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Anemia-Thrombocytopenia-Leukopenia

Blood Transfusion Reduces Mortality
The physicians who presented this study that showed increased mortality in anemic heart attack patients also evaluated the effects of a blood transfusion to reverse the anemia in this large group of heart attack victims.

A blood transfusion was associated with a significant reduction in mortality in heart attack patients with low hematocrit (below 33%). In patients with very low hematocrit (below 24%), transfusion was associated with a 64% reduction in mortality. In patients with hematocrit between 24.1 and 27.0, transfusion reduced mortality by 31%. Mortality was reduced by transfusion by 25% in those with a hematocrit between 27.1 and 30.

These numbers show that the greater the severity of anemia, the more likely a heart attack patient will benefit from a blood transfusion. Mortality actually increased when transfusions were administered to nonanemic patients, possibly a result of transfusion-related complications.

Despite numerous published studies showing the lethal effects of anemia in heart attack patients, only 4.7% of the elderly patients in this study received a blood transfusion. The physicians concluded, "More aggressive use of transfusion in the management of lower hematocrit levels in elderly patients with acute coronary disease may be warranted."

Blood Tests That Detect Anemia
When you obtain a CBC/Chemistry blood test, there are several indicators that measure the number and quality of red blood cells, along with the oxygen-carrying capacity of these cells. The three most important that indicate an anemic state are

If your blood test results indicate even borderline anemia, seek professional assistance to ascertain the underlying cause. Since aging itself predisposes people to anemia, consider specific supplements, hormones, and/or drugs that help boost blood cell production.

Anemia and Cancer
Anemia is common in cancer patients. Conventional cancer therapies (chemotherapy, radiation, and tes-tosterone blockade) often induce anemia. Elevated levels of cytokines seen in cancer patients (such as tumor necrosis factor-alpha) also suppress red blood cell formation. Since cancer cells thrive in a low oxygen environment (hypoxia), the cancer patient's red blood cell count, hematocrit, and hemoglobin should be in the upper one-third range of normal.

The importance of avoiding anemia is well established in scientific literature. A study was conducted to systematically review and obtain an estimate of the effect of anemia on survival in cancer patients. The study was reported in the journal Cancer and found that the increased risk of mortality in cancer patients who were anemic was 65% (Caro et. al. 2001).

Despite these data, most oncologists fail to adequately treat for anemia. (One reason for this is that insurance companies refuse to reimburse for expensive antianemia drugs unless the patient is severely anemic, often 25% below the lowest number on the standard reference range.)

It should be noted that cancer patients who are the most ill are often the most anemic, reinforcing the fact that antianemic drug therapy should be used more often. The Life Extension Foundation does not usually recommend blood transfusions for cancer patients because of potential immune-suppressing effects. Cancer patients need to maintain healthy immune function.

Anemia Predicts Mortality
Anemia is a strong predictor of early death in the elderly. In a study, anemic individuals aged 70-79 were 28% more likely to die over a 5-year time period. Anemic people aged 80-89 were 34% more likely to die, while those aged 90-99 were 48% more likely to die over a 5-year period. Cerebrovascular disease (stroke) was the most common disease associated with anemia. If you are over age 65, it is a life-or-death matter to correct an anemic state (Kikuchi et al. 2001).

Conventional physicians often tell their elderly patients that anemia is normal. While it is true that anemia is epidemic in the elderly, this is no excuse to leave it untreated. The Life Extension Foundation urges people to have an annual CBC/Chemistry blood test that can detect anemia and a host of other correctable life-threatening abnormalities. Those who have health insurance can sometimes have this blood testing done at no charge at their own physician's office. If the blood test reveals that you are anemic, follow the recommendations in this protocol.

How to Correct Anemia
You or your physician can determine if you are anemic by taking a standard CBC/Chemistry blood test. This test measures red blood cell count, hematocrit, hemoglobin, and other hematological indicators of an anemic state.

If you are anemic, it is important that your physician determine what is causing the anemia. Sometimes anemia is the first sign of cancer or serious internal bleeding.

However, it is often the aging process itself that causes people to become anemic. Aged men are usually deficient in testosterone. Testosterone deficiency can induce anemia (Zitzmann et al. 2000; Bain 2001). Aged women and men usually secrete low levels of melatonin. Melatonin deficiency has been linked with anemia (Foldes et al. 1988; Vaziri et al.1996; Herrera et al. 2001).

Low levels of folic acid, vitamin B12, and other nutrients can induce anemia (Baik et al. 1999; Andres et al. 2000). Excess levels of the proinflammatory cytokines can also induce an anemic state by attacking the blood cell forming proteins (erythropoietin) (Ratajzak et al. 1997; Pertosa et al. 2000). Supplements that suppress these dangerous cytokines include the DHA fraction of fish oil, vitamin K, DHEA, and nettle leaf extract (Eichbaum et al. 1979; De Caterina et al. 1994; Kipper-Galperin et al. 1999). The prescription drug pentoxifylline is also effective in suppressing the proinflammatory cytokines that can reduce red blood cell production in the body (Navarro et al. 1999; Aihara et al. 2001).

If supplements such as folic acid, B12, iron, melatonin, and DHA fish oil fail to correct anemia, then testosterone replacement and pentoxifylline drug therapies should be considered. If anemia continues to persist, see if your physician will prescribe the drug Procrit or Epogen. As noted earlier, the high cost of these drugs will keep most people from being able to afford them unless their health insurance will pay for it. If Procrit or Epogen is prescribed, it is especially important for most people to take supplemental iron because these drugs will cause iron to be utilized to help form new red blood cells. Some people taking Procrit or Epogen fail to have good results because their physicians forget to prescribe an iron supplement.

It is important to note that when treating life-threatening anemia, the only effective therapy is immediate blood transfusion because it can take up to 6 weeks for Procrit or Epogen to reverse an anemic state.

You can review information about testosterone replacement in the Male Hormone Replacement protocol. Specific information about the off-label use of the drug pentoxifylline may be found on the Life Extension website (www.lef.org).

THROMBOCYTOPENIA

Thrombocytopenia is a multisystem, life-threatening disorder of unknown cause that was first observed and described in 1924. Thrombocytopenia is characterized by microvascular leakage with platelet aggregation. The disease is most common in adults and is associated with pregnancy as well as diseases such as HIV, cancer, bacterial infection, and vasculitis.

Many drugs can induce thrombocytopenia mediated by drug-dependent antiplatelet antibodies. Management of patients with unexpected thrombocytopenia who are taking multiple drugs remains a difficult clinical problem (Rizvi et al. 1999).

Platelet damage generally accompanies thrombocytopenia, releasing a substance into the bloodstream that dramatically increases platelet adhesiveness and causes further complications.

In some cases of megaloblastic anemia (anemia conditions that have a common failure mechanism in which the body is unable to synthesize adequate amounts of normal DNA), there is concomitant leukopenia and thrombocytopenia, reflecting the abnormal development of white blood cells and platelets (McMullin et al. 1999).

Anemia chronic disease (ACD) often accompanies or can cause thrombocytopenia and leukopenia. This is a condition found in patients who have chronic infections, noninfectious inflammatory diseases (such as rheumatoid arthritis), and neoplasms. The following are characteristics of this type of anemia:

Decreased red blood cell (RBC) lifespan: The cause is completely unknown.
Impaired iron metabolism: Iron accumulates in the body, but its absorption by red blood cells is impaired.
This disease contributes to the further reduction of red and white blood cells, complicating the treatment of anemia and anemia-associated diseases.

A specific natural therapy to restore healthy platelet production is 5 capsules a day of standardized shark liver oil, containing 200 mg of alkylglycerols per capsule. Studies have shown that shark liver oil can boost the production of blood platelets. Studies have also shown the immune enhancement capabilities of shark liver oil (Pugliese et al. 1998). As will be discussed later, melatonin may be an effective and safe therapy to treat thrombocytopenia.

Shark oil capsules should be taken in high doses for a maximum period of only 30 days; otherwise, too many blood platelets might be produced.

Studies have shown that supplemental melatonin in doses of 10-40 mg a night can protect and restore normal blood cell production caused by the toxicity of chemotherapy (Lissoni et al. 1994, 1996, 1997a; Neri et al 1998). A study was performed in 80 patients with metastatic solid tumors to evaluate the benefits of melatonin. Patients received either chemotherapy alone or chemotherapy plus 20 mg each night of melatonin. Thrombocytopenia was significantly less frequent in patients receiving melatonin (Lissoni et al. 1997b).

Melatonin may also be an especially effective and safe therapy to correct thrombocytopenia, a condition characterized by a decrease in the number of blood platelets. A study was performed to evaluate the influence of melatonin on chemotherapy toxicity. Patients randomly received chemotherapy alone or chemotherapy plus melatonin (20 mg each evening). Thrombocytopenia was significantly less frequent in patients treated with melatonin (Lissoni 2002).

Other common side effects of cancer chemotherapy, such as malaise, asthenia, stomatitis, and neuropathy, occurred less frequently in patients receiving melatonin. These corroborated previous studies showing that the administration of melatonin during chemotherapy can prevent some side effects, especially myelosuppression (blood cell production suppression) and neuropathy (Lissoni et al. 1997b).

LEUKOPENIA

Preventing and Treating
Chemotherapy-Induced Leukopenia
Cancer patients using cytotoxic chemotherapy drugs should be placed on an FDA-approved immunoprotective drug(s) at the first sign of immune impairment. A blood test will determine weakened immune status. Depending on the type of cancer and the chemotherapy regimen that will be used, some of these FDA-approved drugs may include:

• Neupogen, a granulocyte-colony stimulating factor drug (G-CSF).
• Leukine, a granulocyte macrophage-colony stimulating factor (GM-CSF).

These FDA-approved drugs stimulate the production of T-lymphocytes, macrophages, and other immune cells that are valuable in preventing the toxic effects on the bone marrow during chemotherapy. These immune-protecting drugs also enable chemotherapy to be given at a higher dose that may make it more effective. Stimulated macrophages are powerful tumor killers, as has been demonstrated by clinical studies using interleukin-2 and GM-CSF or G-CSF. In addition, colony growth factors are able to accelerate the regeneration of blood cells following chemotherapy. Current clinical experience with GM-CSF and G-CSF has shown that severe neutropenia (immune impairment) due to chemotherapy drugs may be prevented or at least decelerated, thus reducing the number of severe infections (Bradstock 2002).

• Immune cytokines such as alpha-interferon and interleukin-2. Interferon directly inhibits cancer cell proliferation and has already been used in the therapy of hairy cell leukemia, Kaposi's sarcoma, and malignant melanoma. Interleukin-2 allows for an increase in the cytotoxic activity of natural killer (NK) cells (Rook et al. 1983; Blaise et al. 1993; Tur et al. 1998; Somos et al. 2000; Keilholz et al. 2002a, 2002b).
• Retinoic acid (vitamin A) analog drugs enhance the efficacy of some chemotherapy regimens and reduce the risk of secondary cancers (Riecken et al. 1999; Hong et al. 2000).
• T-cell suppressor inhibiting agents such as cimetidine prevent cancer cells from prematurely shutting down the immune system (Mavligit et al. 1981; Lahat et al. 1989; Wen et al. 1994).

The proper administration of these drugs can dramatically reduce the immune damage that chemotherapy inflicts on the body and increase the cancer cell-killing efficacy of conventional chemotherapy drugs. If you are on chemotherapy, and your blood tests show immune suppression, you should demand that your oncologist use the appropriate immune restoration drug(s).

The patient can self-administer melatonin, tocopherol succinate, and many other nutrients that have been shown to protect immune function and improve chemotherapy efficacy. These nutrients have saved the lives of cancer patients in clinical trials. Refer to the Cancer Chemotherapy protocol for information about using melatonin and vitamin E. The administration of the FDA-approved drugs, however, is still important to certain cancer patients, even though nutrients such as melatonin have similar mechanisms of action.

To treat low white blood cell counts, the FDA-approved drugs Neupogen or Leukine may be considered by your immunologist or hematologist. Drugs such as Neupogen, Leukine, and Intron A (alpha-interferon) can restore immune function debilitated by toxic cancer chemotherapy drugs.

SUMMARY

• Anemia
• Thrombocytopenia
• Leukopenia

Anemia

1. For pernicious anemia, vitamin B12, in the form of methylcobalamin should be taken orally or sublingually, 2000-4000 mcg daily. Methylcobalamin has the added benefit of protecting neurotransmitters and enhancing cognitive function. If blood tests do not show a rapid improvement, consider B12 injections.
2. For folic acid-deficiency anemia, 1600-5000 mcg a day of folic acid should be taken, along with vitamin B12.
3. For iron-deficiency anemia (IDA), take the minimum amount of iron needed to correct the deficient state. Iron Protein Plus contains 300 mg of iron protein succinylate, equivalent to 15 mg of elemental iron per capsule.
4. Certain trace minerals have been shown to improve the oxygen transport abilities of red blood cells:
   • Zinc, 30-60 mg daily
   • Selenium, 200 mcg daily
   • Copper, 2-3 mg daily
5. Elevated levels of proinflammatory cytokines cause systemic inflammation and may damage red blood cell-forming proteins. The following supplements have been shown to reduce levels of proinflammatory cytokines:
   • DHA from fish oil may be obtained in Super GLA/DHA; 3 softgels twice daily are recommended.
   • Vitamin K, 10 mg daily.
   • DHEA, 50 mg daily for men and 15-25 mg daily for women. (DHEA is a steroidal hormone that declines with aging. Refer to the DHEA Replacement Therapy protocol for specific recommendations. DHEA may be contraindicated in those with hormone-related cancers.)
   • Nettle leaf extract, 120 mg daily.
   • The prescription drug pentoxifylline may be advised if nutritional supplements do not reduce levels of systemic inflammation. Suggested dose is 400 mg twice daily.
6. Melatonin deficiency has been linked to anemia; 3-10 mg at bedtime is recommended.

Thrombocytopenia

1. Melatonin, 10-40 mg a night (some people may only be able to tolerate 3 mg a night of melatonin).
2. Standardized shark oil capsules may boost the production of blood platelets, 2000-10,000mg [containing 20% alkylgycerols (400-1000mg)] daily in divided dosages.
   Caution: At these higher dosages a complete blood cell count must be done every 30 days to avoid an overproduction of platelets.
3. Take a potent multinutrient supplement such as Life Extension Mix (3 tablets 3 times a day) to guard against a nutritional deficiency.

Leukopenia

1. Melatonin may help prevent against the toxicity of chemotherapy and protect against damage to blood cells; 10-40 mg a night (some people may be able to tolerate only 3 mg of melatonin a night).
2. Take a potent multinutrient supplement such as Life Extension Mix (3 tablets 3 times a day) to guard against a nutritional deficiency.
3. Vitamin A (retinoic acid) drugs may enhance the effectiveness of some chemotherapeutic agents. Discuss this option with your physician.
4. Ask your physician to consider prescribing immune cell-boosting drugs such as Neupogen, Leukine, alpha-interferon, and interleukin-2 before leukopenia develops. These drugs are not totally free of side effects and have to be carefully monitored for safety and efficacy.

Regular blood testing should be done to monitor the effectiveness of any blood cell-boosting therapy you are taking.

For more information

Contact the National Heart, Lung, and Blood Institute Information Center, (301) 251-1222.

Product availabiliTY

Iron Protein Plus, methylcobalamin (a sublingual vitamin B12), Life Extension Mix, standardized shark liver oil capsules, folic acid, DHEA, Super GLA/DHA, Super K, copper, zinc, selenium, vitamin A, nettle leaf extract, and melatonin can be obtained by telephoning (800) 544-4440 or by ordering online.