Effort Thrombosis With Sepsis
Kevin deWeber, MD
THE PHYSICIAN AND SPORTSMEDICINE - VOL 27 - NO. 5 - MAY 99
In Brief: This report of a recreational athlete who had arm discomfort, fever, headache, and emesis frames a discussion of the diagnosis and treatment for primary upper-extremity deep vein thrombosis (PUEDVT). An unusual aspect of the case was sepsis without typical risk factors. Treatment of PUEDVT usually involves immediate anticoagulation and local thrombolysis followed by evaluation for postthrombosis management; septic thrombophlebitis usually responds to intravenous antibiotics. Postthrombosis management is somewhat controversial, but first-rib resection is frequently recommended for patients who have thoracic outlet compression. This patient returned to unrestricted athletics without surgical intervention.
Primary upper-extremity deep vein thrombosis (PUEDVT) is the most common vascular problem in athletes (1). Named Paget-Schroetter syndrome by Hughes (2), who reviewed 320 cases from the medical literature, the condition is also referred to as effort thrombosis because 70% of cases have been associated with unaccustomed or vigorous activity (3). Athletic activity in particular has been cited as the cause in about 20% of all cases (1).
A case of PUEDVT in a physically active young man serves here as the basis for a review of the recognition, evaluation, and management of PUEDVT. The case described is unusual because the condition was accompanied by sepsis in the absence of any typical risk factors for septic thrombophlebitis.
A 30-year-old man who was a family physician in the US Army presented at a hospital emergency department with right-arm discomfort, fever, severe headache, and emesis, claiming to have an infected upper-extremity deep vein thrombosis (DVT).
History. The patient reported the onset 1 week earlier of slight venous distention in his right (nondominant, throwing) arm. Two days after the onset of swelling, he had developed malaise, mild night sweats, and a low-grade fever. On the night before being seen, he had had a high fever, rigors, and moderate deep shoulder pain.
He recalled no traumatic event but had been doing intense weight lifting every other day and playing left field on a softball team. He denied having any shortness of breath, chest pain, recent central venous catheterization, or prior use of intravenous (IV) drugs. He did report a small, superficial laceration to his right index finger that had occurred around the time of onset of venous distention and healed quickly. His medical history was unremarkable and he was taking no prescribed medications.
Physical exam. On presentation, the patient was alert, oriented, normotensive but tachycardic, and febrile at 103.9°F (39.9°C). His physical exam was significant for asymmetrically prominent veins over the entire right arm and upper-arm girth that was 3 cm greater on the right. No obvious source of infection was present.
Lab tests. Initial lab tests, done to evaluate for the patient's fever, rigors, nausea, and vomiting, were remarkable for pancytopenia. The white blood cell count was 3,800/mm3(normal, 3,200 to 9,800/mm3) with dramatic left shift; hemoglobin level was 12.6 g/dL (normal for men, 13.6 to 17.2 g/dL), and his platelet count was 97,000/mm3 (normal, 150,000 to 450,000/mm3). The patient's lactate dehydrogenase (LDH) level was elevated at 1,068 U/L (normal, 50 to 150 U/L), his aspartate aminotransaminase (AST) and alanine aminotransferase (ALT) levels were elevated at 127 U/L and 111 U/L, respectively (normal for both, 0 to 35 U/L), and his creatine phosphokinase (CPK) level was elevated at 565 U/L (normal, 0 to 130 U/L). The patient's electrolytes, blood urea nitrogen (BUN), creatinine, and urinalysis were normal.
Imaging studies. A chest x-ray revealed a right middle-lobe nodular density, left lower-lobe infiltrate, and small bilateral pleural effusions. Duplex ultrasonography and plethysmography of the right upper extremity and shoulder were normal, but a venogram revealed occluded basilic, axillary, and subclavian veins, with extensive collateral flow into the internal jugular vein (figure 1).
Diagnosis. The patient was diagnosed as having PUEDVT; sepsis was suspected pending results of blood cultures.
Treatment. The patient was initially treated for DVT with IV heparin sodium, and for the suspected sepsis with oral vancomycin hydrochloride and ceftriaxone sodium. He was admitted to the hospital and treated with oxygen by nasal cannula for mild hypoxemia that developed shortly after admission. The patient's hypoxia resolved after 24 hours, and the fever resolved within 36 hours of antibiotic treatment.
On the third day of hospitalization the patient's admission blood cultures grew Staphylococcus aureus in two of three sets, so ceftriaxone was discontinued and IV gentamicin sulfate was added. A computed tomogram (CT) of the chest was then obtained. It revealed several wedge-shaped densities, the largest measuring 3 cm in the right middle lobe, a finding highly suggestive of septic emboli.
Because the patient's arm signs and symptoms remained unchanged after 48 hours, he was transferred to a tertiary medical facility for treatment by a vascular surgeon. There, a 5-French angiographic catheter was placed in the cephalic vein and fluoroscopically advanced to the thrombus near the junction of the cephalic and axillary veins. The basilic vein contained a thrombus extending nearly to the antecubital fossa and could not be cannulated. An infusion of 62,500 units of urokinase per hour was begun and maintained for 24 hours.
A repeat venogram showed a now-patent axillary vein but persistently occluded subclavian vein (figure 2). The catheter was advanced into the subclavian vein next to the thrombus and the urokinase infusion was continued for another 24 hours, after which a venogram revealed patency of the subclavian and brachiocephalic veins and much-diminished collateral flow (figure 3). The edges of the subclavian vein appeared only slightly irregular, indicating a small residual thrombus. The catheter was removed and oral anticoagulation with warfarin sodium was begun. When the patient's international normalized ratio (INR) reached 2.5 (therapeutic range for warfarin, 2.0 to 3.0), IV heparin was discontinued.
After 5 days of IV antibiotics, two sets of blood cultures were obtained, and both were negative.
Follow-up. Just before discharge on day 12 of hospitalization, a central line was placed in the left internal jugular vein for an additional 16 days of IV antibiotic (cefazolin sodium) to complete a 28-day course. This was followed by 14 days of oral ciprofloxacin hydrochloride and rifampin.
The patient was treated with warfarin for 3 months, after which a CT angiogram of his right thoracic outlet revealed no compression of the subclavian or axillary veins. Six weeks after discontinuation of the warfarin, a complete workup for hypercoagulability was negative.
The patient returned to exercise after discharge, and to athletics after the 28-day course of IV antibiotics. Eighteen months after onset of thrombosis the patient was still asymptomatic and participating in athletics with no restrictions.
PUEDVT is primarily a condition of the young, healthy, and active. It should be considered if such a patient presents with or reports aching and swelling of an arm and prominent arm veins following vigorous upper-limb activity or abnormal arm positioning. In contrast, secondary DVT of the upper extremity is due to an underlying pathologic condition or related therapy, most commonly congestive heart failure, malignancy, an indwelling catheter, or hypercoagulability.
Pathogenesis. PUEDVT generally has a traumatic pathogenesis (1). Sometimes the condition can result from a blow to the shoulder. More commonly, however, it develops as a result of chronic repetitive minor trauma to the axillosubclavian vein during vigorous activity. Sports cited as preceding upper-extremity thrombosis include baseball, weight lifting, gymnastics, basketball, hockey, tennis, golf, football, handball, squash, rowing, boxing, swimming, volleyball, softball, and parachute jumping (1,2,4,5).
Trauma is not required, however. Thirteen percent to 32% of patients have reported no particular activity before their thrombosis, and many have awakened from sleep with the condition, presumably from an abnormal arm position that causes pressure on the vein wall (2,4).
Impingement by structures in the thoracic outlet (eg, a hypertrophied anterior scalenus muscle, first rib, clavicle, or cervical rib) may often predispose a person to PUEDVT from trauma. Reactive changes within the vessel wall then result in thrombus formation either by occlusion of the lumen or release of thromboplastic substances (1).
Signs and symptoms. Swelling of the arm is usually the first symptom of PUEDVT, although pain, discomfort, or discoloration may occur initially. The whole arm often becomes swollen to a variable degree. While swelling is the most common presenting finding, sometimes it becomes apparent only after arm exercise. Pain is usually described as a dull ache; numbness and heaviness occur frequently as well.
Physical examination demonstrates nonpitting edema in virtually all patients. The superficial veins of the arm are usually prominent; anterior chest and shoulder veins often become visible. Pulses are normal, and the arm often has a dusky color and mottling. Palpable cords are inconsistently present in the axilla or proximal arm, and tenderness may be present along the brachial and axillary veins. Constitutional symptoms are rare (1,2).
Lab testing in uncomplicated PUEDVT is not necessary other than establishing a baseline INR, partial thromboplastin time, and complete blood count before treatment with anticoagulants.
Diagnostic imaging. Color flow duplex ultrasonography can usually be used to diagnose the condition, but false-negative results can occur, as in this patient. The diagnosis may require confirmation with venography, which also provides IV access for treatment.
Initial treatment. Before the advent of modern treatment methods, conservative therapy with arm elevation with or without IV heparin was the standard treatment for upper-extremity DVT. Although the initial response was usually good, 64% to 77% of patients continued to have significant residual symptoms of swelling, pain, easy fatigability, or superficial thrombophlebitis (4). This often led to the need for job reclassification or even to disability.
Significant advances in the treatment of PUEDVT have been made in the last 20 years, markedly reducing the incidence of chronic symptoms. Immediate treatment with IV heparin for 4 to 7 days is important to halt clot propagation, and local, catheter-directed urokinase in the acute phase is now the most effective modality for achieving thrombolysis and vein patency. After thrombolytic therapy is concluded, anticoagulation with oral warfarin for 3 months is widely used (5).
The success rate for thrombolysis with catheter-directed (as opposed to systemic) urokinase ranges from 69% to 94% (6,7). The time from symptom onset to beginning of thrombolysis, however, affects the success rate. The greatest success in achieving vein patency with no residual thrombus occurs if thrombolysis is begun within about 7 days of symptom onset (6), although initiating thrombolysis up to 10 to 14 days after onset is reasonable (3).
Postthrombolysis management. Management after thrombolysis (failed or successful) is less straightforward than immediate thrombolytic treatment. My literature search revealed no prospective randomized trials on the value and proper timing of treatments such as thoracic outlet decompression by first-rib resection, balloon angioplasty, vein patch angioplasty, or vein stents.
To achieve a reasonable consensus based on the available data, 25 vascular surgeons with a special interest in venous disease and considerable experience with axillosubclavian vein thrombosis met in 1995 to discuss the topic (3). As indicated by responses to a questionnaire, a large majority of the surgeons (96%) agreed that further therapy should be based on positional venography after thrombolysis. Although the test's prognostic value is unproven, it reveals extrinsic axillosubclavian vein compression in 70% to 100% of PUEDVT patients (3,6).
For cases in which no compression is demonstrated or only a short residual occlusion exists, 95% of the surgeons' responses favored conservative therapy only. For patients who have thoracic outlet compression, 86% favored surgical release (usually first-rib resection) after the period of oral anticoagulation. For cases in which significant residual stenosis is present (more than 50% narrowing), the majority favored further intervention, though opinion was split on the use of surgery vs balloon angioplasty.
The surgeons (3) and authors of other studies (8,9) have found, overall, that 80% to 90% of patients treated with thrombolysis followed by surgical thoracic outlet decompression were returned to a long-term asymptomatic state.
Sepsis. Septic thrombophlebitis in upper-extremity DVT is usually associated with indwelling IV catheters or IV drug abuse (10). My literature search yielded no report of PUEDVT in which a healthy person not using IV drugs presented with septic thrombophlebitis. It seems reasonable to assume that in my patient, the minor skin laceration, nasal vestibule trauma, or tooth brushing caused a transient bacteremia while the thrombus was present. The thrombus likely trapped potential bacterial pathogens, protected them from removal by the immune system, and acted as a nidus for infection.
Treatment for septic DVT usually requires only IV antibiotics in addition to the thrombosis treatment (11). If IV antibiotic treatment is not effective within 24 to 48 hours, surgical exploration should be undertaken.
S aureus septic thrombophlebitis leads to complications in the form of deep-seated infections (septic emboli, endocarditis, meningitis, or abscess) in 45% of cases, and recurrence is likely unless the sepsis is treated with 4 weeks of IV antibiotics (12).
Other complications. Nonfatal pulmonary embolism occurs in about 12% of patients who have PUEDVT (13). Recurrence of PUEDVT is also a significant problem. About 14% of patients presenting with acute effort thrombosis have a history of a prior episode, usually on the contralateral side (14). Prompt diagnosis and treatment can reduce the risk of chronic, disabling symptoms of venous insufficiency and return most patients to full athletic participation.
The views expressed in this article are those of the author and do not reflect the official policy or position of the US Army, US Department of Defense, or US government.
Dr deWeber is a board-certified family physician at the US Army Health Clinic in Schweinfurt, Germany, and a member of the American Academy of Family Physicians and the Alpha Omega Alpha Medical Honor Society. Address correspondence to Kevin deWeber, MD, CMR 457 Box 682, APO AE 09033; address e-mail to [email protected].