Additional Risk Factors Associated with Thrombosis and Pregnancy Morbidity in Antiphospholipid Antibody-Positive Patients

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Additional Risk Factors Associated with Thrombosis and Pregnancy Morbidity in Antiphospholipid Antibody-Positive Patients

Antiphospholipid syndrome (APS) is a well-known autoimmune prothrombotic condition that can cause significant health problems. It can lead to arterial thrombosis, venous thrombosis, and pregnancy morbidities like premature births due to eclampsia, preeclampsia, placental insufficiency, or recurrent spontaneous abortions. But managing patients with positive antiphospholipid antibodies (aPL) who don’t show thrombotic or obstetric symptoms is a challenge in clinical practice.

Study Design and Methods

This was a cross-sectional cohort study at Peking University People’s Hospital. They screened 453 patients with positive aPL. Out of these, 297 had persistent positive aPL. They compared asymptomatic aPL carriers with those who had thrombotic and obstetric APS. Using univariate and multivariable logistic regression, they looked at how different risk factors related to APS clinical manifestations. They also measured levels of circulating markers of neutrophil extracellular traps (NETs), like cell-free DNA and citrullinated histone H3 (Cit-H3), in different groups of aPL-positive carriers and APS patients.

Key Findings

  • Arterial Thrombosis Risk Factors: Smoking (odds ratio [OR] = 6.137, 95% confidence interval [CI] = 2.408–15.637, P = 0.0001), hypertension (OR = 2.368, 95% CI = 1.249–4.491, P = 0.008), and having an underlying autoimmune disease (OR = 4.401, 95% CI = 2.387–8.113, P < 0.001) were significant additional risk factors.
  • Venous Thrombosis Risk Factors: Smoking (OR = 4.594, 95% CI = 1.681–12.553, P = 0.029) and the presence of an underlying autoimmune disease (OR = 6.330, 95% CI = 3.355–11.940, P < 0.001) were associated with venous thrombosis.
  • Pregnancy Morbidity Risk Factor: Only the presence of an underlying autoimmune disease (OR = 3.301, 95% CI = 1.407–7.744, P = 0.006) showed a significant association with APS pregnancy morbidity.
  • NETs and APS: APS patients and aPL patients with autoimmune diseases had higher circulating levels of cell-free DNA and Cit-H3 compared to aPL carriers without underlying autoimmune diseases. Also, neutrophils conditioned with APS patients’ sera released more NETs than those treated with aPL carriers’ sera without underlying autoimmune diseases.

Discussion

  • Hypertension (HTN): HTN has been linked to increased thrombosis risk in aPL-positive patients in other studies. This study shows it’s a potential independent risk factor for arterial thrombosis (but not venous) in Chinese aPL-positive carriers. For example, hypertensive aPL-positive patients had more cerebral vascular accidents in some studies.
  • Smoking: There have been conflicting views on smoking’s role. In this Chinese study, it strongly associated with both arterial and venous thromboembolic events. Cultural and ethnic differences in smoking prevalence might explain the discrepancies in different studies. China has a high per capita cigarette consumption rate.
  • Underlying Autoimmune Disease: Inflammation plays a role in hemostasis. Systemic autoimmune diseases can lead to hypercoagulability. This study confirms that an underlying autoimmune disease is an important risk factor for both arterial and venous thrombosis in Chinese aPL-positive carriers. Regarding pregnancy, only the presence of an underlying autoimmune disease was a significant risk factor. Previous studies have looked at other factors like complement activation and angiogenic factor imbalance, but this study’s finding about autoimmune disease aligns with the idea that it’s a consistent aPL-associated obstetric risk.

Conclusion

This is the largest study of Chinese aPL-positive carriers to identify additional risk factors. The cross-sectional design has limitations, like not being able to show causal relationships and not accounting for some confounding variables. But it provides valuable data. It helps physicians risk-stratify aPL-positive Asian patients. Longitudinal studies are needed to confirm these findings. Overall, it highlights the importance of considering these additional risk factors in managing APS patients.

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doi: 10.1097/CM9.0000000000001964

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