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Thrombolysis in massive P. E. in pregnancy. A case report and review

Ghassan-S Kiwan MD, Ramzi-W Banda MD, Eric-TMcWilliams,MB,MRCPI.

Case Report
Discussion
Conclusions
References

The diagnosis and treatment of pulmonary embolism demands an inter-disciplinary approach combining medical, surgical and radiologic specialties.

Pulmonary embolism has a wide spectrum of acuity from patients who are hemodynamically stable, to those who are hypotensive and in cardiogenic shock. Despite substantial advances, mortality and recurrence rates remain high. In the International Co-operative Pulmonary Embolism Registry of 2454 patients, the three month mortality rate was 17.5% (ref. 1-4). The management of patients with acute pulmonary embolism remains difficult, particularly when cardiogenic shock is involved (ref. 1). Thrombotic venous thrombo-embolism is the most frequent cause of pulmonary embolism compared to embolism from many other sources including air, bone marrow, arthroplasty cement, amniotic fluid, tumor, talc and sepsis. In studies conducted in USA (ref. 2-3), the incidence of venous thrombo-embolism was about 1 in 1000 per year. It was more common in men; the incidence doubles for each 10 years of age. By extrapolation, it is estimated that more than 250,000 patients are hospitalized annually in the USA with venous thrombo-embolism. According to different studies (Ref .4-5-6), men have higher fatality rates than women (13.7% vs. 12.8%) and blacks have higher fatality rates than whites (16.1% vs. 12.9%). (Ref. 1- 30) .

Thrombolytic therapy is an important consideration in patients with severe massive pulmonary embolism. It is, however, less certain in patients having right ventricular dysfunction who are normotensive and hemodynamically stable.

2D echocardiography is becoming a very important diagnostic tool in pulmonary emboli (Ref.7), in right ventricular dysfunction and right atrial thrombosis, which occurs more rarely than left atrial thrombosis (Ref. 26). The following case report shows the direct echocardiographic evidence of thrombolytic efficacy with tPA in pulmonary embolism and the dramatic improvement of pulmonary hypertension as well as symptoms.

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Case Report: A 31 year old G5 P4 lady presented at 37 weeks gestation with palpitations, acute shortness of breath, chest pain, dizziness and brief syncope occurring while standing up from bed causing minor posterior head trauma. Prior to that she had complained of left calf tenderness. On admission, her vital signs revealed a sinus tachycardia of 120/min, blood pressure of 110/50mmhg and a respiratory rate of 40/min. Her JVP was increased. Cardiac exam revealed the apex at normal position with right parasternal heave, normal S1, loud P2, and a systolic ejection murmur of 2/6 at the left lower sternal border. The lungs were clear. There was mild swelling of the left leg more than the right leg. Neurological exam was unremarkable.

Admission laboratory values revealed the following: hemoglobin 9.7, white blood count 14 K/cumm, platelets 319 K/cumm, normal electrolytes, creatinine, glucose, PT and PTT. Arterial blood gases at room air showed pH 7.41, pCO2 28, pO2 78, and saturation of 90%. The ECG showed a sinus tachycardia with S1Q3 and anterior inverted T-wave. The suspected diagnosis was pulmonary embolism. Venous Doppler showed a left deep vein thombosis with a floating thrombus.

Transthoracic echocardiogram showed a 6 cm snake-shaped right atrial thrombus with pulmonary hypertension of at least 60 mm Hg and severe dilatation of the right ventricle with flattening of the septum (Ref. Fig 1). IV heparin was started immediately after the venous doppler. The fetal vital signs, fetal ultrasound and monitoring were normal.

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Fig. 1

Saturation transiently improved then the patient had a sudden deterioration developing chest pain, sinus tachycardia of 130 per minute and hypotension at 70/40mmhg with profuse sweating. These symptoms persisted for 30-45 minutes but responded to iv saline bolus. However, oxygen saturation remained at around 88-90% despite 100% of oxygen therapy.

A repeated transthoracic echo showed the disappearance of the right atrial thrombus confirming  its migration. A V/Q lung nuclear scan (fig. 2-panel A) was consistent with massive right and mild left side pulmonary embolus.

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Fig. 2

Considering her unstable condition, thrombolytic therapy (r-tPA) was given (100 mg IV bolus). She had a dramatic improvement in her general condition. Her blood pressure rose to 120/70mmhg, saturation normalized and she reverted to normal sinus rhythm at 88 per minute. A repeated transthoracic echocardiogram showed dramatic improvement of her pulmonary hypertension as well as significant regression of the right ventricular dilatation and normalization of the septal wall motion.

36 hours later she complained of headache and right hemiplegia then went into a sudden deep coma necessitating intubation and mechanical ventilation. Heparin was discontinued. A brain CT scan showed a left subdural hematoma with severe left cerebral edema and midline shift (fig.3) Drainage of the subdural hematoma was undertaken using external ventricular drainage with ICP monitoring. The latter was elevated but eventually normalized with Mannitol. The severity of the subdural hematoma did not explain the whole neurological picture and cerebral infarcts secondary to paradoxical right to left cardiac emboli were highly suspected.

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Fig. 3

The patient then had a temporary inferior vena cava umbrella installed. The next day she had an uneventful cesarian section with a delivery of a completely normal healthy baby boy. She improved dramatically with a residual right hemiparesis. Subsequently she had placement of a permanent inferior vena cava umbrella. A recurrent left subdural hematoma occurred and was drained adequately. From then on, she had marked overall improvement. Repeat V/Q scan showed an improvement of her pulmonary defect. She finally left the hospital on therapeutic oral anti-coagulation. Her neurological deficits resolved completely. A repeated V/Q scan one week and three months later demonstrated improvement then complete resolution of her PE. (fig.2-panel B,C).

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Discussion: There are three FDA approved regimens for thrombolysis in pulmonary embolism.The one preferred is the tPA regimen given as a fixed dose of 100 mg as a continuous peripheral intravenous infusion over two hours. It is no longer believed that low to medium doses of streptokinase or urokinase are as rapidly effective or as safe (Ref. 18). Bleeding is a possible side effect.

The convenience, rapid effect and relative safety of this therapeutic approach since its approval by the FDA in 1990, had led to its increasing use in the management of pulmonary embolus. Certain particular points differentiate thrombolysis for pulmonary embolism from thrombolysis for acute myocardial infarction.

There is a 14 day time window as opposed to 6-12 hours time window for acute myocardial infarct. The best results are obtained when treatment is started within one day of the pulmonary embolism. Concomitant Heparin is not administered while the thrombolytic agent is being infused. Heparin is resumed at the conclusion of the thrombolytic therapy when an immediate PTT is less than 80 second.

According to the Thrombosis Interest Group of Canada, thrombolytic therapy may be considered for patients with massive venous thrombo-embolism (i.e. ilio-femoral venous thrombosis or pulmonary emboli with hemodynamic instability). The best results are obtained if treatment is given within the first few days from onset of symptoms. Pregnancy and head trauma or injury within the last month are relative but not absolute contra-indications to thrombolytic therapy (Ref. 20-21-22). Women developing VTE (venous thrombo-embolism) during pregnancy require special attention and if hemodynamically stable, heparin is usually initiated intravenously with a bolus of 5000 u followed by a maintenance dose of 30,000 to 36,000 u/24 hours as a continuous iv infusion, with a therapeutic range of APTT. Low molecular weight heparin may be considered as an alternative because of the lower potential for bleeding, thrombocytopenia and osteoporosis (Ref. 27).

Despite heightened awareness, pulmonary embolism remains a major cause of maternal mortality in the antenatal period and has not decreased in incidence over the last 30 years. Case reports about thrombolytic therapy in pregnant women are infrequent; they mainly involve steptokinase in mechanical prosthetic valve thrombosis or pulmonary emboli (Ref. 23-24-28 –31-32-33-34).

There is still a risk of hemorrhage in pregnancy and particularly during delivery and post-partum, by using t-PA for thrombolytic therapy. However, it may be harmless for the fetus (Ref. 25) and its use appears to be safe according to the few reported cases.

Use of thrombolytic therapy should be considered when there is a great danger to the patient, however, the advantages and disadvantages should be weighed (Ref. 24). It can be life saving in massive pulmonary embolism, with cardiogenic shock or overt hemodynamic instability (Ref. 8). As stated, there appears to be a 14 day window for its effective administration (Ref. 9). Controversy persists regarding the use of thrombolytic therapy in patients with stable systemic arterial pressure and right ventricle dysfunction. In this population, rapid improvement of RV function and pulmonary perfusion accomplished with thrombolysis, in addition to IV Heparin may lead to a lower rate of recurrence than with IV Heparin alone (Ref. 10).

The MAPPET Registry (Ref. 11) suggested that patients who are initially treated with thrombolysis plus anticoagulation had a better clinical outcome than those who were initially treated with anticoagulation alone. Despite reports and opinions regarding the benefit of surgical treatment versus thrombolytic therapy or percutaneous transvenous embolus fragmentation for massive pulmonary emboli (Ref.14), no studies exist comparing these alternatives. If aggressive intervention is warranted in patients with contra-indication to or failure of thrombolytic therapy, transvenous catheter embolectomy (Ref. 12) or open surgical embolectomy (Ref. 13) should be considered (Ref. 29).

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Conclusions: Echocardiography is becoming a very useful noninvasive test in the management of patients with massive pulmonary embolism. Thrombolytic therapy Is also being more frequently used and has its clear indications.

Studies have shown that in this condition, thrombolysis improves mortality and morbidity.

It generally leads to rapid improvement of symptoms. There is an indication for thrombolytic therapy in the treatment of pregnant women with massive PE. Most reported cases of thrombolytic therapy in pregnancy have used streptokinase, but as our case llustrates, t-PA appears to be very effective and reasonably safe. It is recommended that an international registry be established to collect data and facilitate analysis. More prospective studies need to investigate this therapeutic alternative. Though potential benefits must be weighed against the risk of major hemorrhage, pharmacological thrombolysis may be mandatory for severe and life-threatening cases, especially in hospitals without on site cardiac invasive facilities on site and available back up cardiothoracic surgery.

The authors wish to acknowledge the use of Saudi Aramco Medical Services Organization facilities for the data and study which resulted in this paper. The authors were employed by Saudi Aramco during the time the study was conducted and the paper written.

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    Questions, contributions and commentaries to the Authors: send an e-mail message (up to 15 lines, without attachments) to echo-pcvc@pcvc.sminter.com.ar , written either in English, Spanish, or Portuguese.

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