Clinical Assessment - Mrs. Latha, 58F with Severe Thrombocytopenia

Peripheral Smear Report (Dr. Kuladeepa, 22/07/2026)

• RBCs: Mild anisopoikilocytosis, predominantly normocytic normochromic, few microcytic hypochromic cells, occasional ovalocytes
• WBCs: Normal in count, morphology, and distribution
• Platelets: Reduced in number
• Parasites: None
• Immature cells: None
• Impression: Thrombocytopenia

Diagnostic Framework

Working Diagnosis: Secondary ITP (most likely) or Primary ITP

• Severe thrombocytopenia (plt 4000 → 14000 over 5 days - partial spontaneous rise but still dangerous)
• Active mucocutaneous bleeding (petechiae, gum bleeding, hematuria)
• Anemia (Hb 9 - likely from bleeding + possibly chronic disease)
• Normal WBC, normal LFT/RFT
• No infection identified (dengue, malaria, HIV, HCV negative)
• Isolated thrombocytopenia on smear with no schistocytes

Further Workup - What Still Needs to be Done

Tests Already Sent (Awaiting):

• ANA (for SLE - important secondary cause in a woman this age)
• Vit B12 (to explain ovalocytes + mild anemia)
• TSH (thyroid disease association with ITP)

Additional Tests to Order NOW:

Bleeding Risk Assessment

• Plt 14,000 + hematuria + gum bleeding = significant mucocutaneous bleeding
• At counts <30,000, treatment is indicated even if asymptomatic
• At counts <10,000 with active bleeding → IVIG + steroids combination is the standard

Treatment Plan

IMMEDIATE (she has plt 14,000 + active bleeding):

• Dexamethasone 40 mg PO/IV daily × 4 days (preferred over prednisone per current guidelines - faster response)
• OR Prednisolone 1 mg/kg/day if dexamethasone not available

• IVIG 1 g/kg IV single dose (can repeat in 1-2 days if inadequate response)
• IVIG + corticosteroids together produce more sustained response than IVIG alone
• Works within 24-48 hours - important since she has active bleeding

• Tranexamic acid 500-1000 mg TID orally - for mucosal bleeding (gum + hematuria)
• Avoid NSAIDs, aspirin, and any drug affecting platelet function
• Review and stop any potentially offending antihypertensive
• Switch antihypertensive to amlodipine if not already on it (thiazides and furosemide must be stopped)
• Urine dipstick + microscopy to quantify hematuria

• Generally NOT indicated in ITP (platelet survival is minutes in the circulation due to antibodies)
• Reserve for life-threatening bleeding (CNS bleed, uncontrolled visceral hemorrhage) where it is given as a temporizing bridge

HOSPITAL ADMISSION:

• Plt <20,000
• Active bleeding at multiple sites (hematuria + gum bleeding)
• Needs IV therapy and monitoring
• Diagnosis not yet confirmed (secondary causes pending)

Red Flags to Watch For In Hospital

Summary Differential Diagnosis (in order of probability)

1. Primary ITP - isolated thrombocytopenia, no schistocytes, normal WBC, female > 50 yrs
2. Secondary ITP from SLE - 58F, ANA pending, must rule out
3. Drug-induced thrombocytopenia - check her antihypertensive list
4. H. pylori-associated ITP - very common in India, test and treat
5. Evans syndrome (ITP + AIHA) - anemia + thrombocytopenia, check DAT
6. Antiphospholipid syndrome - thrombocytopenia + possible future thrombosis risk

Do Steroids Alter These Tests?

1. Bone Marrow Biopsy

2. Antiphospholipid Antibodies (APLA Panel)

• Steroids reduce overall immunoglobulin synthesis non-specifically. Since anticardiolipin antibodies (aCL) and anti-beta2GP1 are IgG/IgM immunoglobulins, long-term or high-dose steroids can lower their titres
• The effect on lupus anticoagulant (LA) is different - LA is a functional clotting assay (dRVVT/DPTA), not an immunoglobulin titre test. Steroids have no direct effect on LA - it depends on the presence of antibody in plasma at the time of testing, not immune suppression status
• Short-course dexamethasone (4 days) is unlikely to significantly suppress aCL/anti-beta2GP1 enough to cause a clinically false negative
• However, the ISTH (International Society on Thrombosis and Haemostasis) recommends confirming positive APLA tests at 12 weeks to establish persistence - a steroid-suppressed result at week 1 that becomes negative at week 12 could be genuinely negative, not a false negative

3. Direct Antiglobulin Test (DAT / Direct Coombs)

• DAT detects IgG and/or complement (C3d) coating red cells
• Steroids suppress anti-RBC antibody production and can clear IgG from red cell surfaces within days to weeks
• A patient with Evans syndrome (ITP + AIHA) who gets dexamethasone may have a DAT that turns negative within 3-7 days of starting treatment
• If DAT is done after steroids are started and returns negative, you cannot confidently exclude Evans syndrome

Bottom Line: Order of Priority Before Starting Dexamethasone

• After the CBC tomorrow, what do you do next based on the platelet response?
• After the 4 days of dex, what is the next treatment step?
• After dex fails or gives partial response, what are the options?

Response Assessment After Dexamethasone 40 mg × 4 Days

Standard Response Definitions (International Working Group, 2009 - still current)

When to Check CBC and Reassess

Day 7 (tomorrow for your patient)

• First CBC post-dex - this is your early response marker
• Dexamethasone typically peaks platelet count around days 5-14
• If plt > 30,000 with no bleeding → Response achieved
• If plt still < 30,000 or active bleeding continues → early signal of non-response

Day 14

• Second CBC - confirm the response is holding
• Peak effect of the dex cycle is usually seen here
• This is where you formally classify response vs. non-response

Day 28 (1 month)

• Third CBC - critical checkpoint
• Dexamethasone response is often not sustained - up to 50-80% of adults relapse within 3-6 months
• At 1 month: assess whether response is sustained, partial, or lost

Does She Need Continued Medicine? - The 3 Scenarios

Scenario A: Good Response by Day 14 (plt > 100,000)

• Do NOT start maintenance steroids - prolonged steroids cause more harm than benefit (osteoporosis, diabetes, hypertension - especially relevant since she is already hypertensive)
• No taper needed after pulse dexamethasone (unlike prednisolone, dex pulse is not tapered)
• Monitor CBC at: 1 month → 3 months → 6 months → 12 months
• If plt stays > 30,000 and no bleeding → observe only, no medicine
• If she relapses (plt drops < 30,000 or bleeding returns) → move to second-line

Scenario B: Partial Response (plt 30,000-100,000 at Day 14)

• If asymptomatic and no bleeding → observe and monitor closely
• Repeat dexamethasone 40 mg × 4 days can be given (up to 3 cycles, 4 weeks apart) - each cycle can incrementally improve response
• Add H. pylori testing if not done - eradication alone can raise platelets in H. pylori-associated ITP
• Monitor CBC every 2 weeks until stable

Scenario C: No Response by Day 14 (plt < 30,000 or active bleeding persists)

Practical Monitoring Schedule for Mrs. Latha (Summary)

Day 7   → CBC (early response check - tomorrow)
Day 14  → CBC + classify response formally
Day 28  → CBC (is response sustained?)
Month 3 → CBC (newly diagnosed → persistent phase begins)
Month 6 → CBC
Month 12 → CBC (persistent → chronic phase if still thrombocytopenic)

• Any new bleeding (mucosal, hematuria, CNS symptoms)
• BP control (steroids + hypertension = monitor closely)
• Platelet trend (not just single value)

Key Points Specific to This Patient

1. She is 58, hypertensive - avoid prolonged steroids. Pulse dex is the right choice over daily prednisolone for this reason.
2. H. pylori - if not yet tested, test now. A positive result + eradication can resolve ITP without any further immunosuppression in 50% of H. pylori-positive ITP cases.
3. If she needs second-line - eltrombopag is the most practical first choice in India (oral, well-tolerated, does not need hospitalization). Start at 25 mg/day and titrate.
4. Newly diagnosed phase lasts until 3 months. If she still has thrombocytopenia at 3 months → reclassify as persistent ITP and reconsider second-line more seriously.
5. Target platelet count for ongoing management is NOT 100,000 - it is > 30,000 with no bleeding. Above this threshold, the risk of spontaneous serious bleeding is very low and treatment may be withheld even if platelets are not fully normal.

Situation Assessment

What to Do Right Now

Step 1 - Add IVIG (do not wait)

• IVIG 1 g/kg IV as a single infusion over 6-8 hours
• Expected platelet rise: within 24-72 hours
• This works via a different mechanism (Fc receptor blockade) than steroids - the combination is additive
• Per Rosen's: "IVIG in addition to corticosteroids should be considered for patients with platelet counts less than 10,000-20,000 mm³ or significant bleeding... use of glucocorticoids with IVIG can be associated with a more sustained response than IVIG alone"

Step 2 - Repeat CBC in 48-72 hours after IVIG

• If plt rises to > 30,000 → Response achieved, observe and monitor
• If plt does not rise even after IVIG → Confirmed steroid + IVIG non-response → escalate

Step 3 - Second Dexamethasone Cycle at Day 28

If No Response After IVIG + 2nd Dex Cycle (by Day 28-35)

Best Second-Line Choice: Eltrombopag (TPO-RA)

• Start at 25 mg/day orally (lower dose in Indian patients due to pharmacogenomic differences)
• Titrate up to 75 mg/day based on platelet response
• Takes 2-4 weeks to show full effect
• Does NOT suppress the immune system (safer than rituximab in an older hypertensive)
• Monitor LFTs monthly - can cause hepatotoxicity
• Take on empty stomach - food (especially dairy) reduces absorption by 50%
• Response rate approximately 65-80%

Rituximab (alternative if eltrombopag not available/affordable)

• 375 mg/m² IV weekly × 4 doses
• Response in ~60%, but response may not be sustained long-term
• Risk: hypogammaglobulinemia, infections, delayed immune reconstitution
• Less preferred at age 58 than TPO-RA

Splenectomy

• Most durable response (87% at 1 month per 2019 meta-analysis)
• But: hold for at least 12 months from diagnosis before considering
• Age 58 + hypertension = higher surgical/anesthetic risk
• If ever done, vaccinate for encapsulated organisms (pneumococcus, meningococcus, Haemophilus) at least 2 weeks before surgery

One Important Question to Revisit

Summary Action Plan Right Now

1. IVIG 1 g/kg IV today - do not delay further
2. Repeat CBC in 48-72 hours post-IVIG
3. H. pylori stool antigen - send today if not already done
4. If plt rises > 30,000 → monitor weekly for 4 weeks
5. If plt still < 30,000 at Day 28 → second dex cycle 40 mg × 4 days
6. If no response after 2 cycles + IVIG → start eltrombopag 25 mg/day
7. Reassess diagnosis at any point if she fails 2 second-line agents - BMB would then be warranted

Short Answer: Almost Certainly Steroid-Related, But You Must Rule Out Infection

Why Steroids Cause Leukocytosis

How to Differentiate Steroid Leukocytosis vs. Infection

The Vomiting - Steroid Cause

• High-dose dexamethasone causes GI irritation - nausea and vomiting is one of the most common side effects, especially if taken orally without food
• She is Day 6 - the 4-day dex pulse is complete, so this is likely the aftermath of the GI irritation
• Dehydration from multiple vomiting episodes compounds the picture

However - Do NOT Skip These Checks

Do Now:

1. Procalcitonin (PCT) - single most useful test here
   • If PCT < 0.25 ng/mL → bacterial infection very unlikely, steroid effect
   • If PCT > 0.5 → take infection seriously regardless of clinical picture
2. CRP - less specific but useful trend marker
3. Urine routine + microscopy + culture - she had hematuria earlier; UTI is the most likely occult infection in a 58-year-old woman on steroids
4. Blood culture × 2 - if she looks even mildly unwell or PCT elevated
5. Repeat peripheral smear - look for toxic granulation in neutrophils or left shift - if absent, strongly favors steroid effect
6. Review her dex dosing - oral or IV? With food or without?

The Platelet Rise to 20,000

Management Right Now

For the vomiting/dehydration:

• IV fluids - normal saline or Ringer's lactate to correct dehydration
• IV ondansetron 4-8 mg for nausea/vomiting
• IV pantoprazole 40 mg - gastroprotection (steroids + vomiting = GI mucosal risk)
• Hold oral medications until vomiting settles

For the leukocytosis:

• Do NOT start antibiotics empirically if no fever, no localising signs, PCT normal
• Empiric antibiotics in an ITP patient on steroids carry their own risks and may confound future cultures
• Wait for PCT and urine culture before deciding

If PCT elevated or urine culture positive:

• Start targeted antibiotic therapy
• Do not stop steroids - they are still needed for her ITP - but be aware that steroids will mask fever and slow the clinical picture of deterioration

Bottom Line

• No fever
• WBC 25,000 with neutrophilia (within expected steroid range)
• Vomiting starting post-dexamethasone course
• Platelet rise (steroids working)