Approach to bleeding disorders (coagulopathy): Clinical sciences

Coagulopathy refers to dysfunction in any step of the coagulation cascade, resulting in impaired blood clot formation. The most important coagulopathies include medication-induced coagulopathy, an acquired factor inhibitor, hemophilia A, hemophilia B, severe von Willebrand disease, chronic liver disease, and vitamin K deficiency.

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, fresh frozen plasma, or cryoprecipitate. 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 look at stable patients, and start with a focused history and physical exam. Your patient is likely to report easy bruising possibly in combination with a history of deep soft tissue bleeding, such as muscle hematomas and joint hemarthrosis. They might also have a history of excessive bleeding after trauma or surgery, which is typically delayed hours to days after the event; as well as a family history of abnormal bleeding. Additionally, the physical exam typically reveals ecchymoses and hematomas; and you may even find evidence of current bleeding. With these history and physical findings, consider a bleeding disorder.

Once you consider a bleeding disorder, order a CBC with peripheral smear, CMP, and a coagulation profile, including PT, aPTT, fibrinogen, and D-dimer. The CBC typically reveals normal platelet count, meaning there’s no consumption of platelets and the patient’s bone marrow is unaffected. Next, the peripheral smear shows normal red blood cells with no schistocytes, which rules out the presence of microangiopathic hemolytic anemias, such as disseminated intravascular coagulation! Moreover, normal fibrinogen and D-dimer levels confirm the absence of blood clot formation! However, prolonged PT, aPTT, or both, are highly suggestive of coagulopathy, so be sure to rule out medications associated with coagulopathy!

For example, heparins, like unfractionated heparin and low molecular weight heparin, bind to antithrombin, enhancing its inactivation of coagulation factors. Next, warfarin, which is a vitamin K antagonist, inhibits the production and activation of factors II, VII, IX, and X in the liver. Other important anticoagulant medications include factor Xa inhibitors like rivaroxaban and direct thrombin inhibitors like argatroban. If these medications are present, diagnose medication-induced coagulopathy!

Now, once you rule out medications as a cause of coagulopathy, your next step is to perform a one-to-one mixing study. In this diagnostic procedure, you are mixing the patient's abnormal plasma with normal donor plasma. Once mixed, order a PT and aPTT, and check to see if clotting times improve!

If the clotting times don’t improve, diagnose coagulopathy due to an acquired factor inhibitor! In this case, autoantibodies present in your patient’s blood are directed against the clotting factors in both the patient’s and the donor’s plasma, inhibiting their activity. As a result, either the PT or aPTT will remain prolonged. Acquired factor inhibitors are associated with certain medications, like antibiotics and immunomodulatory drugs; with several underlying conditions, including malignancies, autoimmune diseases like rheumatoid arthritis and lupus; and with pregnancy and the postpartum period..

On the flip side, if either the PT or aPTT improve after the mixing study, your patient is presenting with a factor deficiency! In this case, the presence of normal factors in the donor plasma are able to overcome the factor or factors that are deficient in your patient’s plasma. To further investigate which factor or factors are deficient in your patient’s plasma, start by assessing which of the coagulation tests is prolonged.

First up, let’s consider a normal PT with a prolonged aPTT, which indicates a problem with the intrinsic coagulation pathway. The intrinsic pathway is called intrinsic because all the factors needed to activate it are found within the blood. It’s initiated when factor XII binds to collagen at the site of an injury. The other factors involved in this pathway are XI, IX, and VIII. On the flip side, the extrinsic pathway is activated when tissue factor, or factor III, which is found outside the blood, binds to factor VII. Both pathways lead to the final common pathway, starting with the activation of factor X, and also involving factors V, II, and I.