Understanding haemorrhagic risk following thrombolytic therapy in patients with intermediate-risk and high-risk pulmonary embolism: a hypothesis paper

Abstract

While systemic intravenous thrombolysis decreases mortality in patients with high-risk pulmonary embolism (PE), it clearly increases haemorrhagic risk. There are many contraindications to thrombolysis, and efforts should aim at selecting those patients who will benefit most, without suffering complications. The current review summarises the evidence for the use of thrombolytic therapy in PE. It clarifies the pathophysiological mechanisms in PE and acute cor pulmonale that increase the risk of bleeding following thrombolysis. It discusses future management challenges, namely tailored drug administration, new treatment monitoring techniques and catheter-directed thrombolysis.

Catheter directed thrombolytic therapy and aspiration thrombectomy in intermediate pulmonary embolism with long term results

“…Today, the choice lies between streptokinase, recombinant tissue plasminogen activator and urokinase. The choice of procedure and tools differs based on the severity of the PE and estimated bleeding risk [7]. There are only a few prospective clinical trials examining CDT alone [8][9][10], ultrasound facilitated CDT [11,12] or CBT with thrombus fragmentation and/or mechanical thrombectomy [12,13] in the setting of intermediate-risk PE, but a head to head comparison of different techniques remains non-existant.…”

“…One-year follow-up The present study shows similar results, but the primary end-point was reached only in 90% of patients with CDT, and additional thombectomy was done in 9.6% of the patients to achieve the primary end-point, which was reached finally in 100% of the patients. The main disadvantages of CDT are still the high bleeding risk [7] and the limited effectiveness of the thrombolytic drug in old thrombi. Bleeding can be puncture related or due to the systemic effect of the thrombolytic drug.…”

The effect of fibrinolytic therapy on 30-day outcome in patients with intermediate risk pulmonary embolism - propensity score-adjusted analysis

“…In addition, patients in the highest PS quartile had significantly higher values of cardiac troponin I compared to quartiles I and II, which further supports their higher risk. In such subset of patients, wait-ing for hemodynamic deterioration to occur could be dangerous, since it can abruptly progress to shock or need for cardiopulmonary resuscitation, which puts them in a significantly higher risk of death and probably less effective "rescue thrombolysis" [23,24,25]. Therefore, Kearon et al [26], in the CHEST guidelines, propose that in patients without hypotension, deterioration in markers such as increased heart rate, a decrease in systolic BP (which remains > 90 mmHg), worsening gas exchange, progressive right heart dysfunction on echocardiography, or an increase in cardiac biomarkers, may also prompt the use of FT.…”

Fibrin Matrices as (Injectable) Biomaterials: Formation, Clinical Use, and Molecular Engineering

“…Note that the binding to these newly exposed C‐terminal lysines is typically stronger ( K D ≈ 10 −8 m ) than that to the original intrachain binding ( K D ≈ 10 −5 –10 −6 m ), as intact fibrin contains no C‐terminal lysines . Also a number of other factors can contribute to plasmin activation (Figure B), for example, the bacteria‐derived streptokinase and staphylokinase, which have been clinically employed in fibrinolytic therapies for the treatment of thrombosis, although with concerns about the risk of hemorrhage . Another clinically evaluated fibrinolytic agent is desmoteplase (derived from vampire bat saliva), which shows a highly selective fibrin‐bound activation of plasminogen, thereby avoiding the problematic systemic activation of plasmin .…”