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Abbreviations: CTPA, computed tomography angiography; BNP, brain natriuretic peptide; MDCTA, multidetector-row computer tomography angiography; UFH, unfractionated heparin; LMWH, low molecular weight heparins

Case presentationThis case concerns a woman 35 years old, primipara, with a

spontaneous conception. In her medical history never included pills, not known abortion, never active smoker, without any known history of thrombophilia, not known trauma to the lower extremities, a BMI <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.

When her Human Horionic Gonadotropin was 2221IU/ml, she was attended at the first time from her Gynecologist, where an inta-uterine pregnancy was diagnosed. A gestation sac 1.14cm with a normal lecithic sac and an obvious fetus 0.11cm were detected. The ovaries were normal without corpus luteum and the cervix was closed with a length of 3.67cm. She was taken advice and came back after two weeks when the CRL was 6+2, the fetus’s heart rate was positive and a subchorionic hematoma 2.64x0.85x0.75cm was observed. Progesterone tablet 100mg 1x3p.os and creme progesterone per vaginal in the morning 1x1 was given to her. The pregnancy was getting on normally and the values of blood tests including the fibrinogen, prothrombin, and APTT were in the normal range. (PT patient11.5, PT controls 11.5, INR 1.00, APTT 28.9, Fibrinogen 380).

After two weeks, the woman was examined again. The fetus was alive and was corresponded to the age of the pregnancy. The subchorionic hematoma was smaller 1.53x0.59cm.

At eleven weeks and five days, the pregnant woman came back to her doctor complaining about a settled severe pain on her right lung, especially on her right scapula with the rid distribution. She didn’t a present fever or caught. The fetus was alive with heartbeat 171.43bpm, CRL 2.23cm, and gestational sac 4.38cm. The subchorionic hematoma remained at the same dimensions. The vagina cultures presented

staphylococcus and cefuroxime was given to her for fourteen days.

The auscultation of the lungs ascertained a limited lung whispering on the right middle lobe of the lung and an absent lung whispering 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, FIBRINOGEN 937.3, D-dimers 4.3. The suspicion of a right lung embolism was very high.

The woman was examined by a cardiologist for the pain. Her physical examination, ECG, the ultrasound and Doppler of the heart were normal.

A pulmonologist examined the primipara. Her blood gases were normal. The pain on the right scapula and the lung whispering were attributed to freezing of the muscles and nerves co-ordinate of that part of the body. The orthopedic gave the same diagnosis for the primipara (Figure 1).

The urgency departments of two Hospitals refused to perform lung x-Ray to her because of the first trimester of pregnancy and denied the admission to the hospital

A second pulmonologist examined the pregnant woman. The saturation of blood and acid-base equilibrium was normal and the diagnosis was the same: freezing of the muscles and nerves.

During these two days, the primipara except the feeling of severe pain she was not able to lie down. The next day she presented sputum with blood. An otolaryngologist examined the woman but he did not find an obvious reason for the bleeding.

The woman was admitted urgently to the hospital. Her hemodynamic state was normal and she never presented fever. The D-Dimers and fibrinogen were more increased. Some young doctors supported that these values of fibrinogen and D-dimers were enhanced due to pregnancy. Because the symptoms were getting worse, a lung x-ray was performed. The x-ray indicated a shadow right pericardiac of the lung. The suspicion of pulmonary embolism was intense. A

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.

Pulmonary embolism in the first trimester of pregnancy

Volume 11 Issue 1 - 2020

Orfanoudaki Irene M Obstetric Gynecology, University of Crete, Greece

Correspondence: Orfanoudaki Irene M, Obstetric Gynecology, University of Crete, Greece, 22 Archiepiskopou Makariou Str, 71202, Heraklion, Crete, Greece, Tel +30 6945268822, +302810268822, Email

Received: January 19, 2020 | Published: January 28, 2020

Summary

Pulmonary embolism in the first trimester of pregnancy without a known medical history is a very rare complication, which if it is misdiagnosed and left untreated leads to sudden 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, the most important causes are hereditary factors. Many times the pregnant woman ignores her familiar hereditary history and her hemostatic system is progressively activated for the hemostatic challenge of pregnancy and delivery. The hemostatic changes produce enhance 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.

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

Obstetrics & Gynecology International Journal

Case Report Open Access

Pulmonary embolism in the first trimester of pregnancy 24Copyright:

©2020 Orfanoudaki

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

triplex of the pelvis and legs was performed which was normal. Also, a heart ultrasound was repeated with normal results (Figure 2).

A CTPA – Computed tomography angiography of the pulmonary artery was performed which elevated the existence and lesions of an

acute pulmonary embolism of the right middle and low lobe with two possible small obstructions of the right low lobe signs were Sat 99% with FiO2 21%, arterial blood pressure 95/53mm Hg and pulses 94/min (Figure 3).

Figure 1 ECG of primipara.

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

Pulmonary embolism in the first trimester of pregnancy 25Copyright:

©2020 Orfanoudaki

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

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.

Pulmonary embolism in the first trimester of pregnancy 26Copyright:

©2020 Orfanoudaki

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

DiscussionThe disturbances of coagulation factors are not so obvious in

the usual screening test in the general population, and they are not 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 of the country. The family history may be known or unknown. The predisposing factors for coagulation may be absent, but the pregnant woman can present coagulation clots everywhere in her body anytime during her pregnancy. Progesterone may be necessary at first weeks of pregnancy or throughout of two trimesters depending on cervical length, uterus contractions, subchorionic hematomas, vaginal blood, known abortions, absent corpus luteum.

It is not ethical to administrate anticoagulant drugs in any pregnant woman for fear that a thrombus may be formed and an embolism may arise. This administration has a danger for the pregnant woman and a cost for the health system and the country or the woman personally. In the first trimester of pregnancy the suspicion of pulmonary embolism is not so expected as in other trimesters, but when a pregnant woman is presented with severe pain, the formation of blood clots (thrombi) and obstruction of vessels liable to that point of body must be the first differential diagnosis if other predisposing factors are absent for this sign. The ethical subject cost versus benefit is an issue managing such patients. Our therapeutic efforts aim to save the mother at first and fetus as second, and the baby not to be affected by drugs or radiation.

Pulmonary embolism has no specific signs and symptoms.¹ The abrupt onset of pleuritic chest pain, hypoxia and shortness of breath is the classic presentation of pulmonary embolism. The sole physical finding may be chest wall tenderness upon palpation, without a history of trauma.

Pleuritic chest pain occurs in 84% of patients and suggests that the embolus may be smaller and is located more peripherally. The incidence of physical signs in a pregnant woman with a recognized pulmonary embolism are¹: tachypnea 96%, rates 58%, accentuated second heart sound 53%, tachycardia 44%, fever 43%, diaphoresis35%, S3 or S4 43%, thrombophlebitis 32%, lower extremity edema 24%, cardiac murmur 23%, cyanosis 19%.

Physical examination findings are quite variable in pulmonary embolism². Patients with massive pulmonary embolism are in shock. Patients with acute pulmonary infraction are presented with acute onset of pleuritic chest pain, breathless and hemoptysis. Patients with acute embolism without infraction have nonspecific physical signs.² Patients with multiple pulmonary emboli are presented with physical signs of pulmonary hypertension.

A thrombus formation is predisposed from endothelial injury, stasis or turbulence of blood flow and blood hypercoagulability, the so-called Virchow triad.3–5

Respiratory and hemodynamic consequences are associated with pulmonary embolism.2

Routine laboratory findings may be no diagnostic and helpful in pulmonary embolism.

Non-imaging methods

If there are not present any cause2 and risk factor6 for pulmonary embolism and venous thromboembolic disease in pregnancy7 then the screening will include Antithrombin III deficiency, protein C or protein

S deficiency, Factor V Leiden, Plasminogen abnormality, Plasminogen activator abnormality, fibrinogen abnormality, Resistance to activated protein C, lupus anticoagulant, homocystinuria, occult neoplasm, connective tissue disorders.

D-dimer concentration rises gradually during pregnancy. Negative results indicate a low likelihood of venous thromboembolism and reliably exclude pulmonary embolism.8 The negative predictive value of D-dimer testing for suspected DVT in pregnancy is high.9

Ischemia -modified albumin levels10 present 93% sensitivity and 75% specificity for pulmonary embolism.

In the blood, the count of white cells may be normal or elevated. When a pregnant woman presents a low PO2, the positive predictive value for pulmonary embolism is very high. Serum troponin levels due to acute right ventricular myocardial stretch.11 Elevated troponin levels in the pulmonary embolism are correlated with increased mortality.12,13

When the levels of brain natriuretic peptide (BNP) or its precursor, N-terminal pro-brain natriuretic peptide-NT-proBNP are elevated, will provide prognostic information,14 such as subsequent complications and mortality.

Imaging methods

The teratogenetic and oncogenetic effects of radiation in the human fetus need careful consideration. It has not yet established the increased risk of teratogenicity in human beings associated with the minimum dose of radiation. Radiation exposure of 0.1 Gy at any time during gestation is regarded as a practical threshold beyond which induction of congenital abnormalities is possible.14–16

Despite these, the mortality of an untreated pulmonary embolism in a pregnant woman far outweighs the potential oncogenic and teratogenic risk incurred by fetal exposure to diagnostic imaging.

The criterion standard for diagnosing pulmonary embolism is Multidetector-row Computer Tomography Angiography (MDCTA).17 CT scanning is safe to be performed in all trimesters of pregnancy18. During CT scanning the fetal radiation exposure varies from 0.00033 to 0.01308 rad.18

MDCTA sensitivity varies from 57-100% and its specificity 64-100%.19,20

When MDCTA is not available, the criterion standard is Pulmonary Angiography.

In most cases of pulmonary embolism, the chest radiograph is abnormal but nonspecific.21 In ECG, most abnormal findings are tachycardia and nonspecific ST-T wave abnormalities. V/Q scanning is performed when CT is not available or is contraindicated.22 MRI has sensitivity 85% and specificity 96%.23 Transesophageal echocardiography presents sensitivity and specificity 59% and 77%, for central and peripheral pulmonary embolism.24

Duplex ultrasonography demonstrates the presence of deep venous thrombi at any site.25 For the diagnosis of deep venous thrombosis, the standard imaging study is venography. The differential diagnoses are extensive2 and the physician should be very suspicious and consider very carefully all these diagnoses for not missing a patient with pulmonary embolism.

Pulmonary embolism in the first trimester of pregnancy 27Copyright:

©2020 Orfanoudaki

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

If a high level of suspicion exists for a pulmonary embolism in pregnancy, empiric anticoagulation is recommended. Heparin and fibrinolysis are safe in pregnancy. Unfractionated Heparin -UFH- and Low Molecular Weight Heparins-LMWH- are preferred drugs for management pulmonary embolism in pregnancy. Heparins activate antithrombin III, prevent the conversion of fibrinogen to fibrin and reduce the size and frequency of pulmonary embolism. Heparins don’t cross the placenta,26 don’t carry risks of teratogenesis or fetal hemorrhage, but bleeding at the uteroplacental junction is possible.27 The major risks of heparin concern the mother and include hemorrhage, heparin allergies-induced thrombocytopenia, and heparin-induced osteopenia.

During pregnancy, heparin requirements may be enhanced due to increased plasma volume, glomerular filtration and renal clearance, increased circulating levels of heparin-binding proteins and increased heparin degradation by the placenta.28,29 LMWHs in comparison to unfractionated heparin undergo less binding to heparin-binding proteins, but they present increased clearance and degradation. Higher LMWH doses may be required to reach target anti-Xa activity30 in pregnant women.

At first suspicion of pulmonary embolism, full-dose LMWH or full dose of unfractionated IV heparin should be administered. Warfarin crosses the placental barrier and can cause fetal malformations, for this reason, is contraindicated

LMWH presents great bioavailability (predictable therapeutic effect), longer duration of anticoagulant effect, subcutaneous administration, safe way of administration and monitoring, less-heparin induced thrombocytopenia.27–30 The longer life in comparison with unfractionated heparin and the increased cost is the disadvantages of LMWH.

Several LMWH products in proper dosing have been found safer and more effective than unfractionated heparin for prophylaxis and treatment of pulmonary embolism. As there are available many different LMWH products around the world, which have pharmacokinetic differences, dosing is highly product-specific. For initial anticoagulation therapy, the preferred choice is fractionated LMWH which is administered subcutaneously.

Pregnant women with pulmonary embolism may be treated with LMWH throughout their pregnancy and be continued during pregnancy and 4-6 weeks postpartum for a total of at least 6 months.

Unfractionated iv heparin presents a shorter half-life than LMWH and it is difficult to titrate for therapeutic effect. Protamine produces UFH reversibility. When the pregnant woman is likely to have immediate surgery the UFH is preferred. UFH is given by a bolus intravenous administration, followed by IV infusion, increased or decreased by 10-30%, with titration of dose to goal a stable aPTT.31 When a therapeutic and stable aPTT31 is achieved, iv heparin can be converted to either subcutaneous UFH or LMWH. The monitoring of anti-Xa levels for suitable LMWH dosing is suggested by some authors.31,32

Unfractionated heparin, LMWHs are not secreted in breast milk in clinically significant amounts and are safe in breastfeeding fetus.

To avoid venous thromboembolic disease in pregnancy, mobilization and graduated stocking are recommended.33 The overall

recurrence rates in pregnancy venous thrombosis have ranged from 1.4% to 11.1%.34,35

Thrombosis risk factors in pregnancy include inherited and acquired thrombophilic conditions in varying degrees such as the highest risk being antithrombin deficiency type 1 and the lowest risk with factor V leiden.36,37 Other risk factors include the mass index 25kg/m2 or more and immobilization for longer than one week.

It is an important issue pregnant woman who knows her family’s medical history and especially disturbances of coagulation factors. In pregnancy, the hemostatic system is progressively activated to prepare the parturient for the hemostatic challenge of delivery. Normal pregnancy is associated with a hypercoagulable state. This state contributes to physical and hormonal changes associated with pregnancy. Endothelial injury, stasis of blood flow and blood hypercoagulability predispose to the formation of thrombus.

It is crucial, every sign of the woman’s body to be estimated for correct diagnosis. Delays in the correct diagnosis and therapy are crucial for the lives both of two, mother and fetus. Despite the objections of other health professionals, the doctor has to persist in possible patient’s diagnosis and proper investigation must be achieved as soon as possible, so a proper medication to be administered.

Careful consideration must be given about the advantage or disadvantage of anticoagulation drugs and effects.

AcknowledgmentsNone.

FundingNone.

Conflicts of interest The authors declare there are no conflicts of interest.

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