Annals of B Pod: Phlegmasia Cerulea Dolens
/HISTORY OF PRESENT ILLNESS
The patient is a female in her late 60’s presenting with acute onset of left arm pain and swelling. She initially noticed pain in her left arm with movement while helping her family move earlier on the day of presentation. While changing, she noticed that her arm was swollen to the mid humerus. She feels that this swelling came on over several hours. The patient developed numbness and tingling in the fingers of her left arm two hours prior to presentation. She was concerned that this was not improving and decided to come to the emergency department (ED). She denied any injuries or central venous access attempts through her left arm. She had not had any blood clots previously. She had some mild chest pain and light-headedness in ED triage which subsequently resolved.
Past Medical History: Chronic kidney disease, diabetes mellitus II, coronary artery disease, Congestive heart failure, sarcoidosis
Past Surgical History: Cardiac stenting, appendectomy, cholecystectomy, implantable cardioverter-defibrillator (ICD) placement, gastrectomy sleeve
Medications: Aspirin 81, atorvasatin, carvedilol, plavix, estrodiol vaginal cream, ezetimibe, isosorbide mononitrate, metformin, insulin basaglar, insulin novolog
Allergies: None
Physical exam
Vitals: HR 78, BP: 158/75, RR: 18, SpO2 100% ORA, T 98.8F
The patient is comfortable and in no acute distress. The patient has generalized edema of the left arm extending from the fingertips to the mid-humerus. There is erythema of the skin overlying the swelling with cyanotic discoloration of the left hand and fingertips. The left hand is subjectively cool compared to the right. Radial pulses are symmetric bilaterally; however, the left ulnar pulse is nonpalpable with a normal right ulnar pulse. The patient has decreased active flexion and extension of the left fingers due to pain. The remainder of the physical examination is unremarkable.
Notable Diagnostics
CBC: unremarkable, BMP: unremarkable
X-ray imaging of the left hand, wrist, and forearm: chronic degenerative changes without acute fracture or bony abnormality.
CT Angiography (CTA) of left upper extremity: concern for occlusion of distal ulnar artery at the level of the ulnar styloid with lack of contrast distal to the occlusion; diffuse soft tissue swelling from the distal humerus to the left hand (Figures 1 and 2).
Hospital Course
The patient was initiated on a therapeutic heparin drip in the emergency department with vascular surgery consultation. Vascular surgery recommended left upper extremity duplex ultrasonography to evaluate for thrombosis with ongoing anticoagulation to be determined by that study. They did not recommend any surgical intervention for the ulnar artery occlusion. Left upper extremity ultrasonography was positive for acute occluding deep vein thrombosis of the subclavian vein. Vascular surgery attributed the subclavian thrombosis to the patient’s ICD. Hematology was consulted and recommended lifelong anticoagulation. A hypercoagulability work-up was unremarkable, and there was no evidence to suggest disseminated intravascular coagulation (DIC). She had improvement of the swelling in her left arm with return of sensation and function during her five-day hospital course. The patient was ultimately discharged on apixaban to follow-up in hematology clinic.
Discussion
Pathophysiology
Deep vein thrombosis (DVT) is defined as the formation of a clot in the venous circulation. It is typically caused by areas of altered blood flow, such as near venous valves or areas of endothelial dysfunction. Platelets bind leukocytes and create a clot through local hypoxia and activation of the pro-inflammatory cascade. Endothelial dysfunction may be traumatic or systemic in nature. Hypercoagulable states such as pregnancy or obesity increase the likelihood of clot formation in these local areas with alterations of blood flow and endothelial dysfunction. [1]
Phlegmasia Cerulea Dolens (PCD) is a rare condition characterized by DVT with evidence of critical limb ischemia in the affected limb. Occlusion of venous outflow leads to increases in interstitial pressure. In the short term this can manifest with swelling, cyanosis, and intractable extremity pain. Further increases in interstitial pressure can lead to obstruction of arterial flow, cyanosis, and, in severe cases, limb gangrene. Although PCD is associated with DVT, there may be concurrent arterial embolic disease which is an extremely rare and poorly understood occurrence. [2]
Epidemiology
Upper extremity deep vein thrombosis (UE DVT) is an uncommon occurrence, comprising between 5 and 10% of all deep venous thrombosis, with an annual incidence of 0.4 to 1 cases per 100,000. Venous access, both peripheral and central, is a common risk factor and has been present in 60% of those with UE DVT. Malignancy is another common risk factor and is present in approximately one-third of patients with UE DVT. Repetitive overhead movement which exacerbates a pre-existing thoracic outlet obstruction may incite UE DVT. Thrombophilic disorders may also predispose to UE DVT. An inciting factor is not always identified for UE DVT, as between 20 and 30% of patients have no clear cause. [3,4,9]
Phlegmasia Cerulea Dolens of the upper extremities is an extremely rare clinical entity, estimated to occur in 2-5% of patients with UE DVTs. Risk factors are similar to those of upper extremity DVT and include hypercoagulable states, malignancy, infection (specifically phlebitis), trauma, major surgery, hypertonic solution infusion, and medical device presence such as central venous access or indwelling cardiac pacemakers. Afflicted individuals tend to have multiple medical comorbidities including malignancy (37%), congestive heart failure (26%), and/or infection (26%). It is hypothesized that these conditions lead to decreased distal perfusion in the setting of an UE DVT. [2,5]
Clinical Presentation
Upper extremity DVT frequently presents with acute onset of pain and swelling in the affected arm. The pain is often localized to the axilla, neck, or shoulder and may be described as a feeling of heaviness or pressure in the arm. These symptoms occur after strenuous overhead activity such as repetitive lifting in over half of patients. The symptoms of PCD include those of UE DVT but with further evidence of developing compartment syndrome including cyanosis, more pronounced edema, paresthesia, and intractable pain which is typically more distal than that of an UE DVT. Physical examination of the affected extremity will typically demonstrate edema. There may be cyanotic discoloration of the hands and fingers which is likely to represent PCD. Dilated superficial collateral veins on the chest and proximal extremity (Urschel’s sign) may be present. Reduced arterial blood flow may be present and typically represents PCD when it is. [2,5,11]
Diagnosis and Evaluation
In patients with low to moderate suspicion for UE DVT, D-dimer may be helpful to exclude thrombosis. If there is suspicion for PCD, D-dimer testing may be helpful as part of a coagulopathy evaluation but should not be used to exclude thrombosis as it does not evaluate for other sources of vascular insufficiency such as venous com- pression or stenosis. [10] Duplex ultrasonography is the initial test of choice to evaluate for UE DVT as it is noninvasive and inexpensive with sensitivity ranging from 56 to 100% and specificity ranging from 94 to 100%. Variations in sensitivity are thought to be related to operator technique, patient habitus, and difficulty evaluating the subclavian vein beneath the clavicle. [12] Following duplex ultrasonog- raphy, CT venography may be considered to evaluate for central venous obstruction; however, there is limited data supporting its use for evaluation of more distal upper extremity veins. [13] Ultimately, catheter-based venography is the gold-standard for diagnosis of thrombosis of the upper extremity deep veins. In cases of suspected PCD, this may be an appropriate diagnostic option as interventions may be indicated. Concurrent angiography may be considered with clinical evidence of arterial insufficiency, such as in PCD. [7,14]
Treatment and Prognosis
Initial therapy for UE DVT consists of symptomatic management with NSAIDs, elevation of the effected extremity, and therapeutic anticoagulation. Compression of the upper extremity can be considered but has limited evidence supporting its use. Upper extremity DVT alone can often be managed on an outpatient basis with direct-acting oral anticoagulants alone. [15] In the setting of PCD, the patient should be initiated on a heparin drip as further inpatient treatment and possible surgical intervention may be indicated. Catheter-directed therapy has become the mainstay of treatment for PCD in the setting of UE DVT. [8,16] Therapeutic aspirin may be considered if catheter-based thrombolysis is likely as this may counteract platelet-based thrombogenicity following thrombolytic therapy. [9] Surgical thrombectomy may be considered in patients who cannot undergo catheter-directed thrombolysis. For patients with PCD and concurrent compartment syndrome, fasciotomy may be considered in consultation with vascular surgery. [2,5,7]
Upper extremity DVT alone has low mortality; this is biased by a large portion of the population who are young and have a primary DVT precipitated by activity. For those with secondary DVT, mortality is significantly higher, ranging from 15 to 50%. [17] Likewise, PCD carries substantial morbidity. Amputation rates range from 20 to 50% of patients with PCD of the upper extremity. Mortality of upper extremity PCD ranges from 26 to 91%, as many affected individuals are critically ill with multiple medical comorbidities. [5]
SUMMARY
Upper extremity DVT is an uncommon occurrence with a varying clinical presentation. At one end of the spectrum, there are younger individuals with primary DVT that can be managed in the outpatient setting with direct oral anticoagulation. At the other end, there are older individuals with multiple medical comorbidities who develop a DVT secondary to factors such as critical illness or medical device placement. There is substantial morbidity and mortality for those patients. PCD is a rare disease entity in which a DVT leads to significant edema that decreases arterial perfusion with immediate threat to the involved limb. There is significant morbidity and mortality associated with the development of PCD. Management of PCD involves initiation of anticoagulation and may require catheter-directed thrombolytic therapy or thrombectomy and more severe cases may require fasciotomies due to the concurrent development of compartment syndrome.
AUTHORED BY Jeremy sobocinski, MD
Dr. Sobocinski is a PGY-3 in Emergency Medicine at the University of Cincinnati
EDITING BY DR. Olivia Gobble AND THE ANNALS OF B POD EDITORS
References
1.Navarrete S, Solar C, Tapia R, Pereira J, Fuentes E, Palomo I. Pathophysiology of deep vein thrombosis. Clin Exp Med. 2022 Apr 26.. Epub ahead of print.
2. Zhang J, Wang Y, Du Y, Zhao L. Phlegmasia Cerulea Dolens in the Upper Extremity: A Case Report and Literature Review. Ann Vasc Surg. 2021 Oct;76:601.e7-601.e11. Epub 2021 Jun 25.
3. Mustafa S, Stein PD, Patel KC, Otten TR, Holmes R, Silbergleit A. Upper extremity deep venous thrombosis. Chest. 2003 Jun;123(6):1953-6.
4.Grant J D, Stevens SM, Woller SC, et al.. Diagnosis and management of upper extremity deep-vein thrombosis in adults. Thromb Haemost. 2012;108(6):1097–1108. Crossref. PubMed.
5. Greenberg J, Troutman DA, Shubinets V, Dougherty MJ, Calligaro KD. Phlegmasia Cerulea Dolens in the Upper Extremity: A Case Report and Systematic Review and Outcomes Analysis. Vasc Endovascular Surg. 2016 Feb;50(2):98-101. Epub 2016 Feb 11.
6. Bolitho DG, Elwood ET, Roberts F. Phlegmasia cerulea dolens of the upper extremity. Ann Plast Surg. 2000 Dec;45(6):644-6.
7. Kammen BF, Soulen MC. Phlegmasia cerulea dolens of the upper extremity. J Vasc Interv Radiol. 1995 Mar-Apr;6(2):283-6.
8. Erdoes LS, Ezell JB, Myers SI, Hogan MB, LeSar CJ, Sprouse LR 2nd. Pharmacomechanical thrombolysis for phlegmasia cerulea dolens. Am Surg. 2011 Dec;77(12):1606-12.
9. Joffe HV, Kucher N, Tapson VF, Goldhaber SZ; Deep Vein Thrombosis (DVT) FREE Steering Committee. Upper-extremity deep vein thrombosis: a prospective registry of 592 patients. Circulation. 2004 Sep 21;110(12):1605-11. Epub 2004 Sep 7.
10. Merminod T, Pellicciotta S, Bounameaux H. Limited usefulness of D-dimer in suspected deep vein thrombosis of the upper extremi- ties. Blood Coagul Fibrinolysis. 2006 Apr;17(3):225-6.
11. Lindblad B, Tengborn L, Bergqvist D. Deep vein thrombosis of the axillary-subclavian veins: epidemiologic data, effects of different types of treatment and late sequelae. Eur J Vasc Surg. 1988;2(3):161.
12. Mustafa BO, Rathbun SW, Whitsett TL, Raskob GE. Sensitivity and specificity of ultrasonography in the diagnosis of upper extremity deep vein thrombosis: a systematic review. Arch Intern Med. 2002 Feb 25;162(4):401-4.
13. Chung JW, Park JH, Yin YH, Park SH, Yoon CJ, Choi YH. Role of CT venography in the diagnosis and treatment of benign thoracic central venous obstruction. Korean J Radiol. 2003 Jul;4(3):146-52.
14. Di Nisio M, Van Sluis GL, Bossuyt PM, Büller HR, Porreca E, Rutjes AW. Accuracy of diagnostic tests for clinically suspected upper extremity deep vein thrombosis: a systematic review. J Thromb Haemost. 2010;8(4):684. Epub 2010 Feb 6.
15. Karabay O, Yetkin U, Onol H. Upper extremity deep vein thrombosis: clinical and treatment characteristics. J Int Med Res. 2004 Jul-Aug;32(4):429-35.
16. Said A, Sahlieh A, Sayed L. A comparative analysis of the efficacy and safety of therapeutic interventions in phlegmasia cerulea dolens. Phlebology. 2021 Jun;36(5):392-400. doi: 10.1177/0268355520975581. Epub 2020 Nov 25.
17. Flinterman LE, Van Der Meer FJ, Rosendaal FR, Doggen CJ. Current perspective of venous thrombosis in the upper extremity. J Thromb Haemost. 2008 Aug;6(8):1262-6. doi: 10.1111/j.1538-7836.2008.03017.x. Epub 2008 May 15.
