Causes of Increased ESR (Erythrocyte Sedimentation Rate) - Mnemonic NAPKIN

The erythrocyte sedimentation rate (ESR) is a simple, inexpensive, and commonly ordered blood test that measures how quickly red blood cells settle at the bottom of a test tube over one hour. A faster-than-normal sedimentation rate indicates the presence of inflammation or disease.

While ESR is a non-specific marker, it is highly useful in screening and monitoring conditions such as infections, autoimmune diseases, malignancies, and pregnancy-related changes.

To easily recall the major causes of increased ESR, students and healthcare professionals often use the mnemonic “NAPKIN.”

Mnemonic: NAPKIN

The mnemonic NAPKIN summarizes the major conditions that elevate ESR:

• N – Neoplasia
• A – Anemia / Autoimmune diseases
• P – Pregnancy
• K – Kidney disease
• I – Infection / Inflammation
• N – Neoplasm (repeated for emphasis on malignancy)

Detailed Explanation of Causes

1. N – Neoplasia

Malignant tumors are often associated with increased ESR.

• Tumors cause chronic inflammation and increased fibrinogen levels, which enhance red blood cell aggregation.
• ESR is particularly high in multiple myeloma, lymphoma, metastatic cancers, and certain leukemias.

Clinical Relevance: In multiple myeloma, ESR can be extremely elevated due to increased immunoglobulins.

2. A – Anemia / Autoimmune Diseases

Anemia:

• In anemia (especially iron deficiency anemia), ESR increases because fewer red cells in plasma settle more quickly when aggregated.
• Low hematocrit → reduced resistance → faster sedimentation.

Autoimmune Diseases:

• Conditions like rheumatoid arthritis, systemic lupus erythematosus (SLE), and temporal arteritis cause persistent inflammation.
• Elevated cytokines stimulate liver production of acute-phase proteins (e.g., fibrinogen), which promotes rouleaux (stacking of RBCs) and increases ESR.

3. P – Pregnancy

• ESR naturally rises during pregnancy due to hormonal and hematological changes.
• Increase in plasma fibrinogen and globulins accelerates red blood cell sedimentation.
• This is physiological, not pathological, and usually peaks in the second and third trimesters.

4. K – Kidney Disease

• Chronic kidney disease (CKD), especially with nephrotic syndrome, elevates ESR.
• This happens due to altered plasma protein composition (low albumin, high fibrinogen and globulins).
• Uremia-related systemic inflammation also plays a role.

Example: In end-stage renal disease (ESRD), persistently high ESR is common.

5. I – Infection / Inflammation

Perhaps the most common cause of elevated ESR.

Both acute and chronic infections raise ESR:

• Acute infections: Pneumonia, tuberculosis, urinary tract infections
• Chronic infections: Osteomyelitis, subacute bacterial endocarditis

Inflammatory diseases: Polymyalgia rheumatica, vasculitis, inflammatory bowel disease

Mechanism: Infection → release of cytokines → increased acute-phase reactants (fibrinogen, CRP) → enhanced rouleaux formation → high ESR.

6. N – Neoplasm (repeated)

The mnemonic repeats Neoplasm to emphasize its significance. In many cancer-related conditions, ESR not only serves as a diagnostic clue but also as a marker for prognosis and treatment monitoring.

Mechanism Behind Increased ESR

The rate of erythrocyte sedimentation depends on:

1. Plasma protein composition – Increased fibrinogen and globulins cause RBCs to stick together and settle faster.

2. Red blood cell shape and number – Conditions like anemia alter sedimentation speed.

3. Inflammatory activity – Elevated acute-phase proteins accelerate ESR.

Thus, ESR acts as an indirect marker of inflammation and systemic disease activity.

Clinical Applications of ESR

Screening test: Helps detect hidden infections, autoimmune disorders, or cancers.

Monitoring tool: Useful in tracking disease progression and response to treatment (e.g., in tuberculosis or temporal arteritis).

Not diagnostic alone: Must always be interpreted alongside history, physical examination, and other investigations (e.g., CRP, imaging, biopsy).

Comparative Table: Causes of Increased ESR (Mnemonic – NAPKIN)

Mnemonic	Cause	Mechanism	Example Conditions
N	Neoplasia	Chronic inflammation, ↑ fibrinogen	Multiple myeloma, lymphoma
A	Anemia / Autoimmune	Low hematocrit / chronic inflammation	Iron deficiency anemia, SLE, RA
P	Pregnancy	↑ Fibrinogen, hormonal changes	2nd & 3rd trimester
K	Kidney disease	Altered plasma proteins, inflammation	CKD, nephrotic syndrome
I	Infection / Inflammation	Cytokines ↑ acute-phase proteins	TB, pneumonia, osteomyelitis
N	Neoplasm (repeat)	Tumor-related inflammation	Leukemia, metastatic cancers

Limitations of ESR

While ESR is useful, it has several limitations:

• Non-specific – many conditions elevate ESR.
• Slow to rise and fall – does not reflect acute changes as quickly as C-reactive protein (CRP).
• Can be influenced by unrelated factors (age, sex, obesity).

Frequently Asked Questions (FAQ)

Q1. What is considered a high ESR?

• Men: >15 mm/hr (under 50 years), >20 mm/hr (over 50 years)
• Women: >20 mm/hr (under 50 years), >30 mm/hr (over 50 years)

Q2. Can ESR be elevated in healthy individuals?

Yes, ESR can rise in pregnancy, aging, and mild anemia without disease.

Q3. Which is more reliable – ESR or CRP?

CRP is more specific and rises faster in acute inflammation, but ESR is still valuable for monitoring chronic conditions.

Q4. Why is ESR so high in multiple myeloma?

Because of excess immunoglobulins and fibrinogen, which enhance rouleaux formation of RBCs.

Q5. Can ESR help diagnose tuberculosis?

Yes, TB is a classic cause of markedly elevated ESR, but ESR alone is not diagnostic—other tests like chest X-ray, sputum analysis, or PCR are required.