Blood Res 2017; 52(3):
Published online September 25, 2017
https://doi.org/10.5045/br.2017.52.3.231
© The Korean Society of Hematology
1Department of Laboratory Medicine, JCHO Hokkaido Hospital, Sapporo, Japan.
2Department of Internal Medicine, JCHO Hokkaido Hospital, Sapporo, Japan.
3Hokkaido University, Health Care Center, Sapporo, Japan.
Correspondence to : Masashi Ohe. Department of Internal Medicine, JCHO Hokkaido Hospital, Nakanoshima 1 Jo, 8-chome 3-18, Sapporo 062-8618, Japan. masshi@isis.ocn.ne.jp
PGPS is a rare EDTA-dependent phenomenon that causes platelets to degranulate in vitro, resulting in a gray appearance on the blood film, similar to that observed in a case of gray pseudo-syndrome (GPS). However, unlike GPS, this phenomenon occurs only when the blood is collected with EDTA as an anticoagulant and not when it is collected with sodium citrate or heparin as the anticoagulant. Typical electron microscopy of PGPS reveals the degranulation of EDTA-exposed platelets. Although we did not perform electron microscopy, we measured serotonin levels and confirmed the degranulation of δ-granules. The pathophysiology of degranulation appears to result from a humoral factor (presumably an antibody) that induces the release of α- and δ-granule contents without platelet aggregation [1]. Crossover studies using the EDTA-anticoagulated plasma of a patient with PGPS mixed with normal patients' platelets demonstrated the degranulation of normal patients' platelets, just as the PGPS platelets degranulate in EDTA. Therefore, it is speculated that some factor in the plasma of the patient with PGPS is responsible for the degranulation. This factor is possibly an antibody against a hidden site in the platelet that is exposed after the reaction with EDTA [2,3]. The present case is particularly unusual in that platelet aggregation was present in addition to PGPS; these findings have been previously reported [1,4,5]. Mant et al. [5] reported on cases of EDTA-induced platelet degranulation with aggregation caused by a plasma factor, which was not IgG, IgM, fibrinogen, or albumin; they considered that it was an undefined abnormal plasma component that, on exposure to EDTA, develops antiplatelet activity.
In the present case, although the normal platelets of a healthy control subject were mixed with the patient's plasma, neither degranulation nor aggregation was found. Moreover, PGPS completely ameliorated approximately 2 months after discharge, when AOSD was controlled with a combination of PSL and TAC. Based on these results, we speculate that hyper-inflammation-associated platelet dysfunction and plasma factor may cause degranulation and aggregation. However, the obvious mechanism by which platelet degranulation and aggregation occur remains unclear.
Blood Res 2017; 52(3): 231-233
Published online September 25, 2017 https://doi.org/10.5045/br.2017.52.3.231
Copyright © The Korean Society of Hematology.
Sumiyo Miyakawa1, Masashi Ohe2*, Haruki Shida2, Tetsuya Horita2, Ken Furuya2, and Satoshi Hashino3
1Department of Laboratory Medicine, JCHO Hokkaido Hospital, Sapporo, Japan.
2Department of Internal Medicine, JCHO Hokkaido Hospital, Sapporo, Japan.
3Hokkaido University, Health Care Center, Sapporo, Japan.
Correspondence to:Masashi Ohe. Department of Internal Medicine, JCHO Hokkaido Hospital, Nakanoshima 1 Jo, 8-chome 3-18, Sapporo 062-8618, Japan. masshi@isis.ocn.ne.jp
PGPS is a rare EDTA-dependent phenomenon that causes platelets to degranulate in vitro, resulting in a gray appearance on the blood film, similar to that observed in a case of gray pseudo-syndrome (GPS). However, unlike GPS, this phenomenon occurs only when the blood is collected with EDTA as an anticoagulant and not when it is collected with sodium citrate or heparin as the anticoagulant. Typical electron microscopy of PGPS reveals the degranulation of EDTA-exposed platelets. Although we did not perform electron microscopy, we measured serotonin levels and confirmed the degranulation of δ-granules. The pathophysiology of degranulation appears to result from a humoral factor (presumably an antibody) that induces the release of α- and δ-granule contents without platelet aggregation [1]. Crossover studies using the EDTA-anticoagulated plasma of a patient with PGPS mixed with normal patients' platelets demonstrated the degranulation of normal patients' platelets, just as the PGPS platelets degranulate in EDTA. Therefore, it is speculated that some factor in the plasma of the patient with PGPS is responsible for the degranulation. This factor is possibly an antibody against a hidden site in the platelet that is exposed after the reaction with EDTA [2,3]. The present case is particularly unusual in that platelet aggregation was present in addition to PGPS; these findings have been previously reported [1,4,5]. Mant et al. [5] reported on cases of EDTA-induced platelet degranulation with aggregation caused by a plasma factor, which was not IgG, IgM, fibrinogen, or albumin; they considered that it was an undefined abnormal plasma component that, on exposure to EDTA, develops antiplatelet activity.
In the present case, although the normal platelets of a healthy control subject were mixed with the patient's plasma, neither degranulation nor aggregation was found. Moreover, PGPS completely ameliorated approximately 2 months after discharge, when AOSD was controlled with a combination of PSL and TAC. Based on these results, we speculate that hyper-inflammation-associated platelet dysfunction and plasma factor may cause degranulation and aggregation. However, the obvious mechanism by which platelet degranulation and aggregation occur remains unclear.