Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia.
Timika Malaria Research Program, Papuan Health and Community Development Foundation, Timika, Indonesia.
Am J Hematol. 2024 Feb;99(2):223-235. doi: 10.1002/ajh.27152. Epub 2023 Nov 27.
Splenomegaly frequently occurs in patients with Plasmodium falciparum (Pf) or P. vivax (Pv) malarial anemia, but mechanisms underlying this co-occurrence are unclear. In malaria-endemic Papua, Indonesia, we prospectively analyzed red blood cell (RBC) concentrations in the spleen and spleen-mimetic retention in 37 subjects splenectomized for trauma or hyperreactive splenomegaly, most of whom were infected with Plasmodium. Splenomegaly (median 357 g [range: 80-1918 g]) was correlated positively with the proportion of red-pulp on histological sections (median 88.1% [range: 74%-99.4%]; r = .59, p = .0003) and correlated negatively with the proportion of white-pulp (median 8.3% [range: 0.4%-22.9%]; r = -.50, p = .002). The number of RBC per microscopic field (>95% uninfected) was correlated positively with spleen weight in both Pf-infected (r = .73; p = .017) and Pv-infected spleens (r = .94; p = .006). The median estimated proportion of total-body RBCs retained in Pf-infected spleens was 8.2% (range: 1.0%-33.6%), significantly higher than in Pv-infected (2.6% [range: 0.6%-23.8%]; p = .015) and PCR-negative subjects (2.5% [range: 1.0%-3.3%]; p = .006). Retained RBCs accounted for over half of circulating RBC loss seen in Pf infections. The proportion of total-body RBC retained in Pf- and Pv-infected spleens correlated negatively with hemoglobin concentrations (r = -.56, p = .0003), hematocrit (r = -.58, p = .0002), and circulating RBC counts (r = -.56, p = .0003). Splenic CD71-positive reticulocyte concentrations correlated with spleen weight in Pf (r = 1.0; p = .003). Retention rates of peripheral and splenic RBCs were correlated negatively with circulating RBC counts (r = -.69, p = .07 and r = -.83, p = .008, respectively). In conclusion, retention of mostly uninfected RBC in the spleen, leading to marked congestion of the red-pulp, was associated with splenomegaly and is the major mechanism of anemia in subjects infected with Plasmodium, particularly Pf.
脾肿大常发生在感染恶性疟原虫（Pf）或间日疟原虫（Pv）的贫血患者中，但这种共病发生的机制尚不清楚。在印度尼西亚巴布亚疟疾流行地区，我们前瞻性地分析了 37 名因创伤或反应性脾肿大而接受脾切除术患者的脾脏和脾脏样保留的红细胞（RBC）浓度，其中大多数感染了疟原虫。脾肿大（中位数 357g[范围：80-1918g]）与组织学切片上红髓比例呈正相关（中位数 88.1%[范围：74%-99.4%]；r=.59，p=.0003），与白髓比例呈负相关（中位数 8.3%[范围：0.4%-22.9%]；r=-.50，p=.002）。在 Pf 感染（r=.73；p=.017）和 Pv 感染（r=.94；p=.006）的脾脏中，每视野 RBC 数（>95%未感染）与脾脏重量呈正相关。在 Pf 感染的脾脏中，估计保留的总 RBC 比例中位数为 8.2%（范围：1.0%-33.6%），明显高于 Pv 感染（2.6%[范围：0.6%-23.8%]；p=.015）和 PCR 阴性者（2.5%[范围：1.0%-3.3%]；p=.006）。保留的 RBC 占 Pf 感染中所见循环 RBC 丢失的一半以上。Pf 和 Pv 感染的脾脏中保留的总 RBC 比例与血红蛋白浓度（r=-.56，p=.0003）、红细胞压积（r=-.58，p=.0002）和循环 RBC 计数（r=-.56，p=.0003）呈负相关。Pf 中脾脏 CD71 阳性网织红细胞浓度与脾脏重量呈正相关（r=1.0；p=.003）。外周和脾脏 RBC 的保留率与循环 RBC 计数呈负相关（r=-.69，p=.07 和 r=-.83，p=.008）。总之，脾脏中主要是未感染 RBC 的保留导致红髓明显充血，与脾肿大有关，是感染疟原虫（特别是 Pf）的患者贫血的主要机制。
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