Approach to bleeding disorders (platelet dysfunction): Clinical sciences

Chapters:

Watch video only

Introduction0:00–0:42

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.

Unstable Patient0:42–1:50

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.

Stable Patient1:50–2:29

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.

Labs2:29–3:00

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!

Medication-induced platelet dysfunction3:00–3:42

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.

Acquired Causes of Platelet Dysfunction3:42–3:48

Uremic platelet dysfunction3:48–4:20

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.

Liver disease4:20–5:27

Now, let’s move on to platelet dysfunction due to liver disease. In this case, your patient will have a history of chronic liver disease, like fibrosis or cirrhosis; and their physical exam will reveal signs of portal hypertension, like splenomegaly, hepatomegaly, and ascites.
If labs show elevated AST, ALT, and bilirubin levels, diagnose platelet dysfunction due to chronic liver disease! Platelet function is impaired with liver disease because they tend to produce inadequate levels of thromboxane A2 and express abnormal cell surface glycoproteins receptors!
Now, here’s a high-yield fact! In addition to abnormal platelet function, chronic liver disease increases bleeding risk by other mechanisms.
First, the liver is not making enough thrombopoietin, which leads to decreased platelet production by the bone marrow. In addition, an enlarged spleen sequesters more platelets than usual, which further reduces the number of circulating platelets.
Finally, damaged hepatocytes are not producing enough clotting factors. Finally, let’s take a look at acquired platelet dysfunction due to a myeloid neoplasm!

Myeloid Neoplasm5:27–6:13

Your patient may report a history of fever, night sweats, fatigue, and weight loss. Next, the CBC will usually reveal high cell counts, which could include red blood cells, white blood cells, and even platelets; while the peripheral smear may reveal dysplastic or neoplastic cells.
These findings are suggestive of acquired platelet dysfunction due to a myeloid neoplasm! Myeloid neoplasms include myelodysplastic syndromes, myeloproliferative neoplasms, and leukemias.
These disorders are associated with changes in platelet membrane glycoproteins and receptors, which alter their function and eventually result in bleeding!

Labs - Normal6:13–7:00

Okay, now that you have ruled out chronic conditions that can cause acquired platelet dysfunction, you should consider von Willebrand disease.
Next, order additional labs, including a von Willebrand factor level, von Willebrand factor activity, and factor VIII activity.
Here’s a clinical pearl! Von Willebrand factor is a protein that bridges platelets and exposed endothelium, facilitating platelet adhesion.
It also acts as a transport protein for factor VIII in the circulation, protecting factor VIII from inactivation. Deficiency or dysfunction of von Willebrand factor leads to inadequate platelet adhesion, and in more severe cases, factor VIII activity is also decreased leading to a slightly prolonged aPTT.

Von Willebrand Disease7:00–7:52

If the von Willebrand factor level or activity are low, regardless of factor VIII activity, diagnose von Willebrand disease and assess the underlying cause.
Acquired von Willebrand disease can occur in malignancy or myeloproliferative conditions; autoimmune conditions; and shear stress in the circulatory system, like from severe aortic stenosis or a left ventricular assist device.
Additionally, this condition can be also associated with hypothyroidism or certain medications, like valproic acid and ciprofloxacin.
If you identify an underlying cause, diagnose acquired von Willebrand disease! However, if your patient does not have an underlying condition associated with acquired von Willebrand Disease, diagnose inherited von Willebrand Disease, which is often associated with a family history of bleeding.

Inherited Platelet Function Disorder7:52–8:32

On the flip side, if von Willebrand factor level, von Willebrand activity, and factor VIII activity are normal, consider an inherited platelet function disorder!
Next, order platelet function testing, such as platelet aggregometry or platelet flow cytometry. If platelet function testing is abnormal, this confirms the diagnosis of an inherited platelet function disorder.
Some examples include Bernard-Soulier syndrome, a genetic defect in platelet adhesion; Glanzmann thrombasthenia, a genetic defect in platelet aggregation, and Chediak-Higashi syndrome, a genetic defect in platelet granule release.

Review8:32–9:09

Alright, as a quick recap… Platelet function disorders involve defects in platelet adhesion, activation, or aggregation.
If you suspect platelet dysfunction, first, rule out medication-induced platelet dysfunction. Next consider acquired causes of platelet dysfunction, including uremia, liver disease, and myeloid neoplasms.
If none of these are present, order additional testing for von Willebrand disease, which can be either acquired or inherited.
Finally, if von Willebrand disease testing is normal, order platelet function testing to confirm the diagnosis of