History

Fact Explanation
Symptoms of pre-eclampsia Pre-eclampsia can occur due to recurrent thrombosis of the placental bed. Pregnant ladies present with record of high blood pressure, visual disturbances, proteinuria, generalized body swelling and seizures. [1,3]
Neurological complications Seizures and chorea can be the presenting complains of Anti- Phospholipid Syndrome (APS). Patients with APS can also develop transverse myelitis, causing sensory and motor impairment below the affected spinal cord level. [1,2]
Cutaneous manifestations Patients with APS can have skin ulcerations and digital gangrenes. [1]
Symptoms of venous thrombosis Deep vein thrombosis presents with severe pain and swelling of the extremities commonly affecting the left lower limb. This may be due to the compression of the left common iliac vein by the enlarged uterus. Sudden severe chest pain, cough and hemoptysis are classic symptoms of pulmonary embolization. [1]
Symptoms of recurrent arterial thrombosis Patients with APS are at risk of thrombotic complications. They can present with sudden neurological impairment or with focal weakness due to cerebrovascular accidents. Development of ischemic limbs and distal gangrenes is another presentation. Sudden severe abdominal pain can occur due to mesenteric angina secondary to mesenteric thrombosis. [1]
Multiorgan failure Patients with catastrophic antiphospholipid syndrome (CAPS), a severe form of the disease can present with multiorgan failure. It is due to multiple thrombotic phenomena affecting major organs' perfusion. This can occur during the pregnancy and also during the postpartum period. [1]
History of recurrent miscarriages Patients with APS have a history of recurrent spontaneous miscarriages. These miscarriages usually occurs between 10th to 24th weeks of gestation. [1,2]
History of autoimmune diseases Patients with other autoimmune diseases (like systemic lupus erythematosus) can manifest secondary APS (primary APS refers to the occurrence of APS with no other associated autoimmune diseases). [1]
Fetal and neonatal complications APS can cause preterm labour, oligohydramnios, intrauterine growth restriction and fetal distress. [1]
References
  1. DI PRIMA FA, VALENTI O, HYSENI E, GIORGIO E, FARACI M, RENDA E, DE DOMENICO R, MONTE S. Antiphospholipid Syndrome during pregnancy: the state of the art J Prenat Med [online] 2011, 5(2):41-53 [viewed 18 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3279165
  2. ETEMADIFAR M, DEHGHANI L, TAHANI S, TOGHIANIFAR N, RAHAIMI M, ESKANDARI N. Neurological manifestations in patients with antiphospholipid syndrome. Iran J Neurol [online] 2013, 12(4):172-5 [viewed 18 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/24250929
  3. MARCHETTI T, COHEN M, DE MOERLOOSE P. Obstetrical antiphospholipid syndrome: from the pathogenesis to the clinical and therapeutic implications. Clin Dev Immunol [online] 2013:159124 [viewed 18 August 2014] Available from: doi:10.1155/2013/159124

Examination

Fact Explanation
Signs of cutaneous involvement Livedo reticularis, skin necrosis and ulceration and digital gangrenes can be seen in patients with APS. Some patients have photosensitive rashes. [1]
Auscultation of the heart Cardiac auscultation can reveal mitral valve and aortic valve regurgitation. Mitral regurgitation produces a high pitched pansystolic murmur, whereas aortic regurgitation produces an early diastolic murmur. [1]
Blood pressure Assessment of the blood pressure is important as maternal hypertension is a common association of APS. [1]
References
  1. DI PRIMA FA, VALENTI O, HYSENI E, GIORGIO E, FARACI M, RENDA E, DE DOMENICO R, MONTE S. Antiphospholipid Syndrome during pregnancy: the state of the art J Prenat Med [online] 2011, 5(2):41-53 [viewed 18 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3279165

Differential Diagnoses

Fact Explanation
Systemic lupus erythematosis (SLE) [1] SLE is another common connective tissue disorder. LA and aCL antibodies can be detected in both conditions.
Rheumatic chorea [1] Chorea is another complication of APS and rheumatic fever.
Congenital thrombophilia Congenital causes of thrombophilia include antithrombin III deficiency, protein C deficiency and protein S deficiency. Patients present with recurrent deep vein thrombosis and thrombotic complications. [2]
Paroxysmal nocturnal hemoglobinuria (PNH) Patients with PNH are susceptible for venous thrombosis in addition to hemolytic anemia and bone marrow failure. [3]
Sickle cell anemia Sickle cell anemia is an inherited hemoglobinopathy which has increased risk of thrombosis. Hemoglobin electrophoresis enables the detection of Hb S. [4]
Physiological hypercoagulability in pregnancy Pregnancy is a hypercoagulable state. It is due to increase in factor VII, factor VIII, Factor X, von Willebrand factor, and fibrinogen levels in blood. [5]
References
  1. SANNA G.. Central nervous system involvement in the antiphospholipid (Hughes) syndrome. [online] 2003 February, 42(2):200-213 [viewed 18 August 2014] Available from: doi:10.1093/rheumatology/keg080
  2. CHAN M. Y., ANDREOTTI F., BECKER R. C.. Hypercoagulable States in Cardiovascular Disease. Circulation [online] December, 118(22):2286-2297 [viewed 19 August 2014] Available from: doi:10.1161/​CIRCULATIONAHA.108.778837
  3. BRODSKY R. A.. How I treat paroxysmal nocturnal hemoglobinuria. Blood [online] December, 113(26):6522-6527 [viewed 19 August 2014] Available from: doi:10.1182/blood-2009-03-195966
  4. FRENETTE PAUL S., ATWEH GEORGE F.. Sickle cell disease: old discoveries, new concepts, and future promise. J. Clin. Invest. [online] 2007 April, 117(4):850-858 [viewed 19 August 2014] Available from: doi:10.1172/JCI30920
  5. BATTINELLI ELISABETH M., MARSHALL ARIELA, CONNORS JEAN M.. The Role of Thrombophilia in Pregnancy. Thrombosis [online] 2013 December, 2013:1-9 [viewed 19 August 2014] Available from: doi:10.1155/2013/516420

Investigations - for Diagnosis

Fact Explanation
Antiphospholipid antibody (aPL) aPL antibody is usually present in almost all patients with APS, but its mere presence does not diagnose APS. [1,2,3]
Lupus anticoagulants (LA) LA is an autoantibody which prolong the clotting time by reducing the coagulant potential. [1,2,3]
Anticardiolipin antibodies (aCL) Similar to LA, aCL antibody reduces the coagulant potential and prolongs the activated partial thromboplastin time. Presence of LA or aCL antibodies and clinical symptoms of APS is necessary for making the diagnosis of APS. [1,2,3]
Coagulation profile Activated partial thromboplastin time is usually prolonged due to the presence of LA and aCL antibodies. Assessment of dilute Russell Viper venom time (dRVVT), kaolin clotting time and plasma clotting time can also be done and all are prolonged. [1]
Full blood count Thrombocytopenia, and anemia can be detected in full blood count. [1]
References
  1. DI PRIMA FA, VALENTI O, HYSENI E, GIORGIO E, FARACI M, RENDA E, DE DOMENICO R, MONTE S. Antiphospholipid Syndrome during pregnancy: the state of the art J Prenat Med [online] 2011, 5(2):41-53 [viewed 18 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3279165
  2. DERKSEN R H W M. How to treat women with antiphospholipid antibodies in pregnancy?. [online] 2001 January, 60(1):1-3 [viewed 18 August 2014] Available from: doi:10.1136/ard.60.1.1
  3. ZHENG XJ, DENG XL, LIU XY. [Pregnancy outcome in 54 patients with antiphospholipid syndrome: a retrospective clinical study]. Beijing Da Xue Xue Bao [online] 2014 Apr 18, 46(2):323-8 [viewed 18 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/24743831

Investigations - Fitness for Management

Fact Explanation
Renal function test Patients with APS can develop renal infarction and cortical necorsis leading to deminished renal function. Altered electrolyte profile and raised serum creatinine are indicative of renal failure. [1]
Fetal ultrasound scan Multiple placental infarctions can cause placental insufficiency and intrauterine growth retardation. Measurement of amniotic fluid index is also important as oligohydroamnios is another recognized complication of APS. If intrauterine growth retardation is suspected fetal ultrasound scan should be repeated every 3-4 weeks. Uterine and umbilical artery Doppler assessments are indicated to assess the fetal well being and perfusion. [1]
References
  1. DI PRIMA FA, VALENTI O, HYSENI E, GIORGIO E, FARACI M, RENDA E, DE DOMENICO R, MONTE S. Antiphospholipid Syndrome during pregnancy: the state of the art J Prenat Med [online] 2011, 5(2):41-53 [viewed 18 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3279165

Investigations - Followup

Fact Explanation
Full blood count Low platelet levels can be observed in HELLP syndrome. [1]
Blood picture Patients with APS can develop HELLP syndrome and hemolytic anemia. [1]
Hepatic transaminases Elevated transaminases are a component of HELLP syndrome. [1]
References
  1. DI PRIMA FA, VALENTI O, HYSENI E, GIORGIO E, FARACI M, RENDA E, DE DOMENICO R, MONTE S. Antiphospholipid Syndrome during pregnancy: the state of the art J Prenat Med [online] 2011, 5(2):41-53 [viewed 18 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3279165

Investigations - Screening/Staging

Fact Explanation
Antiphospholipid antibody (aPL) Although universal screening for APS is not indicated, if the patient has symptoms and signs suggestive of APS (recurrent miscarriages, thrombotic phenomena) assessment of aPL is indicated. [1]
References
  1. DI PRIMA FA, VALENTI O, HYSENI E, GIORGIO E, FARACI M, RENDA E, DE DOMENICO R, MONTE S. Antiphospholipid Syndrome during pregnancy: the state of the art J Prenat Med [online] 2011, 5(2):41-53 [viewed 18 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3279165

Management - General Measures

Fact Explanation
Health education Patients with APS and pulmonary hypertension should be advised not to get pregnant. They should be using a permanent method of contraception. It is better to delay the pregnancy, if the patient has uncontrolled hypertension or recent thrombotic events. All patients should consult proper medical advise before getting pregnant and should be followed up closely during the period of pregnancy. Patients should be educated about the possible maternal and fetal complications. They should be capable of identifying the complications of the disease (thrombotic phenomena, seizures, impending eclampsia). [1,2]
References
  1. DI PRIMA FA, VALENTI O, HYSENI E, GIORGIO E, FARACI M, RENDA E, DE DOMENICO R, MONTE S. Antiphospholipid Syndrome during pregnancy: the state of the art J Prenat Med [online] 2011, 5(2):41-53 [viewed 18 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3279165
  2. MARCHETTI T, COHEN M, GRIS JC, DE MOERLOOSE P. Diagnosis and management of obstetrical antiphospholipid syndrome: where do we stand? Pol Arch Med Wewn [online] 2013, 123(12):713-20 [viewed 18 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/24382555

Management - Specific Treatments

Fact Explanation
High dose prednisone and low-dose aspirin Combination of high dose prednisone (40–60 mg daily) and low-dose aspirin (75 mg daily) is indicated in the treatment of APS during the early pregnancy. [1,2]
Heparin and low-dose aspirin Heparin and low dose aspirin are used in the treatment of APS, as this reduces the incidence of thrombotic complications associated with APS. Prophylactic heparin is indicated for patients with a prior history of recurrent miscarriages. If the patient has had a thrombotic complication (Eg: stroke) they need therapeutic doses of heparin to achieve full anticoagulation. Low molecular heparin should be stopped at least before 12 hours of labor or planned Cesarean section and should be restarted during the post partum period to minimize the risk of deep vein thrombosis. [1,2]
Intravenous immunoglobulin Intravenous immunoglobulin when used in high doses is proven to reduce the pregnancy related complications. [2]
References
  1. DI PRIMA FA, VALENTI O, HYSENI E, GIORGIO E, FARACI M, RENDA E, DE DOMENICO R, MONTE S. Antiphospholipid Syndrome during pregnancy: the state of the art J Prenat Med [online] 2011, 5(2):41-53 [viewed 18 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3279165
  2. DERKSEN R H W M. How to treat women with antiphospholipid antibodies in pregnancy?. [online] 2001 January, 60(1):1-3 [viewed 18 August 2014] Available from: doi:10.1136/ard.60.1.1