Incidence, prevalence, and clinical significance of abnormal hematologic indices in compensated cirrhosis

Abstract

Background & aims: Patients with cirrhosis develop abnormal hematologic indices (HI) from multiple factors, including hypersplenism. We aimed to analyze the sequence of events and determine whether abnormal HI has prognostic significance.

Methods: We analyzed a database of 213 subjects with compensated cirrhosis without esophageal varices. Subjects were followed for approximately 9 years until the development of varices or variceal bleeding or completion of the study; 84 subjects developed varices. Abnormal HI was defined as anemia at baseline (hemoglobin, < or =13.5 g/dL for men and 11.5 g/dL for women), leukopenia (white blood cell counts, < or =4000/mm3), or thrombocytopenia (platelet counts, < or =150,000/mm3). The primary end points were death or transplant surgery.

Results: Most subjects had thrombocytopenia at baseline. Kaplan-Meier analysis showed that leukopenia occurred by 30 months (95% confidence interval, 18.5-53.6), and anemia occurred by 39.6 months (95% confidence interval, 24.1-49.9). Baseline thrombocytopenia (P = .0191) and leukopenia (P = .0383) were predictors of death or transplant, after adjusting for baseline hepatic venous pressure gradient (HVPG), and Child-Pugh scores. After a median of 5 years, a significant difference in death or transplant, mortality, and clinical decompensation was observed in patients who had leukopenia combined with thrombocytopenia at baseline compared with patients with normal HI (P < .0001). HVPG correlated with hemoglobin and white blood cell count (hemoglobin, r = -0.35, P < .0001; white blood cell count, r = -0.31, P < .0001).

Conclusions: Thrombocytopenia is the most common and first abnormal HI to occur in patients with cirrhosis, followed by leukopenia and anemia. A combination of leukopenia and thrombocytopenia at baseline predicted increased morbidity and mortality.

Figure 1

Kaplan–Meier failure curve for the occurrence of thrombocytopenia, anemia, and leukopenia in the entire cohort (n = 213). 77% of the patients had thrombocytopenia at baseline; whereas the median time to occurrence for anemia was 39.6 months (95% CI, 24.1–49.9), and leukopenia was 30 months (95% CI, 18.5–53.6).

Figure 2

Kaplan–Meier failure curve for the occurrence of thrombocytopenia, anemia, and leukopenia in patients (n = 34) with normal HI at baseline. 59% of the patients developed thrombocytopenia on follow-up, with a median time to occurrence of 28 months. Anemia occurred in 35%, and leukopenia occurred in 21% of patients.

Figure 3

Kaplan–Meier survival analysis of death/transplant among the HI groups (P < .0001). Thrombo, thrombocytopenia only; Thrombo and Leuko, thrombocytopenia and leukopenia. Pairwise comparisons by log-rank test: leukopenia combined with thrombocytopenia vs normal, P < .0001; leukopenia combined with thrombocytopenia vs thrombocytopenia, P = .0002; thrombocytopenia vs normal, P = .0314.

Figure 4

Kaplan–Meier survival analysis of death among the HI groups (P = .0093). Thrombo, thrombocytopenia only; Thrombo and Leuko, thrombocytopenia and leukopenia. Pairwise comparisons by log-rank test: leukopenia combined with thrombocytopenia vs normal, P = .0053; leukopenia combined with thrombocytopenia vs thrombocytopenia, P = .0280.

Figure 5

(A) Correlation curve showing a relationship between WBC and HVPG at baseline (Spearman correlation, −0.31; P < .0001, n = 213). (B) Correlation curve showing a relationship between Hgb and HVPG at baseline (Spearman correlation, −0.35; P < .0001, n = 213).

Figure 6

HVPG among different HI groups expressed in median with interquartile ranges. Thrombo, thrombocytopenia only; Thrombo and Leuko, thrombocytopenia and leukopenia. Pairwise comparisons: Leukopenia combined with thrombocytopenia vs normal, P < .05. Leukopenia combined with thrombocytopenia vs thrombocytopenia, P < .05. Thrombocytopenia vs normal, P < .05.