Approach to bleeding disorders (platelet dysfunction): Clinical sciences

Platelet dysfunction, also known as a platelet function disorder or thrombocytopathy, involves defects in the adhesion, aggregation, or activation of platelets. Based on the underlying cause, platelet dysfunction can be either acquired or inherited. Acquired platelet dysfunction includes medication-induced platelet dysfunction, uremic platelet dysfunction, platelet dysfunction due to liver disease and myeloid neoplasms, and acquired von Willebrand disease. On the flip side, inherited platelet dysfunction includes inherited von Willebrand disease, and conditions like Bernard-Soulier syndrome and Glanzmann thrombasthenia.

Now, if your patient presents with a chief concerns suggesting a bleeding disorder, perform an ABCDE assessment to determine if the patient is unstable or stable. If unstable, stabilize their airway, breathing, and circulation. Next, obtain IV access, start IV fluids, and consider transfusion of blood products, such as packed red blood cells. Finally, put your patient on continuous vital sign monitoring, including blood pressure, heart rate, and pulse oximetry; and if needed, don’t forget to provide supplemental oxygen!

Now here’s a clinical pearl to keep in mind! Unstable patients with bleeding disorders might present with hemorrhagic shock, so you must quickly locate the source of bleeding in order to stabilize the patient! They may have neurologic changes from intracranial bleeding; hematemesis or hematochezia from gastrointestinal bleeding; or vaginal bleeding from postpartum hemorrhage. If unclear, consider obtaining a CT angiography or endoscopy, and consulting the surgery team for interventions to stop the bleeding.

Okay, let’s go back to the ABCDE assessment and take a look at stable patients and medication-induced cases. Start by obtaining a focused history and physical examination. Your patient will typically report easy bruising, and mucocutaneous bleeding, like epistaxis, gastrointestinal bleeding, or menorrhagia. They might also have a history of excessive bleeding after trauma or surgery, which typically occurs immediately following the event. Additionally, the physical exam typically reveals petechiae, purpura, and ecchymoses. With these findings, consider a bleeding disorder!

Now, once you consider a bleeding disorder, order a CBC with peripheral smear; a CMP; and a coagulation profile, including PT, aPTT, fibrinogen, and D-dimer. If the results show a normal platelet count on the CBC; normal platelets on the peripheral smear; a normal PT and aPTT, suggesting a normal coagulation cascade; and normal fibrinogen and D-dimer levels, which rules out the presence of blood clot formation, you should consider platelet dysfunction!

Okay, now that you suspect platelet dysfunction, assess for use of medications that alter platelet function. These include aspirin and other nonsteroidal anti-inflammatory drugs, or NSAIDs. These medications impair platelet aggregation by inhibiting the COX-1 enzyme, which is required to synthesize thromboxane A2, a potent platelet activator.

On the other hand, P2Y12 inhibitors, like clopidogrel, block the P2Y12 receptor on the platelet surface, eventually reducing platelet activation. If your patient uses any of these medications, diagnose medication-induced platelet dysfunction.

On the flip side, if you rule out medications as a cause, consider acquired causes of platelet dysfunction.

First, let’s focus on uremic platelet dysfunction! These patients have a history of chronic kidney disease with symptoms of uremia like nausea, anorexia, and muscle cramps. Additionally, the physical exam may reveal a pericardial friction rub. If the labs show a glomerular filtration rate of less than 15 milliliters per minute with an elevated BUN, diagnose uremic platelet dysfunction, which is associated with reduced activation of the platelet fibrinogen receptor and dysfunction of the platelet granules.