What is the workup and treatment for thrombocytopenia (low platelet count)?

From the Guidelines

The workup and treatment of thrombocytopenia begins with identifying the underlying cause through a comprehensive evaluation including complete blood count, peripheral blood smear, and assessment of medication history, with the goal of addressing the underlying cause while managing bleeding risk through appropriate platelet count maintenance 1.

Initial Management

Initial management depends on platelet count severity and bleeding risk. For immune thrombocytopenia (ITP), first-line treatment includes corticosteroids such as prednisone 1 mg/kg/day for 2-4 weeks with subsequent taper, or dexamethasone 40 mg daily for 4 days 1.

• Intravenous immunoglobulin (IVIG) at 1 g/kg for 1-2 days may be used for rapid platelet increase in emergency situations 1.
• Second-line options include thrombopoietin receptor agonists like eltrombopag (starting at 50 mg daily) or romiplostim (1 μg/kg weekly subcutaneously), rituximab (375 mg/m² weekly for 4 weeks), or splenectomy 1.

Specific Etiologies

• For drug-induced thrombocytopenia, discontinuation of the offending agent is essential.
• Heparin-induced thrombocytopenia requires immediate cessation of all heparin products and initiation of alternative anticoagulation such as argatroban (initial infusion 2 μg/kg/min) or bivalirudin.
• Thrombotic thrombocytopenic purpura necessitates urgent plasma exchange and corticosteroids.

Platelet Transfusions

• Platelet transfusions are generally reserved for active bleeding with counts below 50,000/μL or for procedures when counts are below 50,000-100,000/μL, but should be avoided in TTP and HIT unless life-threatening bleeding occurs 1.

Treatment Approach

The treatment approach must be tailored to the specific etiology, with the goal of addressing the underlying cause while managing bleeding risk through appropriate platelet count maintenance. Second-line or maintenance therapy in persistent or chronic ITP aims to establish a durable platelet response and to minimize bleeding events with a treatment that is safe, tolerable, and convenient for long-term management 1.

From the FDA Drug Label

Nplate is indicated for the treatment of thrombocytopenia in: Adult patients with immune thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy Pediatric patients 1 year of age and older with ITP for at least 6 months who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. Use the lowest dose of Nplate to achieve and maintain a platelet count ≥ 50 × 10^9/L as necessary to reduce the risk for bleeding. Nplate should be used only in patients with ITP whose degree of thrombocytopenia and clinical condition increases the risk for bleeding. Nplate should not be used in an attempt to normalize platelet counts

The workup and treatment of thrombocytopenia involves using Nplate (romiplostim) in patients with immune thrombocytopenia (ITP) who have had an insufficient response to other treatments such as corticosteroids, immunoglobulins, or splenectomy. The goal of treatment is to achieve and maintain a platelet count ≥ 50 × 10^9/L to reduce the risk of bleeding.

• Key considerations:
  • Use the lowest effective dose of Nplate.
  • Monitor platelet counts weekly during the dose adjustment phase and monthly after a stable dose is achieved.
  • Adjust the dose based on platelet count response.
  • Avoid situations or medications that may increase the risk of bleeding.
  • Nplate is not indicated for myelodysplastic syndrome (MDS) or other causes of thrombocytopenia besides ITP 2 2.

From the Research

Evaluation of Thrombocytopenia

• Thrombocytopenia is a platelet count of less than 150 × 10^3 per μL and can occur from decreased platelet production, increased destruction, splenic sequestration, or dilution or clumping 3
• Examination of the blood film is essential in the investigation of any patient with thrombocytopenia, and the context in which thrombocytopenia occurred, its severity, timing, and association with bleeding are important clues to the diagnosis 4
• Patients with a platelet count greater than 50 × 10^3 per μL are generally asymptomatic, while patients with platelet counts between 20 and 50 × 10^3 per μL may have mild skin manifestations such as petechiae, purpura, or ecchymosis 3

Treatment of Thrombocytopenia

• Transfusion of platelets is recommended when patients have active hemorrhage or when platelet counts are less than 10 × 10^3 per μL, in addition to treatment (when possible) of underlying causative conditions 3, 5
• Patients with platelet counts of less than 50 × 10^3 per μL should adhere to activity restrictions to avoid trauma-associated bleeding 3
• Thrombopoietin receptor agonists (TPO-RAs; romiplostim or eltrombopag), rituximab, or splenectomy may be used as subsequent treatment for adult immune thrombocytopenia (ITP) 6

Management of Specific Conditions

• Heparin-induced thrombocytopenia requires alternative anticoagulation at a therapeutic dose 5
• Immune thrombocytopenia requires immunomodulatory treatment 5
• Sepsis and trauma are the most common causes of thrombocytopenia in the ICU, and treatment of the underlying disease will also increase platelet counts 5

Platelet Transfusions

• Platelet transfusions are indicated in patients with impaired platelet production or increased platelet destruction, but could be deleterious in patients with increased intravascular platelet activation 5
• The evidence for a benefit of prophylactic platelet transfusions is weak and controversial 5
• If the platelet count does not increase after transfusion of 2 fresh ABO blood group-identical platelet concentrates, ongoing platelet consumption and high-titer anti-HLA class I antibodies should be considered 5