What causes thrombocytopenia (low platelet count) in a 59-year-old female?

Thrombocytopenia in a 59-Year-Old Female: Differential Diagnosis and Evaluation

A platelet count of 100,000/mm³ in a 59-year-old female requires systematic evaluation to distinguish between decreased production, increased destruction, sequestration, or dilutional causes, with the most common etiologies in this age group being drug-induced thrombocytopenia, immune thrombocytopenia (ITP), and underlying systemic conditions. 1

Initial Diagnostic Approach

Confirm True Thrombocytopenia

• Exclude pseudothrombocytopenia first by examining the peripheral blood smear for platelet clumping and repeating the platelet count in a tube containing heparin or sodium citrate 2, 1
• Pseudothrombocytopenia occurs in approximately 0.1% of adults due to EDTA-dependent platelet agglutinins 3

Determine Acuity

• Obtain or review previous platelet counts to distinguish acute from chronic thrombocytopenia 1
• Acute thrombocytopenia (new onset) suggests drug-induced causes, infection, or heparin-induced thrombocytopenia (HIT) 3
• Chronic thrombocytopenia suggests ITP, liver disease, or bone marrow disorders 4

Key Historical and Physical Examination Elements

Critical History Points

• Medication review: Specifically assess for heparin exposure (within past 3 months), antibiotics (especially ceftriaxone), quinidine/quinine, sulfonamides, antiplatelet agents, and chemotherapy 3, 2, 5
• Bleeding symptoms: Type and severity of bleeding (petechiae, purpura, mucosal bleeding, menorrhagia) 3
• Recent infections: Viral illnesses, HIV risk factors, hepatitis 3
• Alcohol use and liver disease symptoms: Jaundice, ascites 3
• Autoimmune symptoms: Arthralgias, rash, photosensitivity suggesting lupus or antiphospholipid syndrome 3, 6
• Thrombotic events: Deep vein thrombosis, pulmonary embolism, stroke (suggests HIT, antiphospholipid syndrome, or thrombotic microangiopathy) 3, 6

Physical Examination Priorities

• Splenomegaly: Presence argues against ITP (found in <3% of ITP patients) and suggests liver disease, lymphoproliferative disorder, or sequestration 3
• Hepatomegaly and stigmata of liver disease: Jaundice, spider angiomas, palmar erythema 3
• Lymphadenopathy: Suggests lymphoproliferative disorder 3
• Bleeding manifestations: Petechiae, purpura, ecchymoses, retinal hemorrhages 3

Common Causes by Category

Drug-Induced Thrombocytopenia

• Heparin-induced thrombocytopenia (HIT): Occurs 5-14 days after heparin initiation (or earlier if recent exposure within 3 months), with platelet count typically 30-70,000/mm³ and >50% decrease from baseline 3, 5
• If HIT suspected, calculate 4T score and discontinue heparin immediately if platelet count falls below 100,000/mm³ 3, 5
• Ceftriaxone: Requires specialized drug-dependent platelet antibody testing during acute episode or within 3 weeks 2
• Other common culprits: Quinidine, sulfonamides, antiplatelet agents 3

Immune Thrombocytopenia (ITP)

• Most likely diagnosis in isolated thrombocytopenia without systemic illness, splenomegaly, or abnormal blood smear 3
• Diagnosis of exclusion after ruling out other causes 3
• More common in women; bleeding risk increases with age >60 years 3
• At platelet count of 100,000/mm³, treatment is generally not indicated unless bleeding symptoms present or invasive procedures planned 3

Liver Disease and Splenic Sequestration

• Chronic liver disease causes thrombocytopenia through multiple mechanisms: decreased thrombopoietin production, splenic sequestration, and direct marrow suppression 3
• Look for other signs of liver dysfunction and portal hypertension 3

Pregnancy-Related (if applicable)

• Gestational thrombocytopenia: Most common cause during pregnancy (75% of cases), typically platelet count >70,000/mm³, occurs late gestation, resolves postpartum 3
• HELLP syndrome: Hemolysis, elevated liver enzymes, low platelets with hypertension/preeclampsia 3

Thrombosis with Thrombocytopenia Syndromes

• Antiphospholipid syndrome: Thrombosis with thrombocytopenia, requires specific antibody testing 3, 6
• Thrombotic microangiopathies: TTP, HUS with schistocytes on smear, hemolysis, renal dysfunction 3, 6
• Disseminated intravascular coagulation: Abnormal coagulation studies, elevated D-dimer 3, 6

Essential Laboratory Evaluation

Initial Testing

• Complete blood count with differential: Assess for isolated thrombocytopenia vs. pancytopenia 3
• Peripheral blood smear: Examine for schistocytes (TMA), platelet clumping (pseudothrombocytopenia), abnormal white cells (leukemia), large platelets (ITP) 3, 2
• Coagulation studies (PT/INR, aPTT): Normal in ITP, abnormal in DIC or liver disease 3
• Liver function tests: AST, ALT, bilirubin, albumin 3
• HIV testing: If risk factors present 3

Additional Testing Based on Clinical Context

• Drug-dependent antibody testing: If ceftriaxone or other drug-induced thrombocytopenia suspected, must be collected during acute episode 2
• HIT antibody testing: If 4T score intermediate or high probability 3
• Antiphospholipid antibodies: If thrombosis present 6
• Bone marrow examination: Generally not required for ITP diagnosis unless atypical features present (age >60, abnormal blood counts beyond thrombocytopenia, splenomegaly, failure to respond to treatment) 3

Clinical Significance of Platelet Count 100,000/mm³

• Bleeding risk is minimal at this level in the absence of other hemostatic defects 3
• No increased risk of complications with neuraxial procedures at counts >100,000/mm³ 3
• Treatment generally not indicated for ITP at this level unless bleeding symptoms, planned invasive procedures, or high-risk activities 3
• Activity restrictions not required at counts >50,000/mm³ 1

Common Pitfalls to Avoid

• Failing to exclude pseudothrombocytopenia before extensive workup 2, 1
• Missing HIT diagnosis in patients with recent heparin exposure, which can occur up to several weeks after discontinuation and carries high thrombotic risk 3, 5
• Assuming ITP without excluding other causes, particularly in patients >60 years with new-onset thrombocytopenia 3
• Overlooking medication history, especially recent antibiotic use (ceftriaxone) or heparin exposure 2, 5
• Not recognizing thrombosis with thrombocytopenia syndromes that require urgent specific treatment (HIT, TTP, antiphospholipid syndrome) 6