Thrombophilia
Thrombophilia refers to inherited or acquired disorders that can result in an increased chance for abnormal blood clotting. During pregnancy this can cause microscopic clots to form in the placenta depriving the fetus of adequate blood flow. Several tests have been developed to assist in assessing the clotting capacity of a patient.
Candidates for Thrombophilia testing typically include: recurrent pregnancy loss, infertility, implantation failures, In vitro fertilization and embryo transfer (IVF-ET) failures, thromboembolic disease at a young age with no associated trauma, positive family history or whose thrombosis involves an unusual site. Compared to fertile women, a finding of a higher incidence of thrombophilia in women submitted to repeat cycles of in vitro fertilization (IVF) and implantation failure has become increasingly common.
Thrombophilia Fertility Tests
Activated Partial Thromboplastin Time (APTT) – this test looks at a variety of factors involved in the normal blood clotting process. If any of these factors has a defect the blood will take longer than normal to clot. The consequence of such a defect can result in hemorrhaging. In terms of pregnancy this type of deficiency has been associated with failed implantations and recurrent pregnancy loss.
Antithrombin – a protein in the blood that blocks the formation of blood clots by inhibiting the procoagulation (cause blood to clot) factors XIa, IXa, Xa and IIa. It is an inherited condition in which an abnormal gene (inherited from a parent with the disease) leads to low levels or reduced function of the protein. This can cause abnormal blood clotting.
Factor V Leiden – is a protein involved in the normal blood clotting process. Once the blood has sufficiently clotted, the Factor V Leiden protein becomes inactivated. Some people inherit a defective Factor V Leiden gene (a point mutation). This genetic defect makes the Factor V Leiden protein much more difficult to inactivate, resulting in excessive clotting. The Factor V Leiden defect has been associated with: recurrent pregnancy loss, late abortions, fetal death/growth retardation (IUGR) and pregnancy complications such as pre-eclampsia (a condition in pregnancy characterized by a sharp increase in blood pressure).
Factor VII – a protein that is part of the cascade of clotting factors involved in the process of forming a protective blood clot. Diagnosis is typically made through activated partial thromboplastin time (aPTT) test, prothrombin time (PT) test and thrombin time (TT) test. A prolonged clotting time indicates a deficiency of this protein. Diagnosis can be confirmed with a factor VII assay. Factor VII deficiency is usually severe. People with severe factor VII are prone to joint bleeds. In addition to spontaneous nosebleeds, people can experience bleeds in the stomach, intestines and urinary tract. Head bleeds and muscle bleeds have also been reported. Also, women can have severe menorrhagia (heavy or extended menstrual flow).
Factor VIII (Von Willebrand Factor) – a protein that is part of the cascade of clotting factors involved in the process of forming a protective blood clot. Diagnosis is typically made through activated partial thromboplastin time (aPTT) test, prothrombin time (PT) test and thrombin time (TT). A prolonged clotting time indicates a deficiency of this protein. R aised maternal plasma levels of clotting factor VIII tend to be associated with an increased risk of recurrent pregnancy loss (RPL).
Factor X – a protein that is part of the cascade of clotting factors involved in the process of forming a protective blood clot. T ypically identified by testing for Antithrombin activity which normally inhibits this factor. If there is an antithrombin deficiency, this protein can cause abnormal clotting.
Factor XI – a protein that is part of the cascade of clotting factors involved in the process of forming a protective blood clot. T ypically identified by testing for Antithrombin activity which normally inhibits this factor. If there is an antithrombin deficiency, this protein can cause abnormal clotting. Also detected by activated partial thromboplastin time (APTT) testing. APTT is especially sensitive for functional deficiencies in this factor resulting in blood taking longer than normal to clot.
Factor XII – a protein that is part of the cascade of clotting factors involved in the process of forming a protective blood clot. D etected by activated partial thromboplastin time (APTT) testing. APTT is especially sensitive for functional deficiencies in this factor resulting in blood taking longer than normal to clot.
Factor XIII – a protein that is part of the cascade of clotting factors involved in the process of forming a protective blood clot. Genetic variations in the gene for the Factor XIII protein have been associated with an abnormally enhanced ability to form a blood clot. Women who are homozygous for Factor XIII mutations also have a high risk for recurrent spontaneous abortion.
Homocysteine – is an amino acid that, when elevated, can adversely affect many factors involved in the clotting pathway. It can either enhance blood clotting (procoagulation) activity or reduce the ability to stop blood clotting (anticoagulation). Elevated homocysteine levels can be acquired by vitamin deficiencies (folic acid, vitamins B6 and B12). Or elevated homocysteine levels can be inherited as a genetic defect in the enzyme MTHFR, an enzyme involved in the conversion of homocyeteine. High homocysteine levels make it harder to conceive, increase the risk of early miscarriages and increase the chance of pregnancy complications.
MTHFR – is a recessive gene that leads to an accumulation of high levels of homocysteine that subsequently promotes thrombophilia. Typically, all copies of the MTHFR gene (homozygous) need to have the mutation in order to have a significant impact. Mutations of the MTHFR gene are associated with a significant risk for recurrent pregnancy loss (RPL) and birth defects. It has also been linked to third trimester and post-partum complications.
Plasminogen Activator Inhibitor – 1 (PAI-1) – is an enzyme involved in the process of breaking down blood clots. Elevated levels of this enzyme are associated with excessive clotting. Abnormal levels of PAI-1 are associated with pregnancy complications such as: recurrent pregnancy loss (RPL), pre-eclampsia (a condition in pregnancy characterized by a sharp increase in blood pressure), fetal growth retardation and fetal death.
Protein C – a potent anticoagulant that plays a major role in the body’s ability to stop or regulate blood clotting. Protein C deficiency can either be inherited or acquired. In pregnancy this deficiency can disrupt the blood supply to the fetus or cause thrombosis in the placenta. The end result can be implantation failure, recurrent pregnancy loss (RPL), fetal death, fetal growth retardation (IUGR), pre-eclampsia or still birth.
Protein S – binds to Protein C to aid in the normal blood clotting process. Protein S deficiency can either be inherited or acquired, and results in abnormally prolonged clotting. In pregnancy this deficiency can disrupt the blood supply to the fetus or cause thrombosis in the placenta. The end result can be implantation failure, recurrent pregnancy loss (RPL), fetal death, fetal growth retardation (IUGR), pre-eclampsia (a condition in pregnancy characterized by a sharp increase in blood pressure) or still birth.
Prothrombin – a protein in the blood that is required in order for it to clot. A mutation in the Prothrombin gene results in excess production of the Prothrombin protein, making the blood more likely than normal to clot. Pregnancy complications from this mutation include: recurrent pregnancy loss (RPL), placental abruption (a condition in which the placenta detaches to some extent from the wall of the uterus), fetal death and pre-eclampsia (a condition in pregnancy characterized by a sharp increase in blood pressure).
