Treatment

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How would you treat this patient?

a
Rituximab
Not recommended as first-line treatment for newly diagnosed immune thrombocytopenia (ITP).
b
Thrombopoietin receptor agonist
Not recommended as first-line treatment for for newly diagnosed immune thrombocytopenia (ITP).
c
Corticosteroids
Recommended first-line treatment for newly diagnosed immune thrombocytopenia (ITP).
d
Platelet transfusion
Platelet transfusions may result in transient increase in platelet count (for a few hours), but should be reserved for the patient with immune thrombocytopenia (ITP) who is actively bleeding and should be administered with Intravenous immune globulin (IVIG), which may increase the lifespan of donor platelets.
e
Intravenous immune globulin (IVIG)

IVIG raises the platelet count within 1 to 4 days in 80% of patients, but effects last only 1 to 2 weeks. IVIG is indicated in patients with active serious bleeding and in those with very low platelet counts (<10 x 109/L), who are at increased risk for serious bleeding.

Glucocorticoid treatment is the standard initial therapy for patients with ITP

What are the recommended steroid regimens for newly diagnosed ITP?

a
Dexamethasone 40 mg daily x 4 days
Correct. This regimen can be repeated up to three times if poor initial response.
b
Dexamethasone 100 mg x 1 dose
c
Prednisone 1 mg/kg PO daily
Starting dose can be between 0.5–2 mg/kg daily to a maximum of 80 mg daily.
d
Prednisone 5 mg PO daily

Is there anything to choose between prednisone 1 mg/kg and the 4-day dexamethasone regimen?

According to the 2019 ASH guideline, you might consider dexamethasone over prednisone if rapid initial platelet response is important. This recommendation is based on the results of a randomized trial comparing prednisone and dexamethasone showing shorter time to response in the dexamethasone arm. In a metanalysis of randomized trials comparing these two steroid regimens, platelet counts were higher at 14 days in patients receiving dexamethasone, but overall responses at 6 months did not differ significantly. Prednisone is associated with higher rates of weight gain and cushingoid appearance, whereas dexamethasone may be associated with higher rates of neuropsychiatric symptoms.

Randomized study of high dose dexamethasone (HD-DXM) vs. prednisone (PDN) for treatment of adult ITP. The incidence of sustained response (SR) and sustained complete response (CR) showed no significant difference between the 2 arms.

The following is a comparison between prednisone 1 mg/kg and the 4-day dexamethasone in treating newly diagnosed adult ITP:

ParameterPrednisoneDexamethasone
Initial response rate60%-80%60-80%
Time to initial response4-14 days2-14 days
Time to peak response7-28 days4-28 days
Sustained response30%-50%30%-50%

How do corticosteroids work in ITP?

a
Decrease platelet clearance
Correct. Steroids are thought to inhibit Fc receptor-mediated clearance of platelets by phagocytic cells.
b
Increase platelet production
Correct
c
Promote integrity of blood vessel wall
This is a platelet-count-independent effect of corticosteroids which may reduce bleeding complications.
d
Reduce antibody production
Correct

In addition to corticosteroids, intravenous immune globulin (IVIG) is considered a first-line therapy. However, the response, while quick, is typically transient and does not lead to sustained responses. IVIG is typically reserved for patients:

  • Who are bleeding or at high risk of bleeding (as an adjunctive treatment).
  • Who are unresponsive to prednisone.
  • Who have contraindications to high-dose corticosteroids.

Let’s look at a comparison in responses with the various first line therapies in immune thrombocytopenia (ITP):

Initial response rateTime to initial responseTime to peak response
Prednisone60-80%4-14 days7-28 days
Dexamethasone60-80%2-14 days4-28 days
IVIG80%1-4 days2-7 days
IVIG, intravenous immune globulin

What if my patient was having a major gastrointestinal (GI) bleed?

a
In addition to steroids, I would consider intravenous immunoglobin (IVIG) but not platelet transfusion
The addition of IVIG to the steroid regiment is a reasonable approach if the bleeding is not life-threatening. Otherwise, the addition of platelet transfusion (next answer) is preferred.
b
In addition to steroids and IVIG, I would consider a platelet transfusion
There are no randomized trials related to treatment of active bleeding in a patient with newly diagnosed ITP, but this three-pronged approach is supported by small observational studies.
c
In addition to steroids, I would consider thrombopoietin receptor agonist
Thrombopoietin receptor agonists take several days to take effect, so they would not be helpful in the setting of an acute bleed. However, as noted on the next slide, clinical practice guidelines recommend initiating a thrombopoietin receptor agonist if the patient with life-threatening bleeding does not response to IVIG and platelet transfusion.
d
I would discontinue all anticoagulant and antiplatelet agents
Correct, though this may be challenging if the patient is taking anticoagulants for a recently diagnosed venous thromboembolism or antiplatelet agents for a coronary stent.

To summarize, treatment for a major bleed includes a combination of corticosteroids, immune globulin (IVIG) and platelet transfusions. For more information click here.

Fortunately, our patient did not have a major bleed.

He was administered dexamethasone 40 mg daily for 4 days. His platelet count was 36 x 109/L on day 4, at which time he was discharged home (most responsive patients will demonstrate improved platelet counts 2-4 days after initiation of corticosteroids, but response may take 5 to 7 days or longer in some patients).

What is the goal of treatment?

a
Normalize platelet count
b
Maintain platelet count > 100 x 10^9/L
c
Maintain platelet count > 30 x 10^9/L

Maintain target platelet count > 20-30 × 109/L to reduce risk of major bleeding.

Spontaneous bleeding is uncommon at platelet counts >30 × 109/L

Platelet count thresholds to consider in a patient with ITP. A normal platelet count is 150-450 x 109/L. ITP, by definition, requires a platelet count < 100 x 109/L. Patients with ITP whose platelet counts fall below 30 x 109/L are typically started on treatment. Risk for bleeding increases once the platelet count < 10 x 109/L. So, as you can see, natural selection has endowed us with a generous cushion in the platelet count!

What if the patient was taking an anticoagulant for a recent deep venous thrombosis or atrial fibrillation? Do the treatment goals change?

a
Yes

Yes, patient should ideally receive treatment to maintain platelet counts above 50 x 109/L.

b
No

Platelet count threshold for treatment in a patient with ITP who is on an anticoagulant such as warfarin or DOAC is typically adjusted upward to < 50 x 109/L.

What is the likelihood this patient will relapse in the next 6 months?

a
10%
b
20%
c
30%
d
40%
e
50%
Immune thrombocytopenia (ITP) is a chronic, relapsing disease. Relapse reported in 50% within 6 months of treatment with corticosteroids and additional 25% beyond 1 year. Chronic ITP develops in up to 70% of adults with this condition.
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