Regenerative Anemia and Hemorrhage

Blood loss and RBC destruction (hemolysis).

About 2–4 days; robust regeneration may take about 7 days.

The bone marrow has not had enough time to release increased reticulocytes.

Blood loss decreases protein; hemolysis usually leaves protein within the reference interval.

↑Bilirubin, bilirubinuria, hemoglobinemia, and/or hemoglobinuria.

Loss of whole blood, including RBCs and plasma/proteins, from the vascular system.

Acute is regenerative; chronic may become non-regenerative from iron deficiency.

RBCs and plasma are initially lost proportionally.

Around 24 hours as interstitial fluid replaces plasma volume.

Reticulocytes appear days 2–4 and peak around day 7.

Proteins by ~day 7; RBC mass by ~2–3 weeks.

Trauma, alimentary blood loss (GI), and hemostatic abnormalities.

Macrophages phagocytose RBCs and recycle the iron.

Iron is repeatedly lost from the body with the blood.

Microcytic-hypochromic anemia.

Anemia + hypoproteinemia.

Fecal occult blood, coagulation panel, effusion analysis, and urinalysis.

1. Immune Mediated
2. Oxidative
3. Mechanical

Accelerated destruction of RBCs.

Intravascular = RBC rupture in blood; extravascular = macrophage phagocytosis of RBCs.

Moderate-to-severe regenerative anemia with reticulocytosis.

Extravascular hemolysis.

It binds haptoglobin and is taken up by macrophages.

Hemoglobinemia in plasma develops, followed by hemoglobinuria (bloody urine)

Hyperbilirubinemia, icterus, icteric plasma, and bilirubinuria.

- autoantibodies macrophages destroy RBCs
- Spherocytes and agglutination.

Heinz bodies, best detected with new methylene blue.

Ghost cells.

Keratocytes and schistocytes.

Mechanical RBC fragmentation as cells encounter abnormal small vessels or fibrin.

Regenerative anemia with normal plasma protein.

Coombs’ test for immune-mediated anemia, Heinz body stain, PCR for organisms, and specialized RBC testing.

Decreased erythropoiesis and ineffective erythropoiesis.

Inflammation, CKD (chronic kidney disease), iron deficiency, and primary bone marrow disease.

Minimal polychromasia, few/no nRBCs, and an inadequate reticulocyte response.

Hypochromasia, target cells, schistocytes, and keratocytes.

Elliptocytes, dacrocytes, schistocytes, and keratocytes.

Anemia of inflammation.

It traps iron in macrophages and decreases intestinal iron absorption.

↓EPO production/ response and shortened RBC lifespan.

Mild normocytic-normochromic non-regenerative anemia with increased marrow iron.

Infection, sterile inflammation, and immune-mediated disease.

Decreased EPO production.
- Iron restriction, uremic toxins, shortened RBC lifespan, inflammation, and GI hemorrhage

↑BUN/creatinine with moderate-to-severe normocytic-normochromic anemia.

Echinocytosis.

Microcytic-hypochromic RBCs.

Insufficient intake (neonates) or chronic external blood loss, especially GI bleeding.

Low Hgb synthesis causes erythroid precursors to divide extra times, lowering MCV.

Insufficient Hgb production decreases MCHC.

Regenerative → microcytic-normochromic → microcytic-hypochromic.

Microcytes, target cells, hypochromasia, schistocytes, and keratocytes (RBC fragmentation)

Thrombocytosis (increases platelets)

Moderate-to-severe anemia with concurrent cytopenias, such as pancytopenia.

Myelophthisis, altered microenvironment, toxins, immune-mediated disease, and myelofibrosis.

Normocytic-normochromic-nonregenerative; iron deficiency is the major exception.

An increased hematocrit.

Dehydration or splenic contraction.

Both HCT and plasma proteins increase.

A true increase in RBC mass.

Primary = RBC neoplasia, polycythemia vera; secondary = increased EPO from hypoxia or rare tumors.