Which coagulation time does Antiphospholipid Syndrome (APS) primarily elongate?

Antiphospholipid Syndrome Primarily Elongates the Activated Partial Thromboplastin Time (aPTT)

Antiphospholipid Syndrome (APS) primarily elongates the activated partial thromboplastin time (aPTT) due to the binding of lupus anticoagulant to the phospholipid component of the test, which inhibits the formation of the prothrombinase complex. 1

Mechanism of aPTT Prolongation in APS

The prolongation of aPTT in APS occurs through the following mechanisms:

• Antiphospholipid antibodies (particularly lupus anticoagulant) interfere with phospholipid-dependent coagulation tests 1
• These antibodies bind to the phospholipid component of the aPTT test, inhibiting the formation of the prothrombinase complex 1
• This interference creates a paradoxical situation where the in vitro test shows prolonged clotting time, but in vivo, patients actually have an increased risk of thrombosis rather than bleeding 1, 2

Laboratory Diagnosis of APS

The International Society on Thrombosis and Haemostasis (ISTH) recommends a specific testing protocol for detecting lupus anticoagulant:

• A prolonged aPTT that does not correct with normal plasma in mixing studies is characteristic of APS 1

• Two parallel tests are recommended for lupus anticoagulant detection 3, 1:

  1. Dilute Russell's Viper Venom Time (dRVVT) - considered the first-line test with highest specificity
  2. LA-sensitive aPTT - performed with silica as activator and low phospholipid content

• Proper testing protocol involves 3, 1:

  • Screening phase
  • Mixing studies
  • Confirmatory testing
  • Repeat testing after >12 weeks to confirm persistence

Important Clinical Considerations

When interpreting aPTT results in suspected APS:

• A prolonged aPTT due to antiphospholipid antibodies is not a contraindication to anticoagulation therapy, which is often necessary in APS patients 1
• Factor VIII increases during pregnancy may mask lupus anticoagulant by shortening the aPTT in pregnant patients with APS 1
• It's crucial to distinguish between lupus anticoagulant and true factor inhibitors (like factor VIII inhibitor), as the latter can lead to fatal bleeding 4
• Some patients with APS may show an activated protein C resistance (APC-R) phenotype with a low APTT ratio without factor V Leiden mutation 5

Clinical Implications of aPTT Prolongation

The prolonged aPTT in APS has significant clinical implications:

• Despite the in vitro prolongation of clotting time, APS patients have an increased risk of both venous and arterial thrombosis 6, 2
• Recurrent thrombosis is a serious problem in APS patients, with the site of first thrombotic event (arterial or venous) typically predicting the site of subsequent events 6
• Anticoagulation therapy is typically required, with intermediate to high-intensity warfarin therapy showing better protection against thrombosis than low-intensity warfarin or aspirin 6

Reporting and Interpretation Guidelines

The ISTH recommends specific reporting practices for APS laboratory testing 3:

• LA should be reported with a final conclusion as positive or negative, with warnings about potential interferences
• Results should be interpreted in clinical context, with knowledge of anticoagulation status
• Two consecutive positive aPL tests at least 12 weeks apart are required to rule out transient positivity
• Triple positivity (LA, anticardiolipin antibodies, and anti-beta2 glycoprotein I antibodies) increases confidence in APS diagnosis

By understanding the characteristic prolongation of aPTT in APS and following proper testing protocols, clinicians can accurately diagnose this condition and implement appropriate anticoagulation strategies to reduce the risk of thrombotic events.