How does antiphospholipid antibody syndrome (APS) cause prolonged prothrombin time (PT)?

From the Guidelines

Antiphospholipid antibody syndrome (APS) typically does not cause prolonged prothrombin time (PT), as the phospholipid concentrations in the PT reagent are much higher than those in the activated partial thromboplastin time (aPTT), thus quenching the lupus anticoagulant activity. In fact, APS is characterized by the presence of antiphospholipid antibodies that interfere with laboratory coagulation tests, but they usually cause a prolonged activated partial thromboplastin time (aPTT) rather than PT 1. When PT is prolonged in APS patients, it's generally due to other factors such as anticoagulant therapy (like warfarin) or concurrent liver disease. The confusion arises because APS antibodies, particularly lupus anticoagulant, can interfere with phospholipid-dependent coagulation assays in the laboratory. These antibodies bind to phospholipids or phospholipid-binding proteins in vitro, creating an apparent anticoagulant effect in test tubes. However, in the body, these same antibodies paradoxically increase thrombotic risk rather than causing bleeding. This discrepancy between laboratory findings and clinical presentation is a hallmark of APS. If a patient with APS shows prolonged PT without being on anticoagulants, additional investigations should be conducted to identify other causes of coagulation abnormalities.

Some key points to consider:

• The baseline PT in patients with lupus anticoagulant is rarely prolonged, as phospholipid concentrations in the PT reagent are higher than those in the APTT 1.
• The phospholipid composition and concentrations vary among commercial thromboplastins, which can affect the results 1.
• The international normalized ratio (INR) is used to standardize PT results, but its suitability for monitoring patients with APS on vitamin K antagonists has been questioned 1.
• The evidence suggests that the PT-INR is generally unaffected by lupus anticoagulant, but alternative laboratory tests may be considered in some cases 1.

In clinical practice, it is essential to consider the potential effects of APS on coagulation tests and to interpret the results in the context of the patient's clinical presentation and other laboratory findings. The most recent guidance from the ISTH-SSC LA/aPL Subcommittee emphasizes the importance of accurate detection and interpretation of antiphospholipid antibodies for the diagnosis of APS 1.

From the Research

Antiphospholipid Antibody Syndrome and Prolonged Prothrombin Time

• Antiphospholipid antibody syndrome (APS) is a thrombophilic disorder characterized by the presence of antiphospholipid antibodies, which can lead to venous or arterial thrombosis 2.
• The syndrome is associated with a range of antibodies, including lupus anticoagulant, anticardiolipin, and anti-beta(2)-glycoprotein-I antibodies 3.
• One of the mechanisms by which APS can cause prolonged prothrombin time (PT) is through the inhibition of prothrombin activation by the prothrombinase complex 4.
• Anti-phosphatidylserine/prothrombin complex antibodies (aPS/PT) have been shown to prolong phospholipid-dependent clotting time and increase the risk of thrombosis in patients with APS 5.
• The presence of aPS/PT antibodies is closely associated with the presence of lupus anticoagulant and can increase the risk of thrombosis in patients with APS 5, 6.

Mechanism of Prolonged Prothrombin Time

• The prothrombinase complex is responsible for the conversion of prothrombin to thrombin, and inhibition of this complex can lead to prolonged PT 4.
• Anti-phospholipid antibodies can bind to phospholipids and prevent the formation of the prothrombinase complex, leading to inhibition of prothrombin activation 4.
• aPS/PT antibodies can also bind to prothrombin and prevent its activation, leading to prolonged PT 5, 6.

Clinical Implications

• Prolonged PT is a common finding in patients with APS, and can be used as a diagnostic criterion for the syndrome 2, 5.
• The presence of aPS/PT antibodies can increase the risk of thrombosis in patients with APS, and may be used as a prognostic marker for thrombotic events 5, 6.
• Further research is needed to fully understand the mechanisms by which APS causes prolonged PT, and to develop effective treatments for patients with this syndrome 2, 6.