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.