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BACKGROUND: Erythrocytapheresis procedures are increasingly used in the treatment of severe acute complications of sickle cell disease (SCD). Some patients who undergo erythrocytapheresis experience dizziness during or after the procedure. There is no data in literature for hemodynamic monitoring of cardiac index (CI) and systemic vascular resistance index (SVRI) during erythrocytapheresis. We have previously shown that impedance cardiography (ICG) and invasive measures of CI by thermodilution techniques are significantly correlated in children. OBJECTIVES: We wanted to evaluate changes in CI and SVRI using ICG and to correlate these with systolic blood pressure (SBP) measurements in SCD patients while undergoing erythrocytapheresis. METHODS: Thirty one SCD patients who had 70 consecutive erythrocytapheresis procedures were included in this IRB approved study. ICG measurements (CI, SVRI, and blood pressure) were taken pre-erythrocytapheresis, 30 minutes after initiation of the procedure, one hour into erythrocytapheresis, and at the end of the procedure. ICG measurements were repeated in symptomatic patients before and after intervention with fluid administration. RESULTS: We evaluated hemodynamic data on 31 SCD patients, average age 12.8±5.2 years and 56% are female. SBP decreased below the base line during 33 procedures and increased above the baseline during 37 procedures. Among patients who had a decrease in SBP, 28/33 (84%) had decreased CI. Among them 22/28 (78%) had increased SVRI. Among patients who had an increase in SBP, 5/37 (14%) had increased CI. Among them 4/5 (80%) also had increased SVRI. Using paired t test, the changes in CI (P CONCLUSIONS:In summary, the hemodynamic changes during erythrocytapheresis are probably multifactorial in origin and may include a combination of SVRI and CI changes. Confirmation of these findings may allow early intervention in some patients and minimize the risk of developing overt clinical symptoms during erythrocytapheresis.

An Erythrocytapheresis program was started at our institution in October 2006 for pediatric patients with sickle cell anemia who suffered from stroke(n=4) or chronic pain syndromes(n=3) with iron overload (n=6). Singer et al. (1999) along with others demonstrated that erythrocytapheresis is useful in preventing iron overload, and decreasing blood viscosity. In spite of the benefits there are many barriers to starting such a program, including repeated intravenous access, cost, location and complications of central venous devices. Five patients received double lumen Titanium 9.6 gauge Vortex pheresis port. Temporary double lumen, femoral pheresis catheters were placed and removed for each procedure in 2 patients exclusively and in a third patient who initially had a port. Non-coring Pheresis 16 gauge high flow needles were used to access ports manufactured initially by Arrow and now BAXA. Immediately after accessing, heparin (1000units/ml) was removed and Altepase (2 mg/ml) was placed in each lumen for 30 minutes. The Carolinas Region American Red Cross performed the pheresis procedure by Cobe Spectra following manufacturer guidelines. Once the procedure was completed each lumen of the port-a-cath was flushed with 1000 units/ml of heparin to fill the volume of the lumens. Ionized calcium levels were monitored and calcium gluconate was given as needed for each procedure. The goal was to keep the patient hemoglobin at 10 g/dl and %sickle hemoglobin less than 30% except for 2 patients in which we set a target percentage of sickle hemoglobin less than 20%. One patient had progressive stenosis and one had a repeat stroke on chronic erythrocytapheresis. These were the only two patients that had progressive disease and these were the only patients who had episodes of % sickle hemoglobin between 31% and 46% (two occasions for each patient). Average time of pheresis was 1 hour and 40 minutes. Initial pheresis procedures were performed in the pediatric intensive care unit (90 procedures) and those with ports were performed in an outpatient setting without increase in complications (20 procedures). All Patients were typed and crossed 2 days before procedure for phenotypically matched blood. The initiation of the pheresis program required cooperation from the American Red Cross, inpatient and outpatient nursing, PICU, radiology, blood bank, laboratory and the practice business managers. The providers and nursing staff developed a standard policy for pheresis port management and an order set for the scheduled monthly procedures. Secure emails between the hematology providers, the Red Cross, hospital blood bank, and nursing staff would confirm scheduled dates, times and the amount of blood needed for each procedure. North Carolina Medicaid usually reimbursed 25% of the pheresis procedure charges which did not include blood products, supplies and physician fees. Two patients with ports have had significant complications: SVC syndrome and Infection associated with surgical placement resulting in port removal. One patient using the femoral pheresis catheter developed atrial flutter during the procedure. Serum ferritin for all patients decreased. None of the patients developed red cell allo-antibodies. All patients’ using femoral pheresis catheters did not have any clinical signs or radiographic abnormalities suggestive of thrombus or scarring. Vortex ports proved reliable in outpatient erythrocytapheresis and required no patient maintenance, admission to the ICU or repeated sedation as needed for femoral catheter placement. Important factors in starting a chronic pheresis program for these complex patients include the following: communication between all involved departments, well equipped location to support cardiac or neurologic complications reliable intravenous access, staff familiar with the Vortex port and pheresis catheters, supportive apheresis team from the American Red Cross, disclosure of possible cost to the institution and standardized policies and procedures for all locations.

Excess red blood cells (RBC) in patients with polycythemia vera (PV) are usually removed by repeated phlebotomy. In order to improve the efficacy of this treatment, we used isovolemic large-volume erythrocytapheresis (EA) by a cell separator. A retrospective analysis of our experience with 69 PV patients (206 EA procedures) is reported. EA induced a rapid, well-tolerated, and long-lasting reduction of Hct, Hb, and RBC counts, as well as an immediate disappearance or reduction of clinical symptoms of PV, while tissue oxygen tension — as measured in 8 patients — increased. Hct was reduced by EA from 56.8% ±5.6% to 41.9% ±6.6%, Hb from 17.5±2.3 to 12.7±2.4 g%, RBC counts from 7.±0.9 to 5.4±0.9×106/mm3. The mean volume of the apherisate was 1410±418 ml, (mean Hct 79.7%±9.3%), and the actual RBC volume removed 1113±367 ml. The isovolemic procedure was well tolerated and the acceptance by patients seemed to be better than with repeated phlebotomy. In 21 patients whose Hct values (Hct before and after EA 58%±5.7% and 41.5%±4.9%) were regularly followed after EA the mean period with Hct

Sickling disorders have long been suspected of decreasing physiologic thresholds for thrombosis, and the sickling process in tissue of being abetted by elements of the hemostatic system. The landscape of the presumed hypercoagulable state, however, has been ill-defined and differences among sickling disorders with regard to its characteristics, if any, undelineated. Learning how this landscape may reflect the pathophysiology of the sickling process may help guide further study of the interactions among the vasculature and the varieties of abnormal erythrocytes resulting from these hemoglobinopathies and define new opportunities to ameliorate the clinical manifestations of "sickle cell disease." Methods: Using laboratory strategies developed to characterize thrombophilia in non-sickling patients with thrombosis, modified for a largely non-European population, 144 patients with sickling disorders were prospectively evaluated for predisposition to thrombosis. A standard group of hemostatic studies was performed using patient samples obtained during steady-state "non-sickling" conditions, by skilled venepuncturists working consistently with this patient group. Genotypes included: HbSS 96/144 (67%); Hb SC 26/144 (18%;) Hb SSTh; 14/144 (9.5%); Hb S/AThal 8/144 (5.5%). 49/144 (34%) patients (pts) received regular automated erythrocytapheresis for prior stroke, recurrent acute chest syndrome or severe pain episodes > 6/yr. Results: As expected, 2/144 (1.4%) of pts were heterozygous for the Factor V Leiden mutation, 0/144 for the Prothrombin 20210 mutation, and 20/144 (14%) heterozygous, 1/144 ( 12 ng/dL in 38/144 patients (26%). Protein S activity levels were 175%, frequently with lesser vWFactor activity (vWF) levels, whereas Hb SSt and SThal more frequently exhibited normal vWA/vWF profiles. Factor VIII activity varied widely, exhibiting no correlation to vWF antigen or activity levels in any of the Hb genotypes. Other thrombophilic conditioners, e.g. antithrombin III activity/Ag, Factor VIII activity, plasmnogen activator inhibitor, and b2-glycoprotein I antibodies were either normal or varied as expected in a " normal," e.g European population, with no correlation to Hb genotype. Conclusions: Thrombophilia in patients with sickling disorders appears to have varied contributors: Hb SC appears most thrombophilic with levels of vWF antigen suggestive of vascular dysfunction and supportive of intravscular platelet adhesion a aggregation. Other genotypes exhibit variable phenotypes, with Hb SThal exhibiting the least thrombogenic phenotype from a aboratory assessment perspective. vWF antigen and Protein S abnormalities emphasize the likely role of inflammation and vascular dysfunction but the dysjunction of vWF and Factor VIII activity hint at greater complexity. Further study of these phenomena and the inclusion of platelet function studies may yield additional insights as to the interaction of sickling erythrocytes, their products and vascular/hemostatic interactions. For now, routine thromboprophylaxis in patients with SC disease appears essential, and likely important in all other genotypes except Hb SThal.

Blood products may contain donor-derived soluble factors such as allergens or antibodies, which when transfused, may cause pathology in the recipient or unexpected test results. Case: We describe a 16 year old female with hemoglobin SC disease who was referred for erythrocytapheresis to reduce the level of sickle hemoglobin prior to a surgical procedure that required general anesthesia. The patient was exchanged with five units of packed red blood cells (PRBC). The following day, routine pre-operative laboratory testing revealed an unexpected positive result in assays for beta subunit of human chorionic gonadotropin (bHCG), an early indicator of pregnancy. The patient denied sexually activity. The result caused postponement of the elective surgical procedure and prompted an abdominal ultrasound study to identify the source of bHCG, which was normal. Methods: Immunoassay was used to determine the bHCG level in the patient (Table 1) and in the residual plasma in each of the transfused units (Table 2). Conclusion: One blood donor, who was unaware of her pregnancy status at the time of donation, harbored a high bHCG level which caused the positive test results in the recipient patient’s serum and urine. If an unexpected result is detected in a recipient of a blood transfusion, it is important to consider the possibility of passive transfusion of the analyte. Table 1: bHCG test results from recipient’s blood following transfusion. Test Result Negative cut-off Qualitative bHCG (serum) Positive < 10 mIU/ml Qualitative bHCG (urine) Positive < 20 mIU/ml Quantititative bHCG (serum) 9 mIU/ml < 5 mIU/ml Table 2: bHCG levels in the segments from the PRBC units transfused. Unit number bHCG, mIU/ml* *Negative cut-off, 1000** 4 0.18 5 0.24

Introduction: Conventional phlebotomy is the standard therapy to remove either erythrocytes or iron in patients with Polycythema Vera (and sec. polyglobulinemia) or patients with hemochromatosis (HC) (and iron overload). This treatment that should be repeated regular has its side effects, is often experienced as inconvenient by the patients and the desired effect is not always reached. We developed an erythrocytapheresis technique based on an isovolemic principle that can be used to remove larger amounts of erythrocytes and is experienced as more convient by the patients. Here we report our experience and compare conventional phlebotomy with either a removal of a the fixed volume of 500 ml or with an exchange volume based on a decrease in Ht ordered by the haematologist. Technique: The erythrocytapheresis was performed according to the standard procedure using a Cobe Spectra. The establish an isovolmic procedure the removed erythrocyte volume was replaced by albumin and ACD anticoagulant with either a volume of 500ml or with a calculated volume to reach the desired Ht. Patients: 29 patients (14 male, 15 female) were entered in this study with a median age of 57 years (range 20–80years). 14 patients were diagnosed as PV patients, 10 with HC, 4 with sec. polyglobulinemia and 1 with sec. iron overload. In 10 patients this therapy was started for reasons of intolerance or insufficient result of repeated phlebotomy. In 19 patients it was used as front line therapy before cytoreductive treatment was started or as supportive care. Results: A total number of 137 procedures were performed. 105 with a fixed volume of 500 ml and 32 with a calculated volume based on the desired decrease of the Ht. The maximum number of procedures was 22 in a patient with phlebotomy resistant HC. All procedures were performed without any clinical problems and experienced as more convenient by those patients who could compare these techniques. In 14 PV patients 47 procedures were performed with a median removal of 16% of the total erythrocyte volume. Compared with conventional phlebotomy this was an improvement in 12 patients with a median increase in erythrocyte removal of 58% (range −14%–81%). In the 10 HC patients 69 procedures with median erythrocyte volume removal of 535 ml was performed. This was a median removal of 22% (range 17–24%) of the total erythrocyte volume and an improvement of median 140% (range 65–216%) compared with phlebotomy. In the other 5 patients the median removed volume was 13% (11–16%) with an improvement of 13% (range 11–16%). The erythrocyte volume removed with the patient tailored volume exchange were all within the range of the volumes removed with the fixed exchange volume technique. Conclusions: Isovolemic erythrocytapheresis is a save and efficient technique either to removed large volumes of erythrocytes or to treat iron overload. Patient tailored volume removal is as yet not more efficient as the fixed volume procedures. Probably this technique can be improved further both technically and by removal larger amounts of erythrocytes.

The follow-up Stroke Prevention Trial (STOP II) attempts to optimize tx therapy for primary stroke prevention in children with SCD who are at increased risk due to an abnormal Doppler ultrasound. A survey of participating investigators (PIs) was performed in order to assess tx practices; 12 PIs out of 26 responded. To begin chronic tx, 42 % of the PIs preferred erythrocytapheresis (ECP), partial or total exchange to bring hemoglobin (Hb) S 30%. Most PIs had a post-tx target hematocrit (Hct) 35–36%, but a third of them did not have one. Pre-tx Hct and/or Hb S (but not post-tx values) were used to predict the timing of the next tx by 83% of the group. When performing ECP, the PIs participated in the decision of how much to exchange pts only 33% of the time; generally ECP was planned by a blood bank physician and/or by machine programming. Chelation began either after 12–30 months of tx (median 18 months), or after serum ferritin 1000–2500 ng/ml (median 2000). 67% of the PIs obtained liver biopsies in all or some of the STOP II pts. Indications for liver biopsies were cited as routine for transfused pts (5 PIs) or depending on ferritin values (6 PIs). Deferoxamine 25–50 mg/kg was infused subcutaneously over 8–10 hours 5–7 nights a week in all pts. Eight PIs reported the use of central venous lines (ports) in some pts to facilitate IV access. Barriers cited to effective chronic tx were: pt compliance with chelation (7 reported it as most important), IV access, pt compliance with tx schedule, hypersplenism, and alloimmunization. We conclude that hematologists :(1) Administer leucoreduced Rh and Kell compatible, S negative PRBC to keep pre-tx Hb S levels

The Haemonetics model 30 cell separator was used for erythrocytapheresis in an adult suffering from tetralogy of Fallot complicated by severe erythrocytosis and coagulopathy. Over a two-week period, the hematocrit was reduced from 81% to 39% after three erythrocytapheresis procedures. Abnormal coagulation was also corrected. The patient uneventfully underwent total surgical correction, during which his blood loss was minimal and his recovery surprisingly smooth.

Thirteen men and one woman (mean age 48.8 yr +/- 6.9, range 36-63) with idiopathic hemochromatosis were treated by erythrocytapheresis. Iron depletion followed 9.60 months treatment (median 24), with 21-203 erythrocytaphereses (mean 93 +/- 61) and total iron removal of 4.2-40.6 g (mean 19 +/- 11.9). Trasferrin saturation decreased from 90 +/- 8.7% to 17 +/- 10.6% and serum ferritin from 3164 micrograms/L +/- 1488 to 60.5 micrograms/L +/- 77.5, and liver iron content normalized in all cases. Initial serum ferritin in the patients who were iron-depleted at 18 months (50%, cumulative percentage) was significantly lower than in those still iron loaded at that time (2280 micrograms/L +/- 940 vs 4049 micrograms/L +/- 1444, p less than 0.02). Clinical improvement was noted in all cases with about a 30% decrease in insulin requirement in most diabetics. Thus erythrocytapheresis appears to be effective and safe in obtaining iron depletion in idiopathic hemochromatosis.

We report on the progress of a new modified method of phlebotomy, erythrocytapheresis, as a means of fast therapeutic removal of erythrocytes from the circulation. We performed erythrocytapheresis in 65 patients. In 18 patients with central venous thrombosis of the eye, the beneficial effect of this procedure proved superior to the traditional approach. In 29 patients with primary or secondary polycythemia, hemoglobin, hematocrit, and blood viscosity could be lowered drastically for up to 11 months by a single erythrocytapheresis. We performed erythrocytapheresis in an effort to deplete the iron stores in patients with hemochromatosis (14 cases) and in patients with porphyria cutanea tarda (4 cases). Several consecutive erythrocytaphereses were necessary, however, to even slightly lower the amounts of stored iron as measured by serum iron, iron-binding capacity, and serum ferritin in these patients. The intervals between treatment were 2 to 11 months, thus much longer than the intervals between blood-lettings. We did not observe any adverse side effects. There was no significant influence on the clotting system, and no reactive thrombocytosis as described after phlebotomies.

An improved method for intermittent-flow erythrocytapheresis in patients with sickle cell disease is reported. The method, a modification of the standard red cell exchange procedure for the Haemonetics 30S unit, dilutes with physiologic saline the patient's blood as it flows from the draw line and before it reaches the centrifugation bowl. The blood dilution (approximately 1.6 parts saline to 1 part blood) is used only during the first two passes, when the proportion of sickle erythrocytes in the patient's blood is still high. Only that amount of bowl supernatant (saline-diluted plasma) necessary to maintain extracorporeal volume below 500 ml is returned to the patient. The method described largely prevents the clumping of sickle erythrocytes in the centrifugation bowl, a complication frequently encountered with the Haemonetics 30S unit. Thus, changing the bowl between passes is avoided. Furthermore, the sickle red cells can be collected with the first pass and cryopreserved for possible future uses including the option of autotransfusion.

We performed exchange transfusions, utilizing the technique of automated erythrocytapheresis, for the treatment of patients with sickle cell anemia. In an attempt to determine guidelines for the use of erythrocytapheresis, we studied the use of this procedure in three distinct clinical situations in nine patients with sickle cell disease. Patients with dangerous complications of sickle cell disease such as acute respiratory distress and priapism responded well to erythrocytapheresis, showing marked improvement within 24-48 hours. Patients with prolonged painful vasoocclusive crises showed only variable improvement after erythrocytapheresis therapy, insufficient to justify exposing the patient to the risks of the procedure. Patients treated to decrease the frequency of painful crises demonstrated no prolongation in symptom-free intervals between crises. Therefore, erythrocytapheresis has its main value in the management of acute, dangerous complications of sickle cell disease.

Background: The current treatment of hereditary hemochromatosis (HH) consists of performing periodic whole blood phlebotomies. Erythrocytapheresis (EA) can remove up to three times more red blood cells per single procedure and could thus have a clinical benefit. A prospective study of 30 consecutive cases of HH were included in a periodic EA program. Methods and patients: EA were performed using a discontinuous flow cell separators. The protocol consisted of a bimonthly EA until normalization of the serum ferritin was reached. The aim was to reduce the total erythrocyte volume by 25–35%, eventually, to adjust the amount so that hematocrit would not drop below 0.25. Results: 530 ± 101 ml of erythrocytes were removed (median 517, range 116–761 ml). Iron depletion (ferritin < 20 μg/l) was achieved in all patients after a mean 6.9 ± 7.6 months, median 5 months, range 1–36 months and a mean 14 EA sessions. The procedures were well tolerated and there were no severe side-effects. Conclusions: We conclude that HH patients treated with EA achieved iron depletion quickly under good conditions of tolerance. The efficacy, speed, tolerability, and more favorable schedule of an EA program facilitate treatment of HH.

Erythroapheresis with RBC replacement was used as an emergency therapy in a patient with anilin poisoning. The same therapy was also performed in a pregnant woman with beta+/HbS anemia at her 40th week of pregnancy, as a prophylactic measure for preventing possible complications from cesarean section. This therapeutic modality was clinically effective confirming that the removal of pathological RBC is a safe procedure of essential value in emergency situations.

To the Editor.— We read with great interest the report of the American Medical Association Panel on Therapeutic Plasmapheresis 1 and were surprised that loiasis with hypermicrofilaremia and overwhelming Plasmodium falciparum malaria were not included in the list of indications for apheresis. At least two reports 2,3 give strong evidence for the efficiency of apheresis in the removal of Loa loa microfilaria. This well-tolerated procedure is particularly useful in avoiding severe toxic reactions—in some cases fatal—occurring in patients with a high microfilarial load being treated with diethylcarbamazine. Similarly, automated erythrocyte exchange transfusion has proved effective in rapidly reducing high P falciparum blood load. Erythrocytapheresis combined with transfusion of packed red blood cells using a flow cell separator and specific chemotherapy should be strongly advocated in cases of malaria with either cerebral, renal, pulmonary, or hemostatic complications and parasitemia in excess of 10%. 4-9 Because apheresis may have a useful, and