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?

a
Warfarin therapy
Warfarin affects primarily the prothrombin time (PT).
b
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.
c
Liver disease
While there may be isolated elevation of aPTT in this setting, the PT/INR is increased more commonly in patients with cirrhosis.
d
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.
e
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?

a
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).
b
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.
c
Disseminated intravascular coagulation (DIC)
The PT/INR are increased more commonly than the aPTT in patients with DIC.
d
Hemophilia B
Hemophilia B, or deficiency of factor IX in the intrinsic pathway, causes isolated elevation in aPTT. However, it is hereditary, not acquired.
e
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.

a
True
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%.
b
False