Intrapulmonary rFVIIa for life threatening pulmonary hemorrhage in a case of relapsing acute lymphoblastic leukemia and platelet refractoriness

Abstract

Platelet refractoriness may lead to life-threatening gastro-intestinal, intracranial or pulmonary hemorrhage that is difficult to control despite massive platelet and red cell transfusion, antifibrinolytic agents, high dose corticosteroids, immunoglobulin and intravenous (I.V.) recombinant activated factor VII (rFVIIa). In cases with pulmonary hemorrhage, intrapulmonary administration of rFVIIa may be more effective in non-responsive cases. We report a 51-year-old man with relapsing acute lymphoblastic leukemia (ALL) and platelet refractoriness, who suffered a life-threatening pulmonary hemorrhage that was refractory to massive platelet transfusion, tranexamic acid, high dose corticosteroids, immunoglobulin and intravenous rFVIIa, but responded immediately to a single intrapulmonary dose of rFVIIa that was inhaled with a jet nebulizer assistance through the endotracheal tube.

Coagulation and Bleeding Management in Pediatric Extracorporeal Membrane Oxygenation: Clinical Scenarios and Review

“…The rationale for the use of intrapulmonary rFVIIa is that intravenously administered rVIIa does not reach the alveoli, whereas intrapulmonary rFVIIa can directly interact with tissue factor in the alveoli to stop bleeding without impairing oxygen transport (41). Use of rFVIIa, either directly applied with bronchoscopy or by nebulizer, has been described by several groups for the treatment of pulmonary hemorrhage using a variety of doses (42–46). Currently, our practice is to use rFVIIa at a dose of 50 μg/kg in 50 mL of saline to be administered by bronchoscope in patients who have existing pulmonary hemorrhage or develop hemorrhage during bronchoscopy.…”

Changes in the Cardiovascular System in Patients with Acute Leukemia after the Use of Polychemotherapy

“…These drugs, however, more often cause coronary necrosis of the myocardium due to coronary spasm, damage to the microvasculature and hypercoagulation. Clinically, various types of arrhythmias are observed, which can cause sudden death, heart failure and cardiogenic shock [2]. In children with ALL at different stages of polychemotherapy, various clinical symptoms (arterial dystonia, cardialgia, functional systolic murmur, etc.)…”

“…A violation of the contraction of a portion of the myocardium -hypokinesis -is often detected. Registration of diastolic dysfunction during Doppler measurements after the first administration of anthracycline antibiotics should be considered as an early manifestation of the cardiotoxic effect of cytostatics [2]. Manifestations of cardiotoxicity in the form of rhythm disturbances of grades III and IV (multifocal ventricular extrasystole, ventricular tachycardia) require Holter monitoring and antiarrhythmic therapy.…”

Commentary on Pilot Trial of a Novel Two-Step Therapy Protocol Using Nebulized Tranexamic Acid and Recombinant Factor VIIa in Children with Intractable Diffuse Alveolar Haemorrhage

“…Several cases reported the successful use of rFVIIa locally administered through bronchoscope to adults with DAH. One case in was given rFVIIa through nebulization after failure of intravenous rFVIIa [16], Direct intrabronchial instillation was the primary method of drug delivery in all reports [17][18][19].…”