How high is too high? INR and acute care physical therapy.
Anticoagulation is frequently indicated for a variety of medical conditions. Maintaining therapeutic anticoagulation over time can be difficult and anticoagulation often exceeds the therapeutic goal. When patients function in a hyperanticoagulated state, risk of hemorrhage is increased. While in a hyperanticoagulated state, patients should minimize their risk of injury by limiting excessive activity and exercise. However, no evidence-based guidelines or recommendations for activity limitations for hyperanticoagulated patients exist at this time. This article consists of a literature review on the risk of hemorrhage in patients with an elevated INR and recommendations for prescribing appropriate exercise while patients are in hyperanticoagulated states.
Drugs used for anticoagulating patients can be separated into unfractionated heparin, Warfarin (Coumadin) and low molecular weight heparins (LMWH). Unfractionated heparin requires IV access and is used for rapid initiation of anticoagulation therapy. Due to the unpredictable anticoagulant effect of heparin and the goal of maintaining a constant dose, in general, the heparin infusion should be continuous and should not be discontinued for activity or physical therapy. Heparin therapy is monitored using the laboratory test, activated partial thromboplastin time (aPTT). The question of how early to initiate activity in a patient with a newly diagnosed DVT who is undergoing treatment with unfractionated heparin is the subject of much debate (1,2,3) and will not be discussed here. The goal of this article, instead, is to discuss activity recommendations for patients who have supratherapeutic anticoagulation documented as elevated INR.
Anticoagulation with Warfarin is most commonly evaluated using the International Normalized Ratio (INR). INR values of healthy individuals who are not anticoagulated will be between 0.8 and 1.2. INR of individuals undergoing anticoagulation therapy varies and depends on the target range indicated by the health condition requiring anticoagulation. Target INR might range from values as low as 2.0 to values as high as 4.5.4,5,6 INR values can also affected by liver health and function. INR is a laboratory test that measures the patient's clotting factors and might be indicated for reasons other than monitoring anticoagulant therapy.
LMWH are heparin fragments with, as the name suggests, lower molecular weights. The LMWH Enoxaparin was approved by the FDA for treatment of DVT in 1993. Enoxaparin allows the physician to initiate anticoagulation without IV access. These drugs have a more predictable anticoagulant effect. Often patients do not require laboratory monitoring. When the anticoagulation effects of LMWH need to be monitored, anti-factor Xa levels are measured. (7)
Given that anticoagulation with LMWH is not usually monitored, and treatment with unfractionated heparin is usually not long term, this discussion on physical activity in a hypercoagulated state will be limited to patients who are anticoagulated with Warfarin and whose anticoagulation levels are monitored using INR values.
Definition of the problem
In cases of anticoagulation, a common treatment goal is to maintain INR between 2 and 3. The challenge for the physician is to maintain this range over an extended time. If INR is found to be greater than 5, Warfarin is held and the physician may order either fresh frozen plasma (FFP) or vitamin K in order to quickly lower the INR to a safer range.
When INR is elevated above the therapeutic range, risk of bleeding is increased. (8, 9,10); however, a prescription of bed rest in the setting of hyperanticoagulation is not necessarily warranted. Bed rest itself presents increased risk of health complications. (11,12,13) Weighing the risks of bleeding in the setting of a supratherapeutic INR against the risks of complications due to bed rest provides a clinical dilemma for the acute care health professional. The evidence describing the negative consequences of bed rest is abundant and well known by acute care practitioners. (11,12,13) The evidence of risk of bleeding with elevated INR, on the other hand, is less well known. Hence, the goal of this article is to describe the documented risks associated with elevated INR to facilitate individual clinical decisions regarding the mobilization of a hyperanticoagulated patient.
Current recommendations of INR and physical activity are usually unreferenced and are based on customary practice rather than research. The recommendations found by searching reference texts and the Internet regarding INR and physical activity include the following: The University of Michigan Health System Cardiovascular website states that patients with INR 5-9.0 should "avoid excessive physical activity while his/her INR is prolonged, and to report immediately signs/symptoms of bleeding." (14) In Paz's Acute Care Handbook for Physical Therapists, (15) "There is no common protocol for activity guidelines for the patient with an INR greater than 3.5, however, most patients continue out of bed activities and activities of daily living with caution or supervision with an INR slightly greater than 3.5. Generally physical therapy intervention is deferred and the patient may be on bed rest if the INR is greater than 6.0." Neither of these recommendations cited research to explain their guidelines.
No randomized controlled trials examining the risks of physical activity in people with elevated INR were found. In the absence of research describing the effect of activity level on risk of hemorrhage in those with elevated INR, a review of the risks and types of frequent complications in those with elevated INR will help therapists evaluate the risks of mobility in this population.
A literature search was performed in PubMed, CINAHL and Medline, using the combined search terms of "bleeding," "hemorrhage," "ambulatory," "nontherapeutic," and "inr(s)." Limitations of English, randomized controlled trial or clinical trial, humans were imposed. Articles were cross-referenced for identification of studies not revealed in the initial search. The search was limited further by applying the following selection criteria: 1) publication in a peer-reviewed journal 2) written in English 3) an outcome measure describing the relationship between elevated INR values and related risk of hemorrhage and 4) adult patient population. The selection criteria revealed five articles describing the risk of hemorrhage associated with an elevated INR in patients undergoing Warfarin therapy. These five articles are described here.
Newman & Zitomirsky examined emergency department records to determine the prevalence of nontherapeutic and coagulopathic INR values among patients receiving Warfarin. (16) Analysis included any patients who were compliant on Warfarin therapy presenting to the ER on whom INR was obtained between the months of Feb 2003 to May 2004, which resulted in 782 patients. Seventy-two percent of the patients included in the analysis were outside of the therapeutic range. INR exceeding 5 was present in 11% of patients included in the analysis. Of those patients with INR greater than 5, 40% exhibited signs of non-traumatic gross bleeding. Forty-three percent of the patients with INR recorded were subtherapeutic. Of those with subtherapeutic INR, 7% had experienced ischemic stoke, venous thromboembolism or cerebral ischemia. Of the patients with therapeutic INR, 9% had non-traumatic bleeding. The most common source of bleeding for all included patients was gastrointestinal followed by intracranial hemorrhage.
Atreja, El-Sameed, Jneid, Hoogwerf, and Peacock described the medical course of patients with elevated INR who presented to the Cleveland Clinic Foundation Emergency Department with the goal of documenting physician adherence with standardized treatment recommendations for supratherapeutic INR. (17) They performed a one-year retrospective review of 96 patients who presented to their ED with an INR > 5. Sixty of these patients had INR between 5.0 and 8.9 and 34 patients had INR > 9.0. Bleeding was present in 29% of patients with INR > 5. Eleven of these 27 patients were identified as having major bleeding episodes. Major bleeding criteria included bleeding in a critical location such as intracranial, bleeding requiring medical intervention or bleeding resulting in a drop in hemoglobin. Of the 27 patients who presented with major bleeding, 11 were of gastrointestinal origin. The next most common sites were urinary and nasal in origin. The risk of bleeding in patients with INR between 5.0 and 8.9 was not different than those with INR > 9.0. The authors did not identify the sources of bleeding as traumatic or non-traumatic in origin. The authors identified certain sources of bleeding as coinciding with instances of major bleeding and others with instances of minor bleeding. The authors stated that instances of GI bleeding included both major and minor bleeds, however, urinary bleeding in this sample was always minor. The authors suggested that the presence and location of bleeding in the ED was more indicative of risk of complication than the actual INR value itself.
Two-thirds of patients with INR > 5 were admitted to the hospital but some of these were due to co-morbidities. Of the 47 patients that presented with INR > 5 and bleeding, 14 out of 47 were discharged directly from the ER. Average length of stay of those who were admitted to the hospital was 3.8 days. INR returned to normal in 49.4 hours for patients that received neither vitamin K nor FFP. The other groups of patients that did receive vitamin K or FFP to treat their elevated INR were all small groups of less than 10 patients.
The authors concluded that the presence and location of bleeding upon presentation might be more indicative of medical stability than the INR value itself. In this population, the therapist needs to pay close attention to tests used to investigate the presence of bleeding and be aware of the test results. Therapists should look for a decrease in hematocrit or wait for the results of tests investigating possible bleeding sources in patients with elevated INR instead of merely evaluating the INR value in isolation.
Hylek, Chang, Skates, Hughes and Singer reviewed the records of patients followed in an ambulatory anticoagulation clinic and identified 114 who had INR greater than 6. (18) Sixteen of these patients had INR greater than 10.0. None of the patients with elevated INR had bleeding at the time they were selected for the study. Upon identification, patients with elevated INR immediately underwent appropriate dosing changes to correct INR. The authors also selected patients for a comparison group whose INR was in the therapeutic range (n=268). The authors then followed all patients for a two-week period to document the complications experienced. In this two-week period, ten patients (10/114) who were identified with elevated INR experienced bleeding. Five out of these ten patients with bleeding and elevated INR experienced major bleeding. The major bleeding episodes consisted of three patients with gastrointestinal bleeding, one with intracerebral bleeding and one with soft tissue bleeding. The authors did not comment on whether any of the bleeding episodes were traumatic in origin. None of the patients in the control group with normal INR experienced bleeding in the two-week measurement period. The majority of patients with INR > 6 (55%) had INR < 4.0 within 48 hours of discontinuing Warfarin therapy.
The results of this article were similar to those of Atreja et al.; (17) however, this study followed patients in an outpatient setting who received regular monitoring of their INR. Atreja et al. included only patients who presented to an ED with various complications. In this non-emergent setting, approximately 10% of patients with INR greater than 6 experienced bleeding in a two week follow up period. Although this risk of bleeding (10%) is still significant, it is much lower than the 30% of those with INR greater than 6.0 who presented to an ED with bleeding in Atreja et al. Similar to Atreja et al., Hylek et al. (18) reported the GI tract as the most common bleeding site.
The remaining articles identified discussed the outcomes of trauma patients as they relate to INR values. (20, 21) In general, age and elevated INR were associated with poorer outcomes in the setting of trauma. Patients over the age of 70 who are on anticoagulant therapy have been shown to have the highest mortality in the setting of trauma. However, these articles did not differentiate between those with greatly elevated INR from those with only slightly elevated INR. Hence, they do not help the clinician decide what INR value is too high for physical activity or physical therapy. These articles only indicate the importance of limiting falls and injury when working with patients with elevated INR.
Recommendations for INR and participation in physical therapy
Clearly, patients with elevated INR are
at increased risk for bleeding. Performing physical therapy with a patient who has an increased risk of bleeding raises two serious questions: 1) Is the patient already actively bleeding internally or externally such that pursuing physical activity is unsafe? 2) Will the patient experience some minor or major trauma during physical therapy that will result in gross bleeding due to his/her highly anticoagulated status?
In order to address these concerns, the therapist needs to monitor blood counts and vital signs closely to ensure that the patient is medically stable and not losing blood prior to treatment. Similarly, the physical therapist needs to stress safety during exercise and other activities to prevent major or minor trauma. These objectives should be observed in hyperanticoagulated patients regardless of the actual INR value.
Given the great range of therapeutic INR values, the specific target anticoagulation range for the individual patient should be considered. Due to the individual needs of the patient, a physician may set a therapeutic range slightly higher or lower than the range usually indicated for his or her condition. Knowing the specific INR goal might also be helpful in discharge planning and in patient education.
After defining the problem and reviewing the literature, these guidelines were developed at the author's acute care practice setting. This setting is a large, university based, acute care hospital that is designated a level 1-trauma center, which serves patients from the entire state.
Exercise Guidelines for Patients with Elevated INR in an Acute Care Setting
If INR is less than 4.0, the patient should be allowed to participate in a physical or occupational therapy evaluation and his or her regular exercise program. Advancing the patient's exercise program or greatly increasing the intensity of exercise should probably wait for the patient to be within his or her therapeutic range. Until that time, therapy should focus on motor learning and improving performance or form at the current intensity level. If INR is between 4.0 and 5.0, resistive exercises should be held, and participation in only light exercise (rating of perceived exertion (22) [less than or equal to] 11) should be observed. If the patient is ambulatory, any unsteadiness should be addressed with the appropriate assistive device and close supervision. All necessary precautions should be taken to avoid a fall, especially if the patient is older (>70).
If INR is greater than 5.0, exercise should be held, or should consist of an evaluation of the patient's current mobility in the hospital to assess the patient's safety and assist in discharge planning. For example, if the patient is currently getting OOB to a bedside commode, a physical or occupational therapist should assess this level of activity to determine whether the patient is safe to continue. Progression of activity should be held until INR decreases. The goal of the therapy evaluation should be to evaluate the current activity level and begin discharge planning. Determining whether the patient's current activity level is safe is the role of the therapist.
If INR is greater than 6.0 the medical team should consider bed rest or decreasing the activity level of the patient until INR is corrected. Remember that, in most cases, INR should be corrected in approximately 2 days. If this is not likely to happen, the physical therapist needs to discuss the case with the physician and weigh the risk of bleeding (which is significant) against the risks associated with bed rest. Patients who have normal mobility (and, as a result, are probably not receiving physical therapy in the acute care setting) may be allowed to mobilize on a case-by-case basis. However, even in those with normal mobility, stairs and resistive exercises should be avoided, if possible, when INR is this high.
Unfortunately the current literature leaves many unanswered questions regarding the effect of activity level on the risk of hemorrhage in the setting of elevated INR. Activity level should be determined in a case-by-case basis with patient safety and good health as the primary goal. The author hopes that this paper will initiate discussions among health care professionals about activity and exercise recommendations in the setting of elevated INR and practitioners will create institution specific activity guidelines appropriate to their own patients. Prior recommendations regarding activity level in the setting of elevated INR simply do not exist. Although current research fails to provide a clear course of action, the medical team is responsible for providing the best care for their patients and making clear, educated recommendations based on clinical experience and the best evidence available.
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Ann Tuzson PT, PhD
Ann Tuzson, PT, PhD is Physical Therapist Clinician IV at the University of Virginia Health Sciences Center in Charlottesville, Virginia. She has been treating patients in the acute care setting for more than 10 years. Dr. Tuzson is an alumna of University of Illinois at Chicago Department of Physical Therapy and of the University of Virginia Departments of Biomedical Engineering and Kinesiology. Dr. Tuzson's research interests include acute care, biomechanics, motion analysis, rehabilitation technology, motor control and motor learning. Department of Therapy Services, PO Box 800719, University of Virginia Health Sciences System, Charlottesville, VA 22908; firstname.lastname@example.org.