Anemia: Or something else? Differential Diagnosis

Blood, hematopoietic organs – immune system (D50-D90).

  • Aplastic anemia – failure of hematopoiesis, the cause of which remains unexplained in most cases.
  • Ascorbic acid deficiency (hypovitaminosis C; avitaminosis C); clinical picture: General bleeding tendency, hemorrhages/bleeding of the skin (perifollicular hemorrhages, petechiae (flea-like bleeding), ecchymoses (small-surface skin bleeding)), wound healing disorders, bleeding into joints, gingivitis (inflammation of the oral mucosa) with gingival hyperplasia (gum proliferation), fatigue and muscle weaknessRisk groups: People with malnutrition (malnutrition) or special dietary habits, as well as people with chronic alcohol abuse and drug abuse.
  • Bleeding anemia, acute (source of bleeding: mainly genital or gastrointestinal).
  • Inflammatory anemia
  • Elliptocytosis – group of rare defects of the membrane skeleton of erythrocytes (red blood cells) with autosomal dominant or autosomal recessive inheritance; blood smear shows numerous elliptical erythrocytes (elliptocytes).
  • G6PD deficiency (glucose-6-phosphate dehydrogenase deficiency) – genetic disease with X-linked recessive inheritance; deficiency of the enzyme glucose-6-phosphate dehydrogenase leads to recurrent hemolysis and chronic anemia; about 13% of all male individuals from Central Africa: mild, clinically irrelevant form; people from Mediterranean countries and China: severe form.
  • Hemoglobinopathies of the β-globin chains (usually manifests in the 2nd year of life).
  • Hemolytic anemia – anemia caused by premature destruction of erythrocytes (red blood cells).
  • Megaloblastic anemia (deficiency of vitamin B12 or folic acid).
  • Myelofibrosis – disease that leads to the progressive obliteration of the bone marrow, resulting in a decrease in blood cells.
  • Renal anemia – anemia associated with kidney disease.
  • Runners Anemia – anemia caused by an increase in blood plasma volume and by increased destruction of blood cells in runners.
  • Sickle cell anemia (med.: drepanocytosis; also sickle cell anemia, sickle cell anemia) – genetic disease with autosomal recessive inheritance affecting erythrocytes (red blood cells); it belongs to the group of hemoglobinopathies (disorders of hemoglobin; formation of an irregular hemoglobin called sickle cell hemoglobin, HbS).
  • Spherocytosis
  • Thalassemia – autosomal recessive hereditary synthesis disorder of the alpha or beta chains of the protein portion (globin) in hemoglobin (hemoglobinopathy/diseases resulting from impaired formation of hemoglobin).
    • Α-Thalassemia (HbH disease, hydrops fetalis/generalized fluid accumulation); incidence: mostly in Southeast Asians.
    • Β-Thalassemia: most common monogenetic disorder worldwide; incidence: People from Mediterranean countries, Middle East, Afghanistan, India and Southeast Asia.
  • Tumor anemia (tumor therapy-associated anemia).

Endocrine, nutritional, and metabolic diseases (E00-E90).

  • Iron utilization disorders
  • Hyperthyroidism (overactive thyroid gland)
  • Hypothyroidism (hypothyroidism)
  • Addison’s disease – primary adrenocortical insufficiency (adrenal insufficiency), which mainly causes a failure of cortisol production, but also leads to a deficiency of mineralocorticoids (aldosterone).
  • Panhypopituitarism – disease that leads to a restriction or complete failure of all pituitary hormones (hormones produced in the pituitary gland).

Infectious and parasitic diseases (A00-B99).

  • Chronic inflammation, unspecified → anemia of inflammation (formerly anemia of chronic disease, ACD); ACD is considered the second most common anemia worldwide after iron deficiency anemia
  • Chronic infections, unspecified
  • Cimicosis – violently itchy, skin symptoms caused by bites of blood-sucking bugs (Cimex lectularis/bedbugs); smokers, singles, persons with dark skin color are particularly affected; Affected individuals have higher RDW-CV (coefficient of variation of red cell size (in percent)) and lower hemoglobin (blood pigment), hematocrit (proportion of all cellular components in the volume of blood), erythrocyte (red blood cell), and MCHC (mean corpuscular hemoglobin concentration: Mean hemoglobin concentration of hematocrit (the red blood cell mass)) than control subjects.
  • Helminthiasis (worm disease).
  • Malaria
  • Parvovirus B19-induced aplastic crisis in hemolytic anemias.
  • Viral infection-associated hemolytic crises in hemolytic anemias.

Liver, gallbladder, and bile ducts – Pancreas (pancreas) (K70-K77; K80-K87).

Mouth, esophagus (esophagus), stomach, and intestines (K00-K67; K90-K93).

Musculoskeletal system and connective tissue (M00-M99).

  • Chronic inflammatory diseases (eg, rheumatoid arthritis).

Neoplasms – tumor diseases (C00-D48).

  • Colon carcinoma colon cancer)
  • Leukemia (blood cancer)
  • Gastric carcinoma (stomach cancer)
  • Hodgkin’s disease – malignant neoplasia (malignant neoplasm) of the lymphatic system with possible involvement of other organs.
  • Myelodysplastic syndrome (MDS) – acquired clonal disease of the bone marrow associated with a disorder of hematopoiesis; defined by:
    • Dysplastic cells in the bone marrow or ring sideroblasts or an increase of myeloblasts up to 19%.
    • Cytopenias (decrease in the number of cells in the blood) in the peripheral blood count.
    • Exclusion of reactive causes of these cytopenias.

    One quarter of MDS patients develop acute myeloid leukemia (AML).

  • Plasmocytoma (multiple myeloma) – systemic disease leading to malignant (malignant) proliferation of plasma cells; the disease leads mainly to bone involvement and blood count changes.
  • Leiomyoma (uterus myomatosus).

Symptoms and abnormal clinical and laboratory findings not elsewhere classified (R00-R99).

  • Chronic inflammation (inflammation) → anemia of chronic inflammation (“anemia of chronic inflammation,” ACI).

Genitourinary system (kidneys, urinary tract – sex organs) (N00-N99).

  • Hypermenorrhea – bleeding is excessive (> 80 ml); usually, the affected person consumes more than five pads/tampons per day
  • Renal insufficiency – process that leads to a slowly progressive reduction in kidney function.

Injury, poisoning, and other consequences of external causes (S00-T98).

  • Lead intoxication (lead poisoning).

Other differential diagnoses

  • Hemolytic crises in G6PD deficiency.
  • Postoperative anemia
  • Polymedication (> 6 medications)
  • Gestational hydropathy

Medication

Anemia

  • Anticoagulants – gastrointestinal blood loss due to e.g. oral anticoagulants, acetylsalicylic acid (in combination with clopidogrel), NSAIDs (nonsteroidal anti-inflammatory drugs).
  • Antiprotozoal agents
    • Analogue of the azo dye trypan blue (suramin).
    • Pentamidine
  • Chelating agents (D-penicillamine, trieethylenetetramine dihydrochloride (Trien), tetrathiomolybdenum).
  • Direct factor Xa inhibitor (rivaroxaban).
  • Immunosuppressants (thalidomide).
  • Janus kinase inhibitors (ruxolitinib).
  • Monoclonal antibodies – pertuzumab
  • MTOR inhibitors (everolimus, temsirolimus).
  • Phenytoin [megaoblastic anemia.]
  • Proton pump inhibitors (PPI; acid blockers) – patients on continuous PPI therapy are more often affected by iron deficiency: this depends on duration of therapy and dosage
  • Thrombin inhibitor (dabigatran).
  • Antivirals

Aplastic anemia

Note: For drugs marked with an asterisk (* ), the association with aplastic anemia is poorly documented. Furthermore, all drugs that can lead to gastrointestinal bleeding and generally increased bleeding tendency. Environmental exposures – intoxications

  • Arsenic
  • Lead
  • Benzene
  • Bismuth
  • Gold
  • Mercury