Blood Viscosity

Earlier, More Accurate Prediction of Cardiovascular Event Risk
Pushpa Larsen, ND
[pic]Ralph Holsworth, DO, recently shared a story with me about a patient he had in Colorado many years ago. He was an intern in a Denver hospital when he admitted a patient diagnosed as having a blood clot in his leg. Dr Holsworth started him on low-molecular-weight heparin subcutaneous injections concurrently with warfarin sodium. He worked the patient up for congenital thrombophilias, cancer, hypothyroidism, and other conditions, and consulted with hematology-oncology on the case. When the patient’s prothrombin time–international normalized ratio exceeded 2.0, Dr Holsworth was instructed by hematology-oncology to discharge the patient. A few minutes later, Dr Holsworth’s pager buzzed. His patient had just collapsed in the parking lot. He rushed down to the emergency department, where cardiopulmonary resuscitation was in progress and assisted in the code. The patient was pronounced dead after several attempts at resuscitation. A mandatory autopsy revealed that the patient had a major pulmonary embolism, resulting in his sudden death.
It was not until several years later that Dr Holsworth learned of the role of whole blood viscosity (WBV) in the formation of thrombi. Dr Holsworth recalled that his aforementioned patient had been discharged with normal vital signs and laboratory test results that provided no indication of the evolving danger. Dr Holsworth later became one of the world’s leading experts in the use of blood viscosity in a clinical setting and asked: “I wonder if this patient would be alive had I been able to evaluate his likely elevated WBV and treat him with antiviscogenic agents. Only then, after lowering his WBV to a safe range, would I have discharged this patient safely to home to his loved ones. I learned early on that a therapeutic international normalized ratio was not to be trusted.”
What Is Blood Viscosity?
Blood viscosity is a measurement of the thickness and stickiness of a patient’s blood. This important hemodynamic biomarker determines the amount of friction against the blood vessels, the degree to which the heart must work, and the quantity of oxygen delivery to the tissues and organs. It is a direct measure of the “flow ability” of blood and is modifiable with existing naturopathic therapies. Blood viscosity is correlated with all known risk factors for cardiovascular disease, including age, sex, smoking, obesity, inflammation, insulin resistance, high blood pressure, low high-density lipoprotein cholesterol, high low-density lipoprotein cholesterol, and others.1-5 Elevated blood viscosity is a strong independent predictor of cardiovascular events.6 In the Edinburgh Artery Study, elevated blood viscosity was the strongest predictor of stroke risk, after controlling all other major risk factors.7,8
It is important to understand the role of blood viscosity as a clinical marker. To do so, one must know something about how the physics of blood flow works and about what affects blood viscosity.
Factors Affecting Blood Viscosity
Five primary factors determine blood viscosity. These include hematocrit, erythrocyte deformability, plasma viscosity, erythrocyte aggregation, and temperature.1
Hematocrit
Hematocrit is the most obvious determinant of WBV. A higher percentage of red blood cells (RBCs) results in thicker blood. Hematocrit accounts for about 50% of the difference between normal blood viscosity and high blood viscosity.
Erythrocyte Deformability
Erythrocyte deformability refers to the ability of RBCs to elongate at high velocity and to bend and fold themselves to pass through the slender passageways of the capillaries. More flexible RBCs result in less viscous blood, and young RBCs are more flexible than older RBCs. Erythrocyte deformability is the second most important determinant of blood viscosity, after hematocrit.
Plasma Viscosity
Plasma viscosity refers to the thickness of the fluid portion of blood (everything except for RBCs, white blood cells, and platelets). Plasma viscosity is highly affected by hydration and by plasma proteins, especially high-molecular-weight proteins such as immunoglobulins and fibrinogen.
Erythrocyte Aggregation
Erythrocyte aggregation reflects the tendency of RBCs to be attracted to each other and to stick together. Red blood cell aggregation is complex, with both plasma proteins and RBC deformability having a role.
Temperature
As with most fluids, blood flows more easily at higher temperatures. It is estimated that a 1°C increase in body temperature results in a 2% decrease in blood viscosity.9
The Physics of Blood Viscosity
Water and plasma are considered newtonian fluids. This means that their viscosity remains the same whether they are flowing fast or slowly. Whole blood, on the other hand, is a non-newtonian fluid, and its viscosity changes with its velocity. This point becomes important clinically when monitoring blood viscosity.
During diastole, blood is subject to lower pressures, or shear. Shear increases rapidly as the ventricles contract in systole and then decreases again as the ventricles relax. During these periods of low shear, the blood slows, cellular components of blood begin to aggregate, and viscosity increases. Blood at diastole can be anywhere from 5 to 20 times as viscous as the same blood at systole. In the next cardiac cycle, viscosity decreases as shear increases and blood components are dispersed, reaching its lowest viscosity at the height of systole (Figure 1).
Viscous Blood Is Abrasive Blood
Blood flows through the vessels in what is described as laminar flow. That is, the blood forms layers (lamina) that slide easily over each other. Looking at the blood vessel from the side, we would see the fastest flowing blood in the center layers, with slower moving blood in the outer layers near the wall of the vessel. Highly viscous blood does not slide as smoothly as less viscous blood, leading to turbulence that can damage the delicate intima of the blood vessel. Turbulence is also generated at curves and bifurcations in blood vessels, particularly the large vessels nearest the heart, which are subject to great changes in pressure with each heartbeat.
Clinical Implications of Altered Blood Viscosity
We see the consequences of hyperviscous blood primarily in damage to the blood vessels, in overwork of the heart, and in decreased delivery of oxygen to the tissues. Highly viscous blood pounding against the walls of the blood vessels leads to abrasion of the single-cell layer of the intima in the carotid, pulmonary, and coronary arteries. The body responds with a protective adaptation, creating a scab (plaque), which eventually calcifies in an effort to protect the blood vessel. The longer-term result, of course, is increased turbulence (because of the no-longer smooth wall) and an ever-narrowing channel for blood flow. This result requires the heart to work harder, pushing the viscous blood out at even higher pressures, further damaging the intimal layer. At the other extreme of the vascular tree, we see decreased perfusion of the tissues as the stiffened erythrocytes of viscous blood scour the capillary linings. The body responds by thickening the capillary walls, decreasing diffusion of oxygen and nutrients into the tissues. This effect is most pronounced in tissues where healthy capillaries are essential for unimpaired function such as the kidneys, eyes, fingers, and toes.
Blood Viscosity Explains Plaque Localization
The effects of blood viscosity, taken together with an understanding of the dynamics of blood flow in a closed circulatory system, explain why it is that atherosclerotic plaques are found only in specific locations in the body.1,10 If cholesterol or inflammation was the primary culprit, plaques would be evenly distributed throughout the body because cholesterol and inflammation are generalized rather than localized. Instead, plaques are found in the curves and bifurcations of the large arteries, and they are located in the exact places where blood flow investigations show that turbulence is the greatest. We all have these areas of turbulent blood flow because we share a common geometry of our vascular tree. Yet, not everyone develops artherosclerotic plaques. The difference lies in the viscosity of the blood traveling through those arteries. Cholesterol and inflammation are important because they contribute to blood viscosity.
Delivery of Oxygen to the Tissues Is Mediated by Blood Viscosity
The capacity of blood to carry oxygen to the tissues is directly correlated with hematocrit. However, it is also inversely correlated with blood viscosity. The relationship of these 2 parameters is expressed as the oxygen delivery index. Within the limits of normal hematocrit values for men and women, improved oxygen delivery index is associated with lower hematocrit levels. A woman with a normal hematocrit actually has a greater ability to deliver oxygen to cells than a man with a higher, but normal, hematocrit.11 The decreased oxygen-carrying capacity of higher-viscosity blood affects cognitive function, as well as the function of any tissue to which robust oxygen delivery is essential (such as the placenta). Given the universal importance of oxygen delivery to the tissues, the relevance of blood viscosity to health maintenance and promotion is clear.
All of this is borne out by hundreds of studies showing that elevated blood viscosity is associated with a host of conditions. A partial list includes diabetes mellitus, insulin resistance, preeclampsia, intrauterine growth retardation, stroke, transient ischemic attacks, atherosclerosis, myocardial infarction, peripheral artery disease, hypertension, headaches, visual field defects, glaucoma, retinopathy, Hodgkin disease, Raynaud disease, sudden deafness, nephrotic syndrome, Alzheimer disease, and more.12-22
The Sex Difference
It is well known that men of any age are at higher risk for cardiovascular events than premenopausal women.11,23 A woman’s risk increases significantly after menopause, and younger women who have hysterectomies are also at increased risk, even if they retain their ovaries (thus an ability to maintain estrogen levels). Why is this? The primary determinants of blood viscosity are highly affected by a woman’s monthly blood loss. The effect on hematocrit is obvious: the monthly loss of 1 to 3 oz of blood will decrease the volume of RBCs. The effect on RBC deformability may be less obvious. Because of monthly bleeding, a woman makes more new blood cells than a man. Her blood contains about 80% more young blood cells and about 85% fewer old blood cells.11 Older RBCs are also more likely to aggregate than are younger RBCs, affecting the third determinant of blood viscosity described herein. In addition, older RBCs are more fragile than younger cells and are more likely to break apart, releasing hemoglobin, a high-molecular-weight protein, into the plasma. Furthermore, plasma-free hemoglobin binds nitric oxide, reducing the ability of nitric oxide to perform its functions as a vasodilator and as an inhibitor of platelet aggregation. Even our fifth determinant of blood viscosity, temperature, may contribute to the lower blood viscosity of premenopausal women because a woman’s basal body temperature is normally increased by 0.5 to 1°C for the second half of her menstrual cycle.
Treatments for Hyperviscosity
We can use the 5 primary determinants of blood viscosity to guide our treatments for hyperviscosity. The objectives of therapy are to optimize hematocrit (Figure 2), improve RBC deformability, decrease plasma viscosity, reduce RBC aggregation, and normalize body temperature.
An easy way to improve blood viscosity is to decrease hematocrit to optimal ranges through blood donation or therapeutic phlebotomy. Dr Holsworth estimates that a hematocrit of 42% is optimal for men, while 38% is optimal for women. Blood donation translates into real-life results. In the Kuopio Ischemic Heart Disease Risk Factor Study,24 a total of 2862 middle-aged men were followed up for a mean of 9 years. During that time, the rate of acute myocardial infarction among non-blood donors was 12.5%, almost 18 times the 0.7% rate among blood donors (P