Exposure to Air Pollution Increases The Risk of Deep Vein Thrombosis

A Review of Baccarelli et al., by Gregory Piazza, MD

Article: Baccarelli A, Martinelli I, Zanobetti A, et al. Exposure to Particulate Air Pollution and Risk of Deep Vein Thrombosis. Arch Intern Med 2008;168:920-927.

May 14, 2008; 8:04 a.m. (EST): Is exposure to particulate air pollution a risk factor for deep vein thrombosis (DVT)?  This case-control study evaluated 870 DVT patients and 1210 control subjects from the Lombardy region of Italy between 1995 and 2005.  The investigators estimated the exposure to particulate matter less than 10 μm (PM10) in aerodynamic diameter using area-specific mean levels obtained from ambient monitors in the year before development of DVT.  Higher mean PM10 levels in the year before examination were associated with abnormal coagulation testing (shortened prothrombin time) in both cases and controls.  After adjustment for clinical and environmental factors that may have contributed to the risk of DVT, each increase in 10 μg/m3 was associated with a 70% increase in the risk of DVT (odd ratio [OR], 1.70; 95% confidence interval [CI], 1.30 to 2.23; p < 0.001).  A linear relationship of exposure to risk was noted over the observed PM10 range.  Interestingly, the association between PM10 level and risk of DVT was weaker in women (OR, 1.40; 95% CI, 1.02 to 1.92; p = 0.02), especially among those using oral contraceptives or hormone replacement therapy.

Although subject to the limitations of a case-control analysis, this study highlights an important association between risk factors for atherosclerosis and venous thromboembolism (VTE).  Recent data have shown that potent risk factors for arterial thrombosis such as hypertension, obesity, and diabetes, also predispose to VTE.  Previous studies have established air pollution as a risk factor for coronary artery disease and stroke.  This study suggests that air pollution should be added to the growing list of factors that increase the risk of both arterial and venous thrombosis. 

This study also highlights the importance of addressing air pollution as a potentially modifiable risk factor for atherosclerosis and VTE and a public health threat.

Gregory Piazza, M.D.
Venous Thromboembolism Fellow
Brigham and Women’s Hospital, Boston, MA

Global Registry on PMT for Acute PE – Development of a Case Report Form

William T. Kuo, MD, FCCP

Vascular and Interventional Radiology, Stanford University Medical Center, Stanford, CA 94305

INTRODUCTION: The Stanford Division of Vascular and Interventional Radiology has drafted a case report form (CRF) for the Global Registry on Percutaneous Mechanical Thrombectomy (PMT) for Acute Pulmonary Embolism.  This draft serves as an initial template for gathering data relevant to the endovascular treatment of massive PE.

We realize there is no widely accepted protocol for catheter-directed treatment of pulmonary embolism, and the PE management algorithm itself varies among institutions.  Furthermore, existing treatment regimens are continuously evolving with the development of new catheters, devices, and treatment protocols.  Consequently, this Case Report Form has been designed to capture data not only on existing catheter-based methods but also on emerging techniques. 

In the final step of completing this document, and prior to its official launch, we open the CRF via the web to commentary and feedback from all interested participants of the North American Thrombosis Forum (NATF).  We are seeking input from all potential collaborators and investigators.  Acceptable ideas and recommendations by consensus will be incorporated into the CRF and contributors acknowledged. 

As part of a worldwide multidisciplinary effort, our goal is to create an effective web-based registry that will study the effects of PMT for acute PE.  Please contact us with questions, comments, and feedback.  We greatly appreciate your input in the creation of this international registry. 

 

Electronic submission of The Global Registry on Percutaneous Mechanical Thrombectomy (PMT) for Acute Pulmonary Embolism CASE REPORT FORM (CRF) requires Adobe Reader version 7.0 or higher.   Mac Ι PC

An Update on the Issues Related to the Contaminant in Heparin

Jawed Fareed, Ph.D, D.SC, Loyola University Medical Center– Maywood, IL., USA.

Click here to view "Comparative Studies on Oversulfated Chondroitin Sulfate and Heparin Contaminant" slide set (PDF: 2.1 MB).

Submitted: May 1, 2008; 4:27 p.m. (EST): Several significant developments have occurred with regard to the contaminant in heparin since our first web posting on NATFonline.org.  The US FDA has introduced quality assurance methods in importing the heparins (API) into the United States.  Working with academic scientists, the agency has introduced the requirements for the NMR analysis and capillary electrophoresis profile of these heparin related products.  As a result, only purified and well-characterized heparin can be imported.  To improve and expedite quality assurance measures with regard to heparin, the US FDA has also initiated various programs utilizing advanced analytical methods and molecular techniques such as the PCR.  In addition to the changing analysis, additional biologic data on heparin may be helpful to assure the quality of heparin.  The US FDA, with USP and other International regulatory agencies, has initiated various procedures to harmonize the International controls for the quality assurance of heparin.  Since about 70% of the heparin isolation originates in China and is used globally for the manufacturing of low molecular weight heparin and other heparin related products, a harmonized procedure for quality assurance is important.  The US FDA has also addressed the identification of the contaminant with various specific groups and experts.  As a result, the main contaminant has now been identified to be hypersulfated chondroitin sulfate.  The synthesis and anticoagulant properties of oversulfated chondroitin sulfate have been reported earlier. (6)  Bovine and shark cartilage can be used to obtain chondroitin sulfate which can be oversulfated by chemical methods and exhibits anticoagulant properties. 

On April 23, two multi-authored publications appeared online reporting on the chemical structure of the contaminant and its association with the nature of adverse events. (7,8)  These publications focused on oversulfated chondroitin sulfate and primarily indicated that this substance is responsible for the adverse events and the reported deaths.  The molecular profile of chondroitin sulfate can be readily adjusted to mimic unfractionated heparin.  The oversulfated chondroitin sulfate is normally not present in heparin.  It contains an unusual tetrasulfated disaccharide unit consisting of a glucuronic acid linked to N-acetylgalactosamine.

Guerrini et al, reported that oversulfated chondroitin sulfate is a contaminant in heparin associated with adverse clinical events. (7)  They examined different lots of heparin that were responsible for the adverse events using NMR methods.  They showed that the disaccharide unit in the contaminant exhibits unusual sulfation pattern, sulfate at the 2-0 and 3-0 positions of the glucuronic acid, in addition to 4-0 and 6-0 position of the galactosamine.  Under normal circumstances heparin is devoid of these structures.  This group compared the structure of the semi-synthetic oversulfated chondroitin sulfate with the contaminant and concluded that these were structurally similar compounds.  It may be true that the detectable contaminant in the recalled heparins is oversulfated chondroitin sulfate, however, it has been commented that the contaminated heparins may also contain other heparin-derived structures and related agents.  The authors used a differential precipitation technique and nitrous acid degradation.  A proper way to remove heparin would have been to use heparinase-1 digestion and the isolation of the residual material.  The differential precipitation and nitrous acid digestion may eventually eliminate other contaminants which may contribute to some of the adverse effects observed with contaminant heparin.  Moreover, the complexity of the adverse reactions is unlikely to be solely dependent on the oversulfated chondrotin sulfate.

The second paper discussed that the contaminant is  primarily responsible for the activation of  kallkrein-kinin system, resulting in the generation of bradykinin which may be the primary mediator of the hypotensive responses seen in patients administered with contaminated heparin. (8) 

While the authors of both of these manuscripts are to be commended for the expeditious work of the preliminary experiments to address their hypothesis—that oversulfated chondroitin sulfate is primarily responsible for the reported adverse events after the administration of contaminated heparin. However, their interpretations are mostly based on speculations and limited preliminary data.

As stated, while oversulfated chondroitin sulfate represents one of the main detectable contaminants, the recalled heparin preparations may also contain several other heparin-like and non-heparin substances, many of which have not been fully investigated and their association with the reported adverse events is not established.

The single case report described by the authors on the patient developing hypotension and other adverse reactions during dialysis represents an incidental finding and the authors fail to describe the nature of anaphylactoid reaction. Moreover, none of the plasma markers such as the bradykinin and other mediators for anaphylaxis were reported. In addition, the authors did not provide the amount of contaminant in the heparin preparation that this patient was exposed. This single case report does not prove cause/ effect for oversulfated chondroitin sulfate in producing anaphylaxis.

The reported amidolytic activity of generated kallikrein represents a non-specific method, which should have been evaluated in conjunction with pre-kallikrein and high molecular weight kininogen levels in various systems studied.  Moreover, the amount of kallikrein generated varied widely and the relevance to bradikynin was not established.  Hypersulfated glycosaminoglycans have been used for therapeutic purposes for some time.  In the in vitro studies, all of these are known to produce varying degrees of activation of prekallikrein into kallikrein.  This includes heparin and therapeutic preparations of mucopolysaccharide polysulfate.  In fact, if bradykinin was the major mediator of the adverse reactions then most patients treated with contaminated heparins would have shown similar symptoms.

The reported in vivo studies utilizing a pig model represent only a few animals per group with wide variations. For example, of the 6 pigs treated with oversulfated chondroitin sulfate contaminated heparin only 2 showed a clear drop in blood pressure. It is not surprising that of the 3 pigs treated with OSCS a profound drop on blood pressure was observed.   Moreover, there are major species variations.  For example, dogs treated with the contaminant do not show any hypotensive effects (data not shown).  This material has never been tested for these observed effects, which may be related to several additional factors such as the molecular weight, degree of sulfation, and the release of other mediators such as nitric oxide.  The authors should have provided supportive evidence of the generation of hypotensive mediators in conjunction with pre-kallikrein and high molecular weight kininogen.  Moreover, the generation of kallikrein in the pig treated with contaminated heparin and oversulfated chondroitin sulfate does not correspond with the observed hypotensive effects in these studies.  Furthermore, the concentration of heparin and related agents were rather high is these studies.
  
From a statistical standpoint, the interpretations on the relevance of contact activation mediated generation of bradykinin in the in vitro studies and pig model may not be relevant to the adverse reactions and deaths. The behavior of oversulfated chondroitin sulfate when injected in combination with heparin may be different when compared with oversulfated chondroitin sulfate administered alone. The authors have stated that 5mg/ Kg of oversulfated chondroitin sulfate - contaminated heparin was given to 6 pigs in a single intravenous dose. The amount of oversulfated chondroitin sulfate in this preparation should have been defined. Moreover, a dose dependent effect of oversulfated chondroitin sulfate was not discussed to justify the anaphylactoid response.

The nature of the reported adverse events related to the use of contaminated heparin is complex and multifactorial, which understandably is related to several clinical factors.  Although this manuscript provides preliminary data on the generation of kallikrein and anaphylotoxins without proper controls of oversulfated chondroitin sulfate alone, heparin and dextran sulfate, these results are highly questionable and should not be considered for a cause/effect for the catastrophic hypotensive syndrome leading to death in over 81 patients. Therefore, until further observations in well-designed and statistically valid studies, this preliminary report should be considered with extreme caution.

The presence of the contaminant has far reaching consequences.  It now has a global impact. Heparin and related products have been recalled in several different countries around the world.  Interestingly, the reported deaths only occurred in the US with the use of unfractionated heparins.  Moreover, there is a concern that the reported effect between the chondroitin sulfate and adverse reactions and dates may not be valid.  Heparin is obtained from a complete exhaustion procedure.  It remains to be a complex agent both commercially and biologically which is not fully characterized until this time.  Since the low molecular weight heparins are prepared by the depolymerization of porcine mucosal heparin, it is expected that the contaminant is present in the available low molecular weight heparin.  It is indeed not surprising that the contaminant is also reportedly present in the low molecular weight heparins produced by using porcine mucosa. However,  since the molecular weight of hypersulfated chondroitin sulfate is nearly 20,000, it is surprising to have this material in the low molecular weight heparins.  However, since all of the low molecular weight heparins are produced by the depolymerization of unfractionated heparin, it is likely to have contaminant products in these agents.  

Regarding the presence of the heparin contaminant, namely oversulfated chondroitin sulfate, in the LMWH preparations, it is surprising that this contaminant was not detected in the contaminated batches of recalled enoxaparin. Because of the high molecular weight nature of oversulfated chondroitin sulfate, it is logical that molecular profiling method may have resulted in an averaged high molecular weight with the contaminants.  This is of particular concern, as the low molecular weight heparins (LMWHs) are usually profiled in the European Pharmacopeial (EP) method which utilizes a detection at 234nm.  When compared, the mixtures of the contaminant with both the heparins and enoxaparins utilizing the narrow range calibrator (NRC) method and the EP method show different results (9). In the NRC method, the contaminant at a 50% level nearly doubled the molecular weight for the enoxaparin preparations. In the case of heparin, only slight increases were noted in the presence of the contaminant. Interestingly, in the EP method, when the contaminant was mixed with enoxaparin at a 50% level it did not produce any significant increase in molecular weight due to the nondetectibility of the oversulfated chondroitin sulfate.  Therefore, it is not surprising that the enoxaparin samples with varying degrees of the contaminant are released. This observation has a major implication on the validity of the EP method for molecular profiling of various LMWHs. The additional requirements from the FDA to include NMR and capillary electropheresis will assure the product origin and composition.

It is reassuring that the regulatory bodies and scientific community is concerned regarding the deliberate alteration of heparin and related products by the addition of a oversulfated chondroitin sulfate.  The failure to quality assure the heparin and enoxaparin for this contaminant, in this era of high technology, indicates inadequate oversight and limitation of resource allocation.  Heparins are multicomponent complex drugs which are not fully characterized at this time.  Therefore, any deliberate attempts to contaminate these agents will be difficult to probe.

Hopefully the regulatory bodies and scientific community will continue to investigate the true nature of the pathogenesis and its causes.  Increased regulatory oversight and inclusion of some of the proposed analytical methods and biological assays will be helpful.

Despite remarkable advances in drug development, a heparin substitute with the wide clinical application attributed to this universal anticoagulant has not been possible.  The newer drugs, including pentasaccharides and parenteral and oral anti-Xa and anti-IIa agents are limited in their indications.  For open heart surgery and dialysis it is difficult to replace heparin.  Heparin and its derivatives have long been used for the management of anticoagulation, and with the newer regulatory oversight recommendation, heparin will sustain and continue to be a crucial drug to manage anticoagulation in years to come.

References:

1. Contaminant detected in heparin material of specified origin in the USA and in Germany: serious adverse events reported: recall measures initiated.  World Health Organization Alert No. 118(& March 2008). http://www.who,int/medicines/publications/drugalerts/Alert_118_Heparin.pdf
2. Notice of Recall from Rotexmedica to Bfarm (German Regulatory Authorities).  Rotexmedica/Bfarm Notice (& March 2008). http:www.akdae.de/20/40/Archiv/2008/2008-310.pdf
3. 2008 Heparin Recall Information. Baxter Investigation Updates (5, 14, 19 March 2008). http://www.baxter.com/products/biopharmaceuticals/heparin.html
4. Baxter provides update on investigation.  Baxter Investigation Update (14 March 2008). http://www.baxter.com/products/biopharmaceuticals/downloads/heparin_03-14-08/pdf
5. Communication. Information on heparin sodium injection.  US Food and Drug Administration. http://www.fda.gov/cder/drug/infopage/heparin/default.htm
6. Maruyama T, Toida T, Imanari T, et al.  Conformational changes and anticoagulant activity of chondroitin sulfate following its O-sulfonation. Carbohydr. Res. 306, 35-43, 1998.
7. Guerrini M, Beccati D, Shriver Z et al.  Oversulfated chondroitin sulfate is a contaminant in heparin associated with adverse clinical events.  Nature Biotechnology 10:p1-7;208, 2008.
8. Kishimoto TK, Viswanathan k, Ganguly T et al.  Contaminated heparin associated with adverse clinical effects and activation of the contact system.  N J Med published at www.nejm.org, April 23, 2008.
9. Ahsan A, Jeske w. Mardiguian J et al.  Feasibility study of heparin mass calibrator as a GPC calibrator for heparins and low molecular weight heparins.  Journal of Pharmaceuticals Sciences, 1994; Vol (83):197-201.

From the Archives: NATF Heparin Contaminant Articles

Contaminant in the Recalled Unfractionated Heparin Preparations: Where is the Problem?: Hoppensteadt DA, Fareed J, Wahi R, Adiguzel C, Bick RL.
http://www.natfonline.org/mar_08/ethrombosis_mar08.php

Addendum: Contaminant in the Recalled Unfractionated Heparin Preparations: Where is the Problem? Loyola University Medical Center
http://www.natfonline.org/mar_08/ethrombosis_mar08.php

Contaminated Heparin: An Update - ARTICLE AND SLIDE SET: Fareed J.
http://www.natfonline.org/mar_08/ethrombosis_mar08.php

Heparin-Induced Thrombocytopenia (HIT) Profile

Debra A. Hoppensteadt, Ph.D., Jawed Fareed, Ph,D, Rakesh Wahi, M.D., Cafer Adiguzel, M.D., Rodger L. Bick, M.D., Ph.D.

Article: Morris TA, Castrejon S, Devendra G, Gamst AC. No difference in risk for thrombocytopenia during treatment of pulmonary embolism and deep venous thrombosis with either low-molecular-weight heparin or unfractionated heparin. CHEST 2007;132:1131-1139.

ABSTRACT: Background: Low-molecular-weight heparin (LMWH) is a popular alternative to unfractionated heparin (UH) for the treatment of pulmonary embolism (PE) and deep vein thrombosis (DVT), in part based on the perception of a lower risk for heparin-induced thrombocytopenia (HIT). To investigate the evidence supporting this perception, we performed a metaanalysis to compare the incidence of thrombocytopenia between LMWH and UH during PE and/or DVT treatment. Methods: Randomized trials comparing LMWH with UH for PE and/or DVT treatment were searched for in the MEDLINE database, bibliographies, and by correspondence with published investigators. Two reviewers independently selected high-quality studies and extracted data regarding heparin-associated thrombocytopenia (HAT), HIT confirmed by laboratory testing, and heparin-induced thrombocytopenia with thrombosis (HITT). Outcome rates between LMWH and UH were compared using a binomial, generalized linear mixed model with a logit link and Gaussian random effects for study. Results: Thirteen studies involving 5,275 patients met inclusion criteria. There were no statistically significant differences in HAT rates between the two treatments (LMWH, 1.2%; UH, 1.5%; p = 0.246). The incidence of documented HIT and HITT was too low to make an adequate comparison between groups. Conclusions: Our review disclosed no statistically significant difference in HAT between LMWH and UH and insufficient evidence to conclude that HIT and HITT rates were different between them. There was no evidence from randomized comparative trials to support the contention that patients receiving treatment for PE or DVT with UH are more prone to these complications than those receiving LMWH.

Review of Morris et al. HIT Rates During VTE Treatment: Questionable Meta-analysis of LMWH versus UFH

Melkon Hacobian, MD; VTE Clinical Fellow, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA 02115

BACKGROUND
Low molecular weight heparin (LMWH) compared with unfractionated heparin (UFH) has less risk of heparin-induced thrombocytopenia (HIT) for the treatment of pulmonary embolism (PE) and deep vein thrombosis (DVT). 

OBJECTIVES
To investigate the evidence supporting this assumption, a meta-analysis was performed by Morris and colleagues to compare HIT rates of LMWH versus UFH during PE or DVT treatment. 

METHODS
Randomized controlled trials from 1985 to 2006, comparing LMWH with UFH to treat PE or DVT, were reviewed by two independent investigators. Thirteen (13) studies were selected for analysis.

CONCLUSION
Morris and colleagues found no statistically significant difference in HIT rates between LMWH and UFH. The rate of HIT was low in both groups.

Low molecular weight heparins (LMWH) and unfractionated heparin (UFH) are effective drugs to treat and prevent venous thromboembolism (VTE). LMWH have been shown to have a lower risk for thrombocytopenia in a number of well designed and population based studies. Morris and colleagues conducted a meta-analysis to compare rates of heparin-induced thrombocytopenia (HIT) in patients treated for VTE with either LMWH or UFH (CHEST 2007; 132: 1131-1139).

They reached the startling conclusion that HIT rates were similar with both LMWH and UFH. In this commentary, I will probe some of the flaws in their manuscript and the design of their investigation.

The first problem was that their definition of HIT had a lot of “noise”. They did not use a standard definition of HIT. A patient with a platelet count as high as 120,000 was classified as having HIT. This was true even if there was no drop in the platelet count after beginning heparin administration. They did not require any laboratory confirmation, such as PF4 testing, for suspected HIT.

The second problem is that they did not include patients receiving LMWH or UFH for prevention of VTE. For this indication, HIT is well established as occurring more often with UFH than LMWH. This is not surprising because heparin prophylaxis continues longer than heparin treatment, thus, raising the likelihood of an adverse immune reaction.

Finally, in a less restrictive meta-analysis that included more trials than Morris et al, RL Levine and colleagues found that with VTE treatment, UFH was far more likely to cause HIT than LMWH (CHEST 2006; 130: 681-687). Morris and colleagues have difficulty explaining this discrepancy.

For now, the major “Take Home” lesson is that HIT occurs more often with heparin prophylaxis than with heparin treatment. The meta-analysis by Morris et al was probably underpowered to show a difference in HIT rates between LMWH and UFH. However, even in their analysis, there was a trend toward more frequent HIT with UFH than with LMWH.

About Melkon Hacobian, MD: Dr. Hacobian completed his internship and residency in Internal Medicine at UMass Memorial Medical Center.  In July of 2008, Dr. Hacobian will begin his Cardiology fellowship at the Maine Medical Center in Portland, ME. As a Venous Thromboembolism Research Group fellow, he is currently involved with investigator initiated and multicenter trials at Brigham and Women's Hospital His current research interests include Warfarin Pharmacogenomics and novel anticoagulant treatment strategies for venous Thromboembolism.  

From the Archives: NATF HIT Articles

Heparin-Induce Thrombocytopenia Education Programs: Steven Baroletti, PharmD, MBA, Brigham and Women’s Hospital, Boston, MA 02115
http://www.natfonline.org/prophylaxis/2008/Baroletti_Summary.pdf

Heparin-Induced Thrombocytopenia (HIT): Management Challenges: Lina Matta, PharmD, Brigham and Women’s Hospital, Boston, MA 02115
http://www.natfonline.org/prophylaxis/Graphics/Content/Matta_Slides.pdf

Heparin-Induced Thrombocytopenia (HIT): Overview: Jeanine M. Walenga, PhD, Loyola University Medical Center, Maywood IL 60148
http://www.natfonline.org/sept_2007/ethrombosis_sept2007.html

HIT: Patient Education—Circulation, Cardiology Patient Page: Baroletti SA, Goldhaber SZ. Circulation 2006;114:e355-e356
http://circ.ahajournals.org/cgi/content/full/114/8/e355

NATF Traveling Fellowship Program: APPLICATION DEADLINE IS JULY 15, 2008

With the goal of exploring the cross-disciplinary diagnosis, treatment, education, and research related to thrombosis, the NATF Traveling Fellowship Program is an annual scientific exchange opportunity for physicians (either Junior Faculty or physicians-in-training), scientists, nurses, or pharmacists.  NATF will provide an award equivalent to $5,000 for lodging and travel for one Fellow selected to visit a North American thrombosis research and education center of his or her choice for up to 10-30 days.

The NATF Traveling Fellow will:

• Work on a joint project with hosting center
• Contribute to the development of a cross-disciplinary approach for the research, diagnosis, treatment, and education thrombosis
• View research facilities and thrombosis diagnosis, treatment, and prevention methods
• Participate in scientific symposia with members of the NATF Board and Scientific Advisory Committee
• Free participation in the 2008 North American Thrombosis Forum Thrombosis Summit (Boston, MA, September 27, 2008) attended by cross-disciplinary medical and scientific leaders
• Present learnings gained through NATF Traveling Fellowship at the Fall 2009 North American Thrombosis Forum Thrombosis Summit
• Serve as an NATF Ambassador

To learn more about the NATF Traveling Fellowship or to apply, please click here.

Benefits of the NATF Traveling Fellowship

• Foster an exchange of scientific information, stimulate research and expanded education, and develop friendships among leaders in thrombosis research, treatment, and patient education
• Serve as a bridge that may be used to forge the future of thrombosis treatment and prevention that includes a cross-disciplinary approach
• Provide a stimulus for leadership by recognizing young medical personnel or scientists with the potential for nationally lowering the rate of life-threatening thrombotic episodes through education, research, and prevention

NATF Committment to Future Leaders

The NATF Traveling Fellowship Program was conceptualized to allow scientists and health professionals (MD, DO, PhD, RN, or PharmD) the opportunity to expand their fund of knowledge, as well as build positive and enduring relationships with others concerned with thrombotic disorders. NATF recognizes the vital impact training programs have on the future of thrombosis research, diagnosis, treatment, and prevention.

Application Requirements

• The Fellow will be selected by the NATF Advisory Committee, Chaired by Dr. Arthur A. Sasahara, MD, Professor of Medicine, Emeritus, Harvard Medical School, and NATF Director.
• The fellowship will be granted based on a demonstrated commitment to excellence in education, research, or clinical practice.
• 3 Letters of reference are required.
• Applicants must be practicing in North America:  Application Deadline is July 15, 2008

The North American Thrombosis Forum is a 501(c)(3) nonprofit organization that focuses on unmet needs and issues related to thrombosis and cardiovascular diseases such as deep vein thrombosis, pulmonary embolism, myocardial infarction, peripheral arterial occlusive disease, and stroke. The five areas of major focus are: 1) basic translational research, 2) clinical research, especially diagnosis and therapy, 3) prevention and education, 4) public policy, and 5) advocacy. NATF's legacy will be to improve patient care, outcomes, and public health by supporting thrombosis-related programs, such as novel research projects, innovative educational programs, public policy initiatives, regulatory issues and advocacy, and to broaden training opportunities for scientists and health professionals (physicians, nurses, pharmacists).

Our offices are located at 1620 Tremont Street, Suite 3022; Roxbury Crossing, MA 02120.  For general information, please call (617) 525-8326 or email: info@NATFonline.org.

Proactive Thrombosis Prevention Lectures: Saturday, March 1, 2008

1.	Stroke Update Farzaneh A. Sorond, MD, PhD
2.	Coronary Stent Thrombosis Frederic S. Resnic, MD, MSc
3.	Peripheral Arterial Disease Update Marie Gerhard-Herman, MD
4.	PE Diagnosis Paul D. Stein, MD
5.	Heparin-Induced Thrombocytopenia Education Programs Steven Baroletti, PharmD, MBA
6.	Generic vs. Brand Name Drugs Jawed Fareed, PhD
7.	Electronic Alerts to Prevent DVT Karen Fiumara, PharmD
8.	Novel Anticoagulants John Fanikos, RPh, MBA
9.	Anticoagulation Update Samuel Z. Goldhaber, MD
10.	Patient Education and Patient Compliance Rita M. Morrison, RN, BSN and Ruth B. Morrison, RN, BSN, CVN
11.	Point-of-Care INR Testing Jack E. Ansell, MD
12.	Patient Advocacy Kelly Clark, NATF Patient Advocate

 

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