History

Fact Explanation
Second and third trimester pregnancy loss [1] A nonrecurrent pregnancy loss after 20 to 24 weeks' gestation is associated with factor V Leiden, protein S deficiency, and the prothrombin G20210A mutation. Antiphospholipid antibodies, specifically lupus anticoagulant and anticardiolipin antibody, can occur in women with systemic lupus erythematosus or other immunologic conditions, can occur as an isolated syndrome, and can be transient. These antibodies cause placental thrombosis and have emerged as well-established risks for second and third trimester pregnancy loss [1] Thrombophilia defects in pregnancy - Heritable : Antithrombin, Protein C, S deficiency Factor V Leiden Prothrombin 20210A Dysfibrinogenaemia Aquired: Antiphospholipid syndromes Complex: Factor VIII rise Hyperhomocysteinaemia [7]
Severe abdominal pain [3] Abnormal placental vasculature and disturbances of hemostasis leading to inadequate maternal-fetal circulation can give rise to abruptio placenta [3]
Loss of the sensation of fetal movements [3] intrauterine fetal death (IUFD) due to disturbances of hemostasis leading to inadequate maternal-fetal circulation [5]
Swelling of hands and face [3] Pre eclampsia as an adverse pregnancy outcome due to disturbances of hemostasis leading to inadequate maternal-fetal circulation. Proteinuria in pre eclampsia causes imbalances of the starling forces which lead to edema [2]
Sudden shortness of breath, cough [2] Hypercoagulable state during pregnancy promotes clot formation,extension,stability. Stasis in large veins of lower extremities from uterine compression leads to deep vein thrombosis which can give rise to pulmonary embolism [3]
Recent surgery, Age >35 years , High parity , High body mass index , Smoking , Immobilization [2] Causes additional risk for clot formation [2]
Family history of thrombotic disorders [4] Thrombophilia can be inherited. Eg: Antithrombin deficiency,Protein C deficiency, Protein S deficiency,Factor V Leiden, prothrombin gene mutation,Dysfibrinogenaemia [6]
References
  1. MICHELS TC, TIU AY. Second trimester pregnancy loss. Am Fam Physician [online] 2007 Nov 1, 76(9):1341-6 [viewed 21 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/18019878
  2. WALKER I. D. Thrombophilia in pregnancy. [online] 2000 August, 53(8):573-580 [viewed 21 August 2014] Available from: doi:10.1136/jcp.53.8.573
  3. KUPFERMINC MJ. Thrombophilia and pregnancy Reprod Biol Endocrinol [online] :111 [viewed 21 August 2014] Available from: doi:10.1186/1477-7827-1-111
  4. VAIMAN D. Genetic regulation of recurrent spontaneous abortion in humans. Biomed J [online] 2014 Sep 2 [viewed 18 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/25179715
  5. BARROS VI, IGAI AM, ANDRES MDE P, FRANCISCO RP, ZUGAIB M. [Pregnancy outcome and thrombophilia of women with recurrent fetal death]. Rev Bras Ginecol Obstet [online] 2014 Feb, 36(2):50-5 [viewed 18 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/24676012
  6. MOTHA MB, PALIHAWADANA TS, PERRY DJ. Recurrent pregnancy loss and thrombophilia. Ceylon Med J [online] 2014 Mar, 59(1):1-3 [viewed 18 October 2014] Available from: doi:10.4038/cmj.v59i1.6730
  7. PARAND A, ZOLGHADRI J, NEZAM M, AFRASIABI A, HAGHPANAH S, KARIMI M. Inherited thrombophilia and recurrent pregnancy loss. Iran Red Crescent Med J [online] 2013 Dec, 15(12):e13708 [viewed 18 October 2014] Available from: doi:10.5812/ircmj.13708

Examination

Fact Explanation
Severe abdominal tenderness [1] Abnormal placental vasculature and disturbances of hemostasis leading to inadequate maternal-fetal circulation can give rise to abruptio placenta [1]
Reduced symphisio fundal height [1] Intra uterine growth restriction due to disturbances of hemostasis leading to inadequate maternal-fetal circulation [2]
Dyspnea [2] Hypercoagulable state during pregnancy promotes clot formation,extension,stability. Stasis in large veins of lower extremities from uterine compression leads to deep vein thrombosis which can give rise to pulmonary embolism [1]
Facial / hand edema [2] Pre eclampsia as an adverse pregnancy outcome due trombophilia. Proteinuria in pre eclampsia causes imbalances of the starling forces which lead to edema [2]
References
  1. KUPFERMINC MJ. Thrombophilia and pregnancy Reprod Biol Endocrinol [online] :111 [viewed 21 August 2014] Available from: doi:10.1186/1477-7827-1-111
  2. MICHELS TC, TIU AY. Second trimester pregnancy loss. Am Fam Physician [online] 2007 Nov 1, 76(9):1341-6 [viewed 21 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/18019878

Differential Diagnoses

Fact Explanation
Cervical insufficiency [1] Causes 2nd trimester pregnancy loss.Can present with painless rupture of membranes.Ultrasonography; hysterography done for further evaluation [1]
Maternal anatomic factors (müllerian duct anomalies, intrauterine adhesions) [1] Can present with unexplained pregnancy loss.Physical examination; ultrasonography; hysterosalpingography; hysteroscopy; pelvic magnetic resonance imaging need for further evaluation [1]
References
  1. MICHELS TC, TIU AY. Second trimester pregnancy loss. Am Fam Physician [online] 2007 Nov 1, 76(9):1341-6 [viewed 21 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/18019878

Investigations - for Diagnosis

Fact Explanation
Clotting profile ( activated partial thromboplastin time (APTT), prothrombin time and thrombin clotting time) [1] The activated partial thromboplastin time (APTT), prothrombin time and thrombin clotting time should be incorporated in the initial screening. The APTT may identify some patients with antiphospholipid antibodies (depending on the sensitivity of the APTT reagent used), but is not sufficient alone to exclude antiphospholipid antibodies. The thrombin clotting time will allow identification of dysfibrinogenaemia. The prothrombin time is useful in the interpretation of low protein C or protein S results [1]
References
  1. WALKER ISOBEL D, GREAVES M, PRESTON F. E. Investigation and management of heritable thrombophilia. Br J Haematol [online] 2001 September, 114(3):512-528 [viewed 21 August 2014] Available from: doi:10.1046/j.1365-2141.2001.02981.x

Investigations - Fitness for Management

Fact Explanation
Full blood count [1] A full blood count should be performed to exclude myeloproliferative disorders [1]
References
  1. WALKER ISOBEL D, GREAVES M, PRESTON F. E. Investigation and management of heritable thrombophilia. Br J Haematol [online] 2001 September, 114(3):512-528 [viewed 21 August 2014] Available from: doi:10.1046/j.1365-2141.2001.02981.x

Investigations - Followup

Fact Explanation
Urine for protein [1] To identify pre eclampsia. (>300 mg of protein in a 24-hour urine sample) [1]
Ultra sound scan abdomen / trans vaginal ultra sound scan [1] To identify thrombophilia associated adverse outcomes. eg: abruptio placenta, intrauterine growth restriction (IUGR) and intrauterine fetal death (IUFD) [1]
References
  1. WALKER I. D. Thrombophilia in pregnancy. [online] 2000 August, 53(8):573-580 [viewed 21 August 2014] Available from: doi:10.1136/jcp.53.8.573

Investigations - Screening/Staging

Fact Explanation
Lupus anticoagulant (LAC) , anticardiolipin antibodies (aCL) [1] The antiphospholipid syndrome (APS), an acquired autoimmune condition, is characterized by the presence of certain features and circulating antibodies. It is defined as the presence of lupus anticoagulant (LAC) and/or anticardiolipin antibodies (aCL) with recurrent miscarriage (RM), thrombosis, preeclampsia, IUGR and placental abruption [1]
Venous doppler of lower limbs [1] To identify deep venous thrombosis and stasis of blood [1]
References
  1. KUPFERMINC MICHAEL J. . Reprod Biol Endocrinol [online] 2003 December [viewed 21 August 2014] Available from: doi:10.1186/1477-7827-1-111

Management - General Measures

Fact Explanation
Pre pregnancy counselling [1] Patients on longterm coumarin must be counselled about the risk to the fetus of maternal coumarin ingestion during pregnancy, and provision must be made to ensure that coumarin is withdrawn and replaced with heparin no later than 6 weeks gestation [1] Preeclampsia, abruptio placenta, intrauterine growth restriction (IUGR) and intrauterine fetal death (IUFD) contribute to maternal and fetal morbidity and mortality [2]
Educate regarding future pregnancy risks [2] In women with a history of recurrent miscarriage, the risk of miscarriage in a subsequent pregnancy is about 40-50% [3] Multiparous women with thrombophilias and severe pregnancy complications there is high (66–83%) recurrence rate in subsequent pregnancies, while the type of complication may change from one pregnancy to the other; e.g. severe preeclampsia to IUGR. High recurrence rate in women with severe preeclampsia/ HELLP syndrome. [2]
References
  1. WALKER I. D. Thrombophilia in pregnancy. [online] 2000 August, 53(8):573-580 [viewed 21 August 2014] Available from: doi:10.1136/jcp.53.8.573
  2. KUPFERMINC MJ. Thrombophilia and pregnancy Reprod Biol Endocrinol [online] :111 [viewed 21 August 2014] Available from: doi:10.1186/1477-7827-1-111
  3. Effectiveness of aspirin compare with heparin plus aspirin in recurrent pregnancy loss treatment: A Quasi experimental study. Iran J Reprod Med [online] 2014 Jan, 12(1):73-6 [viewed 18 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/24799864

Management - Specific Treatments

Fact Explanation
Patients with very high risk of venous thromboembolism [1] Patients who have already been committed to long term anticoagulant prophylaxis should also be considered to be at very high risk during pregnancy. Very high risk patients usually require anticoagulation throughout their entire pregnancy. Coumarins cross the placenta, they have the potential to cause teratogenicity and fetal bleeding and should be avoided during pregnancy. Unfractionated or low molecular weight heparin should be used in doses adjusted to maintain the patient's activated partial thromboplastin time ratio or anti-Xa activity within the therapeutic range throughout the entire pregnancy. Prophylactic anticoagulation should be continued for at least six to 12 weeks after delivery [1]
Patients with high risk of venous thromboembolism [1] Women with a past history of venous thromboembolism (and not currently using anticoagulants) Anticoagulation during pregnancy is indicated [2] for those patients at high risk of pregnancy venous thromboembolism. For such patients it is usually reasonable to use lower prophylactic doses of unfractionated or low molecular weight heparin and to delay introduction of anticoagulant until early to mid second trimester. Prophylactic anticoagulation should be continued for six to 12 weeks postpartum [1]
Patients at moderate risk of venous thromboembolism [1] Women who have no personal history of venous thromboembolism but who have been screened for thrombophilic defects because of a family history of venous thromboembolism and been found to be heterozygous for protein S deficiency, factor V Leiden, or prothrombin G20210A should be considered to be at moderate risk of pregnancy associated venous thromboembolism. However, for these women and their babies the risks associated with antenatal anticoagulation usually outweigh the benefits, and in most of these asymptomatic patients antenatal anticoagulation should be avoided. Like those patients at high and very high risk they should be offered anticoagulant prophylaxis from delivery until at least six weeks postpartum [1]
Management other than anti thrombolytic therapy ( graduated compression stockings) [1] Women assessed to be at increased risk of pregnancy associated venous thromboembolism should be encouraged to wear graduated compression stockings throughout their pregnancy and puerperium. Special graduated compression stockings are designed to decrease or prevent swelling. They keep fluid from pooling in the ankle, calf and thigh [1]
References
  1. WALKER I. D. Thrombophilia in pregnancy. [online] 2000 August, 53(8):573-580 [viewed 21 August 2014] Available from: doi:10.1136/jcp.53.8.573
  2. KHALAFALLAH AA, IBRAHEEM AR, TEO QY, ALBARZAN AM, PARAMESWARAN R, HOOPER E, PAVLOV T, DENNIS AE, HANNAN T. Review of Management and Outcomes in Women with Thrombophilia Risk during Pregnancy at a Single Institution. ISRN Obstet Gynecol [online] 2014:381826 [viewed 18 October 2014] Available from: doi:10.1155/2014/381826