HPS

1. HEMOPHAGOCYTIC SYNDROME
Dr. Sandip Dukare

2. INTRODUCTION
• Hemophagocytic syndrome is a rare disorder of the
mononuclear phagocytic system.
• It is characterized by benign proliferation of
mature histiocytes and uncontrolled phagocytosis of
the platelet, erythrocytes, lymphocytes and their
hematopoietic precursors in the bone marrow.
• It is associated with various infections,autoimmune
ds, malignancies and immunocompromised states.
• Cytopenias result in systemic manifestations.
• Prognosis is grave and mortality ranges upto 50%
in absence of treatment.

3. CASE REPORT 1: HPS associated with
Plasmodium falciparum infection
• 11-month-old child presented with 20-day
H/O- high fever and abdominal distention.
• G/E-lethargic, febrile.
• P/E-pallor, hepatosplenomegaly.
• Lab investigationsanemia,thrombocytopenia,
leucopenia,deranged liver enzymes.
• P/S-microcytic, hypochromic picture with
no e/o any haemoparasite.

4. •
•
•
•
•
Serum ferritin -2193 μg/L.
Platelet count- 90 X109/mm3.
Serum triglycerides- 3.2 mmol/L.
Serum fibrinogen-(0.75 g/L).
BMA- normal cellularity with mature
monohistiocytes containing phagocytosed RBCs.
• BMS- Plasmodium falciparum gametocytes were
identified.
• Treatment with i.v. Artesunate,the patient
became afebrile & recovered gradually.

5. Hemophagocyte in bone marrow smear; (Leishman, ×100)

6. Gametocyte of Plasmodium falciparum in bone
marrow smear; (Leishman, ×100)

7. CASE REPORT 2: HPS - A cause for fatal
outcome in tuberculosis.
• A 17-year-old male presented with
fever,abdominal distention since 15 days.
• G/E-gross pallor,generalized lymphadenopathy.
• USG A/P-free fluid in
abdomen,hepatosplenomegaly and extensive intraabdominal lymphadenopathy.
• CXR- B/L pleural effusion.
• Lab investigations• Anemia,leucopenia thrombocytopenia.
• Peripheral smear—microcytic,moderately
hypochromic anemia.

8. •
•
•
•
•
Serum LDH- (540 U/L).
Serum triglycerides- (280 mg/Dl).
Serum ferritin- (960 mcg/L),
CRP-positive.
Cervical lymph node biopsy-dilated sinuses
containing macrophages with abundant cytoplasm
stuffed with red blood cells.
• BMA-hypocellularity, focal necrotic areas. The M/E
ratio was normal. Myloid and erythroid series
maturation was normal.

9. • BMS- few lymphocytes, reactive plasma cells and
large histiocytes containing engulfed red blood
cells, nuclear debris and platelets.
• Cervical lymph node aspiration cytology- necrotic
material and acid fast bacilli on ZN staining.
• The patient was started on antitubercular therapy
& dexamethasone.
• Significant response was noted and patient
recovered gradually.

10. Histopathology of cervical lymph node. H and E (×400)Sinus histi ocytosis with prominant hemophagocytosis

11. Leishman Stain highlighting hemophagocytic macrophage

12. Bone marrow aspirate (×1000) . Leishman stained smear
showing hemophagocytic macrophages

13. DISCUSSION
• Hemophagocytic syndrome/hemophagocytic
lymphohistiocytosis(HLH)
• It is a rare ds.
• Characterized by benign proliferation of the mature
histiocyte.
• There is uncontrolled phagocytosis of the platelet,
erythrocytes, lymphocytes and their hematopoietic
precursors in the BM giving rise to cytopenias.

14. ETIOLOGY
PRIMARY
(Familial)
INFECTION
IMMUNODEFICIENCY
SECONDARY
(Acquired)
AUTOIMMUNE
METABOLIC
DS.
MALIGNANCY

15. PATHOPHYSIOLOGY
TRIGGERING FACTOR
(MC INFECTION)
INAPPROPRIATE ACTIVATION &
UNCONTROLLED PROLIFERATION
OF THE MACROPHAGES
Th 1 STIMULATED
HYPERCYTOKINEMIA
TRIGGERING OF THE
CYTOKINE CASCADE
FREE OXYGEN RADICAL
RELEASE
ACTIVATED MACROPHAGES
PHAGOCYTOSE RBCS,WBCS,PLATELETS

16. CLINICAL FEATURES
• Onset- abrupt
• Many present with fever of unknown origin.
• Systemic manifestations-pallor,fever,rash,
lymphadenopathy,hepatosplenomegaly,neurological
manifestations.
• It takes a fulminant course and has a fatal outcome.

17. Histiocytic Society Protocol Criteria
1. Fever(>7days)
2. Splenomegaly
3. Cytopenias(>2 lineages)
-Anemia(hb<9.0 g/dl)
-Neutropenia(<1000)
-Thrombocytopenia(<1lk
cells)
4. Hypertriglyceridemia &
Hypofibrinigenemia
5. Haemophagocytosis(bone,
spleen,bone marrow)
6. Natural killer cell
activity(low/absent)
7. Hyperferritinemia(>500
mcg/l)
8. Increased soluble CD
25(>2400 u/ml)

18. Differential Diagnosis
1.
2.
3.
4.
Griscelli syndrome.
X linked lymphoproliferative syndrome.
Autoimmune lymphoproliferative syndromes.
Macrophage activation syndromes.

19. REFERENCES
1. Imashuku S. Differential diagnosis of hemophagocytic
syndrome:Underlying disorders and selection of the most
effective treatment.Int J Hematol 1997;66:135-51.
2. Saribeyoglu ET, Anak S, Agaoglu L, Unuvar A. Secondary
hemophagocyticlymphohistiocytosis induced by malaria
infection in a child with langerhans cell histiocytosis. Pediatr
Hematol Oncol 2004;21:267-72.
3. Ohno T, Shirasaka A, Sugiyama T, Furukawa H.
Hemophagocytic syndrome induced by plasmodium
falciparum malaria infection. Int J Hematol 1996;64:263-6.
4. Aouba A, Noguera ME, Clauvel JP, Quint L.
Hemophagocyticsyndrome associated with plasmodium vivax
infection. Br J Haematol 2000;103:832-3.

20. THANK YOU!....