Blood hyperviscosity with reduced skin blood flow in scleroderma

The vascular complications of scleroderma have previously been attributed to the progressive obliteration of small vessels. Our study was carried out to determine whether abnormalities of blood viscosity occur in this disease, thereby contributing to the ischaemic process. Blood viscosity was measured in 20 patients using a rotational viscometer. At a high rate of shear, blood hyperviscosity was found in 35% of the patients and at a low rate of shear, in 70%. In addition there was a significant increase in the plasma viscosity which implicates changes in plasma proteins (fibrinogen, immunoglobulins) as causing the hyperviscosity. Measurement of the hand blood flow by venous occlusion plethysmography showed reduced flow at 32 degrees , 27 degrees , and 20 degrees C. A unique finding was a delayed recovery of the blood flow after cooling. These observations suggest that the increased resistance to blood flow in skin affected by scleroderma may be caused by an interaction between the occlusive vascular lesion and blood hyperviscosity. In addition, blood flow patterns and hyperviscosity could help distinguish scleroderma from primary Raynaud's disease.     

Increased Whole Blood Viscosity on Cooling in a Patient with Cold Hemoagglutinin Disease

Abstract. The whole blood and plasma viscosities have been evaluated in a patient with cold hemoagglutinin disease at different temperatures and at different shear rates. At 37 and 42 °C, whole blood viscosity values, regardless of the shear rate applied, resulted to be correspondent to the hematocrit value (31%). The values observed were similar to those noted in a patient with chronic bleeding anemia and an approximately equivalent hematocrit (33%). The same was true for plasma viscosity. At 32 °C, whole blood viscosity, regardless of the shear rate, resulted to be higher than expected. The values observed were similar to those noted in a normal subject with a clearly higher hematocrit value (44%) and definitely higher than those noted in the chronic anemia patient. On the contrary, plasma viscosity remained unchanged. These studies indicate that in cold hemoagglutinin disease, red cell aggregation and piling are capable of increasing blood viscosity.     

Digital pressure and flow measurement upon local cooling in Raynaud's disease. Effect of naftidrofuryl

Two local cold provocation tests were carried out in 25 healthy volunteers and in 14 patients with Raynaud's disease, using finger systolic pressure (FSP) and digital blood flow measurements. Mean FSP was significantly lower in Raynaud's patients compared to healthy volunteers at 15 degrees C and 10 degrees C (cuff temperature). Maximal digital flow (at skin temperature of 38 degrees C) was slightly though not significantly lower in Raynaud's patients as compared to normals (27 +/- 3 versus 36 +/- 4 ml/100 ml/min). Upon cooling, statistical significance was reached starting from finger skin temperature of 24 degrees C. Overlap between the two groups was considerable but only 1 out of 13 patients with Raynaud's disease had both tests normal. Ten of the patients participated in a double-blind cross-over trial with naftidrofuryl (200 mg t.i.d.) versus placebo. Significant (p less than 0.05) subjective improvement was noted after 6 weeks with naftidrofuryl but this was not necessarily substantiated by an increased digital flow or pressure in the test situation.     

Increased Whole Blood Viscosity on Cooling in a Patient with Cold Hemoagglutinin Disease

Abstract. The whole blood and plasma viscosities have been evaluated in a patient with cold hemoagglutinin disease at different temperatures and at different shear rates. At 37 and 42 °C, whole blood viscosity values, regardless of the shear rate applied, resulted to be correspondent to the hematocrit value (31%). The values observed were similar to those noted in a patient with chronic bleeding anemia and an approximately equivalent hematocrit (33%). The same was true for plasma viscosity. At 32 °C, whole blood viscosity, regardless of the shear rate, resulted to be higher than expected. The values observed were similar to those noted in a normal subject with a clearly higher hematocrit value (44%) and definitely higher than those noted in the chronic anemia patient. On the contrary, plasma viscosity remained unchanged. These studies indicate that in cold hemoagglutinin disease, red cell aggregation and piling are capable of increasing blood viscosity.     

Comparison of humeral blood flow during rewarming and recooling of the hand in normal subjects or presenting Raynaud's phenomenon

Vascular reactivity to heat and cold was studied in 11 normal subjects without vascular disease and in 23 patients with Raynaud's phenomenon (etiologies: Raynaud's disease, scleroderma, thoracic outlet syndrome). The study of hand and digital temperatures and brachial artery blood flow was performed in ambiant conditions (room temperature 23.5 +/- 1 degree C) and after thermal (cold or warm exposure: 10, 33 and 40 degrees C), mechanical and metabolic modifications (with a wrist tourniquet). In these conditions, blood flow was studied at each temperature, before, during and after 3 minutes ischemia of the hand. Analysis of results showed that vasomotricity possibilities were preserved but that responses were not identical. Patients with primary Raynaud's phenomenon, and even more those with scleroderma as well, had reduced brachial artery blood flow after cooling (10 degrees C). After ischemia, maximal blood flow was also reduced. The microcirculatory disease existing in Raynaud's phenomenon limits the vasodilator capacity of hand vessels, but probably more in tissues with vascular lesions. Vasodilation seems to be limited during exposure to low well as high temperatures, but vasoconstriction capacity is not disturbed.     

Blood viscosity and blood pressure: role of temperature and hyperglycemia

We planned a study to research the relations among blood pressure (BP), viscosity, and temperature in healthy subjects and among BP, viscosity, and glucose in diabetics. With simple random sampling method, 53 healthy and 29 diabetes mellitus (DM) type II subjects were selected. Parameters were determined with capillary viscometer and glucometer at 22°C, 36.5°C, and 39.5°C in healthy subjects, and at 22°C on diabetic patients during OGTT with 75 g of glucose. Statistical evaluations of the data were made with regression analysis, Student t test, Spearman’s correlation, and analysis of variance. When temperature decreased from 36.5°C to 22°C, blood viscosity increased 26.13%. This increase resulted in a 20.72% decrease in blood flow rate. According to the Hagen-Poiseuille equation, the required BP increase for compensation of the resulting tissue ischemia was 20.72%. Also, a 34.73% decrease in erythrocyte deformability and 18.71% increase in plasma viscosity were seen. When temperature increased from 36.5° to 39.5°C, blood viscosity decreased 10.38%. This caused 11.15% decrease in blood flow rate, and 11.15% decrease in BP, according to the equation. Erythrocyte deformability increase of 9.92% and plasma viscosity decrease of 4.99% arose from the temperature rise. There is a correlation between total data for temperatures and viscosities (r = −0.84, P < .001). When the mean value of blood glucose increased from 100 to 400 mg/dL, viscosity increased 25% (r = 0.59, P = .002). In this state, blood flow rate decrease was 20% and BP increase for physiological compensation was 25%. Consequently, temperature, glucose and viscosity levels of blood are important factors for BP.     

Laser Doppler flowmeter and standardized thermal test in normals and Raynaud's phenomenon

The diagnosis of Raynaud's phenomenon alone requires clinical investigations. To determine the stage of the disease, its etiology and pathophysiology, it seems desirable to perform noninvasive tests. Conclusions regarding control o the skin or muscle components of hand blood flow rely on evidence from separate measurements of skin or muscle blood flow. We described a standardized thermal provocation test, then respiratory maneuvers and pharmacological trials, to stimulate the microcirculatory control. The total cutaneous blood flow was continuously registered using a laser Doppler flowmeter. We conducted a prospective study on 100 subjects: 21 normal, 22 primary Raynaud's phenomenon (PRP), 26 secondary (SRP), 31 various microcirculatory diseases. The basal blood flow was lower in cases of severe SRP and acrocyanosis. In comparison with normals, RP cases present a less noticeable reaction to cold. Mild SRPs are more sensitive to cold and do not recover during warming up. Severe RPs are less sensitive to cold as they have a lower basal blood flow. Acrocyanosis cases are not sensitive to thermal variations. Post ischemic reactive hyperemia leads to a constant peak flow. Pharmacological assays were performed (nitroglycerine, Nifedipine) during permanent control of skin and muscle blood flow. Laser Doppler and provocation tests have no etiologic value in a Raynaud's phenomenon investigation; this methodology tries to elucidate the pathophysiology, the prognosis and the therapy of Raynaud's phenomenon.     

Hemodynamic changes in the peripheral circulation after repeat low density lipoprotein apheresis in familial hypercholesterolemia

Repeat low density lipoprotein (LDL) apheresis and blood flow determinations in the forearm and leg were performed in 10 patients (age range, 13-49 years; four male, six female) with familial hypercholesterolemia (eight homozygous, two heterozygous). To perform LDL apheresis, plasma was first separated by a polysulphone hollow fiber filter; then, LDL was selectively removed from plasma by dextran sulphate cellulose beads packed in columns. Blood flows in the forearm and leg were determined at rest and during a reactive hyperemia test (peak flow). This test was performed noninvasively by a strain-gauge plethysmograph with semicontinuous registration of arterial blood flow variables before the first apheresis and 3 weeks after the last of six procedures for apheresis. Resting arterial blood flows in the forearm and leg were slightly increased after repeat LDL apheresis (p less than 0.05). Peak blood flow in the leg significantly increased (+34%, p less than 0.01). No change in peak blood flow in the forearm was observed. Systolic blood pressures were slightly but significantly reduced (p less than 0.05); forearm peripheral resistances were also reduced (p less than 0.05). Flow response was not related to LDL receptor status. Blood and plasma viscosities were determined before and 7 days after the last apheresis. Blood viscosity was significantly reduced after LDL apheresis at shear rates of 11.25-450 sec-1. Plasma viscosity did not change.     

Blood viscosity as a chronic contributing factor of vasodilatation in humans

Since resistance to flow is theoretically determined by arteriolar geometry and blood viscosity, we studied these two factors in 44 normal and 106 hypertensive subjects. Brachial bed vascular resistance was calculated as the ratio between mean pressure and brachial artery flow. Systemic blood viscosity in vitro was determined at 96 per s, while microvessel blood viscosity in vivo was estimated from the haematocrit-viscosity relationship at 240 per s. A resistive radius index was calculated which was only related to the microvessel viscosity: resistance ratio. Compared to normal subjects, hypertensive subjects had higher systemic in vitro blood viscosity (4.75 +/- 0.47 versus 4.50 +/- 0.43 mPa.s; P less than 0.005) and microvessel blood viscosity (2.60 +/- 0.21 versus 2.43 +/- 0.16 mPa.s; P less than 0.001). Hypertensive subjects also had a higher brachial vascular resistance (161 +/- 89 versus 124 +/- 58 mmHg/ml per s; P less than 0.01), but showed a similar resistive radius index (2.47 +/- 0.36 versus 2.57 +/- 0.35) compared to normal subjects. There was a positive correlation between systemic viscosity and brachial artery diameter and a negative correlation between microvessel viscosity and vascular resistance in the normotensive (P less than 0.05 and P less than 0.001, respectively) and hypertensive groups (P less than 0.001 and P less than 0.005, respectively). The resistive radius index was positively related to viscosity in normal and in hypertensive groups (P less than 0.001) but these relationships were significantly different (P less than 0.001), showing that, at the highest viscosities, arterial radius increased less in hypertensive than in normal subjects. Thus, the level of blood viscosity might influence arterial diameter.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of plasma viscosity in platelet adhesion.

Platelet adhesion to the vessel wall is initiated by transport of blood platelets from the bulk flow to the wall. The process of diffusion and convection of the platelets is affected by rheological conditions such as well shear rate, red blood cell (RBC) deformability, and viscosity of the medium. To study the effect of plasma viscosity on platelet adhesion, perfusion experiments with a rectangular perfusion chamber were performed. Reconstituted blood, consisting of washed platelets and washed RBCs, was circulated through this chamber for 5 minutes at a wall shear rate of 300 s-1. Different albumin concentrations were made, to obtain different medium viscosities (0.89 to 1.85 mPa.s). Platelet adhesion decreased with increasing medium viscosity up to viscosities of 0.95 mPa.s, but increased with medium viscosity above this value. Instead of human albumin solution, different plasma viscosities were obtained by dilution of Waldenstr?m plasma with buffer. Plasma was depleted of fibronectin, which gave a final plasma viscosity of 2.0 mPa.s, and was dialyzed against HEPES buffer and subsequently diluted with the dialysis buffer in different fractions (0.89 to 2.00 mPa.s). Perfusions were performed over a purified von Willebrand factor coating on glass, or over an endothelial cell matrix, preincubated with von Willebrand factor. With both surfaces, platelet adhesion was dependent on the plasma viscosity in a similar way: at low plasma viscosities, adhesion was decreased with increasing plasma viscosity, while at higher plasma viscosities, adhesion increased with plasma viscosity. Adhesion values at higher plasma viscosity or at higher human albumin concentrations could be explained by effects of the medium on the rigidity of the RBCs, since platelet adhesion is known to be increased by enhanced RBC rigidity. Effects of the medium on the deformability of the RBCs were measured separately with the laser diffraction method. These experiments confirmed that presence of human albumin or plasma in the measuring suspension increased the rigidity of RBCs. To prevent influence of the medium on the RBCs in perfusion experiments, the RBCs were fixated with glutaraldehyde. Perfusion experiments with fixated RBCs in plasma over a von Willebrand factor preincubated endothelial cell matrix, showed a consequent decrease in adhesion with increasing plasma viscosity, according to the diffusion theories, whereas the increase of adhesion at high plasma viscosities was lacking. This suggests that the latter effect was entirely due to increased transport of platelets by more rigid RBCs.     

Blood flow through the brachial artery at different temperatures in patients with Raynaud's phenomenon

Blood flow through the brachial and radial artery at different temperatures and during reactive hyperaemia was measured in 23 patients with Raynaud's phenomenon (9 patients with Raynaud's disease, 7 - Raynaud's syndrome with thoracic outlet syndrome (TOS), and 8 - Raynaud's syndrome and scleroderma), and 11 control subjects. Blood flow was determined by an ALVAR pulse-wave Doppler system enabling measurement of vessel diameter and blood flow rate. The measurements suggest that the blood flow through brachial artery reflects the changes of blood flow through the hand immersed in water of different temperatures. Maximum vasoconstriction was the same in all groups of Raynaud's phenomenon. The lowest blood flow at higher temperatures and during reactive hyperaemia was found in patients with scleroderma, whereas in the group of TOS and partly in patients with Raynaud's disease one can suspect only functional changes.     

Digital blood flow in cooled and contralateral finger in patients with Raynaud's phenomenon. Comparative measurements between photoelectrical plethysmography and laser Doppler flowmetry.

The effects of cooling of a hand on lateral and contralateral digital skin blood flow were investigated in 18 patients with primary or secondary Raynaud's phenomenon. The aim of the study was to compare photoelectrical plethsmography (PhEP) and laser Doppler flowmetry (LDF). PhEP and LDF were used simultaneously for skin blood flow measurements of the third finger of both hands. One hand was cooled in water from 33 degrees to 3 degrees C in steps of 3 degrees C, each step lasting four minutes. It was followed by a recovery period of ten minutes in room air of 24 degrees C. During stepwise cooling from 33 degrees to 9 degrees C the relative PhEP and LDF values, measured on the cooled hand, decreased to 6.2% +/- 3.2% and 10% +/- 12% respectively. The correlation coefficients between LDF and PhEP varied between 0.79 and 0.99. In the contralateral hand the relative PhEP and LDF values decreased to 38% +/- 30.% and 64% +/- 7.9% respectively. The correlation coefficients between LDF and PhEP values were lower on the contralateral hand and ranged from 0.26 to 0.95. By calculating the LDF/PhEP ratios during cooling and recovery, more specific changes in red blood cell velocities during cooling were studied. Increasing LDF/PhEP ratios suggest increasing red blood cell velocities during cooling at 9 degrees C and a difference in the measuring methods. For testing the severity of Raynaud's phenomenon and the effect of treatment the results of both methods show consistent and quite comparable results when measured on the cooled hand. The effect of indirect cooling on the contralateral hand is, however, less consistent.     

Increased alpha-adrenergic responsiveness in idiopathic Raynaud's disease

In our study of 28 patients with idiopathic Raynaud's disease, the patients had significantly greater digital blood flow responses to intraarterial phenylephrine and clonidine than did normal control subjects. There were no group differences in finger blood flow responses to body heating, reflex cooling, digital ischemia, or to intraarterial tyramine or isoproterenol. There were also no group differences in blood pressure or heart rate during any procedure. These results suggest that patients with idiopathic Raynaud's disease have increased peripheral vascular alpha-adrenergic receptor sensitivity and/or density compared with normal persons.     

Effect of High Concentrations of Leukocytes on Whole Blood Viscosity

Whole blood viscosity of patients withleukemic leukocytosis was compared tothat of normals with a similar totalpacked cell volume (TPCV). Leukocytesin suspension were also studied andfound to have a greater viscosity thanerythrocytes. We found no relation between the magnitude of the leukocytecount and whole blood viscosity. Thepresence of anemia in the patients withleukemia prevented elevation of theirTPCV. This, as well as the normal variability of blood viscosity obscured anyincrease that could have been producedby the greater viscosity of massed leukocytes.

Submitted on February 25, 1971 Revised on April 6, 1971 Accepted on April 7, 1971     

Apparent finger systolic pressures during cooling in patients with Raynaud's syndrome

Despite considerable research, the mechanisms responsible for the vasospasm associated with Raynaud's syndrome are not well understood and there is no reliable diagnostic test. In the present studies, measurements of systolic pressure in locally cooled fingers were used to address these issues. We found that local cooling produced a marked decrease or loss of the apparent finger systolic pressure in patients with Raynaud's syndrome in whom a standardized vasoconstriction had been induced by body cooling. Abnormal responses were encountered in 109 of 125 patients with secondary Raynaud's syndrome, in 21 of 37 patients with primary Raynaud's disease or the syndrome of uncertain cause, and in two of 63 subjects without symptoms of Raynaud's. These data suggest a high accuracy of the test in patients with secondary Raynaud's syndrome and lower accuracy in those with disease of primary or uncertain cause. We studied responses of systolic pressures to alterations in body and local temperatures in fingers with and without low pressures secondary to proximal arterial obstruction. Our data show that although local cooling has a small independent effect that increases vascular tone: (1) sympathetic vasoconstriction induced by body cooling is necessary to produce vasospasm and often produces it without local cooling, (2) high local temperature (30 degrees C) protects from vasospasm, and (3) low finger blood pressure predisposes to it. Delayed opening of the vessels observed after sudden deflation of blood pressure cuffs suggests that abnormal responses of finger systolic pressure to cold represent combined effects of high vascular tone, delayed opening, and local blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Treatment of systemic scleroderma with ketanserin. Randomized, double-blind 6-months study of 27 cases

Twenty-seven patients with systemic scleroderma and Raynaud's phenomenon underwent a randomised double blind therapeutic trial: monotherapy with Ketanserine (80 mg/day for 6 months) against Placebo. The secondary effects were comparable in both groups as were the withdrawals from the trial for aggravation of Raynaud's phenomenon (one in each group). No significant difference was observed between the two groups as regards the evolution of the Raynaud's phenomenon or skin changes. Dysphagia was improved in the Ketanserine group (p less than 0.05) but not in the Placebo group. Some patients in the Ketanserine group experienced an improvement in the Raynaud's phenomenon at the end of the trial period; there were no improvements in the Placebo group. Three haemorrheological parameters (total blood viscosity, plasma viscosity and thixotropism) were abnormal at the beginning of the trial and did not improve by the end in the Ketanserine group. The K infinity coefficient of Quemada's law was normal at the start of the trial and increased after treatment (p less than 0.05).     

Blood rheology during an intensified conventional insulin treatment (ICIT) in insulin-dependent diabetes

Fifteen insulin-dependent diabetes mellitus (IDDM) patients with minor diabetic complications underwent an intensified conventional insulin treatment (ICIT) program consisting of multiple daily insulin injections with an insulin pen. Blood viscosity parameters were measured before the start, after 6 weeks, 1 and 2 years with a Contraves LS30 viscosimeter. At the start several rheological parameters were disturbed in the diabetic subjects. Mean total hemoglobin A1 (HbA1) significantly (at least P less than 0.05) decreased while the plasma free insulin level significantly increased (at least P less than 0.05) under ICIT. During the first 6 weeks hematocrit (P less than 0.01), plasma (P less than 0.05), whole blood (P less than 0.05) and erythrocyte (P less than 0.01) viscosities significantly decreased but they increased again at 1 year of ICIT. Only plasma viscosity (P less than 0.05) remained below the starting value after 1 and 2 years. Normalization of the blood sugar level improved plasma and whole blood viscosity by an insulin-induced dilution phenomenon after 6 weeks. The persisting decrease in plasma viscosity was accompanied by a significant alteration of the plasma protein profile. These findings suggest that metabolic status influences blood rheology in IDDM patients but by different mechanisms on a short- or long-term basis.     

Hematocrit is associated with carotid atherosclerosis in men but not in women

BACKGROUND: It is known that blood and plasma viscosities are associated with clinical manifestations of atherosclerosis, though evidence is not conclusive particularly in women. OBJECTIVE: To verify whether hematocrit and blood and plasma viscosities are independently associated with carotid atherosclerosis and whether their measurement can improve the definition of the global coronary heart disease (CHD) risk. METHOD: Eight hundred and ninety-two participants in a cardiovascular disease prevention campaign were examined with regard to conventional CHD risk factors (age, blood pressure, lipids, glucose, body mass index, waist/hip ratio, cigarette smoking and diabetes), hematocrit and blood and plasma viscosities. According to the degree of carotid atherosclerosis, investigated by echo-Doppler, participants were divided in three groups: those without atherosclerosis, those with a low degree of atherosclerosis and those with a high degree of atherosclerosis. RESULTS: In men, age, blood pressure, intima-media thickness (IMT), hematocrit (47.4+/-3.7%, 47.8+/-3.7%, 48.4+/-3.7%, P<0.05) and blood viscosity (4.69+/-0.51 cP, 4.77+/-0.55 cP, 4.82+/-0.51 cP, P=0.05) increased with increasing degree of carotid atherosclerosis. In women, age, blood pressure, total cholesterol and low-density lipoprotein-cholesterol, IMT and plasma viscosity (1.42+/-0.12 cP, 1.44+/-0.11 cP, 1.46+/-0.13 cP, P<0.05) increased with increasing carotid score. Analysis of covariance (ANCOVA) showed that after adjusting for hematocrit, blood viscosity was no longer different in the three groups. In discriminant analysis, hematocrit, among the hemorheological variables investigated, was independently associated with carotid score in men (F=3.66, P<0.05). Neither hematocrit nor blood and plasma viscosities were significantly associated with carotid score in women. CONCLUSION: These findings suggest that in men, both hematocrit and blood viscosity are related to carotid atherosclerosis but hematocrit would appear to have an independent effect over and above that mediated by viscosity.     

Blood and serum viscosity in cardiologic X syndrome

The aim of this study was to explore if are there blood rheological disturbances in cardiac syndrome X. Two groups were examined: 23 patients (aged 41 divided by 72 years) suffering from cardiac syndrome X (typical anginal pain positive stress test and no lesion in coronary angiograms) and 20 healthy (aged 32 divided by 57 years). Blood samples were drawn from the cubital vein prior to the angiogram. Blood viscosity measurements were performed using the Brookfield Cone/Plate Viscosimeter at 150 s-1 shear rate, and by means of low-shear Contraves viscometer at 1 s-1 (a)nd 4.59 s-1 shear rates. The plasma viscosity was measured by means of Ubbelohde's capillary viscometer. Besides the viscometric examinations the total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides and glucose plasma concentration as well as blood morphology and ESR were determined. All rheological measurements were carried out at the temperature of 37 degrees C immediately after blood drawing. It was stated that blood and plasma viscosity were significantly elevated in syndrome X compared with the control group (p < 0.001). CONCLUSION: The examinations indicate that in patients suffering from Cardiological Syndrome X the whole blood and plasma viscosity are increased.     

Functional vascular disorders: treatment with pentoxifylline

A group of 11 female patients (mean age 33.7 +/- 8 years) with a clearly proven primary Raynaud's syndrome of up to five years' duration were subjected to a two-month oral treatment with 3 X 400 mg pentoxifylline per day. The following parameters were studied without and with exposure to cold conditions: hemodynamics (finger photoplethysmography), red cell deformability (filtration test), various clotting variables (prothrombin activity, antithrombin III, plasma fibrinogen, partial thromboplastin time, thrombin time, thrombelastogram), and clinical symptomatology. After treatment 7 of the 11 patients showed a distinct improvement of peripheral blood flow and of symptoms (decrease or removal of asphyxia attacks, pain, color change) under basal conditions, as well as after exposure to cold. Red cell filtration was significantly (p less than 0.05) improved, increasing by 35% under normal conditions and by 30% after exposure to cold. Positive changes were also found in respect to antithrombin III (increase) and plasma fibrinogen (decrease). The thrombelastogram was unchanged. Clinical and instrumental improvements were probably ascribable to better microcirculatory flow due to increased red cell deformability, reduced viscosity, and decreased fibrinogen, all capable of influencing in various degrees the blood flow at the microcirculatory level.