Although DM was originally thought to be an independent risk factor for DM1,2, more recent data suggest otherwise.
A population-based study involving residents of Olmsted County, Minnesota, calculated the incidence of VTE among patients with DM over a 25-year period and found it to be higher than that of controls 2 . However, in the same study, after controlling for hospitalization for major surgery or medical illness and nursing home confinement, no association between DM and VTE was found2 .
A recent systematic review and meta-analysis of case-control and cohort studies involving over 1 million patients found no significant association between DM and VTE when controlled for common risk factors (eg, obesity, sedentary life style, smoking, hypertension, or dyslipidemia)3. The authors concluded that DM and its complications are not independent risk factors for incident VTE.
Thus, it appears that much of the risk of DVT in DM may be related to its comorbidities and the need for hospitalization, surgery or nursing home stay.
- Petrauskiene V, Falk M, Waernbaum I, et al. The risk of venous thromboembolism is markedly elevated in patients with diabetes. Diabetologia 2005;48:1017-21.
- Heit JA, Leibson CL, Ashrani AA, et al. Is diabetes mellitus an independent risk factor for venous thromboembolism? A population-based case-control study. Thromb Vasc Biol 2009; 29:1399-1405.
- Gariani K, Mavrakanas T, Combescure C, et al. Is diabetes mellitus a risk factor for venous thromboembolism? A systematic review and meta-analysis of case-control and cohort studies. Eur J Intern Med 2016;28:52-58.
Hiccups (AKA singultus) are due to the involuntary contraction of the inspiratory muscles, especially the diaphragm. The hiccup reflex involves an afferent limb ( eg, the phrenic and vagus nerves, sympathetic fibers from T6-T12, brainstem) and an efferent limb, primarily the phrenic nerve1,2. Thus, the irritation of any part of the arc in the head, neck, chest, or abdomen may potentially lead to hiccups.
Conditions involving the chest cavity that may be associated with hiccups include lung cancer, GERD, herpetic esophagitis, myocardial ischemia, bronchitis, empyema, lung masses, pneumonia, pleuritis, and pacemaker lead injury 1-3.
Reports of patients with PE and persistent hiccups (lasting longer than 48 h) have also appeared in the literature1,3. Of interest, in a report involving 3 patients, 2 had submassive or “large” PE, with one displaying the classic EKG changes of S1Q3T3; the size of PE in another was not reported1. In another case report, PE was “not small” and involved the anterior and lateral lower lobe segments of pulmonary artery2. Although the exact mechanism of PE causing hiccups is not clear, irritation of the afferent or efferent limb of the reflex arc in the chest has been postulated.
- Hassen GW, Singh MM, Kalantari H, et al. Persistent hiccups as a rare presenting symptom of pulmonary embolism. West J Emerg Med 202;13:479-483.
- Durning SJ, Shaw DJ, Oliva AJ et al. Persistent hiccups as the presenting symptom of a pulmonary embolism. Chest Disease Reports 2012;2:e2.
- Buyukhatipoglu H, Sezen Y, Yildiz A, et al. Hiccups as a sign of chronic myocardial ischemia. S Med J 2010;103: 1184-85.
Lead aVR is often “neglected” because of its non-adjacent location to other EKG leads (Fig 1) and poor awareness of its potential utility in detecting myocardial ischemia.
In acute coronary syndrome (ACS), ST-elevation (STE) in aVR (≥1mm) with diffuse ST depression in other leads (Fig 2) is usually a sign of severe left main coronary artery (LMCA), proximal left anterior descending (LAD), or 3-vessel coronary disease, and is associated with poor prognosis1-3. In some patients with LMCA thrombosis, the EKG changes may be non-specific but STE in aVR should still raise suspicion for ischemia1. Possible mechanisms for STE in aVR include diffuse anterolateral subendocardial ischemia or transmural infarction of the basal portion of the heart.
The possibility of an anatomical variant of the Purkinje fibers leading to the absence of STE in the anterior leads in some patients with transmural anterior infarction is another reason to pay attention to aVR.
Fig 1. Standard EKG limb leads. Note that aVR is “in the fringes”.
Fig 2. 35 year old female with ACS due to LMCA spasm. Note STE in aVR with ST segment depression in leads V3-6, I, aVL, II, and aVF (Courtesy National Library of Medicine)
- Kossaify A. ST segment elevation in aVR: clinical syndrome in acute coronary syndrome. Clin Med Insights: Case Reports 2013:6.
- Kireyev D, Arkhipov MV, Zador ST. Clinical utility of aVR-the neglected electrocardiographic lead. Ann Noninvasive Electrocardiol 2010;15:175-180.
- Wong –CK, Gao W, Stewart RAH, et al. aVR ST elevation: an important but neglected sign in ST elevation acute myocardial infarction. Eur Heart J 2010;31:1845-1853.
- De Winter RJ, Verouden NJ, Wellens HJ, et al. A new ECG sign of proximal LAD occlusion. N Engl J Med 2008;359:2071-3.
There are no randomized-controlled studies that examine the effectiveness of VTE prophylaxis in debilitated patients following discharge from the hospital, and currently the literature does not recommend prophylaxis for chronic immobility as a single risk factor for VTE (1). However, given the expected morbidity, potential mortality and hospital readmission associated with VTE, prophylaxis should be considered in residents of LTFs with the following comorbidities (2):
- Acute exacerbation of congestive heart failure
- Acute exacerbation of chronic obstructive pulmonary disease
- Acute infection (e. g. pneumonia, urosepsis, skin and soft tissue infections, infectious diarrhea)
- Acute exacerbation of inflammatory/autoimmune diseases
Unless contraindicated, patients should receive prophylactic doses of unfractionated heparin, enoxaparin, or other approved drugs. Mechanical VTE prophylaxis should be used only when the risk of bleeding is considered unacceptably high or when there are drug intolerances or adverse effects.
The need for VTE prophylaxis should be reassessed regularly taking into account patient’s overall health status, mobility, drug tolerance and goals of care.
- Pai M, Douketis JD. Preventing venous thromboembolism in long-term care residents: Cautious advice based on limited data. Cleveland Clin J Med 2010;77: 123-130
- Robinson Am. Venous thromboembolism prophylaxis for chronically immobilized long-term care residents. Ann Long-Term Care 2013;10:30.
Seasonal variation, primarily characterized by a winter peak, has been reported for acute CV events, such as acute myocardial infarction (AMI) and sudden death, aortic rupture or dissection, and ischemic or hemorrhagic stroke, and VTE (1). A meta-analysis involving patients with VTE, primarily with a diagnosis of pulmonary embolism, revealed a 20% absolute increase in the incidence of VTE during January (1).
Potential physiological mechanisms for these observations include increased sympathetic activity, decreased loss of fluids and sodium, increase in LDL cholesterol, increase in serum fibrinogen levels and other coagulation markers, and C-reactive protein, and lower vitamin D levels due to shorter daylight hours during winter months (1,2). At least in the case of AMI in the U.S., the higher incidence in winter is not affected by climate (2). Respiratory virus infections as a cause of acute inflammation leading to CV or VTE events is an intriguing hypothesis (3).
- Dentali F, Ageno W, Rancan E, et al. Seasonal and monthly variability in the incidence of venous thromboembolism. A systematic review and a meta-analysis of the literature. Thromb Haemost 2011;106:439-447.
- Spencer FA, Goldberg RJ, Becker RC, et al. Seasonal distribution of acute myocardial infarction in the Second National Registry of Myocardial Infarction. J Am Coll Cardiol 1998;31:1226-33.
- 3. Woodhouse PR, Khaw KT, Plummer M, et al. Seasonal variations of plasma fibrinogen and factor VII activity in the elderly: winter infections and death from cardiovascular disease. Lancet 1994;343:435-39.
Although warfarin has long been the standard treatment for venous thromboembolism (VTE) and thomboprophylaxis in atrial fibrillation (AF), the need for its frequent monitoring, potential drug interactions, and narrow therapeutic window made it far from ideal. Since 2009, NOACs have become viable alternative agents owing to their more predictable and safer pharmacological profiles. NOACs include several direct factor Xa inhibitors (apixaban, rivaroxaban, edoxaban) and a direct thrombin inhibitor (dabigatran). Approved indications include: (1) thromboprophylaxis in nonvalvular AF; (2) treatment of deep venous thrombosis or pulmonary embolism; and (3) primary prevention of postoperative VTE.
Compared to warfarin, NOACs are associated with a reduced risk of intracranial hemorrhage, and in the case of apixaban, lower risk of gastrointestinal bleeding; rivaroxaban and edoxaban have been associated with a higher risk of gastrointestinal bleeding. Apixaban is also the only NOAC whose dose can be safely reduced in chronic kidney disease, including those on hemodialysis.
1. Baber U, Mastoris I, and Mehran R. Balancing ischaemia and bleeding risks with novel oral anticoagulants. Nat Rev Cardiol 2015;12:66.
2. Ansell JE. Universal, class-specific, and drug-specific reversal agents for the new oral anticoagulants. J Thromb Thrombolysis 2015. Published online October 2015.
Contributed by William L. Hwang, MD.
NOACs (rivaroxaban,apixaban,and dabigatran) are increasingly considered for use after hip and knee arthroplasties due to their demonstrated efficacy against VTE prophylaxis with an acceptable safety profile. When compared to enoxaparin, the risk of VTE appears to be significantly lower with rivaroxaban (relative risk 0.48), and similar with dabigatran and apixaban, while the relative risk of clinically relevant bleeding appears to be significantly higher with rivaroxaban (1.25), similar with dabigatran , and lower with apixaban (0.82) (1).
1. Gomez-Outes, Suarez-Gea L, Vargas-Castrillon E. Dabigatran, rivaroxaban, or apixaban versus enoxaparin for thromboprophylaxis after total hip or knee replacement: systematic review, meta-analysis, and indirect treatment. BMJ 2012;344:e3675.