcers) and the mucosae (glossitis, cheilosis, papillary atrophy, oral ulcers), in order to identify signs suggestive of specific forms of anemia.

In pediatric and older patients, and in patients with neurologic or psychiatric comorbidities, anemia may present with atypical or nonspecific signs and symptoms, such as worsening functional status, behavioral disturbances, motor slowing, falls or cognitive impairment. An integrated geriatric assessment and careful collection of the functional history are essential to avoid underestimating clinically relevant anemic states.

Finally, the correlation between clinical data, vital signs and the results of basic laboratory tests (complete blood count, erythrocyte indices, reticulocytes) is essential for correct diagnosis and for guiding the subsequent choice of further investigations. This integration of clinical assessment and laboratory data represents the basis of truly personalized medicine.

References
1. McPherson RA, Pincus MR. Henry's Clinical Diagnosis and Management by Laboratory Methods. Elsevier. 23rd ed. 2016:527–548.
2. Stauder R, Valent P, Theurl I. Anemia at older age: etiologies, clinical implications, and management. Blood. 2018;131(5):505–514.
3. Johnson-Wimbley TD, Graham DY. Diagnosis and management of iron deficiency anemia in the 21st century. Ther Adv Gastroenterol. 2011;4(3):177–184.
4. Camaschella C. Iron-deficiency anemia. N Engl J Med. 2015;372(19):1832–1843.
5. Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med. 2005;352(10):1011–1023.
6. Koury MJ, Ponka P. New insights into erythropoiesis: the roles of folate, vitamin B12, and iron. Annu Rev Nutr. 2004;24:105–131.
7. Guralnik JM, Eisenstaedt RS, Ferrucci L, Klein HG, Woodman RC. Prevalence of anemia in persons 65 years and older in the United States: evidence for a high rate of unexplained anemia. Blood. 2004;104(8):2263–2268.
8. Cascio MJ, DeLoughery TG. Anemia: Evaluation and Diagnostic Tests. Med Clin North Am. 2017;101(2):263-284.
9. Tefferi A. Anemia in adults: a contemporary approach to diagnosis. Mayo Clin Proc. 2003;78(10):1274-1280.
10. Powell DJ, Achebe MO. Anemia for the Primary Care Physician. Prim Care. 2016;43(4):527-542.