Antiphospholipid Syndrome (APS)
A patient presenting with DVT and recurrent miscarriages most likely has antiphospholipid syndrome (APS), the most common acquired thrombophilia characterized by this exact clinical presentation. 1, 2, 3
Clinical Presentation and Diagnosis
The combination of venous thrombosis and recurrent pregnancy loss is pathognomonic for APS. 3, 4 This syndrome is defined by:
- Venous or arterial thrombosis (including DVT, pulmonary embolism, or unusual site thromboses) 3, 4
- Recurrent pregnancy loss (particularly three or more spontaneous abortions before 10 weeks gestation, or one or more unexplained losses after 10 weeks) 1, 2
- Presence of antiphospholipid antibodies on two occasions at least 12 weeks apart 5
Required Laboratory Testing
All patients with this presentation must be tested for antiphospholipid antibodies, which include: 1, 2
- Lupus anticoagulant - the most specific marker 1, 2
- Anticardiolipin antibodies (IgG and IgM) 1, 2
- Anti-beta-2-glycoprotein I antibodies 3, 4
The American College of Chest Physicians specifically recommends testing for antiphospholipid antibodies in women with recurrent early pregnancy loss, with moderate strength of evidence. 1, 2
Why APS Rather Than Inherited Thrombophilias
While inherited thrombophilias (Factor V Leiden, Prothrombin G20210A, Protein C/S deficiency) can cause DVT, they are not strongly associated with recurrent miscarriages in the same way APS is. 5, 6
- Factor V Leiden and Prothrombin mutations may be associated with second-trimester losses specifically, but not the pattern of recurrent early losses typical of APS 2
- Testing for inherited thrombophilias does not usefully predict recurrence risk after first VTE and is not routinely recommended 5, 6
- APS is the most common acquired thrombophilia and the primary disorder linking both thrombosis and pregnancy complications 3
Pathophysiology
APS antibodies create a prothrombotic state through multiple mechanisms: 4
- Inhibition of natural anticoagulants (Protein C system, tissue factor pathway inhibitor, annexin A5) 4
- Activation of endothelial cells, monocytes, and platelets 4
- Inhibition of the fibrinolytic system 4
- Complement activation 4
Management Implications
Once APS is confirmed, treatment differs significantly from other thrombophilias: 1
- For acute DVT: therapeutic anticoagulation with LMWH or warfarin (INR 2.0-3.0) 1
- For future pregnancies: combined aspirin and heparin therapy to prevent pregnancy loss 1
- Long-term anticoagulation is typically required given the high recurrence risk 1
Critical Pitfall to Avoid
Do not stop at testing for inherited thrombophilias alone - the combination of DVT and recurrent miscarriages mandates antiphospholipid antibody testing, as this is the hallmark presentation of APS. 1, 2 Missing this diagnosis means missing the opportunity for appropriate pregnancy management with combined aspirin-heparin therapy, which significantly improves pregnancy outcomes. 1