Management of Hemophagocytic Lympho-Histiocytosis in Critically Ill Patients

Lemiale, Virginie; Valade, Sandrine; Calvet, Laure; Mariotte, Éric

doi:10.1177/0885066618810403

Cited by 10 publications

(22 citation statements)

References 59 publications

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“…This nding underscores the necessity of a prompt diagnosis and immediate treatment, although ICUacquired HLH is still widely underdiagnosed according to the literature [30]. Persistent fever that is refractory to antibiotics, pancytopenia, major hyperferritinemia, or unexplained chemical hepatitis should lead practitioners to screen patients for HLH [31][32][33]. Although variable and non-speci c, bone-marrow hemophagocytosis is still a hallmark HLH criterion [34][35][36] and was associated with a higher ICU mortality rate in our study.…”

Section: Discussionmentioning

confidence: 54%

Features of hemophagocytic lymphohistiocytosis in the intensive care unit (ICU) : a 260-patient retrospective analysis

Bichon¹,

Bourenne²,

Allardet-Servent³

et al. 2021

Preprint

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Background Adult hemophagocytic lymphohistiocytosis (HLH) is highly lethal in the ICU. The diagnostic and therapeutic emergency that HLH represents is compounded by its unknown pathophysiological mechanisms. Here, we report on a large cohort of adult-acquired HLH in the ICU. We analyzed prognostic factors associated with mortality to define the diagnostic and therapeutic challenges in this specific population, Methods This retrospective study included adult patients diagnosed with HLH in four ICUs in Marseille, France between 2010 and 2020. Patients who fulfilled the HLH-2004 criteria (> 4/8) and/or had an HScore > 169 were diagnosed with HLH. HLH was categorized into four groups according to etiology: sepsis-associated HLH, intracellular infection-associated HLH, malignancy-associated HLH, and idiopathic HLH. Results 260 patients were included: 121 sepsis-associated HLH (47%), 84 intracellular infection-associated HLH (32%), 28 malignancy-associated HLH (11%), and 27 idiopathic HLH (10%). The ICU mortality rate reached 57% (n = 147/260) without a statistical difference between etiological groups. Independent factors associated with mortality in multivariate analysis included age (OR (5 years) = 1.31 [1.16–1.48], p < 0.0001), SOFA score at ICU admission (OR = 1.37 [1.21–1.56], p < 0.0001), degradation of the SOFA score between ICU arrival and HLH diagnosis (Delta SOFA) (OR = 1.47 [1.28–1.70], p < 0.0001), the presence of bone-marrow hemophagocytosis (OR = 5.27 [1.11–24.97], p = 0.04), highly severe anemia (OR = 1.44 [1.09–1.91], p = 0.01), and hypofibrinogenemia (OR = 1.21 [1.04–1.41], p = 0.02). Conclusions In this large retrospective cohort study of critically ill patients, ICU-acquired HLH in adults was associated with a 57% mortality rate, regardless of HLH etiology. Factors independently associated with prognosis included age, presence of hemophagocytosis in bone-marrow aspirates, organ failure at admission, and worsening organ failure during the ICU stay. Whether a rapid diagnosis and the efficacy of specific therapy improve outcome is yet to be prospectively investigated.

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Section: Discussionmentioning

confidence: 54%

Features of hemophagocytic lymphohistiocytosis in the intensive care unit (ICU) : a 260-patient retrospective analysis

Bichon¹,

Bourenne²,

Allardet-Servent³

et al. 2021

Preprint

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“…This can be necessitated due to multiple organ failures, including vasoplegia, 13,14 acute respiratory distress syndrome, 13,15 neurological symptoms such as coma and seizures, 1,13,16 liver failure, 13 coagulopathies particularly as a result of hypofibrinogenemia, 13,17 and kidney failure. 13,18 This case highlights the importance of including HLH in the differential diagnosis of patients presenting with fever or cytokine storm particularly if sepsis or malignancy is suspected and the patient is not responding to appropriate therapy. Application of the HLH-2004 clinical criteria and HScore can be useful in diagnosing this uncommon condition.…”

Section: Discussionmentioning

confidence: 99%

Fever of Multiple Possible Origins

Wiseman

2021

Can Journ Gen Int Med

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A 60-year-old man presented with 1 week of fever despite broad-spectrum antibiotics for presumed pyelonephritis based on extended spectrum bacteriuria, recent bladder catheterization, and a negative search for other infections. He developed a maculopapular truncal rash, and pancytopenia with persistent fevers and worsening inflammatory markers despite modifying then stopping antibiotics. The non-specific clinical features at presentation and absence of hemophagocytosis on the initial bone marrow aspirate confounded multiple subspecialists and delayed the final diagnosis of hemophagocytic lymphohistiocytosis (HLH). Once this syndrome was elucidated, he responded well to dexamethasone and etoposide. An underlying diagnosis of systemic lupus erythematosus with aortic vasculitis was made, which in combination with pyelonephritis likely precipitated HLH. We summarize current concepts, pitfalls, and lessons learned in the diagnosis and management of HLH. RésuméUn homme de 60 ans se présente à l’hôpital à la suite d’une semaine de fièvre malgré la prise d’antibiotiques à large spectre pour traiter une pyélonéphrite soupçonnée, fondée sur une bactériurie à spectre étendu, un cathétérisme vésical récent et une recherche infructueuse d’autres infections. Il a développé une éruption cutanée maculopapulaire sur le tronc et une pancytopénie accompagnée d’une fièvre persistante et d’une augmentation des marqueurs de l’inflammation malgré la modification, puis l’arrêt des antibiotiques. Les manifestations cliniques non spécifiques à la présentation et l’absence d’hémophagocytose lors de la ponction médullaire initiale ont confondu de multiples surspécialistes et retardé le diagnostic définitif de lymphohistiocytose hémophagocytaire (LHH). Une fois que ce syndrome a été élucidé, le patient a bien répondu au traitement par la dexaméthasone et l’étoposide. Un diagnostic sous-jacent de lupus érythémateux systémique accompagné d’une vascularite de l’aorte a été posé qui, combiné à la pyélonéphrite, a probablement précipité la LHH. Nous résumons les concepts actuels, les pièges et les leçons apprises dans le diagnostic et la prise en charge de la LHH.

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“…By univariate analysis, the occurrence of haemorrhage (p = 0.003), PT (p = 0•016), FFP transfusion (p = 0.002), platelets transfusion (p = 0.018), SOFA score (p < 0.001) and mechanical ventilation requirement (p = 0.003) were associated with hospital mortality (Table 2). Patients who experienced a bleeding event had more severe organ dysfunctions (median SOFA score 8 [5][6][7][8][9][10][11][12] Furthermore, we did not find any correlation across the different biological haemostasis parameters (Figure S1). By multivariable analysis, the occurrence of a severe haemorrhage (OR 3.2 [1.2-8.6], p = 0.02) and SOFA score (OR 1.3 per point [1.1-4.5], p < 0.001) were associated with hospital mortality (Figure 3).…”

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confidence: 89%

“…This leads to high levels of circulating pro inflammatory cytokines, responsible for various biological abnormalities and clinical symptoms [5,6]. HLH can be very severe and intensive care unit (ICU) admission is often required due to organ failures [7]. Prognosis of critically ill patients with HLH remains grim with high mortality rates, ranging between 40% and 80% [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Coagulation disorders in patients with severe hemophagocytic lymphohistiocytosis

Valade

Joly

Veyradier

et al. 2021

Preprint

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BackgroundCoagulation disorders are common in patients with hemophagocytic lymphohistiocytosis (HLH), associated with an increased risk of bleeding and death. We aim to investigate coagulation disorders and their outcome implications in critically ill patients with HLH.MethodsWe prospectively evaluated 47 critically ill patients with HLH (median age of 54 years [42-67]) between April 2015 and December 2018. Coagulation assessments were performed at day 1. Abnormal standard coagulation was defined as prothrombin time (PT) <50% and/or fibrinogen <2g/L. HLH aetiology was mostly ascribed to haematological malignancies (74% of patients).ResultsCoagulation disorders and severe bleeding events were frequent, occurring in 30 (64%) and 11 (23%) patients respectively. At day 1, median fibrinogen level was 2·65g/L [1.61-5.66]. Fibrinolytic activity was high as suggested by increased median levels of D-dimers, fibrin monomers, PAI-1 (plasminogen activator inhibitor) and tPA (tissue plasminogen activator). Forty-one (91%) patients had a decreased ADAMTS13 activity (A Disintegrin-like And Metalloproteinase with ThromboSpondin type 1 repeats, member 13). By multivariable analysis, the occurrence of a severe bleeding (OR 3.215 [1.194-8.653], p=0·021) and SOFA score (Sepsis-Related Organ Failure Assessment) at day 1 (OR 1.305 per point [1.146-1.485], p<0·001) were independently associated with hospital mortality. No early biological marker was associated with severe bleeding.ConclusionsHyperfibrinolysis may be the primary mechanism responsible for hypofibrinogenemia and may also participate in ADAMTS13 degradation. Targeting the plasmin system appears as a promising approach in severe HLH-related coagulation disorders.

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Management of Hemophagocytic Lympho-Histiocytosis in Critically Ill Patients

Cited by 10 publications

References 59 publications

Features of hemophagocytic lymphohistiocytosis in the intensive care unit (ICU) : a 260-patient retrospective analysis

Features of hemophagocytic lymphohistiocytosis in the intensive care unit (ICU) : a 260-patient retrospective analysis

Fever of Multiple Possible Origins

Coagulation disorders in patients with severe hemophagocytic lymphohistiocytosis

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