Tromboembolia pulmonar y embarazo

Tromboembolia Pulmonar en el Embarazo

Introducción al Tema

• El Dr. Salvador Jiménez Chaidez presenta la monografía sobre tromboembolia pulmonar en el embarazo, destacando su relevancia médica y social.

• La monografía fue coordinada por el Dr. Carlos Agustín Zapata Caballero y supervisada por el Dr. Miguel Ángel Arias Tories.

Objetivos de la Monografía

• Conocer el impacto médico y social de la trombosis venosa durante el embarazo.

• Recordar la fisiopatología de la trombosis y los factores de riesgo asociados.

• Identificar métodos diagnósticos en embarazadas, especialmente aquellos que utilizan radiación ionizante.

Epidemiología del Tromboembolismo Venoso

• Se observa un aumento del riesgo de trombosis a medida que avanza la gestación, con un pico durante el último trimestre.

• La relación entre trombosis venosa profunda (TVP) y tromboembolismo pulmonar (TEP) es 4 a 1; hasta un 63% de los casos de TVP ocurren ante parto.

Mortalidad Asociada

• El TEP está asociado con una tasa de mortalidad materna del 15%, con una letalidad reportada del 5%.

• En México, las enfermedades respiratorias representan un 3.5% de las muertes maternas, similar a las estadísticas globales.

Datos Específicos del Instituto Nacional

• Desde 2016 hasta 2020, se reportaron 345 casos de TVP en el instituto; solo cuatro confirmados como TEP concomitante.

Contenido Adicional de la Monografía

• Se abordarán adaptaciones fisiológicas en ventilación y hemostasia durante el embarazo, así como algoritmos diagnósticos propuestos por diferentes instituciones internacionales.

Fisiología Respiratoria Durante el Embarazo

• Cambios pulmonares incluyen aumento del volumen tidal hasta un 33% y disminución del volumen residual hasta un 30%.

• Las hormonas del embarazo afectan directamente al centro respiratorio aumentando la frecuencia respiratoria.

Sistema Hemostático Durante el Embarazo

• El sistema hemostático se divide en coagulación y plaquetario para formar un trombo rico en plaquetas, crucial para prevenir hemorragias durante el parto.

Coagulation and Fibrinolysis: Key Mechanisms in Hemostasis

The Role of the Endothelial Cells in Hemostasis

• The vascular endothelium plays a crucial role in hemostasis, balancing between quiescence and activation based on various factors acting on its membrane and nucleus. This balance is essential for maintaining blood fluidity and managing endothelial injury to prevent hemorrhage.

• Anticoagulant agents such as antithrombin III, protein C, plasminogen, tissue plasminogen activator (tPA), and anti-plasmin are vital for maintaining endothelial integrity and vasodilation, ensuring that blood remains liquid under normal conditions.

Coagulation Cascade Activation

• Pro-coagulant factors like fibrinogen, tissue factor, collagen, von Willebrand factor (vWF), and phospholipids activate the coagulation system upon endothelial damage. These elements lead to vasoconstriction and platelet aggregation, ultimately resulting in thrombosis.

• Upon endothelial injury, collagen and tissue factor are released into circulation; tissue factor binds with activated factor VII to amplify the coagulation cascade while exposed collagen activates vWF to facilitate platelet adhesion.

Immune System Interaction with Coagulation

• The activation of coagulation also triggers immune responses by promoting monocyte aggregation and neutrophil extracellular trap formation (NETs), which further perpetuates the coagulation cascade. Platelet activity is critical for forming a fibrin-rich thrombus necessary to halt bleeding effectively.

Phases of Platelet Activity

• Platelet activity can be categorized into three phases: adherence, activation, and aggregation. Proper functioning of these phases is essential for forming an effective thrombus that prevents excessive blood loss during vascular injury.

• Initial responders at an endothelial lesion include platelets alongside immune cells; they begin activating through interactions with clotting factors like activated factor VII and X which catalyze thrombin production—an essential component in coagulation processes.

Thrombin's Role in Clot Formation

• Activated factor X combines with activated factor V and calcium ions to convert prothrombin into thrombin—a pivotal step that leads to fibrin formation necessary for stable clot development. Thrombin facilitates proper fibrin assembly along with platelet aggregation to form a robust thrombus preventing further blood loss from injuries.

Regulation of Fibrinolysis

• Just as there is significant regulation within the thrombosis process, there exists an equally important regulatory mechanism governing fibrinolysis—the breakdown of clots post-hemostasis via plasminogen activators such as tPA or urokinase that inhibit excess clot formation in plasma environments.

Understanding Coagulation and Thrombosis in Pregnancy

Mechanisms of Platelet Activity

• The activation of the immune system following endothelial injury perpetuates platelet activity and coagulation cascades. This process involves three key functions: adherence, activation, and aggregation, which are essential for proper thrombus formation to prevent hemorrhage.

Role of Coagulation Factors

• Endothelial injury leads to the rapid appearance of platelets and immune cells. Tissue factor exposure activates the coagulation cascade via factor VII and activated factor X, enhancing thrombus formation. Ultimately, activated factor X works with activated factor V and calcium to convert prothrombin into thrombin, a crucial coagulation factor that generates fibrin. A fibrin-rich thrombus effectively halts blood loss.

Fibrinolysis During Pregnancy

• There is significant regulation of the thrombosis system at a systemic level alongside a well-defined fibrinolytic system. Changes in coagulation factors during pregnancy vary with gestational age; factors such as fibrinogen and factor VIII peak in the third trimester before returning to non-pregnant levels postpartum. Notably, tissue plasminogen activator (tPA) and antithrombin III decrease significantly during pregnancy, indicating a state of hypercoagulability with hypofibrinolysis aimed at reducing obstetric hemorrhage risk towards delivery.

Hypercoagulability in Pregnancy

• Pregnancy is characterized by hypercoagulability coupled with hypofibrinolysis as a physiological adaptation to minimize obstetric bleeding risks during labor and delivery. The presentation will cover topics including venous thromboembolism pathophysiology, risk factors, diagnostic algorithms from various international guidelines, therapeutic options like heparins, among others related to this condition throughout pregnancy and postpartum periods.

Triad of Virchow's Factors

• The triad of Virchow includes venous stasis, hypercoagulability, and endothelial injury—all significant risk factors for venous thromboembolism (VTE). Venous stasis occurs due to anatomical changes during pregnancy that compress pelvic veins leading predominantly to left-sided stasis; increased pro-thrombotic factors also contribute throughout gestation especially in late stages or postpartum recovery phases. Additionally, both abdominal delivery methods can cause endothelial damage contributing further to VTE risks.

Clinical Presentation of Thrombosis

• When patients cross the thrombosis threshold clinically manifesting as deep vein thrombosis (DVT), it typically presents localized symptoms primarily in the proximal left pelvic limb—this being the most common site during pregnancy for DVT development which may evolve into pulmonary embolism if an embolus travels through venous circulation into pulmonary arteries causing obstruction leading to hypoxia-related clinical signs associated with PE events.

Risk Stratification for Pregnant Patients

• Identifying risk factors associated with VTE is critical; these can be categorized into pre-existing conditions (e.g., history of VTE), obstetric complications (e.g., advanced maternal age), or transient influences (e.g., obesity). Understanding these elements aids healthcare providers in managing pregnant patients effectively against potential thromboembolic events throughout their perinatal journey.

Tromboembolismo Venoso en el Embarazo

Factores de Riesgo Genéticos y Obstétricos

• La concepción de tres o más partos, tabaquismo antes o durante el embarazo, síndrome de anticuerpos antifosfolípidos, paraplejia y venas varicosas son factores que predisponen al tromboembolismo venoso.

• Los factores obstétricos como el embarazo múltiple, preeclampsia, parto prolongado (más de 24 horas), cesárea e hemorragias obstétricas aumentan significativamente el riesgo de tromboembolismo venoso.

• Técnicas de reproducción asistida, hospitalización prolongada y viajes largos sin compresión son factores transitorios asociados al riesgo durante el embarazo.

Antecedentes Personales y Comorbilidades

• Un antecedente personal de trombosis incrementa hasta 23.8 veces el riesgo comparado con quienes nunca han tenido un episodio similar; la edad materna avanzada y la obesidad también son relevantes.

• Condiciones como lupus pueden aumentar el riesgo hasta 7.7 veces; la inmovilización y las venas varicosas son factores críticos para la formación de trombos.

Infecciones Virales y su Impacto

• La infección por SARS-CoV-2 ha sido estudiada desde 2019 por sus efectos sistémicos; se asocia a una activación endotelial significativa que puede llevar a un síndrome de coagulación.

• Se identifican marcadores como un tiempo de tromboplastina alargado y niveles elevados de dímero D (>3000 mg/dL), que pueden predecir mortalidad en embarazadas infectadas.

Diagnóstico del Tromboembolismo Pulmonar (TEP)

• El diagnóstico del TEP en embarazadas es complicado debido a síntomas similares a los cambios normales del embarazo; esto requiere atención especial por parte del personal médico.

• Signos clínicos como edema, dolor unilateral en extremidades pélvicas o claudicación intermitente deben ser evaluados cuidadosamente para descartar TEP.

Estudio Observacional sobre TEP

• El estudio "PEP" (2018) analizó parámetros diagnósticos en pacientes no embarazadas para evaluar su aplicabilidad en embarazadas con sospecha de TEP.

• Reportó una alta incidencia de disnea (54%) y dolor torácico (52%), aunque estos síntomas son inespecíficos durante el embarazo.

Importancia del Tamizaje Adecuado

• Un tamizaje efectivo debe tener alta sensibilidad para incluir correctamente a todos los pacientes con TEP potencial; pruebas específicas ayudan a reducir falsos positivos debido a la baja prevalencia en este grupo.

Clinical Presentation and Laboratory Tests for TEP Risk Assessment

Risk Factors and Clinical Presentation

• The assessment of risk factors, clinical presentation, and laboratory tests is crucial to determine the likelihood of a significant risk or suspicion of pulmonary embolism (TEP), guiding therapeutic interventions or further diagnostic testing.

• Modified probability scales, such as the Geneva scale or the Wells algorithm, help identify patients at risk for TEP, prompting necessary interventions or additional lab tests.

Biomarkers and Imaging Studies

• Key biomarkers for diagnosing TEP include troponin and pro-BNP, particularly in cases involving acute right heart failure associated with massive pulmonary embolism.

• Non-ionizing imaging studies like transthoracic echocardiography, electrocardiograms, and compressive ultrasound are essential in both pregnant and non-pregnant patients to support diagnosis.

Probability Scales in Diagnosis

• Probability scales are used primarily to assess whether intervention is needed for patients with suspected venous thrombosis; they can halt the diagnostic process if no significant risk factors are present.

• The modified Geneva scale evaluates predisposing factors and symptoms/signs to classify patients into low, intermediate, or high clinical probability categories.

Echocardiographic Findings

• Additional studies like transthoracic echocardiograms can reveal right ventricular wall motion abnormalities (McConnell's sign), indicating potential thrombus formation.

• Right ventricular dyskinesia may indicate acute right heart failure due to massive pulmonary embolism; echocardiograms can also measure pulmonary artery pressure.

Diagnostic Ultrasound Efficacy

• Compressive ultrasound of pelvic limbs is considered the gold standard for diagnosing deep vein thrombosis during pregnancy, boasting 96% sensitivity and 97% specificity.

• International guidelines suggest that a positive compressive ultrasound could warrant empirical treatment initiation for TEP.

Ionizing Radiation Studies During Pregnancy

• Studies using ionizing radiation like CT angiography (CTA) and ventilation-perfusion scans (V/Q scans) are deemed safe during late pregnancy and postpartum periods.

• A systematic review from 2019 compared CTA against V/Q scans in pregnant women; it assessed perinatal outcomes across multiple studies involving thousands of pregnancies.

Safety and Efficacy Conclusions

• Both CTA and V/Q scans were found effective during pregnancy with low false-negative rates; however, non-diagnostic results were more common than in non-pregnant populations due to physiological changes during pregnancy.

• Materno-fetal radiation exposure remains within recommended safety thresholds despite increased rates of non-diagnostic results when utilizing these imaging modalities.

Gammagrafía BQ: Pros and Cons

Overview of Gammagrafía BQ

• Gammagrafía BQ requires expert interpretation, while ingestion can occur in various hospital centers without issues.

• Radiation levels are within accepted parameters during pregnancy and postpartum; no increased relative risk for breast cancer linked to these studies.

• The theoretical risk due to systemic estrogen exposure is outweighed by the diagnostic benefits of imaging methods during pregnancy.

International Recommendations on Diagnostic Algorithms

• Various international societies propose diagnostic algorithms for pulmonary embolism (PE) during pregnancy, including recommendations from European Cardiology Society and others.

• A modified GIS algorithm was analyzed in a study involving 510 pregnant patients suspected of having PE, focusing on avoiding ionizing radiation.

Diagnostic Criteria and Risk Assessment

Modified Criteria for Pregnant Patients

• The modified criteria include signs/symptoms of venous thromboembolism (VTE), with a focus on determining D-dimer levels to classify patient risk.

• If D-dimer is below specific thresholds, PE can be safely ruled out without anticoagulant treatment; higher levels indicate the need for further investigation.

Efficacy of the Modified Algorithm

• The study found that the modified algorithm effectively avoided ionizing radiation in 39% of cases but showed decreased efficacy as gestational age increased due to rising thrombosis rates.

• Among 510 patients, only one case of deep vein thrombosis was diagnosed, indicating high safety when following the proposed algorithm.

Clinical Application and Future Directions

Summary of Findings

• The modified algorithm emphasizes clinical signs alongside D-dimer determination; ultrasound may also be used to assess VTE presence directly.

• Key cutoff points for D-dimer vary based on clinical criteria; ongoing evaluation is crucial as variations exist throughout pregnancy.

Diagnostic Effectiveness of Tools in Pregnancy

Evaluation of Diagnostic Tools

• The effectiveness of diagnostic tools is assessed, particularly their ability to diagnose effectively during pregnancy and the postpartum period.

• Initial evaluations focus on whether static tools can aid in diagnosing conditions like deep vein thrombosis (DVT) and pulmonary embolism (PE), with findings indicating low sensitivity and specificity.

Sensitivity and Specificity Findings

• The modified Geneva score shows a specificity of 20% during pregnancy, with a sensitivity of 75%, highlighting significant variability in signs and symptoms.

• Comparative studies suggest that the modified Geneva scale is more effective than the Wells score for diagnosing DVT/PE in pregnant patients.

Risk Stratification Recommendations

• Risk stratification should be based on clinical suspicion using the modified Geneva scale alongside clinical data.

• High-risk patients may require empirical treatment for venous thromboembolism (VTE), while those at low risk should undergo imaging studies starting with pelvic ultrasound.

Diagnostic Algorithm Steps

• If ultrasound results are positive for DVT, empirical treatment is initiated; if negative, further imaging such as chest X-ray or CT angiography may be pursued.

• Non-conclusive results from imaging necessitate expert consultation due to increased inconclusiveness rates during pregnancy caused by physiological changes.

Treatment Protocol Insights

• A negative V/Q scan leads to consideration of alternative imaging; if high clinical suspicion persists despite normal results, further testing is warranted.

• Empirical treatment with low molecular weight heparin (LMWH) is recommended for all patients suspected of PE during pregnancy, regardless of pre-test probability.

Therapeutic Approaches for Pulmonary Embolism

Assessing Patient Stability

• Before initiating therapy for PE, it’s crucial to determine if the patient is hemodynamically stable by evaluating airway management, ventilation status, cardiovascular condition, and mental state.

Standard Treatment Options

• LMWH and unfractionated heparin are considered gold standards for treating PE in pregnant women due to their inability to cross the placental barrier.

• While LMWH is preferred based on cohort studies, its higher cost compared to unfractionated heparin poses financial challenges for long-term anticoagulation throughout pregnancy.

Heparin and Anticoagulation Management in Pregnancy

Heparin Reactions and Cost Considerations

• Heparin can cause allergic reactions or osteoporosis, necessitating continued anticoagulation. The cost of synthetic heparin therapy can be significant for patients.

Therapeutic Techniques for Hemodynamically Unstable Patients

• Various therapeutic techniques are available for hemodynamically unstable patients; inferior vena cava filters have shown effectiveness, especially in those at high risk of thrombosis during pregnancy.

Risks and Complications of Procedures During Pregnancy

• While procedures like thrombolysis can significantly reduce the incidence of pulmonary embolism (PE), they carry a high risk of complications if performed during pregnancy, making preventive measures preferable.

Use of Direct Tissue Factor Activators

• Direct tissue factor activators such as alteplase are recommended under specific conditions during pregnancy but are considered a relative contraindication due to potential risks versus benefits.

Multidisciplinary Management Importance

• A multidisciplinary approach is crucial for managing patients with thromboembolic events (TEP), involving specialists from cardiology, pulmonology, hematology, imaging, intensive care, gynecology, obstetrics, and pulmonary rehabilitation to improve survival rates.

Risk Stratification in Pregnant Patients

• The Royal College of Obstetricians and Gynaecologists proposes a risk stratification system based on various factors to determine the need for prophylaxis against venous thromboembolism (VTE).

Prophylaxis Recommendations Based on Risk Levels

• High-risk patients should receive prenatal prophylaxis with low molecular weight heparin (LMWH). Intermediate-risk patients may require gestational prophylaxis until resolution.

Postpartum Prophylaxis Guidelines

• In the postpartum period, high-risk patients should continue LMWH prophylaxis for at least six weeks. For intermediate-risk cases, it should last at least ten days post-delivery.

Aspirin Use in Thrombosis Prevention

• Patients with significant risk factors should maintain low-dose aspirin preconceptionally to prevent recurrent thrombosis. Upon confirmation of pregnancy, LMWH is added alongside aspirin.

Managing Recurrent Thrombosis During Pregnancy

• In cases of recurrent thrombosis with high-risk factors like mechanical heart valves during pregnancy, warfarin treatment must be switched to LMWH and low-dose aspirin upon confirmation of pregnancy.

Adjustments in Anticoagulation Dosing

• Enoxaparin may be used prophylactically at 40 mg subcutaneously every 24 hours; dosing adjustments may be necessary as gestation progresses due to increased blood volume.

This structured summary provides an organized overview of key points discussed regarding anticoagulation management in pregnant patients while highlighting critical insights into risks and recommendations based on patient profiles.

Understanding Antithrombotic Prophylaxis in Pregnancy

Recommendations for Heparin Dosage

• The Canadian Society of Obstetricians and Gynaecologists recommends a subcutaneous dose of 40 mg of low molecular weight heparin every 24 hours to prevent thrombosis during pregnancy.

• Doses should be increased throughout each trimester due to rising effective circulatory volume, necessitating more frequent doses as renal clearance of heparin increases. Initial dosing can start at 5000 units every 12 hours in the first trimester.

Challenges in Thromboprophylaxis

• Up to 72% of inadequate thromboembolic prophylaxis cases are attributed to failure to administer indicated prophylaxis, often linked to patient adherence issues during pregnancy and postpartum.

• Other significant risk factors include delays in initiating anticoagulation, incorrect or undervalued dosing based on weight and type of heparin used, and insufficient duration of antithrombotic prophylaxis.

Timing Considerations for Heparin Administration

• The timing for resuming prophylaxis after epidural block is crucial; with unfractionated heparin, it is recommended to wait at least one hour post-block or catheter removal before restarting prophylaxis. For low molecular weight heparin, it can resume 12 hours after the block or 4-6 hours post-catheter removal.

• Intermediate or therapeutic doses require a longer waiting period (24 hours post-block) before resuming treatment.

Clinical Implications and Risk Factors

• Thromboembolism is rare but carries a high mortality rate; thus, healthcare professionals must identify risk factors and symptoms associated with pulmonary embolism (PE), especially since pregnancy induces a state of hypercoagulability and hypofibrinolysis. Proper detection thresholds must be adjusted postpartum due to increased risks during this period.

• Deep vein thrombosis (DVT) is common during pregnancy, while PE incidence peaks postpartum, leading to maternal mortality; understanding these dynamics aids in diagnosis and management strategies for affected patients.

Diagnostic Approaches

• In cases suggestive of DVT or PE, compressive ultrasound is recommended for indirect diagnosis; empirical treatment with anticoagulants may also be warranted based on clinical presentation prior to definitive imaging results. Continuous prevention through proper thrombo-prophylaxis during pregnancy and postpartum remains essential for patient safety.