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What drugs are used in bridging therapy?

4 min read

Across the globe, millions of patients on long-term anticoagulant therapy must temporarily stop their medication for surgery or invasive procedures. This interruption creates a risk of dangerous blood clots, necessitating bridging therapy with short-acting agents. Additionally, the term “bridging therapy” also refers to specific cancer treatments, such as those used for multiple myeloma, to control disease progression while awaiting CAR T-cell infusion.

Quick Summary

Bridging therapy employs short-acting drugs to manage risk during the temporary cessation of long-acting treatments. In anticoagulation, this involves parenteral heparins like low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH). In oncology, it uses treatments like chemotherapy, targeted agents, and radiation to control tumor burden while awaiting CAR T-cell therapy.

Key Points

  • Primary Anticoagulation Drugs: Low-molecular-weight heparin (LMWH), such as enoxaparin or dalteparin, and unfractionated heparin (UFH) are the main drugs used to bridge during warfarin interruptions.

  • Oncology Bridging Purpose: For CAR T-cell therapy, bridging treatments control aggressive cancers like multiple myeloma or lymphoma while the T-cells are manufactured.

  • LMWH vs. UFH Usage: LMWH is often used for convenient outpatient bridging, while UFH is typically reserved for hospitalized patients or those with severe renal impairment due to its need for closer monitoring and faster clearance.

  • Oncology Bridging Options: Besides radiation therapy, chemoimmunotherapy and targeted drugs like proteasome inhibitors or IMiDs are used to manage disease burden before CAR T-cell infusion.

  • Individualized Decisions: The choice of bridging therapy and regimen depends on a careful balance of the patient's specific risks, considering factors like bleeding risk in anticoagulation and T-cell health in oncology.

  • Risk in Anticoagulation Bridging: For many patients with atrial fibrillation, bridging with heparin has been shown to increase bleeding risk without significantly decreasing clot risk, meaning bridging is not always necessary for all procedures.

  • Direct Oral Anticoagulants (DOACs): Because of their shorter half-life compared to warfarin, DOACs typically do not require bridging with heparin, as a temporary stop is sufficient before a procedure.

In This Article

Understanding the Purpose of Bridging Therapy

Bridging therapy is a medical strategy used when a patient's primary, long-term treatment must be temporarily interrupted. The “bridge” is a shorter-acting, temporary medication designed to fill the gap and prevent complications until the long-term therapy can be safely resumed. The specific drugs and rationale for bridging depend heavily on the underlying medical condition being managed.

There are two main contexts in which bridging therapy is most commonly discussed: anticoagulation and oncology.

  • Anticoagulation: Patients on chronic oral anticoagulants, most notably warfarin, often need to pause their medication for surgery or an invasive procedure due to the risk of excessive bleeding. Since warfarin has a delayed onset and offset, stopping it prematurely leaves the patient vulnerable to thromboembolism (blood clots) for several days. Bridging therapy with a quick-acting agent is used during this period to maintain a therapeutic level of blood thinning while allowing enough time before the procedure for the effect to wear off.
  • Oncology: In the context of cutting-edge cancer treatments like Chimeric Antigen Receptor (CAR) T-cell therapy, bridging therapy is used to manage aggressive cancers while the personalized T-cell product is being manufactured. This manufacturing process can take several weeks, and bridging therapy helps control the disease during this waiting period, preventing rapid disease progression that could compromise the patient's eligibility for the main CAR T-cell infusion.

Drugs Used for Anticoagulation Bridging

Parenteral (injectable) agents with a rapid onset and short half-life are primarily used for anticoagulation bridging, especially for patients interrupting long-term warfarin therapy.

Low-Molecular-Weight Heparin (LMWH)

LMWH is commonly used for outpatient bridging due to its predictable effect and subcutaneous administration. Examples include Enoxaparin (Lovenox) and Dalteparin (Fragmin). A typical regimen involves stopping warfarin about 5 days before surgery, starting LMWH 3 days prior, and giving the last dose 24 hours pre-procedure. LMWH is restarted post-surgery once bleeding risk is low and continued until warfarin is therapeutic. Routine monitoring is generally not required for LMWH.

Unfractionated Heparin (UFH)

UFH is an intravenous heparin typically used for hospitalized patients or those with severe renal impairment. Its short half-life allows for precise control around surgery. Dosage is adjusted based on activated partial thromboplastin time (aPTT) monitoring.

Limitations of Other Anticoagulants

Direct Oral Anticoagulants (DOACs) have a shorter half-life than warfarin, making bridging with heparin generally unnecessary when interrupting them for procedures. Some earlier practices of bridging for DOACs are now known to increase bleeding risk without preventing clots.

Drugs Used for Oncology Bridging (CAR T-cell Therapy)

Oncology bridging treatments manage aggressive cancers while awaiting CAR T-cell manufacturing.

Chemoimmunotherapy (CIT)

CIT combines chemotherapy and immunotherapy to reduce tumor burden, with regimens chosen to be effective yet minimize toxicity before CAR T-cell infusion.

Targeted Therapies

Targeted therapies offer disease control with potentially less toxicity than traditional chemotherapy.

  • Multiple Myeloma: Examples include proteasome inhibitors (bortezomib), IMiDs (pomalidomide), and anti-CD38 monoclonal antibodies (daratumumab).
  • Lymphoma: Polatuzumab vedotin may be used in lymphoma.

Radiation Therapy (RT)

Radiation can bridge by rapidly reducing localized or bulky tumors, which can improve symptoms and potentially enhance the effectiveness of CAR T-cells. RT can also prime the tumor environment.

Comparison of Bridging Drugs

Feature Anticoagulation Bridging Oncology Bridging (CAR T-Cell)
Purpose To prevent blood clots during temporary interruption of long-acting anticoagulants like warfarin. To control aggressive cancer progression while awaiting CAR T-cell manufacturing.
Primary Drugs Low-Molecular-Weight Heparin (LMWH) like enoxaparin or dalteparin; Unfractionated Heparin (UFH). Chemoimmunotherapy, targeted therapies (e.g., proteasome inhibitors, IMiDs), and radiation therapy.
Administration Subcutaneous injection (LMWH) or intravenous infusion (UFH). Oral medications, intravenous infusions, or localized radiation treatments.
Monitoring INR checks to confirm warfarin offset and onset; aPTT for UFH; generally none for LMWH. Monitoring disease markers (e.g., M-protein in myeloma), imaging, and clinical status.
Key Consideration Balancing the risk of thromboembolism versus bleeding, particularly around surgery. Using an effective regimen that does not negatively impact the manufactured T-cells or cause severe toxicity.

Making the Decision to Bridge

The decision to use bridging therapy is complex and based on individual risks.

Anticoagulation Context

For anticoagulation, risk assessment categorizes patients as low, intermediate, or high risk for clots if warfarin is stopped. High-risk patients, such as those with mechanical heart valves or recent clots, are typically bridged. However, studies like the BRIDGE trial have shown that bridging may increase bleeding risk without preventing clots in many low-to-intermediate risk patients, particularly those with atrial fibrillation.

Oncology Context

Bridging is often necessary for CAR T-cell therapy, but the choice is highly individualized. Factors include cancer aggressiveness, prior treatments, organ function, and potential impact on T-cells. Certain agents like bendamustine should be avoided due to negative effects on T-cell function, and some therapies may require washout periods.

Conclusion

Bridging therapy is a vital strategy using short-acting drugs to manage risks during temporary interruptions of long-term treatments. Whether using heparins for perioperative anticoagulation or targeted therapies and radiation for cancer before CAR T-cell infusion, the specific drugs and approach depend on the patient's condition and risk profile. Advances in risk assessment and careful consideration of regimens have refined bridging therapy use.

Visit PubMed for more information on the latest research in bridging therapy for anticoagulation and oncology.

Frequently Asked Questions

In anticoagulation, bridging therapy is the use of a short-acting, injectable anticoagulant, like heparin, during the temporary interruption of a long-acting oral anticoagulant, such as warfarin, for a surgery or invasive procedure.

Common examples of LMWH used for outpatient bridging therapy include enoxaparin (Lovenox) and dalteparin (Fragmin), administered via subcutaneous injection.

Bridging therapy is necessary for CAR T-cell treatment to control the underlying cancer and prevent rapid disease progression during the several weeks it takes to manufacture the personalized T-cell product.

No, DOACs like dabigatran or rivaroxaban are not typically used for bridging therapy. Because they have a short half-life, a temporary stop is sufficient before a procedure, and bridging with heparin is generally unnecessary and can increase bleeding risk.

Unfractionated heparin (UFH) is usually administered intravenously, requires close laboratory monitoring (aPTT), and is used for hospitalized patients, whereas Low-Molecular-Weight Heparin (LMWH) is given as a subcutaneous injection, does not require routine monitoring, and is often used for outpatient bridging.

For cancer, bridging can involve chemoimmunotherapy, targeted therapies such as proteasome inhibitors and monoclonal antibodies, and localized radiation therapy to reduce tumor burden.

No, bridging therapy is not always necessary. For patients at low to moderate risk of blood clots, particularly those with atrial fibrillation, studies have shown that forgoing bridging can lead to less major bleeding without increasing the risk of thromboembolism.

References

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Medical Disclaimer

This content is for informational purposes only and should not replace professional medical advice. Always consult a qualified healthcare provider regarding personal health decisions.