Dear Editor,

Platelet satellitism (PS) is a rare cause of pseudothrombocytopenia due to the adhesion of platelets to the surfaces of circulating leukocytes. PS occurs when circulating auto-antibodies bind to cryptic antigens exposed because of the calcium-chelating activity of EDTA [1]. The antibody–platelet antigen (antiglycoprotein IIb/IIIa) binds to the Fcγ receptor (CD16) on the cell surface, resulting in the typical PS results in blood smear images [2]. PS can be associated with platelet phagocytosis by neutrophils or, less frequently, monocytes [3]. PS accounts for less than 1% of total pseudothrombocytopenia cases. The reported yearly incidence of 1:12,000 may be underestimated as PS does not cause remarkable scattergram abnormalities in most cases and is usually detected using light microscopy [2]. We report a case of PS around neutrophils, monocytes, and lymphocytes, associated with platelet phagocytosis. The requirement for informed consent was waived by the Institutional Ethics Committees because of the retrospective nature of this study based on a case that occurred in 2017.

A 42-year-old asymptomatic woman presented at Livorno hospital as an outpatient with thrombocytopenia (50×10⁹/L; reference range [RR], 150–400). The Hb concentration was 132 g/L (RR, 114–150), and the leukocyte count was 4.99×10⁹/L (RR, 4.0–11.0). A differential leukocyte count showed (×10⁹/L): neutrophils, 0.9 (RR, 1.8–6.7); lymphocytes, 2.6 (RR, 1.1–3.7); monocytes, 1. 2 (RR, 0.8–1.0); eosinophils, 0.22 (RR, 0.05–0.65); and basophils, 0.07 (RR, 0.00–0.10).

A blood smear review revealed that 100% of neutrophils, 27% of monocytes, and 7% of lymphocytes had from one to more than 20 platelets adhering to the cell surface (Fig. 1A–D, E–J, and K, L, respectively). Approximately 61% of lymphocytes were large granular lymphocytes, 6% of which were PS-positive (Fig. 1L), and a few small lymphocytes exhibited unique platelet adhesion (Fig. 1K). This is the only case described to date in which PS affected four different cell types. Platelet phagocytosis was detected in 20% of neutrophils and 6% of monocytes with PS. Moreover, aspects of pre-phagocytosis and post-phagocytosis (i.e., platelets housed in a pocket on the cell surface and empty vacuoles) were frequently observed.

Figure 1. Platelet satellitism and phagocytosis. ×1,000 magnification. Satellitism seen around neutrophils (A-D), monocytes (E-J), lymphocytes (K), and large granular lymphocytes (L). Damaged neutrophils (C, D) show significantly more sticky platelets than intact ones. Platelet phagocytosis is seen for neutrophils (B, D) and monocytes with pre- and post-phagocytic aspects (F-H and I, J, respectively).

Neutrophils with cytoplasmatic breaks due to damage caused during peripheral blood smear preparation showed significantly more adherent platelets than undamaged cells (Fig. 1C, D). The exposure of a higher number of Fcγ receptors due to cell membrane lesions may explain the polarization of platelets. As a sodium citrate tube for coagulation testing was available, we were able to repeat the cell count and microscopic review, which revealed a platelet count close to the reference value (147×10⁹/L) and the absence of satellitism. Thus, satellitism-related EDTA-dependent PTCP was diagnosed.

After the first reports of platelet adherence to polymorphonucleated cells, the majority of reports mainly described neutrophils. The only case of PS around basophils was described by Liso, et al. [4] in 1981. Fábryová, et al. [5] and Lazo-Langner, et al. [6] each described two cases involving eosinophils. Ravel and Bassart [3], Cesca, et al. [7], and Español, et al. [8] reported satellitism to monocytes, lymphocytes, and large granular lymphocytes, respectively. Table 1 summarizes the reported cases of PS involving monocytes or lymphocytes and those involving two or three different cell types simultaneously. Numerous cases also involved platelet phagocytosis, mainly by neutrophils (case 4, 8, 10, 13, 20, 21, 28), monocytes (case 25), or both neutrophils and monocytes (case 1, 2, 12, 16, 27). In cases diagnosed as having lymphoma or a lymphoproliferative disorder, the cells involved in PS were atypical lymphocytes (case 11, 15, 17, 19, 22, 24, 26), large granular lymphocytes (case 9), or normal lymphocytes (case 18, 23).

Table 1 . Reported cases of PS and satellitism/phagocytosis association during 1974–2020. Isolated neutrophilic satellitism has not been reported

Case No.	Satellitism	Phagocytosis	Reported clinical conditions/diagnosis/disease	*Reported cases: First author, Journal, Year [ref in the text]
1	NE, MO	NE, MO	ND	Ravel, Lab Med, 1974 [3]
2	NE, MO	NE, MO	Pneumonia	Greipp, Blood, 1976
3	MO	NO	Hypo gamma globulin	Djaldetti, Scan J Haematol, 1978
4	NE	NE	Malignant lymphoma	White, Am J Hematol, 1978
5–7	MO	NO	PV, MPD, CLL	Cohen, Acta Haemat, 1980
8	NE	NE	Pelvic inflammation	Yoo, Acta Haemat, 1982
9	NE/LGL	NO	ND	Español, Haematologica, 2000 [8]
10	NE	NE	NH	Lee, Arch Pathol LabMed, 2000
11	AtyLY	NO	MC	Cesca, Haemapathol, 2001 [7]
12	NE, MO	NE, MO	ND	Criswell, Am J Clin Pathol, 2001 [9]
13	NE	NE	ND	Senzel, Blood 2013
14	NE, EO, MO	NO	Vasculitis	Lazo-Langner, Am J Hematol, 2002 [6]
15	AtyLY	NO	MZ	Latger-Cannard, Eur J Haematol, 2009
16	NE	NE, MO	ND	Campbell, Am J Hematol, 2009
17	AtyLY	NO	MZ	Montague, Ann Diagn Pathol, 2013
18	LY	NO	ND	Tun, Indian J Hematol Blood Transfus, 2013
19	AtyLY	NO	NH	Quiròs, Rev Lab Clin, 2013
20	NE	NE	ND	Yoon, Lab Med Online, 2013
21	NE	NE	Tongue malignancy	Paul, Indian J Hematol Blood Transfus, 2013
22	AtyLY	NO	MZ	Degaud, IJLH, 2018
23	LY	NO	ND	Lopez-Molina, IJLH, 2018 [109]
24	AtyLY	NO	B-LPD	Zhu, Blood, 2018
25	MO	MO	H	Bain, Am J Hematol, 2018
26	AtyLY	NO	NH	Gatignol, Ann Biol Clin, 2019
27	NE, MO	NE, MO	Infection	Amoureaux, Morphologie, 2020
28	NE	NE	Pancreatic carcinoma	Sousa, Platelets, 2020

*Reported cases of platelet satellitism/phagocytosis (all cell types) and satellitism around monocytes, lymphocytes and large granular lymphocytes (by year of publication from 1976 to 2020; PubMed, August 31, 2021; keywords used: “pseudo thrombocytopenia,” “platelet satellitism,” “platelet phagocytosis”).

Abbreviations: PS, platelet satellitism; NE, neutrophils; EO, eosinophils; MO, monocytes; LY, lymphocytes; AtyLY, atypical lymphocytes; LGL, large granular lymphocytes; PV, polycythemia vera; MPD, myeloproliferative disorder; CLL, chronic lymphocytic leukemia; NO, absence of phagocytosis; ND, not defined; NH, non-Hodgkin lymphoma; MC, mantle cell lymphoma; MZ, marginal zone lymphoma; B-LPD, B-lymphoproliferative disease; H, Hodgkin lymphoma.

Criswell, et al. [9] reported that in the case of PS, the “greatest clinical relevance is spurious reporting that can lead to unnecessary treatment of thrombocytopenia”; however, the involvement of atypical lymphocytes in most cases of lymphoid neoplasms should be considered a potential non-casual association. Therefore, the recommendation to check platelet counts while simultaneously evaluating for a possible lymphoproliferative disorder is entirely acceptable in cases of PS involving lymphocytes [10].

We thank Dr. Miriam Conte for English language revision of the manuscript.

All three authors contributed to the conception and design of the study. Fiorini F and Fiorini M were involved in clinical evaluation and interpreted the results. La Gioia A supervised the study. All authors read and approved the final manuscript.

The authors declare that they have no conflicts of interest.

None declared.