Time out

Before going any further, let’s take stock of what we know. You are being asked to see a patient with ischemic stroke and an elevated aPTT.

aPTT, activated partial thromboplastin time

What are causes of acquired elevation in the activated partial thromboplastin time (aPTT) with normal prothrombin time?

Warfarin therapy
Warfarin affects primarily the prothrombin time (PT).
Heparin therapy
Although heparin leads to inhibition of multiple clotting factors in the intrinsic, extrinsic and common pathways, it has a preferential effect on the aPTT.
Liver disease
While there may be isolated elevation of aPTT in this setting, the PT/INR is increased more commonly in patients with cirrhosis.
Lupus anticoagulant
Although lupus anticoagulants interfere with phospholipid-dependent clotting reactions in the intrinsic, extrinsic and common pathways, they have a preferential effect on the aPTT.
Acquired factor VIII deficiency
Also known as acquired hemophilia A.

You are doing well! Let’s keep going. What are additional causes of acquired elevation of aPTT with normal prothrombin time?

von Willebrand disease (VWD)
VWD may elevated the aPTT through reduction in factor VIII levels (von Willebrand factor binds and stabilizes factor VIII in the circulation). However, it is a hereditary condition, not acquired (a rare acquired form of VWD is called acquired von Willebrand syndrome).
Factor V (FV) deficiency
FV is part of the common pathway, so a deficiency in the protein causes elevation in both the PT and aPTT.
Disseminated intravascular coagulation (DIC)
The PT/INR are increased more commonly than the aPTT in patients with DIC.
Hemophilia B
Hemophilia B, or deficiency of factor IX in the intrinsic pathway, causes isolated elevation in aPTT. However, it is hereditary, not acquired.
AL amyloidosis
Typically associated with acquired deficiency of factor X, which results in elevated PT and aPTT.

An elevated aPTT is often indicative of a bleeding diathesis. Why did this patient develop a clot, and not a hemorrhage?

True or false: Lupus anticoagulant, heparin induced thrombocytopenia (HIT), disseminated intravascular coagulation (DIC), and liver disease – all causes of an elevated aPTT + thrombosis, are also associated with thrombocytopenia.

Thrombocytopenia is typical for HIT, DIC, and cirrhosis. Although not part of the diagnostic criteria for antiphospholipid antibody syndrome (it is considered a non-criteria hematological feature), thrombocytopenia as a manifestation of the primary antiphospholipid syndrome has been reported with a prevalence between 30% and 46%.