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• Coagulation disorders and thromboembolic diseases during pregnancy can have significant impacts on reproductive outcomes.

Objectives:

• Reviewing normal physiological changes of the coagulation system during pregnancy is necessary.
• Understanding acquired and inherited types of coagulation disorders is key.
• Management considerations during the antenatal, intrapartum, and postpartum periods must be understood.
• Accurate management of patients with or at risk of thromboembolic diseases should be known.
• Knowing the impact of these diseases on reproductive outcome will aid in diagnosis and treatment.

Thrombocytopenia:

• Defined as a platelet count of less than 150 × 109/L; normal platelet count ranges from 150,000 to 400,000.
• Causes during pregnancy include idiopathic reasons (increased consumption or destruction, autoimmune, antiphospholipid syndrome, pre-eclampsia, HELLP syndrome, disseminated intravascular coagulation, thrombotic thrombocytopenic purpura, hypersplenism) and decreased production (sepsis, HIV infection, or malignant marrow infiltration).

Types of Thrombocytopenia During Pregnancy:

• Two common types are gestational (incidental) thrombocytopenia and autoimmune thrombocytopenia.

Gestational Thrombocytopenia:

• Found in 7-8% of pregnancies.
• Usually presents with mild platelet count decrease (100-150,000/ml).
• Rarely associated with bleeding or adverse maternal outcomes.
• Diagnosed by excluding other causes.
• Typically occurs in late pregnancy without a prior history.
• Management involves monitoring platelet counts during pregnancy; intervention isn't usually needed.
• There is no risk for fetal thrombocytopenia.
• It resolves spontaneously after delivery.

Autoimmune Thrombocytopenia (ITP):

• Occurs in 1 out of 5000 pregnancies.
• Caused by autoantibodies against platelet surface antigens; can occur at any stage of pregnancy.
• Fetal thrombocytopenia risk is between 5-10%.

Management of Autoimmune Thrombocytopenia During Pregnancy:

• Serial monitoring of platelet levels is needed.
• Treatment is considered if the count falls below 50*109/L near term.
• Corticosteroids (starting dose 40-60 mg prednisolone) suppress platelet autoantibodies, but may require high doses and can lead to side effects like weight gain, hypertension, and diabetes; also take 2-3 weeks to have a significant effect.
• Intravenous immunoglobulin G (IgG) is more expensive but preferred when rapid platelet increase is required near term, or if treatment is likely to be prolonged or if unacceptably high maintenance doses of prednisolone are required.

Platelet Count and Bleeding Risk:

• Spontaneous bleeding during pregnancy is unlikely if the platelet count is >20 × 109/l.
• Maternal hemorrhage at delivery is likely if the platelet count is less than 50 × 109/l.
• During pregnancy, there is a risk of spontaneous bleeding with a platelet count below 20x109.
• At delivery spontaneousbleeding risk begins with counts below 50x109.
• There is a 5-10% risk of fetal thrombocytopenia.
• Blood sample must be collected for platelet counting, and any test results cannot be predicted by maternal test results.

Delivery Considerations with Thrombocytopenia:

• Vaginal delivery should be facilitated if possible.
• Regional anesthesia should be avoided if the platelet count is <80 × 109/1.
• Fetal blood sampling in labor and instrumental delivery by ventouse should be avoided.
• Other precautions include avoiding assisted delivery to prevent tears, preparing platelets and blood, and active management of the third stage of labor (oxytocin, controlled cord traction).

Suitable Mode of Delivery and Anesthesia:

• Vaginal delivery is preferred under most medical conditions unless pushing is harmful.
• If a C-section is indicated (e.g., breech), general anesthesia should be used to avoid bleeding risk at the site of regional anesthesia.
• Platelet counts during delivery should be above 50x109/L.
• For C-section or epidural anesthesia, the platelet count must be above 80 x10 9/L.

Inherited Coagulation Disorders:

• Von Willebrand disease, carriers of hemophilia A and B, and factor XI deficiency account for over 90% of inherited bleeding disorders in women.

Features of Inherited Coagulation Disorders:

• Hemophilia A (Factor VIII Deficiency) and Hemophilia B (Factor IX Deficiency) are X-linked recessive.
• Von Willebrand Disease (VWD) and Factor XI Deficiency are autosomal dominant.
• Prevalence: Hemophilia A (1 in 10,000 males), Hemophilia B (1 in 100,000 males), VWD (1% of the population, most cases), Factor XI Deficiency (rare).
• Carrier Clotting Factor Levels: ~50% of normal Factor VIII or IX levels in hemophilia carriers; varies in VWD; variable in Factor XI deficiency.
• Effect of Pregnancy: Factor VIII levels rise significantly in Hemophilia A; Factor IX levels rise slightly in Hemophilia B; Factor VIII and VWF levels may rise in VWD, and Factor XI levels do not significantly rise in Factor XI deficiency.
• Bleeding Risk: Moderate risk in hemophilia (depending on factor levels), significant risk in severe VWD, and significant risk not directly related to levels for Factor XI deficiency.
• Management During Pregnancy: Factor assays in early pregnancy and third trimester (fetal sex determination for hemophilia); Factor assays for VWD and potential use of desmopressin or VWF concentrate; Factor assays and may require prophylactic treatment in Factor XI deficiency.

Treatment Options During Delivery:

• Hemophilia: Use Factor VIII concentrate, tranexamic acid, desmopressin (DDAVP) if responsive.
• Hemophilia B: Factor IX concentrate and tranexamic acid.
• VWD: Desmopressin (DDAVP) for Type 1 VWD, VWF concentrate, tranexamic acid.
• Factor XI Deficiency: Factor XI concentrate or antifibrinolytics (tranexamic acid).

Pre-Pregnancy and Antenatal Management for Inherited Hemophilia:

• Counseling prior to pregnancy is essential.
• Management should involve a team with expertise in association with a hemophilia center.
• Baseline coagulation factor assays should be performed as soon as pregnancy is confirmed and repeated in the third trimester.
• Determination of fetal sex (male is affected, female is a carrier) via ULS or fetal DNA sampling in maternal blood.
• Invasive procedures should be covered with a clotting factor.
• Prophylactic treatment with recombinant factors should be provided for those with low factor levels to cover labor and delivery.

Management During Labor and Postpartum Period:

• A clotting factor activity >40 IU/dl is safe for vaginal delivery and >50 IU/dl is adequate for C-section.
• Active management of the third stage of labor helps decrease the risk of bleeding.
• Cord blood should be sent for factor level analysis.
• Vitamin K can be administered orally to the fetus, avoiding IM injection.
• Tranexamic acid or recombinant factor replacement may need to be continued for several days postpartum.
• If a C-section is needed for obstetrical complications only.

DIC (Disseminated Intravascular Coagulation):

• DIC is a serious disorder with widespread activation of the coagulation cascade, resulting in both thrombosis and hemorrhage.
• Excessive bleeding at trauma sites and persistent bleeding from venipuncture sites are clinical presentations.
• Purpuric areas at pressure sites may also indicate incoagulable blood.
• DIC is a secondary condition triggered by an underlying disorder: sepsis (most common), trauma, cancer, obstetric complications (e.g., placental abruption, amniotic fluid embolism), and severe allergic reactions

DIC Pathophysiology:

• Both pathways become equally involved, eventually resulting in excessive coagulation and fibrinolysis, because all of the body's natural clotting resources become depleted.
• Extrinsic pathway is more involved in initiating it, particularly through the release of tissue factor during underlying conditions: sepsis or trauma.
• Prolongation of PT and PTT.
• Decreased platelets.
• Low serum fibrinogen. Decreased platelets count.
• Increased FDP (fibrin degradation products).

DIC Treatment:

• Treatment of the underlying cause is the primary focus; antibiotics for sepsis or removal of dead tissue in trauma.
• Platelet transfusions are used for patients with significant bleeding and thrombocytopenia.
• Fresh frozen plasma (FFP) is administered to replace coagulation factors if PT/aPTT is significantly prolonged and bleeding is ongoing.
• Cryoprecipitate is used for low fibrinogen levels.
• Anticoagulation (Heparin) is cautiously used in cases of overwhelming thrombosis but avoided in patients with active bleeding.

Thromboembolic Diseases During Pregnancy:

• The most common cause of direct maternal death in the UK.
• Pregnancy is associated with a 6-10 fold increase in VTE risk compared to non-pregnant individuals.

without thromboprophylaxis:

• The incidence of DVT has increased to 1-2% after delivery.
• The incidence of PE has increased to 0.1%.
• Deep venous thrombosis alone was more common antepartum, whereas pulmonary embolism was more common in the first 6 weeks postpartum.

Physiological Changes in Coagulation During Pregnancy:

• Virchow's Triad explains the physiological changes to avoid.
• Hypegulability: ↑factors V, VII, VIII, IX, X, XII, fibrinogen, and vWF, ↑antithrombin III, protein C, ↓protein S, ↑plasminogen activator inhibitor.
• Vascular damage needs treating.
• Venous stasis must be avoided.

Risk Factors for Thromboembolic Disease:

• Preexisting factors: maternal age (>35 years), thrombophilia, obesity (>80 kg), previous thromboembolism, severe varicose veins, smoking, malignancy.
• Factors specific to pregnancy: multiple gestation, pre-eclampsia, grand multiparity, caesarean section (especially if emergency), damage to the pelvic veins, sepsis, prolonged bed rest.

Thrombophilias:

• Some women are predisposed to thrombosis through changes in the coagulation/fibrinolytic system that may be inherited or acquired.
• Account for more than 50 percent of all thromboembolic events during pregnancy
• Hereditary causes include Factor V Leiden, Prothrombin G20201A, Hyperhomocysteinemia, Antithrombin deficiency, Protein S deficiency, and Protein C deficiency.
• Acquired thrombophilias include antiphospholipid antibodies or antiphospholipid syndrome.

Antiphospholipid Antibody Syndrome:

• The syndrome with or without anticardiolipin antibodies.
• With a history of recurrent miscarriage or thrombosis.
• Clinical Diagnosis: 3 or more unexplained early miscarriages, fetal death more than 10 weeks, preterm birth before 35 weeks due to severe PE or IUGR.
• Related history of venous or arterial thrombosis
• Laboratory Diagnosis: LA, IgG and/or IgM (medium/high titre) 2 occasions 8 weeks apart, aCL IgG and/or IgM (medium/high titre) 2 occasions 8 weeks apart.

Treatment of Thrombophilia:

• Some recommend empirical treatment with aspirin and/or low-molecular-weight heparin.
• In general, treatment during subsequent pregnancies has consisted of enoxaparin, 40 mg daily in those with previous pregnancy complications or 60 mg daily in those with a prior thromboembolic event.
• In early pregnancy should be given, stillbirth could result.
• Additionally Pre-eclampsia Placental abruption and IUGR could result.

Deep Vein Thrombosis:

• Most venous thrombosis during pregnancy is confined to the deep veins of the lower extremity.
• Commonly occurs in the left leg.
• Compression of the left common iliac vein by the right common iliac artery could be the underlying cause.
• Diagnosis: Clinical features include calf pain (most common), redness and swelling, calf tenderness, and symptoms of underlying diseases predisposing to DVT.

DVT Investigations and Diagnostics:

• Compression ULS: 1st line method with high sensitivity and specificity in diagnosis of proximal DVT.
• Invasive contrast venography: Excludes lower extremity DVT but is not preferable in pregnancy due to radiation exposure.

Treatment of Acute DVT During Pregnancy and Puerperium:

• Management should be performed in an obstetric/medicine clinic.
• Any clinical suspicion of VTE should be investigated asap.
• Risk factor assessment for VTE should be performed and the woman should then be counselled accordingly.
• Graduated compression stockings should be worn in the acute period and for 2 years.

DVT & VTE Treatment:

• Blood should be taken for FBC, renal and liver function tests, clotting screen, and thrombophilia (inherited) screen.
• Appropriate thromboprophylaxis should be commenced w SC LMWH.
• LMWH is continued throughout pregnancy and for at least 12 weeks after delivery.
• Warfarin is not recommended during pregnancy.
• Mobilization and hydration are critical components of treatment.

VTE & DVT prophylaxis:

• Low: mobilization and hydration.
• Moderate and high : antenatal and post natal prophylaxis till 6 weeks.
• Antenatal with LMWH + hydration and mobilization.
• High and intermediate risk : at least 6 weeks of LMWH + hydration and mobilization.
• Enoxaparin is the preferred therapeutic drug.

Pulmonary Embolism:

• It is crucial to recognize PE as a possible diagnosis.
• The most common presentation is mild breathlessness or inspiratory chest pain in a woman who is not cyanosed but may be slightly tachycardic (>90 bpm) with a mild pyrexia (37.5°C).
• In rare cases, massive PE may present with sudden cardiorespiratory collapse.

Diagnostic Standards for Pulmonary Embolism:

• CT pulmonary angiogram is the gold standard investigation.
• Other tests include ventilation perfusion (V/Q) scan, ECG, chest X-ray, and arterial blood gases. (should be performed to exclude other respiratory disease)

Treatments for Pulmonary Embolism:

• D-dimer testing, Multidisciplinary team, call for help , ABC, IV UFH is preferred in acute stage.
• Thrombolysis with streptokinase is reversed for unstable patient (risk of bleeding),.
• Surgical embolectomy can then occur.