Episode 155: Immune Thrombocytopenic Purpura Series, Pt 1- First Line Management
This week, we go back to Classical Hematology! We previously discussed the initial workup and management of ITP in Episode 009, but now it’s time to dig deeper. What do we do once we make the diagnosis? How do we approach management when we have a new diagnosis?
What is the initial workup for a patient with newly diagnosed thrombocytopenia?
Refer to Episode 9 for our approach to thrombocytopenia work-up.
As a refresher:
Our approach to a differential diagnosis for thrombocytopenia - analogous to the “pre”, “intra”, and “post” renal approach to AKI
Pre: Infections/Meds/Toxins
1st: HIV, Hepatitis
2nd: EBV, CMV, Histoplasmosis
Intra: Primary bone marrow failure
Post: Destruction/consumption/splenomegaly/cirrhosis
DIC
ITP
TTP
Platelet clumping
Work-up:
Repeat CBC, peripheral smear, citrated platelet count (rule out platelet clumping), coags (PT/PTT/INR), fibrinogen, HIV serology, Hep B/C serologies, +/- haptoglobin (low in liver disease)
When do we start invoking the diagnosis of ITP?
ITP is likely in patients presenting with acute thrombocytopenia, often with an isolated platelet count <20 (remaining cell lines unaffected)
Formal definition: Platelet count <100 without any identifiable causes
Clinical Presentation
Many are asymptomatic
Mucosal bleeding, petechiae, easy bruising
Bimodal Age Distribution
20-30’s with slight female predominance
60+ with equal predominance
ITP is believed to be an autoimmune condition, but the overall mechanism is not well characterized
Antibody-coated platelets are destroyed by the liver and/or spleen
Antibodies can also induce complement activation, desialylation, and megakaryocyte destruction
Other pathways may not be well characterized
Up to 50% of patients will not have platelet-directed antibodies in circulation
How do we classify ITP?
Newly diagnosed ITP: ITP duration of <3 mo
Persistent ITP: ITP duration of 3-12 mo
Chronic ITP: ITP duration of >12 mo
Remission: Platelet count >100 × 109/L at 12 mo
What are the response criteria (especially important when reviewing literature about ITP)?
Corticosteroid-dependent: Ongoing need for continuous prednisone >5 mg/d (or corticosteroid equivalent) or frequent courses of corticosteroids to maintain a platelet count ≥30 × 109/L and/or to avoid bleeding
Durable response: Platelet count ≥30 × 109/L and at least doubling of the baseline count at 6 mo
Early response: Platelet count ≥30 × 109/L and at least doubling baseline at 1 wk
Initial response: Platelet count ≥30 × 109/L and at least doubling baseline at 1 mo
When do we consider treatment and/or hospital admission for ITP?
In patients with a platelet count >30 and no evidence of bleeding, outpatient observation with close monitoring (and labs) is okay
Consider age, risk factors, high risk medications (anticoagulation, antiplatelets)
In patients with a platelet count between 20 and 30, consider outpatient treatment (usually with steroids)
In patients with a platelet count <20, inpatient treatment is recommended
Case-by-case decisions can be made for patients with chronic ITP
Treatment is aimed at:
Reducing bleeding risk (highest risk with platelets <30 or <50 for those with other risk factors - angiodysplasia, spontaneous intracranial bleeding, frequent falls, anticoagulation)
Achieving remission
Improving quality of life (severe fatigue associated with low platelets)
How do we approach inpatient management for our patient?
The backbone of treatment is corticosteroids. We should see efficacy within 1-2 weeks
Dexamethasone 40mg X 4 days (PO equivalent to IV)
(Alternative) Prednisone 0.5-2mg/kg/day X1-2 weeks, followed by a taper
Blood (2016): Time to response was shorter in the HD-DXM arm compared to conventional prednisone
Total steroid course (including taper) should not continue beyond 6 weeks due to adverse steroid side effects
60-80% of patients will respond to corticosteroids; however a sustained response after steroid discontinuation will be seen in 30-50% of patients
In many cases, we add IVIg 1g/kg X 2 days, especially in patients with platelets <10.
IVIG has an onset of action of 1-4 days. The effects are transient, lasting only 1-4 weeks in 80% of patients
Make sure to check hepatitis B serologies before treating with IVIg - IVIg can make patients look like they are HepB positive which has implications for future therapy (e.g. rituximab)
Platelet transfusions do not generally work (can consider in nuanced situations, life-threatening bleeds)
Although not for clinical use - there are ongoing conversations about the use of rituximab in addition to corticosteroids in the first line setting (conditional recommendation based on low certainty in the evidence). See the draft guidelines from ASH, see here.
When is it safe to discharge our patient from the hospital?
No one size fits all, need to consider comorbid conditions, further bleeding, medications (e.g. anticoagulation)
Patients will require frequent lab checks after discharge
ASH guidelines recommend a platelet count of reliably >20,000 and at least double from their baseline
The goal is technically to maintain a platelet count >30,000 in patients with newly diagnosed ITP
To summarize:
Consider ITP in patients presenting with isolated thrombocytopenia, after ruling out other causes of thrombocytopenia
If you are suspicious for ITP, the frontline management is corticosteroids +/- IVIg in patients with bleeding or severely low platelet counts (<10)
Monitoring for treatment response: aim for a platelet count >20,000, ideally greater than 30,000
Following discharge, patients require close laboratory monitoring as some patients will require additional therapies
Consider secondary ITP in patients not responding to initial therapy
The crew behind the magic:
Show outline: Ronak Mistry
Production and hosts: Vivek Patel, Dan Hausrath, Ronak Mistry
Editing: Resonate Recordings
Shownotes: Karam Elsolh
Graphics, social media management: Ronak Mistry
