Severe anemia, severe leukopenia, and severe thrombocytopenia in patients treated with amphotericin B deoxycholate induction therapy for HIV-associated ankle mycosis: a subgroup analysis of a prospective multicenter cohort study BMC Infectious Diseases

During the study period, 414 patients were assessed for eligibility, of whom 170 were included (Fig. 1). After starting amphotericin B deoxycholate, 73 of 170 patients (42.9%) developed severe anemia, 35 of 170 patients (20.6%) developed severe leukopenia, and 18 of 170 patients developed severe leukopenia. (10.6%) developed severe thrombocytopenia.

Table 1 shows the baseline characteristics of the patients. Compared with patients without severe anemia, more patients with severe anemia had lower BMI, weight loss, lower hemoglobin levels, lower platelet levels, higher serum creatinine levels, and higher AST/ALT ratio, lower sodium levels, and lower sodium levels. The induction therapeutic dose of amphotericin B deoxycholate is >0.58 mg/kg/d (Tables 1 and 2). Compared with patients without severe thrombocytopenia, more patients who developed severe thrombocytopenia had lower baseline platelet levels (Table 3).

Multivariate logistic regression analysis showed that hemoglobin levels<100g/L（OR=5.846，95%CI：2.765～12.363），血清肌酐水平>73.4 μmol/L (OR = 2.573, 95% CI: 1.157 ~ 5.723), AST /ALT ratio > 1.6 (OR = 2.479, 95% CI: 1.167 ~ 5.266), sodium level ≤ 136 mmol/L (OR = 4.342, 95% CI: 1.747 ~ 10.789), and amphotericin B deoxycholate dose > 0.58 mg/kg/d (OR = 2.504, 95% CI: 1.066 ~ 5.882) are independent risk factors associated with the occurrence of severe anemia ( Table 4).

Patients coinfected with tuberculosis and those with low platelet levels were shown to be at higher risk of progression to severe leukopenia.p≤ 0.1). Combined tuberculosis infection (OR=3.307, 95%CI: 1.050～10.420) and platelet level (per 10×109/L) (OR=0.952, 95%CI: 0.911～0.996) were calculated as independent risk factors for severe leukopenia related to the occurrence (Table 4).

Men with platelet levels below 100 × 10⁹ /L was identified as a risk factor associated with progression to severe thrombocytopenia (p≤ 0.1). Platelet level < 100 × 10⁹ /L (OR = 2.935, 95% CI: 1.075 ~ 8.016) was identified as an independent risk factor associated with the development of severe thrombocytopenia (Table 4).

There were no differences in the development of severe anemia, severe leukopenia, and severe thrombocytopenia between survivors and nonsurvivors. There were also no differences at 2 weeks between patients who did not undergo fungal clearance and those who did (Table 5).

The starting dose of amphotericin B for 87 patients was 5 mg on the first day, 10 mg on the second day, 20 mg on the third day, and the therapeutic dose was reached on the fourth day. The starting dose of amphotericin B for 35 patients was 5 mg on the first day, 15 mg on the second day, 25 mg on the third day, and the therapeutic dose was reached on the fourth day. Twenty-seven patients were treated with amphotericin B at a starting dose of 10 mg on the first day, 20 mg on the second day, and a therapeutic dose on the third day. Compared with the 5 mg group on the first day, the 10 mg group (10 mg, 20 mg, daily) on the first day was calculated as an independent risk factor associated with the occurrence of severe anemia (OR = 2.621, 95% CI: 1.107) ~ 6,206) (Table 6).

The group receiving the starting dose of amphotericin B (10 mg, 20 mg daily) showed the highest fungal clearance rate of 96.3% (26/27), which was significantly better than the group receiving the starting dose of amphotericin B (5 mg, 10 mg) group. mg, 20 mg, daily) (60.9%) and the group receiving the starting amphotericin B dose (5 mg, 15 mg, 25 mg, daily) (62.9%). No significant differences were observed between the three groups in terms of progression to severe anemia, severe leukopenia, or severe thrombocytopenia at 2 weeks and survival at 2 and 48 weeks (Table 7).

Figure 2 shows a comparison of changes in hemoglobin levels over time between the group without severe anemia and the group that progressed to severe anemia. At baseline, weeks 1, and 2, the group that progressed to severe anemia had lower hemoglobin levels compared with the group without severe anemia (median hemoglobin level, 91.46 g/L (95% CI, 95.05–87.87 g/L) L), 106.39 g/L (95% CI, 103.25-109.53 g/L), p

< 0.001; 70.74 g/L (95% CI, 68.43–73.05 g/L) vs. 98.54 g/L (95% CI, 96.05–101.02 g/L), p< 0.001; 71.28 g/L (95% CI, 68.28–74.28 g/L) vs. 92.58 g/L (95% CI, 89.63–95.53 g/L), p< 0.001). Within 14 days, 11 patients had hemoglobin levels below 60 g/L. Six people changed amphotericin B deoxycholate to other antifungal drugs within 14 days, with the median day being day 10 (95% CI: 7.42-12.57 days), but the reason for switching was not severe anemia or severe leukemia. Decreased and severe thrombocytopenia. At week 4, the median hemoglobin level in the group that progressed to severe anemia was 87.12 g/L (95% CI, 81.70-92.55 g/L).