Hypercoagulable thrombophilic defects and hyperhomocysteinemia in patients with recurrent pregnancy loss

Am J Reprod Immunol. 2001 Feb;45(2):65-71. doi: 10.1111/j.8755-8920.2001.450201.x.


Problem: Placental perfusion may be compromised by increased thrombosis that leads to pregnancy complications and recurrent pregnancy loss (RPL). Since heritable thrombophilic defects and hyperhomocysteinemia are associated with increased thrombosis, their prevalence was evaluated in RPL patients with special emphasis on combinations of the above pathologies.

Methods of study: Evaluation of the prevalence of heritable thrombophilic defects (protein S, protein C, anti-thrombin III deficiency, and the mutations for factor V Leiden, methylenetetrahydrofolate reductase [MTHFR], and prothrombin gene), hyperhomocysteinemia. and combinations of these pathologies in 36 non-pregnant recurrent aborters compared with 40 parous women.

Results: We found a relatively high prevalence of deficiencies of plasma coagulation proteins in RPL patients compared with the controls. A non-significant different increase in factor V Leiden mutation was detected (6/36 [16%] compared with 2/40 [5%] in the control group, P = 0.14]. Hyperhomocysteinemia was found in 31% of the RPL patients. MTHFR mutation homozygosity was found in 6/36 (16%) of the aborting patients. Combinations of hyperhomocysteinemia and MTHFR mutation were found in three patients, with folate deficiency in two patients, and with B12 deficiency in three.

Conclusions: Combinations of gene mutations, plasma protein deficiencies, and hyperhomocysteinemia, which are associated with an increased thrombotic risk, are more common in RPL patients compared with controls. Large-scale prevalence studies are needed in order to draw conclusions as to the causative relation of such a condition and RPL.

MeSH terms

  • Abortion, Habitual / blood
  • Abortion, Habitual / etiology*
  • Activated Protein C Resistance / complications
  • Adult
  • Factor V / genetics
  • Female
  • Homocysteine / blood*
  • Humans
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Mutation
  • Oxidoreductases Acting on CH-NH Group Donors / genetics
  • Pregnancy
  • Thrombophilia / complications*


  • factor V Leiden
  • Homocysteine
  • Factor V
  • Oxidoreductases Acting on CH-NH Group Donors
  • Methylenetetrahydrofolate Reductase (NADPH2)