Lab Med Online.  2019 Oct;9(4):249-253. 10.3343/lmo.2019.9.4.249.

Therapeutic Plasma Exchange in a Patient with Hemophagocytic Lymphohistiocytosis

• Roh J
• Kim S
• Nah H
• Lee K
• Kim HO

• KMID: 2458687
• DOI: http://doi.org/10.3343/lmo.2019.9.4.249

Abstract

A 22-year old female patient with systemic lupus erythematosus presenting microangiopathic hemolytic anemia was treated with therapeutic plasma exchange 23 times. The patient's condition and laboratory findings (aspartate aminotransferase, alanine aminotransferase, ferritin, total bilirubin, and lactate dehydrogenase) did not improve despite the initial 18 therapeutic plasma exchange treatments. Thrombotic thrombocytopenic purpura was ruled out due to normal ADAMTS-13 activity test result; hemophagocytic lymphohistiocytosis was diagnosed based on fever, splenomegaly, pancytopenia, hypertriglyceridemia, hyperferritinemia, and hemophagocytosis in bone marrow aspiration. The patient's condition improved rapidly upon treatment with a combination of immunosuppressants and cytotoxic agents, and more therapeutic plasma exchanges were performed five consecutive times with prolonged intervals in between. We observed that therapeutic plasma exchange treatment alone was not effective enough to treat hemophagocytic lymphohistiocytosis, unlike thrombotic thrombocytopenic purpura. Therefore, it is necessary to determine and start drug administration promptly in the treatment of hemophagocytic lymphohistiocytosis with thrombotic microangiopathy.

Keyword

Hemophagocytic lymphohistiocytosis; Therapeutic plasma exchange; Thrombotic microangiopathy

MeSH Terms

Alanine Transaminase
Anemia, Hemolytic
Bilirubin
Bone Marrow
Cytotoxins
Female
Ferritins
Fever
Humans
Hypertriglyceridemia
Immunosuppressive Agents
Lactic Acid
Lupus Erythematosus, Systemic
Lymphohistiocytosis, Hemophagocytic*
Pancytopenia
Plasma Exchange*
Plasma*
Purpura, Thrombotic Thrombocytopenic
Splenomegaly
Thrombotic Microangiopathies
Alanine Transaminase
Bilirubin
Cytotoxins
Ferritins
Immunosuppressive Agents
Lactic Acid

Figure

• 

  Fig. 1 Peripheral blood smear shows moderate anisocytosis with mild fragment RBCs (arrows) at the time of admission (Wright Giemsa stain, ×1,000; scale bar, 100 µm).

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  Fig. 2 Hemophagocytosis in bone marrow aspiration smear (Wright Giemsa stain, ×1,000; scale bar, 100 µm).

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  Fig. 3 Changes of laboratory data following therapeutic plasma exchange and drug therapy. (A) Platelet count and hemoglobin levels remained at around the same level. (B) Ferritin and LDH levels increased in the early stage and decreased after administration of the immunosuppressant and cytotoxic medication. (C) Triglyceride and total bilirubin levels increased, despite TPE. Thick arrows below the x-axis indicate the days of therapeutic plasma exchange (TPE) procedures. Vertical dotted line in the graphs indicates the time of medication (immunosuppressant and cytotoxic agent).

Reference

1. Schwartz J, Padmanabhan A, Aqui N, Balogun RA, Connelly . Smith L, Delaney M, et al. Guidelines on the use of therapeutic apheresis in clinical practice–evidence-based approach from the Writing Committee of the American Society for Apheresis: the seventh special issue. J Clin Apher. 2016; 31:149–162.

2. Blombery P, Scully M. Management of thrombotic thrombocytopenic purpura: current perspectives. J Blood Med. 2014; 5:15–23.

3. Pereira A, Mazzara R, Monteagudo J, Sanz C, Puig L, Martinez A, et al. Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome: a multivariate analysis of factors predicting the response to plasma exchange. Ann Hematol. 1995; 70:319–323.

4. Kim DY. Hemophagocytic lymphohistiocytosis in adults – overview, diagnosis, and treatment. Korean J Med. 2015; 88:525–534.

5. Sheth K, Kuo CL, Modi D, Nanavaty S, Scola C. Mortality rate according to cause in patients with hemophagocytic lymphohistiocytosis: a meta-analysis. Ann Rheum Dis. 2016; 75:1248–1249.

6. Henter JI, Horne A, Aricó M, Egeler RM, Filipovich AH, Imashuku S, et al. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007; 48:124–131.

7. Bouffandeau B, Mofredj A, Blanc S. Hemophagocytic syndrome in the critically ill. Intensive Care Med. 2001; 27:948–949.

8. Janka G, Imashuku S, Elinder G, Schneider M, Henter JI. Infection- and malignancy-associated hemophagocytic syndromes. Secondary hemophagocytic lymphohistiocytosis. Hematol Oncol Clin North Am. 1998; 12:435–444.

9. Song KS, Sung HJ. Effect of plasma exchange on the circulating IL-6 levels in a patient with fatal hemophagocytic syndrome associated with bile ductopenia. Ther Apher Dial. 2006; 10:87–89.

10. Sullivan JL, Woda BA, Herrod HG, Koh G, Rivara FP, Mulder C. Epstein-Barr virus-associated hemophagocytic syndrome: virological and immunopathological studies. Blood. 1985; 65:1097–1104.

11. Imashuku S. Advances in the management of hemophagocytic lymphohistiocytosis. Int J Hematol. 2000; 72:1–11.

12. Bosnak M, Erdogan S, Aktekin EH, Bay A. Therapeutic plasma exchange in primary hemophagocytic lymphohistiocytosis: reports of two cases and a review of the literature. Transfus Apher Sci. 2016; 55:353–356.

13. Sanada S, Ookawara S, Shindo T, Morino K, Ishikawa H, Suzuki M. A case report of the effect of plasma exchange on reactive hemophagocytic syndrome associated with toxic shock syndrome. Ther Apher Dial. 2004; 8:503–506.

14. Kfoury Baz EM, Mikati AR, Kanj NA. Reactive hemophagocytic syndrome associated with thrombotic thrombocytopenic purpura during therapeutic plasma exchange. Ther Apher. 2002; 6:159–162.

15. Bae MN, Kwak DH, Park SJ, Choi BS, Park CW, Choi YJ, et al. Acute kidney injury induced by thrombotic microangiopathy in a patient with hemophagocytic lymphohistiocytosis. BMC Nephrol. 2016; 17:4.

16. Kapoor S, Morgan CK, Siddique MA, Guntupalli KK. Intensive care unit complications and outcomes of adult patients with hemophagocytic lymphohistiocytosis: a retrospective study of 16 cases. World J Crit Care Med. 2018; 7:73–83.