What is Capillary Leak Syndrome (Systemic Capillary Leak Syndrome)?

From the Guidelines

Capillary Leak Syndrome (CLS) is a condition characterized by symptoms such as hypoalbuminemia, edema, hypotension, and hyponatremia, often seen in patients treated with certain therapies, including tagraxofusp, and requires careful management to prevent complications. The condition is marked by the leakage of fluid and proteins from blood vessels into surrounding tissues, leading to a range of symptoms, including hypoalbuminemia, which is the most consistent and early manifestation of CLS, as seen in a study of patients treated with tagraxofusp 1. Key features of CLS include:

• Hypoalbuminemia, which can be grade 1 or 2, as reported in patients treated with tagraxofusp 1
• Edema, which can be managed with diuretics
• Hypotension, which requires careful fluid management to prevent shock
• Hyponatremia, which can be managed with fluid restriction and diuretics Management of CLS involves supportive care with careful fluid management, including the administration of parenteral albumin and diuretics, as well as monitoring for symptoms such as thrombocytopenia and neutropenia, which can occur in some patients 1. It is essential to recognize the symptoms of CLS promptly and initiate treatment to prevent complications, such as shock, multi-organ failure, and death. In patients treated with tagraxofusp, premedications, including acetaminophen, diphenhydramine, methylprednisolone, and famotidine, can help mitigate acute infusion-related adverse effects, which may be related to cytokine release from necrotic cells and damaged blasts 1. Overall, CLS is a condition that requires careful management and monitoring to prevent complications and improve patient outcomes.

From the Research

Definition and Characteristics

• Capillary Leak Syndrome (CLS) is a rare clinical syndrome associated with significant morbidity and mortality 2.
• It is characterized by profound vascular leakage, presenting as a classic triad of hypotension, hypoalbuminemia, and hemoconcentration 3.
• The systemic capillary leak syndrome (SCLS) is a rare disease of reversible plasma extravasation and vascular collapse accompanied by hemoconcentration and hypoalbuminemia 4.

Causes and Pathophysiology

• The cause of CLS is unknown, although it is believed to be a manifestation of transient endothelial dysfunction due to endothelial contraction, apoptosis, injury, or a combination of these 4.
• There is an increase in capillary permeability with the extravasation of fluid and plasmatic proteins to the extravascular space, which can lead to hypovolaemic shock 5.
• The role of cytokines has become central in the comprehension of the pathophysiology of CLS, and adhesion molecules are probably also involved in the genesis of capillary leakage 5.

Clinical Presentation and Diagnosis

• Patients experience shock and massive edema, often after a nonspecific prodrome of weakness, fatigue, and myalgias, and are at risk for ischemia-induced organ failure, rhabdomyolysis, and muscle compartment syndromes, and venous thromboembolism 4.
• Diagnosis is made clinically and by exclusion of other diseases that cause similar symptoms and signs, most notably sepsis, anaphylaxis, and angioedema 4.
• Clinical and laboratory findings consistent with an acute episode of CLS include generalized edema, hemoconcentration, hypoproteinemia, and monoclonal gammopathy 5.

Treatment and Management

• Intensive care and supportive therapy constitute the mainstay of the treatment, along with judicious use of crystalloids and colloids such as dextran and starch during the leak phase 2.
• Vasopressor therapy and judicious fluid replacement, possibly with colloid solutions for their osmotic effects, are used to prevent the sequelae of underperfusion 4.
• Continuous renal replacement therapy (CRRT) plays an important role in supportive treatment for severe CLS, especially in patients with severe or refractory hypoxemia 2, 3.
• The association of steroids with furosemide, aminophylline, and terbutaline may be capable of controlling the clinical manifestation of acute episodes in most cases 5.