Blood viscosity and the expression of inflammatory and adhesion markers in homozygous sickle cell disease subjects with chronic leg ulcers.

OBJECTIVE: To determine differences in TNF-α, IL-1ß, IL-10, sICAM-1 concentrations, leg hypoxia and whole blood viscosity (WBV) at shear rates of 46 sec(-1) and 230 sec(-1) in persons with homozygous S sickle cell disease (SCD) with and without chronic leg ulceration and in AA genotype controls. DESIGN: & METHODS: fifty-five age-matched participants were recruited into the study: 31 SS subjects without leg ulcers (SSn), 24 SS subjects with leg ulcers (SSu) and 18 AA controls. Haematological indices were measured using an AC.Tron Coulter Counter. Quantification of inflammatory, anti-inflammatory and adhesion molecules was performed by ELISA. Measurement of whole blood viscosity was done using a Wells Brookfield cone-plate viscometer. Quantification of microvascular tissue oxygenation was done by Visible Lightguide spectrophotometry. RESULTS: TNF-α and whole blood viscosity at 46 sec(-1) and 230 sec(-1) (1.75, 2.02 vs. 0.83, 1.26, p<0.05) were significantly greater in sickle cell disease subjects than in controls. There were no differences in plasma concentration of sICAM-1, IL-1ß and IL-10 between SCD subjects and controls. IL-1ß (median, IQR: 0.96, 1.7 vs. 0, 0.87; p<0.01) and sICAM-1 (226.5, 156.48 vs. 107.63, 121.5, p<0.005) were significantly greater in SSu group compared with SSn. However there were no differences in TNF-α (2, 3.98 vs. 0, 2.66) and IL-10 (13.34, 5.95 vs. 11.92, 2.99) concentrations between SSu and SSn. WBV in the SSu group at 46 sec(-1) and at 230 Sec 1 were 1.9 (95%CI; 1.2, 3.1) and 2.3 (1.2, 4.4) times greater than in the SSn group. There were no differences in the degree of tissue hypoxia as determined by lightguide spectrophotometry. CONCLUSION: Inflammatory, adhesion markers and WBV may be associated with leg ulceration in sickle cell disease by way of inflammation-mediated vasoocclusion/vasoconstriction. Impaired skin oxygenation does not appear to be associated with chronic ulcers in these subjects with sickle cell disease.

Maternal blood viscosity and perinatal outcome in steady-state homozygous sickle cell disease.

Homozygous sickle cell disease (HbSS) is a complicating factor in pregnancy resulting in perinatal morbidity and mortality. One of the hallmarks of sickle cell disease is increased whole blood viscosity. The present study was designed to investigate the effect of the maternal blood viscosity on perinatal outcome in steady-state homozygous sickle disease in 19 women admitted to the labor ward of the University Hospital of the West Indies, Mona. Whole blood viscosity was measured with the Wells-Brookfield viscometer at 370C at low (23 sec-1) and high (230 sec-1) shear rates. Measurements were done at native hematocrit. Perinatal outcome was classified as adverse if there was one or more of the following: admission to nursery, birth weight less than 2.5 kg, 5 minute Apgar score less than 7, caesarean section for fetal distress, perinatal death or death before discharge from nursery. The whole blood viscosity value (mean ± SD) at low shear rate was 2.04 ± 0.55 mPa.s and 2.96 ± 0.80 mPa.s at high shear rate. The hematocrit was 25.13 ± 4.18%. The perinatal outcome was good in 10 (53%) subjects and adverse in 9 (47%) subjects. There was no statistically significant difference in the incidence of adverse perinatal outcome between women with low and high blood viscosities in either the low or high shear rates. Similarly, low or high hematocrit did not significantly affect the incidence of adverse perinatal outcome. This could be attributed to their similarity in the whole blood viscosity and hematocrit values.

Alterations in hemorheological determinants and glycated hemoglobin in black diabetic patients with retinopathy.

Alterations of hemorheological determinants and glycated hemoglobin levels are prominent features of diabetic retinopathy, resulting in the increased whole-blood and plasma viscosities observed in this condition. These variables have been reported to show ethnic variations. The present study was designed to investigate the pattern of alterations in these variables and the possible influence of plasma viscosity in black diabetic retinopathy patients. Forty-two patients, who included 14 males and 28 females (mean age, 62.81 +/- 11.38 years) were studied. The control group consisted of 30 black, nondiabetic, age-matched subjects, including 10 males and 20 females. Relative plasma viscosity, plasma fibrinogen concentration, packed cell volume, and mean glycated hemoglobin were significantly higher in the diabetic subjects compared with the controls. We observed an increase in plasma viscosity in our study population, similar to those reported in previous studies for Caucasians.

Segmental blood flow and rheological determinants in diabetic patients with peripheral occlusive arterial disease.

Vascular abnormalities are more prevalent in the lower extremities in diabetic patients and may cause diminished perfusion to surrounding tissues. We sought to identify blood flow abnormalities in the leg of diabetic patients with peripheral occlusive arterial disease (POAD) and to determine whether these were associated with abnormalities in rheological determinants, namely, plasma fibrinogen concentration (PFC), relative plasma viscosity (RPV), hematocrit (Hct), and whole blood viscosity (WBV). Seventeen diabetic patients with POAD were compared with 40 diabetic patients without POAD and 19 nondiabetic control subjects. Blood flow was measured by venous occlusion plethysmography, RPV was measured by capillary viscometry, WBV was measured by a Wells-Brooksfield viscometer [at high (230 s(-1)) and low (23 s(-1)) shear rates], and PFC was measured by the clot-weight method of Ingram [Ingram, G. I. C. (1961). A suggested schedule for the rapid investigation of acute haemostatic failure. Journal of Clinical Pathology, 14, 356-360]. Ankle blood flow (Q(ak)) was significantly lower in diabetic patients with POAD than in diabetic patients without POAD (P<.05). PFC was higher and Hct was lower in diabetic patients with POAD than in diabetic patients without POAD (P<.05). RPV was 1.97+/-0.15 versus 1.92+/-0.15 in diabetic patients with POAD and diabetic patients without POAD, respectively (P>.05). There was no significant difference in WBV at low or high shear rates between the groups studied. There was a correlation between WBV at low shear rate and arterial flow in the calf (Q(c)) (r=.94) and great toe (r=.95) in diabetic patients with POAD, and between Q(c) and WBV at high (r=-.465) and low (r=-.472) shear rates in diabetic patients without POAD (P<.05). We conclude that vasodilatation occurring in diabetic patients without POAD is severely restricted or absent in diabetic patients with POAD. Increased plasma fibrinogen and plasma viscosity may contribute to this phenomenon.

Are published standards for haematological indices in pregnancy applicable across populations: an evaluation in healthy pregnant Jamaican women.

BACKGROUND: The haematological profile of the pregnant woman has an impact on the outcome of the pregnancy. Published guidelines indicate acceptable levels for haematological indices in pregnancy but they are population specific. Indicators of haemoglobin concentration are the most commonly utilized of the indices. These published international norms are used across populations, however, there is no evidence confirming their applicability to a population such as the Jamaican pregnant woman. This study was therefore undertaken with the intent of documenting the haematological profile of pregnant primigravid Jamaican women and comparing these to the established norms to determine whether the norms apply or whether there was a need to establish local norms. METHODS: This was a longitudinal study done on a cohort of 157 healthy primigravid women ages 15 to 25 and without anaemia, and who were recruited from the antenatal clinic of the University Hospital of the West Indies, Kingston, Jamaica. The haemoglobin concentration, packed cell volume, mean cell volume, mean cell haemoglobin, mean cell haemoglobin concentration, white blood cell count, red blood cell count and platelet count were measured on samples of blood obtained from each consenting participant during each of the three trimesters. The results were analysed using SPSS for windows (Version 11) and the data expressed as means +/- S.D. Means were compared using the student's paired t-test. Comparison was then made with the international norms as recommended by the United States Center for Disease Control (1989). Ethical approval for this study was obtained from the University Hospital of the West Indies/University of the West Indies Ethics Committee. RESULTS: The results showed changes by trimester in all measured variables. For most of the indices the changes achieved levels of significance across trimesters. These changes were however in keeping with the expected physiological response in pregnancy and the values were similar to the published international norms. CONCLUSION: The findings suggest that the international norms for haematological indices in pregnancy are applicable across populations and to the pregnant Jamaican primigravid woman. This finding may be reassuring to others with a similar population and stage of development as Jamaica.

Glycaemic control influences peripheral blood flow and haemorheological variables in patients with diabetes mellitus.

Since persistent uncontrolled hyperglycaemia predisposes to vascular complications in diabetics, this study aimed at assessing the relationship of glycaemic control to plasma fibrinogen concentration, relative plasma viscosity and ankle arterial blood flow in diabetic patients with (N = 28) and without neuropathy (N = 34) compared with non-diabetic controls (N = 21). Glycaemic control was determined by total glycated haemoglobin (GHb) levels. Patients were placed into three categories of glycaemic control, namely good (GHb 4 -< 8%), fair (GHb 8-12%) and poor (GHb > 12%).Compared with non-diabetics, blood flow was significantly higher (p < 0.05) in patients with good but not poor glycaemic control. Fibrinogen was significantly higher in patients with fair and poor glycaemic control than in non-diabetic subjects (p < 0.05). In non-neuropathic patients, viscosity was higher (p < 0.05) in those with fair control and significantly different (p < 0.05) between those with fair and poor control. The results suggest that the initial vasodilatation in the periphery is attenuated by poor glycaemic control, contributing to the decrease in ankle arterial blood flow as a consequence of the simultaneous increase in plasma fibrinogen and viscosity. These adverse changes may contribute to the development of the diabetic foot.

Venodynamic and hemorheological variables in patients with diabetes mellitus.

BACKGROUND: The association between diabetes mellitus and the occurrence of peripheral vascular disease has been well established. However, it is unclear whether the venous circulation is also affected. This study was done to determine whether there is impairment of venous function in the legs of patients with diabetes mellitus and the relationship with rheological parameters. METHODS: Venous occlusion plethysmography was used to assess venous circulation in the legs of 54 diabetic patients at the University Hospital of the West Indies. The venodynamic variables measured were segmental venous capacitance (SVC), maximum venous outflow (MVO), and venous emptying time (VET) at the calf, ankle and great-toe. Plasma fibrinogen concentration (PFC), relative plasma viscosity (RPV) and whole blood viscosity (WBV) were measured by standard techniques. RESULTS: Calf SVC was significantly less in neuropathic diabetic patients (ND) than in non-diabetic subjects (C) (p <0.05). MVO at the calf of ND and non-neuropathic diabetic patients (NND) was significantly lower than in C (p <0.05). VET at the ankle and calf were significantly shorter in ND compared with NND (p <0.05). No statistically significant differences in SVC, MVO and VET among the three groups were observed at the great-toe. PFC was significantly higher in diabetic patients than in the control group. No significant differences were detected in WBV at high or low shear rates. CONCLUSIONS: These findings strongly suggest impairment of venous function in the legs of diabetic patients. This impairment of venous function appears to be unrelated to rheological abnormalities.

Abnormal haemorrheological changes in systematic lupus erythematosus (SLE) [abstract]

Vascular complications are frequently associated with SLE. It is hypothesized that haemorrheological abnormalities may play a role in the aetiology of micro-and-macrocirculatory disorders in SLE. The range of rheological abnormality was determined by measuring the concentration of plasma fibrinogen, serum albumin and relating these abnormalities to change in relative plasma viscosity (RPV) and relative serum viscosity (RSV) in 21 SLE patients. The SLE disease activity index (SLEDAI) was used to define the severity of the disease. Eleven patients were "severe" (SLEDAI score> 12) and ten patients were "limited" (SLEDAI score< 12). RPV and RSV were measured by capillary viscometry. Plasma fibrinogen was determined by a clot-weight procedure and serum albumin and globulin by the Biuret method. Results from the SLE patients were compared with those from a randomly selected control group. A significant increase in RPV (p< 0.001) and RSV (p< 0.05) was recorded for the SLE patients. The patients with severe disease had a significant (p<0.001) increase in RSV but neither in fibrinogen nor RPV as compared with patients with limited disease activity. The increased viscosity in SLE patients may constitute an impediment in blood flow. Furthermore, the higher serum viscosity in patients with severe disease suggests that serum viscosity may provide a useful marker for disease activity. (AU)

The influence of persistent hyperglycaemia of hyperfibrinogenaemia and hyperviscosity in diabetes mellitus

The effect of hyperglycaemia on hyperfibrinogenaemia and its consequence on plasma viscosity was investigated in 69 diabetic patients during the course of hypoglycaemic treatment. Glycaemic control was assessed by measurement of glycosylated haemoglobin (HbA). Plasma fibrinogen concentration (PFC) was determined by a clot-weight method. The relative plasma viscosity (RPV) was measured by capillary viscometry. The mean PFC and RPV were significantly (p<0.001) elevated in the diabetic patients as compared with a non-diabetic control group. Both PFC and RPV showed a distinct, step-wise increase with progressively poorer glycaemic control. The data strongly indicate that persistent hyperglycaemia is associated with a frank hyperfibrinogenaemia and hyperviscous plasma in most of the diabetic patients studied. These abnormal haemorrheological changes could impact adversely on both the haemostatic process and circulation in diabetic patients(Au)

Is there hyperviscosity in Pre-eclampsia?

There are conflicting reports on blood viscosity and its determinants in pre-eclampsia. We investigated the presence of hyperviscosity and its determinants in 24 nulliparous, pre-eclamptic Jamaican women. An equal number of non-pre-eclamptic, gestation-matched women served as controls. There was no statistically significant difference in whole blood, plasma and serum viscosities, as well as their determinants, namely, haematocrit, fibrinogen, IgM and IgG concentrations between the pre-eclamptic and control groups. This suggests that hyperviscosity is not a feature of pre-eclampsia in this Jamaican population.(Au)

Is there hyperviscosity in Pre-eclampsia?

There are conflicting reports on blood viscosity and its determinants in pre-eclampsia. We investigated the presence of hyperviscosity and its determinants in 24 nulliparous, pre-eclamptic Jamaican women. An equal number of non-pre-eclamptic, gestation-matched women served as controls. There was no statistically significant difference in whole blood, plasma and serum viscosities, as well as their determinants, namely, haematocrit, fibrinogen, IgM and IgG concentrations between the pre-eclamptic and control groups. This suggests that hyperviscosity is not a feature of pre-eclampsia in this Jamaican population.

Haemorheological and haemodynamic changes in hypertensive diabetics

We measured plasma fibrinogen concentration (PFC), relative plasma viscocity (RPV), and arterial blood flow at the calf, ankle and great-toe in hypertensive and normotensive patients with diabetes compared with non-diabetic age and sex-matched control subjects. Blood flow after reactive hyperaemia at the ankle was also measured. PFC was measured by a clot-weight procedure. RPV was measured by capillary viscometery, and blood flow by venous occlusion plethysmography.

Haemorheological and haemodynamic changes in hypertensive diabetics

We measured plasma fibrinogen concentration (PFC), relative plasma viscocity (RPV), and arterial blood flow at the calf, ankle and great-toe in hypertensive and normotensive patients with diabetes compared with non-diabetic age and sex-matched control subjects. Blood flow after reactive hyperaemia at the ankle was also measured. PFC was measured by a clot-weight procedure. RPV was measured by capillary viscometery, and blood flow by venous occlusion plethysmography. (AU)

Some clinical factors contributing to the development of the diabetic foot

Clinical neurological studies, blood pressure measurements and some haematological investigations were performed on a random sample of forty-four patients, at the Diabetes Out-Patient Clinic of the University Hospital of the West Indies (UHWI), to examine some of the factors that predispose to the development of the diabetic foot. Our results revealed that 86 percent of the patients had elevated glycosylated haemoglobin (HbA > 9.0 percent), 82 percent had clinical signs of peripheral sensory neuropathy. 29 percent had signs of autonomic neuropathy in addition to peripheral sensory neuropathy. Sixty-one percent (61 percent) of the patients had ankle/arm systolic blood pressure ration less than 1.0 and were diagnosed as having peripheral vascular disease (PVD). The group with neuropathy was found to have a significantly lower diastolic blood pressure (p < 0.0005) than the group without neuropathy. We believe that hyperglycaemia-induced vasodilation (indicated by a lower diastolic blood pressure) in a significant number of diabetics resulted in compensatory shunting of blood from the deeper tissues, including nerves, to periphery. The resulting endoneural hypoxia could be responsible for the unusually high incidence of peripheral sensory neuropathy detected in this sample of diabetic patients. Metabolic factors may also play a role.(AU)

Peripheral occlusive arterial disease in diabetic clinic attendees

Peripheral occlusive arterial disease occurs with a greater frequency in the diabetic population than in the general population. It can have debilitating effects and so early detection and intervention are important. The aim of this study was to investigate the prevalence of peripheral occlusive arterial disease (POAD) among a sample of diabetic patients attending the out-patient clinic at the University Hospital of the West Indies (UHWI), Mona. A sphygmomanometer was used to measure arm and ankle blood pressures in 80 diabetic patients, and the ankle-brachial systolic pressure index (ABI) was determined. The presence or absence of peripheral pulses was detected with the Multi-dopplex (model 1). POAD was defined by the absence of one or more peripheral pulses and/or an ABI < 0.09. Of the 80 diabetic patients examined, 18 (22.5 percent) were found to have POAD. Seventy-eight percent of diabetics with POAD had the disease in both legs. Intermittent claudication was diagnosed in 27.7 percent of patients with POAD. A significantly larger proportion of diabetics with POAD were hypertensive and/or neuropathic (p < 0.05). The results suggest that serious attention should be given to the quantitative screening for POAD in the diabetic patients attending the clinic at the UHWI (AU)

The effect of glycaemic control on peripheral blood flow in diabetics -Poster presentation

Many studies have shown that persistent uncontrolled blood glucose predisposes to several diabetic complications. The aim of this study was to determine the influence of blood glycated haemoglobin levels on plasma fibrinogen concentration - (PFC), relative plasma viscosity (RPV) and ankle blood flow (Qak) in a group of diabetic patients with vascular complications compared with non-diabetic control (C). Qak was measured by the technique of venous occlusion plethysmography. PFC was determined by a clot-weight method. RPV was determined by capillary viscometry. Glycaemic control was determined by measuring glycated haemoglobin levels (GHb). Patients were divided into three categories of glycaemic control, namely good (GHb 4 - 8 percent), moderate (GHb > 8 - 12 percent) and poor (GHb > 12 percent). Qak, PFC and RPV were compared among diabetics with and without peripheral occlusive arterial disease (POAD) and/or neuropathy of various categories of glycaemic control. Qak in diabetics without peripheral occlusive arterial disease (POAD) with good glycaemic control was significantly higher (p <0.05) than that of non-diabetic (C). Qak differed significantly (p < 0.05) between non-neuropathic diabetics (without POAD) (D) with good and poor or good and moderate glycaemic control. PFC was significantly higher (p < 0.05) in all diabetics with POAD, in D with moderate glycaemic control and in neuropathic diabetes (without POAD) (ND) with poor control than in C. RPV was significantly higher (p < 0.05) in D with moderate control and poorly controlled neuropathic diabetics with POAD than in C. RPV differed significantly (p < 0.05) between D with moderate and poor control. The results suggest that in the absence of POAD, an initial vasodilatation occurs in diabetics. The decrease in arterial flow as metabolic control worsens, may be a consequence of the simultaneous increase in plasma viscosity.(AU)

Venous function study in diabetics with neuropathy: a preliminary study

In a previous study, we found a significantly impaired vasodilatory reserve, a reflection of abnormal vasodilation in the feet of diabetics with neuropathy. No study has been done to establish whether our diabetics have abnormal venous function. The present study was designed to examine venodynamic variables in order to determine whether venous impairment was present in our diabetic patients. Venous circulation in the leg was examined in 27 diabetic patients with neuropathy (ND) and compared with 35 non-neuropathic diabetics (NND) and 19 non-diabetic controls (C). Patients and controls were free from signs and symptoms of peripheral occlusive arterial disease. Glycaemic control in the patients was assessed by the measurement of glycated haemoglobin.(AU)