Immune thrombocytopenia: Clinical sciences

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.

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. 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. 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. 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.