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Haptoglobin

SI UNITS (recommended)

CONVENTIONAL UNITS

(Acute-Phase Glycoprotein – Key Marker for Hemolysis, Inflammation & Liver Function)

Synonyms

  • Haptoglobin
  • Hp
  • Hemoglobin-binding protein
  • Acute-phase α2-glycoprotein
  • Hemopexin–related hemolysis marker (complementary test)

Units of Measurement

  • µmol/L
  • g/L
  • mg/dL
  • mg/100 mL
  • mg%
  • mg/mL

Key Conversions

(Molecular weight varies by phenotype; average ≈ 86 kDa)

1 g/L = 100 mg/dL
1 mg/dL = 0.01 g/L
mg% = mg/dL = mg/100 mL
1 mg/mL = 1000 mg/L = 1 g/L
µmol/L depends on exact molecular mass (~86,000 g/mol)

1 g/L≈11.6 µmol/L1\ \text{g/L} \approx 11.6\ \text{µmol/L}1 g/L≈11.6 µmol/L 1 µmol/L≈0.086 g/L1\ \text{µmol/L} \approx 0.086\ \text{g/L}1 µmol/L≈0.086 g/L

Description

Haptoglobin is a plasma glycoprotein synthesized by the liver.
Its main function is to bind free hemoglobin released during red blood cell destruction.

This prevents:

  • Kidney damage
  • Iron loss
  • Oxidative injury
  • Hemoglobin-mediated toxicity

Haptoglobin is a major acute-phase reactant and rises in inflammation.

Physiological Role

1. Hemoglobin Scavenger

Binds free Hb → forms Hb–haptoglobin complex → cleared by macrophages.

2. Protects Kidney

Prevents hemoglobin filtration & tubular toxicity.

3. Prevents Iron Loss

Recycles Hb-iron into the reticuloendothelial system.

4. Anti-oxidant Effect

Free Hb → oxidative stress
Haptoglobin minimizes Hb-driven oxidative injury.

Clinical Significance

LOW Haptoglobin (Most Important)

Primary marker for hemolysis
→ decreased because it is consumed by free hemoglobin.

Causes of Low Haptoglobin

1. Hemolytic Anemia (key diagnostic use)

  • Intravascular hemolysis (most pronounced)
    • Hemoglobinuria
    • Hemoglobinemia
    • DIC
    • TTP/HUS
    • PNH
    • Transfusion reaction
    • Mechanical hemolysis (prosthetic valves)

2. Extravascular Hemolysis

  • Mild decrease
  • Seen in autoimmune hemolysis

3. Liver Disease

Reduced synthesis:

  • Cirrhosis
  • Hepatic failure

4. Congenital Anhaptoglobinemia

Genetic low or absent levels; benign but confuses interpretation.

5. Pregnancy

Mild reduction.

HIGH Haptoglobin

Occurs because it is an acute-phase reactant.

Causes:

  • Infection
  • Inflammation
  • Trauma
  • Stress
  • Burns
  • Malignancy
  • Nephrotic syndrome
  • Glucocorticoid therapy

High levels DO NOT rule out hemolysis
(because inflammation may mask lowering).

Reference Intervals

(Tietz 8E + Mayo + ARUP + BCSH Hemolysis Standards)

Adults

  • 0.3 – 2.0 g/L
    (= 30 – 200 mg/dL)

Children

  • Lower in infancy
  • Adult levels by ~1 year

Hemolysis Cutoffs

  • <0.1 g/L (<10 mg/dL) → strong evidence for hemolysis
  • Undetectable → intravascular hemolysis almost certain (unless liver failure)

Diagnostic Uses

1. Diagnose Hemolytic Anemia (Primary Use)

Interpret with:

  • LDH ↑
  • Indirect bilirubin ↑
  • Reticulocytes ↑
  • Hemoglobinuria
  • Peripheral smear findings
  • Direct antiglobulin test (DAT)

If:

  • LDH high
  • Haptoglobin low
    → hemolysis highly likely.

2. Monitor Hemolytic Disorders

Used in:

  • Autoimmune hemolysis
  • Microangiopathic anemia
  • Transfusion reactions

3. Differentiate Hemolysis vs. Hemorrhage

  • Acute blood loss → normal haptoglobin
  • Hemolysis → low haptoglobin

4. Evaluate Liver Synthetic Function

Low in hepatic failure (reduced synthesis).

5. Detect Intravascular Hemolysis in Dialysis / ECMO

Mechanical RBC destruction → decreased haptoglobin.

Analytical Notes

  • Serum or plasma
  • Hemolysis during sample collection → invalid result
    (because free Hb will falsely lower Hp)
  • Hp is stable, but avoid hemolyzed samples
  • Acute inflammation may increase Hp significantly
  • Genetic absence (0.1–0.3% population) may cause misleadingly low results

Clinical Pearls

  • Low haptoglobin + high LDH = strongest biochemical signature of hemolysis.
  • Inflammation may normalize haptoglobin even during hemolysis → interpret with CRP.
  • In liver failure, haptoglobin falls because of reduced synthesis - mimic hemolysis.
  • Hemoglobinuria strongly suggests intravascular hemolysis, not extravascular.
  • Always interpret haptoglobin with complete hemolysis panel.

Interesting Fact

Haptoglobin polymorphisms (Hp1-1, Hp2-1, Hp2-2) influence antioxidant capacity, cardiovascular risk, and response to oxidative stress.

References

  1. Tietz Clinical Chemistry & Molecular Diagnostics, 8th Edition - Hemolysis Markers.
  2. BCSH Hematology Guidelines - Diagnosis of Hemolytic Anemia.
  3. AABB Standards - Hemolysis Evaluation.
  4. Mayo Clinic Laboratories - Haptoglobin.
  5. ARUP Consult - Hemolysis Workup.
  6. MedlinePlus / NIH - Haptoglobin Test.

Last updated: January 26, 2026

Reviewed by : Medical Review Board

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