What is the most likely cause of thrombocytopenia in a 76‑year‑old woman with a platelet count of 82 ×10⁹/L (down from 201 ×10⁹/L) and an elevated mean platelet volume of 12.7 fL?

Differential Diagnosis of New-Onset Thrombocytopenia with Elevated MPV

The most likely cause of this patient's thrombocytopenia (platelet count 82 × 10⁹/L with elevated MPV 12.7 fL) is peripheral platelet destruction, most commonly immune thrombocytopenia (ITP) or drug-induced thrombocytopenia, given the isolated thrombocytopenia with compensatory increase in platelet size.

Understanding the Elevated MPV

The elevated mean platelet volume (MPV) of 12.7 fL is the critical diagnostic clue in this case:

• An MPV ≥8.8 fL indicates over-destructive (hyperdestructive) thrombocytopenia with 77% sensitivity and 89% specificity, distinguishing it from bone marrow production failure 1
• High MPV reflects increased thrombopoiesis with release of young, larger platelets in response to peripheral destruction 2, 1
• When MPV is inappropriately low for the platelet count, causes include sepsis, splenomegaly, aplastic anemia, chronic renal failure, or myelosuppressive drugs 2

Most Likely Diagnostic Categories

Primary Immune Thrombocytopenia (ITP)

ITP is the most common cause of isolated thrombocytopenia in adults without systemic illness, presenting with elevated MPV due to compensatory platelet production 3:

• Patients with isolated thrombocytopenia in the absence of systemic illness most likely have immune thrombocytopenia or drug-induced thrombocytopenia 3
• The elevated MPV (12.7 fL) strongly supports a hyperdestructive process rather than marrow failure 1, 4
• At age 76, secondary causes must be excluded before diagnosing primary ITP 5

Drug-Induced Thrombocytopenia

Medication review is essential, as drug-induced thrombocytopenia is extremely common in elderly patients:

• Common culprits include antiplatelet agents (aspirin, clopidogrel), anticoagulants (heparin, warfarin, DOACs), antibiotics, anticonvulsants, and NSAIDs 5, 3
• Heparin-induced thrombocytopenia (HIT) should be suspected if heparin exposure occurred within 5-10 days and platelets dropped ≥50% from baseline or fell below 100 × 10⁹/L 5

Secondary Causes Requiring Exclusion

Essential screening tests to identify secondary causes 5:

• HIV and Hepatitis C serology (common viral causes of immune-mediated thrombocytopenia) 5
• Antiphospholipid antibody panel (lupus anticoagulant, anticardiolipin, anti-β2-glycoprotein I) 5
• Thyroid function tests and quantitative immunoglobulins 5
• Peripheral blood smear review to exclude pseudothrombocytopenia, schistocytes, or abnormal cells 5, 3

Diagnostic Algorithm

Step 1: Confirm True Thrombocytopenia

• Exclude pseudothrombocytopenia by repeating platelet count in heparin or sodium citrate tube, as EDTA-induced clumping causes false low counts in ~0.1% of adults 5, 3
• Review peripheral smear directly for platelet clumping, giant platelets, schistocytes, or leukocyte abnormalities 5

Step 2: Categorize by MPV

• MPV ≥8.8 fL → Hyperdestructive thrombocytopenia (sensitivity 77%, specificity 89%) 1
• MPV <7.9-8.8 fL → Hypoproductive thrombocytopenia (marrow failure, myelosuppression) 4
• This patient's MPV of 12.7 fL definitively places her in the hyperdestructive category 1, 4

Step 3: Distinguish Acute vs. Chronic

• Obtain previous platelet counts to determine if this represents acute (new) or chronic thrombocytopenia 3
• The drop from 201 to 82 × 10⁹/L suggests a relatively acute process requiring urgent evaluation 3

Step 4: Emergency vs. Non-Emergency Causes

Emergency causes requiring immediate hospitalization 3:

• Heparin-induced thrombocytopenia (HIT)
• Thrombotic microangiopathies (TTP, HUS)
• HELLP syndrome (if pregnant)
• Active significant bleeding

Non-emergency causes (this patient likely falls here) 3:

• Drug-induced thrombocytopenia
• Immune thrombocytopenia (ITP)
• Chronic liver disease

Management Approach for This Patient

Immediate Assessment

At platelet count 82 × 10⁹/L without bleeding, observation is appropriate 5:

• The American Society of Hematology strongly recommends against treatment for asymptomatic patients with platelets ≥30 × 10⁹/L 5
• No activity restrictions are necessary at counts >50 × 10⁹/L 5
• Full therapeutic anticoagulation can be safely administered at counts ≥50 × 10⁹/L 5

When to Treat

Treatment would be indicated if 5:

• Platelet count drops below 30 × 10⁹/L
• Development of mucocutaneous bleeding (petechiae, purpura, mucosal bleeding)
• Need for invasive procedures
• Concurrent anticoagulation requirement
• Additional bleeding risk factors (age >60 years is one) 5

Outpatient vs. Inpatient Management

Outpatient management is appropriate for this patient 6:

• Platelet count >20 × 10⁹/L with no bleeding allows outpatient care 6
• Hematology follow-up within 24-72 hours is essential 6
• Patient education about warning signs (significant bleeding, fever, rapid platelet decline) is crucial 6

Hospital admission would be warranted if 6:

• Platelet count drops below 20 × 10⁹/L
• Significant mucosal bleeding develops
• Rapid decline in platelet count
• Uncertainty about diagnosis or social concerns 6

Critical Pitfalls to Avoid

• Do not assume ITP without excluding secondary causes (medications, HIV, hepatitis C, antiphospholipid syndrome) 5
• Do not initiate corticosteroids based solely on platelet count without evidence of bleeding or high-risk features 5
• Do not normalize platelet counts as a treatment goal; target is ≥50 × 10⁹/L to reduce bleeding risk 5
• Do not overlook medication review, especially in elderly patients on multiple drugs 5, 3
• Do not assume normal PT/aPTT rules out all bleeding disorders if clinical suspicion persists 5

Specific Causes by MPV Pattern

High MPV (>8.8-10 fL) with thrombocytopenia 2, 1:

• Immune thrombocytopenia (ITP)
• Drug-induced thrombocytopenia
• Post-transfusion purpura
• Sepsis with DIC (early phase)

High MPV with normal platelet count 2:

• Heterozygous thalassemia (12 of 15 patients in one study)
• Iron deficiency (3 of 15 patients)

High MPV with thrombocytosis 2:

• Myeloproliferative disorders
• Inflammation
• Post-splenectomy state
• Iron deficiency

In this 76-year-old woman, the combination of declining platelet count (from 201 to 82 × 10⁹/L) with markedly elevated MPV (12.7 fL) most strongly suggests peripheral platelet destruction, with drug-induced thrombocytopenia and ITP being the leading considerations after excluding pseudothrombocytopenia and secondary causes.