Thrombophilia and Miscarriage
Thrombophilia / hypercoagulation has been associated with an increased risk of miscarriage in numerous studies. Thrombophilia can be inherited, as in the MTHFR and Factor V Leiden gene mutations, but it can also be caused or exacerbated by insulin resistance, vitamin deficiencies, stress, inactivity and obesity. Further, certain supplements and medications have been shown useful in lowering miscarriage risk in those suffering from thrombophilia.
These topics are covered under Thrombophilia and Miscarriage:
Factor V Leiden and Miscarriage
Insulin Resistance and Thrombophilia
General Miscarriage and Thrombophilia Research
92% without physical, hormonal or chromosomal cause for miscarriage have thrombophilia
Three-hundred fifty-one women were referred for thrombosis and hemostasis evaluation after suffering recurrent miscarriages. All patients were referred by a high-risk obstetrician or reproductive medicine specialist after anatomic, hormonal or chromosomal defects had been ruled out. Of the 351 patients, 29 (8%) had no defect. Of the remaining 322 patients, 7 (2%) had a bleeding disorder: 3 with platelet dysfunction, 1 with Factor XIII deficiency, 3 with von Willebrand's and 3 with Osler-Weber-Rendu. The remainder of the patients had a thrombophilia as follows: 195 (60%) had antiphospholipid syndrome, 64 (20%) had Sticky Platelet Syndrome, 38 (12%) had MTHFR mutation, 23 (7.1%) had PAI-1 polymorphism, 12 (3.7%) had Protein S deficiency, 12 (3.7%) had Factor V Leiden, 3 (1%), had AT deficiency, 3 (1%) had Heparin-Cofactor II deficiency, 3 (1%) had TPA deficiency, and 6 (2%) had Protein C deficiency. All patients with thrombophilia were treated with preconception aspirin at 81 mg/day with the immediate post-conception addition of heparin or LMW heparin. The patients with MTHFR were also treated with folate at 5 mg/day + pyridoxine at 50 mg/day. In our experience, thrombophilia is a common cause of recurrent miscarriage and all patients with no anatomical, hormonal or chromosomal defect should be evaluated for thrombophilia or a bleeding disorder. The success rate of normal term delivery in these 312 patients was 94% using ASA + heparin or Dalteparin. In addition, side effects of therapy were minimal.
http://www.ncbi.nlm.nih.gov/pubmed/15678268
Women with low fibrinogen have a five fold risk of miscarriage
To assess the relationship between hemostatic factors and miscarriage, 134 pregnant women presenting to the emergency department were recruited and followed through 22 weeks' gestation. Cases were women experiencing a miscarriage and controls were women who maintained their pregnancy. Cases had lower mean levels of fibrinogen and factor VII antigen compared with controls (3.1 g/L vs. 3.7 g/L and 89% of normal vs. 109% of normal, respectively). Regression analyses found that women with fibrinogen levels below 3.0 g/L had a five-fold increased risk of miscarriage (odds ratio = 5.1) and women with factor VII antigen levels below 94% of normal had a threefold increased risk of miscarriage (odds ratio = 3.3).
http://www.ncbi.nlm.nih.gov/pubmed/11444363
78% of women with repeat miscarriage suffer from acquired and/or inherited thrombophilia
90 patients affected by unexplained repeat miscarriage were enrolled and tested for hemostatic alterations. These women were tested for inherited and/or acquired thrombophilia by MTHFR C677T gene polymorphism, factor V Leiden gene polymorphism, PTHRA20210G gene polymorphism, protein S deficiency, protein C deficiency, antithrombin III deficiency, lupus anticoagulant, and anticardiolipin antibodies Ig G and Ig M. Acquired and/or inherited thrombophilia are strongly associated with repeat miscarriage when other common causes of miscarriage were excluded. 78% of tested women showed hemostatic abnormalities. Several women with combined thrombophilic defects were also identified by our data.
http://www.ncbi.nlm.nih.gov/pubmed/19707467
Thrombophila more common in women with recurrent miscarriage
In this case-control study, we determined the percentages of three thrombophilic mutations (factor V leiden, prothrombin, and MTHFR) amongst 20 cases with repeat spontaneous miscarriage and 20 control normal parous women. Results: There were high statistically significant increases in the number of cases with factor V, prothrombin, and MTHFR gene mutations compared with normal control and the percentage of multiple gene mutations was higher than single gene mutation. Conclusion: The prevalence of thrombophilic mutations is higher in cases of repeat spontaneous miscarriage than control.
Thrombophilia associated with fetal growth restriction
Inherited thrombophilia, such as factor V Leiden, prothrombin, and MTHFR mutations; gene polymorphisms of detoxification enzyme (CYP1A1); growth factors (insulin-like growth factor-I); and hormones such as angiotensinogen and CYP17 are involved in the pathogenesis of fetal growth restriction.
http://www.ncbi.nlm.nih.gov/pubmed/16052406
Inflammation causes thrombosis in the placenta, regardless of thrombophilia in the mother
Placental thrombosis has been found in women with unexplained recurrent miscarriage independent of thrombophilia. In addition, proinflammatory changes, for example, altered Th1 to Th2 cytokine ratio and complement activation, have been repeatedly demonstrated in these women.