System for determining an underlying cause of anemia

A method of detecting a cause of anemia selected from the group consisting of:

• sickle cell anemia, hereditary spherocytosis, hemolytic anemia, alpha thalassemia hemoglobinopathy, anemia of a chronic disease or a neoplastic disorder, anemia of a hemoglobinopathy, B12 and/or folate deficiency, hematological disease, chronic disease secondary to liver disease with or without alcohol, iron deficiency, acute or chronic phase reaction, dimorphic anemia and gastrointestinal bleeding, the method comprising:
• (a-i) obtaining or having obtained a blood sample from an individual having anemia;
• (a-ii) testing the blood sample for blood parameters comprising:
• mean corpuscular hemoglobin concentration (MCHC) level, reticulocyte count, hemoglobin level, mean corpuscular volume (MCV), ferritin level, B12 level, folate level, methylmalonic acid content, one or more markers of liver function, and C-reactive protein (CRP) level;
• (a-iii) measuring the blood parameters in the blood sample;
• and
• (a-iv) selecting and evaluating the measured blood parameters in each of the following specific combinations to detect a cause of anemia:
• (b) if the blood sample MCHC level is elevated compared to a defined standard for MCHC and the blood sample reticulocyte count is normal or elevated compared to a defined standard reticulocyte count, sickle cell anemia or hereditary spherocytosis is detected;
• (c) if the blood sample MCHC level is low or normal compared to the defined standard for MCHC or if the blood sample reticulocyte count is low compared to the defined standard reticulocyte count, and the blood sample hemoglobin level is not lower than a defined cutoff for hemoglobin, anemia of a chronic disease or a neoplastic disorder is detected;
• (d) if the blood sample MCHC level is low or normal compared to the defined standard for MCHC, the blood sample hemoglobin level is lower than a defined cutoff for hemoglobin, the blood sample MCV is low compared to a standard for MCV, and the blood sample ferritin level is low compared to a defined cutoff for ferritin, iron deficiency or alpha thalassemia hemoglobinopathy is detected;
• (e) if the blood sample MCHC level is low or normal compared to the defined standard for MCHC, the blood sample hemoglobin level is lower than a defined cutoff for hemoglobin, the blood sample MCV is low compared to a standard for MCV, and the blood sample ferritin level is normal or high compared to a defined cutoff for ferritin, then performing a hemoglobinopathy evaluation to detect an anemia of a chronic disease, hemolytic anemia, or anemia of a hemoglobinopathy, wherein:
• (e-i) if the blood sample reticulocyte count is normal compared to the defined standard reticulocyte count and the hemoglobinopathy evaluation is normal, anemia of a chronic disease is detected;
• (e-ii) if the blood sample reticulocyte count is elevated compared to the defined standard reticulocyte count and the hemoglobinopathy evaluation is normal, hemolytic anemia is detected;
• or
• (e-iii) if the blood sample reticulocyte count is normal or elevated compared to the defined standard reticulocyte count and the hemoglobinopathy evaluation is abnormal, anemia of a hemoglobinopathy is detected;
• (f) if the blood sample MCHC level is low or normal compared to the defined standard for MCHC, the blood sample hemoglobin level is lower than a defined cutoff for hemoglobin, the blood sample MCV is elevated by at least 10% compared to a standard for MCV, and the blood sample ferritin level is normal or high compared to a defined cutoff for ferritin, the blood sample B12 and/or folate levels are lower than defined cutoffs for B12 and/or folate, and the blood sample methylmalonic acid content is elevated, a B12 and/or folate deficiency is detected;
• (g) if the blood sample MCHC level is low or normal compared to the defined standard for MCHC, the blood sample hemoglobin level is lower than a defined cutoff for hemoglobin, the blood sample MCV is elevated by at least 10% compared to a standard for MCV, and the blood sample ferritin level is normal or high compared to a defined cutoff for ferritin, the blood sample B12 and/or folate levels are higher than defined cutoffs for B12 and/or folate, and the blood sample reticulocyte count is normal or elevated compared to the defined standard reticulocyte count, sickle cell anemia or hereditary spherocytosis is detected;
• (h) if the blood sample MCHC level is low or normal compared to the defined standard for MCHC, the blood sample hemoglobin level is lower than a defined cutoff for hemoglobin, the blood sample MCV is elevated by at least 10% compared to a standard for MCV, and the blood sample ferritin level is normal or high compared to a defined cutoff for ferritin, the blood sample B12 and/or folate levels are higher than defined cutoffs for B12 and/or folate, and the blood sample reticulocyte count is low compared to the defined standard reticulocyte count, then performing a hepatic function panel to detect a hematological disease or chronic disease secondary to liver disease with or without alcohol, wherein:
• (h-i) if the blood sample one or more markers of liver function are within the a defined range for the one or more markers of liver function, hematological disease is detected;
• or
• (h-ii) if the blood sample one or more markers of liver function are not within the defined range for the one or more markers of liver function, chronic disease secondary to liver disease with or without alcohol is detected;
• (i) if the blood sample MCHC level is low or normal compared to the defined standard for MCHC, the blood sample hemoglobin level is lower than a defined cutoff for hemoglobin, the blood sample MCV is normal compared to a standard for MCV, and the blood sample ferritin level is low compared to a defined cutoff for ferritin, iron deficiency is detected;
• (j) if the blood sample MCHC level is low or normal compared to the defined standard for MCHC, the blood sample hemoglobin level is lower than a defined cutoff for hemoglobin, the blood sample MCV is normal compared to a standard for MCV, and the blood sample ferritin level is high compared to a defined cutoff for ferritin, acute or chronic phase reaction is detected;
• (k) if the blood sample MCHC level is low or normal compared to the defined standard for MCHC, the blood sample hemoglobin level is lower than a defined cutoff for hemoglobin, the blood sample MCV is normal compared to a standard for MCV, the blood sample ferritin level is normal compared to a defined cutoff for ferritin, the blood sample reticulocyte count is normal compared to the defined standard reticulocyte count, and the blood sample C-reactive protein (CRP) level is normal compared to a defined cutoff for CRP level, anemia of a chronic disease or dimorphic anemia is detected;
• (l) if the blood sample MCHC level is low or normal compared to the defined standard for MCHC, the blood sample hemoglobin level is lower than a defined cutoff for hemoglobin, the blood sample MCV is normal compared to a standard for MCV, the blood sample ferritin level is normal compared to a defined cutoff for ferritin, the blood sample reticulocyte count is elevated compared to the defined standard reticulocyte count, and the blood sample C-reactive protein (CRP) level is normal compared to a defined cutoff for CRP level, hemolytic anemia or gastrointestinal bleeding is detected;
• and
• (m) if the blood sample MCHC level is low or normal compared to the defined standard for MCHC, the blood sample hemoglobin level is lower than a defined cutoff for hemoglobin, the blood sample MCV is normal compared to a standard for MCV, the blood sample ferritin level is normal compared to a defined cutoff for ferritin, the blood sample reticulocyte count is low or normal compared to the defined standard reticulocyte count, and the blood sample C-reactive protein (CRP) level is elevated compared to a defined cutoff for CRP level, then performing a complete metabolic panel (CMP) wherein if the CMP is abnormal, anemia of a chronic disease is detected.