Thrombolytic Therapy for Acute Life-Threatening Pulmonary by byrnetown69


									Case Communications

Thrombolytic Therapy for Acute Life-Threatening Pulmonary
Thromboembolism in a Pregnant Woman
Shabtai Varsano MD and Yehoshua Smorzik MD
Department of Pulmonary Medicine, Sapir Medical Center, Meir Hospital, Kfar Saba, and Sackler Faculty of Medicine,
Tel Aviv University, Ramat Aviv, Israel

Key words: pregnancy, pulmonary embolism, thrombolysis, tissue plasminogen activator, abortion
                                                                                                                IMAJ 2008;10:740–741

Pregnancy is a procoagulant state that       blood pressure 132/84
minimizes intrapartum blood loss but         mmHg. Auscultation re-
also increases the rate of thromboembolic    vealed reduced vesicular
events. In the United States in 2000–2001,   breathing over the right
the overall risk of venous thromboembo-      lower lobe. The patient
lism was 1.72 per 1000 deliveries and the    was obese (body mass
risk of mortality was 1.1 per 100,000 de-    index 33). Laboratory
liveries, with a death rate of 2.4% among    findings showed: arterial
cases of pulmonary thrombembolism [1].       blood gas while breath-
Massive PTE is one of the commonest          ing room air pH 7.503,
causes of maternal/pregnancy-related death   pO2 56 mmHg, pCO2 23
in the western world. In contrast to the     mmHg, base excess -4.4,
unequivocal use of systemic thrombolytic     and bicarbonate 18.2.
                                                                           Chest CT-angiography showing an obstructing embolus in the
therapy in massive PTE in the general        Oxygen saturation on          right main pulmonary artery
population, in pregnancy such therapy        2 L/m O2 nasal prongs
was rarely reported, particularly in PTE.    was 96%. A chest film
Moreover, recent clinical guidelines for     showed hyperlucency of the right upper systemic rhTPA (100 mg/2 hr, Actylase®,
anticoagulant and antithrombotic therapy     lobe. Electrocardiogram showed sinus Boehringer Ingelheim GmbH, Germany)
do not address the issue of thrombolysis     tachycardia, S1, Q3, T3 pattern, and T was immediately instituted with a sub-
during pregnancy [2]. The present report     wave inversion in leads V1-V3. Pulmonary sequent improvement in O2 saturation.
describes the evolution of severe PTE        thromboembolism was suspected. A A compression ultrasound-Doppler of
in early pregnancy and discusses its         ventilation-perfusion scan resulted in high the lower extremities was performed on
complicated management decisions, with       probability for PTE. D-dimers were elevat- the seventh day due to leg pain, and a
special attention to systemic thrombolytic   ed to 3900 ng/ml. Troponin was normal. deep vein thrombosis of the left popliteal
therapy using recombinant human tissue       Doppler echocardiography showed normal and saphenous veins was demonstrated.
plasminogen activator.                       left ventricle and dilated hypokinetic right Obstetric consultation resulted in a clear
                                             ventricle. Estimated systolic pulmonary recommendation to terminate the preg-
Patient Description                          artery pressure was 59 mmHg.                    nancy. A chest angio-computed tomogra-
A 39 year old woman at 11 weeks gesta-           A diagnosis of sub-massive PTE was phy scan done on the 12th day, before
tion of her sixth pregnancy was admit-       reached and unfractionated heparin the abortive procedure, revealed multiple
ted to our hospital because of severe        was initiated intravenously at a mean filling defects in the right upper and lower
dyspnea that started the day before. Her     daily dosage of 34,000 units. Mean branches up to the right main pulmonary
past medical history was unremarkable        activated partial thromboplastin time artery [Figure] and similar defects in the
and her family history was negative for      was 46 seconds. The patient remained left lower lobe artery. Repeated Doppler
coagulopathy. On admission, her heart        stable until the fifth day when she sud- echocardiography on the 14th day revealed
rate was 106/min, respiratory rate was       denly experienced increasing shortness normal heart chambers and estimated
24/minutes, oxygen saturation on room        of breath and abdominal pain. Oxygen systolic pulmonary artery pressure of 38
air 89%, temperature 36°C, and systemic      saturation dropped to 90% on 5 L/m O2 mmHg. In view of a lower limb deep vein
                                             nasal prongs and blood pressure fell to thrombosis an inferior vena cava retriev-
PTE = pulmonary thromboembolism              90/60 mmHg. Recurrent PTE with devel- able filter was inserted on the 16th day, a
rhTPA = recombinant human tissue prothrom-   opment of massive PTE was suspected. day before the abortion. On the 17th day,
  bin activator                              Thrombolytic therapy with intravenous aspiration curettage of the uterus was per-

740    S. Varsano and Y. Smorzik                                                                        •   Vol 10   •   October 2008
                                                                                                               Case Communications

formed without complications. Enoxaparin       effects on the fetus. Permanent sequelae      imaging of new thromboemboli in the IVC
was instituted 12 hours later. Six days        have not been observed in children born       filter despite continuous anticoagulation.
after IVC filter insertion a repeated          after maternal thrombolytic therapy or in         In summary, pregnancy and the
compression ultrasound of the legs due         fetuses aborted for reasons unrelated to      postpartum period are hypercoagulable
to recurrent pain and swelling revealed        thrombolytic therapy [3]. Some reports        states of high risk for thromboembo-
an extension of the former thrombus to         documented complications such as              lism, especially PTE. We believe that
the common femoral vein. Ten days after        maternal hemorrhage, preterm delivery,        the experience gained and described
IVC retrievable filter insertion, venography   fetal loss, spontaneous abortion, minor       in the literature so far advocates rhTPA
of the inferior vena cava revealed mal-        vaginal bleeding, massive sub-chorionic       thrombolytic therapy in severe cases of
deviation of the filter's hook and intra-      hematomas, abortion placenta, uterine         pulmonary thromboembolism. The risk of
filter filling defects suspected as thrombi.   bleeding requiring emergency cesarean         untreated severe embolism to the mother
The filter was left in place and warfarin      section, and postpartum hemorrhage that       and fetus is higher than the risk of rhTPA
was added to enoxaparin. Investigation for     required transfusion. However, the com-       therapy. RhTPA should certainly be given
thrombophilia, partially limited by heparin    plication rate of thrombolytic treatment      for massive PTE, and in selected cases
treatment, was negative. The patient was       does not seem higher than in the non-         of sub-massive PTE. We also believe that
discharged from the hospital on the 28th       pregnant population, and complications        in cases of life-threatening pulmonary
day on warfarin.                               occur mostly when thrombolytic therapy        thromboembolism termination of early
                                               is administered intrapartum and if given      pregnancy should also be considered in
Comment                                        concomitantly with heparin or oral anti-      order to protect the mother. We encour-
We describe a woman at 11 weeks gesta-         coagulants [5].                               age physicians to publish their experience
tion of her sixth pregnancy who presented          Our patient first presented with          with similar thromboembolic events that
with sub-massive PTE that soon deterio-        a sub-massive PTE. Whether to treat           require thrombolytic therapy, and clinical
rated into a life-threatening massive PTE.     patients (non-pregnant) suffering from        guidelines committees to review the pub-
The mainstay of treatment for massive PTE      sub-massive PTE with thrombolytic agents      lished experience, even if uncontrolled, so
in non-pregnant individuals, unless there      or with anticoagulation alone is a subject    that recommendations will be incorporated
are contraindications, is urgent throm-        of continuing debate. The findings of a       in future editions of clinical guidelines for
bolysis. This can be achieved preferentially   recent study [4] support early thrombolytic   the management of severe thromboembo-
by injection of a thrombolytic agent like      therapy in sub-massive PE in the general      lic complications during pregnancy.
rhTPA, systemically via a peripheral vein,     population. We could not find reports of
or locally via a pulmonary artery catheter     thrombolytic therapy in sub-massive PTE       References
[2]. Surprisingly, although pregnancy is       during pregnancy. Whether a pregnancy         1. James AH, Jamison MG, Brancazio LR,
considered a procoagulant state and is         should be terminated in the face of mas-         et al. Venous thromboembolism during
an important risk factor for pulmonary         sive/sub-massive pulmonary thromboem-            pregnancy and the postpartum period:
                                                                                                incidence, risk factors, and mortality. Am
thromboembolism, being the most com-           bolism in order to reduce maternal risk          J Obstet Gynecol 2006;194:1311–15.
mon cause of maternal death in certain         is not discussed in the literature either.    2. Use of antithrombotic agents during
countries the issue of thrombolysis during     It seems that each case needs to be ap-          pregnancy: The seventh ACCP Conference
pregnancy is not discussed in recent clini-    proached individually. The mortality rate        on antithrombotic and thrombolytic
cal guidelines. The guidelines [2] issued      among pregnant women with pulmonary              therapy. Chest 2004;126:3(Suppl).
                                                                                             3. Leonhardt G, Gaul C, Nietsch HH, et
by the seventh American College of Chest       thromboembolism is 2.4% [1]. In the case         al. Thrombolytic therapy in pregnancy.
Physicians conference on antithrombotic        of our patient described here, gestation         J Thromb Thrombolysis 2006;21:271–6.
and thrombolytic therapy 2004 ignore this      age was only 11 weeks, in contrast with       4. Konstantinidis S, Geibel A, Heusel G,
issue, probably due to the scarcity of pub-    late pregnancy in most other case reports,       et al. Heparin plus alteplase compared
lished data. This will probably remain the     and we therefore believed it essential to        with heparin alone in patients with sub-
                                                                                                massive pulmonary embolism. N Engl J
case since randomized placebo controlled       terminate the prolonged hypercoagulable          Med 2002;347:1143–50.
studies in this field are unlikely to be       state awaiting her. Obesity and age over      5. Turrentine MA, Braems G, Ramirez MM.
performed.                                     35 were two additional risk factors for          Use of thrombolytics for the treatment
    Is rhTPA use in pregnancy contraindi-      thrombosis during pregnancy in our               of thromboembolic disease during preg-
cated? According to the U.S. Food and          patient [1]. Our cautious approach was           nancy. Obstet Gynecol Surv 1995;50:534–41.
Drug Administration's use-in-pregnancy         reinforced by the persistence of pulmonary
                                                                                             Correspondence: Dr. S. Varsano, Head,
ratings for drugs, rhTPA is rated "C."         thrombi in the angio-CT and the leg DVT a     Asthma Care and Education Unit, Dept. of
Studies have demonstrated that placen-         week after thrombolytic therapy was given,    Pulmonary Medicine, Sapir Medical Center,
tal transfer of rhTPA (molecular weight        by the enlarging DVT, and finally by the      Meir Hospital, Kfar Saba 44281, Israel.
72,000 kD) is too low to cause fibrinolytic                                                  Phone: (972-9) 747-1556
                                                                                             Fax: (972-9) 748-0861
IVC = inferior vena cava                       DVT = deep vein thrombosis                    email:

      • Vol 10 • October 2008                                           Thrombolysis of Pulmonary Emboli in Pregnancy                741

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