Partial Plasma Exchange Research Articles

HDLs in apoA-I transgenic Abca1 knockout mice are remodeled normally in plasma but are hypercatabolized by the kidney

Patients homozygous for Tangier disease have a near absence of plasma HDL as a result of mutations in ABCA1 and hypercatabolize normal HDL particles. To determine the relationship between ABCA1 expression and HDL catabolism, we investigated intravascular remodeling, plasma clearance, and organ-specific uptake of HDL in mice expressing the human apolipoprotein A-I (apoA-I) transgene in the Abca1 knockout background. Small HDL particles (7.5 nm), radiolabeled with (125)I-tyramine cellobiose, were injected into recipient mice to quantify plasma turnover and the organ uptake of tracer. Small HDL tracer was remodeled to 8.2 nm diameter particles within 5 min in human apolipoprotein A-I transgenic (hA-I(Tg)) mice (control) and knockout mice. Decay of tracer from plasma was 1.6-fold more rapid in knockout mice (P < 0.05) and kidney uptake was twice that of controls, with no difference in liver uptake. We also observed 2-fold greater hepatic expression of ABCA1 protein in hA-I(Tg) mice compared with nontransgenic mice, suggesting that overexpression of human apoA-I stabilized hepatic ABCA1 protein in vivo. We conclude that ABCA1 is not required for in vivo remodeling of small HDLs to larger HDL subfractions and that the hypercatabolism of normal HDL particles in knockout mice is attributable to a selective catabolism of HDL apoA-I by the kidney.

Heparin-mediated extracorporeal low-density lipoprotein precipitation: rationale for a specific adjuvant therapy in cardiovascular disease

Various radical measures for the treatment of severe hypercholesterolemia such as partial ileal bypass, portocaval shunt, liver transplantation and plasma exchange have been tested in patients in whom drug and diet failed or were insufficient. Although effective, most of these treatments have severe side effects and are not routinely used. For hypercholesterolemic patients LDL-apheresis has proved to be the most promising and safe way as an adjuvant therapy. Several LDL-apheresis procedures with a varying degree of selectivity and efficiency have subsequently been developed. One of them is the H.E.L.P. system which was introduced in 1984 and has now been widely used. Besides the marked reduction of LDL particles by all techniques it has become apparent that only the H.E.L.P. system results in an equally significant change in hemostaseology, hemorheology and vasomotion because of its simultaneously removal of LDL, Lp(a), fibrinogen and CRP. This contribution reviews the application of the H.E.L.P. system as a valuable therapeutic tool for the treatment of various atherothrombotic and microcirculatory disorders such as prevention of early graft occlusion after coronary artery bypass grafting, treatment of peripheral vascular disease, stroke and preeclampsia.

Effects of partial plasma exchange transfusion on blood flow velocity in large arteries of arm and leg, and in cerebral arteries in polycythaemic newborn infants.

Continuous wave Doppler velocimetry was performed in brachial, femoral and cerebral arteries in four preterm, four small-for-gestational-age (SGA) and eight appropriate-for-gestational age (AGA) polycythaemic newborns before and at 3 and 24 h after partial plasma exchange transfusion and in 18 matched controls at 3 and 24 h after birth. In peripheral arteries, end-diastolic flow velocity was zero in all eight AGA controls, but only in two of the other infants. Consequently, mean flow velocity and red cell transport in AGA controls were significantly lower than in the other five groups, which did not differ. Partial plasma exchange transfusion did not influence flow velocities and red cell transport in peripheral arteries, but normalized the flow velocities in cerebral arteries in all three subgroups of polycythaemic infants, which were lower than in control infants. Cerebral red cell transport in controls increased significantly between 3 and 24 h, and in polycythaemic infants between 0 and 3 h after partial plasma exchange transfusion. In conclusion, reduction in haematocrit had different effects on blood flow velocity and red cell transport of peripheral and cerebral vessels, suggesting that the increased cerebral blood flow velocity after partial plasma exchange transfusion is not simply due to a reduction in viscosity or oxygen content of the blood. The lower peripheral blood flow velocities in normocythaemic AGA infants as compared to all other groups, suggest that the level of maturity is an important determinant for the capacity to regulate blood flow.

Asymptomatic syndrome of polycythemic hyperviscosity: effect of partial plasma exchange transfusion

We determined the cerebral hemodynamic changes in infants with asymptomatic polycythemic hyperviscosity syndrome and whether treatment with partial plasma exchange transfusion (PPET) would affect hemodynamics as well as outcome. From a routine cord blood hematocrit screening, 71 babies were identified as needing to be tested for polycythemic hyperviscosity. In addition to clinical evaluation, each infant had radial artery hematocrit and viscosity determinations, blood gas determinations, cerebral blood flow velocity studies, cranial ultrasonography, and noninvasive intracranial pressure determination. Babies with symptomatic hyperviscosity (n = 17) were treated by PPET, whereas those with asymptomatic hyperviscosity (n = 28) were randomly selected to have PPET (n = 14) or to be observed (n = 14). The remaining babies (n = 26) with normal viscosity served as control subjects. Both hematocrit and viscosity decreased after PPET but remained unchanged in babies with hyperviscosity who were merely observed. Reversal of cerebral blood flow velocity abnormalities was observed after PPET in the infants with symptomatic hyperviscosity, whereas those who had no symptoms had normal results on Doppler studies at the outset, and no significant changes occurred with either PPET or observation. There were two deaths in the group with symptoms. A total of 46 babies returned for follow-up evaluation at a mean age of 30 +/- 7.7 months. Outcome of the control group was no better than that of those who had hyperviscosity, and outcomes did not differ between the babies with symptomatic and those with asymptomatic hyperviscosity, nor between those treated with PPET and those who were only observed. Multivariate analysis revealed that other perinatal risk factors and race rather than polycythemia or PPET, significantly influenced long-term outcome.

Circulating Blood Volume in Appropriate and Small for Gestational Age Full Term and Preterm Polycythaemic Infants

Relative circulating volume (CV) was determined in 31 polycythaemic newborn infants who underwent a partial plasma exchange transfusion (PPET). The infants were divided in four sub-groups: appropriate for gestational age (AGA) term and preterm infants, and small for gestational age (SGA) term and preterm infants. CV was calculated using a regression line between the number of exchange steps and central venous haematocrit values obtained before the procedure and after every exchange step. The median relative CV in all polycythaemic newborn infants was 94.0 (range 69-143) ml/kg. Irrespective of gestational age and birthweight the median relative CV in AGA infants was 86.5 (range 69-107) ml/kg, which differed significantly from the value of 106 (range 85-143) ml/kg found in SGA infants. If a PPET is indicated we recommend to calculate the exchange volume in AGA infants using a relative CV of 86 ml/kg and in SGA infants using a relative CV of 106 ml/kg.

The effect of polycythemia and hypoxia on urinary N-acetyl- β-D-glucosaminidase activity in newborns

Urinary N-acetyl- β-D-glucosaminidase activity was assayed in fullterm and preterm polycythemic neonates, in preterm infants with hypoxia, and in healthy newborns. There were no significant differences between fullterm and preterm babies or between appropriate for gestational age and small for gestational age neonates in the normal group. N-acetyl- β-D-glucosaminidase excretion on the first day of life was significantly raised in polycythemic newborns ( P < 0.01). Fourteen days after partial plasma exchange the enzyme activity returned to normal. N-acetyl- β-D-glucosaminidase activities in preterm babies with respiratory distress syndrome were significantly ( P < 0.01) raised on the 1st, 2nd, 4th days and fell sharply to the 14th day. N-acetyl- β-D-glucosaminidase isoenzyme studies revealed that urine samples taken from preterm babies with respiratory distress syndrome in the first week after birth contained increased amounts of intermediate and B isoenzyme forms while there was a concomitant reduction in the amount of the A form present.

Use of peripheral vessels for exchange transfusion.

During a five and a half year period, exchange transfusions were performed through the peripheral vessels in 201 of the 214 infants (94%) who required either double volume or partial plasma exchange transfusions. Peripheral vessel exchange transfusion is simple, practicable, and safe with few complications. Technical difficulties in catheterizing the peripheral artery and vein may be overcome by using a 24 gauge catheter, which causes no more catheter induced haemolysis than standard umbilical catheters.

Effects of partial plasma exchange transfusion on cerebral blood flow velocity in polycythaemic preterm, term and small for date newborn infants

Isovolemic haemodilution with plasma was performed in 36 newborn infants with polycythaemia 3h after birth. Continuous wave Doppler ultrasonography was used to study the short and longer term influence of partial plasma exchange transfusion on cerebral blood flow velocity in both the anterior cerebral and mid cerebral arterial system up to 24h after haemodilution. The study group consisted of 11 preterm infants, 12 term infants, and 13 small for date infants. After exchange transfusion peripheral venous haemotocrit decreased from 72.5% to 59.4%. In all experimental groups cerebral blood flow velocity (CBFV) before exchange transfusion was significantly lower (18%-44%) than matched controls, and increased to control levels after exchange transfusion. CBFV improved most in preterm infants. After the transfusion the values were no different from the age-, weight-, sex- and parity-matched control groups, and they remained at this level during the next 24 h. No differences could be found between the anterior and mid-cerebral arterial system. When clinical symptoms were present, they subsided in all infants. In conclusion, partial plasma exchange transfusion has a favourable effect for at least 24 h on cerebral blood flow velocity in newborn infants with polycythaemia.

Neonatal Hyperviscosity Association With Lower Achievement and IQ Scores at School Age

A longitudinal study was conducted to determine whether the early neurologic and motor impairment observed in children with neonatal polycythemia and hyperviscosity persisted into school age. Forty-nine children who had neonatal polycythemia and hyperviscosity were evaluated at a mean age of 7 years. Of these, 21 (group 1) received a partial plasma exchange transfusion, whereas 28 (group 2) received symptomatic care. Forty control children (group 3) with a normal neonatal hematocrit were also evaluated. Testing consisted of a battery of measures to evaluate IQ, achievement, neuromotor function, and gross and fine motor skills. Maternal education and IQ were also assessed to avoid potential confounding by differences in the home environment. The neonatal course of the children with polycythemia and hyperviscosity was characterized by an increased number of problems, including hypoglycemia and cyanosis. At 7 years of age, the 49 children who had hyperviscosity (groups 1 and 2) had significantly lower "spelling" and arithmetic achievement test results and gross motor skill scores. Scores for reading, visual motor integration, and neurologic signs did not differ significantly from group 3. Maternal IQ scores were similar for both groups. Left-hand preference was seen in 14% of group 1 and 2 children and 7% of group 3 children (not significant). The scores for IQ, achievement, neuromotor function, and visual motor integration were compared for the hyperviscosity group (groups 1 and 2) and the control group (group 3) by multivariate analysis of variance with sex and hyperviscous group as independent variables and maternal education and maternal IQ as covariates (P = .040).(ABSTRACT TRUNCATED AT 250 WORDS)

Partial Plasma Exchange Transfusion Improves Cerebral Hemodynamics in Symptomatic Neonatal Polycythemia

Cerebral arterial pulsatile flow changes and the effect of partial plasma exchange transfusion on these pulsatile flow patterns were studied in neonatal polycythemia/hyperviscosity syndrome by transcutaneous Doppler technique. Twenty-two infants with cord blood hematocrit greater than 58% (greater than 2 SD above the mean) were studied from a total of 2,400 infants who were screened for cord hematocrit over a 6-month period. Each of 22 infants had the following initial studies: radial artery hematocrit, viscosity, intracranial pressure measurement, and anterior cerebral arterial Doppler study to determine pulsatility index, mean systolic, mean end diastolic, and mean flow velocities, and area underneath the curve of the velocity tracings/min. Twelve of 22 infants had radial artery hematocrit less than 63%, were normoviscous (less than 13.5 cps, 11.25 sec-1) and were designated as control infants. Ten (study infants) were polycythemic (hematocrit greater than or equal to 63%) and hyperviscous (greater than or equal to 13.5 cps, 11.25 sec-1). All study patients were treated by partial plasma exchange transfusion. Initial studies were repeated after exchange transfusion. Control infants were not treated. Prior to exchange procedure, the polycythemic hyperviscous infants had significantly higher hematocrit, viscosity, and pulsatility index; the other Doppler measurements and heart rate were lower than those of control babies. The exchange procedure resulted in significantly decreased hematocrit, viscosity, and pulsatility index and increase in the other Doppler measurements, heart rate, and intracranial pressure. All postexchange measurements of study infants were not statistically different from the control infants. These data suggest that neonatal polycythemia/hyperviscosity syndrome may be associated with abnormal cerebral hemodynamics that could improve with partial plasma exchange transfusion.

PARTIAL PLASMA EXCHANGE IN PATIENTS WITH AIDS AND KAPOSI'S SARCOMA. PLASMAPHERESIS IN AIDS

Intensive plasma exchange was performed in seven male homosexual patients with AIDS and Kaposi's sarcoma. Serial 1.2 plasma volume exchange procedures were performed three times a week for six weeks. In five of the patients, plasma replacement included gamma globulin in the form of plasma (two patients), or an IV IgG preparation (three patients). No changes in the mean number of helper-inducer or suppressor-cytotoxic cells were noted during the treatment period or the weeks following completion of the last procedure. The mean mitogenic response of the patients' lymphocytes to PHA increased by 32.4% during the course of the plasmapheresis procedures (p less than .05), but returned to baseline over the eight weeks following treatment. Mitogenic responsiveness to PWM did not significantly increase during the course of treatment. No regression of Kaposi's sarcoma lesions was found in any of the patients treated.

Gastrointestinal Injury in Polycythemic Term Infants

Necrotizing enterocolitis is uncommon among term infants. In this group, necrotizing enterocolitis has been associated with two risk factors: polycythemia and umbilical catheterization. During a randomized trial of partial plasma exchange transfusion for treatment of polycythemia, an increased risk of gastrointestinal problems was noted. Eight hyperviscous patients treated with partial plasma exchange transfusion, no symptomatically treated patients, and no control infants developed typical necrotizing enterocolitis (blood in the stools, pneumatosis, and systemic signs). The incidence of necrotizing enterocolitis was significantly greater among patients treated with exchange transfusion compared with patients treated symptomatically or control subjects (P less than .001).

Neonatal Hyperviscosity: Randomized Study of Effect of Partial Plasma Exchange Transfusion on Long-Term Outcome

The use of partial plasma exchange transfusion in newborns with polycythemia and hyperviscosity was evaluated. Ninety-three infants with polycythemia and hyperviscosity were randomly assigned to receive either partial plasma exchange transfusion or symptomatic treatment; the infants were matched with control infants without polycythemia. Neonatal course and outcome at 1 and 2 years were evaluated for each of the three groups. Polycythemic infants had more fine motor and speech problems at 1 year of age than did control infants. At 2 years of age, polycythemic infants had more gross motor delays, neurologic diagnoses, fine motor abnormalities, and speech delays than did the control infants. There was no significant difference at 1 year between the polycythemic infants who had received partial plasma exchange transfusion and those given only symptomatic care. At 2 years, the group receiving partial plasma exchange transfusion had fewer neurologic diagnoses and fine motor abnormalities.

Efficacy of several plasma components in a young boy with chronic thrombocytopenia and hemolytic anemia who responds repeatedly to normal plasma infusions.

This report describes a patient with thrombocytopenia, microangiopathic hemolytic anemia, proteinuria, and microscopic hematuria that could be transiently improved by the infusion of plasma or various plasma components. An increase in platelet count following the transfusion of normal plasma was predictable and reproducible. In therapeutic trials with commercially available plasma components, factor VIII preparations were effective for inducing an increase in the platelet count and improving hemolytic anemia, but albumin, gamma-globulin, factor IX, and fibronectin preparations were ineffective. Serum from normal donors also relieved the symptoms of this condition in our patient. Partial plasma exchange (1,000 ml/m2 of body surface area) was performed with albumin instead of normal plasma, but there was no significant effect on platelet count or anemia. Large, multimeric von Willebrand factor components of the factor VIII complex (VIII/vWF) were found in the patient's plasma when his platelet count was normal, but their levels were reduced when the platelet count was decreased. The multimers of the patient's plasma were larger than those in normal plasma, but smaller than those in normal platelet lysate. Although the pathogenesis of this disease remains unknown, we conclude that transfusions of normal plasma, serum or factor VIII concentrate provide a factor that causes significant improvement in the thrombocytopenia and hemolytic anemia. Furthermore, large VIII/vWF multimers are possibly directly involved in pathogenesis of this disease.

Angiotensin-1-converting enzyme (ACE) activity in human serum following plasma exchange.

Although angiotensin-1-converting enzyme (ACE), which catalyzes both the conversion of angiotensin 1 to angiotensin 2 and the hydrolysis of bradykinin, is known to be present in serum, little information is available about its source or turnover characteristics. We determined the removal and recovery characteristics of serum ACE for two normal subjects and 16 patients, with various diseases, who were undergoing partial plasma exchange. Cholesterol was removed as predicted, but the average actual removal of ACE, 70% of that originally present, was 28% greater than predicted. Recovery of serum levels of ACE after plasma exchange was 34% on Day 1, 62% on Day 3, 94% on Day 5, and 104% on Day 8, and the level remained relatively constant thereafter up to 28 days of study. The pattern of recovery of serum ACE is more compatible with a system of synthesis and release of ACE than with a simple exchange mechanism from sites on the plasma membrane of the endothelial cell or a shift of the enzyme from one space to another.

Normal coagulation findings, thrombocytopenia, and peripheral hemoconcentration in neonatal polycythemia

The criteria used for partial plasma exchange transfusion in 32 of 42 polycythemic newborn infants with capillary hematocrits greater than or equal to 70% were a venous hematocrit greater than 65% and two or more clinical "symptoms," or a venous hematocrit greater than or equal to 70%. Coagulation tests performed on 20 infants before and after the partial plasma exchange transfusion were normal for age. Low platelet counts found in six of the 32 patients were associated with venous hematocrits of greater than or equal to 70%. In three patients the platelet counts (less than 100,000/microliters) increased to greater than or equal to 130,000/microliters after three days. In 20 of 32 infants in whom partial plasma exchange transfusions were performed, peripheral venous hematocrits prior to the exchange were 8.5% higher than umbilical venous hematocrits. Following treatment the venous hematocrits (umbilical and peripheral) did not show a statistically significant difference. Thus, the study revealed coagulation findings normal for age, thrombocytopenia in 20% of polycythemic infants, hemoconcentration, and a sluggish peripheral venous circulation.

Neonatal Hyperviscosity II. Effect of Partial Plasma Exchange Transfusion

To determine the effect of partial plasma exchange transfusion, 20 newborn infants with neonatal hyperviscosity were randomly assigned to observation or treatment with partial plasma exchange transfusion within the first eight hours after birth. They were studied for organ involvement by roentgenogram, blood count, coagulation studies, and neurologic behavior and were followed up using the Brazelton Neonatal Behavior Assessment scale at 8, 24, and 72 hours and 2 weeks of age; in addition, ten control infants without hyperviscosity of similar birth weights and gestational ages were also studied. Exchange transfusion improved blood viscosity but both hyperviscous groups showed a higher proportion of abnormal results than did the control subjects. Infants receiving exchange transfusions subsequently improved during the period from 8 hours to 2 to 3 weeks of age, until they were indistinguishable from the control subjects. Neurologic improvement in hyperviscous infants who had not received exchange transfusions were significantly slower during this period. At 8 months of age, abnormal neurologic and developmental findings were impressive in both groups; no significant differences in neurologic abnormalities were noted at that time. Developmental delays, tremors, spastic diplegia, and monoparesis were found in four of six untreated infants and five of ten infants who had received exchange transfusions. A fine tremor was present in one control child.

Partial plasma exchange using albumin replacement: removal and recovery of normal plasma constituents

Using albumin and crystalloid as the only replacement fluids, the effect of partial plasma exchange on the removal and recovery of normal plasma constituents was studied. The results of 30 procedures on 10 individuals were evaluated. Four patterns of removal are described: reduction in the concentration of fibrinogen and C3 were greater than would be expected based upon the extent of the exchange, while IgG, IgM, cholesterol, alkaline phosphatase and SGPT were removed as expected. Reduction of serum glutamicoxalacetic transaminase (SGOT), lactate dehydrogenase (LDH), amylase, and creatine phosphokinase (CPK) averaged 17% less, and uric acid, calcium and K+ averaged 53% less than expected. Concentrations of HCO-3 and glucose did not change. The mean recovery for all constituents except fibrinogen, C3, cholesterol. IgG and IgM was near 100% at 48–72 hr postpheresis. The 72-hr recovery of fibrinogen and complement was 66% and 60%, respectively. Cholesterol recovery was also slow, requiring a minimum of 1 wk to reach prepheresis levels. Measured at a time when quantitative IgM levels were still reduced, alloantibody agglutinating activity (anti-A and anti-B) in a postpheresis sample exceeded prepheresis agglutinating activity. These data demonstrated that, depending upon quantity and frequency of pheresis, partial plasma exchange using albumin replacement may cause progressive marked reduction in concentrations of immunoglobulin, complement, fibrinogen, and cholesterol. Furthermore, newly synthesized antibody may have increased biologic activity.

The management of polycythaemia in the newborn infant

The management of polycythaemia with hyperviscosity in newborn babies who are clinically well, or who only have minor signs, is not clear. Forty-nine such babies were randomly divided so that 24 were given a partial plasma exchange transfustion and the others were left hyperviscous. The babies were compared with normal controls. Clinical signs were more frequent in exchanged babies, and one developed necrotizing entercolitis. Of the hyperviscous babies 41% had plethoric lungs, 12% abnormal electrocardiograms, 9% were hypocalcaemic and 30% hypomagnesaemic. Behavioural testing after birth revealed differences in both groups when compared with controls. There were more poor scores in the exchange transfusion group. Neurological examination did not reveal marked differences among the groups. Developmental and neurological achievement at 8 mth of age was normal in all the babies. In the present study it is suggested that newborn babies with hyperviscosity who are clinically well or who only have minor signs do not necessarily benefit from partial plasma exchange transfusion.

Partial Plasma Exchange Using Albumin Replacement: Removal and Recovery of Normal Plasma Constituents

Using albumin and crystalloid as the only replacement fluids, the effect of partial plasma exchange on the removal and recovery of normal plasma constituents was studied. The results of 30 procedures on 10 individuals were evaluated. Four patterns of removal are described: reduction in the concentration of fibrinogen and C3 were greater than would be expected based upon the extent of the exchange, while IgG, IgM, cholesterol, alkaline phosphatase and SGPT were removed as expected. Reduction of serum glutamicoxalacetic transaminase (SGOT), lactate dehydrogenase (LDH), amylase, and creatine phosphokinase (CPK) averaged 17% less, and uric acid, calcium and K+ averaged 53% less than expected. Concentrations of HCO-3 and glucose did not change. The mean recovery for all constituents except fibrinogen, C3, cholesterol. IgG and IgM was near 100% at 48-72 hr postpheresis. The 72-hr recovery of fibrinogen and complement was 66% and 60%, respectively. Cholesterol recovery was also slow, requiring a minimum of 1 wk to reach prepheresis levels. Measured at a time when quantitative IgM levels were still reduced, alloantibody agglutinating activity (anti-A and anti-B) in a postpheresis sample exceeded prepheresis agglutinating activity. These data demonstrated that, depending upon quantity and frequency of pheresis, partial plasma exchange using albumin replacement may cause progressive marked reduction in concentrations of immunoglobulin, complement, fibrinogen, and cholesterol. Furthermore, newly synthesized antibody may have increased biologic activity.