Which medications are used to increase platelet count in thrombocytopenia?

Medications That Increase Platelet Counts

Thrombopoietin receptor agonists (romiplostim and eltrombopag) are the primary platelet-increasing medications for immune thrombocytopenia, with response rates of 60-88% and 70-80% respectively, while corticosteroids and intravenous immunoglobulin remain first-line agents for acute management. 1, 2

First-Line Agents for Immune Thrombocytopenia (ITP)

Corticosteroids

• Prednisone 1 mg/kg orally daily for 21 days followed by taper is the preferred first-line treatment for adults with ITP requiring therapy, yielding longer duration of response compared to short-course regimens. 2
• Dexamethasone 40 mg orally daily for 4 days produces a faster but less durable response and serves as an alternative to prednisone. 2
• Initial response rates are 70-80%, with 15-20% of patients achieving durable complete remission. 3, 1
• Common adverse effects include osteoporosis, skin thinning, hypertension, GI ulcers, avascular necrosis, immunosuppression, and psychosis. 3

Intravenous Immunoglobulin (IVIg)

• Dosing is 0.8-1 g/kg as a single infusion (or 0.4 g/kg/day for 5 days), indicated when rapid platelet elevation is required for active bleeding or urgent procedures. 1, 2
• Response occurs rapidly, with many patients responding within 24 hours, typically achieving peak response in 2-4 days. 3
• Up to 80% of patients respond initially, though responses are usually transient, returning to baseline in 2-4 weeks. 3
• Headaches are the most common adverse effect (often moderate to severe); rare serious toxicities include renal failure, thrombosis, and aseptic meningitis. 3

Anti-D Immunoglobulin

• Dosing is 50-75 μg/kg intravenously, with response rates similar to IVIg (dose-dependent). 3
• Only appropriate for Rh-positive, non-splenectomized patients; contraindicated if hemoglobin is already reduced or autoimmune hemolysis is present. 2
• Mild hemolytic anemia is expected and dose-limiting; rare but serious cases of intravascular hemolysis, DIC, and renal failure have been reported. 3

Thrombopoietin Receptor Agonists (TPO-RAs)

Romiplostim

• Administered subcutaneously at 1-10 mcg/kg weekly, with 60-88% of patients responding and platelet counts typically rising within 1-2 weeks. 1, 4
• Peak platelet counts occur over a 2-3 week period after dosing, with median time to peak concentration of 14 hours and half-life of 3.5 days (range 1-34 days). 4
• Strongly recommended for patients at bleeding risk who relapse after splenectomy or have contraindications to splenectomy and have failed at least one other therapy. 2
• May be considered before splenectomy in patients at bleeding risk who have failed one line of therapy. 2

Eltrombopag

• Dosed orally at 25-75 mg daily for ITP, with response rates of 70-80% in clinical trials. 1, 5
• In the RAISE study, 60% of patients achieved sustained platelet response (≥50 × 10⁹/L for 6 out of last 8 weeks) compared to 10% with placebo. 5
• Mandatory monitoring of liver function tests is required, as 13% of patients develop abnormalities. 1
• Increases in platelet counts are typically detected within 1 week, with maximum response after 2 weeks. 5

Second-Line Immunomodulatory Agents

Rituximab

• Response rates of approximately 60% in ITP patients, with 40% achieving complete response. 1
• Responses generally occur after 1-2 weeks to 6-8 weeks of treatment. 1
• May be considered for patients at bleeding risk who have failed corticosteroids, IVIg, or splenectomy, though evidence is weaker than for TPO-RAs. 2

Mycophenolate Mofetil (MMF)

• Dosing is 250-1000 mg twice daily, progressively increased over 3 weeks. 1
• Platelet increase occurs in 39% of patients with refractory ITP. 1

Dapsone

• Dosing is 75-100 mg/day orally, with moderate corticosteroid-sparing effects. 1
• Mandatory G6PD screening is required in at-risk males before initiation to prevent hemolytic anemia. 1

Older Immunosuppressive Agents

Cyclophosphamide

• Increases platelet counts in 60-80% of patients, with 20-40% maintaining normal counts for 2-3 years after discontinuation. 3
• Serious adverse effects include alopecia, teratogenicity, infertility, hemorrhagic cystitis, and increased risk of myelodysplasia/acute leukemia. 3

Vinca Alkaloids

• Produce transient platelet increases lasting 1-3 weeks in two-thirds of patients, but sustained response (<3 months without treatment) occurs in less than 10%. 3
• Potential adverse effects include neutropenia, fever, thrombophlebitis, and neuropathy. 3

Danazol

• Variable response rates ranging from 10-80% across case series. 3
• Adverse effects include weight gain, headaches, alopecia, amenorrhea, and liver dysfunction (41% with abnormal LFTs). 3

Specialized Indications

Thrombocytopenia in Chronic Liver Disease

• Avatrombopag and lusutrombopag are FDA-approved TPO-RAs for thrombocytopenia in chronic liver disease patients scheduled for procedures, requiring 2-8 day course completion before the procedure. 1
• Lusutrombopag achieved platelet counts >50 × 10⁹/L in 3.6 times more patients than placebo, with significant reduction in platelet transfusions (71% placebo vs 35% lusutrombopag). 3
• Avatrombopag met primary endpoints with significant reduction in platelet transfusion needs (RR 2.46 for high-dose, 2.36 for low-dose). 3

Critical Pitfalls to Avoid

• Do not base treatment decisions solely on platelet count—bleeding severity, risk factors (hypertension, advanced age, anticoagulation need), and quality of life must guide therapy. 2, 6
• Do not use anti-D in Rh-negative patients, splenectomized individuals, or those with anemia from bleeding or autoimmune hemolysis. 2
• Do not perform routine bone marrow examination in typical ITP cases—diagnosis is clinical exclusion. 2
• Periodic assessment for bone marrow reticulin formation is recommended with TPO-RAs, though routine monitoring protocols are not established. 1
• Observation without treatment is appropriate for patients with platelet counts >30 × 10⁹/L without bleeding symptoms, regardless of absolute count. 2