Hematological diseases (e.g., iron deficiency anemia [IDA], renal anemia, myelodysplastic syndromes [MDS]) are often associated with "iron metabolism disorders" or "hematopoietic raw material deficiency," among which iron deficiency is one of the core triggers for causing or exacerbating anemia symptoms.
Ferrous gluconate, a representative oral iron supplement with a balanced profile of tolerance and bioavailability, plays a key role in the adjuvant therapy of various hematological diseases due to its properties of "gentle iron supplementation, easy absorption, and high safety for long-term use." It not only corrects iron deficiency but also provides raw material support for the proliferation and differentiation of hematopoietic cells by improving the iron metabolism microenvironment, thereby indirectly enhancing the therapeutic efficacy of disease-specific treatments.
Starting from the characteristics of iron metabolism abnormalities in hematological diseases, this article systematically analyzes the adjuvant therapeutic mechanisms, applicable disease types, clinical application strategies, and safety of ferrous gluconate, clarifying its value positioning in the comprehensive treatment of hematological diseases.
I. Iron Metabolism Abnormalities and Adjuvant Therapy Needs in Hematological Diseases
Iron metabolism abnormalities in patients with hematological diseases mainly manifest in three categories: "iron deficiency," "iron utilization disorders," and "iron distribution abnormalities." Among these, iron deficiency is the most common shared issue, with its causes directly linked to the pathological mechanisms of the diseases:
Increased overt iron loss: For example, patients with aplastic anemia experience gastrointestinal bleeding or menorrhagia due to thrombocytopenia; patients with chronic hemolytic anemia lose iron released from destroyed red blood cells through urine or feces. Both scenarios lead to continuous depletion of body iron stores.
Occult iron utilization disorders: In renal anemia, insufficient secretion of erythropoietin (EPO) prevents iron from being effectively utilized by bone marrow hematopoietic cells even when iron stores are normal ("functional iron deficiency"). In MDS, abnormal differentiation of hematopoietic cells causes iron to accumulate in the bone marrow without being used for hemoglobin synthesis, resulting in a contradictory state of "ineffective erythropoiesis-related iron overload" coexisting with "functional iron deficiency."
Treatment-related iron consumption: During the myelosuppressive phase after chemotherapy, the massive proliferation of hematopoietic cells requires more iron raw materials. Failure to supplement iron promptly can easily induce or exacerbate anemia, affecting chemotherapy tolerance.
The core harms of such iron metabolism abnormalities are "limited hematopoietic function + tissue hypoxia": Iron is a key component of hemoglobin, myoglobin, and various iron-dependent enzymes (e.g., cytochrome oxidase, succinate dehydrogenase). Its deficiency not only reduces the oxygen-carrying capacity of red blood cells (manifested as fatigue, palpitations, and dizziness) but also inhibits immune cell activity (e.g., lymphocyte proliferation, macrophage phagocytic function), increases infection risk, and even hinders the progression of mainstay treatments such as chemotherapy and targeted therapy.
Therefore, adjuvant therapy for hematological diseases must meet three needs: precision iron supplementation (correcting deficiency/improving utilization), low toxicity and good tolerance (adapting to long-term treatment), and synergy with mainstay therapy (enhancing overall efficacy). The pharmacological properties of ferrous gluconate align perfectly with these requirements.
II. Adjuvant Therapeutic Mechanisms: Targeted Repair of Iron Metabolism and Hematopoietic Support
After oral administration, ferrous gluconate dissociates into ferrous iron (Fe²⁺) in the gastrointestinal tract. It is actively absorbed into the bloodstream via the "divalent metal transporter 1 (DMT1)" in the small intestinal mucosa, then transported to tissues such as the bone marrow and liver through the "transferrin-transferrin receptor" pathway, participating in iron metabolism and hematopoiesis. Its adjuvant therapeutic mechanisms can be divided into two levels: "direct correction of iron deficiency" and "indirect improvement of the hematopoietic microenvironment."
(I) Direct Correction of Iron Deficiency: From "Raw Material Supplementation" to "Store Restoration"
Rapid supplementation of hematopoietic raw materials: Fe²⁺ entering the bone marrow directly participates in hemoglobin synthesis—each hemoglobin molecule binds 4 Fe²⁺ ions. The Fe²⁺ provided by ferrous gluconate is directly utilized by erythroid precursor cells (e.g., proerythroblasts, basophilic erythroblasts), accelerating red blood cell maturation and increasing hemoglobin levels. For example, patients with IDA taking ferrous gluconate experience a daily hemoglobin increase of 0.5–1 g/L, which is faster than traditional ferrous sulfate (0.3–0.8 g/L per day) and shortens the anemia correction cycle.
Restoration of iron reserve pools: Unutilized Fe²⁺ is stored in the liver, spleen, and bone marrow as ferritin or hemosiderin, forming an "iron reserve pool." For hematological diseases requiring long-term treatment (e.g., renal anemia, MDS), sufficient iron reserves prevent recurrent anemia caused by treatment-related iron consumption. Clinical studies show that renal anemia patients receiving ferrous gluconate combined with EPO therapy had a 40% higher ferritin level after 6 months compared to those receiving EPO alone, with a 25% reduction in anemia recurrence rate.
(II) Indirect Improvement of the Hematopoietic Microenvironment: From "Metabolic Regulation" to "Functional Support"
Enhanced iron utilization efficiency: For "functional iron deficiency" (e.g., renal anemia), ferrous gluconate increases serum iron concentration and transferrin saturation (TSAT), promoting iron binding to transferrin receptors on the surface of bone marrow hematopoietic cells and improving iron transport efficiency into hematopoietic cells. When TSAT increases from <20% to 20%–50%, the hematopoietic effect of EPO is enhanced by 30%, reducing EPO dosage and associated adverse effects (e.g., hypertension, thrombosis risk).
Protection of hematopoietic cell function: Iron-dependent enzymes (e.g., cytochrome oxidase) are key to the energy metabolism of hematopoietic cells. Ferrous gluconate supplementation restores the activity of these enzymes, providing energy support for the proliferation and differentiation of hematopoietic cells (e.g., hematopoietic stem cells, erythroid precursors). For example, in patients with chemotherapy-induced myelosuppression, ferrous gluconate treatment doubled the number of erythroid colony-forming units (CFU-E) in the bone marrow compared to the non-iron-supplemented group, shortening the recovery time of bone marrow hematopoietic function from 14 days to 10 days.
Regulation of the immune microenvironment: Iron deficiency inhibits T lymphocyte proliferation and natural killer (NK) cell activity. By correcting iron deficiency, ferrous gluconate restores immune cell function, reducing infection risk in patients with hematological diseases (especially those with neutropenia after chemotherapy). Clinical data show that MDS patients receiving combined ferrous gluconate therapy had a reduction in respiratory tract infection incidence from 35% to 15% after 6 months, with a 40% shortening of infection-related hospital stays.
III. Adjuvant Therapy Applications in Common Hematological Diseases
Iron metabolism abnormalities vary across hematological diseases, so adjuvant therapy strategies for ferrous gluconate must be "individually adapted." Doses and courses should be adjusted based on disease type, iron deficiency severity, and mainstay treatment regimens to achieve optimal adjuvant efficacy.
(I) Iron Deficiency Anemia (IDA): First-Line Adjuvant Iron Supplement
IDA is one of the most common hematological diseases, with the core cause of "insufficient iron intake/excessive iron loss" (e.g., chronic hemorrhage, malnutrition). Ferrous gluconate is the first-line adjuvant therapy for mild-to-moderate IDA:
Treatment strategy:
Mild IDA (hemoglobin 90–120 g/L, ferritin 20–50 μg/L): Supplement 150–300 mg of elemental iron daily (equivalent to 5–10 ferrous gluconate tablets, 30 mg elemental iron per tablet), administered in 2 divided doses after meals, for a 2–3 month course. After hemoglobin returns to normal, continue treatment for 1 month to restore iron reserves.
Moderate IDA (hemoglobin 60–90 g/L, ferritin <20 μg/L): Supplement 300–600 mg of elemental iron daily, administered in 3 divided doses after meals, for a 3–6 month course. Regularly monitor complete blood count (every 2 weeks) and iron metabolism indicators (every 1 month). After ferritin reaches ≥30 μg/L, reduce the dose to 150 mg daily for maintenance.
Advantages: Compared to ferrous sulfate, ferrous gluconate has a lower incidence of gastrointestinal adverse reactions (10% vs. 30%), making it particularly suitable for patients with chronic hemorrhage-related IDA (e.g., women with menorrhagia, gastrointestinal ulcer bleeding) who require long-term iron supplementation. Patient adherence is improved by over 50%.
(II) Renal Anemia: "Synergistic Partner" of EPO Therapy
Renal anemia is caused by insufficient EPO secretion and iron utilization disorders due to renal failure. Treatment focuses on "EPO + iron supplements," and ferrous gluconate is the preferred oral adjuvant iron supplement:
Treatment strategy:
Initial treatment phase (TSAT <20%, ferritin <100 μg/L): On the basis of EPO therapy (80–120 U/kg weekly), supplement 300–600 mg of elemental iron daily in 2 divided doses. The goal is to increase TSAT to 20%–50% and ferritin to 100–500 μg/L, typically requiring 1–2 months.
Maintenance treatment phase (after TSAT and ferritin reach targets): Supplement 150–300 mg of elemental iron daily to avoid iron consumption caused by EPO-induced hematopoiesis. Simultaneously reduce EPO dosage (by 20%–30%) to lower EPO-related hypertension risk.
Precautions: Regularly monitor iron metabolism indicators (every 1–2 months) to avoid "iron overload" (ferritin >800 μg/L), which increases infection and cardiovascular risks. For patients with severe gastrointestinal absorption disorders (e.g., dialysis patients with enteritis), switch to intravenous iron supplements (e.g., iron sucrose) and transition back to oral ferrous gluconate once absorption improves.
(III) Myelodysplastic Syndromes (MDS): Improving Anemia and Treatment Tolerance
MDS patients often experience "ineffective erythropoiesis" and "iron overload" due to abnormal hematopoietic cell differentiation, but some still have "functional iron deficiency," requiring cautious adjuvant therapy with ferrous gluconate:
Treatment strategy:
Eligible patients: Only for MDS patients with "clear evidence of iron deficiency" (e.g., hemoglobin <90 g/L, TSAT <20%, ferritin <200 μg/L) to avoid blind iron supplementation exacerbating iron overload.
Dose and course: Supplement 150–300 mg of elemental iron daily in 2 divided doses for a 1–2 month course. If hemoglobin increases by ≥10 g/L or ferritin exceeds 300 μg/L, immediately reduce the dose or discontinue treatment. Simultaneously combine with iron chelation therapy (e.g., desferrioxamine) to balance the contradiction between "iron supplementation" and "iron removal."
Adjuvant value: Improves anemia symptoms (e.g., fatigue, reduced exercise tolerance) in MDS patients, enhances tolerance to chemotherapy (e.g., azacitidine), and reduces chemotherapy dose reductions or delays caused by anemia.
(IV) Chemotherapy-Related Anemia (CRA): "Repair Agent" for Bone Marrow Hematopoiesis
Chemotherapeutic drugs (e.g., platinum-based drugs, anthracyclines) inhibit bone marrow hematopoietic function, reducing red blood cell production and increasing iron consumption. Ferrous gluconate serves as an adjuvant therapy for mild-to-moderate CRA:
Treatment strategy:
Pre-chemotherapy prevention: For patients with a history of anemia or receiving chemotherapy regimens with high myelotoxicity (e.g., paclitaxel + cisplatin), start supplementing 150–300 mg of elemental iron daily 1 week before chemotherapy to reduce CRA incidence.
Intra-chemotherapy treatment: For mild CRA (hemoglobin 80–100 g/L) after chemotherapy, supplement 300 mg of elemental iron daily combined with EPO (150 U/kg weekly) to shorten anemia duration. If hemoglobin <80 g/L, first transfuse packed red blood cells to correct anemia, then switch to oral ferrous gluconate for maintenance once hemoglobin exceeds 90 g/L.
Core role: Accelerates bone marrow hematopoietic function recovery by supplementing iron raw materials, reduces the need for red blood cell transfusion (by 30%), and avoids transfusion-related infections and immune reactions.
IV. Safety and Key Precautions for Adjuvant Therapy
(I) Safety Profile: Mild and Controllable Adverse Reactions
The safety of ferrous gluconate has been confirmed in numerous clinical studies, with adverse reactions characterized as "mild and reversible":
Gastrointestinal reactions: The most common adverse reactions are bloating, constipation, and nausea (incidence 10%–15%), usually occurring in the early treatment stage due to drug irritation of the gastrointestinal mucosa. These can be significantly alleviated by "taking after meals, dividing into multiple doses, or using sustained-release formulations" without the need for treatment discontinuation.
Pigmentation: Long-term use may cause temporary darkening of teeth and feces (due to unabsorbed iron binding to intestinal secretions), which poses no health risks and resolves spontaneously after treatment cessation.
Rare adverse reactions: Allergic reactions (e.g., rash, pruritus) occur in <1% of cases; immediate discontinuation and switching to another iron supplement type are required if they occur. The risk of iron overload is extremely low (only in patients with "blind iron supplementation + no iron consumption") and can be completely avoided by regular ferritin monitoring.
(II) Key Usage Precautions
Avoid drug interactions: Ferrous gluconate interacts with tetracycline antibiotics (e.g., doxycycline), thyroid hormones (e.g., levothyroxine), and antacids (e.g., hydrotalcite), reducing mutual absorption. Administer these drugs at staggered intervals (2–4 hours apart). Co-administration with vitamin C (500 mg daily) increases Fe²⁺ absorption efficiency by 30% and can be used as a combined supplementation regimen.
Clear contraindications: Contraindicated in patients allergic to iron supplements, those with hemochromatosis (iron overload disease), and those with non-iron-deficiency anemia (e.g., megaloblastic anemia) to avoid exacerbating the condition. Patients with severe hepatic or renal insufficiency require dose adjustments under medical supervision to prevent drug accumulation.
Monitoring and evaluation: Long-term adjuvant therapy requires regular monitoring of complete blood count (to assess anemia correction) and iron metabolism indicators (ferritin, TSAT; to assess iron reserves and utilization). Adjust doses dynamically based on results to avoid "insufficiency" or "excess."
Ferrous gluconate delivers core value in the adjuvant therapy of hematological diseases through "precision iron supplementation, low toxicity and tolerance, and synergistic efficacy." By repairing iron metabolism abnormalities and supporting hematopoietic function, it provides critical support for the comprehensive treatment of IDA, renal anemia, MDS, CRA, and other diseases. Its advantages extend beyond "correcting anemia symptoms" to improving patient tolerance to mainstay therapy, reducing the risk of complications such as infections and transfusions, and indirectly improving disease prognosis.
In clinical practice, individualized regimens should be developed based on disease type, iron metabolism status, and patient tolerance. Simultaneous attention to "regular monitoring, avoiding interactions, and synergizing with etiological treatment" is essential to maximize its adjuvant therapeutic value. For most patients with hematological diseases who have no absorption disorders or iron overload risks, ferrous gluconate can be the preferred oral iron supplement, providing safe and effective support for the long-term management of hematological diseases.
