Table 1 Characteristics of the studies included in the meta-analysis

Choi 2019 [9]

Retrospective longitudinal study

Korea

2005-2016

Mean:

63.4 ± 15.8

thrombocytopenia (45)

non-thrombocytopenia

(50)

thrombocytopenia (32)

non-thrombocytopenia (137)

Mean: 58.4 ± 11.0

thrombocytopenia:

platelet count < 100 × 10³ /mm³

CLcr < 30 mL/min

L. Crass 2019 [10]

Retrospective study

America

2007-2018

Mean:

54

thrombocytopenia (57)

non-thrombocytopenia (76)

thrombocytopenia (35)

non-thrombocytopenia (173)

Mean: 88

thrombocytopenia:

platelet count < 112.5 × 10³ cells/μL

eGFR < 60 mL/min/1.73 m²

Dong 2014 [23]

Retrospective monocenter observational study

China

2008-2013

Mean:

58.6 ± 19.9

thrombocytopenia (8)

non-thrombocytopenia (5)

thrombocytopenia (23)

non-thrombocytopenia (34)

Mean: 64.5 ± 12.5

thrombocytopenia:

decrease in platelet count of ≥25% and a final count of < 100 × 10⁹ /L

CLcr < 30 mL/min

Fujii 2014 [24]

Retrospective study

Japan

2011

Median:

64.0 ± 17.4 (21–86)

thrombocytopenia (6)

non-thrombocytopenia (10)

thrombocytopenia (31)

non-thrombocytopenia (44)

Median: 56.6 ± 10.0 (37.0–84.5)

thrombocytopenia:

≥ 30% decrease in platelet count from the baseline value

eGFR < 30 ml/min/1.73 m²

Giunio-Zorkin 2019 [11]

Retrospective observational cohort study

Canada

2013-2017

Mean:

58 ± 17 (Thrombocytopenia patients)

49 ± 22 (Non-thrombocytopenia patients)

thrombocytopenia (11)

non-thrombocytopenia (27)

thrombocytopenia (7)

non-thrombocytopenia (57)

Mean: 69 ± 16 (Thrombocytopenia patients)

65 ± 21 (Non-thrombocytopenia patients)

thrombocytopenia:

platelet count

<  100 × 10⁹ /L or ≥ 50% reduction from baseline

serum creatinine > 90 μmol/L for females;

>  100 μmol/L for males

Hiraki 2012 [25]

Prospective study

Japan

―

Mean:

64.6 ± 10.9

thrombocytopenia (3)

non-thrombocytopenia (0)

thrombocytopenia (2)

non-thrombocytopenia

(3)

Mean:54.9 ± 10.7

thrombocytopenia:

a decrease in the PLT count of ≥50%

CLcr < 60 ml/min

Hirano 2014 [26]

Retrospective study

Japan

2010-2012

Mean:

69.0 ± 11.5 (Thrombocytopenia patients)

62.4 ± 17.2 (Non-thrombocytopenia patients)

Thrombocytopenia (7)

non-thrombocytopenia (3)

thrombocytopenia (22)

non-thrombocytopenia (43)

Mean: 57.5 ± 11.9 (Thrombocytopenia patients)

55.2 ± 11.5 (Non-thrombocytopenia patients)

thrombocytopenia:

a decrease in the patient’s platelet count to < 10 × 10⁴ /μL or a reduction of ≥30% from their baseline value

CLcr < 30 mL/min

Han 2022 [34]

Retrospective study

China

2015-2021

Mean: 69.67 ± 16.39

Thrombocytopenia (39)

non-thrombocytopenia (88)

Thrombocytopenia (34)

non-thrombocytopenia (159)

―

thrombocytopenia:

platelet count of < 100 × 10⁹ /L

CLcr < 60 mL/min

Hsu 2022 [35]

Retrospective cohort study

Taiwan

2019

Mean:

71.0 ± 16.1 (Thrombocytopenia patients)

66.7 ± 15.2 (Non-thrombocytopenia patients)

Thrombocytopenia (21)

non-thrombocytopenia (23)

Thrombocytopenia (31)

non-thrombocytopenia (23)

―

thrombocytopenia:

platelet count of < 100 × 10⁹ /L or a decrease of in 25% or more from the baseline

CLcr < 60 mL/min

Jones 2015 [27]

Retrospective single-center cohort study

America

2007-2012

Median:

6 (1–13) (Thrombocytopenia patients)

9 (3.1–14.7) (Non-thrombocytopenia patients)

thrombocytopenia (21)

non-thrombocytopenia (16)

thrombocytopenia (27)

non-thrombocytopenia (98)

Median: 23.8 (7.4–44.7) (Thrombocytopenia patients)

27.3 (13.8–47.3) (Non-thrombocytopenia patients)

thrombocytopenia:

platelet count of

<  100,000 platelets/mm³ or a reduction of ≥30% from the baseline platelet count

CLcr < 60 ml/min/1.73 m²

Kim 2019 [12]

Retrospective study

Korea

2005-2015

Mean:

70.6 ± 13.3 (Thrombocytopenia patients)

69.1 ± 10.5 (Non-thrombocytopenia patients)

Thrombocytopenia (13)

non-thrombocytopenia (9)

thrombocytopenia (16)

non-thrombocytopenia (22)

Mean: 55.2 ± 9.5 (Thrombocytopenia patients)

57.3 ± 10.6 (Non-thrombocytopenia patients)

thrombocytopenia:

platelet count of < 150 × 10⁹ /L or a decrease of at least 50% from the baseline

Chronic kidney disease

Kawasuji 2021 [36]

Monocentric, retrospective, observational study

Japan

2013-2019

Median:

71 (58.5–78)

thrombocytopenia (22)

non-thrombocytopenia (13)

thrombocytopenia (26)

non-thrombocytopenia (57)

Median:

57.1 (48.0–64.2)

thrombocytopenia:

platelet count of

<  112.5 × 10³/μL

or a decrease of in 25% or more from the baseline

CL_CRC-G ≤ 60 mL/min

Komatsu 2022 [37]

Prospective interventional study

Japan

2017-2020

Median:

68(61-75) (Patients within therapeutic range)

70(63-74) (Patients above therapeutic range)

thrombocytopenia (3)

non-thrombocytopenia (4)

thrombocytopenia (10)

non-thrombocytopenia (20)

Median:

54.0(45.7-64.6) (Patients within therapeutic range)

67.4(57.8-75.9) (Patients above therapeutic range)

thrombocytopenia:

decrease of in 30% or more from the baseline

CLcr < 50 mL/min

Lima 2020 [13]

Retrospective cohort study

Brazil

2015-2017

Median:

67 (34–101) (Thrombocytopenia patients)

61 (18–90) (Non-thrombocytopenia patients)

thrombocytopenia (6)

non-thrombocytopenia (16)

thrombocytopenia (4)

non-thrombocytopenia (34)

Median: 65.5 (51.1–81) (Thrombocytopenia patients)

68 (34–160) (Non-thrombocytopenia patients)

thrombocytopenia:

decrease in platelet count of ≥20% from the baseline level and a final count of < 100 × 10³ /mm³

CLcr < 30 mL/min

Lin 2006 [28]

Retrospective case-control study

Taiwan

2002-2004

Mean:

53.6 ± 19.4 (renal insufficiency patients)

58.2 ± 21.0 (non-renal insufficiency patients)

anemia (6)

non-anemia (11)

thrombocytopenia (11)

non-thrombocytopenia (6)

pancytopenia (0)

non-pancytopenia (17)

anemia (17)

non-anemia (28)

thrombocytopenia (16)

non-thrombocytopenia (29)

pancytopenia (4)

non-pancytopenia (41)

―

anaemia:

haemoglobin < 10 mg/dL

thrombocytopenia:

platelet count < 100 × 10⁹ platelets/L

pancytopenia:

ANC < 500 × 10⁶ /L

serum creatinine ≥1.3 mg/dL for women

and ≥ 1.5 mg/dL for men

Moraza 2015 [29]

Retrospective observational study

Spain

―

Median:

73 (23-91)

hematological toxicity (2)

non-hematological toxicity (1)

hematological toxicity (14)

non- hematological toxicity (21)

Median:

68.5(41.3-103)

hepatotoxicity:

HR ≥ 25%

PR ≥ 25%

and/or NR ≥ 50%

HR: rate of reduction in the level of hemoglobin; PR: rate of reduction in platelet count; NR: rate of reduction in neutrophil count.

CLcr < 30 ml/min

Maray 2022 [38]

Retrospective study

spain

2001-2012

Median:

61.36 (51.39–71.73)

thrombocytopenia (14)

non-thrombocytopenia (24)

thrombocytopenia (49)

non-thrombocytopenia (233)

Median:

86.20 (70.00–103.60)

thrombocytopenia:

decrease of at least 50% from the baseline platelet count

Acute Kidney Injury (AKIN) II or greater

Plachouras 2006 [30]

Retrospective study

Greece

2004-2005

Mean:

61.4 ± 13.5

myelosuppression (4)

non-myelosuppression (2)

Myelosuppression (7)

non-myelosuppression (12)

―

myelosuppression:

hematocrit decreased to 30% or the platelet count decreased to < 140 × 10⁹ platelets/L

Chronic renal failure

Qin 2021 [39]

Retrospective study

China

2014-2020

Median:

63.0 (45.3 ~ 71.3) (Anemia patients)

55.0 (37.0 ~ 66.0) (Non-anemia patients)

anemia (11)

non-anemia (45)

anemia (21)

non-anemia (221)

Median:

60.0 (55.0-66.0) (Anemia patients)

62.8 (55.0-71.3) (Non-anemia patients)

anemia:

Hb count to 75% of the baseline value

eGFR < 60 ml/(min·1.73m²)

Rabon 2018 [31]

Retrospective study

America

2014-2016

Median:

59 (43-66) (Thrombocytopenia patients)

53 (36-64) (non-thrombocytopenia patients)

thrombocytopenia (21)

non-thrombocytopenia (22)

thrombocytopenia (36)

non-thrombocytopenia (80)

Median: 78 (62-92) (Thrombocytopenia patients)

83 (67-98) (non-thrombocytopenia patients)

thrombocytopenia:

platelet count < 150 × 10⁹ /L or platelet count < 75% of 112.5 × 10⁹ /L or a reduction of ≥50% from baseline platelet count

eGFR < 30 mL/min/1.73 m²

Sato 2020 [40]

Retrospective cohort study

Japan

2011-2014

Mean: 57.4 ± 23.3

thrombocytopenia (3)

non-thrombocytopenia (5)

thrombocytopenia (14)

non-thrombocytopenia (15)

Mean: 55.1 ± 20.8 (Thrombocytopenia patients)

53.4 ± 24.5 (non-thrombocytopenia patients)

thrombocytopenia:

platelet count of < 100 × 10⁹ /L or at least a decrease of in 50% more from the baseline

Chronic kidney disease

Takahashi 2011 [32]

Retrospective study

Japan

2007-2009

Mean:

60.7 ± 19.9 (Thrombocytopenia patients)

56.3 ± 20.2 (non-thrombocytopenia patients)

thrombocytopenia (74)

non-thrombocytopenia (77)

thrombocytopenia (54)

non-thrombocytopenia (126)

Mean: 54.1 ± 13.6 (Thrombocytopenia patients)

55.0 ± 14.1 (non-thrombocytopenia patients)

thrombocytopenia:

≥ 10 × 10⁴ cells/mm³ decrease from the baseline or ≥ 30% reduction from the baseline

CLcr < 50 mL/min

Thirot 2021 [41]

Retrospective study

Belgian

2016

Median: 65 (21–95)

thrombocytopenia (30)

non-thrombocytopenia (84)

thrombocytopenia (13)

non-thrombocytopenia (101)

Median: 76 (34–178)

thrombocytopenia:

platelet count of < 150 × 10⁹ /L and ≥ 30% reduction from the baseline

CLcr < 60 mL/min

Wu 2006 [33]

Retrospective case-control study

Taiwan

2002-2004

Mean:

72.1 ± 10.8 (renal insufficiency patients)

56.8 ± 20.4 (non-renal insufficiency patients)

anemia (20)

non-anemia (8)

thrombocytopenia (22)

non-thrombocytopenia (6)

pancytopenia (6)

non-pancytopenia (22)

anemia (23)

non-anemia (40)

thrombocytopenia (27)

non-thrombocytopenia (36)

pancytopenia (4)

non-pancytopenia (59)

―

thrombocytopenia:

platelet count < 100 × 10⁹ platelets/L

anemia:

hemoglobin level < 10 mg/dL

pancytopenia:

ANC < 500 × 10⁶ neutrophils/L

patients with end-stage renal disease (ESRD)

Wu 2022 [42]

Retrospective study

Taiwan

2018-2019

Median: 62 [16–99]

anemia (10)

non-anemia (32)

thrombocytopenia (24)

non-thrombocytopenia (18)

anemia (5)

non-anemia (35)

thrombocytopenia (18)

non-thrombocytopenia (22)

Median: 64 [40–110]

thrombocytopenia: PLT < 125 × 10⁹ cells/L and a decrease ≥25% of PLT from baseline levels

anemia: a reduction of ≥25% of Hb compared with the baseline.

CLcr < 60 mL/min