VTE PREVALENCE

VTE impacts thousands of patients each year

Approximately 900,000 VTE events occur annually in the United States2

Approximately 50% of VTE events are associated with a recent hospital admission3

Only 40% to 50% of medical patients receive adequate thromboprophylaxis4

At least one-third of VTE cases are associated with inherited thrombophilia5

Antithrombin & VTE Risk

Finding the balance between VTE risk and AT levels is critical in hATd patients

  • Patients with AT levels between 61 and 75 IU/dL have a 6 times greater risk of VTE6
  • Even AT levels that are considered normal (between 86 and 100 IU/dL) significantly increase the risk for VTE6

Data reflect events that occurred in the absence of transient risk factors (ie, surgery, trauma, prolonged bed rest [>1 week], pregnancy/puerperium, and combined oral contraceptive use). Risk assessed in comparison to patients with normal AT levels (or levels >100 IU/dL).

*Including those with cancer, liver disease, and nephrotic syndrome.

†Odds ratio adjusted for sex, age, body mass index, and thrombophilia (all defects except that under study). From a case-controlled study of 1401 patients with a first objectively documented VTE and 1847 healthy controls to assess the risk of VTE associated with varying plasma levels of AT, protein C (PC), and protein S (PS). Patients with surgery- or pregnancy-related VTE were tested for AT, PC, and PS at least 3 months after operation or delivery, in order to avoid changes in plasma levels of the naturally occurring anticoagulants related to these conditions.

Pregnant women are up to 5x more likely to experience VTE 
compared to the general population7

Learn how AT levels change during pregnancy

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MITIGATING VTE RISK

Functional Evaluation of AT Activity

The risks of hereditary antithrombin deficiency can be mitigated with functional evaluation of antithrombin activity, including laboratory testing, as well as with long-term management to address and reduce risks during future procedures or other high-risk life events

Mitigating VTE Risk
  • Unexplained VTE at a younger age (<50 years)
  • Recurrent spontaneous or unusually extensive spontaneous VTE
  • Unexplained arterial thromboembolism in a younger patient
  • Unexplained VTE at an unusual site
  • Recurrence of VTE while adequatedly anticoagulated
  • Family history of spontaneous VTE
  • Family history of known thrombophilia, even if patient is asymptomatic
  • Functional anththrombin assays are most commonly used and are recommended for initial testing for antithrombin deficiency9
  • Initial testing should be completed a few weeks after thrombotic event—heparin use may decrease antithrombin levels by 30%8
  • High specificity and sensitivity; positive predictive value = 96%9
  • Asymptomatic individuals with antithrombin deficiency typically are not started on long-term anticoagulation; however they need to receive DVT prophylaxis in high-risk situations, such as surgery, pregnancy, or childbirth
  • Patients with antithrombin deficiency who have had a VTE event should be considered for long-term anticoagulation
Mitigating VTE Risk

Whom to Test8
  • Unexplained VTE at a younger age (<50 years)
  • Recurrent spontaneous or unusually extensive spontaneous VTE
  • Unexplained arterial thromboembolism in a younger patient
  • Unexplained VTE at an unusual site
  • Recurrence of VTE while adequatedly anticoagulated
  • Family history of spontaneous VTE
  • Family history of known thrombophilia, even if patient is asymptomatic

How to Test: Functional Antithrombin Assays
  • Functional anththrombin assays are most commonly used and are recommended for initial testing for antithrombin deficiency9
  • Initial testing should be completed a few weeks after thrombotic event—heparin use may decrease antithrombin levels by 30%8
  • High specificity and sensitivity; positive predictive value = 96%9

Management8
  • Asymptomatic individuals with antithrombin deficiency typically are not started on long-term anticoagulation; however they need to receive DVT prophylaxis in high-risk situations, such as surgery, pregnancy, or childbirth
  • Patients with antithrombin deficiency who have had a VTE event should be considered for long-term anticoagulation

The effect of drugs that use antithrombin to exert their anticoagulation may be altered when THROMBATE III is added or withdrawn. Regularly perform coagulation tests suitable for the anticoagulant used (eg, aPTT and anti-Factor Xa activity) to avoid excessive or insufficient anticoagulation. Additionally, monitor the patients for the occurrence of bleeding or thrombosis.

Thrombate III in surgical procedures

Case Study: Intraoperative Heparin Resistance

  • Hereditary antithrombin deficiency is very rare in the population, but it is an important topic to discuss because there is an increased risk of VTE in the sepatients
  • So what is hereditary antithrombin deficiency? It is a hereditary autosomaldominant disorder that typically reduces functional antithrombin levels to 40% to 60% of normal
    • The overall incidence of hereditary antithrombin deficiency in the general population is very low, between 0.02% and 0.2%
    • However, patients with hereditary antithrombin deficiency are about 20 times more likely to have a VTE compared with the general population, which means that up to 3% of patients with thrombotic events may have hereditary antithrombin deficiency
    • The risk of VTE is much higher in hereditary antithrombin-deficient patients than it is in patients with other thrombophilias like factor VLeiden or prothrombin gene mutation
    • As proceduralists, we need to be concerned about hereditary antithrombin deficiency because these patients have an increased risk of VTE during procedures and deliveries
    • For example, up to 70% of pregnant women with hereditary antithrombin deficiency without thromboprophylaxis may experience thromboembolic complications during pregnancy
  • Patients with antithrombin deficiency also have an increased risk of VTE when undergoing surgeries, including vascular,orthopedic, bariatric, and cardiac surgeries
  • Because of this, patients who experience heparin response issues need awork-up to determine the cause. Some centers may even consider antithrombin level testing in certain patients prior to a procedure
  • Hereditary antithrombin deficiency can be the reason why surgical patients don't have the expected response to heparin anticoagulation
  • So what do we do when we encounter someone with hereditary antithrombin deficiency?
    • We know that they may have about half the level of antithrombinactivity compared with people in the general population, which carrieswith it the risk of VTE
    • It also means that we need to consider using FFP or antithrombin concentrate during the procedure to improve heparin responsiveness
  • We also know that recurrent thrombosis and occasional fatal thromboembolism are possible in patients with hereditary antithrombin deficiency, so patients with a history of thrombosis should be maintained on anticoagulant therapy
  • We have to understand that these patients, while they require very specific prophylactic therapy to prevent DVT or PE periprocedurally, are also very likely to have low-heparin response if they have a procedure that requires anticoagulation with heparin
  • Patients with hereditary antithrombin deficiency are at the highest risk for bloodclots in certain situations such as surgery, the use of oral contraceptives, pregnancy, childbirth, and when they already have had a blood clot in the past
  • Before surgeries involving heparinization, patients with hereditary antithrombin deficiency require careful perioperative management necessary to prevent thrombosis
  • One way to do that is with antithrombin concentrate
  • THROMBATE III is an antithrombin concentrate that temporarily replaces themissing antithrombin in patients with hereditary antithrombin deficiency
  • It is simple to use, with one dosing formula, and provides for convenient storageand reconstitution. It can also be used before, during, and after surgery
  • So, what about when a patient with hereditary antithrombin deficiency comes tothe operating room for a procedure that is going to require heparin?
  • Let's take a look at Frederick, a 52-year-old male with peripheral vascular disease and lower-extremity claudication requiring surgical intervention
    • He has a medical history of hypertension, hyperlipidemia, and long-termanticoagulation with apixaban after recurrent DVTs in his early 40s. Hewas diagnosed at this time with hereditary antithrombin deficiency
    • He also had family members who died from thrombotic-related diseaseand they very likely had hereditary antithrombin deficiency as well
  • Following a previous procedure, Frederick's postoperative antithrombin activity level was 27%, and at the 6-week follow-up, his level was still persistently low at 35%
  • He continued on long-term anticoagulation due to his history of recurrent DVTs
  • Frederick is now going to have a lower extremity vascular procedure and is going to need anticoagulation at the time of the procedure
  • Because we know that, on average, antithrombin deficient patients are walking around every day with about half of the normal antithrombin level, we can presume that Fredrick will not respond normally to heparin
  • What most people suggest for a person like Frederick is that at the time of his procedure, he should be given FFP or antithrombin concentrate to return his antithrombin to a more normal level
  • With Frederick's antithrombin level around 35%, a massive amount of plasma would be required in an effort to return his antithrombin to a more normal level
  • Administration of antithrombin concentrate peri procedurally is an option that would alleviate this volume concern. Unlike plasma, a concentrate can be prepared relatively quickly with no need for thawing
  • One such antithrombin concentrate is THROMBATE III. THROMBATE III is indicated in patients with hereditary antithrombin deficiency for treatment and prevention of thromboembolism and for prevention of perioperative and peripartum thromboembolism
  • Hypersensitivity reactions may occur. Should evidence of an acute hypersensitivity reaction be observed, promptly interrupt the infusion and begin appropriate treatment
  • Please refer to the Important Safety Information that will be presented at the end of this video
  • After receiving THROMBATE III for his procedure, Frederick should continue to receive THROMBATE III daily for the remainder of hospitalization until he can restart his long-term anticoagulation with a pixaban
  • Coagulation tests should be performed to avoid excessive or insufficient anticoagulation, and Frederick should be monitored for bleeding or thrombosis
  • Functional plasma AT levels should be measured with amidolytic or clotting assays; immunoassays should not be used
  • Physicians may be reluctant to restart anticoagulation peri procedurally, but incases likeFrederick's, it's important that his antithrombin levels are raised tonormal with supplementation or that he is returned to his apixabananticoagulation
  • Right after the surgery, you wouldn't use a full-strength anticoagulant. Instead, you would use an antithrombin concentrate, such as THROMBATE III
  • In clinical studies with THROMBATE III, the most common adverse reactions that occurred in ≥5% of subjects were dizziness, chest discomfort, nausea, dysgeusia, and pain (cramps)
  • In the future, if more procedures requiring discontinuation of Frederick's long-termanticoagulation are necessary, THROMBATE III can be used to reduce clotting risks

Key Takeaways

Patient History

  • Frederick is a 52-year-old male with peripheral vascular disease and lower-extremity claudication requiring surgical intervention
  • Medical history of hypertension, hyperlipidemia, and long-term anticoagulation with apixaban after recurrent DVTs in his early 40s
  • Father had pulmonary embolism, sibling with sudden death

Postoperative Evaluation and Management

  • Postoperative antithrombin activity level found to be 27%
  • At 6-week follow-up, patient found to have persistently low antithrombin level of 35%
  • Diagnosis of hATd made and patient continued on lifetime anticoagulation

Surgical Course

  • Apixaban is held for 4 days prior to elective femoral-popliteal bypass
  • Intraoperatively, patient receives 5000 IU IV heparin during vascular anastomosis
  • After the incision is closed, distal pulses are not evident by palpitation or Doppler ultrasound examination
  • The bypass is re-explored and found to be full of clot
  • Additional heparin 10,000 IU given and thrombectomy performed
  • New clots form in surgical field
  • Activated clotting time (ACT) is checked and found to be low—only 180 seconds
  • A total of 20,000 IU additional heparin is given to achieve target ACT of 250 seconds, and procedure is finally completed successfully

Treatment Plan/Management

  • In the future, when stopping his long-term anticoagulation is required, Frederick can be protected from clotting risk with THROMBATE III at the time of the procedure
  • Many surgical procedures require cessation of long-term anticoagulation to prevent hemorrhage during surgery, exposing Frederick to risk of VTE
  • Preoperatively, THROMBATE III daily dosing should be started when apixaban is stopped
  • THROMBATE III can be continued until the postoperative risk of bleeding allows resumption of long-term anticoagulation

When an infusion of THROMBATE III is indicated for a patient with hereditary deficiency to control an acute thrombotic episode or prevent thrombosis during or following surgical or obstetrical procedures, raise the AT level to normal and maintain this level for 2 to 8 days, depending on the indication for treatment, type and extent of surgery, patient’s medical condition, past history and physician’s judgment. Base the concomitant administration of heparin in each of these situations on the medical judgment of the physician.

Hypothetical case profile is not intended to convey clinical diagnostic or therapeutic recommendations.

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AT III Deficiency

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AT Levels & Heparin

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THROMBATE III vs FFP

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Important Safety Information

THROMBATE III (antithrombin III [human]) is indicated in adult and pediatric patients with hereditary antithrombin deficiency for treatment and prevention of thromboembolism and for prevention of perioperative and peripartum thromboembolism.

Hypersensitivity reactions may occur. Should evidence of an acute hypersensitivity reaction be observed, promptly interrupt the infusion and begin appropriate treatment.

Because THROMBATE III is made from human blood, it may carry a risk of transmitting infectious agents, eg, viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent, and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent. There is also the possibility that unknown infectious agents may be present in the product.

Perform coagulation tests to avoid excessive or insufficient anticoagulation and monitor for bleeding or thrombosis. Measure functional plasma AT levels with amidolytic or clotting assays; do not use immunoassays.

In clinical studies, the most common adverse reactions (≥ 5% of patients) were dizziness, chest discomfort, nausea, dysgeusia, and pain (cramps).

The anticoagulant effect of heparin is enhanced by concurrent treatment with THROMBATE III in patients with hereditary AT deficiency. Thus, in order to avoid bleeding, the dosage of heparin (or low molecular weight heparin) may need to be reduced during treatment with THROMBATE III.

Please see full Prescribing Information for THROMBATE III..

References

  1. Di Minno MND, Dentali F, Lupoli R, Ageno W. Mild antithrombin deficiency and risk of recurrent venous thromboembolism: a prospective cohort study. Circulation. 2014;129(4):497-503.
  2. Centers for Disease Control and Prevention. Impact of blood clots on the United States Infographic. Updated May 15, 2024. Accessed April 10, 2025. https://www.cdc.gov/blood-clots/toolkit/impact-of-blood-clots.html.
  3. Heit JA, Crusan DJ, Ashrani AA, Petterson TM, Bailey KR. Effect of a near-universal hospitalization-based prophylaxis regimen on annual number of venous thromboembolism events in the US. Blood. 2017;130(2):109-114.
  4. Benjamin MW, Koomson A, Ismaiel H. Analysis of adherence to thromboprophylaxis and incidence of venous thromboembolism after lower limb orthopaedic surgery. Cureus. 2021;13(11): e19746.
  5. Middeldorp S, Nieuwlaat R, Kreuziger LB, et al. American Society of Hematology 2023 guidelines for management of venous thromboembolism: thrombophilia testing. Blood Adv. 2023;7(22):7101-7138.
  6. Bucciarelli P, Passamonti SM, Biguzzi E, et al. Low borderline plasma levels of antithrombin, protein C and protein S are risk factors for venous thromboembolism. J Thromb Haemost. 2012;10(9):1783-1791.
  7. Springel EH, Malhotra T. Thromboembolism in pregnancy. Updated June 6, 2025. Accessed July 8, 2025. https://emedicine.medscape.com/article/2056380-overview.
  8. Foy P, Moll S. Thrombophilia: 2009 update. Curr Treat Options Cardiovasc Med. 2009;11(2):114-128.
  9. Kottke-Marchant K, Duncan A. Antithrombin deficiency: issues in laboratory diagnosis. Arch Pathol Lab Med. 2002;126(11):1326-1336.