Hemophagocytic histiocytosis: etiology, intensity and effect on hematological parameters

Abstract

Phagocytsis of mature and developing blood cells by histiocytes is known as hemophagocytosis (HP). Though an uncommon condition, histiocytic hyperplasia with HP is seen in a wide variety of hematological and non hematological conditions, mainly as a reactive phenomenon. The present study was designed to determine the etiology of hemophagocytosis, its intensity (extent of disease) in the bone marrow and its effect on hematological parameters. The study was conducted in the Department of Pathology, Pakistan Institute of Medical Sciences (PIMS), Islamabad. The period of study spanned from March 2003 to March 2005. Variable degrees of HP (mild, moderate, severe) were observed in the bone marrow smears of 250 patients having different underlying disorders. Hemophagocytic syndrome (HPS) with clinical and biochemical derangement, was observed in 24 (9.4%) patients. HPS was mostly associated with infection. The etiological distribution of patients in different groups of disorders was: non malignant hematological conditions (NMHC) (56.80%), infections (24.80%), storage disorders (4.40%), malignant hematological condition (4.40%), autoimmune disorder (1.20%) and miscellaneous group (8.40%). The distribution of patients in different grades of intensity was: grade I (mild) (35 .50%), grade II (moderate) (45.40%), grade III (severe) (19.60%). All of these patients had reactive (benign) hemophagocytosis. We had no patient with primary histiocytic malignancy or malignant histiocytosis. NMHC was the largest group showing HP. Megaloblastic anemia ranked on the top in this category with peripheral cytopenia and increased degree of HP. Infection associated HP was the second largest group mainly with moderate and severe degree ofHP. Eighteen patients had HPS. There was apparently no effect of age on either intensity of HP or Qr. ~l~od counts in .-,":'''~: ';; '~ . our study. With the increase in the intensity of HP there wa ''''e dy decline 'n the blood cell counts. As a result of increased intensity of HP in g ~ III, t1'!~t,proup ~~an • ..~.'."-"i':"::..') ; ....... :; I i ii _, Hb (6.37gmJdl) and platelet count (81.SSx103/L) were low compared to other groups. The mean Hb of grade II was significantly decreased compared to the mean of grade I (P<.Ol), the mean Hb of grade III was significantly decreased compared to grade I (P <.001), and grade II (P<.Ol). In the case of total leukocyte count, the mean of grade II was significantly decreased compared to grade I (P< .OS). The mean TLC of grade III was significantly decreased compared to grade I (P< .01), while the difference of the means was not significant between grades II and III (P> .OS). The mean platelet count of grade II was significantly decreased compared to grade I (P<.Ol). The mean platelet count of grade III was significantly reduced compared to grade I (P<.OOl) and grade II (P<.OOl). The present study thus reveals that the main statistically significant effect of increasing intensity of HP was on Hb and platelet count. The cellularity of bone marrow apparently had no effect on the intensity of HP, since most of our patients either had increased cellularity (1S2; 60.80%) or normal cellularity (S3 ; 21.20%) as compared to decreased cellularity, (4S; 18%). Pathogenesis of peripheral cytopenia in patients of HP appears to be multifactorial and depends upon the underlying disease process, immunosuppression, immune destruction of cells, drug therapy and above all the exaggerated HP with or without hemophagocytic syndrome, associated with hypercytokinemia particularly Interferongamma and TNF -alpha. Additional investigations are required to elaborate the role of the microenvironment in the pathogenesis and intensity of HP and its effect on blood cell counts.