Intrapleural r-tPA in Association with Low-Molecular Heparin May Cause Massive Hemothorax Resulting in Hypovolemia

Abstract

The use of intrapleural instillation of recombinant tissue plasminogen activator (r-tPA) in the treatment of pleural infection may increase pleural fluid drainage associated with a clinical and imaging improvement, leading to a faster resolution. The use of r-tPA is generally well tolerated. Here we report 2 cases of massive pleural hemorrhage resulting in life-threatening hypovolemia, in 2 patients treated with intrapleural r-tPA for a pleural infection, who were simultaneously receiving systemic anticoagulation (1 therapeutic, the second prophylactic) with low-molecular weight heparin. It appears that the decision of treating pleural infection with r-tPA in patients receiving therapeutic or prophylactic systemic anticoagulation must be well balanced and in case of association of these compounds, close monitoring is necessary.

Phase I trial of the single-chain urokinase intrapleural LTI-01 in complicated parapneumonic effusions or empyema

“…These included abnormalities of the screening coagulation profile, known platelet dysfunction, or use of antiplatelet agents. Patients could receive deep vein thrombosis (DVT) prophylaxis but not full anticoagulation, given reports of increased bleeding risk (34,35). Patients with a glomerular filtration rate of less than 30 were also excluded.…”

A case of hemothorax secondary to intrapleural fibrinolytic therapy: Considerations for use of fibrinolytics in high-risk patients

“… STUDY Sample Size Effusion type Intrapleural thrombolytic therapy use Anticoagulation or antiplatelet use Maskell et al, 2005 [ 11 ] 427 adults Empyema; Parapneumonic complicated effusion Placebo or streptokinase Unspecified Ruiz et al, 2006 [ 12 ] 1 adult Empyema Alteplase Nil Gervais et al, 2008 [ 13 ] 66 adults Empyema (27 patients), parapneumonic complicated effusion (26 patients), hemothorax (8 patients), postoperative effusion (4 patients), and malignant effusion (1 patient). Alteplase 1 patient warfarin, 2 Patient Low molecular weight heparin and 1 Patient unfractionated heparin Goralski et al, 2009 [ 14 ] 1 adults Benign Effusion Alteplase nil Chai and Kuan 2011 [ 15 ] 1 adult Parapneumonic complicated effusion Streptokinase Nil Anevlavis et al, 2011 [ 16 ] 2 adults Parapneumonic complicated effusion Alteplase Prophylactic dose of subcutaneous low-molecular weight heparin (tinzaparin 3,500 IU) …”

Life-threatening pleural hemorrhage following intrapleural enzyme therapy and successful treatment with fibrin-thrombin sealant pleurodesis: a case report

“…A further two case reports of massive hemothorax, resulting in hypovolemic shock, were reported by Anevlavis et al . [ 7 ] in adults who received intrapleural alteplase while receiving low-molecular-weight heparin (tinzaparin). Additionally, Goralski et al .…”

“…2014 [ 13 ] Retrospective observational study 107 adults tPA and DNase Unfractionated heparin × 1, chronic liver disease and ↑prothrombin time × 1 Hemorrhage requiring transfusion in two patients Anevlavis et al . 2011 [ 7 ] Case series Two adults Alteplase Therapeutic dose tinzaparin (14,000 IU), Prophylactic tinzaparin (3500 IU) Two massive pleural hemorrhages Chai and Kuan, 2011 [ 17 ] Case report One adult Streptokinase Nil Massive pleural hemorrhage Goralski et al . 2009 [ 9 ] Case report and literature review One adult Alteplase Nil Severe pleural hemorrhage Gervais et al .…”

“…Whether or not anticoagulation constitutes an absolute contraindication is not widely agreed upon. And although bleeding complications seem to be perceived as rare [ 6 ], there are a number of reports of severe pleural bleeding requiring transfusion or emergency surgery [ 7 – 9 ]. In those requiring surgery, an active focal bleeding site is infrequently found and thoracotomy and decortication is often described [ 7 – 9 ].…”