secondary hemophagocytic syndrome

Clinical and Laboratory Characteristics and Differential Diagnosis between Secondary Hemophagocytic Syndrome and Sepsis

COMPLICATIONS OF ANTITUMOR TREATMENT , , , ,

VG Potapenko1,2, MYu Pervakova2, AV Titov1, OV Goloshchapov2, SV Lapin2, EA Surkova2, AV Klimovich1, OP Mironova1, NN Petrova1, NYu Chernookaya1, EV Karyagina3, NV Skorobogatova1, ES Pavlyuchenko4, EA Karev4, NA Potikhonova5, VA Dubkova6, AYu Kaskov7, AV Rysev7, TG Kulibaba6, NV Medvedeva1

1 Municipal Clinical Hospital No. 31, 3 Dinamo pr-t, Saint Petersburg, Russian Federation, 197110

2 IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

3 Municipal Hospital No. 15, 4 Avangardnaya str., Saint Petersburg, Russian Federation, 198205

4 II Mechnikov North-Western State Medical University, 41 Kirochnaya str., Saint Petersburg, Russian Federation, 191015

5 Russian Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024

6 Saint Petersburg State University, 7/9 Universitetskaya nab., Saint Petersburg, Russian Federation, 199034

7 II Dzhanelidze Saint Petersburg Research Institute of Emergency Medicine, 3 Budapeshtskaya str., Saint Petersburg, Russian Federation, 192242

For correspondence: Vsevolod Gennad’evich Potapenko, 3 Dinamo pr-t, Saint Petersburg, Russian Federation, 197110; Tel.: +7(905)284-51-38; e-mail: potapenko.vsevolod@mail.ru

For citation: Potapenko VG, Pervakova MYu, Titov AV, et al. Clinical and Laboratory Characteristics and Differential Diagnosis between Secondary Hemophagocytic Syndrome and Sepsis. Clinical oncohematology. 2019;12(3):329–37 (In Russ).

doi: 10.21320/2500-2139-2019-12-3-329-337

ABSTRACT

Background. Secondary hemophagocytic syndrome (SHPS) and sepsis, although very similar in their clinical manifestations and laboratory parameters, essentially differ in terms of methods of their treatment. SHPS therapy is aimed at immunosuppression, whereas in sepsis anti-infectious treatment is required. To choose the correct therapy a rapid differential diagnosis is necessary.

Aim. Search and analysis of criteria of differential diagnosis between SHPS and sepsis.

Materials & Methods. The data of 102 patients were analyzed: 55 SHPS patients (median age 60 and range 18–81 years) and 47 sepsis patients (median age 60 and range 18–89 years). SHPS was diagnosed on the basis of HLH-2004 and H-Score criteria. Sepsis was confirmed by documented inflammatory lesions and systemic inflammatory reactions. Microbiologically confirmed sepsis was reported in 10 (21 %) patients. In all sepsis patients multiple organ failure was identified.

Results. The study of SHPS and sepsis groups revealed significant differences (p < 0.05) in the levels of C-reactive protein, procalcitonin, creatinine, albumin, and sodium. It was also found out that splenomegaly rate and the levels of triglycerides, ferritin, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in SHPS were significantly higher than in sepsis, but the levels of glycosylated ferritin (%GF), fibrinogen, leukocytes, neutrophils, and thrombocytes were lower. The following medians (quartiles 1–3) were reported in SHPS and sepsis, respectively: triglycerides (mmol/L) were 3.1 (2.3–3.8) and 1.5 (0.8–2.7), total ferritin (ng/mL) was 7,170 (3,159.2–12,551.0) and 1,274 (559.0–3,041.5), %GF was 26.5 (16.7–37.3) and 54.5 (37.7–71.8), fibrinogen (g/L) was 2.8 (1.4–4.4) and 5.3 (2.8–6.8), ALT (IU/L) was 50 (20–102) and 30 (15.3–55.5), AST (IU/L) was 66 (40.0–105.6) and 36 (24.6–78.0), leukocytes (×109/L) were 3.7 (2.1–5.5) and 8.9 (6.5–14.5), thrombocytes (×109/L) were 56 (25.2–93.5) and 157 (97–308). According to ROC analysis the areas under the curve were as follows: 0.88 for neutrophil level, 0.85 for total ferritin, %GF, leukocytes, and thrombocytes, 0.74 for triglycerides, 0.71 for fibrinogen, 0.65 for sodium, and 0.61 for ALT and AST.

Conclusion. In differential diagnosis between SHPS and sepsis most important are the levels of total ferritin, its glycosylated fraction, and triglycerides; less important are fibrinogen, neutrophils, thrombocytes and spleen size. As diagnosis and differential diagnosis between SHPS and sepsis are based on the sum total of clinical and laboratory markers, none of the specified characteristics can serve as a reliable parameter if taken separately.

Keywords: secondary hemophagocytic syndrome, sepsis, ferritin, glycosylated ferritin, triglycerides, hyperferritinemia.

Received: November 20, 2018

Accepted: May 15, 2019

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Secondary Hemophagocytic Syndrome in the Adult Patients. Literature Review and Authors’ Experience

RARE HEMATOLOGICAL TUMORS AND SYNDROMES , , , ,

VG Potapenko1,2, NA Potikhonova4, VV Baikov2, MB Belogurova1, IA Lisukov3, AV Klimovich1, SV Lapin2, MO Ivanova2, VM Kravtsova2, EI Podol’tseva1, NV Medvedeva1, BV Afanas’ev2

1 Municipal Clinical Hospital No. 31, 3 Dinamo pr-t, Saint Petersburg, Russian Federation, 197110

2 R.M. Gorbacheva Scientific Research Institute of Pediatric Hematology and Transplantation; Academician I.P. Pavlov First St. Petersburg State Medical University, 12 Rentgena str., Saint Petersburg, Russian Federation, 197022

3 I.I. Mechnikov North-Western State Medical University, 41 Kirochnaya str., Saint Petersburg, Russian Federation, 197022

4 Russian Scientific Research Institute of Hematology and Transfusiology under the Federal Medico-Biological Agency, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024

For correspondence: Vsevolod Gennad’evich Potapenko, Municipal Clinical Hospital No. 31, 3 Dinamo pr-t, Saint Petersburg, Russian Federation, 197110; Tel.: +7(812)230-19-33; e-mail: potapenko.vsevolod@mail.ru

For citation: Potapenko V.G., Potikhonova N.A., Baikov V.V., Belogurova M.B., Lisukov I.A., Klimovich A.V., Lapin S.V., Ivanova M.O., Kravtsova V.M., Podol’tseva E.I., Medvedeva N.V., Afanas’ev B.V. Secondary Hemophagocytic Syndrome in the Adult Patients. Literature Review and Authors’ Experience. Klin. Onkogematol. 2015;8(2):169–84. (In Russ.).

ABSTRACT

Background & Aims. The hemophagocytic syndrome is a dangerous hyperinflammatory syndrome usually caused by an infection. It is a result of excessive cell activation in the mononuclear phagocyte system which is manifested itself through cytopenia, systemic inflammatory reaction, liver and spleen impairment. Since the disease is rare and its diagnosing is very complicated, this syndrome has not been studied thoroughly and is overlooked very often. The aim of this work is to describe authors’ experience in dealing with the secondary hemophagocytic syndrome (HPS) and to present a literature review.

Methods. Clinical and laboratory data of 15 patients aged 16 to 64 (median age 48 years) with secondary HPS observed over the period from 2009 till 2013 were analyzed. Secondary HPS was diagnosed in patients with malignant lymphoproliferative and infectious diseases. HPS signs were found in lymphoproliferative disorders (n = 5), chronic active EBV-infection (n = 3), allogeneic hematopoietic stem cell transplantation (n = 3), acute leukemia (n = 1), multiple myeloma (n = 1), pneumonia (n = 1), and glomerulonephritis (n = 1). 8 patients underwent treatment for HPS: etoposide (n = 1), glucocorticoids (n = 1), intravenous immunoglobulin (n = 2), combination of rituximab + glucocorticoids (n = 2), etoposide + cyclosporine A (n = 1), as well as combined HLH-2004 chemotherapy (n = 1). The median observation period was 42 months.

Results. Among 15 adult patients enrolled into the retrospective analysis, malignant lymphoproliferative disorders and chronic EBV-infection were most common underlying disorders in case of secondary HPS. Early diagnosing is very complicated, because diagnostic criteria accepted at present are typical for the late-phase HPS. The above factors require development of more sensitive and universal diagnostic criteria.

Conclusion. In oncohematological practice, the secondary HPS is a severe complication requiring differential diagnosing with other critical conditions and intensive care. In case of HPS associated with oncohematological disorders, patients require close monitoring throughout the antitumor treatment period and after it.

Keywords: secondary hemophagocytic syndrome, lymphoma, Epstein-Barr virus, etoposide, hematopoietic stem cells transplantation.

Received: December 9, 2014

Accepted: February 7, 2015

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