In 1961 Proctor and Rapaport improved the design of the PTT by adding particulate substances (kaolin) in order to activate massively the contact factors (this is where the APTT name comes from) of the coagulation cascade and to shorten the coagulation time. The PTT was essentially a modification of the re-calcification time by removing platelets from plasma and by adding negatively charged phospholipids to speed up coagulation. , who needed a test to assess the progress in the purification of factor VIII concentrates to be used for hemophiliacs. The APTT (formerly known as PTT) was designed in the 1950s by Langdell et al. The test also evolved from the original manual-visual clot detection technique to the more sophisticated coagulometers. The PT evolved rapidly (upon the introduction of VKA treatment) with new thromboplastins derived from animal tissues (mostly brain) and recombinant preparations. The name “prothrombin time” is a misnomer as it implies that the PT is sensitive to factor II (prothrombin), which was probably one the few coagulation factors known at that time. The PT was designed by Armand Quick in 1935, who needed a simple test to investigate patients with jaundice. Schematic representation of the coagulation cascade highlighting the factors to which PT and APTT are responsive.Ī comprehensive history of the development of the two tests is beyond the scope of this article, and can be found elsewhere. However, and at variance with widespread opinion, the APTT may be variably prolonged, depending on the brand of LMWH used. Low molecular weight heparin (LMWH) does not influence the PT. This addition is required for assessing the therapeutic international normalized ratio (INR) during co-administration of vitamin K antagonists (VKA) and UFH in the treatment of acute venous thromboembolism (VTE). The APTT is also sensitive to the presence of unfractionated heparin (UFH), whereas the PT not substantially influenced by the presence of this drug in plasma due to the fact that commercial thromboplastins are added with exogenous heparin inhibitors. Furthermore, the PT and APTT are variably sensitive to the presence of circulating anticoagulants directed against specific coagulation factors or against negatively charged phospholipids in complex with proteins, such as the lupus anticoagulants (LAC). Importantly, none of the two is sensitive to factor XIII deficiency ( Figure 1). In brief, they are both sensitive to factor X, V, II and fibrinogen, whereas the PT is only sensitive to factor VII deficiency and the APTT is sensitive to pre-kallikrein, high molecular weight kininogen (HMWK), factor XII, XI, IX and VIII deficiencies. They can hence be considered as global coagulation tests sensitive to deficiencies of many coagulation factors. They are defined as the time (seconds) needed to clot platelet-poor plasma upon addition of coagulation triggers, such as tissue factor in complex with phospholipids and calcium chloride (in the PT), or negatively charged phospholipids-activators and calcium chloride (in the APTT). The prothrombin time (PT) and the activated partial thromboplastin time (APTT) are the most requested tests to investigate patients with congenital or acquired coagulopathies and drug monitoring.

In this opinion paper we review the current state-of-the-art for result reporting and attempt to give practical guidance on how PT and APTT should be reported in different clinical conditions for which the tests are requested. The APTT has been historically reported as clotting time or as ratio (patient-to-normal clotting time).

Unfortunately, this limitation has been frequently overlooked, and the INR has been (and is currently) used as a universal system of results harmonization. Therefore, there are some theoretical and evidence-based considerations that make the INR formally invalid when the test is used to analyze patients in other clinical settings. The INR scale has been devised to harmonize results stemming from different thromboplastins from patients on treatment with vitamin K antagonists. PT results have been reported as clotting time, percentage activity, PT-ratio (patient-to-normal clotting time) and as international normalized ratio (INR). Varied result reporting have been introduced over the years for the two tests, thus making their interpretation rather confusing in different clinical settings. Prothrombin time (PT) and activated partial thromboplastin time (APTT) are the most widely used tests to investigate coagulation abnormalities.

Inr normal range meaning