cumadin

[rinksgal]

Darrell is on cumadin and so far its not where they want it to be. its only 1.4 This is due to the 3 blood clots they found... hes currently on 7.5 mg. of cumadin and they almost increase it to 10.mg today, but wanted to know what he was taking medicine whys... and anyway they told him to stop taking fish oil. and restest tuesday..Guess they thin this could be interfering with his blood levels..

We saw the radiation oncologist today... and his concerns with darrell are the new pleural effusion, which he said could be cause from cancer, or the radiation, and or emphasema.. which darrells never been told he has... Also his concerns are the liver, tumors in lymphnodes, and the new indertermiate nodule in Darrellls lower right lobe... We'll see with follow up scans that will be done in January...Is anyone else on cumadin and have they had problems with getting the right levels set ?? His liver lesions are stable and no new growth which was good, and skrinage with the lymphnodes, he said over all good report, buts whats good if there still cancer.... I worry so much about this man that I love... He now thinks I have a boyfriend... he said hes sorry, he knows better, but guess hes worried because theres not been no intimacy in our relationship for months. I tell him it doesn't matter to me, but I can see why he worrys about it. He has no reason to though!!I just want him to live and beat this damn disease!!! We don't ask for prognosis, it doesn't matter, do they really know any ways.. We'll know if and when its starting to kick his butt... We'll know... they won't need to tell us.. we already know the statistics.., so why ask prognosis. everyone is different... God I hate this disease!! I hate lc and I will do something to help him or someone sometime during my life.. There needs to be more awareness... I want to help!!!!

Christy

[kimblanchard]

Hi Christy,

Bill has been on coumadin for months. His protyme levels are checked every other week and his dose is adjusted accordingly. It's an ongoing thing.

Hang in there sweetie!

Peg

[shirleyb]

There are foods that interact with the blood thinners. Check to see which ones they are. From what I know green vegs and cranberries should not be eaten. Keep a log of what Darrel is eating and see if you find any other items that might be effecting how the meds are working.

My heart goes out to you and Darrel. To not only deal with the lung cancer but now this too. Keep up on this though. From what our onc told us .. they lose more LC patients to blood clots than the cancer.

My prayers and thoughts are with you.

Shirley

[Donna G]

When I read this topic I said to myself , boy thay should talk to Shirley , I scaned down and there she was! Thanks Shirley for reaching back and helping out.

[kimblanchard]

My mother just started on cumadin a few weeks ago and each week they check her level. The doctor said that it can be a constant adjustment. My mother also asked (since my father is on it as well - heart valve surgery) if she should stay away from certain foods and the doctor said to eat what she wants - try to eat lots of different things - and they will adjust her level accordingly.

Take care.

Kim

[rinksgal]

Shirley our doctor said the same thing, that he loses more lc patients due to blood clots than the cancer its self.. which is hard for me to deal with since no one warned us about blood clots and how to look for them. duh!! shouldn't they warn us about this!!!! This makes me so dang angry!!! Also Darrell was told to eat normal, or whatever he wants but to be consitent in what he eats... Like you said its not like we don't already have enough to deal with, with out this dang worry!!! Thanks for your responses...

Christy

[Botley]

Hi,

Just wanted to post some information regarding Coumadin you need to really watch your intake of foods with Vitamin K. The foods with Vitamin K may be eaten but it should be consistent every day (not excessive amounts) and do not vary it. The following foods have moderate or high amounts of Vitamin K: Asparagus, Avocado, Beef Liver, Broccoli, Brussels Sprouts, Cabbage (this includes Coleslaw & Sauerkraut), Collard Greens, Endive, Garbanzo Beans, Green Scallions, Kale, Lentils, Lettuce, Mustard Greens, Seaweed, Soybeans, Swiss Chard, Turnip Greens. Certain oils, alcohol, and teas may also affect how warfarin/coumadin works in your body. Do Not drink green tea. Also, Multi Vitamins try to get one without Vitamin K. Ask your Doctor about any supplements or over the counter medications (aspirin) you may take too as they may also have adverse effects. Generally, coumadin should be taken about the same time every day -- for people on warfarin/coumadin therapy Dr.'s will often times have patiens take the medication in the evenings anywhere from 5-7pm (2 hour window) so the results of testing will not be thrown off by patients varying the time when they take their medications. Just thought some of this information may be of help to you.

Take Care,

Botley

[Guest]

Hi Christy

I've been taking Coumadin since I was diagnosed with Atrial Fibrillation in March of this year. Had a Cardioversion done in May this year and am in normal sinus rhythm. Stopped taking the Coumadin for 10 days prior to my lung surgery and then put back on it three days after surgery. My nodule was found during a routine chest x-ray when I was admitted to the hospital for the Atrial Fibrillation.

I have been going for my Protime levels every two weeks - it's been hard to get it back up to the therapeutic levels since the surgery. Protime was 2.1 ten days ago so it is slowly creeping up to the 2.3 level.

I concur with Botley about Vitamin K - I received quite a bit of literature from the doctor about diet. Also was told to stop riding my bicycle (even wtih a helmet) because the risk of falling off and banging my head wasn't worth it due to blood being thinned out and risk of hemorrahge(not sure of spelling). Not riding my bicycle is the only drawback for me in having to take Coumadin. I'm not a big fan of most of the Vitamin K foods/veggies either. I eat salads and broccoli (salads mostly) almost every day.

I have found two websites about Coumadin that I found to be interesting:

http://www.rxlist.com/cgi/generic/warfarin.htm

and

http://coumadin.com/consumer/consumerPr ... tion.shtm#

Hope you find the websites of interest.

EileenM

[shellybug68]

My father is on Coumadin too. They have a lot of problems getting his levels where they want them. For months his levels stayed in the 1.3- 1.5 area and he went as high as 15mg daily. Thankfully they have now settled to about 2.1 and he has been taking 11mg daily for about a month. He gets his levels checked weekly. Dad worries about how much he takes too because it seems everyone in the office is only taking around 5 - 7mg. I guess it is due to his large body size. Take care, Shelly

[john]

I think herapin does not have to be monitored as closely. The only problem is that it is given by injection.

Low molecular weight herpin might be another option and he won't have to worry as much about diet, *I think*.

The kidneys have to be functioning well if LMWH is given

In an article I read 20% have patients on warfarin/coumadin have a

recurrence with thrombosis vs 7% of patients on LMWH.

Also there is some evidence that LMWH may help fight the cancer

http://www.google.com/search?q=lmwh+can ... 8&oe=UTF-8

http://www.careinternet.com/caregiver/warfarin.php

[john]

http://cancerres.aacrjournals.org/cgi/c ... 60/21/6196

LMWHs in Patients With Cancer

Leo R. Zacharski, MD

Heparin -- generally UFH -- is an important adjunct in oncology practice, where it is used to treat and prevent thrombosis, to preserve venous access for catheter devices, to prevent thrombotic complications of bone marrow transplantation, and to treat disseminated intravascular coagulation (DIC).

In addition to these traditional uses, however, heparin may also have anti-tumorigenesis properties. The heparin molecule is a polysaccharide glycosaminoglycan (GAG) molecule that can exist with very heterogeneous chain lengths, with variations in the position and the degree to which the chain is sulfated. Although GAGs superficially resemble one another, they each have fundamentally different properties. GAGs are put together as a hexadecimal code, in which 6 different disaccharide couplets can be linked side-by-side to create long-chain molecules with very different properties. The physiologic roles of the GAGs include hemostasis, inflammation, cell growth and organogenesis, embryogenesis, angiogenesis, wound healing, and neoplasia. It is therefore believed that heparin, as a GAG, may have direct effects on tumorigenesis.

Early Trial Data With Heparin

The preclinical evidence for the effect of heparin on malignancy was first published by Alfred Goerner.[21] In this study, Dr. Goerner took chips of tumor and incubated them in either a control media or in the presence of heparin for varying lengths of time. He then implanted the chips under the skin of an experimental animal and observed that tumors incubated in the presence of heparin failed to grow.

In the many animal studies that followed these early observations, heparin was shown to be capable of reducing tumor cell (TC) migration from vasculature, reducing motility within tissues, and reducing the incidence of induced DIC. Heparin was also demonstrated to increase TC circulation time, and thus the effects of chemotherapy and immunotherapy on the tumor, and to inhibit pulmonary metastasis and the uptake of radiolabeled fibrinogen into the tumor bed. The most important finding from these animal studies was that heparin inhibits primary tumor growth and prolongs the survival of the tumor-bearing animals.

Based on these animal studies, several mechanisms have been proposed to explain the experience of heparin use in human malignancy, the most important of which are inhibition of angiogenesis, inhibition of tumor cell proteases, and inhibition of growth factors and other coagulation factors.

Clinical Trials in Patients With Cancer

In a study of the effect of heparin on hospital mortality in acutely ill medical patients, 1358 consecutive acute care admissions were randomized to low-dose (5000 units bid) UFH or no heparin.[22] Overall, mortality was significantly lower (P < .05) in the UFH-treated group (7.8%) compared with the no-heparin group (10.9%). In the subset of patients with cancer, mortality was reduced by 42%, from 32.1% (n = 56) in the untreated group to 18.6% (n = 43) in the UFH group. In a retrospective analysis of perioperative heparin on survival, 336 patients were randomized to either low-dose heparin or to placebo.[23] There was a 3-year cancer mortality of 21.4% in the control group vs a mortality rate of 9.4% in the heparin group. Of interest, among heparin-treated patients, a meta-analysis of 90-day mortality in cancer patients treated for DVT indicated a 67% reduction in mortality favoring the LMWH group (11.7%) compared with the UFH group (28.8%).[23]

In a multicenter clinical trial, 277 patients with small-cell lung cancer were randomized to subcutaneous heparin or control for a period of 5 weeks at a dosage of 5000 U twice daily.[24] All patients also received chemotherapy and/or radiation therapy. The 138 patients who received anticoagulant treatment compared with the 139 who did not receive heparin demonstrated improved complete response rates (37% vs 23%, P = .004), a longer median survival (317 vs 261 days, P = .01), and improved survival at 1, 2, and 3 years. No important bleeding or thrombocytopenia events were related to heparin therapy. The authors concluded that anticoagulant treatment with heparin for small-cell lung cancer was of value.

The heparin-binding growth factor that drives colon cancer angiogenesis, bFGF, increases the tumor venous drainage and drives urokinase and urokinase receptor expression in colorectal cancer cells. Likewise, VEGF is a well-known heparin-binding growth factor that stimulates angiogenesis. Both serum levels of VEGF and vessel density predict survival in colon cancer.

Since LMWH is a better inhibitor of various heparin-binding growth factors, including bFGF, VEGF, and MGSA, and since LMWH is suitable for long-term outpatient therapy at effective doses, clinical trials have evaluated the use of LMWH in patients with cancer.

In a prospective, randomized, double-blind trial, von Tempelhoff and colleagues[25] compared the LMWH certoparin with UFH for thrombosis prophylaxis during primary surgery and for cancer survival during postsurgical follow-up in women with previously untreated breast and pelvic cancer. The study was controlled for tumor cell and organ type, stage, and standard treatment; heparin was given for approximately 7 days postoperatively. In patients with pelvic malignancy, estimated survival data indicated that LMWH compared with UFH significantly reduced mortality at about 2 years (P = .0066), but there was no effect in patients with breast cancer.

In a prospective randomized trial of 603 patients with colorectal cancer having curative surgery, razoxane was administered as an antimetastatic agent.[26] The study failed to show a benefit from razoxane on the course of resected colon cancer. However, on subgroup analysis using Kaplan-Meier survival analysis curves, a difference in outcome was noted in those patients who had been treated with prophylactic subcutaneous UFH compared with those who had not: the UFH treatment conferred a statistically significant improvement in survival at 5 years.

DVT Prophylaxis and Cancer Outcomes

In patients treated for DVT prophylaxis, UFH has been shown to significantly improve cancer outcome. There is similar but more limited evidence for using LMWH to treat DVT.

In a retrospective analysis of data from a prospective randomized trial of low-dose UFH administered for DVT prophylaxis in 230 patients with resected Duke's B and C colorectal cancer, the interval to or the prevalence of recurrence was evaluated.[27] There was no significant difference in disease recurrence in patients receiving UFH compared with those not receiving UFH (30% in each group). The interval from surgery to recurrence of cancer was slightly longer in the UFH-treated group than in the nonheparin group, but was also not statistically significant. However, life table analysis over a period of 96 months demonstrated a significant long-term overall mortality benefit for patients in the UFH-treated group compared with the non heparin group.

In a meta-analysis of patients with or without cancer comparing LMWH to UFH for treating proximal DVT, there was a statistically significant reduction in the relative risk of death in cancer patients receiving LMWH compared with those receiving UFH. In patients without cancer, no difference was noted. [28]

Conclusions

Prospective randomized studies in cancer patients using LMWHs rather than UFH should be undertaken in light of the more predictable pharmacokinetics, relative ease of administration, and relative safety of LMWHs. For this to occur, however, a change in thinking must take place. For nearly the last half century, cancer treatment has been dominated by the "search and destroy" paradigm involving cytotoxic chemotherapy, immunotherapy, and radiation therapy. While this approach has produced undoubted benefits, the possibility remains that growth modulation may also work as a therapeutic approach. Testing this hypothesis will require targeting various tumor growth factors, angiogenesis, cell-cell interactions, the integrity of the tumor cell matrix, and various tumor cell proteases as well as oncogene expression in an attempt to alter, in a favorable direction, the outcome of malignancy.

[john]

rinksgal,

Lovenox is actually low molecular weight herapin. So Darrel was on this before the coumadin. I think it is standard to start on LMWH and switch to coumadin since it is taken orally.

I think lovenox can be used for a long time. The main issues are cost and it is given by injection. Also the kidneys must be ok. I believe he won't have to be monitored as closely and the INR (measurement to measure clotting? basically) will be kept in range more easily

After more research lovenox is not something that can be given at home. Some LMWHs can be administered intramuscularly not intravenously like Lovenox.

LMWHs that can be given in the muscle can be given at home. Since different LMWHs manufactured by different companies can not be used interchangeably

Dalteparin is a LMWH that I *think* can be used on an outpatient basis

Hope everythink works out ok.

--------------------------------------------------------------------------------

July 9, 2003 — Dalteparin was more effective than warfarin for preventing recurrence of venous thromboembolism in cancer patients, according to the results of a multicenter randomized trial published in the July 10 issue of the New England Journal of Medicine. The editorialist suggests that this low-molecular-weight heparin should become the new agent of choice.

"Oral anticoagulant therapy is problematic in patients with cancer," write Agnes Y. Y. Lee, MD, and colleagues from the Randomized Comparison of Low-Molecular-Weight Heparin vs. Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer (CLOT) investigators. "Secondary prophylaxis with low-molecular-weight heparin may be a more effective and practical alternative to oral anticoagulant therapy."

In this study, cancer patients with acute, symptomatic proximal deep-vein thrombosis, pulmonary embolism, or both received dalteparin, 200 IU/kg subcutaneously once daily for 5 to 7 days and a warfarin derivative for six months targeted to an international normalized ratio (INR) of 2.5, or dalteparin alone for six months (200 IU/kg once daily for one month, followed by a daily dose of approximately 150 IU/kg for five months).

Recurrent venous thromboembolism occurred in 27 of 336 patients in the dalteparin group and in 53 of 336 patients in the warfarin group (hazard ratio, 0.48; P = .002). At six months, the probability of recurrent venous thromboembolism was 17% in the warfarin group and 9% in the dalteparin group.

There were no significant differences between the groups in terms of rate of major bleeding (6% vs. 4%), rate of any bleeding (14% and 19%), and six-month mortality (39% vs. 41%).

The authors note that the open-label design of this study could be a potential source of bias, but that a double-blind design would be neither feasible nor safe in cancer patients.

Pharmacia funded this study and supplied the study drug.

In an accompanying editorial, Rodger L. Bick, MD, PhD, from the University of Texas Southwestern Medical School in Dallas, notes that the cost of low-molecular-weight heparins has been overestimated. Except for some patients with renal insufficiency, anticoagulation does not need to be monitored, and reduced recurrence reduces overall medical costs.

He notes that this study "provides clear evidence that low-molecular-weight heparin should become the therapeutic and prophylactic agent of choice in cancer-associated thromboembolic disease."

N Engl J Med. 2003;349:109-111, 146-153

[carlton]

Hi Christy--- I to am on coumadin, had some edema in lower legs and doc thought it best to start coumadin. It doestake awhile to get the right dose that wouldbe effective for him. Know it is a pain but he will have to keep getting it checked. It is a good preventitive against blood clots. You don,t need that problem. So hang in there. Carlton

[shirleyb]

Randy did the lovenox at home for almost 3 months. His cancer was not found when he started throwing the blood clots. The blood clots were our first indication that something was wrong. We had no idea he had cancer and the doctors never pursued why he was having blood clots. It was only after having a stroke did we find out he had cancer. The cost is extreme for the lovenox and that is why they usually switch over to cumidin/warfine. When Randy was first getting the blood clots, we were going to the doctor every 4 days for INR's. You would have thought that the doctors would have done more tests to find out why he was having issues with blood clots (he had 14 major ones before the stroke)but they didn't do a d**n thing. They told him he was having blood clots because he had psoriasis.

My only advise is ask questions, push the doctors for answers and if you don't like how they are treating you for asking, find someone who will help you.

I pray that no one has to go through what we went through ever!!!

[rinksgal]

I want to thank everyone for their replys, They almost increased his cumadin to 10mg.. but doctor wanted to know everything he was taking. Anyways he had him quit taking fish oil...Since he quit taking it his test yesterday came back at 2.4 ... So hes suppose to continue on with the 7mg for now.. We'll see what the next test is... Darrell was almost scared at the thought of taking 10mg.. but they told him they've had patients taking as much as 15mg...

John, thanks for all of your information, I have looked at it... I mentioned to Darrell about some of the other options possibly.. He did say though that even though he was able to give himself the shots of lovenox that he really didn't want to do this on a regular basic..

Thanks everyone!! I appreciate so much how everyone on this board replies so quickly.. I mean it seems like anytime I or someone else needs information, that so many people know the answer or offers support!! I really appreciate this site so much!!

Thanks!! Christy

[teresag]

Just a couple of corrections/suggestions:

1) UFH heparin is not low molecular weight heparin. UFH stands for unfractionated heparin; it is dosed in units & LMW heparin is dosed in mgs. The two are metabolized differently and really cannot be compared.

2) Coumadin does take a while to regulate. Hang in there. I tell patients to eat the high-vitamin K foods in small amounts, and they don't have to cut them out entirely. After all, many of them contain significant other nutrients. The key is to not overdo any one of the foods on the list. But follow what your own provider suggests.

3) The clotting test for monitoring coumadin is either the PT (prothrombin time) or, preferably, the INR, which is standardized, unlike the PT.

So if you have an INR drawn at two different labs, they can still be compared, unlike the PT. Normal INR = 1.0.

3) Lovenox is given subcutaneously, like insulin. Many patients take it successfully at home, just as with insulin.

Hope this info is helpful. - Teresa

[Guest]

Lovenox is LMWH

[john]

The Anticoagulant Heparin: A Possible New Cancer Treatment?

Leo Zacharski, M.D., and Robert G. Lerner, M.D.

Dr. Zacharski is Professor of Medicine, Dartmouth Medical School, Hanover, New Hampshire, and Associate Chief of Staff, VA Medical Center, White River Junction, Vermont.

The Case of Mrs. B.

A 79-year-old woman -- we will call her Mrs. Benchley -- came to her local hospital with pain and swelling in her right leg. She also complained of shortness of breath and pain on the left side of her chest when she did breathe. Over the previous two months, she had felt increasingly tired and had developed a dry cough. Mrs. Benchley had always been healthy, suffered from no serious illnesses, never smoked and was physically active.

After running a few tests, doctors found a small cancerous tumor in her lung. They also found enlargement of the lymph nodes, which indicated that the cancer had probably spread to other parts of the body. A biopsy, or examination of a sample of tissue removed from the lung tumor, confirmed that Mrs. Benchley had metastatic adenocarcinoma of the lung. Adenocarcinoma is one of the many types of cancer.

As for the pain and swelling in Mrs. Benchley's leg, tests revealed that she had deep vein thrombosis of a vein in her right leg. Also called DVT, deep vein thrombosis is a condition in which a blood clot blocks or reduces the flow of blood through one of the body's main veins. It can cause pain and swelling and can sometimes be life-threatening. For reasons that are not completely understood, it often occurs together with cancer.

For her DVT, Mrs. Benchley was given the usual treatment, which is IV heparin in the hospital, followed by warfarin, an oral anticoagulant (blood thinner) at home. Sold under a variety of brand names, heparin is a prescription anticoagulant that slows the rate of blood clot formation. It can both prevent formation of blood clots after surgery and, as in the case of Mrs. Benchley, help dissolve blood clots that have already formed. Warfarin, (usually sold under the brand name Coumadin®), is an oral anticoagulant.

As for the lung cancer, Mrs. Benchley's doctors did not recommend radiation or surgery and she decided against chemotherapy. Soon her DVT symptoms improved and she was sent home with a prescription for warfarin.

Unfortunately, however, the warfarin did not prevent another blood clot problem. Mrs. Benchley was readmitted to the hospital a month later with DVT, now in her left leg. She was again treated with IV heparin, did well and returned home. This time, instead of warfarin, she was prescribed a form of heparin called enoxaparin, which she could inject herself.

One year later, Mrs. Benchley returned to the hospital for a checkup. She had continued to lead an active life and had been surprisingly well, except for some shortness of breath with exertion. She had had no further problems with DVT. A chest X-ray showed that the spread of her lung cancer had slowed considerably. She was told to continue on a low dose of a form of heparin called low molecular weight heparin (sometimes abbreviated as LMWH).

Two Interesting Points

Mrs. Benchley is not unique, and her story illustrates two points. One is that the anticoagulant warfarin sometimes seems to lose its normal effectiveness against DVT in cases where the DVT occurs along with cancer. For some reason, heparin, a different kind of anticoagulant, seems to remain effective against DVT even with the presence of cancer.

A potentially more significant issue, however, is whether taking heparin to treat blood clotting problems may have somehow slowed down the growth of Mrs. Benchley's lung cancer. Based on cases like hers, doctors have begun to wonder if the human body's blood clotting mechanism may somehow play a role in the growth of cancerous tumors. If that is so, then it would explain why a drug like heparin that fights blood clotting might actually stop or slow down tumor growth.

Can Heparin Fight Cancer?

Recent research results have backed up the theory that the body's coagulation mechanism may play a part in the development of some cancers, as well as offering some explanation of why heparin might interfere with cancer.1,2,3,4,5,6 Heparin has been shown to fight the growth of tumors in animals in various ways.7,8,9,10,11 Some of these studies have also shed light on why heparin, and not warfarin, might have this effect.12 There is also preliminary evidence that LMWH treatment prolongs survival in patients with both DVT and cancer.13

The possible reasons for this are not completely understood. To put them as simply as possible, cancerous tumors are usually surrounded by a substance called fibrin. Fibrin promotes the growth of the tumor and the growth of new blood vessels that supply the tumor with necessary nutrients. Heparin interferes with fibrin formation and perhaps directly inhibits the formation of new blood vessels. Both heparin and LMWH may also inhibit tumor growth in other ways.14,15,16

Summary

Whatever the exact mechanisms involved, there is mounting evidence that the anticoagulant drug heparin may fight the growth of at least some kinds of cancerous tumors.17 In experiments using rats, treatment with heparin has decreased the likelihood that cancer will metastasize, or spread throughout the body. Similar studies on humans have been promising, though not conclusive.18

The interaction of the body's coagulation mechanisms, heparin and cancer is an extremely complex issue. Cancer, itself, comes in many forms and acts in many different ways. While we await the results of further research, a person facing a decision about cancer treatment -- especially someone with lung cancer or DVT -- may wish to discuss heparin treatment with their doctor.

March 2001 Email this article to a friend

References

1. Norrby K: 2.5 kDa and 5.0 kDa heparin fragments specifically inhibit microvessel sprouting and network formation in VEGF165-mediated mammalian angiogenesis. Int J Exp Pathol 2000 Jun;81(3):191-8. return

2. Kato M, Maeta H, Kato S, Shinozawa T, Terada T: Immunohistochemical and in situ hybridization analyses of midkine expression in thyroid papillary carcinoma. Mod Pathol. 2000 Oct;13(10):1060-5. return

3. Arkel YS: Thrombosis and cancer. Semin Oncol 2000 Jun;27(3):362-74 return

4. Tyan ML: Effects of inositol, LiCl, and heparin on the antibody responses to SRBC by normal and immunodeficient XID mice. Proc Soc Exp Biol Med. 2000 Jul;224(3):187-90. return

5. Collen A, Smorenburg SM, Peters E, Lupu F, Koolwijk P, Van Noorden C, van Hinsbergh VW: Unfractionated and low molecular weight heparin affect fibrin structure and angiogenesis in vitro. Cancer Res. 2000 Nov 1;60(21):6196-200. return

6. Pascall JC, Ellis PD, Brown KD: Characterisation of the rat heparin-binding epidermal growth factor-like growth factor gene promoter. Biochim Biophys Acta 2000 Jul 24;1492(2-3):434-40. return

7. Lapierre F, Holme K, Lam L, Tressler RJ, Storm N, Wee J, Stack RJ, Castellot J, Tyrrell DJ: Chemical modifications of heparin that diminish its anticoagulant but preserve its heparanase-inhibitory, angiostatic, anti-tumor and anti-metastatic properties. Glycobiology 1996 Apr;6(3):355-66. return

8. Hejna M, Raderer M, Zielinski CC: Inhibition of metastases by anticoagulants. J Natl Cancer Inst 1999 Jan 6;91(1):22-36. return

9. Prandoni P, Piccioli A, Girolami A: Cancer and venous thromboembolism: an overview. Haematologica 1999 May;84(5):437-45. return

10. Zacharski LR, Wojtukiewicz MZ, Costantini V, Ornstein DL, Memoli VA: Pathways of coagulation/fibrinolysis activation in malignancy. Sem. Thrombos. Hemostas.18:104-116, 1992. return

11. Callander N, Rapaport SI: Trousseau's syndrome West J Med 1993 Apr;158(4):364-71. return

12. Hull RD, Raskob GE, Pineo GF, Green D, Trowbridge AA, Elliott CG, Lerner RG, Hall J, Sparling T, Brettell HR, et al.: Subcutaneous low-molecular-weight heparin compared with continuous intravenous heparin in the treatment of proximal-vein thrombosis. N Engl J Med. 1992 Apr 9;326(15):975-82. return

13. Smorenburg SM, Hutten BA, Prins MH: Should patients with venous thromboembolism and cancer be treated differently? Haemostasis 1999 Dec;29 Suppl S1:91-7. return

14. Zacharski LR, Ornstein DL, Mamourian AC: Low-molecular-weight heparin and cancer. Semin Thromb Hemost. 2000;26 Suppl 1:69-77. return

15. Sylvester DM, Liu SY, Meadows GG: Augmentation of antimetastatic activity of interferon and tumor necrosis factor by heparin. Immunopharmacol Immunotoxicol. 1990;12(2):161-80. return

16. Syrokou A, Tzanakakis G, Tsegenidis T, Hjerpe A, Karamanos NK: Effects of glycosaminoglycans on proliferation of epithelial and fibroblast human malignant mesothelioma cells: a structure-function relationship. Cell Prolif. 1999 Apr-Jun;32(2-3):85-99. return

17. Ornstein DL, Zacharski LR: The use of heparin for treating human malignancies. Haemostasis. 1999 Dec;29 Suppl S1:48-60. return

18. Smorenburg SM, Hettiarachchi RJ, Vink R, Buller HR: The effects of unfractionated heparin on survival in patients with malignancy--a systematic review. Thromb Haemost. 1999 Dec;82(6):1600-4. return

[Donna G]

Wow, now that is interesting! Donna G

[shirleyb]

I know this is too late to be a benefit for Randy, but I wonder if anyone has brought John's response to this issue to their doctor. Somehow in my soul, I think that as group we are hitting on something here.

Could it be as Oprah says, listen to what God is telling you in your heart and follow it. I feel like God is screaming at me to ask you to please follow up on this interesting tidbit of information with your doctors. If it would benefit just one of you, then I would say, maybe there is a better chance out there for those who have been told there is nothing left to try.

If there is nothing else to try according to the doctors, then what can this hurt if it is given properly?

I just feel like God is screaming at me .....give it a chance. Maybe this is the miracle we are all looking to give us more time. I can't answer that but man, I have this screaming voice in my soul that says it is worth a shot.

Best of luck to all. You are all in my prayers.

Shirley