AGE OF TRANSFUSED BLOOD & COMPLICATIONS AFTER SURGERY 

Everyday, thousands of people undergoing surgery will require transfusions with lifesaving blood stored in hospital blood banks.  Because of the very small risk of passing infections along to patients with blood transfusions, and because some studies have suggested that blood transfusions might depress immune function, doctors try to reserve blood transfusions only for those patients at greatest risk of complications, including death, from severe anemia.  However, it has long been known that blood, which can be thought of as a living liquid human tissue, deteriorates while being stored, even under refrigerated conditions.  Although fresh blood can be stored for up to 42 days under optimal conditions, the levels of natural substances in red blood cells necessary for proper function begin to decline within few hours after collection from a donor.  At the same time, the living cells within the donated blood continue to churn out metabolic waste substances that can have an adverse effect on very sick patients receiving large volume blood transfusions. 

Because individual hospitals can never precisely predict how many blood transfusions will be required from one day to the next, blood banks need to keep a small surplus of blood products on hands at all times.  Since these products are highly perishable, and can only be stored for a limited time before being discarded, most blood banks release their older stocks of blood for transfusion first, much as your neighborhood grocery store places the oldest containers of milk at the front of the shelf.  Older blood, in addition to containing higher levels of potentially toxic metabolites, simply does not take up and unload life-sustaining oxygen as efficiently and as quickly as fresh blood does.  Additionally, the red blood cells contained in older bags of blood are more fragile, and are more easily ruptured (also referred to as hemolysis), further reducing the available number of blood cells available following transfusion (the breakdown products of ruptured red blood cells can also be toxic to the liver and kidneys in patients with abnormal liver and kidney function).  A new research study, just published in the New England Journal of Medicine, has cast further, important, light on this topic. 

In this study, nearly 3,000 patients undergoing open-heart surgery were evaluated after being transfused with almost 9,000 units of blood that had been stored for 14 days or less.  The complications and death rates for this group of patients were then compared to a similar group of almost 11,000 open-heart surgery patients who had received “older” blood, which had been collected and stored for more than 14 days.  On average, blood given to the first group of patients was about 11 days old, while the blood transfused into the second group of patients was, on average, about 20 days old (the latter is still well within current blood storage and transfusion guidelines).  

When comparing the clinical outcomes for these two otherwise matched groups of patients, the researchers found that the incidence of serious complications and risk of death were significantly higher among the patients receiving the “older” blood.  Specifically, more patients receiving “older” blood remained on a mechanical ventilator for 3 or more days than did the patients receiving “newer” blood (9.7% vs. 5.6%, respectively), and these patients were also more likely to suffer severe infections than the patients who received “newer” blood (4.0% vs. 2.8%, respectively).  Similarly, the risk of kidney failure, which is associated with a high risk of death in critically ill patients, was also significantly higher in patients receiving “older” blood (2.7% vs. 1.6% in patients receiving “newer” blood, respectively).  Finally, and most importantly, the likelihood of death within 1 year of surgery was also significantly higher among the patients receiving “older” blood than was observed in the patients transfused with “newer” blood (11.0% vs. 7.4%, respectively).  

This study is a real eye-opener, because it suggests that significant increases in the risk of serious complications and death may be associated with transfusions of even relatively fresh blood, at least in patients undergoing major cardiac surgery.  Whether or not the same degree of adverse effects occur in patients undergoing other types of major surgery was not addressed by this study, although the mechanisms of transfusion-associated illnesses and death are generally thought to be similar irrespective of the type of surgery, and are likely more related to the number and severity of co-existing illness within individual patients.   

The findings of this study should generate further review of the current collection and storage guidelines for blood products, although the typically tight supply of lifesaving blood products at most hospitals means that a significant change in the allowable duration of blood product storage is not likely to change much at all.  At the same time, I expect that hospital blood banks will probably begin taking a closer look at which patients receive transfusions with “older” blood versus “newer” blood.  A prudent approach, based upon the results of this study, would be to develop an algorithm whereby the sickest patients would automatically receive blood that has been stored for less than 14 days, while less seriously ill patients requiring blood transfusions would receive the “older” blood products. 

OBESITY, BLOOD PRESSURE, AND HEART SIZE IN CHILDREN

As most of us know, the incidence of obesity among both adults and children in the developed world has been skyrocketing.  Obesity has long been known to be associated with a variety of life-shortening conditions, including high blood pressure, coronary artery disease, congestive heart failure, diabetes, stroke, liver disease and arthritis, among other ailments. 

Chronic high blood pressure (hypertension), by itself, can lead to irreversible damage to the heart, brain, kidneys, retinas and other vital organs.  In the case of the heart, a chronically elevated blood pressure causes the heart to have to work harder, resulting in progressive thickening of the heart’s main pumping chamber, the left ventricle.  Over time, the enlarged and increasingly stiff left ventricle can begin to fail, resulting in the development of congestive heart failure (CHF).  Historically, CHF has been viewed as a disease of the elderly, often occurring after decades of poorly controlled hypertension, or after heart attacks have further damaged the left ventricle.  However, the rising incidence of obesity among children has raised concerns that we may be on the cusp of an epidemic of early-onset obesity-related hypertension and coronary artery disease among young adults.  A timely new research study in the Journal of Pediatrics confirms that such an epidemic may be just around the corner.

In this small study, 44 obese and 22 non-obese children (average age was 8 years) were evaluated for blood pressure and left ventricular size.  Not surprisingly, average blood pressure readings were significantly higher in the obese children.  In fact, 48% of the obese children had documented episodes of hypertension during their daily activities.  Similarly, the obese kids were found to already have enlarged left ventricles, as measured by echocardiography. 

This study reveals the unpleasant truth that pre-pubertal obese children are at markedly increased risk of developing hypertension and left ventricular enlargement (hypertrophy), and should raise alarm bells for any parent with an overweight or obese child.  The presence of confirmed high blood pressure and left ventricular hypertrophy in these kids, and at an average age of only 8 years, almost certainly means that these children will face an extraordinarily high future risk of hypertension-related ailments, and early death, unless they are able to shed their excess weight. 

 Dr. Wascher is an oncologic surgeon, professor of surgery, a widely published author, and the Director of the Division of Surgical Oncology at Newark Beth Israel Medical Center

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Send your feedback to Dr. Wascher at rwascher@doctorwascher.net
 

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Copyright 2008.  Robert A. Wascher, MD, FACS.  

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The more that we understand about how Vitamin D works in the body, the greater becomes our appreciation of its myriad health-related effects.  Previously, this essential vitamin was considered primarily in terms of its important role in the absorption of calcium.  (Calcium not only provides strength for our bones, but also plays a critical role as a cofactor in thousands of vital chemical reactions occurring in every cell in our body.)  Unique among vitamins, our bodies can actually create Vitamin D as a result of exposure to natural sunlight.  However, variations in exposure to sunlight and in skin pigmentation, and in the availability of adequate Vitamin D in our diets, results in wide variations in the level of the active form of Vitamin D in the blood of individuals.  Because of these variations, an estimated one-third to one-half of all adults, and especially older adults, have low blood levels of this crucial vitamin.

Two new studies add further scientific evidence strongly suggesting that Vitamin D may also be important in maintaining a healthy cardiovascular system, and in reducing the risk of developing at least some forms of cancer. 

In the journal Circulation, researchers from the famed Framingham Heart Study evaluated more than 1,700 adults, with an average age of 59, and without a prior history of cardiovascular disease (except for high blood pressure).  During more than 5 years of follow-up, on average, the incidence of cardiovascular events was tracked in these research study volunteers, and these cardiovascular events were then correlated with Vitamin D levels in the blood of the same participants.  The cardiovascular events tracked in this study included the new onset of cardiac chest pain (angina), heart attacks, heart failure, strokes, and leg pain due to inadequate blood supply.  

During the course of this study, 120 volunteers experienced a new cardiovascular event.  Interestingly, study volunteers with high blood pressure appeared to experience significant cardiovascular protection from high levels of Vitamin D in their blood, while patients without hypertension did not.  Among the volunteer patients with high blood pressure, those with the lowest levels of Vitamin D in their blood experienced more than twice as many serious cardiovascular events when compared with hypertensive patients who had the highest levels of Vitamin D in their blood. 

Recent research has suggested that chronic Vitamin D deficiency may be associated with increased blood pressure, enlargement of the heart, and an increase in the levels of chemicals in the blood that are associated with inflammation.  Vitamin D supplementation, in small research trials, appears to be able to improve these adverse effects of Vitamin D deficiency.  However, to actually verify that Vitamin D supplementation can reduce the risk of cardiovascular events in patients with high blood pressure, it will be necessary to follow this excellent Framingham Heart Study research trial with another study that randomizes hypertensive, Vitamin-D-deficient volunteers between Vitamin D pills and placebo pills (“sugar pills”).  Only then will we be able to clarify the true role of Vitamin D deficiency (and supplementation) in cardiovascular disease and health.  Meanwhile, it would seem prudent to make sure that your diet contains adequate daily levels of Vitamin D, and that you avail yourself to reasonable (though not excessive) levels of sun exposure, especially if you have hypertension.  (If you are fair-skinned, then please observe the present recommendations regarding safe exposure levels to the sun’s rays.)  Of course, please check with your personal physician first, before embarking upon any major changes in diet or dietary supplements, or any other major lifestyle changes. 

VITAMIN D & BREAST CANCER RISK

There have been a number of studies suggesting that higher levels of Vitamin D in the blood may be associated with a somewhat decreased risk of developing certain cancers.  The data for the possible anti-cancer effects of Vitamin D has been most pronounced for colon and rectal cancer, although not all studies have confirmed this beneficial health effect for Vitamin D.  Other studies have also suggested that increased Vitamin D intake may be associated with a modest reduction in the risk of developing breast cancer, as well.  Most of these studies, however, have relied upon surveys in which study volunteers have estimated their dietary Vitamin D intake, a method of research that is subject to significant potential inaccuracies.  A new study from Germany, just published in the journal Carcinogenesis, has taken a scientific approach similar to the study of Vitamin D’s effect on cardiovascular health that I have just reviewed (above).

In this study, two groups of postmenopausal women, each numbering almost 1.400 in size, were evaluated.  One group consisted of women who had been diagnosed with breast cancer between 2002 and 2005, while the second group consisted of age-matched women without a prior history of breast cancer.  The level of Vitamin D was measured in all of these study volunteers, and then correlated with the presence or absence of a history of breast cancer. 

When comparing the women with the highest blood levels of Vitamin D against the women with the lowest levels, the results were rather striking.  Having the highest levels of Vitamin D in the blood was associated with a nearly 70% reduction in the risk of breast cancer, in this population of Northern European women, when compared to similar women with low Vitamin D levels.  Because this research study directly measured levels of Vitamin D in the blood, the results are not dependent upon the subjective recollections of study participants.  One limitation of this study, however, is that it does not completely prove that Vitamin D deficiency alone is directly causing an increased risk of breast cancer.  As I have already mentioned, the absorption of Vitamin D, and the regulation of its level in the blood, are controlled by highly complex biochemical mechanisms.  There may be other factors at work that simultaneously increase the risk for breast cancer and decrease the levels of Vitamin D in the blood (i.e., this is the critically important difference between a “cause-and-effect” relationship, on the one hand, and a mere “association” between two unrelated processes or events, on the other hand).

Once again, the next logical step in this area of study would be to perform a new clinical study in which postmenopausal women with low levels of Vitamin D in the blood were randomized between high-dose Vitamin D supplements and placebo pills, and were then followed for at least 5 years.  Only this type of study would definitively answer the question of whether of not Vitamin D deficiency, by itself, increases the risk of developing breast cancer after menopause.  
 

GREEN TEA & COLON AND RECTAL CANCER

Much has been written about the potential health benefits of green tea, and especially the antioxidant polyphenols contained within this ancient beverage.  As in most areas of cancer research, conflicting results have been published regarding the role of green tea polyphenols as potential cancer prevention aids.  Certainly, however, there is ample laboratory data (in cell cultures and in animal models) suggesting that green tea polyphenols may be able to block key mechanisms of cancer cell development.

A new study, also just published in the journal Carcinogenesis, adds to the growing body of data suggesting that green tea polyphenols can indeed block critical cancer-causing biochemical pathways, at least in laboratory rats.

In this research study, laboratory rats were used to assess the effects of green tea polyphenols in the prevention of colorectal cancer.  The rats were injected with azoxymethane, a chemical known to induce colon cancer in rats fed a high-fat diet.  The rats were divided into 3 groups, with 2 groups receiving green tea dietary supplements (either low-dose or high-dose supplementation), and a third group that received no green tea supplementation in their diet.  At the end of the study, the animals were euthanized, and the cells lining their colons were then examined under a microscope for changes consistent with an early transition to colon cancer.

The researchers in this study discovered that the rats who received green tea supplementation had significantly fewer pre-cancerous changes in the cells lining their colons when compared to the rats that received no green tea supplementation.  Furthermore, the rats that receive the highest dose of green tea supplementation had the least number of pre-cancerous changes in colon cells among the 3 groups of rats.  Several cancer-associated proteins (including beta-catenin and cyclin D1) were also studied in the colon cells of each group of rats and, once again, the levels of these proteins were significantly lower in the rats who had consumed the green tea supplements, and especially in the group of rats that received the highest dose of green tea polyphenols.  These results strongly suggest that, at least in rats, several key cancer-associated biochemical reactions can be blocked by green tea polyphenols, and that microscopic evidence of early pre-cancerous changes in the cells lining the colon is also reduced by green tea supplementation.  Unfortunately, countless previous research studies in rats and mice have failed to show comparably favorable results in humans.  One could imagine a similar study being performed in humans, with the collection of small biopsies of the colon and rectum performed during routine screening colonoscopy.  The role of green tea supplements in the prevention of colon and rectal cancer could then be evaluated objectively in humans.  Meanwhile, I will continue to take my own daily supplements of green tea in liquid and capsule form.
 

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Send your feedback to Dr. Wascher at rwascher@doctorwascher.net
 

Copyright 2008.  Robert A. Wascher, MD, FACS.  All rights reserved.

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