Patient Is Clotting: What Do You Mean, the aPTT Is Prolonged?

Dennis Williams, MD; Duncan C. MacIvor, MD


February 21, 2013

In This Article

Clinical Presentation

A 30-year-old woman with a history of systemic lupus erythematosus presented to the emergency department with a 24-hour history of headache and altered mental status. Her medical history included multiple episodes of deep vein thrombosis and 4 spontaneous abortions. An initial head CT showed a left posterior frontal lobe lesion. Subsequent MRI and clinical exam supported the diagnosis of an acute cerebral infarct. Initial laboratory testing was within normal limits except for a prolonged activated partial thromboplastin time (aPTT) of 51 seconds (reference range, 23-29 seconds) and thrombocytopenia (platelet count, 70,000/uL). The prothrombin time (PT) was within normal limits.

The coagulation cascade. Physiologic hemostasis is a complex interplay between proteins (procoagulants, anticoagulants, fibrinolytics) and cells (endothelial cells, platelets, red and white blood cells). Classic laboratory evaluation of hemostasis artificially divides these elements in vitro into separate reactions on the basis of the classic coagulation cascade comprising the extrinsic, intrinsic, and common pathways, as shown in the Figure.

Figure. Classic coagulation cascade.

The cascade represents a sequence of proteolytic enzyme reactions culminating in the generation of a fibrin clot. The extrinsic pathway includes only factor VII, which reacts with tissue factor to activate factor X and is measured in the lab by the PT. The intrinsic pathway includes factor XII (in a complex with prekallikrein [PK] and high-molecular-weight kininogen [HMWK]), factors XI, IX, and VIII, and is measured by the aPTT. The extrinsic and intrinsic pathways converge on the activation of factors X to Xa to commence the common pathway, which includes factors X and II (prothrombin) and fibrinogen. This common pathway affects both the PT and aPTT. Platelets do not participate in these in vitro reactions.

Clot-based in vitro coagulation tests such as the PT and aPTT are performed by mixing citrated, platelet-depleted patient plasma with calcium and reagent phospholipid. The latter substitutes for the in vivo role of the activated platelet membrane. In the PT, reagent tissue factor complexes with native factor VII to activate factor X and the common pathway. In the aPTT, the reaction begins with a negatively charged surface-activating substance (kaolin, celite or ellagic acid) which activates factor XII in the presence of PK and HMWK. In vitro only, this complex activates factor XI and the intrinsic cascade en route to the common pathway. The time to initial clot detection is the endpoint of both reactions.