Modifiers of severity of AI
| Entity . | Specific factors . | Mechanism . |
|---|---|---|
| Bleeding | Menstruation, gastrointestinal blood loss, repeated blood draws for diagnostics | Development of true iron deficiency |
| Vitamin deficiencies | Cobalamin | Impaired erythropoiesis, hemolysis |
| Folic acid | Impaired erythropoiesis, hemolysis | |
| Vitamin D | Increased hepcidin formation and iron retention | |
| Hemolysis | In autoimmune diseases | Immunoglobulin or complement mediated |
| In infectious diseases | Plasmodium- or Babesia-mediated hemolysis; stimulation of erythrophagocytosis; hemolysis in association with viral infections (eg, EBV, CMV) | |
| In malignancies | Immunoglobulin or complement mediated | |
| Renal dysfunction | Reduced hepcidin excretion | Iron retention and impaired dietary absorption |
| Reduced Epo formation | Impaired erythroid maturation | |
| Uremic toxins | Impaired erythroid progenitor differentiation | |
| Infection | Helicobacter pylori infection | Reduced dietary iron absorption |
| Parvovirus B19, CMV, EBV, HIV, HCV | Pancytopenia, impaired red cell proliferation, hemolysis | |
| Leishmania, Plasmodium | Bone marrow infiltration | |
| Medication | Cytotoxic chemotherapy (including rheumatologic and nephrologic indications) | Impaired erythroid progenitor proliferation and apoptosis |
| Nonsteroidal antirheumatic drugs | Subclinical bleeding | |
| ACE blockers, proton pump inhibitors, neuroleptics | Impaired erythroid progenitor proliferation | |
| Antiplatelet therapy | Subclinical bleeding | |
| Heparins | Hepcidin reduction, subclinical bleeding | |
| Radiotherapy | Erythroid progenitor damage | |
| Hormones | Estrogens/testosterone | Hepcidin regulation |
| Thyroid hormones | Reduced erythroid progenitor proliferation | |
| Genetic polymorphisms | Transferrin, TMPRSS6, divalent metal transporter 1 | Impaired iron absorption |
| Hepcidin | Amelioration or reduction of iron transfer from enterocytes and macrophages | |
| Dietary habits | Low heme iron content | Reduced bioavailability and absorption of dietary iron |
| Obesity | Increased hepcidin levels | Cellular and dietary iron retention |
| Hematological malignancies | Myelodysplasia, smoldering lymphoma | Dyserythropoiesis, bone marrow inflammation and inflammation |
| Age-related factors | Chronic inflammatory status based on chronic diseases, renal impairment, vitamin deficiencies, subclinical myelodysplasia | Dyserythropoiesis, hepcidin-mediated iron retention, reduced Epo activity |
| Entity . | Specific factors . | Mechanism . |
|---|---|---|
| Bleeding | Menstruation, gastrointestinal blood loss, repeated blood draws for diagnostics | Development of true iron deficiency |
| Vitamin deficiencies | Cobalamin | Impaired erythropoiesis, hemolysis |
| Folic acid | Impaired erythropoiesis, hemolysis | |
| Vitamin D | Increased hepcidin formation and iron retention | |
| Hemolysis | In autoimmune diseases | Immunoglobulin or complement mediated |
| In infectious diseases | Plasmodium- or Babesia-mediated hemolysis; stimulation of erythrophagocytosis; hemolysis in association with viral infections (eg, EBV, CMV) | |
| In malignancies | Immunoglobulin or complement mediated | |
| Renal dysfunction | Reduced hepcidin excretion | Iron retention and impaired dietary absorption |
| Reduced Epo formation | Impaired erythroid maturation | |
| Uremic toxins | Impaired erythroid progenitor differentiation | |
| Infection | Helicobacter pylori infection | Reduced dietary iron absorption |
| Parvovirus B19, CMV, EBV, HIV, HCV | Pancytopenia, impaired red cell proliferation, hemolysis | |
| Leishmania, Plasmodium | Bone marrow infiltration | |
| Medication | Cytotoxic chemotherapy (including rheumatologic and nephrologic indications) | Impaired erythroid progenitor proliferation and apoptosis |
| Nonsteroidal antirheumatic drugs | Subclinical bleeding | |
| ACE blockers, proton pump inhibitors, neuroleptics | Impaired erythroid progenitor proliferation | |
| Antiplatelet therapy | Subclinical bleeding | |
| Heparins | Hepcidin reduction, subclinical bleeding | |
| Radiotherapy | Erythroid progenitor damage | |
| Hormones | Estrogens/testosterone | Hepcidin regulation |
| Thyroid hormones | Reduced erythroid progenitor proliferation | |
| Genetic polymorphisms | Transferrin, TMPRSS6, divalent metal transporter 1 | Impaired iron absorption |
| Hepcidin | Amelioration or reduction of iron transfer from enterocytes and macrophages | |
| Dietary habits | Low heme iron content | Reduced bioavailability and absorption of dietary iron |
| Obesity | Increased hepcidin levels | Cellular and dietary iron retention |
| Hematological malignancies | Myelodysplasia, smoldering lymphoma | Dyserythropoiesis, bone marrow inflammation and inflammation |
| Age-related factors | Chronic inflammatory status based on chronic diseases, renal impairment, vitamin deficiencies, subclinical myelodysplasia | Dyserythropoiesis, hepcidin-mediated iron retention, reduced Epo activity |
ACE, angiotensin convertin enzyme; CMV, cytomegalovirus; EBV, Epstein-Barr virus; HCV, hepatitis C virus.