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Türk Kardiyol Dern Arş - Arch Turk Soc Cardiol 2013; 41:228-232   PMID: 23703559

  Volume: 41  Issue: 3 April 2013   
TKD|Intracranial hemorrhage due to pulmonary thromboembolism in heparin therapy and therapeutic management of patients hospitalized with massive pulmonary embolism after discharge

Intracranial hemorrhage due to pulmonary thromboembolism in heparin therapy and therapeutic management of patients hospitalized with massive pulmonary embolism after discharge

Pulmoner tromboemboli tedavisi için heparin kullanırken intrakraniyal kanama gelişen ve masif pulmoner tromboemboli nedeniyle tekrar hastaneye yatırılan hastada tedavi yönetimi

Dr. Feyzullah Beşli, Dr. Mesut Keçebaş, Dr. Mehmet Fethi Alişir, Dr. Fatih Güngören

Summary– A patient with a history of intracranial hemorrhage who was hospitalized due to massive pulmonary thromboembolism (PTE) was presented. A 59-year-old female patient had an intracranial hemorrhage while under anticoagulant therapy because of emergent   PTE after a knee operation. Therefore, the anticoagulant therapy was discontinued. Forty seven days after the cessation of the anticoagulant treatment, the patient was admitted to the emergency department with complaints of acute dyspnea and presyncope. Transthoracic echocardiography showed signs of right ventricular overload. Contrast-enhanced thorax computed tomography showed a saddle-like filling defect on the level of pulmonary trunk bifurcation extending into both main pulmonary arteries. The patient was diagnosed as  a massive PTE. Fibrinolytic treatment could not be given due to the history of cerebrovascular bleeding while under heparin infusion therapy. Clinical improvement could not be achived with heparin therapy, so pulmonary angiography and thrombus aspiration were planned. The patient’s clinical status had improved after thrombus aspiration. After the thrombus aspiration, bemiparin treatment was given under  effective anti-factor Xa level monitorization   Lower extremity Doppler ultrasonography demonstrated subacute-chronic thrombosis in the right popliteal vein, then inferior vena cava filter was implanted. In this patient group with a contraindication for  thrombolytic therapy, percutaneous aspiration of the  pulmonary thrombus can be preferred. In such patients, for anticoagulant therapy, unfractioned heparin with close aPTT follow-up or low molecular weight heparin therapy with antifactor Xa follow-up can be used.
Department of Cardiology, Uludağ University, Faculty of  Medicine, Bursa, Turkey

Submitted on : 05.04. 2012   Accepted for publication on: 08.10. 2012

Address of correspondence: Dr. Feyzullah Beşli.  Uludağ Üniversitesi Tıp Fakültesi, Kardiyoloji Anabilim Dalı, Görükle Kampüsü, 16000 Nilüfer, Bursa.
Phone: +90 224 - 295 16 40 - 41  e-mail: feyzullahbesli@hotmail.com


PTE    Pulmonary thromboembolism
TR       Tricuspid regurgitation

Acute pulmonary thromboembolism (PTE) is a frequently encountered cardiovascular emergency with a challenging diagnosis. Mortality rates are nearly 25-30 % in untreated cases , and drops to 2-8 % in treated  cases. Acute massive PTE is a life-threatening clinical  condition which courses with shock, and hypotension. Removal of the occlusive pathology in the arterial bed to restore blood flow is the vital  emergency procedure to be targeted. In the management of PTE, anticoagulants, thrombolytic therapy, vena cava filters, and embolectomy procedures can be employed.[1-5]

    In this paper, management strategy applied on a patient who had suffered from  complication of intracranial bleeding emerged during PTE therapy, and also developed massive PTE manifestations during the follow-up period after her discharge.


    A 59-year-old obese woman with hypertension consulted to a medical center because of a sudden onset of dyspnea developed after a knee surgery performed for  bilateral gonarthrosis. In this medical center intravenous unfractionated heparin was initiated with the diagnosis of acute PTE. On the 5th  day of the treatment,  somnolence, vision loss, and speech impairment had developed with resultant referral of the patient to our medical center. Heparin dose schedule, and aPTT data of the patient up to his presentation to our clinics could not be obtained, while her platelet counts were normal on admission. Cranial computed tomography revealed an image consistent with an acute phase hemorrhagic area measuring 3 x2 cm, and  extending from the  parieto-occipital area into the left ventricle, and detection of displacement of nearly 1.5 cm  from left to right necessitated monitorization of the patient in collaboration with the clinic neurosurgery. During in-hospital follow-up period,  upon regression of the symptoms with once daily subcutaneous doses 0.4 mg enaxaparin , and antiedematous therapy, her anticoagulant therapy was terminated, and she was discharged.

    The patient consulted to the emergency department 47 days later with  severe dyspnea, and complaints of presyncope. The patient was anxious, and had shortness of breath. Her respiratory rate was increased. Her  blood pressure was 80/50 mmHg, and heart rate (HR) was regular, and 115 bpm. Cardiovascular examination revealed regular, but rapid heart rate, and a 2/6 systolic murmur was heard over mesocardiac area. On electrocardiogram sinus rhythm at a rate of 115/min, T-wave inversion in  precordial (V1-V4) leads, incomplete right bundle branch block, and S1Q3T3 pattern were observed.

    On her first admission, her  arterial blood gas, and biochemical analysis results under room temperature  were as follows: pO2,  74 mmHg; pCO2,  29 mmHg; oxygen saturation, 85 %, higher D-dimer concentration,  3.9 mg/L, and troponin levels within normal limits. On her transthoracic echocardiogram, left ventricular diameters were  38-22 mm with normal heart wall movements.A D-shape appearance of the left ventricle during both systole, and diastole was seen. Paradoxical movements of the interventricular septum was observed. Right cardiac chambers were extremely dilated (right ventricle  48 mm), and serious tricuspid regurgitation (TR) was noted. Her systolic pulmonary pressure was 80 mm Hg. Right/left ventricular ratio was estimated  as >1.1 Contrast-enhanced thoracic CT with the initial diagnosis of PTE demonstrated  a saddle-like filling defect extending from the bifurcation of the pulmonary trunk into  both main pulmonary arteries. Besides a partial filling defect was seen in branches of pulmonary artery perfusing  lower, and upper lobes of both lungs (Figure 1).

Figure 1. Contrast-enhanced thorax CT images of the patient with initial diagnosis of pulmonary embolism

Figure 2 (A, B)  selective angiograms of the  right, and left pulmonary arteries (C,D) Catheters were placed into right, and left pulmonary arteries over   0.035 F guidewires. In the superior, and inferior pulmonary arteries of both sides images consistent with thrombi are noted. Catheter was moved to -and –fro, and thrombus was disintegrated, and residual particles were removed by aspiration. Postprocedural appearance of the right, and left pulmonary arteries

    Thrombolytic treatment could not be given to the patient diagnosed as massive PTE because of previously experienced cerebrovascular bleeding. The patient was administered 0.9 % NaCl infusion (100 ml/hr), and nasal oxygen (3 l/min) therapy. The case was evaluated in collaboration with the clinics of neurology, and IV unfractionated heparin infusion was initiated. Dosage of the unfractionated  heparin was adjusted in accordance with monitored aPTT levels. Upon persistence  of her respiratory distress at 24th hour of the treatment, pulmonary angiography was performed. Over a 0.035 Fr guide wire (Radiofocus Guidewire M-angled type 0.035 inch 180 cm ga-35) inserted through a 6 Fr inguinal sheath, and a catheter (Turcon NB Advantage Picard Cerebral Angiographic) was advanced into the pulmonary artery. Contrast media injected through catheter and an image consistent with  thrombi in the right, and left superior, and inferior   pulmonary arteries were revealed (Figure 2a, b). Catheter was moved to- and- fro to fragment thrombus, and residual fragments were aspirated. After the procedure,  and injection of the contrast agent right, and  left pulmonary arteries, and their branches were clearly visualized (Figure 2c, d).

    A marked clinical improvement was achieved. Venous Doppler examination of the lower extremities performed on the same day demonstrated an image consistent with  subacute-chronic thrombus. Following 5 days of intravenous unfractionated heparin therapy, low molecular weight heparin (bemiparin 10.000 IU sc. at 6-day intervals) was initiated.  The patient had a history of bleeding, so the dosage of bemiparin was adjusted as one daily subcutaneous doses of 7.500 IU administered at 6-day intervals while targeting an active anti-factor Xa level of   0.6-1 IU/ml.

    A vena cava filter was implanted under bemiparin therapy. K vitamin antagonists were not initiated because of inherent risk of bleeding. The patient was prescibed low molecular weight heparin to be used during the follow-up period under anti-factor Xa monitorization


    Despite advances in the treatment modalities, mortality rates of massive PTE ranges between 20, and 30 percent.[6-7] Transthoracic echocardiograpy, measurements of troponin, and pro-B-type natriuretic peptide have important roles in the management of the patients.  Prevention of early, and late phase recurrences is also important in the successful management of PTE. In patients who experience episodes of PTE for the first time,  cessation of anticoagulant therapy induce recurrent PTE attacks in 2.5, and 4.5 % of the cases. Guidelines recommend anticoagulant therapy with warfarin to be continued for at least three months in patients with the first-time diagnosis of  idiopathic PTE. In patients with a lower risk of bleeding who prefer antiplatelet therapy, life-long anticoagulant therapy can be recommended. In patients who suffered from idiopathic PTE episodes for the second time, life-long anticoagulant therapy is advised.[8] Since intracranial bleeding occurred during anticoagulant therapy delivered for the management  of her first-time PTE episode, anticoagulant therapy recommended in the guidelines was not prescribed for this patient to be used after hospital discharge. As a result of this approach, massive PTE developed in our patient.

    Heparin therapy should be initiated soon after diagnosis of PTE is established, and thrombolytic therapy should be administered in the absence of contraindications. Maximal benefit is seen in the treatment initiated within the first 48 hours within  the onset of manifestations. This time interval can be extended up to 14 days. Management of  patients with massive PTE who had previously suffered from  intracranial bleeding is rather challenging. Since thrombolytic therapy was absolutely  contraindicated in our patient, percutaneous embolectomy was performed as recommended by the guideline.[8] A vena cava filter was implanted in our patient who presented with recurrent PTE with concomitant thrombus detected in the deep veins of the  lower extremity.

    In the patient group with a history of intracranial bleeding, choice of anticoagulant therapy during acute phase requires meticulous care. Incidence of intracranial bleeding during treatment of PTE was reported as  0.5 %, and 1.4 % in patients younger and older  than 65 years of age, respectively .[9] Major bleeding can be seen in 5 % of the patients on unfractionated heparin therapy.[10] Especially in obese individuals initial storage of heparin in adipose tissues, then its redistribution might cause an increase in bleeding complications. In  this patient group, aPTT should be closely monitored during heparin therapy. Low molecular weight heparin does not require monitorization during its clinical usage under normal conditions, however in patients with a history of serious bleeding it can only be used under close anti-factor Xa monitorization. Because of difficulties in complying with oral anticoagulant therapy after hospital discharge, we didn’t prefer to use this therapy in this patient. Therefore, low molecular weight heparin was preferred for the first week at 3 daily, then at monthly intervals under close monitorization with anti-factor Xa measurements. In the guidelines, duration of the anticoagulant therapy in patients with a history of intracranial bleeding has not been precisely stated.  Since intracranial bleeding because of  heparin use developed in our patient, duration of the treatment was initially determined as 6 months. Maintenance of anticoagulant therapy will be decided based on the results of  echocardiograms, thoracic CT, and pulmonary perfusion scanning to be performed at 6th month of the follow-up period.

    In conclusion, in patients with a history of intracranial bleeding, management of massive PTE   requires a very attentive approach. In this patient group with a contraindication to thrombolytic treatment, percutaneous embolectomy should not be delayed. Low molecular  weight heparin can be used in this patient group concurrently with close monitorization of anti-factor Xa levels.

Conflict of interest: None declared


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Anahtar sözcükler: Antikoagülanlar/terapötik kullanım; heparin; intrakraniyal kanama; pulmoner emboli/ilaç tedavisi; tromboemboli/ilaç tedavisi.

Key words: Anticoagulants/therapeutic use; heparin; intracranial bleeding ; pulmonary embolism/drug therapy; thromboembolism/drug therapy.

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