Thromboembolism and Toxic Shock Syndrome: A Case Presentation and Literature Update

Journal of Thrombosis and Thrombolysis 17(2), 133–137, 2004. C 2004 Kluwer Academic Publishers, Manufactured in The Netherlands.
Thromboembolism and Toxic Shock Syndrome: A Case Presentation and Literature Update U.M. Musharrafieh,1 G.W. Jamaleddine,2 A.T. Taher,3 W.Y. Almawi,4 Z.A. Tabbara5 Department of 1Family Medicine and 2,3,5Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon; 4College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Bahrain Abstract. A case of progressive shock and multisystem organ failure is reported for an 18 year old Lebanese woman, clinically diagnosed as toxic shock syndrome (TSS). The patient developed cough and dyspnea during hospitalization; chest CT angiography revealed thromboembolism of the pulmonary artery. CBC analysis showed leukocytosis with a white cell count (WCC) with a marked increase in PT and PTT coupled with reduced protein S, antithrombin III, and protein C levels. The patient improved gradually and was discharged from the hospital 7 days later on oral anticoagulation, and was followed up for six months with no disease recurence or complications. To our knowledge, this is the first reported case in the literature of toxic shock syndrome associated with pulmonary thromboembolism. Key Words. toxic shock syndrome, pulmonary thromboembolism, sepsis Abbreviations. TSS, toxic shock syndrome, DIC, disseminated intravascular coagulopathy. Introduction Toxic shock syndrome (TSS) is a severe illness which affects primarily otherwise healthy young women of child bearing age, and fatality ratios of 10– 15% and mortality rate of 8% were reported [1,2]. Whereas TSS traditionally occurred during menstruation phase, increased frequency of postpartum cases of TSS was reported [1]. Insofar as many cases do not satisfy the classical definition for TSS proposed by the Centers for Disease Control, revised diagnostic criteria for TSS were proposed based on the probable cause and other factors [3]. The clinical diagnosis of TSS is based on a constellation of abnormal clinical and laboratory tests [1]. Clinical features include sudden onset of high grade fever, hypotension, polymorphous skin rash, hepatic, renal failure, non-focal neurologic symptoms, disseminated intravascular coagulopathy (DIC) and various additional symptoms such as myalgias, vomiting, and diarrhea [3]. The clinical course depends on the extent of the organ failure, a result of decreased tissue perfusion during hypotension [4]. TSS may precipitate fatal complications ranging from re- fractory shock, oliguric renal failure, ventricular arrhythmia, and pulmonary complications which include non-cardiogenic pleural edema and adult respiratory distress syndrome [3,4]. Pulmonary embolism (PE) in adults is associated with high mortality index [5,6], and is associated with a number of pathological conditions, including sickle cell disease, congenital heart disease, cancer, alveolar damage, among others [5]. Infectious predisposing factors for pulmonary embolism reportedly included tuberculosis, schistosomiasis [7], neonatal intravascular pneumonia [8], and DIC with sepsis in adults [9]. Respiratory failure in TSS ranges from interstitial and alveolar edema to ARDS in 10% of the cases [10], and the main pulmonary manifestations of TSS include severe capillary congestion with occasional thrombi, intra-alvealar hemorrahage and edema, areas of atelectasis and presence of hyaline membranes [11]. Although a number of inherited and acquired factors may precipitate PE, the link between TSS and subsequent development of PE was not previously shown. Here we report the case of 19 year old young Lebanese woman presenting with non-menstruating TSS, complicated by pulmonary artery thromboembolism. To the best of our knowledge, this was not previously reported with TSS. Case Report The patient A 19 year old woman complaining of severe myalgias and fatigue, presented with severe diarrhea, vomiting, hypotension and high-grade fever. While previous medical history did not reveal any ailments, she reported camping two days earlier in which she consumed canned (and probably non-sanitory) food. Her last menstrual cycle was 3 weeks prior to presentation; no tampon use, pelvic inflammatory disease or Address for correspondence: Dr. Umayya Musharrafieh, American University of Beirut Medical Center, Beirut, P.O. Box: 113-6044, Lebanon. Fax: 961-1-744-464; E-mail: um00@ aub.edu.lb 133 134 Musharrafieh et al. intra-uterine device insertion were reported. Previous insect bites, surgery or trauma were absent, however the patient reported taking amoxcillin (500 mg tablet) once prior to presentation. Physical examination Physical examination revealed a sick-looking woman, slightly disoriented and severely lethargic, body temperature of 39.5◦ C, blood pressure 50/30 mmHg, pulse and respiratory rates of 150/min and 32/min, respectively. A diffuse non-pruritic erythema (sunburn-like rash) covered the face, extremities and body, with dehydration, conjunctivitis and pharyngitis with strawberry tongue and severely injected mucous membrane, and Chest X-ray revealed congestion. While heart examination appeared normal, there were mild basal crackles bilaterally, and the abdomen was soft with hyperactive bowel sounds. There was no meningeal signs or neck stiffnes, and pelvic examination was normal. Laboratory investigations CBC analysis showed leukocytosis with a white cell count (WCC) of 14.5 × 109 /L and polymorphonuclear cells count of 92%, with a slight reduction in both hematocrit (35%) and platelets (124 × 109 /L) (Table 1). There was an elevation in BUN (36 mg/dL), creatinine (4.6 mg/dL), LDH (726 IU/ml), and CPK (293 IU/L), and a marked increase in PT (52.4 sec; control 11.4 sec) and PTT (76.8 sec; control Table 1. Hematological and Biochemical Profile of the Patient Test Haematology White cell count Polymorphonuclear cells Hematocrit Platelets Chemistry BUN Creatinine Calcium LDH Fibrinogen CPK Protein (total) Albumin Protein S Anti-thrombin III Protein C Blood Gases PaO2 PaCO2 Bicarbonates pH Units Patient Reference range ×109 cells/L % 14.5 92 4.5–11.0 40–65 % ×106 /L 35 124 37–46 150–450 mg/dL mg/dL mg/dL IU/ml gm/L IU/L gm/L gm/dL % % % 36 4.6 6.2 726 0.6 293 43 26 53 68.5 47.5 8–25 0.6–1.4 8.5–10.5 200–480 2–4 10–195 62–83 36–54 65–140 73–130 70–130 mmHg mmHg mmol/L 54 34 23 7.44 32–45 21–28 7.35–7.45 27 sec). Serum phosphorous (2.6 mg/dL), fibrinogen (0.6 gm/L), and albumin (26 gm/dL) were reduced, and serum calcium, alkaline phosphatase, SGOT, total protein, and globulins were normal (Table 1). Blood culture and urine cultures were normal, and a high cervical and vaginal swabs, together with rectal and nasal swabs were all negative. Stool examination was positive for PMNs but negative for bacterial or parasitic organisms. Patient follow-up The patient received 12 liters of volume expanders within the first 24 hours of admission with a slight improvement in blood pressure (80/60 mm Hg) and urine output. Intravenous ceftriaxone (2 gm) and vancomycin (1 gm) were administered, and the working diagnosis was toxic shock syndrome. On day 3 the patient developed cough and pleuritic chest pain with mild dyspnea, but blood gases (PaO2 , PaCO2 , bicarbonate, pH) were normal (Table 1). Repeat chest radiograph revealed left lower lobe consolidation with congestion and CT chest angiography showed bilateral pleural effusion with bilateral lower lobe consolidation. There was a 1-cm filling defect in the main pulmonary artery in its superior portion, suggesting pulmonary embolus (Fig. 1), with both venous scan of the lower extremities and echocardiography being normal. Coagulation activity status Patient was started on anticoagulant therapy. Protein S (53%), antithrombin III (68.5%), and protein C (47.5%) were below normal, while normalized-activated protein C ratio of 0.96 (normal > 0.85) and anticardiolipin antibody levels were within normal range. The patient improved gradually, with severe desquamation noted all over body, in praticular over the forehead, upper extremity, palms and soles (Fig. 2). With serial coagulation studies showing slow and gradual return towards normal values, the patient was discharged from the hospital 7 days later on oral anticoagulation, and was followed up for six months with no disease recurence or complications. Discussion Although TSS was initially described as an infectious syndrome with high grade fever, refractory hypotension and renal failure [12], it was subsequently shown that this multi-system disease was frequent among women, with the majority of cases (92%) occuring during menstruation [13]. Non-menses related TSS was encountered in 7.4%, while 65% of menstrual TSS was seen in women younger than 25 years [14]. Non-menstrual (NM) TSS affects individuals of any age, sex, or race, and may be associated with staphylococcal infection at any site [15]. Thromboembolism and Toxic Shock Syndrome 135 Fig. 1. CT angiography of the chest showing a filling defect (arrow) in the main pulmonary artery. The clinical diagnosis of TSS is based on a constellation of abnormal clinical and laboratory tests. Although the isolation of a causative organism was not possible in our case, the patient fulfilled the clinical criteria for TSS [16]. Whereas hypotension, acute renal failure, thrombocytopenia, myalgias, dermatologic manifestation, pulmonary congestion and DIC indicated a multisystem involvement, the development of acute respiratory symptoms prompted investigation into PE which could not be explained otherwise. There were no identifiable predisposing factors for embolism, which appeared to be more probable in DIC setting which aggravates the course of thrombosis [5]. PE in adults is associated with high mortality index [5,6], and is associated with a number of pathological conditions, which may include infectious episodes including tuberculosis, schistosomiasis [7], neonatal intravascular pneumonia [8], and DIC with sepsis in adults [9]. The patient was diagnosed to have sepsis and concomittant DIC, as was confirmed by the thrombocytopenia, prolonged PT and PTT, together with a decrease in the levels of antithrombin III, fibrinogen, protein C and protein S. Insofar as the levels of antithrombin III, protein C and protein S decline in severe infection, sepsis, and septic shock, their low levels serve as sensitive indicators of poor outcome, evidenced by their levels among nonsurvivors compared to survivors [17,18]. Similarly, a slow spontanous recovery towards normal values predict a favourable outcome [19], as was the case here. The sudden onset of pulmonary symptoms with a homogenous segmental consolidation and hypoxemia despite adequate antibiotic administration suggested an acute thrombotic event rather than pneumonia. Although pulmonary vascular thrombi reportedly occurred in up to 100% of cases of disseminated intravascular coagulopathy in autopsy findings, most of the pathologic findings tend not to correlate with signs and symptoms of organ impairment [20], and the diagnosis of pulmonary thrombosis was frequently overlooked. In contrast, to most cases of DIC where thrombi are assessed in autopsy specimens [10], diagnosis of PE in this case was made on clinical grounds. Although both lung fields were affected, CT angiograpphy confirmed the involvment of only the major right pulmonary artery, and the 136 Musharrafieh et al. Fig. 2. Desquamation noted over palms of feet and toes. severity of damage to pulmonary vessels was directly related to the time of diagnosis. This was supported by the finding that occlusive damage was limited to a single arterial trunk with early diagnosis of PE [21]. The link between TSS and PE remains to be established. Previously, a case of sepsis-induced DIC due to pneumonia associated with diffuse and selective thrombosis in pulmonary arteries resulting in sudden death from pulmonary massive emboli was reported [22], and a case of streptococcal TSS who died after deterioration of cardiopulmonary status was also documented, although thrombi were observed in pulmonary arteries and venules that were laden heavily with bacteria [10]. The only diagnosed case of TSS secondary to a thrombotic event was described in a Chinese woman with TSS and a rapidly deteriorating neurological status leading to death despite supportive treatment. CT findings of the brain resembled those in venous thrombosis and superior sagittal sinus thrombosis [23]. In our hands, this was the only clinically diagnosed PE event occurring as a complication in TSS. In conclusion, patients with TSS who develop pulmonary symptoms must be evaluated for possible PE, so as to avoid serious complications. References 1. Eriksson BK, Andersson J, Holm SE, Norgren M. Epidemiological and clinical aspects of invasive group A streptococcal infections and the streptococcal toxic shock syndrome. Clin Infect Dis 1998;27:1428–1436. 2. Sharma S, Kumar A. Septic shock, multiple organ failure, and acute respiratory distress syndrome. Curr Opin Pulm Med 2003;9:199–209. 3. Herzer CM. Toxic shock syndrome: Broadening the differential diagnosis. Am Board Fam Pract 2001;14:131–136. 4. Slotman GJ. Prospectively validated prediction of organ failure and hypotension in patients with septic shock: The Systemic Mediator Associated Response Test (SMART). 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