eMedicine Specialties > Hematology > Coagulation, Hemostasis, and Disorders

Antithrombin Deficiency: Treatment & Medication

Author: Arun Rajan, MD, Clinical Fellow, Medical Oncology Branch, National Cancer Institute/National Institutes of Health
Coauthor(s): Sara J Grethlein, MD, Associate Dean for Graduate Medical Education, Professor, Department of Internal Medicine, Division of Hematology and Oncology, State University of New York Upstate Medical University; Rajalaxmi McKenna, MD, FACP, Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems
Contributor Information and Disclosures

Updated: Oct 4, 2009

Treatment

Medical Care

  • In a patient with a known inherited antithrombin deficiency (AT deficiency), management of the acute thrombotic event depends on the type of antithrombin deficiency, because a variable response to large doses of heparin occurs in some of these patients. When a therapeutic response to intravenous heparin is not achievable, additional support with an antithrombin concentrate may be necessary.39
    • Low molecular weight heparins (LMWHs) also require antithrombin for their antithrombotic action. Not much is known about the use of LMWHs in these patients.
    • The synthetic anti–factor Xa pentasaccharide also requires adequate amounts of antithrombin for its action.
  • Patients who have had an episode of DVT and whose antithrombin deficiency has been recognized should receive lifelong oral anticoagulation to protect them from recurrent VTE, the development of thrombosis at other sites, or both. Patients who present with atypical site thrombosis, such as mesenteric or hepatic vein thrombosis, should be placed on lifelong anticoagulation immediately. A variety of precipitating factors, such as taking oral contraceptives or hormone replacements (which should be discontinued), may precede the development of VTE. Patients with known antithrombin deficiency need aggressive antithrombotic prophylaxis during high-risk situations such as surgery and pregnancy.
  • In the future, in patients with antithrombin deficiency (AT deficiency), synthetic direct thrombin inhibitors that do not require antithrombin for their anticoagulant effect (eg, argatroban) could be tried. Such inhibitors are also more desirable, because they may obviate the need for exposure to biologic products such as plasma or antithrombin concentrate, currently required for the adequate anticoagulant action of presently available agents.
  • Few adequate clinical trials have been carried out to answer the question of the possible utility of antithrombin concentrates in pregnancy-related disorders.
  • In animal models of hepatic failure as well as in human studies, replacement with antithrombin concentrates at variable time points has generated differing results, with some showing control of DIC without any obvious impact on bleeding, whereas others have not had any significant impact on outcome.
  • In patients undergoing orthotopic liver transplantation, it has been suggested that prophylactic administration of antithrombin concentrates may be beneficial in minimizing the DIC. Once again, large, prospective, multicenter randomized clinical trials are needed, because published clinical data have shown both efficacy and a lack of it. In this context, note that, in a very small study involving children undergoing orthotopic liver transplantation, administration of antithrombin concentrate (along with fresh frozen plasma [FFP], prostaglandin E1, and LMWH) was beneficial in reducing the frequency of hepatic arterial thrombosis.
  • Antithrombin supplementation has been suggested to be useful in patients with the following conditions or those undergoing the following procedures (The value of replacement in all of these procedures and conditions has not been clearly proven in unbiased trials):
    • Malignancies
    • Sepsis
    • Shock
    • Open heart surgery
    • Orthopedic procedures
  • A phase III, double-blind, placebo-controlled, randomized multicenter trial found that administration of high-dose antithrombin within 6 hours of the onset of sepsis and septic shock in adults had no effect on 28-day all-cause mortality rates. Increased bleeding occurred in patients who received the antithrombin concentrate and heparin (low or therapeutic doses of heparin).
  • Each unit of FFP obtained from a blood bank contains whatever "normal" level of antithrombin the individual donor had. If a patient requires 3000 U of antithrombin, that patient would require 3000 mL of FFP given rapidly to raise the level of antithrombin in the recipient. Clearly, volume overload becomes a problem in such patients, particularly more so in patients with an inability to tolerate large volumes. Thus, FFP replacement is not a reasonable source of repeated antithrombin replacement; rather, FFP is a choice only when no concentrate is available.
  • Pooled plasma treated with solvent-detergent (PLAS+SD) is available to treat any condition in which FFP is typically used and for which no factor concentrate is available. Viral inactivation using the solvent-detergent (SD) process has been used in preparation of coagulation factor concentrates in the past. In vitro treatment of donor plasma with 1% of the solvent tri(n-butyl) phosphate (TNBP) and 1% of the detergent Triton X-100 leads to significant inactivation of a broad spectrum of lipid-enveloped viruses.
    • Studies of viral inactivation using the SD process show significant inactivation of the human pathogenic viruses hepatitis B (HBV) and C (HCV) and human immunodeficiency virus (HIV). Other lipid-enveloped viruses (eg, Sindbis virus, bovine viral diarrhea virus) have also been used to monitor inactivation.
    • PLAS+SD is ABO blood type specific, and SD-treated plasma should be ABO compatible with the recipient's red blood cells.
    • The frozen product is supplied in 200-mL bags. Each 200-mL bag has been demonstrated to raise factor levels by approximately 2-3%, with 4-6 bags raising the factor level of a 70-kg person by approximately 8-18%.
    • Monitoring of specific factor levels before and after product infusion is important to ensure that hemostatically adequate levels are achieved and maintained to provide adequate hemostasis.

Surgical Care

Replacement with antithrombin concentrate is necessary in patients with known antithrombin deficiency (AT deficiency). In patients with acute severe trauma, some studies suggest a beneficial effect with prophylactic replacement. The frequency of antithrombin replacement depends on the half-life of the product, but in the presence of active bleeding, more frequent replacement should be based on antithrombin levels.

In acquired disorders, correction of antithrombin levels allows heparin to exert its full antithrombotic effect. Such replacement is necessary to maintain a minimum of 80% antithrombin activity until the full therapeutic effect of oral anticoagulants is obtained. Serial assessment of antithrombin levels is necessary to assure the adequacy of the dosing.

Consultations

  • Close consultation with a hematologist is necessary.
  • Obtain consultation with a geneticist as needed.
  • The support of a laboratory equipped to assay antithrombin activity is necessary in patients receiving antithrombin replacement therapy.

Diet

A healthy, normal diet is appropriate.

Activity

A patient's activity level depends on the clinical circumstance. Activity in patients with acute venous thromboembolic disease depends on their overall clinical status. Patients with antithrombin deficiency (AT deficiency) and thrombosis should receive in-hospital treatment for their acute illness.

Medication

A nonrandomized open-label phase III trial of recombinant human antithrombin (rhAT) in patients with hereditary antithrombin deficiency (AT deficiency) in high-risk situations for thrombosis (nonpregnant surgical patients or pregnant patients scheduled for cesarean section or delivery induction) was completed in February 2008 and approved by the US Food and Drug Administration (FDA) in early 2009 and marketed under the trade name ATryn.Recombinant human antithrombin is also approved for use in Europe for the prophylaxis of venous thromboembolism in the surgery of patients with congenital antithrombin deficiency (AT deficiency).

Plasma-derived antithrombin has been approved by the FDA for use in patients with hereditary antithrombin III deficiency (ATIII deficiency). In patients with a congenital deficiency of antithrombin III, replacement/prophylaxis is recommended (1) before or following major surgery, (2) during bed rest for longer than 24 hours (because of the increased risk of thrombosis), (3) for thrombosis during pregnancy to allow heparin to be effective, and (4) for acute DVT/PE.

Many acquired causes have been associated with antithrombin deficiency (AT deficiency); however, none of them has garnered FDA approval based on published clinical trials. It must be stated that, in patients with shock and DIC due to trauma, sepsis, or hepatic coma, the duration of DIC symptoms was significantly shorter in patients treated with antithrombin III alone than in patients who received heparin alone. The duration of symptoms with the combined use of heparin and antithrombin III was between the other two. As expected, patients with DIC due to polytrauma who were also receiving heparin had a greater tendency to bleed.

The reader is encouraged to review the FDA package insert with each product that is used for therapy.

FFP has traditionally been the source of factors to treat coagulation factor deficiencies for which no concentrates are available. Alpha2-plasmin inhibitor falls into that category.

Careful screening of blood donors and viral testing of donated blood (HBV surface antigen [HBsAg] and antibody to HBV core antigen [HBcAg], HCV, antibody to HIV-1 and HIV-2, HIV p24 antigen, antibodies to human T-cell lymphotropic virus [HTLV]-I and HTLV-II, screening for an elevated alanine aminotransferase [ALT] level) have improved the safety of blood products, but risks remain for a variety of reasons, including failure to detect infections during the "window," or incubation period, before the results of currently available tests become positive.

Other types of infections continue to cause concerns, including those for which we currently do not screen, do not have tests, or do not know of their presence. Some of the previously mentioned emerging pathogens include HIV-2, HIV type O, hepatitis G virus (HGV), TT virus (TTV), human herpesvirus (HHV)-8, the SEN family of viruses, and prions causing Creutzfeldt-Jakob disease (CJD) and new variant CJD (nvCJD).40,41,42

Higher risks of virally transmitted illnesses remain among patients who are recipients of multiple units of FFP. The use of solvent (TNBP) and detergent (Triton X-100) to treat pooled human plasmas results in significant inactivation of lipid-enveloped viruses (eg, HIV, HCV, HBV). The greater degree of viral safety assured by this treatment has led to the exclusive use of PLAS+SD instead of FFP in some countries (eg, Norway, Belgium).

SD-treated plasma delivers consistent and reproducible levels of coagulation factors. In contrast to the extreme variability in FFP, no leukocytes are present, and physiologic inhibitor levels are mostly in the normal range, with the exception of a moderate reduction in the levels of alpha2-plasmin inhibitor (~0.48 IU/mL) and protein S (~0.52 IU/mL). In addition, coagulation zymogens are not activated, levels of other plasma proteins and immunoglobulins are normal, and all lots have anti–hepatitis A virus (HAV) antibody levels of more than 0.8 IU/mL, providing passive administration of antibody, which may neutralize HAV. SD-treated plasma also lacks the largest von Willebrand multimers and has a proven efficacy in the treatment of a variety of bleeding disorders.

PLAS+SD's disadvantages include minor allergic reactions as observed with other blood products but which respond to antihistamines. This product should not be given to patients with known immunoglobulin A (IgA) deficiency.

Alpha2-plasmin inhibitor recovery after use of PLAS+SD: Mean recovery of alpha2-plasmin inhibitor was 237% ± 146% in 7 patients who had received SD plasma and albumin during plasma exchange after they had undergone plasmapheresis to hypofibrinogenemic levels (<125%).43 All coagulation factor levels are stable for approximately 12 months when stored at -18°C, but PLAS+SD should be used within 24 hours of being thawed.

All PLAS+SD units should be ABO compatible with each patient's red blood cells. Adverse effects include minor allergic reactions and volume overload. Rarely, citrate toxicity, hypothermia, other metabolic problems (if large volumes are used rapidly), and noncardiogenic pulmonary edema arise. Antibody-induced positive direct antiglobulin test results and hemolysis may also occur rarely.

See below for further details of the use of PLAS+SD instead of FFP.

Newer emerging technologies, such as those using nucleic acid chemistry, are being used to inactivate viruses, bacteria, and parasites with an attempt to also remove prions, thus making blood and blood components safer than they are today. These newer technologies attempt to preserve the clinically useful components of blood while improving its safety. These methodologies could be used to improve the safety of a wide variety of products.

Recognition of the importance of the lysine-binding sites in various interactions in the fibrinolytic pathway led to the synthesis of lysine analogues such as EACA (epsilon amino-caproic acid) (6-aminohexanoic acid [Amicar]) and trans- p-aminomethyl-cyclohexane carboxylic acid (AMCA, tranexamic acid [Cyklokapron]). These synthetic lysine analogues induce a conformational change in plasminogen when they bind to its lysine-binding site. The plasminogen has the shape of a prolate ellipsoid after EACA binds to it. It elongates into a long structure in which the interaction between the parts of plasminogen as they existed is lost. In vivo, they probably prevent plasminogen activation and, in large doses, also bind plasmin, thereby preventing it from binding to its substrate, fibrin.

When looking at binding sites on plasminogen for EACA, the tightest binding is to kringle 1 followed by kringles 4 and 5. The interaction with kringle 2 is weak, and kringle 3 does not interact at all. A model of the structure of kringle 4 shows that the shallow trough formed by the hydrophobic amino acids is surrounded by positively and negatively charged amino acids at an ideal distance to interact with EACA (see Bibliography).

EACA is the most widely used antifibrinolytic drug in the United States. The minimal dose needed to inhibit either normal or excessive fibrinolysis is unknown. EACA is absorbed well orally, and 50% is excreted in the urine in 24 hours. Generally, an initial loading dose is followed by a maintenance dose to adequately inhibit fibrinolysis until excess bleeding is controlled. The maintenance dose is then gradually tapered until it can be stopped. Rarely, myopathy and muscle necrosis develop. Lower doses are adequate when bleeding involves the urinary tract, since as concentrations are 75-100 times higher in urine than in plasma.

AMCA is also rapidly excreted in the urine, with more than 90% excreted in 24 hours. However, its antifibrinolytic effect lasts longer than EACA. AMCA inhibits fibrinolysis at lower plasma concentrations, although its serum half-life is similar to that of EACA. Therefore, AMCA can be given less frequently and at lower doses.

The dose of EACA and AMCA must be reduced when renal failure is present.

Aprotinin (Trasylol), a third antifibrinolytic drug obtained from bovine lung, is a nonhuman protein inhibitor of several serine proteases, including plasmin. It is approved by the FDA for use in patients undergoing open heart surgery to reduce operative blood loss. Aprotinin administration has also reduced blood loss and transfusion requirements in patients undergoing orthotopic liver transplantation and in patients undergoing elective resection of a solitary liver metastasis originating from colon cancer. Aprotinin is the most expensive of the 3 drugs discussed here, and it is now only available via a limited-access protocol. Fergusson et al reported an increased risk for death compared with tranexamic acid or aminocaproic acid in high-risk cardiac surgery.44

Antithrombin Supplements

Antithrombin concentrates are used to raise the plasma antithrombin level from a reduced value to approximately 120%. The goal is to maintain the level of antithrombin activity at a minimum of about 80% at all times. Serial monitoring of levels is necessary to ensure an adequate level. The anticoagulant effect of heparin is enhanced by antithrombin; thus, monitoring of the aPTT is necessary to determine the need to reduce the heparin dosage when heparin is being concomitantly administered with antithrombin. Both HBV and HIV are inactivated in this product, but viral transmission has not been completely eliminated. A recombinant product would solve that problem.

Dosage calculation guidelines
The required dose = (%desired –%baseline) × body weight (kg) divided by 1.4.

This calculation is based on an expected rise of 1.4% with 1 IU/kg given intravenously. Recoveries vary from patient to patient and are also affected by the underlying disease. Therefore, baseline and 20-minute postinfusion samples should be tested for antithrombin activity to determine the initial response to a dose. Subsequently, predose trough level and immediate postdose values provide trough and peak values to help in further dosing. Minimum levels of approximately 80% are suggested. Surgery, bleeding, and active thrombosis all affect the level and half-life. The disappearance time in normal volunteers was 22 hours, but this is physiologic information. Following the initial loading dose to raise the value to 120%, approximately 60% of that dose is administered every 24 hours as a maintenance dose.


Antithrombin III, human (ATnativ, Thrombate III)

A serine protease inhibitor (an alpha2-globulin) that inactivates thrombin, plasmin, and other serine proteases of coagulation, including factors IXa, Xa, XIa, XIIa, and VIIa. Made from pooled human plasma and is heat treated. Do not refrigerate after reconstitution, and administer within 3 h of reconstitution.

Adult

Loading dose: 50 U/kg IV infusion over 20-30 min

Maintenance dose: Approximately 60% of initial dose repeated qd if no continuing loss (ie, with surgery or bleeding); another method that has been used to calculate a dose is the following simple formula: Total initial dose = [100 – AT III activity in %] X body weight (kg) divided by 1.4

Monitor activity serially and repeat doses more frequently if AT activity drops to less than 80%; expect a shorter half-life when AT concentrates are given together with heparin; any cause of increased consumption or loss also shortens survival, thus requiring more frequent replacement to try to maintain a minimum level of 80% at all times; in patients with a congenital deficiency, the initial 50% disappearance time of ATIII was about 22 h with a subsequent biologic half-life of 3.8 d based on functional assays; continuous IV infusions have also been used in some clinical circumstances
Successful management of pregnancy resulting in normal delivery has been reported with a dose of 75 U/kg twice weekly from the eighth week followed by 60 U/kg once or twice weekly from the 16th week in conjunction with heparin

Pediatric

Administer as in adults, based on body weight; administer continuous IV infusion of AT concentrate at a dose of 40 U/kg; along with heparin, this has been used to treat DIC in newborns; doses of 40-60 U/kg have been used as the initial loading dose in newborns, with subsequent doses depending on rate of drop of AT activity; the baselines are normally reduced in neonates and premature infants.

Administration of PO vitamin K antagonists in absence of concomitant therapeutic thrombin inhibition may result in coumarin necrosis; review all medications carefully, including antipsychotics, to determine whether they can be discontinued; aspirin alone cannot substitute for therapeutic doses of vitamin K antagonists in the long-term management of patients with congenital AT deficiency; expect a shorter half-life when AT concentrates are given together with heparin

Documented hypersensitivity; drugs that may reduce AT levels (eg, estrogens) should not be administered

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Reported adverse reactions are similar to those of blood products (ie, shortness of breath, hives, chest pain, fever, light-headedness); slowing rate of infusion and/or discontinuation of the product may become necessary; concomitant use of drugs such as antihistaminics and steroids may be necessary to treat or prevent allergic manifestations; deficiency of AT is associated with miscarriage and fetal growth retardation due to thrombosis limiting placental growth
Current recommendation for the use of heparin during pregnancy is not logical because of adequate functional AT required for antithrombotic activity, particularly at low doses of heparin; despite this, patients have been managed with prophylactic heparin alone during pregnancy, with varying outcomes; some may need AT replacement, but it is expensive, not readily available for long-term use, and poses the risks of virally transmitted illnesses to mother and infant
Patients on long-term PO vitamin K antagonists should be cautioned not to become pregnant because of known teratogenic effects; this is a plasma-derived product that raises the potential risks of virally transmitted infections such as hepatitis and HIV despite viral inactivation and screening of donors; as in the case of hemophiliacs, nvCJD or transmissible spongiform encephalopathies (TSE) remain a potential concern with use of plasma-derived products


Antithrombin, recombinant (Atryn)

Antithrombin (AT) regulates hemostasis by inhibiting thrombin and factor Xa, key proteases for blood coagulation. Indicated for prevention of perioperative and peripartum thromboembolic events in patients with hereditary AT deficiency. Not indicated for treatment of thromboembolic events.

Adult

Administer IV using infusion set with 0.22 micron inline filter; administer loading dose over 15 min, then immediately follow with continuous infusion
Target level is to restore and maintain AT activity levels at 80-120% of normal (0.8-1.2 IU/mL); initiate 24 before surgery for surgical patients

Surgical patients:
Loading dose: IU = [(100 - baseline AT activity) divided by 2.3] X body weight (kg)
Maintenance dose: IU/h = [(100 - baseline AT activity) divided by 10.2] X body weight (kg)

Pregnant women:
Loading dose: IU = [(100 - baseline AT activity) divided by 1.3] X body weight (kg)
Maintenance dose: IU/h = [(100 - baseline AT activity) divided by 5.4] X body weight (kg)

Monitor AT activity 2 h after treatment initiation and adjust dose:
AT level <80%: Increase dose by 30% and recheck AT level 2 h after each dose adjustment
AT level 80-120%: No dose adjustment; recheck AT level 6 h after treatment initiation
AT level >120%: Decrease dose by 30% and recheck AT level 2 h after each dose adjustment

Pediatric

Not established

Coadministration with heparin or low molecular weight heparin increases anticoagulant effect; anticoagulants that use AT to exert their anticoagulant effect may alter half-life of recombinant AT (monitor aPPT and antiFactor Xa level)

Documented hypersensitivity to goat and goat milk proteins

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Do not shake following reconstitution; common adverse events include hemorrhage and infusion site reaction

Antihemophilic Agents

Use inhibitors of fibrinolysis together with FFP replacement for minor surgical procedures (eg, dental extractions, sinus surgery) so that they can be accomplished on an outpatient basis with the use of a single dose of product.

Concern about the possible relationship to acute thrombotic events remains, although a causal relationship is being questioned because the underlying disease state determines the site and extent of thrombosis.


Pooled plasma, solvent-detergent treated (PLAS+SD)

See details of discussion under Medical Care. SD treatment of pooled human plasma removes lipid-enveloped viruses, making this product safer than untreated FFP. SD treatment, however, does not remove all viruses from plasma. Efficacy and safety has been proven in the treatment of several coagulopathies. Per the package insert from the American Red Cross, the half-life of the coagulation factors in recipients of this product were similar to normal values at the time they were measured.
If available, SD-treated plasma can be used in patients with alpha2-antiplasmin deficiency, because no concentrate is available to treat this coagulation factor deficiency. As with any bleeding disorder, serial measurement of the specific coagulation factor in question is essential to assure hemostatic adequacy of levels. On average, 1 U of SD plasma raises factor levels by ~2-3%, whereas 4-6 U raises factor levels by ~8-18% in a 70-kg person. These numbers do not specifically apply to alpha2-antiplasmin and are being provided only as a general guide.
Serial monitoring of required alpha2-antiplasmin levels is necessary to follow these patients. This product should be stored at -18°C or colder, and thawed at 30-37°C in a water bath with very gentle shaking; once thawed, keep at room temperature and use as soon as possible, preferably within 24 h. Do not store thawed material in the cold.

Adult

10-15 U/kg IV or 1 U (200-mL bag) IV, initially, depending on the cardiovascular tolerance of the patient and the rapidity of the desired effect

Pediatric

Administer as in adults, based on body weight

Documented hypersensitivity; IgA deficiency

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

Viral contamination and infection are possible but unlikely because of prescreening; ineffective in patients with factor IX inhibitors; may induce an anamnestic response; use in pregnancy only when specifically indicated; see the package insert with regard to the lack of mutagenicity and the lack of reproduction toxicity by the residual small amounts of TNBP and Triton X-100; no studies have been conducted on the carcinogenicity

More on Antithrombin Deficiency

Overview: Antithrombin Deficiency
Differential Diagnoses & Workup: Antithrombin Deficiency
Treatment & Medication: Antithrombin Deficiency
Follow-up: Antithrombin Deficiency
Multimedia: Antithrombin Deficiency
References
Further Reading
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Keywords

antithrombin deficiency, AT deficiency, antithrombin III, AT III, ATIII, antithrombin 3, anticoagulation, anticoagulant, coagulation factors, hemostatic pathway, coagulation pathway, serine protease inhibitor, deep vein thrombosis, DVT, venous thrombosis, pulmonary embolism, PE, venous thromboembolism, VTE, thrombotic disease,

acute respiratory distress syndrome, ARDS, venoocclusive disease, veno-occlusive disease, VOD, bone marrow transplantation, BMT, chronic leg ulcerations, severe venous varicosities, postphlebitic syndrome, low molecular weight heparin, low-molecular-weight heparin, LMWH, pooled plasma treated with solvent-detergent, PLAS+SD, ATryn, Budd-Chiari syndrome, estrogen, hormone replacement therapy, HRT

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Contributor Information and Disclosures

Author

Arun Rajan, MD, Clinical Fellow, Medical Oncology Branch, National Cancer Institute/National Institutes of Health
Arun Rajan, MD is a member of the following medical societies: American Medical Association and American Society of Clinical Oncology
Disclosure: Nothing to disclose.

Coauthor(s)

Sara J Grethlein, MD, Associate Dean for Graduate Medical Education, Professor, Department of Internal Medicine, Division of Hematology and Oncology, State University of New York Upstate Medical University
Sara J Grethlein, MD is a member of the following medical societies: American Society of Hematology
Disclosure: Nothing to disclose.

Rajalaxmi McKenna, MD, FACP, Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

Medical Editor

David Aboulafia, MD, Medical Director, Bailey-Boushay House; Clinical Professor, Department of Medicine, Division of Hematology, University of Washington
David Aboulafia, MD is a member of the following medical societies: American College of Physicians, American Medical Association, American Medical Directors Association, American Society of Hematology, Infectious Diseases Society of America, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Marcel E Conrad, MD, (Retired) Distinguished Professor of Medicine, University of South Alabama
Marcel E Conrad, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for the Advancement of Science, American Association of Blood Banks, American Chemical Society, American College of Physicians, American Physiological Society, American Society for Clinical Investigation, American Society of Hematology, Association of American Physicians, Association of Military Surgeons of the US, International Society of Hematology, Society for Experimental Biology and Medicine, and Southwest Oncology Group
Disclosure: No financial interests None None

CME Editor

Rebecca J Schmidt, DO, FACP, FASN, Professor of Medicine, Section Chief, Department of Medicine, Section of Nephrology, West Virginia University School of Medicine
Rebecca J Schmidt, DO, FACP, FASN is a member of the following medical societies: American College of Osteopathic Internists, American College of Physicians, American Medical Association, American Society of Nephrology, International Society of Nephrology, National Kidney Foundation, Renal Physicians Association, and West Virginia State Medical Association
Disclosure: Abbott Grant/research funds Speaking and teaching; Genzyme Honoraria Consulting; Amgen Honoraria Speaking and teaching; Ortho Biotech Honoraria Speaking and teaching

Chief Editor

Emmanuel C Besa, MD, Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Thomas Jefferson University
Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, and New York Academy of Sciences
Disclosure: Nothing to disclose.

 
 
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