What is the initial workup and treatment for a patient presenting with thrombocytopenia (low platelet count)?

Thrombocytopenia Workup

Initial Diagnostic Approach

The diagnosis of thrombocytopenia is based primarily on history, physical examination, complete blood count (CBC), and peripheral blood smear examination to exclude other causes 1, 2.

First Step: Confirm True Thrombocytopenia

• Exclude pseudothrombocytopenia by collecting blood in a tube containing heparin or sodium citrate and repeating the platelet count 3
• This eliminates laboratory artifact from platelet clumping with EDTA anticoagulant 3

Essential Initial Laboratory Tests

• Complete blood count with differential 1
• Peripheral blood smear examination - look for platelet clumping, abnormal platelet size/morphology, schistocytes (suggesting thrombotic microangiopathy), or abnormalities in other cell lines 1, 2
• HIV and HCV testing (grade 1B recommendation) 1, 2
• Prothrombin time (PT) and activated partial thromboplastin time (aPTT) 1

When Additional Testing is Needed

• Bone marrow examination is NOT necessary for patients presenting with typical isolated thrombocytopenia, regardless of age (grade 2C) 1, 2
• Further investigations are indicated only if there are abnormalities beyond thrombocytopenia in the blood count or smear (such as anemia, leukopenia, or atypical cells) (grade 2C) 1, 2

Critical History Elements

• Bleeding symptoms: unexplained/extensive bruising, epistaxis, menorrhagia, bleeding with procedures or dental extractions 1
• Medication review: identify drugs that interfere with platelet function or cause thrombocytopenia 1, 3
• Timing: distinguish acute versus chronic thrombocytopenia by reviewing previous platelet counts 3
• Associated symptoms: fever, jaundice, neurologic changes (suggesting thrombotic thrombocytopenic purpura), pregnancy status 1, 3
• Risk factors: recent infections, HIV/HCV risk factors, alcohol use, family history 1, 4

Physical Examination Focus

• Bleeding manifestations: petechiae, purpura, ecchymosis, mucosal bleeding 1, 3
• Lymphadenopathy and hepatosplenomegaly (suggesting lymphoproliferative disorder or chronic liver disease) 1, 4
• Syndromic features: hearing loss, cardiac abnormalities, facial/bone dysmorphisms (suggesting inherited platelet disorders) 1

Secondary ITP Screening

• H. pylori screening should be considered in patients where eradication therapy would be used if positive (grade 2C) 1, 2
• Liver function tests if hepatic disease suspected 1
• Pregnancy test in women of childbearing age 1

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Treatment Approach

When to Treat

Treatment thresholds are based on platelet count AND bleeding symptoms, not platelet count alone:

• Platelet count <10,000/μL: Treatment indicated regardless of bleeding 1, 2
• Platelet count 10,000-30,000/μL with significant mucous membrane bleeding: Treatment indicated 1, 2
• Platelet count <30,000/μL in newly diagnosed ITP: Treatment suggested (grade 2C) 1
• Platelet count >30,000/μL without bleeding: Treatment generally not required 1

Hospitalization Criteria

For newly diagnosed ITP with platelet count <20,000/μL: Hospital admission is suggested to confirm diagnosis, establish care, determine platelet trend, and assess bleeding risk (conditional recommendation) 1

For established ITP with platelet count <20,000/μL: Outpatient management is suggested if patient has established hematology care and no significant bleeding (conditional recommendation) 1

For platelet count ≥20,000/μL: Outpatient management is suggested for asymptomatic patients or those with minor mucocutaneous bleeding (conditional recommendation) 1

Mandatory hospitalization for:

• Platelet count <20,000/μL with significant mucous membrane bleeding 1, 2
• Severe, life-threatening bleeding at any platelet count 1
• Suspected thrombotic microangiopathy, heparin-induced thrombocytopenia, or HELLP syndrome 3, 5

First-Line Treatment for ITP

Corticosteroids are preferred as initial therapy (grade 2B) 1, 2:

• Longer courses of corticosteroids (>6 weeks including taper) are NOT recommended; use short courses (≤6 weeks) instead (strong recommendation) 1
• Monitor closely for hypertension, hyperglycemia, mood disturbances, gastric irritation, glaucoma, myopathy, and osteoporosis 1

Intravenous immunoglobulin (IVIG):

• Use with corticosteroids when rapid platelet increase is required (grade 2B) 1, 2
• Dose: 1 g/kg as single dose, may repeat if necessary (grade 2B) 1, 2
• Use as first-line if corticosteroids contraindicated (grade 2C) 1

Anti-D immunoglobulin:

• Use in Rh-positive, non-splenectomized patients if corticosteroids contraindicated (grade 2C) 1, 2

Management of Life-Threatening Bleeding

Administer all three simultaneously 1, 2:

• High-dose parenteral corticosteroids 1, 2
• IVIG 1, 2
• Platelet transfusions 1, 2

Second-Line Treatment (After Corticosteroid Failure)

Splenectomy is recommended for patients who have failed corticosteroid therapy (grade 1B) 1

• Should be delayed at least 12 months unless severe disease unresponsive to other measures (grade 2C) 1
• Laparoscopic and open approaches offer similar efficacy (grade 1C) 1

Thrombopoietin receptor agonists (e.g., romiplostim):

• Recommended for patients at bleeding risk who relapse after splenectomy or have contraindication to splenectomy and failed at least one other therapy (grade 1B) 1
• May be considered after failing one line of therapy (corticosteroids or IVIG) without splenectomy (grade 2C) 1
• Romiplostim dosing: Start 1 mcg/kg subcutaneously weekly, adjust by 1 mcg/kg increments to achieve platelet count ≥50,000/μL, maximum 10 mcg/kg weekly 6

Rituximab:

• May be considered for patients at bleeding risk who have failed one line of therapy (grade 2C) 1

Secondary ITP Management

HIV-associated ITP:

• Treat HIV infection with antiretroviral therapy first unless clinically significant bleeding (grade 1A) 1
• If ITP treatment needed: corticosteroids, IVIG, or anti-D (grade 2C) 1

HCV-associated ITP:

• Consider antiviral therapy in absence of contraindications (grade 2C) 1, 2
• If ITP treatment needed: IVIG is preferred initial treatment (grade 2C) 1, 2

H. pylori-associated ITP:

• Administer eradication therapy for confirmed infection (grade 1B) 1, 2

Platelet Transfusion Guidelines

Prophylactic transfusion thresholds:

• Consider if platelet count <10,000-20,000/μL in stable patients 5
• Consider if platelet count <50,000/μL before invasive procedures 3, 5
• Do NOT transfuse prophylactically in ITP or thrombotic thrombocytopenic purpura 5

Therapeutic transfusion:

• Active hemorrhage at any platelet count 3
• Life-threatening bleeding 1, 2

Special Populations

Pregnancy:

• Platelet count >50,000/μL: No routine treatment 1, 2
• Platelet count <10,000/μL: Treatment required 1
• Treatment options: Corticosteroids or IVIG (grade 1C) 1, 2
• Mode of delivery based on obstetric indications, not maternal platelet count (grade 2C) 1

Common Pitfalls

• Do not withhold antithrombotic therapy based solely on thrombocytopenia - certain conditions (antiphospholipid syndrome, heparin-induced thrombocytopenia) cause both bleeding and thrombosis 7, 3
• Do not attempt to normalize platelet counts - treat to achieve safe hemostatic level (≥50,000/μL) to reduce bleeding risk 6
• Do not use prolonged corticosteroid courses - increases toxicity without additional benefit 1
• Ensure follow-up with hematologist within 24-72 hours of diagnosis for outpatients 1