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Cancer, Coagulation, and Anticoagulation

^a Hematology-Oncology Department, Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA; ^b Dana-Farber Cancer Institute, Boston, Massachusetts, USA

Correspondence: Anthony Letai, M.D., Ph.D., Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA. Telephone: 617-632-6077; Fax: 617-632-5822; e-mail: aletai{at}partners.org

	Abstract

Top Abstract Introduction Thrombophilia of Malignancy Chemotherapy and Thrombosis Indwelling Central Lines and... Treatment of Thromboembolic... Heparin versus Warfarin LMWH Anticoagulants as Anticancer... Conclusions References

 
Thromboembolic disease affects about 15% of cancer patients and presents a challenge to the oncologist for both prophylaxis and treatment. Although long known to be associated with malignancy, the underlying biochemical mechanisms are poorly understood. Both low-dose warfarin and low molecular weight heparin are effective strategies for prophylaxis of venous thromboembolism, including those involving venous access devices. Current treatment options for venous thromboembolism include heparin (unfractionated and low molecular weight), warfarin, and internal vena cava filters. The appropriate use of these therapeutic options in cancer patients is reviewed herein. There is suggestive evidence that heparin may be superior to warfarin in the long-term treatment of venous thromboembolism. Whether anticoagulants might also improve cancer survival rates independent of their effect on thromboembolism deserves further investigation.

Key Words. Cancer • Heparin • Warfarin • Coagulation • Thrombosis • Pulmonary embolism • Small-cell • Chemotherapy • Breast

	Introduction

Top Abstract Introduction Thrombophilia of Malignancy Chemotherapy and Thrombosis Indwelling Central Lines and... Treatment of Thromboembolic... Heparin versus Warfarin LMWH Anticoagulants as Anticancer... Conclusions References

 
One of the most frequent hematological complications encountered by the practicing oncologist is disordered coagulation. Thromboembolic disease affects approximately 15% of all cancer patients [1]. This includes superficial and deep venous thrombosis, pulmonary emboli, thrombosis of venous access devices, as well as arterial thrombosis and embolism. It is the second leading cause of death for cancer patients [2], although obviously in many of these patients, thromboembolic disease represents only one of many complications of the end-stage patient.

In this paper we will focus on the hypercoagulable states associated with cancer and the role of chemotherapy in inducing thrombosis. We will review the problem of central venous catheters and their associated thrombotic risk in cancer patients. We will describe aspects of treatment of thromboembolic disease which are peculiar to cancer patients and focus on the relative roles of coumadin, heparin, and low molecular weight heparin (LMWH) in this treatment. Finally, we will summarize the data concerning the use of anticoagulants as antineoplastic agents.

	Thrombophilia of Malignancy

Top Abstract Introduction Thrombophilia of Malignancy Chemotherapy and Thrombosis Indwelling Central Lines and... Treatment of Thromboembolic... Heparin versus Warfarin LMWH Anticoagulants as Anticancer... Conclusions References

 
Cancer and its treatment can affect all three arms of Virchow's classical triad of causation of thromboembolic disease: alteration in blood flow, damage of endothelial cells, and elaboration of procoagulants. Cancer can affect blood flow by mechanical effects on blood vessels near a tumor. Also, the angiogenesis induced by many tumors causes the creation of complexes of blood vessels that are aberrant in appearance and have very disordered flow. In fact, flow in these vessels can vary not only in magnitude, but also in direction. Endothelial cells can also be damaged directly by tumors or chemotherapy.

Procoagulants can be increased on the surface of cancer cells, and may also be secreted into the blood stream by cancer cells [3]. Examples of molecules elaborated by cancer cells that can predispose to disordered coagulation include tissue factor, a Vitamin K-dependent cysteine protease that activates factor X, and a mucin procoagulant that activates prothrombin. Furthermore, chemotherapy treatment can cause a reduction in levels of the anticoagulant proteins C and S. Indwelling venous access devices may also predispose to thrombosis by altering blood flow, damaging endothelial cells, and serving as a surface upon which procoagulants can promote thrombosis.

In addition, other factors can cause dysregulation of the normal mechanisms of thrombosis and hemostasis. Certain tumors cause thromboembolism by direct extension and blockage of neighboring vessels. The best-known example is probably renal cell carcinoma, which can be associated with internal vena cava (IVC) thrombus by direct extension of tumor into this vessel. Long-term survival of patients with this disorder has been reported after complete resections of the tumor and thrombosed vessel, sometimes even including the right ventricle.

Other tumors are associated with a secondary thrombocytosis [4]. However, there is not an association of this thrombocytosis with activation of the clotting cascade or clinical thromboembolism. Tumor cells may activate platelets in yet other cases. It is hypothesized that the resulting platelet aggregation may assist in the implantation of metastases, and perhaps even in protection from the host immune system.

	Chemotherapy and Thrombosis

Top Abstract Introduction Thrombophilia of Malignancy Chemotherapy and Thrombosis Indwelling Central Lines and... Treatment of Thromboembolic... Heparin versus Warfarin LMWH Anticoagulants as Anticancer... Conclusions References

 
Chemotherapy itself can increase the risk of thromboembolic disease. This has been best studied in breast cancer where tamoxifen and cytotoxic chemotherapy both appear independently to increase the risk for venous thrombosis [5-10]. The increase in risk appears to be greatest in postmenopausal patients. An increased risk for arterial thrombosis has also been observed [7, 11]. It should be noted, however, that many of the chemotherapy regimens in these studies contained more drugs (up to seven) than are typically present in today's one, two, or three-drug regimens.

It is reasonable to ask if there is an effective strategy to prevent thrombosis in breast cancer patients receiving chemotherapy. Perhaps the best data are from a British study in 1994 [12]. Three hundred and eleven metastatic breast cancer patients receiving "first or second-line" chemotherapy were enrolled within four weeks of initiating the chemotherapy. One hundred and fifty-nine received a sham pill and sham internationalized normalized ratio (INR) in a double-blinded fashion. One hundred and fifty-two received low-dose warfarin at 1 mg daily for six weeks; after six weeks, the warfarin dose was adjusted to attain an INR between 1.3 and 1.9. Patients were screened with an ultrasound if they had symptoms of venous thrombosis. A positive ultrasound finding was confirmed by venography. There was a statistically significant difference in thrombotic events between these groups. In the placebo arm, there were six deep venous thromboses (DVTs) and one pulmonary embolus (PE); in the warfarin arm, there was one PE. There was no difference in bleeding events between the arms; there were two major bleeding events, one fatal, in the placebo arm and a single nonfatal bleeding event in the warfarin arm. There was no difference in survival between the groups.

Because of concern that the benefit in preventing nonfatal thromboembolic events did not justify the expense and labor involved in giving low-dose warfarin, a follow-up study in 1995 estimated that low-dose warfarin would be not only cost-effective, but also cost-saving [13]. The amount saved was estimated to be 2,443 Canadian dollars per 100 patients. Based on this study, low-dose warfarin may be an option for patients who are receiving breast cancer chemotherapy and do not have a contraindication. However, such a practice has not been widely adopted in the USA. It is important to see if a simpler regimen of warfarin at 1 mg per day would also be effective. Such a regimen would certainly be even cheaper and more convenient and could be easily applied to patients receiving chemotherapy for other cancers.

Another drug that is commonly associated with derangement of coagulation is L-asparaginase, used almost exclusively in the treatment of acute lymphoblastic leukemia. This drug effects the depletion of L-asparagine, which in turn inhibits production of many plasma proteins, including fibrinogen, plasminogen, antithrombin III, protein C and protein S. Thrombotic complications often manifest as stroke or seizures, arise in 1%-14% of patients treated [14]. Unfortunately, since hemorrhage is also a potential complication of this drug, prophylactic anticoagulation is not employed. Adminstration of antithrombin III (AT III) has been shown to correct laboratory abnormalities, but has not been shown to affect clinical outcomes. As depleted fibrinogen can lead to bleeding, many physicians follow fibrinogen levels on patients treated with L-asparaginase and transfuse cryoglobulin if levels fall too low. Recent evidence indicates that patients with inherited defects in coagulation, such as Factor V_Leiden AT III deficiency, are at significantly increased risk of thrombosis due to L-asparaginase [15].

	Indwelling Central Lines and Venous Thrombosis

Top Abstract Introduction Thrombophilia of Malignancy Chemotherapy and Thrombosis Indwelling Central Lines and... Treatment of Thromboembolic... Heparin versus Warfarin LMWH Anticoagulants as Anticancer... Conclusions References

 
Patients with cancer often receive central venous access catheters for administering chemotherapy, blood products, fluids, medicines, and also for drawing blood for diagnostic tests. There is good evidence that these create an increased risk for DVT of the ipsilateral upper extremity. Although rates of symptomatic thrombosis are lower, clots have been venographically documented in 38%-62% of venous access devices [16, 17]. Several factors have been identified that may influence the risk of thrombosis. Left subclavian lines are at higher risk than the right [18]. Polyvinyl chloride or polyethylene lines are more likely to lead to PE than are polyurethane or siliconized lines [19]. A triple lumen catheter may be more thrombogenic than a double lumen. A line requiring two punctures for insertion was more thrombogenic than those placed with a single puncture. Finally, the type of fluid infused through the line may affect the thrombosis rate: infusion of total parenteral nutrition fluid has been found to be more thrombogenic than infusion of crystalloid fluid [20].

Upper extremity DVTs (UEDVT) can indeed give rise to PE. Asymptomatic cancer patients with indwelling central lines were screened with ultrasound to look for UEDVTs. In those with positive results, a nuclear ventilation/perfusion (V/Q) scan was then obtained regardless of whether the patient had symptoms of PE. Of 86 patients with UEDVT, 13 (15%) were considered to have PE by a high-probability V/Q scan [19]. Four of the 13 had signs or symptoms of PE. Of note, two of the 13 ultimately died of massive PE despite anticoagulation with heparin. In a study of patients (only a minority of whom had cancer) presenting with symptomatic UEDVTs, PE was found in 36% (8 of 22), based either on a high-probability lung ventilation/perfusion scan or pulmonary angiography [21]. Other investigators found that the relative risk was 3.4 when PE from catheter-related UEDVT was compared with other causes of UEDVT [22].

UEDVTs associated with indwelling catheters are therefore common and carry with them a significant risk for PE as well as the local morbidity associated with the thrombosis. Additionally, such thrombosis may lead to other costly procedures to clear or replace the central line. Are these DVTs preventable? In a randomized, prospective trial, Bern and coworkers demonstrated that 1 mg per day of warfarin is a safe and effective prophylaxis against thrombosis in cancer patients with central venous catheters [16]. Consecutive cancer patients receiving portacaths placed by surgeons were enrolled. If they had no contraindications to anticoagulation, they were randomized to receive either 1 mg per day of warfarin or no drug. Warfarin was initiated three days prior to the placement of the portacath. The distribution of cancers in both arms was similar. In those receiving warfarin, four out of 40 (9.5%) had thrombi; in the 40 patients who did not receive warfarin, 15 out of 40 (37.5%) had thrombi (p < 0.001). Similar results have been obtained in a study of British cancer patients receiving central venous lines [23]. A LMWH (dalteparin, Fragmin^®) also demonstrated benefit in preventing central catheter-associated thrombosis in cancer patients in a randomized, prospective trial [17].

Taken together, these studies show: A) UEDVT is common in cancer patients with indwelling lines; B) pulmonary embolus is a significant risk of these DVTs, and C) 1 mg per day of warfarin is a safe, cheap, and effective way to reduce the risk of UEDVT. Anticoagulation of indwelling central lines should be considered in all cancer patients who do not have a specific contraindication.

	Treatment of Thromboembolic Disease in Cancer Patients

Top Abstract Introduction Thrombophilia of Malignancy Chemotherapy and Thrombosis Indwelling Central Lines and... Treatment of Thromboembolic... Heparin versus Warfarin LMWH Anticoagulants as Anticancer... Conclusions References

 
Should the treatment of thromboembolic disease be any different for cancer patients than it is for noncancer patients? One concern is that cancer patients who are anticoagulated might have an increased risk of hemorrhage due to tumor, thrombocytopenia, or concurrent coagulation disorders. Retrospective studies do not provide a clear answer. Some did not find coexistent malignancy to be a risk factor for major hemorrhage during anticoagulation [24, 25] while some did [26]. In a prospective cohort study, cancer patients who received warfarin for the treatment of DVT and/or PE were no more likely than controls to have hemorrhage [27, 28]. A second concern is that compared to patients with nonmalignant disease, cancer patients are more likely to have a recurrence on warfarin or after warfarin is stopped [29-32]. Some authors suggest that instead of anticoagulating for 6-24 weeks for a first DVT, cancer patients need to be anticoagulated until there is no evidence of disease. Therefore, in treating a cancer patient with thromboembolic disease, the oncologist faces a situation where there may be a slightly greater risk of hemorrhage, but also a greater risk of recurrent thrombosis. In most nonmoribund cancer patients, anticoagulation for thromboembolic disease is usually begun unless potential contraindications exist.

Special conditions may be present which might present a relative or absolute contraindication to anticoagulation. Oncologists are often confronted with a patient with a brain tumor who requires anticoagulation for a DVT. There has been a long-standing reluctance to treat these patients with therapeutic anticoagulation due to the fear of intracranial hemorrhage. An alternative therapy that has been used is an IVC filter. There are no good prospective randomized studies to evaluate the relative safety and efficacy of IVC filter placement versus anticoagulation in this setting. A retrospective series can give us only rough estimates of efficacy and complication rates. The chance of recurrent PE after IVC filter placement is in the 3%-20% range [33, 34] and the rate of local thrombotic complication (IVC clot, DVT progression, recurrent DVT, or postphlebitic syndrome) ranges from 5%-57% depending on the series [33-37]. For comparison, the risk of thromboembolic events in similar patients treated with anticoagulants was 5%-20% [33, 36, 38]. The risk of intracerebral hemorrhage, the main concern of most clinicians in anticoagulating patients with brain metastases, was 0%-5% [33, 35, 38, 39]. In general, bleeding complications occurred in the setting of supratherapeutic anticoagulation. In summary, there are not enough data to make a definitive recommendation for therapy in the setting of a patient with both thromboembolic disease and brain metastasis. However, anticoagulation is a noninvasive, inexpensive, reversible intervention that has the advantage of treating the underlying clotting diathesis present in many of these patients. Although they reduce the PE risk, IVC filters do not correct the underlying coagulation defects and may themselves undergo thrombosis with its consequent lower extremity morbidity. This latter complication makes IVC filters an unattractive but sometimes unavoidable option.

Because they are highly vascular, renal cell and melanoma metastases to the brain are held in special regard by many clinicians, as these can have spontaneous hemorrhage. However, no trials have studied their risk of bleeding during anticoagulation. Until further safety information is available, anticoagulating patients with these metastases to the brain should be avoided.

	Heparin versus Warfarin

Top Abstract Introduction Thrombophilia of Malignancy Chemotherapy and Thrombosis Indwelling Central Lines and... Treatment of Thromboembolic... Heparin versus Warfarin LMWH Anticoagulants as Anticancer... Conclusions References

 
Does long-term heparin therapy afford any advantage over warfarin in the treatment of thromboembolic disease in cancer patients? No prospective randomized trial has compared heparin with warfarin for the treatment of thromboembolic disease. However, in an extensive retrospective analysis of patients with Trousseau's syndrome, a condition in which recurrent, migratory thromboembolism is found in patients with adenocarcinoma, it was found that 19% of patients benefited from warfarin therapy while 65% benefited from heparin therapy [40]. In a more recent retrospective review, cancer patients treated with warfarin for their first venous thromboembolism (VTE) had a recurrence rate of 22% within three months in contrast to those treated with heparin (standard or low molecular weight) who had a recurrence rate of 7% [32]. The clinical experience of many practicing oncologists also supports this impression. There are also anecdotal reports of patients with Trousseau's syndrome responding well to LMWH, which allows for their convenient outpatient treatment.

On a biochemical level, heparin has several antithrombotic mechanisms that warfarin lacks. Heparin can release tissue plasminogen activator and tissue factor pathway inhibitor (TFPI) from endothelial binding sites and increase their circulating levels. TFPI is a tri-domain protein that binds to the complex formed by tissue factor, factor VIIa, and factor X and suppresses the generation of Xa by tissue factor [41]. Heparin (both unfractionated and low molecular weight), but not warfarin, can increase the circulating amount of this protein and also increase its specific activity. Since tissue factor is an important stimulus to coagulation in cancer patients, activation of TFPI by heparin may contribute greatly to the overall antithrombotic effect of heparin.

Despite the impressive biochemical and retrospective clinical data already mentioned, there are no prospective clinical studies that address whether heparin is better than warfarin in the treatment of the first thromboembolic event in the cancer patient. Given the availability of LMWH and the added incentive of outpatient treatment for many of these VTE, a study comparing three to six months of warfarin versus three to six months of LMWH in cancer patients with VTE should have high priority.

Recurrent VTE in cancer patients on anticoagulant therapy is not uncommon. Prandoni [29] showed that recurrent VTE in oncology patients was 1.72 times more likely than for patients without cancer. There are no clear clinical data to guide the response to this situation. If a cancer patient has recurrent thromboembolism while on therapeutic doses of warfarin, the oncologist has three choices: A) continue warfarin at a higher target INR; B) switch to continuous intravenous unfractionated heparin or intermittent subcutaneous LWMH, or C) put in an IVC filter.

	LMWH

Top Abstract Introduction Thrombophilia of Malignancy Chemotherapy and Thrombosis Indwelling Central Lines and... Treatment of Thromboembolic... Heparin versus Warfarin LMWH Anticoagulants as Anticancer... Conclusions References

 
A recent addition to the anticoagulant armamentarium in the USA is LMWH. LMWH is prepared by chemical or enzymatic degradation of unfractionated heparin. Three LMWH preparations are currently available in the USA: enoxaparin (Lovenox^®), dalteparin (Fragmin^®), and ardeparin (Normiflo^®). Compared with traditional unfractionated heparin, LMWH has a narrower range of molecular weight distribution; unfractionated heparin contains molecules in the 5,000-30,000 dalton range, compared with LMWH molecules that are clustered in the 2,000-8,000 dalton range. LMWH is readily and consistently absorbed from a subcutaneous administration and has low serum protein and cellular binding which produces a bioavailability of over 85% compared with 15% for unfractionated heparin. LMWH is primarily excreted by the kidney with an elimination half-life of 3.5-4.5 h compared with 1.5 h for unfractionated heparin. The high bioavailability and longer half-life allow for twice-a-day or even daily dosing schedules based on weight to maintain therapeutic anticoagulation. Standard measurements of anticoagulation such as the partial thromboplastin time (PTT) are not usually prolonged and need not be regularly followed. If one does wish to evaluate the extent of anticoagulation with LMWH, an assay measuring the level of inhibition of factor Xa activation must be obtained. A level between 0.4-0.7 is generally considered therapeutic, but must be measured against a standard curve constructed using that specific LMWH.

There are now many reports which have demonstrated that LMWH is at least as safe, effective, and cost-effective as unfractionated heparin in treating deep venous thrombosis and even nonmassive PE in the general population [42-46]. In a prospective trial that randomized patients to unfractionated heparin or enoxaparin, analysis of the subgroup of patients who had cancer demonstrated that, as in the overall group, enoxaparin given twice a day was as effective as unfractionated heparin in the prevention of recurrent venous thromboembolism [47]. A retrospective analysis of the cancer patients participating in a number of trials comparing the safety and efficacy of unfractionated heparin and LMWH has also demonstrated a trend toward a mortality benefit independent of bleeding of recurrent thromboembolic disease in those cancer patients receiving LMWH [48, 49]. While intriguing, this finding must be validated in a prospective fashion to affect meaningfully the management of thromboembolic disease in cancer patients. In any case, LMWH offers the oncologist the opportunity to treat the majority of uncomplicated DVT cases safely, effectively, and cost-effectively at home. In the future, home LMWH treatment may also extend to the cancer patient with uncomplicated PE as well.

	Anticoagulants as Anticancer Therapy

Top Abstract Introduction Thrombophilia of Malignancy Chemotherapy and Thrombosis Indwelling Central Lines and... Treatment of Thromboembolic... Heparin versus Warfarin LMWH Anticoagulants as Anticancer... Conclusions References

 
A final issue is whether anticoagulation provides any benefit in treating the underlying malignant disease. In vitro studies show that warfarin, heparin, fibrinolytics, and even antiplatelet agents inhibit tumor growth and metastasis [50]. Thrombin and fibrin have been found to contribute to the adhesion and implantation of tumor cells, so antifibrin or antithrombin agents might exert their effects by inhibiting this implantation. Furthermore, heparin has been found to inhibit vascular endothelial growth factor, tissue factor, and platelet-activating factor, each of which may contribute to angiogenesis. It has also been hypothesized that fibrin deposits around tumors may offer protection against immune surveillance, so that anticoagulants might aid in immune clearance of small deposits of cancer cells. Although there are many hypotheses for in vitro antitumor activity of anticoagulants, the practical question is whether anticoagulants affect cancer mortality in a clinical setting.

The use of anticoagulants as an adjunct to cytotoxic chemotherapy has been studied in patients with small-cell lung cancer (SCLC). In a prospective randomized trial centered in a VA hospital, patients were given radiation therapy and chemotherapy for SCLC, and randomized to receive either warfarin or no anticoagulant therapy [51, 52]. The warfarin dose was targeted to give a prothrombin time twice that of control. Patients with either extensive or limited-stage cancers were enrolled. There was a statistically significant prolongation of survival demonstrated for those patients who received warfarin (median survival 49.5 weeks) compared with those who did not (median survival 23.0 weeks). Response rate was not significantly affected, but survival and time to relapse were. A follow-up study looking at warfarin as an adjunct in the treatment of prostate, colorectal, head and neck, and non-SCLC showed no survival benefit in these relatively chemotherapy-insensitive tumors [52].

In 1989, Cancer and Leukemia Group B (CALGB) described a trial randomizing patients with extensive stage SCLC to one of three arms [53]. Arm 1 received MACC (methotrexate, adriamycin, cytoxan, CCNU); arm 2 received MACC plus warfarin (PT 1.5-2 times control); arm 3 received alternating MEPH (mitomycin, etoposide, cisplatin, hexamethylmelamine) and MACC. There was a statistically insignificant (p = 0.14) overall survival advantage for arm 2 with similar advantageous trends for the warfarin arm for partial response, complete response, and failure-free survival (FFS). There was a statistically significant difference (p = 0.027) in overall response rate of 67% versus 51% favoring the warfarin arm.

In 1997, the CALGB published a study of warfarin added to a combination of ACE (adriamycin, cytoxan, and etoposide) and PCE (cisplatin, cytoxan, and etoposide) in the treatment of limited-stage SCLC patients [54]. The warfarin arm showed a survival benefit that did not reach statistical significance (p = 0.12). The survival curve plateaus were not, however, superimposable. Responders to chemotherapy who received warfarin had greater than twice the survival time (33 month versus 13.75 month, p = 0.05).

Another study examined the utility of subcutaneous unfractionated heparin as an adjunct to chemotherapy in the treatment of extensive and limited-stage SCLC. The heparin was administered in two or three daily subcutaneous doses starting at 500 U/kg/day, and adjusted to keep the PTT at two to three times the control value. Heparin was given for five weeks. The heparin-treated group experienced an increase in complete response (37% versus 23%, p = 0.004) as well as an increased median survival (317 versus 261 d, p = 0.01) [55]. In this study as in the others, anticoagulant was administered only near the time when chemotherapy was given. Despite the relatively short period of anticoagulation, benefits of improved survival were realized months to years later. This is analogous to the situation in venous thromboembolism, where the benefits of early short-term heparin therapy can be realized as a decreased rethrombosis rate many months later.

These results, obtained in a prospective, randomized fashion, suggest that there may be some survival benefit to anticoagulation in the treatment of SCLC. The effect is probably not large, judging by the difficulty in reaching statistical significance in the CALGB studies, but there does appear to be a consistent small benefit. The administration of low levels of anticoagulant is, in general, much less toxic and expensive than the addition of another chemotherapy agent, or the use of high-dose chemotherapy with stem cell support. While intriguing, however, the data are not sufficiently convincing to alter current clinical practice. With the introduction of the LWMH, there is renewed interest in determining whether anticoagulation may improve survival in oncology patients.

	Conclusions

Top Abstract Introduction Thrombophilia of Malignancy Chemotherapy and Thrombosis Indwelling Central Lines and... Treatment of Thromboembolic... Heparin versus Warfarin LMWH Anticoagulants as Anticancer... Conclusions References

 
Thromboembolic disease is a frustrating and common complication of malignancy. The biochemical basis of the thrombophilia of malignancy is poorly understood and studies to unravel its cause and relationship to the underlying malignancy are sorely needed. Current treatment for DVT and PE in cancer patients includes heparin, warfarin, and sometimes IVC filters. The last option is usually reserved for those patients who are not candidates for anticoagulation. Since heparin provides some additional antithrombotic effects that warfarin lacks, it will be important to study whether LMWH may be better than warfarin in the long-term treatment of venous thromboembolism. Furthermore, there is suggestive evidence that warfarin and heparin may actually enhance cancer survival rates; prospective studies are currently underway to address this issue. The introduction of LMWH should greatly improve the convenience of anticoagulation therapy for oncology patients.

	Acknowledgments

 
This work was supported by NIH grants CA09172-24 (A.L.), HL54838 (D.K.), and HL61222 (D.K.).

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Top Abstract Introduction Thrombophilia of Malignancy Chemotherapy and Thrombosis Indwelling Central Lines and... Treatment of Thromboembolic... Heparin versus Warfarin LMWH Anticoagulants as Anticancer... Conclusions References

 

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