Pulmonary Embolism in the First Trimester of Pregnancy

Obstetrics & Gynecology International Journal

Case Report Open Access Pulmonary embolism in the first trimester of pregnancy

Summary Volume 11 Issue 1 - 2020 Pulmonary embolism in the first trimester of pregnancy without a known medical history Orfanoudaki Irene M is a very rare complication, which if it is misdiagnosed and left untreated leads to sudden Obstetric Gynecology, University of Crete, Greece pregnancy-related death. The sings and symptoms in this trimester are no specific. The causes for pulmonary embolism are multifactorial but in the first trimester of pregnancy, Correspondence: Orfanoudaki Irene M, Obstetric the most important causes are hereditary factors. Many times the pregnant woman ignores Gynecology, University of Crete, Greece, 22 Archiepiskopou her familiar hereditary history and her hemostatic system is progressively activated for the Makariou Str, 71202, Heraklion, Crete, Greece, Tel +30 hemostatic challenge of pregnancy and delivery. The hemostatic changes produce enhance 6945268822, +302810268822, Email coagulation and formation of micro-thrombi or thrombi and prompt diagnosis is crucial to prevent and treat pulmonary embolism saving the lives of a pregnant woman and her fetus. Received: January 19, 2020 | Published: January 28, 2020 Keywords: pregnancy, pulmonary embolism, mortality, diagnosis, risk factors, arterial blood gases, electrocardiogram, ventilation perfusion scan, computed tomography pulmonary angiogram, magnetic resonanance, compression ultrasonography, echocardiogram, D-dimers, troponin, brain natriuretic peptide, foetal radiation, radiation exposure, thrombolysis, heparin, low molecular weight heparin, anticoagulant, prevention, thromboprophylaxis

Abbreviations: CTPA, computed tomography angiography; staphylococcus and cefuroxime was given to her for fourteen days. BNP, brain natriuretic peptide; MDCTA, multidetector-row computer The auscultation of the lungs ascertained a limited lung whispering tomography angiography; UFH, unfractionated heparin; LMWH, low on the right middle lobe of the lung and an absent lung whispering molecular weight heparins on the beneath lobe. The blood tests were normal but fibrinogen and D-dimers were unusually elevated. PT 10.8, APTT 29.2, INR 1.0, Case presentation FIBRINOGEN 937.3, D-dimers 4.3. The suspicion of a right lung This case concerns a woman 35 years old, primipara, with a embolism was very high. spontaneous conception. In her medical history never included pills, The woman was examined by a cardiologist for the pain. Her not known abortion, never active smoker, without any known history physical examination, ECG, the ultrasound and Doppler of the heart of thrombophilia, not known trauma to the lower extremities, a BMI were normal. <25Kg/m2, very active, without medical co-morbidities, without travel of 4 hours or more in the past. She had not any disease up to then. A pulmonologist examined the primipara. Her blood gases were normal. The pain on the right scapula and the lung whispering were When her Human Horionic Gonadotropin was 2221IU/ml, attributed to freezing of the muscles and nerves co-ordinate of that she was attended at the first time from her Gynecologist, where an part of the body. The orthopedic gave the same diagnosis for the inta-uterine pregnancy was diagnosed. A gestation sac 1.14cm with primipara (Figure 1). a normal lecithic sac and an obvious fetus 0.11cm were detected. The ovaries were normal without corpus luteum and the cervix was The urgency departments of two Hospitals refused to perform lung closed with a length of 3.67cm. She was taken advice and came x-Ray to her because of the first trimester of pregnancy and denied the back after two weeks when the CRL was 6+2, the fetus’s heart rate admission to the hospital was positive and a subchorionic hematoma 2.64x0.85x0.75cm was observed. Progesterone tablet 100mg 1x3p.os and creme progesterone A second pulmonologist examined the pregnant woman. The per vaginal in the morning 1x1 was given to her. The pregnancy saturation of blood and acid-base equilibrium was normal and the was getting on normally and the values of blood tests including the diagnosis was the same: freezing of the muscles and nerves. fibrinogen, prothrombin, and APTT were in the normal range. (PT During these two days, the primipara except the feeling of severe patient11.5, PT controls 11.5, INR 1.00, APTT 28.9, Fibrinogen 380). pain she was not able to lie down. The next day she presented sputum After two weeks, the woman was examined again. The fetus with blood. An otolaryngologist examined the woman but he did not was alive and was corresponded to the age of the pregnancy. The find an obvious reason for the bleeding. subchorionic hematoma was smaller 1.53x0.59cm. The woman was admitted urgently to the hospital. Her At eleven weeks and five days, the pregnant woman came back to hemodynamic state was normal and she never presented fever. The her doctor complaining about a settled severe pain on her right lung, D-Dimers and fibrinogen were more increased. Some young doctors especially on her right scapula with the rid distribution. She didn’t a supported that these values of fibrinogen and D-dimers were enhanced present fever or caught. The fetus was alive with heartbeat 171.43bpm, due to pregnancy. Because the symptoms were getting worse, a lung CRL 2.23cm, and gestational sac 4.38cm. The subchorionic hematoma x-ray was performed. The x-ray indicated a shadow right pericardiac remained at the same dimensions. The vagina cultures presented of the lung. The suspicion of pulmonary embolism was intense. A

Submit Manuscript | http://medcraveonline.com Obstet Gynecol Int J. 2020;11(1):23‒28. 23 ©2020 Orfanoudaki. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and build upon your work non-commercially. Copyright: Pulmonary embolism in the first trimester of pregnancy ©2020 Orfanoudaki 24

triplex of the pelvis and legs was performed which was normal. Also, acute pulmonary embolism of the right middle and low lobe with two a heart ultrasound was repeated with normal results (Figure 2). possible small obstructions of the right low lobe signs were Sat 99% with FiO 21%, arterial blood pressure 95/53mm Hg and pulses 94/ A CTPA – Computed tomography angiography of the pulmonary 2 min (Figure 3). artery was performed which elevated the existence and lesions of an

Figure 1 ECG of primipara.

Figure 2 Heart Ultrasound of primapara at the time of severe pain.

Citation: Orfanoudaki IM. Pulmonary embolism in the first trimester of pregnancy.Obstet Gynecol Int J. 2020;11(1):23‒28. DOI: 10.15406/ogij.2020.11.00484 Copyright: Pulmonary embolism in the first trimester of pregnancy ©2020 Orfanoudaki 25

Figure 3 Pictures of CTPA–Computed tomography angiography. The control for thrombophilia was shown: FV Leiden heterozygous, G20210 heterozygous, MTHFR normal, the antibodies against phosphatidylserine IgM was 24.1 with highest limit 25 and IgG 32,1 with the highest limit 25. The rest control was normal. The enoxaparin was changed 0.8 twice per day. The fetus was developing normally and there were no pathologic findings from the pregnancy. The Nuchal translucency and PAPP-A test were normal, amniocentesis indicated 46, XX fetus and the ultrasound of fetal heart was normal. The baby was born with a normal delivery at 39 weeks of pregnancy, with Apgar score, 9,10,10,10 and birth weight 2920 gr. The puerpera continued the enoxaparin in therapeutic doses for four months. After four years she born her second child with enoxaparin 0,45 twice from the begging of the pregnancy till four months.

Discussion S deficiency, Factor V Leiden, Plasminogen abnormality, Plasminogen activator abnormality, fibrinogen abnormality, Resistance to activated The disturbances of coagulation factors are not so obvious in protein C, lupus anticoagulant, homocystinuria, occult neoplasm, the usual screening test in the general population, and they are not connective tissue disorders. required for all pregnant women as a screening test. As well as, these tests have a significant cost for the woman and the health system D-dimer concentration rises gradually during pregnancy. Negative of the country. The family history may be known or unknown. The results indicate a low likelihood of venous thromboembolism and predisposing factors for coagulation may be absent, but the pregnant reliably exclude pulmonary embolism.8 The negative predictive value woman can present coagulation clots everywhere in her body anytime of D-dimer testing for suspected DVT in pregnancy is high.9 during her pregnancy. Progesterone may be necessary at first weeks Ischemia -modified albumin levels10 present 93% sensitivity and of pregnancy or throughout of two trimesters depending on cervical 75% specificity for pulmonary embolism. length, uterus contractions, subchorionic hematomas, vaginal blood, known abortions, absent corpus luteum. In the blood, the count of white cells may be normal or elevated.

When a pregnant woman presents a low PO2, the positive predictive It is not ethical to administrate anticoagulant drugs in any pregnant value for pulmonary embolism is very high. Serum troponin levels woman for fear that a thrombus may be formed and an embolism may due to acute right ventricular myocardial stretch.11 Elevated troponin arise. This administration has a danger for the pregnant woman and a levels in the pulmonary embolism are correlated with increased cost for the health system and the country or the woman personally. In mortality.12,13 the first trimester of pregnancy the suspicion of pulmonary embolism is not so expected as in other trimesters, but when a pregnant woman When the levels of brain natriuretic peptide (BNP) or its precursor, is presented with severe pain, the formation of blood clots (thrombi) N-terminal pro-brain natriuretic peptide-NT-proBNP are elevated, will and obstruction of vessels liable to that point of body must be the first provide prognostic information,14 such as subsequent complications differential diagnosis if other predisposing factors are absent for this and mortality. sign. The ethical subject cost versus benefit is an issue managing such patients. Our therapeutic efforts aim to save the mother at first and Imaging methods fetus as second, and the baby not to be affected by drugs or radiation. The teratogenetic and oncogenetic effects of radiation in the Pulmonary embolism has no specific signs and symptoms.¹ The human fetus need careful consideration. It has not yet established the abrupt onset of pleuritic chest pain, hypoxia and shortness of breath increased risk of teratogenicity in human beings associated with the is the classic presentation of pulmonary embolism. The sole physical minimum dose of radiation. Radiation exposure of 0.1 Gy at any time during gestation is regarded as a practical threshold beyond which finding may be chest wall tenderness upon palpation, without a history 14–16 of trauma. induction of congenital abnormalities is possible. Pleuritic chest pain occurs in 84% of patients and suggests that the Despite these, the mortality of an untreated pulmonary embolism embolus may be smaller and is located more peripherally. The incidence in a pregnant woman far outweighs the potential oncogenic and of physical signs in a pregnant woman with a recognized pulmonary teratogenic risk incurred by fetal exposure to diagnostic imaging. embolism are¹: tachypnea 96%, rates 58%, accentuated second heart The criterion standard for diagnosing pulmonary embolism is sound 53%, tachycardia 44%, fever 43%, diaphoresis35%, S3 or S4 Multidetector-row Computer Tomography Angiography (MDCTA).17 43%, thrombophlebitis 32%, lower extremity edema 24%, cardiac CT scanning is safe to be performed in all trimesters of pregnancy18. murmur 23%, cyanosis 19%. During CT scanning the fetal radiation exposure varies from 0.00033 18 Physical examination findings are quite variable in pulmonary to 0.01308 rad. embolism². Patients with massive pulmonary embolism are in shock. MDCTA sensitivity varies from 57-100% and its specificity 64- Patients with acute pulmonary infraction are presented with acute 100%.19,20 onset of pleuritic chest pain, breathless and hemoptysis. Patients with acute embolism without infraction have nonspecific physical signs.² When MDCTA is not available, the criterion standard is Pulmonary Patients with multiple pulmonary emboli are presented with physical Angiography. signs of pulmonary hypertension. In most cases of pulmonary embolism, the chest radiograph is 21 A thrombus formation is predisposed from endothelial injury, abnormal but nonspecific. In ECG, most abnormal findings are stasis or turbulence of blood flow and blood hypercoagulability, the tachycardia and nonspecific ST-T wave abnormalities. V/Q scanning 22 so-called Virchow triad.3–5 is performed when CT is not available or is contraindicated. MRI has sensitivity 85% and specificity 96%.23 Transesophageal Respiratory and hemodynamic consequences are associated with echocardiography presents sensitivity and specificity 59% and 77%, pulmonary embolism.2 for central and peripheral pulmonary embolism.24 Routine laboratory findings may be no diagnostic and helpful in Duplex ultrasonography demonstrates the presence of deep venous pulmonary embolism. thrombi at any site.25 For the diagnosis of deep venous thrombosis, the standard imaging study is venography. The differential diagnoses are Non-imaging methods extensive2 and the physician should be very suspicious and consider If there are not present any cause2 and risk factor6 for pulmonary very carefully all these diagnoses for not missing a patient with embolism and venous thromboembolic disease in pregnancy7 then the pulmonary embolism. screening will include Antithrombin III deficiency, protein C or protein

If a high level of suspicion exists for a pulmonary embolism in recurrence rates in pregnancy venous thrombosis have ranged from pregnancy, empiric anticoagulation is recommended. Heparin and 1.4% to 11.1%.34,35 fibrinolysis are safe in pregnancy. Unfractionated Heparin -UFH- and Thrombosis risk factors in pregnancy include inherited and Low Molecular Weight Heparins-LMWH- are preferred drugs for acquired thrombophilic conditions in varying degrees such as the management pulmonary embolism in pregnancy. Heparins activate highest risk being antithrombin deficiency type 1 and the lowest risk antithrombin III, prevent the conversion of fibrinogen to fibrin and with factor V leiden.36,37 Other risk factors include the mass index reduce the size and frequency of pulmonary embolism. Heparins 25kg/m2 or more and immobilization for longer than one week. don’t cross the placenta,26 don’t carry risks of teratogenesis or fetal hemorrhage, but bleeding at the uteroplacental junction is possible.27 It is an important issue pregnant woman who knows her family’s The major risks of heparin concern the mother and include hemorrhage, medical history and especially disturbances of coagulation factors. heparin allergies-induced thrombocytopenia, and heparin-induced In pregnancy, the hemostatic system is progressively activated to osteopenia. prepare the parturient for the hemostatic challenge of delivery. Normal pregnancy is associated with a hypercoagulable state. This During pregnancy, heparin requirements may be enhanced due to state contributes to physical and hormonal changes associated increased plasma volume, glomerular filtration and renal clearance, with pregnancy. Endothelial injury, stasis of blood flow and blood increased circulating levels of heparin-binding proteins and increased hypercoagulability predispose to the formation of thrombus. heparin degradation by the placenta.28,29 LMWHs in comparison to unfractionated heparin undergo less binding to heparin-binding It is crucial, every sign of the woman’s body to be estimated proteins, but they present increased clearance and degradation. Higher for correct diagnosis. Delays in the correct diagnosis and therapy LMWH doses may be required to reach target anti-Xa activity30 in are crucial for the lives both of two, mother and fetus. Despite the pregnant women. objections of other health professionals, the doctor has to persist in possible patient’s diagnosis and proper investigation must be achieved At first suspicion of pulmonary embolism, full-dose LMWH or full as soon as possible, so a proper medication to be administered. dose of unfractionated IV heparin should be administered. Warfarin crosses the placental barrier and can cause fetal malformations, for Careful consideration must be given about the advantage or this reason, is contraindicated disadvantage of anticoagulation drugs and effects. LMWH presents great bioavailability (predictable therapeutic Acknowledgments effect), longer duration of anticoagulant effect, subcutaneous administration, safe way of administration and monitoring, less- None. heparin induced thrombocytopenia.27–30 The longer life in comparison with unfractionated heparin and the increased cost is the disadvantages Funding of LMWH. None. Several LMWH products in proper dosing have been found safer and more effective than unfractionated heparin for prophylaxis Conflicts of interest and treatment of pulmonary embolism. As there are available The authors declare there are no conflicts of interest. many different LMWH products around the world, which have pharmacokinetic differences, dosing is highly product-specific. 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Citation: Orfanoudaki IM. Pulmonary embolism in the first trimester of pregnancy.Obstet Gynecol Int J. 2020;11(1):23‒28. DOI: 10.15406/ogij.2020.11.00484