Pathology

Pathology/C/3

Anemia of blood loss

出血性貧血（失血性貧血）

タグ
High-yield / ポイント

1. Blood loss anemia (hemorrhage)

Acute blood loss

  • Immediate danger is hypovolemic shock, not the anemia itself.
  • Compensation: ↑EPO → increased RBC production over time.
  • Morphology: typically normocytic, normochromic early.

Chronic blood loss

  • Common sources: GI tract (polyps, ulcers, cancers) and urogenital tract (e.g., menstrual bleeding).
  • Sustained loss → iron stores used up → secondary iron deficiency anemia.
  • Morphology: microcytic, hypochromic.

2. Hemolytic anemia (↑RBC destruction) — overview

Key features:

a) Decreased RBC lifespan

b) Compensatory ↑erythropoiesis → reticulocytosis

c) Accumulation of breakdown products (bilirubin, etc.)

d) Marrow erythroid hyperplasia; severe cases → extramedullary hematopoiesis

Patterns of hemolysis

Intravascular hemolysis

  • RBC destruction in circulation → hemoglobinemia, hemoglobinuria, hemosiderinuria
  • Hb casts may injure kidney → acute tubular necrosis
  • Unconjugated bilirubin → jaundice

Extravascular hemolysis

  • RBC removal by macrophages in spleen/liver
  • No hemoglobinemia/hemoglobinuria
  • Can cause pigment gallstones, splenomegaly, jaundice

3. Selected high-yield causes of hemolytic anemia

3.1 Hereditary spherocytosis

  • Inherited membrane/cytoskeleton defects (often AD) → spherocytes (round, hyperchromic, no central pallor)
  • Less deformable → trapped and destroyed in spleen (extravascular hemolysis)

Clinical

  • Anemia + jaundice
  • Splenomegaly
  • Pigment gallstones (common)
  • Aplastic crisis with parvovirus B19

Tx: splenectomy may help but ↑infection risk

3.2 Sickle cell disease

  • β-globin mutation (Glu→Val at position 6) → HbS
  • Deoxygenation → HbS polymerizes → sickling (initially reversible; repeated episodes damage membrane → irreversible)

Consequences

  1. Chronic hemolytic anemia

  2. Microvascular occlusion → ischemia/infarcts (bone, brain, kidney, lung, etc.)

Clinical

  • Pain (vaso-occlusive) crises
  • Acute chest syndrome
  • Stroke
  • Functional asplenia → infections

3.3 Thalassemias

  • Reduced synthesis of α or β chains → unpaired chain precipitation → RBC damage
  • Microcytic hypochromic anemia, target cells, marrow expansion with skeletal changes; hepatosplenomegaly (extramedullary hematopoiesis)

3.4 G6PD deficiency

  • RBCs vulnerable to oxidative stress → episodic intravascular hemolysis
  • Oxidized Hb precipitates → Heinz bodies; splenic removal → bite cells
  • Triggers: drugs (e.g., sulfonamides), infections; more severe in males (X-linked)

3.5 Autoimmune hemolytic anemia (AIHA)

Diagnosis: direct Coombs test (IgG and/or C3 on RBCs)

  • Warm AIHA (IgG, active at 37°C)
    • Often idiopathic or associated with autoimmune disease
    • Extravascular hemolysis; can create spherocytes
    • Drug-associated examples include penicillin, α-methyldopa
  • Cold AIHA (IgM, active <30°C)
    • IgM binds in cooler extremities; complement deposition persists → extravascular hemolysis

3.6 Mechanical hemolysis

  • Traumatic hemolysis: repetitive mechanical injury (e.g., artificial valves, extreme exercise)
  • Microangiopathic hemolytic anemia (MAHA): small vessel lesions (DIC, malignant HTN, vasculitis, disseminated cancer) → schistocytes

3.7 Paroxysmal nocturnal hemoglobinuria (PNH)

  • Acquired PIGA mutation → loss of complement-protective surface proteins → complement-mediated RBC lysis
  • Hemolysis classically “nocturnal” conceptually (more complement fixation with acidosis during sleep)

💡 High-yield: Acute blood loss → shock risk; chronic blood loss → iron deficiency. Hemolysis: intra- vs extravascular. Classic entities: hereditary spherocytosis (spherocytes + splenomegaly), sickle cell (vaso-occlusion), G6PD (Heinz bodies/bite cells), AIHA (Coombs+), MAHA (schistocytes).