Immune thrombocytopenia: Clinical sciences

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Introduction0:00–1:00

Immune thrombocytopenia, or ITP for short, is an autoimmune condition characterized by a dysregulated immune system that produces autoantibodies against platelets.
As a result, platelets are coated by these antibodies and marked to get destroyed by macrophages in the spleen and liver.
Additionally, these autoantibodies damage megakaryocytes, preventing the bone marrow from pumping out more thrombocytes and compensating for the loss.
Now, based on the underlying cause, ITP can be classified as primary ITP, which has no identifiable trigger, or secondary ITP, which can occur as a result of medication side effects and infections, as well as immunodeficiency or autoimmune conditions.
Regardless of the type, this is a diagnosis of exclusion, meaning you should first rule out other potential causes of thrombocytopenia to diagnose ITP!Now, if your patient presents with a chief concern suggesting ITP, first, perform an ABCDE assessment to determine if they are unstable or stable.

Unstable1:00–2:31

If unstable, stabilize the airway, breathing, and circulation. Next, obtain IV access and start IV fluids.
Once other conditions are ruled out and diagnosis of ITP is confirmed, start immediate treatment with glucocorticoids, such as prednisone, which inhibit the production of anti-platelet autoantibodies.
Next, you should always give intravenous immunoglobulins, or IVIG IVIGs, which bind and inactivate antibodies already present in the circulation, thereby preventing the coating of platelets and subsequent platelet destruction by macrophages.
Finally, put your patient on continuous vital sign monitoring, including blood pressure, heart rate, and pulse oximetry, and if needed, don’t forget to transfuse blood products, such as packed red blood cells and platelets.Now here’s a clinical pearl!
Unstable patients with ITP might present with hypotension from hemorrhagic shock, so you must quickly locate the source of bleeding in order to stabilize the patient!
Some clues to look out for include neurologic changes from intracranial bleeding; hematemesis or hematochezia from GI bleeding; or vaginal bleeding from postpartum hemorrhage.
If the location of bleeding is unclear, consider further testing like CT angiography or endoscopy. Alright, now let's return to the ABCDE assessment and discuss stable patients.

Stable2:31–4:12

Start by obtaining a focused history and physical examination. Your patient will typically report easy bruising; as well as mucosal bleeding like epistaxis; menorrhagia; and gastrointestinal bleeding, such as melena, hematemesis, or hematochezia.
Additionally, history may reveal immediate excessive bleeding following a trauma or surgery. In some cases, the patient might report recent infections, immunodeficiency or autoimmune conditions, or a recent introduction of new medications or vaccines.
The physical exam will reveal a well-appearing patient with signs of bleeding, including non-palpable, flat petechiae; purpura; and ecchymoses.
In some cases, you might observe subconjunctival hemorrhages, or active bleeding like epistaxis. Now, here’s a high-yield fact!
Primary hemostasis involves platelet adhesion, activation with granule content release, and aggregation to form a platelet plug.
Defects in primary hemostasis, or platelet disorders, usually cause bleeding of skin and mucous membranes, as well as immediate bleeding after surgery.
On the other hand, secondary hemostasis involves activation of the coagulation cascade, ending with fibrin formation that forms a stable mesh over the platelet plug.
Defects in secondary hemostasis, or coagulation disorders, tend to cause bleeding deep in muscles and joints, as well as delayed bleeding after surgery!
With these findings, you should suspect primary hemostatic disorder, so your next step is to order labs, including a CBC with peripheral smear, PT, aPTT, and fibrinogen, as well as D-dimer.

ITP 4:12–5:17

In individuals with ITP, the CBC will reveal a platelet count below 100.000 platelets per microliter and the peripheral smear will show a reduced number of platelets with no other abnormalities.
And, since there’s only platelet destruction without blood clot formation, PT, aPTT, fibrinogen, and D-dimer will be normal.With these findings, you can exclude other causes of thrombocytopenia, such as disseminated intravascular coagulation and hemolytic uremic syndrome, and diagnose ITP!
Once you make the diagnosis, your next step is to determine whether or not your patient is dealing with secondary ITP, which can occur as a result of medication side effects and infections, as well as autoimmune and immunodeficiency conditions.
First, let’s focus on medication-induced ITP. This can be associated with antibiotics, anticonvulsants, quinine, glycoprotein IIb/IIIa inhibitors, NSAIDs, and even vaccines.

Medication-induced ITP5:17–5:57

If your patient recently started a medication from one of these classes, you should suspect medication-induced ITP. First, be sure to discontinue the suspected medication!
Next, wait several days and check the platelet count again. If the platelet count improves, the diagnosis is medication-induced ITP, so counsel your patient to avoid this medication class lifelong.
However, if there’s no causative medication, you can rule out medication-induced ITP. At this point, you need to evaluate your patient for other potential causes of secondary ITP, including infections, autoimmune disease, and immunodeficiency.

Additional labs5:57–6:26

Do this by ordering additional labs including HIV, HCV, and H. pylori testing; ANA, antiphospholipid antibodies, Coombs test; and immunoglobulin levels.First, let’s focus on infections.
If the HIV, HCV, or H. pylori testing comes back positive, you can diagnose secondary ITP due to infection.

Secondary ITP - Infection 6:26–6:38

Moving on to autoimmune conditions. If lab results show a positive ANA, antiphospholipid antibodies, or anemia with a positive Coombs test, diagnose secondary ITP due to an autoimmune condition.

Secondary ITP - Autoimmune condition6:38–7:31

ANA can be positive in many autoimmune disorders, such as systemic lupus erythematosus; while antiphospholipid antibodies are highly suggestive of antiphospholipid syndrome.
Finally, if your patient has anemia with a positive Coombs test, which suggests autoimmune hemolytic anemia, your patient is dealing with Evans syndrome!Now, here’s another clinical pearl!
Other autoimmune conditions associated with ITP include autoimmune thyroid disease, inflammatory bowel disease, and rheumatoid arthritis.
But keep in mind these associations are rare, so don’t screen for them unless disease-specific symptoms are present.Lastly, let’s consider immunodeficiency!
If labs reveal low immunoglobulin levels, diagnose secondary ITP due to an immunodeficiency syndrome, such as common variable immune deficiency or selective IgA deficiency.

Secondary ITP - Immunodeficiency syndrome7:31–7:53

Keep in mind that, in these individuals, history will typically reveal frequent infections.Alright, once you diagnose secondary ITP and its cause, focus on management.

Treatment7:53–9:15

First, treat the underlying cause of ITP. For example, begin treatment with antivirals or antibiotics for infection, immunomodulators for autoimmune disease, or immunoglobulins for immunodeficiency.
Next, first-line medications include glucocorticoids, which suppress antibody production. During treatment, monitor the patient’s platelet count, which will typically improve within a few days.
Once you see the improvement, slowly taper glucocorticoids over 4 to 6 weeks. In some cases, you might need to add IVIG during the initial days of treatment.If these medications fail to improve the platelet count, proceed with second-line treatment, which includes thrombopoietin-receptor agonists, like romiplostim; and immunomodulators, like rituximab.
Again, don’t forget to monitor platelets during treatment, but keep in mind these medications might take weeks to improve the platelet count!
Finally, if the second-line medications fail, consider consulting your surgery team for the third-line treatment, which is splenectomy.
Splenectomy is generally reserved for severe cases and those who have persistent bleeding or thrombocytopenia after one year of treatment.
Now, let’s go back to our lab results and take a look at individuals with normal findings. In this case, you’ve ruled out secondary causes of ITP, so you can diagnose primary ITP!

Primary ITP9:15–10:16

Again, start with the first-line treatment, which relies on glucocorticoids and possibly IVIG. If the patient’s platelets fail to improve, proceed with second-line treatment, including thrombopoietin-receptor agonists and immunomodulators.
Lastly, in severe cases, consider consulting your surgery team for a splenectomy! One last clinical pearl!
Indications for inpatient treatment of ITP include a platelet count of less than 20,000 platelets per microliter and the presence of active bleeding.
You should also admit the patient at higher platelet counts if they are presenting with factors associated with an increased risk of bleeding.
These include advanced age, chronic medical illness, or anticoagulant or antiplatelet medication use. Patients without these features can be treated as outpatients.
Alright, as a quick recap… Immune thrombocytopenia is an autoimmune condition characterized by a platelet count below 100,000 platelets per microliter and an increased risk of bleeding.

Review10:16–10:58

ITP is a diagnosis of exclusion, meaning you should first rule out other potential causes of thrombocytopenia to diagnose this condition!
Management starts with first-line medications, like glucocorticoids and possibly IVIG. If the platelet count fails to improve, proceed with the second-line medications, which include thrombopoietin-receptor agonists and immunomodulators.
Finally, in individuals who have persistent bleeding or thrombocytopenia after one year of treatment, consider splenectomy!
Immune thrombocytopenia: Clinical Sciences: Video | Osmosis