Normal Plasma Volume Research Articles

Volume Overload and Quantitated Plasma Volume: How Effective Is Intravenous Diuretic Therapy in Patients Hospitalized for Decompensated Chronic Heart Failure?

The assessment and management of fluid volume overload has been a recurrent and perplexing issue in the management of patients hospitalized and often re-hospitalized with decompensated heart failure (DHF). The objective of this study was to quantitate plasma volume (PV) status in patients with DHF, and to determine the effectiveness of standard in-hospital diuresis management in reducing volume overload, and if the quantitation of PV could serve as a tool to guide more effective in-hospital diuretic therapy to achieve practice guideline-recommended euvolemia. PV was measured in patients with a history of chronic HF admitted to hospital for management of clinically determined volume overload. Intravascular volume was determined by a validated radiolabeled-albumin dilutional technique (Volumex, Daxor Corp., NY, NY) at hospital admission and at hospital discharge. Normal PV is defined pre hoc as measured volumes within ±8% of the expected normal value; mild volume expansion is ≤20% of predicted normal value. Volume status reported as absolute value and percentage of the normal value for the individual patient. The coefficient of variation of the analytic technique is <3.5%. Changes in quantitated volume status pre-post diuretic therapy were compared to clinical parameters of volume assessment [body weight change; net fluid input and urine output (I/Os)]. Twenty-seven patients were evaluated (73±9 yrs, sCr 1.7±0.8 mg/dL, LVEF 40±18%, LOS (length of stay) 6.3±2.1 days). All patients except 3 received intravenous loop diuretic therapy (furosemide) at 10-20 mg/hr for average of 5±2 days. The remaining 3 patients received oral furosemide equivalent of 80-160 mg per day. Admission to discharge PV and clinical parameters are shown below. Quantitated PV demonstrates that patients with DHF are significantly intravascularly volume expanded and that usual clinically-guided diuretic therapy only marginally impacts volume status at discharge despite large reductions in body weight and high net negative I/Os. Mobilization of interstitial volume intravascularly likely accounts for this disparity and suggests that DHF patients require longer periods of, or more effective diuretic therapy, to achieve euvolemia. Longer LOS may, however, be compensated by lower rates of 30-day re-hospitalization.Tabled 1AdmissionDischargeMeasured PV4.7 ± 1.1 Liters4.3 ± 1.0 LitersNormal Expected PV(Euvolemia)3.2 ± 0.4 LitersPV Expansion+46 ± 30%+32 ± 22% (p=0.214)Change in Body Weight−7.0 ± 4.6 kgNet I/Os−7.4 ± 6.5 Liters Open table in a new tab

Acquired Inhibitors of Coagulation Factors: Part I—Acquired Hemophilia A

Acquired hemophilia A (AHA) is a rare, but often severe, bleeding disorder caused by autoantibodies against clotting factor VIII (FVIII). AHA occurs more frequently in the elderly and in association with several conditions, such as malignancies, autoimmune diseases, postpartum, or drug exposure; however, about half of the cases remain idiopathic. At variance with congenital hemophilia, where hemarthroses are the most common bleeding symptoms, hemorrhages in AHA involving soft tissues (muscle, skin) are more frequently reported. AHA is diagnosed in patients: with negative personal or family bleeding history; in which prolonged activated partial thromboplastin time is not corrected after mixing and incubating equal volumes of patient and normal plasma for ~2 hours at 37°C; FVIII levels are reduced; and a specific FVIII-inhibiting activity is detected. Prompt recognition and treatment of AHA are mandatory, as inadequate management and complications of the disease are associated with high mortality rates. Therapeutic approaches should aim to control acute bleeds, eradicate FVIII-autoantibody production, treat associated diseases, and when possible, eliminate them. Present knowledge about this often overlooked and challenging condition has significantly increased following establishment of recent national and international studies, as will also be reviewed in this article.

A Large-Pore IEF Gel Electrophoresis Separates the Complex in Both of ADAMTS13 Bound to VWF and to the IgG Autoantibodies From the Unbound in Plasma Milieu

Abstract 1160 Backgrounds and Aims:Thrombotic thrombocytopenic purpura (TTP) is a life-threatening generalized disorder caused by a deficiency of ADAMTS13 activity due to its gene mutations (Upshaw-Schulman syndrome), and/or acquired autoantibodies to this enzyme. ADAMTS13 specifically cleaves the peptide bond between Tyr1605 and Met1606 within the A2 domain of von Willebrand factor (VWF). Recent studies with immunoprecipitation methods using anti-VWF antibody coated beads indicated that a small portion (3–4% of the total) of plasma ADAMTS13 is bound to VWF (Feys HB et al. JTH 7:2088, 2009). This experiment determined the amount of ADAMTS13 bound to VWF in an indirect fashion, but the complex may dissociate during washing procedures or by conformation change after binding to the antibody. Thus, we used an isoelectric focusing (IEF) to separate the complex in a direct fashion. However, the molecular size of VWF-ADAMTS13 complex is assumed to be enormously huge, and therefore a regular polyacrylamide IEF gel does not properly work. So, we employed a large-pore composite IEF gel consisting 0.75% agarose and 1.25% polyacrylamide containing 2% of Pharmalyte (pI range 3.0–10). By this method followed by western blot detection using a non-neutralizing anti-ADAMTS13 monoclonal antibody (WH2-11-1), we identified that an ADAMTS13-VWF complex is detected as a sharp band at pI 7.4. The specificity of this band was identified by a lack in plasma of type 3 von Willebrand disease (VWD), and a new emergence of the band in type 3 VWD plasma spiked with purified VWF (Hori et al, 57th ISTH meeting, P-MO-479). We applied this IEF analysis to detect the complex of ADAMTS13-its autoantibodies. Patients and Methods:ADAMTS13 activity was measured by chromogenic act-ELISA, and acquired idiopathic (ai-) TTP with severe deficiency of ADAMTS13 activity due the presence of its autoantibodies is a target in this study. VWF and ADAMTS13 were purified from normal plasma. A large-pore composite IEF gel electrophoresis was performed as previously described. Results and Discussion:Two forms of ADAMTS13, unbound (pI 5.3) and bound (pI 7.4) to VWF in a volume of 10 uL normal plasma (NP), were directly identified on the IEF gel followed by western blotting (Fig. left). Each plasma of type 3 VWD or USS lacked the complex (VWF-ADAMTS13) band with pI 7.4, but it was generated in vitro just after spiking the purified VWF or ADAMTS13 to the respective deficient plasma by the IEF (Fig. not shown). [Display omitted] Next, when a volume of 3uL NP was analyzed, only one band with pI of 5.3 (5.1–5.5) was observed. In ai-TTP patients with severe deficiency of ADAMTS13 activity (<3% of the control), plasma had no or faint band of ADAMTS13 (Fig. middle). However, when we mixed the equal volume of patient plasma with ai-TTP with severe deficiency of ADAMTS13 activity and NP, the results on IEF gel showed appearance of 3 major bands with pIs of 5.3, 5.9 and 6.5, together with other many minor bands, and the unbound (free) ADAMTS13 almost disappeared (Fig. right). Then, the IgG purified from patient plasma of ai-TTP was mixed with NP or purified ADAMTS13, the complex band had a pI of 5.9 (5.5–6.3). These results indicated a possibility that the IEF analysis could be used to detect the autoantibodies to ADAMTS13, regardless of the neutralizing or non-neutralizing counterparts, in a totally different fashion to the enzyme immunoassay. Disclosures:Matsumoto:Alexion Pharma: Membership on an entity's Board of Directors or advisory committees. Soejima:The Chemo-Sero-Therapeutic Research Institute: Employment. Fujimura:Baxter BioScience: Membership on an entity's Board of Directors or advisory committees; Alexion Pharma: Membership on an entity's Board of Directors or advisory committees.

Phosphodiesterase 4 inhibition attenuates plasma volume loss and transvascular exchange in volume expanded mice

Phosphodiesterase 4 inhibition attenuates plasma volume loss and transvascular exchange in volume expanded mice

A 40-year-old man with recurrent fainting, hypotension, lower limb edema and oliguria with body weight gain and secondary erythrocytosis

Dr. Berti de Marinis, Dr. Allemand: In November 2009, a 40-year-old man was urgently hospitalized after orthostatic syncope secondary to severe hypotension. Three days before admission, he had experienced profuse sweating and contracted diuresis after intense effort (a long run to reach a stadium to see a rugby match) followed by the onset of fever, sore throat and a flu-like syndrome associated with palpitations. The past medical history was relevant to hypothyroidism treated with hormone replacement therapy, and previous episodes of abdominal pain due to bilateral kidney stones, treated with lithotripsy. Physical examination on arrival at the emergency department showed pallor, body mass index 32.93, body weight 102 kg, redness of the pharynx, hardening of the calves with no signs of edema. The vital signs were: temperature 37.6 C, blood pressure (BP) 92/54 mmHg, heart rate (HR) 108 beats per min, respiratory rate 16 breaths per min, oxygen saturation by pulse oximetry 100% without oxygen supplementation. Laboratory analyses revealed: hemoglobin (Hb) 227 g/l, hematocrit (Ht) 64.3%, white blood cells (WBC) 18.84 9 10/l, neutrophils (N) 14.71 9 10/l, platelets 289 G/L, serum creatinine 151 lmol/l, blood urea nitrogen (BUN) 10.5 mmol/l, urine specific gravity 1084, and C-reactive protein (CRP) 13.82 mg/l, troponin 0.01 lg/l. Findings on electrocardiography, chest radiography and echocardiography were normal, there were no signs of deep vein thrombosis on compression ultrasound (CUS), and only a modest splenomegaly was found on abdominal ultrasound (diameter 12.5 cm). Given the increase in d-dimer levels (508 ng/l), pulmonary embolism was excluded by multislice computed tomography. The patient was administered 2.5 l of saline, and was admitted to our internal medicine ward with a diagnosis of ‘‘hemoconcentration secondary to dehydration’’. He arrived with sustained hypotension, tachycardia and fainting, prompting the intravenous infusion of more fluids (1,000 ml of saline and 500 ml of colloids), followed by a gradual return to normal blood pressure values and adequate diuresis. Urea, creatinine and urine specific gravity also returned to normal. Further laboratory and instrumental analyses performed on admission to the ward showed normal levels of IgG, IgA, IgM and complement fractions, and a low level of serum protein (49.2 g/l) with a normal albumin concentration, but no measurable IgG k monoclonal gammopathy with elevated b2 microglobulin (2.65 mg/l) and the absence of Bence Jones protein. Any presence of infection, renal insufficiency, nephrotic/nephritic syndrome or hepatic or cardiac insufficiency was ruled out. The hematocrit remained high (about 60%) despite the return to a normal plasma volume. Therapeutic phlebotomy was performed to prevent any complications of hyperviscosity with a return to a normal hematocrit. Erythropoietin assay was normal, and the search for the V617F Jak2 mutation was negative, excluding polycythemia vera. G. Berti de Marinis I. Bertozzi E. Allemand F. Tezza M. L. Randi F. Fabris (&) Department of Medical and Surgical Sciences, Padua University Medical School, via Giustiniani 2, 35128 Padova, Italy e-mail: fabrizio.fabris@unipd.it

Development of a new modified Bethesda method for coagulation inhibitors: the Osaka modified Bethesda method

The Nijmegen assay for the factor VIII (F-VIII) inhibitor is recommended by the International Society on Thrombosis and Haemostasis/Scientific and Standardization Committee. However, due to cumbersome and complicated preprocessing, it is presently difficult to introduce this assay into hospital laboratories. We used buffered plasma that was made by addition of 1 volume of 1 mol/l HEPES buffer at pH 7.35 to 9 volumes of plasma to form the test samples. The inhibitor titer was calculated by the remaining rate of F-VIII coagulation activity (F-VIII:C), using the ratio of actual value to the theoretical value. Five hundred microliters of the buffered test plasma and the control (30 mmol/l HEPES buffered saline at pH 7.35) were each mixed with equal volumes (500 μl) of normal pooled plasma in a test tube (11 mm internal diameter and 6.5 ml volume capacity), and incubated at 37°C for 2 h. In our modified Bethesda method, there were no significant changes in pH and F-VIII:C of control and test mixtures after incubation tests for stability. With the modified method, the inhibitor titers (mean, SD) from examining three hemophilia A plasma samples (F-VIII:C, <1-3%) and 40 normal samples (F-VIII:C, 34.5-168.3%) were 0.032, 0.057 and -0.009, 0.057, respectively. By our method, the F-VIII inhibitor titer of type I inhibitor-positive samples was higher than the Nijmegen method, and for type II inhibitor-positive samples, the titer was similar. We believe that our method can be applied to not only the type I inhibitor, but also to assays of type II inhibitor, without cumbersome and complicated preprocessing.

Autonomic control and antioxidant status during early pregnancy in formerly preeclamptic women

In formerly pre‐eclamptic women plasma volume is lower (LPV group) than in women who had a normal pregnancy and normal plasma volume (NPV). Blood pressure variability (BPV), heart rate variability (HRV) and baroreflex sensitivity (BRS) were compared in women with LPV (47.7 ml/kg lean body mass, n=7) and NPV (57.2 ml/kg lbm, n=7) before and during a new pregnancy at 8, 12, 16 and 20 weeks during pregnancy. The anti‐oxidant status was assessed if changes in oxidative stress were related to those in BRS. Systolic BP was slightly (about 5 mmHg) lower in LPV than in NPV before and during pregnancy. Before pregnancy low frequency LF‐BPV and LF‐HRV were slightly greater in LPV than in NPV. However, during pregnancy, both LF‐BPV and LF‐HRV were slightly lower in LPV than NPV. BRS increased during pregnancy by 20% in NPV and by 40% in LPV, but between group differences were not statistically significant. Overall these data indicate that autonomic adaptations to pregnancy and changes in BPV, HRV and BRS were comparable in women with LPV and NPV. Remarkably, plasma anti‐oxidant levels fell during pregnancy in NPV from 484 to 384 μM Trolox equivalents and in LPV and from 487 to 413 μM Trolox equivalents. These data indicate that oxidative stress increases during early pregnancy and therefore are in contrast with previous suggestions that increased oxidative stress decreases BRS.

The influence of thermal factors on post‐exercise haemodynamics in endurance exercise‐trained men

The influence of thermal factors on post‐exercise haemodynamics in endurance exercise‐trained men

Acquired Hemophilia: An Overview on Diagnosis and Treatment

Acquired hemophilia (AH) is a rare but severe bleeding diathesis characterized by autoantibodies against a clot- ting factor, in most cases Factor VIII (FVIII). This bleeding disorder occurs more frequently in the elderly and may be as- sociated with several conditions, such as malignancies, autoimmune diseases, postpartum or drugs; however, about half of cases remain idiopathic. At variance with congenital hemophilia, in which hemarthroses are the most common bleeding manifestations, in patients with AH hemorrhages involving soft tissues (muscle, skin) are more frequently reported. AH is diagnosed in patients without previous personal or family bleeding history in which prolonged activated partial throm- boplastin time is not corrected after mixing and incubating for 2-4 hours at 37°C equal volumes of patient and normal plasma, FVIII:C levels are reduced and a specific FVIII inhibiting activity is detected and measured by the Bethesda assay or its Nijmegen modification. A prompt recognition of this life-threatening bleeding disorder and an early and aggressive treatment are mandatory, as diagnostic delays or inadequate treatments are associated with high mortality rates (up to 44% in literature). Therapeutic approach of AH is devoted to stop acute bleeds and to eradicate the FVIII autoantibody. Bleed- ing episodes can be treated with FVIII concentrates or desmopressin in patients with low titer inhibitors, but FVIII bypass- ing agents (activated prothrombin complex concentrates and recombinant activated FVIIa) are required for those with high-titer inhibitors or more severe bleeds. Steroids alone or in combination with cyclophosphamide are effective for eradicating autoantibodies in most cases. More recently, increasing evidence suggests a role for rituximab in this setting, in particular as a second-line approach.

Blunted Autonomic Response to Volume Expansion in Formerly Preeclamptic Women with Low Plasma Volume

We hypothesize that low plasma volume in normotensive formerly preeclamptic women reflects reduced venous storage capacity. To test this hypothesis, we compared circulatory and autonomic responses to acute volume loading between women with low and those with normal plasma volume. In 24 normotensive formerly preeclamptic women at least 6 months postpartum, we administered 500 mL of iso-oncotic fluid by constant intravenous infusion in 30 minutes, while recording changes in heart rate, blood pressure, cardiac output, and measuring active plasma renin and alpha-atrial natriuretic peptide concentrations. We estimated arterial sympathetic control, cardiac autonomic regulatory balance, and baroreflex sensitivity using spectral analysis. Intergroup and intragroup changes were analyzed nonparametrically. 17 women (71%) had low plasma volume and 7 (29%) had normal plasma volume. Plasma volume expansion induced comparable changes in blood pressure, heart rate, baroreflex sensitivity, and active plasma renin concentration in low plasma volume and normal plasma volume. Cardiac output and alpha-atrial natriuretic peptide increased in low plasma volume but not in normal plasma volume. Volume expansion reduced sympathetic activity ( from 2.41 to 1.76 mm Hg(2), P = .03) in normal plasma volume but not in low plasma volume ( from 2.72 to 2.48 mm Hg(2), P > .05). The sympathoinhibitory response to volume expansion is diminished in low plasma volume, which suggests that cardiovascular reflex function is impaired. We speculate that this defect contributes to circulatory maladaptation to pregnancy, sympathetic dominance, and the development of gestational hypertensive disease.

Cardiac Adaptation to Pregnancy in Women with a History of Preeclampsia and a Subnormal Plasma Volume

In former preeclamptics, a subnormal plasma volume (LPV) predisposes to hemodynamic maladaptation to pregnancy. Here, we assessed the initial cardiovascular response to pregnancy in LPV (n = 20), in former preeclamptics with normal plasma volume (NPV) (n = 35) and in parous controls (CONTR) (n = 9) by echocardiography, blood pressure and heart rate (HR), before pregnancy, and by 5 and 7 weeks amenorrhea. Data analysis was by nonparametric tests. LPV differed from NPV and CONTR, by a consistently lower E/A ratio (ratio of peak mitral flow velocity in early diastole [E] and that during atrial contraction [A]) and an early-pregnancy rise in left atrial diameter (LAD). Both NPV and LPV differed from CONTR by an early-pregnancy rise in HR. The consistently lower E/A ratio together with the early-pregnancy LAD rise in LPV indicate diastolic dysfunction. The early-pregnancy rise in HR suggests sympathetic dominance in the autonomic control of the circulation.

Rituximab in the Treatment of Acquired Hemophilia a (AHA): A Novel Eradicating Therapy?

Background: Acquired inhibitors against factor VIII (FVIII), also termed Acquired Hemophilia A (AHA), occur rarely in the nonhemophilic population. Its incidence is approximately 1 to 4 per million/year. The incidence of AHA increases with age and a major peak is seeing in patients aged 68 to 80 years. These autoantibodies are associated with high rate of morbidity (90% of severe bleeding in affected patients) and mortality (8–22% of the cases). The diagnosis of AHA is based on the demonstration of an isolated prolongation of the activated partial thromboplastin time (APTT), not corrected by incubating the patient's plasma with equal volumes of normal plasma (mixing study), associated with FVIII reduced levels and formal evidence of a FVIII inhibitor in a patient with no previous personal or family history of bleeding. In approximately half of affected patients there is no identification of relevant concomitant diseases. The bleeding pattern in AHA is characterized by hemorrhages into the skin, muscles or soft tissues, and mucous membranes. Rituximab (Mabthera®; Roche; Switzerland) is a chimeric monoclonal antibody against the pan B-cell antigen CD20 that induces a rapid in vivo depletion of normal B lymphocytes. Primarily developed to treat B-cell non Hodgkin Lymphomas, more recently, Rituximab has demonstrated effectiveness in a number of autoantibody-mediated diseases including AHA. Case Report: We treated a 69-year-old diabetic and hypertensive patient with AHA. In March 2007, the diagnosis was made by a prolonged APTT (ratio 2.74 sec), not corrected by the mixing study, and FVIII inhibitor 320 Bethesda units. The patient had no evidence of malignancy, autoimmune disease or use of drugs. His bleeding manifestations were large ecchymosis of upper and lower extremities for almost a year, and at admission to the hospital, a hematoma of left calf and gengival bleeding. First line therapy consisted of steroids and cyclophosphamide (CFM). The steroids had to be withdraw after one week of use, because of very difficult glycemic control. The CFM were use in the dose of 50mg/day adding an total accumulative dose of 3g. This protocol were used considering the incapacity of the patient to tolerate higher dose of CFM due to leukopenia. After treatment, the patient was evaluated and neither normalization of APTT nor improvement of clinical findings happened. Therefore, considering all the above, it was decided to use Rituximab 375mg/m2, weekly, for four weeks. In June 2007, the patient received and tolereted very well all the infusions. In August 2007, he had no bleeding symptoms and his APTT was normal. At his laterest visit to the clinic in July 2008, an year after finishing his treatment, he was still very well and his bleeding tests were normal.Conclusion: Rituximab should be considered a treatment option for AHA.

The Relation Between Venous Reserve Capacity and Low Plasma Volume

Prepregnant low plasma volume (LPV) is associated with subsequent gestational hypertensive disease. It is unknown to what extent an LPV affects the venous reserve capacity (VRC). We tested the hypothesis that LPV reduces the VRC, as indicated by presyncope or altered cardiovascular changes in response to head-up tilt. In 52 nonpregnant women with a history of preeclampsia or recurrent miscarriage, the authors assessed plasma volume, stroke volume, and cardiac output and determined blood pressure, heart rate, and autonomic responses to stepwise inflicted head-up tilt. 12 participants had LPV, which related to presyncope when compared with subjects with normal plasma volume (NPV). Women with LPV without presyncope demonstrated a circulatory response comparable to NPV women at the expense of consistently higher heart rate. LPV decreases the capacity to cope with head-up tilt without affecting the response pattern, suggesting reduced VRC.

Quantitative Analysis of Fluid Balance During Abdominal Surgery

Surgical injury causes acute sequestration of interstitial fluid in injured tissue. Fluid sequestration treated with IV fluid administration can lead to postoperative complications related to excessive intravascular volume. Quantitative prediction of interstitial fluid sequestration may foster a better understanding of the relationship between fluid administered and the resulting balance between intra- and extravascular fluid. We developed a mathematical model describing the dynamic distribution and transport of fluid and proteins with the goal of quantifying the balance of fluid between intra- and extravascular compartments. Fluid volume changes in the plasma, interstitial and urine compartments were calculated for a simulated 4 h abdominal surgery in a 70 kg male. To validate the model, we compared the results obtained with those measured by segmental bioelectrical impedance on 30 patients undergoing elective abdominal surgery. The model predicted that, compared to the normal state, surgical injury would result in the sequestration of 705 mL of interstitial fluid in injured tissue, whereas plasma volume would undergo a 356 mL decrease. During surgery, it was not possible to obtain a normal plasma volume, even with fluid replacement at a rate of almost 20 mL x kg(-1) x h(-1). Bias and limit of agreement on interstitial fluid volume changes in body segments between bioelectrical impedance and model prediction were -131 and 325 mL, respectively for limbs, and -157 and 834 mL for the trunk. The model shows that increasing the fluid replacement rate above 10 mL x kg(-1) x h(-1) does not have the desired effect on plasma volume but instead increases the interstitial volume.

A Low Plasma Volume in Formerly Preeclamptic Women Predisposes to the Recurrence of Hypertensive Complications in the Next Pregnancy

Formerly preeclamptic women with a subnormal plasma volume (PV) have an increased risk to develop a hypertensive disorder in a subsequent pregnancy as compared to women with normal PV. In the current study we tested the hypothesis that formerly preeclamptic women who develop recurrent disease in their next pregnancy differ from their counterparts with an uneventful next pregnancy by a lower pre-pregnant PV, a lower venous capacitance, smaller rises in these indices in early pregnancy, a lower renal adaptive response, and a lower response to mild exercise. We enrolled 33 formerly preeclamptic women in this study. Only 14 conceived within the study period, with seven of them developing a recurrent hypertensive disorder in their next pregnancy (RECUR), while seven had an uneventful next pregnancy (NORM). Before pregnancy and at 12 weeks of gestational age, we compared the following variables between these subgroups: PV, venous capacitance, effective renal plasma flow (ERPF), glomerular filtration rate (GFR), and the responses in stroke volume (SV) and heart rate (HR) to mild exercise. To estimate venous capacitance, we infused 500 mL of a modified gelatine solution in 30 minutes while recording the change in cardiac output (pulse contour analysis). The ratio of percent change in blood volume to percent change in cardiac output in response to a standardized small volume load provides an estimate for venous capacitance. RECUR differed from NORM by a 20% lower pre-pregnant PV (P <.02) and venous capacitance (0.29 [0.11-0.55] vs 0.86 [0.64-2.03] P = .002). NORM and RECUR were comparable with respect to pregnancy-induced rise in PV, renal hemodynamics and function, and response to mild exercise at 12 weeks. Newborn weight correlated positively with pre-pregnancy PV (R(2) = 0.53 and P = .04). Formerly preeclamptic women with a recurrent hypertensive disorder in their next pregnancy differed from their counterparts with an uneventful next pregnancy by a lower pre-pregnant PV and a lower venous capacitance, the latter two indices correlating also inversely with the incidence of fetal growth restriction. The preserved acute response to volume-related stimuli in women with a low pre-pregnant PV supports the view that the predisposition of low pre-pregnant PV to adverse pregnancy outcome may result from a concomitant, PV-dependent change setpoint and/or gain in the stimulus/response interrelation of the volume regulatory system.

Plasma volume expansion and transcapillary fluid exchange in skeletal muscle of albumin, dextran, gelatin, hydroxyethyl starch, and saline after trauma in the cat*

To compare 5% albumin, 6% dextran 70, 3.5% gelatin, 6% hydroxyethyl starch 130/0.4, and saline regarding their plasma volume expanding effect after a surgical skeletal muscle trauma and their simultaneous effects on transvascular fluid exchange in skeletal muscle. Controlled, prospective, randomized laboratory study. University research laboratory. Thirty-six adult cats. Systemic arterial pressure and tissue volume variations of and blood flow to a surgically isolated and autoperfused calf muscle placed in a plethysmograph were recorded. Arterial and venous pressures to the muscle were kept constant. After preparation, plasma volumes were determined by a I albumin tracer technique just before and 3 hrs after a bolus infusion of the plasma expander (25 mL/kg). Plasma volume was 20.9 +/- 2.9 mL/kg (n = 36) just before infusion of the plasma expander (normal plasma volume for the cat is 34-37 mL/kg). The remaining volume expansion of the infusion after 3 hrs was 6.8 mL/kg for albumin, 11.2 mL/kg for dextran, 1.8 mL/kg for gelatin, 2.2 mL/kg for hydroxyethyl starch, and 0.9 mL/kg for saline. Plasma volume decreased by 1.1 mL/kg when no solution was given (n = 6 per group). Colloid osmotic pressure was better preserved with dextran and albumin than with the other solutions. Albumin and dextran reduced muscle volume by absorption after 3 hrs, whereas the initial absorption turned to net filtration in the gelatin and hydroxyethyl starch groups. Saline infusion increased muscle volume by filtration for about 20 mins, followed by an approximately constant volume. The relatively poor plasma expansion for all solutions analyzed can most likely be explained by increased transcapillary leakage due to increased microvascular permeability following trauma. Under such circumstances, for equal volumes, plasma expansion was better preserved with 6% dextran 70 than with 5% albumin, which was better than 3.5% gelatin, 6% hydroxyethyl starch 130/0.4, and saline.

Uterus myomatosus als Ursache für Erythrozytose

Myoma-induced erythrocytosis is a rare clinical picture which is probably largely misunderstood. Pre- and postmenopausal women are affected. The characteristics of this syndrome are raised haemoglobin and haematocrit values, erythrocytosis at normal plasma volumes and the fact that these values are promptly and permanently corrected by myomectomy or hysterectomy. Myomatous erythrocytosis syndrome (MES) can be the explanation of normal haematological parameters in patients with myoma-related hypermenorrhoea and menorrhagia.

Low Plasma Volume Coincides With Sympathetic Hyperactivity and Reduced Baroreflex Sensitivity In Formerly Preeclamptic Patients

Preeclampsia is associated with enhanced sympathetic activity as well as subnormal plasma volume. Meanwhile, in over 50% of these complicated pregnancies, the subnormal plasma volume has been found to persist for a prolonged period after pregnancy. The objective of this study is to test the hypothesis that in normotensive formerly-preeclamptic women, persistence of a subnormal plasma volume coincides with enhanced sympathetic activity and with it, an altered autonomic control of blood pressure. Forty-eight formerly-preeclamptic women participated in this study. After measurement of their plasma volume by iodine 125-albumin indicator dilution, they were subdivided into a group with a normal plasma volume (plasma volume > 48 ml/kg lean body mass) and a group with a subnormal plasma volume (< or = 48 ml/kg lean body mass). We performed spectral analysis on their beat-to-beat blood pressure and heart rate recordings and compared both groups using non-parametric tests. Formerly-preeclamptic women with a subnormal plasma volume had a higher sympathetic activity (P = .001) and a lower baroreflex sensitivity (P = .04) than their counterparts with a normal plasma volume. In normotensive formerly-preeclamptic women, a subnormal plasma volume coincides with a higher sympathetic activity in the blood pressure regulation and lower baroreflex sensitivity. Whether these alterations in the autonomic control mechanisms are a cause or effect of the subnormal plasma volume remains to be elucidated.

Formerly Preeclamptic Women With a Subnormal Plasma Volume Are Unable to Maintain a Rise in Stroke Volume During Moderate Exercise

In formerly preeclamptic women with a low plasma volume, the recurrence rate of preeclampsia is higher than in women with a normal prepregnant plasma volume. In a recent study, we demonstrated that the low plasma volume subgroup also had a subnormal venous capacitance. In the present study, we determined the impact of subnormal plasma volume on the hemodynamic response to moderate exercise. We performed this study in the follicular phase of the menstrual cycle, in 31 formerly preeclamptic women with a subnormal plasma volume (low-PV) and eight parous controls. The exercise consisted of 60 minutes of cycling in the supine position at 35% of the individualized maximum capacity. Before, during, and after cycling, we measured the percentage change in heart rate, stroke volume, and cardiac output. Before and after exercise, we measured the effective renal plasma flow (ERPF, para-amino-hippurate [PAH] clearance), glomerular filtration rate (GFR, inulin clearance), circulating levels of alpha-atrial natriuretic peptide (alpha-ANP), and active plasma renin concentration (APRC). The response to exercise of formerly preeclamptic women with a subnormal plasma volume differed from that in controls by a lack of rise in stroke volume, a smaller rise in cardiac output and alpha-ANP, and a greater fall in GFR. The responses in heart rate, ERPF, and APRC did not differ between the two groups. The response to moderate exercise of formerly preeclamptic women with a subnormal plasma volume differs from that in healthy parous controls with a normal plasma volume and suggests a lower capacity to raise venous return in conditions of a higher demand for systemic flow. The lower capacity to raise venous return in these conditions is associated with more cardiovascular drift. The physiologic consequence is a lower aerobic endurance performance during moderate exercise.

Maternal Hemoglobin Concentration during Pregnancy and Risk of Infant Leukemia.

Little is known about the etiology of childhood leukemia. Elevated birth weight (> 4000 g) is gaining acceptance as a risk factor, particularly for children diagnosed < 2 years of age, but the underlying biological or physiological explanation for this association has yet to be defined. At least three recent studies have demonstrated a positive association with childhood leukemia and maternal anemia during pregnancy. Physiologic anemia of pregnancy, which results from normal plasma volume expansion, is thought to produce optimal blood viscosity for the low flow area of the placenta and is associated with the highest average birth weights in the offspring. We therefore hypothesized that maternal physiologic anemia of pregnancy would have a positive association with infant leukemia. To test this hypothesis, we utilized data from a case-control study conducted by the Children's Oncology Group (COG) that consisted of 240 incident cases of acute infant leukemia (< 12 months of age) diagnosed between 1996 and 2002 and 255 controls obtained by random digit dialing. Maternal blood counts were obtained by medical record abstraction. Information regarding the patients' diagnoses and cytogenetic/molecular abnormalities were obtained from COG institutions. Physiologic anemia of pregnancy was defined as a hemoglobin concentration of < 11 g/dL in the second or third trimester of pregnancy (WHO classification). Anemia earlier in pregnancy is more frequently due to nutritional deficiencies and can be associated with poor fetal outcomes and thus was excluded. Maternal hemoglobin values from the second or third trimester were available for 178 case and 180 control mothers. Data were analyzed using unconditional logistic regression. We found no evidence that physiologic anemia of pregnancy was associated with birth weight of > 4000 g (odds ratio (OR) 1.05, 95% confidence interval (CI)=0.55–1.99) Overall, the OR for physiologic anemia of pregnancy and risk of infant leukemia was 0.85 (95%CI=0.53–1.37). The association remained non-significant when cases were divided into acute myeloid leukemia (AML) (n=63) and acute lymphocytic leukemia (ALL) (n=115) with ORs of 0.64 (95%CI=0.32–1.30) and 0.98 (95%CI=0.58–1.66), respectively. The association was also not significant when cases were stratified by MLL gene abnormality status (OR=0.77; 95%CI=0.42–1.40 and OR=0.88; 95%CI=0.45–1.73, for cases with (n=92) and without (n=62) an MLL gene abnormality, respectively). These associations remained non-significant when the data were adjusted for birth weight, maternal race, and birth order. More stringent criteria for anemia also did not modify the results. We found no evidence for an increased risk of infant leukemia in the offspring of mothers with physiologic anemia of pregnancy. This work was supported by NIH R01 CA79940 and the Children's Cancer Research Fund.