The Iron Overload Syndromes
The Iron Overload Syndromes
Phlebotomy is the mainstay of treatment in both symptomatic and asymptomatic individuals with HH and clinical or biochemical evidence of iron overload (Figure 2). The main reason for institution of therapy is to prevent development of cirrhosis as the survival in treated patients before development of cirrhosis is similar to that of the general population. Therapeutic phlebotomy includes two phases, an initial induction phase to induce iron depletion followed by maintenance phase to prevent excess iron reaccumulation.
There is general agreement that premenopausal women with a SF <200 μg/L and postmenopausal women and men with SF <300 μg/L do not require treatment. There is no clear consensus in asymptomatic subjects especially with mild to moderate elevation of SF (i.e. SF 200–300 μg/L, but below 1000 μg/L) and normal liver tests. These individuals are at a low risk of developing HH-associated signs and symptoms. Watchful waiting is an option although volunteer blood donation or prophylactic phlebotomy given its low risk and potential benefit is suggested. In symptomatic patients, however, therapy should be initiated to try and ameliorate symptoms and prevent progression to organ damage. Although most symptoms including fatigue, increased skin pigmentation and insulin requirements in diabetic patients respond to therapy, arthropathy is less responsive and may in fact worsen as iron may persist in the synovial and cartilage even after adequate phlebotomy. Furthermore, HCC, the most dreaded complication of cirrhosis continues to be a threat even after adequate iron depletion.
In patients in whom therapeutic phlebotomy is indicated, therapy should be initially started once or twice a week as tolerated until iron stores are reduced to the desired end point. One unit (400–500 mL) of blood removes about 200–250 mg of iron. The SF should be followed while on phlebotomy and measured after removal of every 1–2 g of iron. Once the SF reaches below the target level 100 μg/L or lower, the SF should be checked more frequently to prevent iron deficiency. After the goal SF ≤ 50 μg/L has been achieved, maintenance phlebotomy is typically needed 2–4 times per year. A secondary goal is to reduce the TS below 50%. The hematocrit should be checked prior to each venesection and should be within 10 points or no lower than 20% below the initial hematocrit level. If phlebotomy results in anaemia prior to iron depletion, the frequency of phlebotomies may need to be reduced to once every 2 weeks. Although phlebotomy treatment does not generally improve established cirrhosis, the degree of fibrosis may improve. Pharmacological doses of vitamin C accelerate mobilisation of iron and this rapid mobilisation may precipitate sudden death from cardiac dysrhythmias. Therefore, supplemental vitamin C should be avoided by patients undergoing phlebotomy.
Therapeutic erythrocytapheresis (TE) wherein iron is removed as haemoglobin, is useful in cases of massive iron overload to achieve the required SF level in a shorter period of time. A pilot study comparing HH treated with TE treated with phlebotomy showed a reduction of almost 70% in both the total number and the duration of treatments in the TE group.
Treatment of Iron Overload
Phlebotomy is the mainstay of treatment in both symptomatic and asymptomatic individuals with HH and clinical or biochemical evidence of iron overload (Figure 2). The main reason for institution of therapy is to prevent development of cirrhosis as the survival in treated patients before development of cirrhosis is similar to that of the general population. Therapeutic phlebotomy includes two phases, an initial induction phase to induce iron depletion followed by maintenance phase to prevent excess iron reaccumulation.
There is general agreement that premenopausal women with a SF <200 μg/L and postmenopausal women and men with SF <300 μg/L do not require treatment. There is no clear consensus in asymptomatic subjects especially with mild to moderate elevation of SF (i.e. SF 200–300 μg/L, but below 1000 μg/L) and normal liver tests. These individuals are at a low risk of developing HH-associated signs and symptoms. Watchful waiting is an option although volunteer blood donation or prophylactic phlebotomy given its low risk and potential benefit is suggested. In symptomatic patients, however, therapy should be initiated to try and ameliorate symptoms and prevent progression to organ damage. Although most symptoms including fatigue, increased skin pigmentation and insulin requirements in diabetic patients respond to therapy, arthropathy is less responsive and may in fact worsen as iron may persist in the synovial and cartilage even after adequate phlebotomy. Furthermore, HCC, the most dreaded complication of cirrhosis continues to be a threat even after adequate iron depletion.
In patients in whom therapeutic phlebotomy is indicated, therapy should be initially started once or twice a week as tolerated until iron stores are reduced to the desired end point. One unit (400–500 mL) of blood removes about 200–250 mg of iron. The SF should be followed while on phlebotomy and measured after removal of every 1–2 g of iron. Once the SF reaches below the target level 100 μg/L or lower, the SF should be checked more frequently to prevent iron deficiency. After the goal SF ≤ 50 μg/L has been achieved, maintenance phlebotomy is typically needed 2–4 times per year. A secondary goal is to reduce the TS below 50%. The hematocrit should be checked prior to each venesection and should be within 10 points or no lower than 20% below the initial hematocrit level. If phlebotomy results in anaemia prior to iron depletion, the frequency of phlebotomies may need to be reduced to once every 2 weeks. Although phlebotomy treatment does not generally improve established cirrhosis, the degree of fibrosis may improve. Pharmacological doses of vitamin C accelerate mobilisation of iron and this rapid mobilisation may precipitate sudden death from cardiac dysrhythmias. Therefore, supplemental vitamin C should be avoided by patients undergoing phlebotomy.
Therapeutic erythrocytapheresis (TE) wherein iron is removed as haemoglobin, is useful in cases of massive iron overload to achieve the required SF level in a shorter period of time. A pilot study comparing HH treated with TE treated with phlebotomy showed a reduction of almost 70% in both the total number and the duration of treatments in the TE group.