Clinical Decision Making in Patients with Deep Vein Thrombosis (DVT) or Pulmonary Embolism (PE) By: Bekah Jarosinski

Objectives What is a DVT and how does a PE occur? What is the clinician’s role in patients with a DVT or PE? What is the current best evidence for treatment in patients with a DVT or PE? Lab values What happens if they are not properly coagulated? Is there a difference in treatment of upper vs lower extremity DVT? Is there any evidence of consequences for holding eval/treatment orders (bed rest) or beginning early mobility of a patient with DVT or PE?

What is a DVT? Blood clot that forms in the deep veins of the body. It is made up of RBCs, fibrin, and activated platelets. Typically occurs due to venous stasis, which causes damage to the endothelial lining of blood vessels. The vessel starts to inflame and activates coagulating factors. Can be symptomatic or asymptomatic. Symptoms include increased warmth, swelling, and pain. DVT can be caused by blood not circulating well, cardiac diseases, thicker blood, enzymatic imbalances, immobility, and post-surgery. Post-thrombotic syndrome can result due to vessel irritation. “Known as the silent killer” Most common place for a thrombus to break off and become an embolus is in the leg. Occasionally it can come from collagen or other tissue, part of a tumor, air bubbles, or fat from a broken long bone. Lung or heart disease can increase chances of and symptoms of PE. Postthrombotic syndrome causes edema in the LE, leg pain, skin discoloration, and ulcers. It causes permanent damage to the veins via pulmonary hypertension.

What is a PE? Embolus travels from the deep vein and becomes lodged in the small pulmonary arteries. This can lead to a blockage of the vessels of the lung, causing cell death. Symptoms differ based on the area of lung involvement, size, and associated comorbidities. Most Common: SOB Chest pain Sanguineous Cough 1 in 5 individuals with PE die, while another 40% die within 3 months of PE. A PE leads to chronic thromboembolic pulmonary hypertension and reduced oxygenation. Over time, a PE can lead to R heart failure --> CHF

Risk Factors for DVT/PE Family/Past Medical history Heart Disease Cancer Surgery BED REST Long trips Smoking Inflammatory bowel disease Age INACTIVITY Overweight Supplemental estrogen Pregnancy Runs in the family (inherited blood-clot disorders) CVD (CHF) pancreatic, ovarian and lung cancers Over 60 increases your risk 1 in 5 individuals with PE die, while another 40% die within 3 months of PE.

Current Best Evidence In most acute care hospitals, clinicians tend to be on the conservative side and place bed rest orders for patients with DVT and PE, until the patient is properly coagulated. Doctors will prescribe blood thinners (heparin, lovenox, warfarin, coumadin) and have mechanical compression stockings in place as soon as a diagnosis is made. In Feb. 2016, The American Physical Therapy Association (APTA), in conjunction with the Cardiovascular & Pulmonary and Acute Care sections of APTA came up with 14 CPRs to help guide therapists. Handout Advocate for a culture of mobility and physical activity Screen for risk of VTE Provide preventative measures for LE DVT Recommend mechanical compression as a preventative measure for LE DVT Identify the likelihood of LE DVT when signs and symptoms are present Communicate the likelihood of LE DVT and recommend further medical testing. Verify the patient is taking an anticoagulant Mobilize patients who are at therapeutic level of anticoagulation. Recommend mechanical compression for patients with LE DVT Mobilize patients after IVC filter placement once hemodynamically stable. Consult with the medical team when a patient is not anticoagulated and without an IVC Screen for fall risk Recommend mechanical compression when signs and symptoms of PTS are present Implement management strategies to prevent future VTE. Academy of Acute Care Physical Therapy – APTA, 2017

Current Best Evidence Continued Have to use best clinical judgement if a patient is not on anticoagulation medications or has not yet reached therapeutic values What do the lab values look like? Use the current algorithm developed by the APTA in 2016. Wells Clinical Prediction Rule is another great tool to use when determining if a patient is at high or low risk of having or developing a DVT or PE. There is significant support in the research for mobilizing patients as soon as their anticoagulation medications have made their INR and PT therapeutic.

Wells Clinical Prediction Rule Active Cancer (treatment ongoing or within previous 6 months) Paralysis, paresis or recent plaster immobilization of the LE Recently bedridden for 3 days or more, or major surgery within the previous 12 weeks requiring anesthesia Localized tenderness along the distribution of the deep venous system Entire leg swelling Calf Swelling at least 3cm larger than asymptomatic leg (measured 10cm below tibial tub) Pitting Edema confined in symptomatic leg Collateral superficial veins (nonvaricose) Previous DVT Subtract 2 if there is an alternative diagnosis at least as likely as a DVT High probability of DVT if >3 Mod 1-2 Low 0

(Academy of Acute Care Physical Therapy – APTA, 2017)

Therapeutic Ranges Blood for Serum Viscosity Prothrombin time can be measured in two different ways: 1. INR: How coagulated the blood is. Higher the number the thinner the blood is. Lower the number, the increased risk there is for DVT formation. Therapeutic ranges for this number is based upon a specific diagnosis and the bodies ability to adapt to it’s changes conditions (chronic) 2. Prothrombin time: How long it takes for blood to clot. Activated Partial Thromboplastin time Makes sure the right dose of heparin is being used Prothrombin Time Makes sure the right dose of Coumadin is used Anti-Factor Xa Assay: Different ways to treat blood-clotting disorders. Different molecular structures. Academy of Acute Care Physical Therapy – APTA, 2017

Clinical judgement in treating patients who are not properly anticoagulated. Level V evidence – Expert opinion Consider the risks vs the benefits of the POC when lab values are outside of therapeutic ranges. Length of immobilization, ability to receive anticoagulants, acute vs chronic changes in lab values. Have to get a composite of the patient as a whole. What does their HPI and PMH look like? How many risk factors are associated with this patient. Work as an interdisciplinary team. Should still encourage light, bed level, therapeutic active and passive ROM. Should not mobilize patient if the LE DVT is located above the knee. If anticoagulation therapy is contraindicated, doctors may consider placing an inferior vena cava filter if risk of PE is high. Risks  Some kind of physiological event (Such as an embolus traveling to the lungs. ) Benefits  Early mobility (Which has been shown to increase their chances of a better prognosis) A patient that is on bed rest and continues to be on bed rest will only increase their chances of having an adverse event occur. So you have to weigh the pros and cons together in a team Contraindications to anticoagulation What is their diagnosis, symptoms, length of disease? When the body undergoes a change in it’s lab values due to surgery, injury, or disease, it takes a while for it to adapt. In the acute phase, abnormal lab values can stress the cardiovascular and respiratory system affecting a patient’s ability to move and exercise. Academy of Acute Care Physical Therapy – APTA, 2017

UE vs LE DVT and Treatment A big difference between the formation of UE vs LE DVTs, is how they are formed. UE DVT is typically due to a primary etiology (disease), while LE DVT is due to a secondary etiology (immobilization after surgery). Central venous catheter insertion has increased the number of DVTs seen in the UEs. Brachial, subclavian and axillary v. most commonly involved. More likely to use LMWH vs other anticoagulants in the UE. Can lead to thoracic outlet syndrome, if DVT is over brachial plexus. If the patient has a central venous line and vascular access is still needed, the patient needs to be on anticoagulants for as long as the central venous line is in as well as 3 months after removal. If DVT is due to cancer, patient should be on anticoagulants for at least 3-6 months. Best practice is to make sure patient is properly anticoagulated before movement. Primary upper extremity deep venous thrombosis is a rare disease occurring spontaneously, without clinically apparent risk factors (idiopathic thrombosis) or after strenuous exercise (effort thrombosis). Effort thrombosis is more common in athletic populations. (Baskin, J. L., Pui, C., Reiss, U., Wilimas, 2009)

Is there any evidence of consequences for holding eval/treatment orders or beginning early mobility of a patient with DVT or PE? There is a lot of controversy surrounding this topic based around two different sets of beliefs. Many clinicians believe that early mobilization for a patient will prevent the venous stasis and DVTs from forming. On the other hand, there are clinicians who believe that we should immobilize a patient (bed rest) and give them anticoagulants to prevent a thrombus from breaking off proximally and traveling to the lungs as a PE.

A meta-analysis of bed rest versus early ambulation in the management of pulmonary embolism, deep vein thrombosis, or both. - Aissaoui N, Martins E, Mouly S, et. al., 2009 Methods: Used 3 databases. The meta-analysis looked at the outcomes of patients with DVT, PE or both and whether they were managed with bed rest or early ambulation, in addition to anticoagulation. Used a total of 5 studies with 3048 patients. Relative risk (RR) and confidence interval (CI) were used to look at incidence of new PE, new or progression of DVT, and death from all causes. Results: When compared to bed rest, early mobility was not associated with an increased risk of new PE. (RR 1.03; 95% CI 0.65-1.63; p=0.90) Early mobilization was associated with a decreased risk of new PE and new or progression of DVT compared to bed rest (RR 0.79; 95% CI 0.55-1.14; p=0.21)  and a decreased risk of new PE and overal mortality. (RR 0.79; 95% CI 0.402-1.56; p=0.50) All patients were on an anticoagulant therapy treatment. It is also important to note that none of these numbers are clinically significant. (p=<.05) Patients in the ambulatory group were able to walk with the anticoagulant therapy between days 0 and 2 depending on the study. Patients confined to bed rest were in bed between 3 and 9 days.

Study Conclusion According to this study, it appears that there are no consequences to early mobility vs bed rest in a patient that is properly anticoagulated While this study does lean more towards early mobility compared to bed rest, it is important to note that none of their findings were clinically significant with a p value of equal to or less than .05. Need to use clinical judgement when deciding on moving a patient vs keeping them on bed rest.

In Conclusion Once a patient has reached their therapeutic INR range based on the patient’s individual medical diagnosis, there is evidence that mobilizing a patient will not cause a new DVT or PE to occur. Typically, it takes 3 days for a heparin drip to thin and break down the clot. Patients who are not treated with an anticoagulant have a 20% chance of the clot breaking off and causing a PE, warranting the current CPG. Unfortunately, there is not a lot of research available on early mobility and the presence of DVT in patients that are not on an anticoagulant therapy. Clinical judgement, patient self-monitoring of symptoms, and the interdisciplinary team are the best factors in deciding whether or not a patient who isn’t on anticoagulants, or has not yet reached therapeutic levels, should be mobilized. At this time, there is no evidence proving that early mobility will increase chances of PE in patients who are anticoagulated. There is a higher risk of a patient having a PE due to a DVT if they are not on anticoagulant.

Resources Aissaoui, N., Martins, E., Mouly, S., Weber, S., & Meune, C. (2009). A meta-analysis of bed rest versus early ambulation in the management of pulmonary embolism, deep vein thrombosis, or both. International Journal of Cardiology, 137(1), 37-41. doi:10.1016/j.ijcard.2008.06.020 Baskin, J. L., Pui, C., Reiss, U., Wilimas, J. A., Metzger, M. L., Ribeiro, R. C., & Howard, S. C. (2009). Management of occlusion and thrombosis associated with long-term indwelling central venous catheters. The Lancet, 374(9684), 159-169. doi:10.1016/s0140-6736(09)60220-8 Czihal , M., & U. H. (2011). Upper Extremity Deep Venous Thrombosis. Vascular Medicine, 37-40. doi:10.1002/9780470692042.ch7 Hillegass, E., Puthoff, M., Frese, E. M., Thigpen, M., Sobush, D. C., & Auten, B. (2015). Role of Physical Therapists in the Management of Individuals at Risk for or Diagnosed With Venous Thromboembolism: Evidence-Based Clinical Practice Guideline. Physical Therapy, 96(2), 143-166. doi:10.2522/ptj.20150264 http://c.ymcdn.com/sites/www.acutept.org/resource/resmgr/docs/2017-Lab-Values-Resource.pdf http://www.mayoclinic.org/diseases-conditions/pulmonary-embolism/symptoms-causes/dxc-20234744 http://www.mayoclinic.org/diseases-conditions/deep-vein-thrombosis/basics/definition/con-20031922 http://www.merckmanuals.com/professional/cardiovascular-disorders/peripheral-venous-disorders/deep- venous-thrombosis-dvt http://www.medicinenet.com/deep_vein_thrombosis/article.htm