Treatment for Thrombocytopenia
When Treatment is Indicated
Treatment is rarely indicated in patients with platelet counts above 50 × 10⁹/L unless they have active bleeding, require surgery, have comorbidities predisposing to bleeding, need anticoagulation therapy, or have professions/lifestyles predisposing to trauma 1. For patients with no bleeding or only mild skin manifestations (bruising and petechiae), observation alone is recommended regardless of platelet count 1.
Treatment thresholds vary by clinical context:
- Platelet counts 20-30 × 10⁹/L or higher: Do not routinely require treatment in asymptomatic patients 1
- Platelet counts <20 × 10⁹/L: Consider treatment, especially with mucous membrane bleeding 1
- Platelet counts <10 × 10⁹/L: High risk of serious bleeding; treatment typically indicated 1, 2
First-Line Treatment for Immune Thrombocytopenia (ITP)
Corticosteroids (Standard Initial Therapy)
Prednisone is the standard initial first-line therapy, given at 0.5-2 mg/kg/day until platelet count increases to 30-50 × 10⁹/L, which may require several days to several weeks 1. To avoid corticosteroid-related complications, prednisone should be rapidly tapered and stopped in responders, and especially in non-responders after 4 weeks 1.
Dexamethasone 40 mg/day for 4 days offers an alternative with high initial response rates (50-86%) and substantial sustained responses 1. One study showed 4 cycles of dexamethasone (40 mg/day for 4 days) given every 14 days produced an 86% response rate with 74% having responses lasting a median of 8 months 1.
Intravenous Immunoglobulin (IVIg)
For pediatric patients requiring treatment, a single dose of IVIg (0.8-1 g/kg) or a short course of corticosteroids should be used as first-line treatment 1. IVIg should be used if a more rapid increase in platelet count is desired 1.
For adults, IVIg at 1 g/kg (1-2 infusions over 2 days) produces platelet increases within 24 hours, faster than corticosteroids 1. Initial response rates are comparable to corticosteroids but with shorter time to response 1. Rare but serious toxicities include renal failure and thrombosis 1.
Anti-D Immunoglobulin
A single dose of anti-D can be used as first-line treatment in Rh-positive, non-splenectomized patients 1. Anti-D therapy is not advised in children with decreased hemoglobin due to bleeding or with evidence of autoimmune hemolysis 1.
Emergency Treatment for Life-Threatening Bleeding
For patients with uncontrolled bleeding or active CNS, GI, or genitourinary bleeding, combine prednisone and IVIg for emergency treatment 1. High-dose methylprednisolone may also be useful in this setting 1. Other rapidly acting therapies include platelet transfusion (possibly in combination with IVIg) and emergency splenectomy 1.
Platelet transfusions are recommended when patients have active hemorrhage or platelet counts <10 × 10⁹/L 2.
Second-Line Treatment Options
Thrombopoietin Receptor Agonists (TPO-RAs)
TPO-RAs are not immunosuppressive, have undergone rigorous randomized controlled studies, and demonstrate high efficacy 1, 3.
Romiplostim (Nplate): Initial dose is 1 mcg/kg subcutaneously weekly, adjusted by 1 mcg/kg increments until platelet count ≥50 × 10⁹/L is achieved, with a maximum dose of 10 mcg/kg 4. Most adult patients achieve and maintain platelet counts ≥50 × 10⁹/L with a median dose of 2-3 mcg/kg 4.
Eltrombopag: Platelet responses (>50 × 10⁹/L) achieved in 70-81% of patients receiving 50-75 mg doses, with response by day 15 in over 80% of patients 1.
Rituximab
Rituximab (375 mg/m² weekly × 4) produces responses in 60% of patients with complete response in 40%, typically within 1-8 weeks 1. It should be considered for patients with significant ongoing bleeding despite treatment with IVIg, anti-D, or conventional corticosteroids 1. Rituximab may also be considered as an alternative to splenectomy in chronic ITP 1.
Splenectomy
Splenectomy is recommended for patients with chronic or persistent ITP who have significant or persistent bleeding, lack of responsiveness or intolerance to other therapies, and/or need for improved quality of life 1. Splenectomy should be delayed for at least 12 months unless accompanied by severe disease 1.
Splenectomy has high initial response rates (85%) but up to 30% of responders relapse within 10 years 3. Patients require prophylactic polyvalent pneumococcal, meningococcal C conjugate, and H. influenzae b vaccines at least 4 weeks before (preferably) or 2 weeks after splenectomy 1.
Other Second-Line Options
Multiple immunosuppressive agents are available with varying response rates 1:
- Azathioprine (1-2 mg/kg): Response in up to two-thirds of patients, but slow onset (3-6 months) 1
- Cyclosporin A (5 mg/kg/day for 6 days then 2.5-3 mg/kg/day): 50-80% response rate in 3-4 weeks 1
- Mycophenolate mofetil (1000 mg twice daily): Up to 75% response rate in 4-6 weeks 1
- Danazol (200 mg 2-4 times daily): 67% response rate but requires 3-6 months 1
- Dapsone (75-100 mg): Response in up to 50% of patients within 3 weeks 1
Special Populations
Pregnancy
Pregnant women with platelet counts >50 × 10⁹/L do not routinely require treatment 1. Treatment is required for women with platelet counts <10 × 10⁹/L, and for those with counts 10-30 × 10⁹/L in their second or third trimester who are bleeding 1.
Corticosteroids and IVIg are the first-line treatments for maternal ITP 1. Prednisone at low dose (10-20 mg/day) is given initially and adjusted to the minimum dose producing a hemostatically effective platelet count 1. A maternal platelet count of >50 × 10⁹/L is considered sufficient to prevent complications from excessive maternal bleeding at vaginal delivery or cesarean section 1.
For epidural or spinal anesthesia, obstetric anesthetists generally recommend a platelet count of at least 75 × 10⁹/L, though hematologists believe 50 × 10⁹/L is adequate for cesarean section 1.
Pediatric Patients
Children with no bleeding or mild bleeding should be managed with observation alone regardless of platelet count 1. For pediatric patients requiring treatment, a single dose of IVIg (0.8-1 g/kg) or a short course of corticosteroids should be used as first-line treatment 1.
High-dose dexamethasone may be considered for children with significant ongoing bleeding despite initial treatment or as an alternative to splenectomy 1.
Newborns (of Mothers with ITP)
The neonatal platelet count should be measured for 3-4 days after birth 1. Brain imaging should be performed if the platelet count at birth is <20 × 10⁹/L, or if the count is 20-50 × 10⁹/L even without neurologic abnormalities 1.
Treatment with IVIg is appropriate if the infant's platelet count is <20 × 10⁹/L without evidence of intracranial hemorrhage 1. Newborns with counts >50 × 10⁹/L should not be treated with IVIg or glucocorticoids 1.
Common Pitfalls and Caveats
Pseudothrombocytopenia must be ruled out first by examining the peripheral blood smear or collecting blood in tubes containing heparin or sodium citrate 3, 2. This is caused by platelet clumping due to EDTA and can lead to unnecessary treatment.
Bone marrow examination is unnecessary in children and adolescents with typical features of ITP 1. It is also not necessary before initiating corticosteroids or IVIg therapy 1.
Do not use Nplate (romiplostim) in patients with myelodysplastic syndrome (MDS) as it may accelerate progression to acute myelogenous leukemia 4. Nplate should not be used to normalize platelet counts, only to achieve counts ≥50 × 10⁹/L to reduce bleeding risk 4.
Avoid long-term corticosteroid use due to significant adverse effects including hypertension, hyperglycemia, osteoporosis, excessive weight gain, and psychosis 1, 3.
Thrombocytopenia does not protect against thrombosis - antithrombotic therapy should not be withheld because of thrombocytopenia alone 5. Some conditions like heparin-induced thrombocytopenia and antiphospholipid syndrome can cause both bleeding and thrombosis 2.