Thrombolytic treatment of right atrial thrombus in a patient with B cell acute lymphoblastic leukemia: a case report

Abstract

Right atrial thrombus is a severe complication of central venous catheterization (CVC). Concomitant pulmonary embolism may aggravate the clinical picture by causing or increasing shortness of breath and decreasing effort capacity, palpitations, and tricuspid valve regurgitation. A 32-year-old female patient with B cell acute lymphoblastic leukemia receiving chemotherapy was treated with alteplase thrombolysis because of the development of catheter-related right atrial thrombus and accompanying pulmonary embolism. On echocardiography, it was observed that the thrombus in the right atrium had regressed completely, but thrombus was seen in the right main pulmonary artery. The same dose of alteplase was given 2 days later. There was no significant change in the echocardiography. Therefore, ultrasound-assisted catheter-directed thrombolysis was applied. Clinical and radiological improvement was observed.

Introduction

Right atrial thrombi are divided into type A and type B. Type A atrial thrombi originate from deep vein thrombi. They are mobile and prone to embolism. On the other hand, type B thrombi originate from abnormal atrial structures, or the catheter in the atrium, and are attached to the right atrial wall. One of the most severe complications of central catheterization is the catheter-induced right atrial thrombus (CRAT). CRAT can cause serious consequences like pulmonary embolism, septic embolism, arrhythmias, mechanical problems of heart function, and even systemic embolization in the case of patent foramen ovale. Right heart thrombi (RHT) have been reported in 4–18% of cases with acute pulmonary thromboembolism (PTE) [1]. Our aim in this case report was to share that anti-coagulant and thrombolytic therapy can be effective as a non-invasive and non-surgical treatment in a patient that has B cell acute lymphoblastic leukemia with right atrial thrombus.

Case report

A 32-year-old patient was diagnosed with B cell acute lymphoblastic leukemia (B-ALL) 6 months ago. She has had a permanent catheter (Hickman adult catheter, 7F two–lumen) for 5 months for chemotherapy. She presented to chest diseases polyclinic with difficulty in walking, dyspnea, and hemoptysis for 20 days. Computed tomography (CT) did not differentiate embolism or infection in her pulmonary scan. The chest diseases department started low molecular weight heparin (LMWH) 6000 anti-FXa iu/0.6 ml twice a day. LMWH dosage was set up to anti-FXa level. Ventilation-perfusion scintigraphy showed that there was hypoperfusion in the lungs, especially on the right basal segment. Venous Doppler ultrasound evaluated her upper and lower extremity in terms of etiology. Vein blood flow was normal and thrombus was not observed. In view of tachycardia and dyspnea, possiblity of PTE was entertained. Her pulmonary CT angiography was compatible with subsegmental embolism. Thrombus was observed at the right jugular catheter’s lower end and in the right atrium (Fig. 1a). Echocardiography of the patient revealed an echodensity of 38 × 30 mm size starting from the lateral wall of the right atrium, entering and exiting the right ventricle, obliterating the tricuspid valve, and possibly compatible with a thrombus (Fig. 1b). The catheter was then withdrawn. In the physical examination, she had tachycardia, no fever, and reduced breath sounds in the right basal area. Sinus tachycardia was observed in the electrocardiography of the patient. Laboratory parameters of the patient are shown in (Table 1). The patient was given LMWH 6000 anti-FXa iu/0.6 ml twice a day for 20 days. We loaded 10 mg alteplase (Boehringer Ingelheim Pharma GmbH & Co.KG, GERMANY) intravenous in 15 min after 10 h of the last LMWH dose. Maintenance of 65 mg was achieved in 3 h. After 8 h, we continued with LMWH medication in the same dose. On the next day, echocardiography showed reduced thrombus size of 18 × 22 mm. After the treatment, the patient’s tachycardia decreased, and dyspnea regressed. Two days after thrombolytic therapy, 2D echocardiography showed that the right atrial thrombus had regressed completely, but a thrombus was seen in the right main pulmonary artery. Mean pulmonary artery pressure was measured as 48 mmHg, and moderate tricuspid regurgitation was observed. Left ventricle ejection fraction was measured as 60%. For this reason, the aforementioned treatment protocol was applied to the patient once again in a day, 10 mg of alteplase was loaded intravenously in 15 min repeatedly, 65 mg of alteplase was given in 3 h as maintenance, then LMWH 6000 anti-FXa iu/0.6 ml was administered twice daily after 8 h. At the end of the two treatment protocols, a total of 150 mg of alteplase was given to the patient. On repeat echocardiography, no significant change was observed. For this reason, ultrasound-assisted catheter-directed thrombolysis (USAT) was performed on the patient 1 day later. In USAT, an 8 FR sheath was placed in the left common femoral vein for right heart catheterization. Mean pulmonary arterial pressure was 52 mmHg. Pulmonary angiography performed through a pigtail catheter showed occlusive thrombus in the right main pulmonary artery and non-occlusive thrombus in the left pulmonary artery branches. The USAT infusion catheter was placed in the right main pulmonary artery. A second venous sheath was then placed in the right common femoral vein. A USAT catheter was placed in the left pulmonary artery through this venous sheath. Alteplase was initiated for a total of 48 h for each lung at 1 mg/h (a total of 96 mg of alteplase for both lungs). Two hundred fifty unit/h of heparin infusion was started in each venous sheath (total 500 units/h) (Fig. 2). In control pulmonary CT angiography, the thrombus load decreased. Right to left ventricular (RV/LV) end diastolic diameter ratio were observed below 1.0. Pulmonary embolism can overload the right ventricle (RV), resulting in dilatation of the right ventricle and decreased contractility. Increased RV/LV end diastolic diameter ratio on computed tomography pulmonary angiography images is the strongest predictor of all-cause mortality in acute pulmonary embolism (PE). An RV/LV end diastolic diameter ratio above 1.0 indicates an increased risk of all-cause death, adverse outcome, and pulmonary embolism–related death [2]. In the repeat echocardiography, mean pulmonary artery pressure decreased (28 mmHg), wall-motion abnormality was not observed in the interventricular septum, and mild tricuspid regurgitation was observed. Left ventricle ejection fraction was measured as 65%. The following day, the patient’s symptoms had improved, with no rest dyspnea. The patient was discharged from the hospital on oral anticoagulation.

Fig. 1.

a Computed tomography angiography showing a thrombus in the right atrium (upper white arrow) and right jugular catheter (white arrow at the bottom). b Transthoracic echocardiography apical view showing a thrombus(38 × 30 mm) in the right atrium (white arrow)

Table 1.

Laboratory parameters before and after treatment procedure

Parameter	Before first alteplase	After first alteplase	Before second alteplase	After second alteplase	Before EKOS	After EKOS
D–Dimer (mg/L)	2.54	43.28	3.6	32.3	7.73	27.2
Fibrinogen (mg/dL)	424	209	607	487	505	387
PT (s)	15	18.7	18.4	19.5	17	18.2
INR	1.15	1.38	1.36	1.46	1.2	1.35
APTT (s)	34	49	44	44.5	41	45.2
Platelet count (× ${10}^3$/µL)	146	196	239	243	230	225

PT prothrombin time, INR ınternational normalized ratio, APTT activated partial thromboplastin time

Fig. 2.

Ultrasound-assisted catheter-directed thrombolysis (alteplase infusion, 48 h) (white arrows show left and right pulmonary artery)

Discussion

Thrombosis is a common complication associated with central venous catheter use. Inconsistent incidence rates of central venous catheter-related thrombosis (CRT) are reported in the literature and vary according to host factors, catheter characteristics, cannulation site, and the infusates administered. Prevention of thrombosis is more beneficial than treatment in CRT. To reduce the risk of thrombosis, it is recommended that central venous catheters be placed in the right jugular vein, with the tip at the junction of the superior vena cava and the right atrium [3, 4]. There was no control study to define the optimal management related to the treatment methods, including anticoagulation therapy, systemic thrombolysis, surgical thrombectomy, and percutaneous interventions.

USAT is an alternative method with lower bleeding risk, allowing localized administration of the thrombolytic agent. However, right atrial thrombus can be of different types, and the operator must be highly experienced to avoid perforation and fragmentation of the thrombus during catheter insertion. Shokr et al. initiated unfractionated heparin while catheter-directed thrombolysis was in progress, and thereafter bridged to warfarin. Eventually, the problem was resolved completely [5].

Alteplase is being increasingly used for thrombolytic therapy in central venous catheterization (CVC)-associated right atrial thrombi. Cesaro et al. instituted thrombolytic therapy for a total of 6 days, with twice-per-day coagulation monitoring. Oozing was noted from venipuncture sites, but was mild enough to continue therapy. Catheter was removed following lysis and almost all thrombus regressed [6].

Percutaneous intravascular removal of CRAT is recommended when other treatment modalities are contraindicated due to the risk of vascular injury, technical difficulties, especially when dealing with large thrombi, and lack of experienced operators. Mukharji and Peterson performed percutaneous removal of CRAT successfully with fluoroscopic and transesophageal echocardiographic guidance, using a basket retrieval device advanced to the right atrium via the left femoral vein [7].

Rose et al. reviewed 177 cases with RHT and described an improved survival rate with thrombolytic therapy that was statistically significant compared to either anticoagulation therapy or surgery [8].

In some patients, surgery or thrombolytic therapy may not be appropriate. Portugues et al., in the case of pulmonary embolism and intracardiac type A thrombus, considering the high risk of hemorrhage due to surgery and the patient’s clinical stability, applied conservative treatment instead of thrombolytic therapy or surgical embolectomy. They injected a bolus of unfractionated heparin and then started the infusion. On the third day, the patient became completely asymptomatic. The echocardiographic evaluation on the fourth day of hospitalization showed no signs of intracardiac thrombus [9].

Although the optimal method in CRAT treatment is controversial, anticoagulation therapy is recommended if there are no contraindications to anticoagulation, and in the absence of cardiac abnormalities and endocarditis, which are indications for surgery. Thrombolytic therapy is preferred when CRAT is associated with PTE. Surgery is suggested if the following conditions are observed: The thrombus is larger than 6 cm, anticoagulation and thrombolytic therapy are contraindicated or unresponsive, and if the cardiac pathology has a surgical indication. Active visceral bleeding, intracranial tumor or aneurysm, history of non-hemorrhagic cerebrovascular accident in the past year, hemorrhagic cerebrovascular accident, and severe hepatic/renal failure can be given as examples of contraindications of thrombolytic therapy. In addition, surgery is the most appropriate method if patent foramen ovale is present in the right atrial thrombi.

In this case, the coexistence of pulmonary embolism with CRAT was one of the important factors in our preference for thrombolytic therapy over surgery. Another factor in our preference for this treatment was the increased mortality and morbidity due to the fact that the patient had B-ALL. In this case, a positive clinical course was observed, with thrombolytic therapy and nearly complete thrombus resolution with USAT and improvement of right ventricular functions. This case report highlights the importance of reducing surgery-related mortality and morbidity and considering less invasive strategies such as isolated anticoagulation and thrombolytics in these patients.

Conclusion

In conclusion, catheter removal should be the first step in managing a CRAT. Surgical thrombectomy is not superior to anticoagulation or thrombolytic therapy; however, it is preferred in certain situations. In case of contraindication to anticoagulation and surgery, a simple catheter removal is an option. Percutaneous intravascular removal of the thrombus is an alternative if performed by an experienced personnel. Systemic thrombolysis and percutaneous interventional treatments can be applied in most catheter-related right atrial thrombi; the results are pretty successful. Nevertheless, prospective studies are needed to identify risk factors for development of thrombus and determine the optimal management of CRAT patients. However, co-morbidity is likely to remain an essential issue in the treatment choice.

Funding

None.

Declarations

Ethical approval

Since this is a case report, we did not take the ethical clearance as there was no change in the treatment protocol.

Informed consent

A written informed consent was obtained from the patient authorizing radiological examination, documentation, and treatment procedure and publication.

Conflict of interest

All the authors declare that they have no conflict of interest.

Human and animal rights

There were no infringements of human/ animal rights in this investigation.