Approach to bleeding disorders (thrombocytopenia): Clinical sciences

Thrombocytopenia is defined as a platelet count of less than 150,000 cells per microliter. Mild thrombocytopenia is often asymptomatic, while platelet counts less than 50,000 are frequently associated with bleeding.

Based on the underlying cause, thrombocytopenia can be associated with thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, disseminated intravascular coagulation, and bone marrow abnormalities; as well as liver disease, heparin-induced thrombocytopenia, and immune thrombocytopenia.

Now, if your patient presents with a chief concern 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, give IV fluids, and consider transfusion of blood products, such as packed red blood cells and platelets. Finally, put your patient on continuous vital sign monitoring and, if needed, 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. Start by obtaining a focused history and physical examination. Your patient will typically report easy bruising; as well as 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. The physical exam usually 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, CMP, and a coagulation profile, including PT, aPTT, fibrinogen, and D-dimer.

If the platelet count is less than 150,000 and the peripheral smear shows true thrombocytopenia without platelet clumping, diagnose thrombocytopenia!

Now, once you diagnose thrombocytopenia, assess the CBC and peripheral smear. If the CBC shows thrombocytopenia in combination with anemia, and the peripheral smear reveals fragmented red blood cells, known as schistocytes, diagnose microangiopathic hemolytic anemia, or MAHA.

This group of disorders is characterized by an uncontrolled formation of thrombi in small blood vessels that consume platelets, leading to thrombocytopenia. At the same time, they create turbulence and shearing forces that destroy passing red blood cells, leading to anemia!

Now, MAHA is seen in several different conditions, including thrombotic microangiopathy, or TMA for short; and disseminated intravascular coagulation, or DIC for short. To differentiate between these conditions, assess the patient’s coagulation profile!

If the coagulation profile is normal, diagnose TMA and assess the underlying cause. First, let’s focus on thrombotic thrombocytopenic purpura, or simply TTP, which typically occurs in adults and is characterized by fever and possibly neurological symptoms, like headaches and seizures.

Labs often reveal elevated creatinine levels, which suggests renal failure. With these findings, consider TTP, and order an ADAMTS13 activity level and check for ADAMTS13 inhibitors. If the ADAMTS13 activity is less than 10 percent, and ADAMTS13 autoantibody inhibitors are detected, diagnose TTP!

In a normal condition, ADAMTS13, which is an enzyme, breaks down von Willebrand factor or vWF. However, a deficiency of ADAMTS13 activity level results in excess von Willebrand factor and uncontrolled platelet activation and consumption!

Let’s take a look at hemolytic uremic syndrome or HUS. On the flip side, HUS, is typically seen in children and young adults. These patients might report fever, recent abdominal pain, and bloody diarrhea. History may also reveal recent travel, particularly to areas with a potential for foodborne illnesses; while dietary history may include consumption of undercooked meat. Labs often reveal elevated creatinine levels.

At this point, consider HUS and order additional labs, including stool cultures, a Shiga toxin test, and complement testing.

If you identify complement factor autoantibodies or a complement gene mutation, diagnose atypical HUS.

On the other hand, if the stool culture is positive for E. coli or Shigella, or if the Shiga toxin test is positive, diagnose Shiga toxin-associated HUS.

Now that we’ve covered TMA, let’s go back and take a look at DIC! Your patient is likely to report an acute onset of bleeding, which is typically associated with a triggering event like sepsis, trauma, malignancy, or obstetric complications, such as placental abruption.

The physical exam might reveal signs of organ dysfunction, like respiratory distress, jaundice, or decreased urine output.

Finally, keep in mind that in DIC, the massive formation of blood clots depletes thrombocytes and clotting factors, so labs will typically reveal a prolonged PT and aPTT.

And since fibrinogen is converted into fibrin during blood clot formation, fibrinogen levels might be low. However, since fibrinogen is also an acute phase reactant, fibrinogen levels could be elevated despite the ongoing blood clot formation.