Isolated Prolongation of Activated Partial Thromboplastin Time: Not Just Bleeding Risk!

Abstract

Activated partial thromboplastin time (aPTT) is a fundamental screening test for coagulation disturbances. An increased aPTT ratio is quite common in clinical practice. How the detection of prolonged activated aPTT with a normal prothrombin time is interpreted is therefore very important. In daily practice, the detection of this abnormality often leads to delayed surgery and emotional stress for patients and their families and may be associated with increased costs due to re-testing and coagulation factor assessment. An isolated, prolonged aPTT is seen in (a) patients with congenital or acquired deficiencies of specific coagulation factors, (b) patients receiving treatment with anticoagulants, mainly heparin, and (c) individuals/patients with circulating anticoagulants. We summarize here what may cause an isolated prolonged aPTT and evaluate the preanalytical interferences. The identification of the cause of an isolated prolonged aPTT is of the utmost importance in ensuring the correct diagnostic workup and therapeutic choices.

Keywords: activated partial thromboplastin time (aPTT); bleeding patient; circulating anticoagulants; coagulation factor defect; intrinsic pathway; mixing test.

Figure 1

Sequence of events that occur during secondary hemostasis and the role of screening tests [1]. The intrinsic pathway is initiated when blood comes into contact with negatively charged surfaces, such as collagen exposed in the damaged vessel wall, activating Factor XII. Factor XIIa activates Factor XI to its active form, Factor XIa. Factor XIa, along with its cofactor, Factor VIII, activates Factor IX to Factor IXa. Factor IXa, in the presence of Factor VIII and calcium ions, activates Factor X to Factor Xa. The extrinsic pathway is initiated via the release of tissue factor from damaged tissues outside the blood vessels. Tissue factor forms a complex with Factor VII, leading to the activation of Factor VII to its active form, Factor VIIa. Factor VIIa, along with tissue factor, activates Factor X to Factor Xa. Both the intrinsic and extrinsic pathways converge at Factor Xa, which is a key enzyme in the coagulation cascade. Factor Xa combines with Factor V and calcium ions to form the prothrombinase complex, which converts prothrombin (Factor II) into thrombin (Factor IIa).Thrombin plays a central role in the coagulation cascade, converting fibrinogen into fibrin. The two common screening tests, prothrombin time (PT) and activated partial thromboplastin time (aPTT), help assess the clotting ability of the blood and detect any abnormalities or deficiencies in the clotting factors. Prothrombin time measures the extrinsic pathway of the coagulation cascade. It assesses the time taken for the formation of a clot after the addition of tissue factor to plasma and primarily evaluates the function of factors I, II, V, VII, and X. Activated partial thromboplastin time (aPTT) measures the intrinsic pathway of the coagulation cascade. It evaluates the time taken for the formation of a clot after the addition of an activator to plasma and primarily assesses the function of factors I, II, V, VIII, IX, X, XI, and XII.