[Veno-venous extracorporeal membrane oxygenation for capillary leak syndrome during induction chemotherapy in acute myeloid leukemia].

A 44-year-old woman was diagnosed with acute myeloid leukemia (RUNX1::RUNX1T1 translocation) and received induction chemotherapy with idarubicin hydrochloride and cytosine arabinoside. The pneumonia that had been present since admission worsened, and a drug-induced skin rash appeared. On day 17, she presented with respiratory failure and shock, complicated by hemoconcentration and hypoalbuminemia. This was considered capillary leak syndrome due to pneumonia and drug allergy, so she was started on pulse steroid therapy and IVIG, and was intubated on the same day. On day 18, venovenous-extracorporeal membrane oxygenation (VV-ECMO) was started due to worsening blood gas parameters despite ventilatory management. Bronchoalveolar lavage fluid was serous, and both blood and sputum cultures yielded negative. The patient was weaned from VV-ECMO on day 26 as the pneumonia improved with recovery of hematopoiesis. She was disoriented, and a CT scan on day 28 revealed cerebral hemorrhage. Her strength recovered with rehabilitation. After induction chemotherapy, RUNX1::RUNX1T1 mRNA was not detected in bone marrow. The patient received consolidation chemotherapy, and has maintained complete remission. Severe respiratory failure during induction chemotherapy for acute leukemia can be fatal, but VV-ECMO may be lifesaving.

Polycythemia as an Uncommon Finding in 2 Children, One With Systemic Capillary Leak Syndrome and the Other With Protein-losing Enteropathy Caused by CD55 Deficiency.

We report 2 children with distinct causes of polycythemia, 1 from systemic capillary leak syndrome (SCLS) and the other from protein-losing enteropathy (PLE) caused by CD55 deficiency. There is only a single case series about polycythemia in children with SCLS, but none on polycythemia in children with PLE. We present a 10-year-old girl with hypoalbuminemia, polycythemia, and edema who died as a result of an SCLS attack and a 1-year-old girl with PLE who was successfully treated with eculizumab. Our experience suggests that hematologists should be alert for SCLS and PLE in children with relative polycythemia.

Trauma-induced capillary leak syndrome after penetrating chest injury: Manifestation of massive ascites and pulmonary secretions aggravated by transfusion.

Trauma with prolonged shock can cause systemic capillary leak syndrome regardless of the site of injury and a transfusion can aggravate it. The systemic capillary leak induces both an abdominal compartment syndrome and pulmonary edema, and a transfusion can aggra-vate these sequelae within hours. In our case, 21-year-old man with a penetrating injury in his left thorax experienced delay in rescue and definitive surgery. To manage life-threatening shock, massive blood transfusion and crystalloids had been infused. Cardiopulmonary cerebral resuscitations were performed 2 times during the surgery. Massive amount of pulmonary secretions emitted from his airways with severe hypoxia along with development of massive ascites causing abdominal compartment syndrome, while the surgery was underway. After temporary abdominal closure, he was moved to the intensive care unit and underwent venovenous extracorporeal membranous oxygenation. He recovered without any notable complications. It is important to prevent and correct the shock rapidly by appropriate rescue, controlling the source and infusing less amount of crystalloid and transfusion.

[Idiopathic systemic capillary leak syndrome: 2 cases with misleading presentation]. / Syndrome de fuite capillaire idiopathique : 2 cas cliniques de présentation trompeuse.

INTRODUCTION: Idiopathic systemic capillary leak syndrome (ISCLS) also known as Clarkson syndrome is a rare and sudden life-threatening entity. Three consecutive phases are described. A first non-specific prodromal phase often manifests as "flu-like" symptoms and precedes capillary leak phase with major hypovolemic and distributive shock leading to serious and frequent multiorgan dysfunction syndrome (MODS). Severe hypovolemia contrasts with edema, and hemoconcentration with hypoalbuminemia. ISCLS is characterized by these two clinical and biological paradoxes. Subsequent recovery phase exhibits organ function restoration along with interstitial/intravascular volumes normalization. The latter occurs spontaneously and systematically in patients surviving from leak phase. OBSERVATIONS: We report here two ISCLS cases admitted in intensive care unit (ICU) both enhancing initial misdiagnosis possibly lowering prognosis and outcome. Our first 28-year-old female patient was admitted for « polycythemia vera ¼ although hemoconcentration was attributable to hypovolemia. She presented circulatory arrest during the second bloodletting session and complicated with MODS. In and out ICU favorable outcome was noted on intravenous immunoglobulin therapy. A second 57-year-old male patient was admitted in ICU for severe "myositis" (myalgia and rhabdomyolysis) although rectified diagnosis retained compartment syndrome (muscular severe edema following capillary leak). Rapid and refractory hypovolemic shock appeared with subsequent MODS leading to death. CONCLUSION: ISCLS pathophysiology remains unknown but certainly implies transitory endothelial dysfunction. Impossibility of randomized controlled trial for this exceptional disease led to based-on-experience therapeutic guidelines implying symptomatic care (cardiac output surveillance, nephroprotection, prudent fluid intake, prudent vasoactive amine use) and specific therapies (intravenous aminophylline during severe flares). Although enhancing controversial and even deleterious effects during the acute phase, polyvalent immunoglobulins are effective for relapse prevention. Syndromic diagnosis is difficult, but its precocious finding constitutes a key-element in better outcome before organ failure.

Clinical features of 47 secondary hemophagocytic lymphohistiocytosis patients complicated with capillary leak syndrome.

The clinical features of patients with secondary hemophagocytic lymphohistiocytosis (sHLH) complicated with capillary leak syndrome (CLS) remain controversial. The data of 259 sHLH patients were retrospectively analyzed. The clinical manifestations, laboratory findings, treatment, and prognosis of the CLS-sHLH group and non-CLS-sHLH group were compared. The levels of fibrinogen, albumin, and serum calcium in the CLS-sHLH group were lower than in the non-CLS-sHLH group, and serum triglycerides in the CLS-sHLH group were higher than in the non-CLS-sHLH group (P < 0.05). Univariate analysis showed that fibrinogen level was an independent prognostic factor in sHLH patients complicated with CLS. The median survival time was significantly shorter in patients with fibrinogen ≤ 1.3 g/L than in patients with fibrinogen > 1.3 g/L (P < 0.05). Patients with improved CLS conditions in the CLS-sHLH group had significantly increased albumin and serum calcium after treatment (P < 0.05); patients without improved conditions in the CLS-sHLH group also had significantly increased albumin after treatment (P < 0.05), but the serum calcium did not change significantly (P > 0.05). sHLH patients complicated with CLS had significantly worse prognosis than without CLS. Significant reduction in fibrinogen may be an independent prognostic factor for poor prognosis in sHLH patients complicated with CLS.

Microalbuminuria assessment after thoracic surgery: Early identification of complication risks.

INTRODUCTION: Microalbuminuria (MA) is considered a reflection of systemic capillary leak and an early marker of acute stress reaction to the surgical insult, proportional to the severity of the initiating condition and predictive of the individual response to surgical stress. OBJECTIVES: We conducted a prospective study to assess for the variation of MA within 4 days after thoracic surgery. We correlated observed MA levels with both their respective PaO2 /FiO2 respiratory ratio and the onset of postoperative complications. METHODS: This single-centre study enrolled 255 consecutive patients having an American Society of Anaesthesiologists (ASA) score ≤ 3. The mean age was 62 years with 67% male. All patients were scheduled for elective pulmonary resection. MA was measured in urine samples as the albumin-to-creatinine ratio (A/C), prior to, at and after extubation up to 96 hours. PaO2 /FiO2 was measured at extubation and on the first postoperative day. RESULTS: Overall, preoperative A/C levels resulted normal, with a significant average increase at extubation which peaked 6 hours later (P < 0.001). Larger postoperative A/C increases were observed in patients who developed postoperative complications, compared to those without these complications (P < 0.019). Moreover, patients undergoing major open pulmonary resections had larger postoperative A/C increases, compared to those undergoing minor video-assisted thoracic surgery resections (P < 0.006). At the time of extubation, A/C was inversely related to the PaO2 /FiO2 ratio (r = -0.25; P = 0.038). Peak A/C > 61 mg/g (P = 0.0003) was associated with postoperative cardio-pulmonary complications (OR 3.85; P = 0.003). CONCLUSION: Within 6 hours after extubation, MA assessment may be a rapid and relatively inexpensive method for better predicting perioperative risk in an ASA score ≤ 3 population.

Hyperviscosity-related splenic infarction, gastrointestinal ischaemia-reperfusion injury and transient dysarthria in a patient with distributive shock due to idiopathic systemic capillary leak syndrome (Clarkson's syndrome).

Clarkson's syndrome, also known as idiopathic systemic capillary leak syndrome, is characterised by vascular hyperpermeability resulting in intravascular hypovolaemia and shock. A clinician should consider the diagnosis if other causes of shock, for example, sepsis and anaphylaxis, are ruled out and concomitant hyperviscosity is not caused by a myeloproliferative disease. Here, we describe a patient presenting with severe plasma leakage and assumable blood hyperviscosity leading to splenic infarction, gastrointestinal ischaemia-reperfusion syndrome and transient dysarthria. Our patient was first suspected of polycythaemia vera and phlebotomies were performed. Awareness of this syndrome and subsequent correct treatment is essential to prevent complications and to reduce mortality. As in our patient, most patients with Clarkson's syndrome have a monoclonal gammopathy, light-chain-type kappa. Prophylactic treatment with intravenous immunoglobulin (IVIg) is advised to prevent recurrence of capillary leak. Our patient did not suffer from another symptomatic episode after starting IVIg.

Epidemiology, risk factors, and prognosis of capillary leak syndrome in pediatric recipients of stem cell transplants: a retrospective single-center cohort study.

CLS involves sudden loss of intravascular fluids into the interstitial spaces. CLS was described as a possible complication after SCT. Few studies report the incidence of CLS in pediatric populations. We aimed to assess CLS incidence, its risk factors, and impact on the survival. The clinical charts of patients <18 years of age transplanted at our institution between 2002 and 2012 were reviewed. CLS was defined by weight gain >3% in 24 hours and positive intake balance despite furosemide administration. In total, 234 patients underwent 275 allogeneic SCT procedures in the analyzed time frame. Fifteen patients developed CLS (5.4%). The probability of developing CLS was significantly increased in patients suffering from sepsis (14.3% vs 0.6%, P<.001). Patients with CLS exhibited an increased risk of acute GvHD in the first 30 days after SCT (10.8% vs 1.8%, P=.002). Ten of the patients with CLS required intensive care. CLS strongly impacts OS at day +100 after SCT and is a predictive factor of TRM at the same date (42.9% vs 5%, P<.0001). The biological relation among sepsis, GvHD, and CLS development in terms of cytokine release and endothelial damage warrants further studies.

Systemic capillary leak syndrome: a case-report.

We report a case of a patient presenting with episodic hypotension, tachycardia and oedema, with an elevated serum IgG kappa paraprotein level. She was diagnosed as having systemic capillary leak syndrome and upon commencing oral theophylline has had no further presentations. The patient has since progressed to multiple myeloma.

[Risk factors for capillary leak syndrome in children with hematological malignancies].

OBJECTIVE: To investigate the risk factors for capillary leak syndrome (CLS) in children with malignant hematologic diseases. METHODS: Thirty children with hematological malignancies complicated with CLS were analyzed with multiple logistic regression analysis. RESULTS: At the test level of 0.05, hypoxemia and septicemia were found to significantly correlate with CLS in these children, and the number of white blood cells before CLS and severe bone marrow suppression were near the test level. CONCLUSION: Hypoxemia and septicemia are risk factors for CLS in children with malignant hematologic diseases.

Idiopathic systemic capillary leak syndrome in children.

Adult subjects with systemic capillary leak syndrome (SCLS) present with acute and recurrent episodes of vascular leak manifesting as severe hypotension, hypoalbuminemia, hemoconcentration, and generalized edema. We studied clinical disease characteristics, serum cytokine profiles, and treatment modalities in a cohort of children with documented SCLS. Six children with SCLS were recruited from the United States, Australia, Canada, and Italy. Serum cytokines from SCLS subjects and a group of 10 healthy children were analyzed. Children with SCLS (aged 5-11 years old) presented with at least 1 acute, severe episode of hypotension, hypoalbuminemia, and hemoconcentration in the absence of underlying causes for these abnormalities. In contrast to what is observed in adult SCLS, identifiable infectious triggers precipitated most episodes in these children, and none of them had a monoclonal gammopathy. We found elevated levels of chemokine (C-C motif) ligand 2 (CCL2), interleukin-8, and tumor necrosis factor α in baseline SCLS sera compared with the control group. All patients are alive and well on prophylactic therapy, with 4 patients receiving intravenous or subcutaneous immunoglobulins at regular intervals. The clinical manifestations of pediatric and adult SCLS are similar, with the notable exceptions of frequent association with infections and the lack of monoclonal gammopathy. Prophylactic medication, including high dose immunoglobulins or theophylline plus verapamil, appears to be safe and efficacious therapy for SCLS in children.

Systemic capillary leak syndrome revealing a diffuse large B-cell lymphoma.

We report on a 75-year-old woman who presented with recurrent episodes of hypotension, anasarca, renal failure, hypoalbuminaemia without proteinuria, suggestive of systemic capillary leak syndrome (SCLS). Further investigations led to a diagnosis of diffuse large B-cell lymphoma. Secondary SCLS associated with non-Hodgkin lymphoma is reviewed.

Capillary leak syndrome in trauma: what is it and what are the consequences?

TICS is a complex disease that is clearly multifactorial in the traumatically injured patient (Fig. 2). Although systemic inflammation that occurs directly as a result of injury plays the most prominent role, the local tissue and organ injury effects of trauma not only cause local capillary leak and edema but also further amplify the SIRS response. High volume fluid administration and hypoproteinemic states further exacerbate the problem. All of this leads to organ dysfunction and failure, which is the third leading cause of death following injury. Strategies to treat TICS and attenuate its effects once it occurs by targeting inflammatory pathways have been wholly unsuccessful. The mainstay of therapy for TICS is prevention and minimization of its lethal effects. Newer resuscitation strategies such as hemostatic resuscitation and early goal-directed therapies are currently the best available strategies to combat TICS. Whether these result in better outcomes remains to be seen and the authors anxiously await the results of well-designed prospective trials.

[Breathing difficulties in children subjected to bone marrow transplantation]. / Dificultad respiratoria en el niño sometido a trasplante de médula ósea.

Up to 60% of all children that receive to bone marrow transplantation (BMT) develop respiratory distress. It constitutes a common complication in this kind of patients, due to the increasing number of therapeutic applications of BMT and to improvement in the therapeutic approach to the problems associated with this procedure. We describe the different causes of respiratory distress after BMT in relation to its initiation or the presence of infection in its origin. The diagnosis and treatment are also reviewed.

Síndrome de extravasamento capilar sistêmico / Systemic capillary leak syndrome

A síndrome de extravasamento capilar sistêmico é rara e causada por aumento da permeabilidade capilar. Várias etiologias estão envolvidas. No nosso serviço de Dermatologia, a principal é a psoríase instável. Diversos tratamentos são usados e muitos ainda estão em estudo. Nosso objetivo foi apresentar esta situação clínica potencialmente fatal que ocorre em nossa especialidade.

The systemic capillary leak syndrome is rare and caused by increased capillary permeability. Several etiologies are involved. In our Department of Dermatology the main one is unstable psoriasis. Several treatments are used and many are still under study. Our objective was to present this potentially fatal medical condition that occurs in our specialty.

Four-limb compartment syndrome associated with the systemic capillary leak syndrome.

Systemic capillary leak syndrome, or the Clarkson syndrome, is an extremely rare condition in which increased capillary permeability results in a massive shift of fluid into the extravascular space. This is followed rapidly by hypotensive shock, haemoconcentration, and, potentially, substantial oedema of the limbs resulting in an acute compartment syndrome. It is important for orthopaedic surgeons to be aware of this syndrome as our medical colleagues, who initially care for these patients, are less familiar with the diagnosis and the need for emergency management of the associated compartment syndrome should it develop. There have been fewer than 100 cases of this entity reported. This case report is the first to describe the subsequent development of a compartment syndrome in all four limbs. Clinical vigilance and continuous monitoring of intracompartmental pressure is necessary in these patients in order to help reduce limb-threatening complications.