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Summary Peripheral blood lymphocyte sets and serum immunoglobulins were examined in 15 patients with thalassaemia intermedia, aged between 5 and 30 years. They were divided in three clinical groups: Group I, non-splenectomized, with serum iron (SI) lower than 200 μg/dl; Group II, splenectomized with serum iron lower than 200 μg/dl; and Group III, splenectomized with serum iron levels greater than 200 μg/dl. High absolute lymphocyte counts were observed in the majority of patients, whether splenectomized or not. Following splenectomy, marked increases were observed in absolute number of lymphocytes and percentages of circulating surface immunoglobulin (SIg) bearing B lymphocytes, mouse rosette forming cells (MRFC) and ‘null’ cells. The increases in circulating B lymphocytes following splenectomy were due exclusively to cells bearing SIgM and/or SIgD. No changes were observed in numbers and proportions of circulating SIgA or SIgG bearing cells. Serum IgA levels were high in the majority of patients studied whether splenectomized or not. Following splenectomy increases in serum IgA and serum IgG were observed which seemed to relate to increasing SI levels. No significant changes occurred in serum IgM levels. Absolute numbers of circulating T lymphocytes were unaffected by splenectomy or SI levels. Changes were observed, however, in distribution of T lymphocyte subsets with decreases in number of Tμ cells and concomitant increases in numbers of non-Tμ, non-Tγ cells. Tγ cells were the least affected by splenectomy and increasing SI. The results are compatible with the proposition that iron participates in the regulation of lymphoid cell migration and in the modulation of expression of cell surface markers. The findings also illustrate the role of the spleen in the control of lymphocyte migration and immunoglobulin production.

We have found bioassayable somatomedin activity to be subnormal in 20 of 32 children and adults with beta-thalassemia. The levels were comparable to values reported in growth hormone-deficient subjects. Since patients with thalassemia are not growth hormone deficient, the data suggest the possibility of defective hepatic biosynthesis of somatomedin. Increased iron stores in these patients, who have secondary hemosiderosis of many organs, including the liver, may depress somatomedin activity. Therapy for one year with daily subcutaneous infusions of the iron-chelating agent deferoxamine had no effect on mean bioassayable serum somatomedin activity.

This is the first case report of cataracts in patients with thalassemia major. Desferrioxamine, an iron-chelating agent is being used with increasing frequency in the treatment of transfusion-induced iron overload. There has been some concern in the literature about possible cataract formation with use of this drug. It is therefore important to document any lens opacities seen prior to administration of desferrioxamine, or record the appearance of lens opacities after its use. The possible eitology of these lens opacities is discussed.

27 patients aged 5-28 yrs. with Thal were studied by exercise testing (ET) (Bruce protocol) and by M mode echocardiography (Echo). Hemoglobin (Hgb) was determined 1 hr. prior to ET. 19/27 had no digitalis therapy (DIG). Endurance time: 16/27 had low endurance time (END) ( 2 standard deviations below the PM) at maximal exercise (ME), not related to age or Hgb. 4/27 (2 boys, 2 girls) had increased HR at ME, not related to age or Hgb. EF and left ventricular internal diameter shortening on Echo were not predictors of HR. Dysrhythmias: 1/27 developed ventricular premature contractions (runs of 2 or 3) not seen on 24 hr. taping or standard ECG. 1/27 showed atrial premature beats. 1/27 on DIG showed sinus arrests during recovery. ST segments-T waves: No changes of ischemia were noted. Conclusions: (a) 60% of patients with Thal showed decreased END that correlated with decreased Hgb (

Desferrioxamine (DF) has recently proven to be extremely efficacious in inducing iron excretion when administered as an IV or SC infusion. To determine appropriate IV drug doses for thalassemic children of different ages, we performed 17 dose-response studies on patients from 5 to 26 years old. Each child received 4 one-week courses of IV DF at doses of 20, 40, 60 and 80mg/kg. Three patients received SC DF by portable infusion pump at 20 mg/kg over 8 hours for one week and 16 hours another week. At 20 mg/kg, drug efficiency (urinary Iron excretion/theoretical maximum excretion) was 55% in the youngest group but fell rapidly as the dose was increased. In contrast, drug efficiency was 86% in patients over 11 years and dropped off slowly to 62% at 80 mg/kg. At the same dose, SC DF given over 8 hours was shown to be almost as effective as 16 hours SC and 24 hours IV DF, permitting over-night SC administration. Thus, drug dose and route of administration should be adjusted according to age and requirements.

The identification of patients with thalassemia major who will clearly benefit from splenectomy is often difficult. Modell (Br Med Bull 32:270,1976) has evaluated transfusion requirements based upon weight, mean hemoglobin level and amount of administered whole blood. We have modified this index using the pre-transfusion Hb level and quantity of packed red cells. Transfusion requirements, expressed as the volume of transfused packed RBC's in one year divided by weight at mid-year, were studied in 48 patients with thalassemia major and intact spleens and 18 patients after splenectomy. The patients with spleens (3-24 years old) required 131-367 ml/kg/yr (mean 223) to maintain a pre-transfusion Hb level of 7.8-9.8 g/dl. The 18 patients (5-28 years old) who underwent splenectomy required 80-155 ml/kg/yr (mean 126) to maintain a pre-transfusion Hb level of 8.3-10.6 g/dl. In 8 patients studied before and at least six months after splenectomy, the amount of administered blood decreased 24-74% (mean 48%), despite an increase in the mean pre-transfusion Hb level from 8.5 to 9.6 g/dl. Post-splenectomy transfusion requirements in all eight patients were in the predicted range. As illustrated by these data, the transfusion index allows easy identification of those patients with Cooley's anemia who will benefit from splenectomy and permits prediction of the decrease in blood requirements following splenectomy.

Patients with homozygous B-thalassemia of ten have moderate to severe epistaxis and/or a petechial rash with normal platelet count, PT and PTT. For this reason we have studied platelet function (P1 F). Pre-transfusion evaluation included: Duke bleeding time (BT), PF3 release (Stypven), aggregation (epinephrine, ADP, collagen), PT, PTT and platelet count. PI F was abnormal in 13/30 patients(43%) studied: 10/13 had recurrent epistaxis and/or petechial rashes. 3 had minimal symptoms; 13/13 had abnormal aggregation with epinephrine, 10/13 with ADP, and 10/13 with collagen; only 1 also had slightly low PF3 release; BT was abnormal in 3/13. At time of study platelet count was normal in all, PT and PTT in most; none were receiving anti-aggregating drugs. Patients' platelets were isolated, washed by Ardlie buffer method, lysed and analyzed spectophotomet-rically for iron. No iron deposition in platelets was detected by this method. In other experiments, donor platelets were washed or gel-filtered to render them free of donor plasma; test plasma was then added to platelets and platelet aggregation assays were performed. Normal donor platelets were abnormal when tested in plasma from patients with abnormal P1 F; platelets from 3 patients with abnormal P1 F functioned normally in normal plasma but abnormally in “abnormal” plasma. Abnormalities of platelet aggregation are detectable in 1/2 symptomatic patients. Our data suggest that the P1 F abnormalities detected in β-thalassemia may be due to a plasma Inhibitor, rather than an intrinsic platelet defect.

Echocardiographic studies in 44 subjects with thalassemia major(Thal) aged 5-27 years with body surface area(BSA) 0.8-1.9M2 were compared to 54 normals(N) of similar age and BSA. Hemoglobin of the Thals was maintained by transfusion at 11.4 gms.% ± 3.2 S.D. Of 39 Thals(Group 1) studied prior to Desferrioxamine therapy only 1 was on therapy for heart failure. Five patients (Group 11) aged 9-15 years were studied to assess left ventricular(LV) function because of recent onset of failure. In comparison to normal data 95% confidence limits, Group 1 subjects had increased LV end diastolic dimension(LVD) in 23/39(59%) and increased left atrial dimension(LAD) in 21/39(54%); LV wall thickness was above the mean normal values in 33/39(85%) patients. In Group 11, normal data 95% confidence limits were exceeded in 4/5 for LVD and 5/5 for LAD. Remarkably good LV function was found in Group 1 subjects, including 9 over 20 and 22 over 15 years of age. However, once heart failure was apparent(Group 11), LV function was markedly reduced and despite treatment for failure progression to death occurred within 1-11 months.