Plasma Hyperviscosity Research Articles

Aspartame induced dyslipidemia and plasma hyperviscosity in Albino Wistar rats

Aspartame is a low-calorie sweetener that has been used for decades in place of sugar. However, there has been conflicting reports on the use and safety profile of aspartame associated with several diseases especially cancer and cardiovascular diseases. This study therefore aims to determine the effects of aspartame on some cardiovascular indices. Thirty seven (37) young Albino Wistar rats weighing between 110g-140g were used for this study. The rats were divided into five groups; control (5) received 5 ml of distilled water. Group 1 (n=8) received 5 ml of diet soda, group 2 (n=8) received 5 ml diluted (1:1) diet soda, Group 3 (n=8) received 5 ml aspartame 45 mg/kg b.w, Group 4 (n=8) received 5 ml of aspartame 22.5 mg/kg b.w. The various doses of aspartame and diet soda were administered orally daily for ten weeks. Weight of the rats were taken weekly, at the end of the experimental period, the rats were sacrificed and blood samples collected into plain sample bottles and tri sodium citrate bottles. Lipid profile (total cholesterol, HDL-C, LDL-C &.triglyceride) were analyzed spectrophotometrically, fibrinogen and blood viscosity were also measured. Results showed that the aspartame and diet soda significantly increased total cholesterol, triglyceride, LDL-C, fibrinogen and plasma viscosity and significantly decreased HDL cholesterol. In conclusion, consumption of aspartame as a sweetener can impact negatively on cardiovascular haemodymic factors. Therefore, its intake should be discouraged.

Aspartame induced dyslipidemia and plasma hyperviscosity in Albino Wistar Rats

Aspartame is a low-calorie sweetener that has been used for decades in place of sugar. However, there has been conflicting reports on the use and safety profile of aspartame associated with several diseases especially cancer and cardiovascular diseases. This study therefore aims to determine the effects of aspartame on some cardiovascular indices. Thirty seven (37) young Albino Wistar rats weighing between 110g-140g were used for this study. The rats were divided into five groups; control (5) received 5 ml of distilled water. Group 1 (n=8) received 5 ml of diet soda, group 2 (n=8) received 5 ml diluted (1:1) diet soda, Group 3 (n=8) received 5 ml aspartame 45 mg/kg b.w, Group 4 (n=8) received 5 ml of aspartame 22.5 mg/kg b.w. The various doses of aspartame and diet soda were administered orally daily for ten weeks. Weight of the rats were taken weekly, at the end of the experimental period, the rats were sacrificed and blood samples collected into plain sample bottles and tri sodium citrate bottles. Lipid profile (total cholesterol, HDL-C, LDL-C and triglyceride) were analyzed spectrophotometrically, fibrinogen and blood viscosity were also measured. Results showed that the aspartame and diet soda significantly increased total cholesterol, triglyceride, LDL-C, fibrinogen and plasma viscosity and significantly decreased HDL cholesterol. In conclusion, consumption of aspartame as a sweetener can impact negatively on cardiovascular haemodymic factors. Therefore, its intake should be discouraged.

SAT-484 Pituitary Microadenoma and Cerebral Venous Thrombosis in a Patient with Transient Adipsic Diabetes Insipidus after Treatment for Craniopharyngioma

Background Craniopharyngioma is a rare embryonic sellar malformation, that can present with headache, motor and cranial nerve palsies. Treatment of large masses involves surgical excision followed by radiation therapy. Hypopituitarism and diabetes insipidus are some of the post-operative complications. Rarely, patients may develop inability to appreciate fluid losses, resulting in marked hypernatremia and dehydration associated with life-threatening lower extremity thrombosis and pulmonary embolism. We present a patient developing cerebral venous thrombosis resulting from transient adipsic diabetes insipidus accompanied by new-onset pituitary microadenoma. Clinical A 39-year-old female post-excision and radiation therapy for craniopharyngioma developed hypopituitarism and diabetes insipidus. Three months after initiating radiotherapy, she presented with headache and inability to sense thirst. She took desmopressin 100 mcg tablet only three times for the past month. There was hypernatremia at 154 meq/L (Normal Value 135-145 meq/L) and hyperprolactinemia at 235 ng/mL (NV 5.11-26.19 ng/ml). Contrast-enhanced MRI revealed cerebral venous thrombosis and a pituitary microadenoma. Thrombosis has been attributed to plasma volume contraction and consequent plasma hyperviscosity. She was started on enoxaparin, hydration with hypotonic solution, desmopressin 100 mcg tablet and bromocriptine 2.5 mg tablet for the possibility of new-onset prolactin secreting pituitary microadenoma. There was decrease in headache severity and normalization of sodium level. She was discharged on apixaban 2.5 mg tablet twice a day, bromocriptine, levothyroxine 100 mcg tab daily, desmopressin daily or at least twice a week and hydrocortisone 20 mg tab daily. After three months, she had increased ability to sense thirst but still had occasional headaches. Imaging showed partial resolution of thrombosis. Prolactin decreased to 0.925 ng/mL (NV 3-20 ng/ml). In general, prolactinomas have serum prolactin that parallel tumor size. Rarely, minimal prolactin elevations may be consistent with a prolactinoma, but a non-prolactin secreting mass should first be considered in the presence of a microadenoma. The initially elevated prolactin has been attributed to disruption of dopamine inhibition to the pituitary lactotrophs. Serial imaging of the pituitary microadenoma appears to be a reasonable follow-up. Prompt evaluation must be done should there be any signs and symptoms of hormonal hypersecretion or if there is increase in size of the microadenoma. Conclusion This is the first case to demonstrate cerebral venous thrombosis and new-onset pituitary microadenoma in a patient developing transient adipsic diabetes insipidus after treatment for craniopharyngioma. These entities must be included in the workup of patients presenting with headache. No relevant disclosures.

Clinical conditions responsible for hyperviscosity and skin ulcers complications

In this brief review, we have examined some clinical conditions that result to be associated to an altered hemorheological profile and at times accompanied by skin ulcers. This skin condition may be observed in patients with the following condtions, such as primary polycythemic hyperviscosity (polycythemia, thrombocytemia) treated with hydroxyurea, primary plasma hyperviscosity (multiple myeloma, cryoglobulinemia, cryofibrinogenemia, dysfibrinogenemia, and connective tissue diseases), primary sclerocythemic hyperviscosity (hereditary spherocytosis, thalassemia, and sickle cell disease). In addition, it may be present in patients with secondary hyperviscosity conditions such as diabetes mellitus, arterial hypertension, critical limb ischemia and chronic venous insufficiency.

Association between hemorheological alterations and metabolic syndrome

The contribution of hemorheological alterations in the prothrombotic condition in patients with metabolic syndrome (MS) remains a question of debate. We aimed to determine the association between MS and hemorheological parameters by means of a case-control study in 61 MS patients and 89 controls without MS. We determined blood viscosity at 230 s(-1) (Brookfield DVIII viscosimeter); plasma viscosity (Fresenius capillary plasma viscosimeter); erythrocyte aggregation at stasis and 3 s(-1) (MA-1 erythrocyte aggregometer); erythrocyte deformability (Rheodyn SSD at shear stresses of 12, 30 and 60 Pascals) and fibrinogen, along with anthropometric, lipidic and inflammatory parameters. MS patients showed increased blood viscosity (p = 0.018), plasma viscosity (p < 0.001), fibrinogen (p < 0.001), erythrocyte aggregation (p < 0.001), and decreased erythrocyte deformability (p = 0.033). In the multivariate regression analysis, fibrinogen and triglycerides predicted plasma viscosity and erythrocyte aggregability, whereas erythrocyte deformability was associated with alterations in the hydrocarbonate metabolism. Blood viscosity related to abdominal obesity. The logistic regression analysis revealed that of all the MS components, only hypertriglyceridemia independently predicts plasma hyperviscosity (OR 3.75 CI 1.44-9.77 p = 0.007) and erythrocyte hyperaggregability (OR 2.41 CI 1.00-5.80 p = 0.050). Erythrocyte hyperaggregability (EA > 8.23) and hyperfibrinogenemia (fibrinogen > 358 mg/dL) were independent predictors of MS: OR 3.34, 95% CI 1.40-7.93, p = 0.006 and OR 2.42 95% CI 1.04-5.66, p = 0.041, respectively. We conclude that MS is associated with an altered hemorheological profile related to inflammatory, lipidic and glucose intolerance parameters which could favor the development of thrombo-embolic and athero-thrombotic events in MS patients.

The plasma hyperviscosity syndrome as an oncological emergency

Drug Prescribing for Patients with Chronic Kidney Disease in General Practice: a Cross-Sectional Study

Military Cold Injury During the War in The Falkland Islands 1982: An Evaluation of Possible Risk Factors

Throughout the history of war, there have been many instances when the cold has ravaged armies more effectively than their enemies. Delineated risk factors are restricted to negro origins, previous...

Influence of ACTH-(1-24) and plasma hyperviscosity on free radical production and capillary perfusion after hemorrhagic shock.

The authors investigated the effects of ACTH-(1-24) and a high-viscosity solution in the restoration of microvascular function during resuscitation. They injected NG-monomethyl-L-arginine (L-NMMA) and superoxide dismutase (SOD) before ACTH-(1-24) in hamsters resuscitated with the hyperviscous solution to determine the role of ROS and NO in ACTH-(1-24) protective mechanism in the cheek pouch. Hemorrhagic shock (HS) was induced by withdrawing blood to reduce mean arterial pressure (MAP) to 30 mm Hg for 45 min. Animals were injected with ACTH-(1-24) and resuscitated with dextran of low molecular weight (70 kDa) and a small amount (4%) of dextran of high molecular weight (500 kDa) plus ACTH-(1-24), or autologous (shed) blood withdrawn during HS. Microvascular effects were characterized by measuring blood flow, perfused capillary length (PCL), arteriolar diameter, and red blood cell (RBC) velocity. ROS were assayed at the beginning and after 45 min of HS and after 10 and 90 min of resuscitation. Resuscitation with either shed blood or dextrans 70/500 resulted in the restoration of MAP, whereas PCL, RBC velocity, and arterial diameter decreased significantly. ROS increased significantly after HS, 10 and 45 min of resuscitation. ACTH-(1-24) plus dextrans 70/500 increased MAP immediately; it increased vasodilation and PCL, and attenuated significantly ROS production and leukocyte adhesion during resuscitation. L-NMMA injected after 30 min of HS did not change the protection exerted by ACTH-(1-24) and dextrans 70/500, while SOD increased their protective effects. ACTH-(1-24) appears to enhance the protective effects on the endothelium exerted by increased plasma viscosity by significantly decreasing the oxidative stress and the leukocyte adhesion during resuscitation.

Le « syndrome des jambes lourdes » chez les athlètes surentraînés est-il le reflet de désordres hémorhéologiques ?

Introduction. – The aim of this work is to evaluate if the feeling of heavy legs in athletes is correlated with overtraining syndrome-related hemorheological disturbances. Results. – The subjects who quoted the item: “I have the feeling of heavy legs” had higher plasma viscosity and higher red cell aggregation parameters. The overtraining score was correlated positively with plasma viscosity, and aggregability parameters. The feeling of heavy legs was correlated with plasma viscosity and aggregability. Conclusion. – These findings suggest that the feeling of heavy legs in overtrained athletes is related to overtraining syndrome-related hemorheologic disturbances, namely mild plasma hyperviscosity and mild erythrocyte hyperaggregability.

Clinical application of therapeutic erythrocytapheresis (TEA)

Therapeutic erythrocytapheresis (TEA) has been used in different diseases such as polycythemia vera (PV), secondary erythrocytosis or hemochromatosis as a process of the less cumbersome but more expensive phlebotomy. TEA is preferred in emergency conditions such as thrombocytosis or in conditions such as porphyria cutanea tarda (PCT) or erythropoietic porphyria when plasma exchange (PEX) is often combined with TEA to reduce extracellular levels of uroporphyrin which contribute to plasma hyperviscosity. TEA is often combined with drug therapy that varies from etoposide in PV to EPO and desferoxamine which are used to mobilize and reduce iron stores in hemochromatosis. Benefits from this combination may be more long lasting than expected. Nonetheless for TEA, there is no standard protocol and, clinical experience with this therapy remains highly anecdotal. Therapeutic red cell-exchange (TREX) has been used with much interest over the years, starting with the management of hemolytic disease of the newborn and later used to correct severe anemia in thalassemia patients thereby preventing iron overload. It has also been used for the management of complications of sickle cell disease such as priapism, chest syndrome, stroke, retinal, bone, splenic and hepatic infarction or in preparation for surgery by reducing HbS to less than 30%. Automated apheresis has also favored the use of TREX in conditions such as paroxysmal nocturnal hemoglobinuria and aniline poisioning, arsenic poisioning, Na chlorate intoxicatons and CO intoxications, hemoglobinopathies, autoimmune hemolytic anemia, reactions due to ABO incompatibility, in preparation for ABO incompatible bone marrow transplantation or for preventing anti-D immunization after the transfusion of D + cells to D − recipients. Another field of application has been in the emergency management of intraerythrocytic parasite infections such as malaria and babesiosis. Application of TREX may be wide but its real use remains limited. In our personal experience, in 16 years, only 167 TREX procedures have been carried out in a total of 13,747 therapeutic procedures. This represents only 1.21% of the total.

Factors involved in the biochemical etiology of human seminal plasma hyperviscosity.

Semen rheology was studied to elucidate the biochemical basis of seminal plasma hyperviscosity. Semen proved to fit in with a power law model, by presenting a pseudoplastic behavior. Apparent viscosity at 230 s(-1) and 25 degrees C (eta(a)) was 4.3 /- 0.2 cp and 5.4 +/- 0.4 cp in normal and high-consistency semen, respectively. The effect of enzymes and mucolytic agents on human seminal plasma viscosity were evaluated by incubating normal and hyperviscous semen pool aliquots with trypsin, dithiothreitol, EDTA, alpha-amylase and deoxyribonuclease I. After incubation, trypsin treatment reduced eta(a) by 36% in normal semen and by 44% in hyperviscous semen. There was a decrease in eta(a) following incubation of hyperviscous samples with dithiothreitol (33%) and alpha-amylase (44%) that was not observed in the normal consistency samples. No decrease was observed in eta(a) after EDTA or DNAse treatment of both groups. Comparison of normal and hyperviscous seminal plasmas revealed no difference in the concentration of total proteins, DNA, or in the percentage of water content. These findings indicate that the primary substances responsible for basic normal semen rheologic behavior are proteins. A comparison of rheological properties between normal and hyperviscous semen samples indicates the existence of a highly organized network in the latter group, in which disulfide bonds and oligosaccharide chains complexed to the peptide core may play a key role.

Hemorheological changes and overproduction of cytokines from immune cells in mild to moderate dementia of the Alzheimer’s type: adverse effects on cerebromicrovascular system.

An association between hemorheological alterations (i.e., whole-blood and plasma hyperviscosity, reduced erythrocyte deformability, increased red cell aggregation, hyperfibrinogenemia and increased acute-phase protein levels) and the mild stage of senile dementia of the Alzheimer’s type (DAT) was suggested in the present study. In particular, hyperfibrinogenemia and the increase of erytrhocyte aggregation were correlated with the increased generation and release of TNF-α and IFN-γ (spontaneous release and IL-2-modulated release) from natural killer (NK) lymphocytes (CD16+, CD56+, CD3- cells) of patients with DAT; whereas a normal cytokine release from NK cells was found in healthy old subjects and in patients with vascular dementia (VaD). The in vitro and in vivo administration of the hemorheologic drug pentoxifylline (PTX) significantly reduced spontaneous and IL-2-modulated cytokine overproduction from NK cells (in vitro effects with 500 U/ml and 1000 U/ml/NK cells) and improved all the hemorheological parameters. Taken together, these data suggest that disturbances of cerebrovascular flow and of hemorheology could be considered a negative component related to the pathogenesis and progression of DAT neurodegeneration. The association between hemorheological changes and alterations of TNF-α and IFN-γ release from NK may indicate a potential immunorheologic mechanism associated with cerebrovascular damage in DAT and could suggest the use of vascular protective drugs as support of the main pharmacological and non-pharmacological therapy of AD.

Effects of red blood cell hyperaggregation on the rat microcirculation blood flow.

This study presents the effects of red blood cell (RBC) hyperaggregation on the blood flow and pressure in the rat mesentery and cremaster network. We exclusively studied in situ non-vasodilated organs, in order to maintain the physiological regulation mechanisms. Dextran 500 was injected at different concentrations to increase RBC aggregation. The aggregation rate was measured on very small blood samples with an erythroaggregameter (SEFAM) which evaluated the disaggregating shear stress (tau D) needed to break the RBC aggregates. Microscopic observations and laser Doppler velocimetry were used to quantify the flow rate. The plasmatic dextran concentration (C) increase had different correlated effects: for example, tau D increased from 3 dynes cm-2 (for the control sample) to 14 dynes cm-2 (for C = 75 microM L-1); the flow rate was reduced threefold and very large aggregates were observed in the venules; the arteriolar pressure increased while venular pressure decreased. In order to differentiate the effects of RBC hyperaggregation from those of plasma hyperviscosity (due to dextran 500) on microcirculatory blood flow, we injected an RBC antiaggregating drug (troxerutine) (50 or 100 mg kg-1 i.v.). The consequences were a high reduction for (tau D) (from 14 dynes cm(-2)-9 dynes cm-2), smaller aggregates and higher blood flow in the venules. No effect of troxerutine was observed on plasma viscosity (plasma control: 1.9 cP with or without troxerutine; plasma with dextran at C = 75 microM L-1: 2.45 cP with or without troxerutine). The results strongly suggest that RBC aggregation has a significant influence on blood flow rate in the microcirculatory network.

Does colloid-induced plasma hyperviscosity in haemodilution jeopardize perfusion and oxygenation of vital organs?

The infusion of dextran solutions is associated with haemodilution and, under some conditions, with a slight increase in plasma viscosity. To clarify the compound effects of simultaneous haemodilution and plasma viscosity increases on macro- and microhaemodynamics, we investigated the changes in arterial perfusion (radiolabelled microspheres, 15 microns ø) and oxygenation (tissue Po2) of vital organs using an animal model of plasma hyperviscosity. In nine splenectomized beagles plasma viscosity was increased step by step from 1.06 (baseline) to 2.14, and 2.99 mPa.s by infusion of small amounts (4% of total blood volume) of an ultra-high-molecular-weight dextran (50% w/v, mw: 500,000). Despite the significant increase in plasma viscosity, cardiac output as well as specific organ blood flows in heart, brain, liver, and muscle rose steadily with each step of viscosity, while the haematocrit declined from 0.31 to 0.24 and 0.20, respectively. Medians of tissue Po2 in liver peaked at a viscosity of 2 mPa.s and returned to baseline values at 3 mPa.s, whereas in non-working skeletal muscle Po2 values were maximal at 3 mPa.s. These results indicate that the impact of plasma viscosity on the rheological properties of whole blood is completely offset by the concomitant reduction of haematocrit. Thus, the comparatively minor changes in plasma viscosity observed after prolonged use of clinical dextrans and other colloids in no way compromise the perfusion and oxygenation of vital organs.

Effect of Oral Administration of Sulodexide on Fibrinolysis and Plasma Viscosity: A Pilot Study

The purpose of this pilot study was to examine the effects of a new enteric-coated formulation of sulodexide, a glycosaminoglycan extracted from mammalian intestine, on blood, plasma and serum viscosity, and fibrinolysis in patients with plasma hyperviscosity. Six outpatients with plasma viscosity exceeding 1.40cP were administered oral sulodexide 100mg once daily for 7 days. On days 1 and 7 whole blood and plasma viscosity were measured before administration of sulodexide and 2, 4 and 8 hours after drug administration; at the same time functional and antigenic PAI (plasminogen activator inhibitor) and functional and antigenic tPA (tissue plasminogen activator) were evaluated to investigate the fibrinolytic balance of patients.

Ticlopidine Lowers Plasma Fibrinogen in Patients with Polycythaemia Rubra Vera and Additional Thrombotic Risk Factors

Thirty-seven patients affected by polycythaemia rubra vera (PRV) and with at least one additional thrombotic risk factor (overt vascular disease, diabetes mellitus, treated hypertension, smoking habit, plasma hyperviscosity, hyperfibrinogenemia) were enrolled in a double-blind randomized placebo-controlled study, and 18 were given ticlopidine 250 mg, b.i.d., for 60 days. All the patients had previously been submitted to cytoreduction, and PRV was under control in all cases at the start of the study. During the study, the haematological parameters were controlled every 15 days, and venesection was performed if haematocrit was greater than 46%. Whole blood viscosity, at low and high shear rates, plasma viscosity, and fibrinogen were measured on days 0 and 60. In the ticlopidine group, we recorded a significant 13.14% reduction of the mean fibrinogen level after treatment (390 +/- 63 vs. 449 +/- 97 mg/dl, p less than 0.01). All the other haemorheological parameters were not significantly modified by ticlopidine treatment, nor were there significant modifications recorded in the placebo group. Our study shows that ticlopidine may reduce a probable thrombotic risk factor (hyperfibrinogenemia) in PRV patients.

HIV infection associated with the plasma hyperviscosity syndrome

HIV infection associated with the plasma hyperviscosity syndrome

Myeloma--the integral role played by the professional nurse.

Myeloma is a malignancy of plasma cells which are terminally differentiated B-lymphocytes. The diagnosis may be made incidentally at routine blood testing, when an abnormality is found in the plasma proteins on electrophoresis. More usually the patients are symptomatic, with bone pain, anaemia, evidence of renal failure, or the metabolic abnormalities associated with increased plasma calcium and urate levels. Effective treatment will extend survival from 7 to approximately 30 months and at the same time improve the quality of life. Treatment is multidisciplinary, prominently involves the professional nurse and may arbitrarily be divided into two stages. Firstly, reversible lesions, such as dehydration and plasma hyperviscosity must be corrected, hypercalcaemia and hyperuricaemia improved and, if necessary, renal dialysis undertaken. Secondly, but of equal importance, is the need for specific therapy to be directed against the tumour itself, and both cytotoxic agents and irradiation have an important role to play. More recently, newer approaches have included high dose chemotherapy and bone marrow transplantation.

Paraproteinaemias and platelet aggregation: Role of whole blood aggregometry

Whole blood and optical platelet aggregation were measured in normals and in patients with paraproteinaemias; extent of aggregation was correlated with paraprotein concentrations in patients and in normals after addition of different doses of paraproteins; threshold aggregating concentrations of several agonists were also determined in whole blood and in PRP from both groups of subjects. The results indicate that patients with macromolecular monoclonal component bear a “hyperaggregable” state which can be probably ascribed also to plasma hyperviscosity and which is better detected with the impedance aggregometer.

Is increased plasma viscosity a risk factor for high blood pressure?

Data from several epidemiologic studies have suggested that, among other variables, hematocrit and fibrinogen may constitute risk factors for high blood pressure. As part of a population survey for cardiovascular risk factors, plasma viscosity and hemoglobin were measured. Blood pressure was determined under standardized conditions according to the recommendations of the AHA. A two-stage age-sex-stratified cluster sample of 5,312 persons, aged twenty-five to sixty-four years, was selected from a mixed urban/rural target population of 282,279 (total population approximately 533,000). A net response of 79.3% was achieved. Multiple logistic regression analyses including plasma viscosity, hemoglobin, body mass index, alcohol consumption, smoking behavior, and total serum cholesterol as independent variables were run controlling for both age and sex. Plasma viscosity appeared as a significant main effect in all analyses and demonstrated the strongest association with high blood pressure next to body mass index. Whether this association implies a causal relationship cannot be answered from cross-sectional data. However, even if plasma hyperviscosity represents a secondary phenomenon in hypertension, it might be of prognostic relevance. There is evidence that increased plasma viscosity may contribute to myocardial hypertrophy. Therefore hypertensives with impaired blood fluidity might constitute a subgroup at particular risk for cardiovascular complications. When antihypertensive drugs are selected, their influence on blood viscosity should be taken into account.