Newly Diagnosed SLE With APLS and Right Atrial Thrombus

Abstract

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder manifesting in myriad of forms and could affect almost any body system or organ. Antiphospholipid syndrome (APLS) is a relatively common scenario in SLE. Both arterial and venous thrombosis is a hallmark feature of APLS. Among others, intracardiac thrombus is a rare and potentially life-threatening presentation. It could occur in any heart chamber whereas the right atrium is the least common location. The treatment is based on anticoagulation preferably with warfarin along with treatment of SLE. We describe a young patient with newly diagnosed SLE with APLS complicated by right atrial thrombus formation. We are, therefore, adding to the scant literature on right atrial thrombi in SLE and increasing awareness of readers of this serious and potentially deadly condition if left unrecognized.

Introduction

Systemic lupus erythematosus is a chronic autoimmune disorder potentially affecting almost every organ system or tissue in the body. Antiphospholipid syndrome is characterized by the presence of lupus anticoagulant (LAC), anticardiolipin antibodies (aCL), and anti-β₂-glycoprotein I (β₂ GPI) antibodies and manifests with venous and arterial thrombosis and/or pregnancy complications (recurrent fetal loss and placental insufficiency). It could be primary or secondary, SLE being the most common cause of the latter. ¹ Cardiac manifestations include valvulopathies, coronary artery disease, myocardial dysfunction, pulmonary hypertension, and intracardiac thrombus. ² Mechanisms of heart injury include thrombosis and immune-mediated injury. Intracardiac thrombus is a rare manifestation. Left or right heart can be involved. Here, we will present an unusual case of new-onset SLE with APLS and right atrial thrombus.

Case Report

A 26-year-old man presented with fevers, chills, joint pain in his left wrist, left shoulder, profuse diarrhea, and intermittent vomiting as well as left-sided chest pain for 10 days. Four months earlier, he developed right lower extremity swelling, was diagnosed with deep venous thrombosis of the lower extremity, and started on rivaroxaban. He had no significant past medical history, noncontributory family, or social history; no medications other than recently started anticoagulation. He was found to have fever of 102.4 °F, leukocytes of 27.3 × 10 9/L with absolute neutrophilia, hemoglobin of 9.5 g/dL, platelets of 280 × 10 9/L, procalcitonin of 11.2 ng/mL, and blood culture positive for Streptococcus equisimilis, treated with IV antibiotics. Computed tomography angiography of the chest showed segmental pulmonary embolism, left lower lobe consolidation with moderate loculated effusion. Pleural fluid was tapped and found to be exudative with no growth. Urinalysis showed 4 g/day of proteinuria with pyuria/hematuria and granular casts. Further work-up revealed positive antinuclear antibody test, high positive anti-double-stranded DNA of 439 IU/mL, low C4 at 12 mg/dL, positive direct antiglobulin test, high positive beta-2 glycoprotein IgG of 53 U/mL, low positive anticardiolipin IgG of 43 U/mL, positive LAC, and negative extractable nuclear antigen. Giving concern for endocarditis, patient underwent transesophageal echocardiography that revealed a large 2 × 1.5 cm irregular right atrial mass with freely mobile portions at the Inferior vena cava-right atrium (IVC-RA) junction consistent with a thrombus. He was subsequently started on enoxaparin with transition to warfarin. He was diagnosed with SLE based on clinical criteria including arthralgia, fever, serositis, and nephrotic range proteinuria (Figures 1 and 2). Laboratory criteria included positive anti-β₂ GPI IgG, low C4, and high positive dsDNA. Some features could have been confounded by concomitant infectious process. He was treated with steroids with a slow taper and later mycophenolate mofetil and hydroxychloroquine. Antiphospholipid syndrome was confirmed upon positive antiphospholipid antibodies (aPL) in 3 months.

Figure 1.

Mid esophageal 150° right ventricle (RV) inflow view.

Figure 2.

Modified bicaval view.

Discussion

Systemic lupus erythematosus is an autoimmune disease that can involve multiple organs. Antiphospholipid syndrome is a notorious and serious condition in the setting of an underlying systemic autoimmune disease, particularly SLE. Antiphospholipid syndrome is present in approximately 35% of cases. ¹ It is characterized by recurrent thrombosis and obstetric morbidity. Less frequent clinical manifestations include neurologic (stroke, transient ischemic attack), hematologic abnormalities (thrombocytopenia, thrombotic microangiopathy, autoimmune hemolytic anemia), pulmonary involvement (pulmonary arterial hypertension, pulmonary thromboembolic disease, diffuse alveolar hemorrhage), and cutaneous manifestations (livedo, cutaneous necrosis and infarction, and others). ³ One study found that the frequency of thrombosis and pregnancy complications were greater in patients with APLS with SLE than in those with primary APLS. ⁴

Cellular activation by aPL results in procoagulant and proinflammatory effects, activation of complement, and driving thrombotic complications of APLS. Additional risk factors such as smoking, pregnancy, estrogen-containing oral contraceptives, inherited thrombophilia, and cancer contribute to increased thrombotic risk. ⁴

The diagnosis is based on clinical features, mainly thromboembolism and pregnancy comorbidities along with positive aPL in different combination obtained twice 12 weeks apart. ⁵

The mainstay of treatment of APLS is anticoagulation to prevent and treat initial episode of acute thrombosis, or secondary thrombosis prevention. Some asymptomatic individuals with positive aPL may benefit from low-dose aspirin for primary thrombosis prevention. Warfarin is generally preferred in management of individuals with acute thrombosis with indefinite duration for secondary thrombosis prevention due to high rate of recurrent thrombosis. Direct-acting anticoagulant may be reasonable only in selected cases in patients with lower-risk features such as single venous thromboembolism. ⁶ Recurrent thromboembolism despite active anticoagulation warrants adding aspirin, hydroxychloroquine, higher International normalized ratio (INR) goal, or even switching to low-molecular-weight heparin.

The nature of cardiac masses is usually tumor or thrombus. Myxoma is the most common cardiac neoplasm and is typically located in the left atrium (75%) attached to atrial septum while left atrial thrombus is more common in the left atrial appendage. Right atrial thrombus is rare (15%). ⁷ Right atrial thrombi may arise from venous emboli entrapped in the right heart or occur in situ under low-flow conditions.

Our patient was diagnosed with SLE and secondary APLS complicated by right atrial thrombus. The pathophysiology of this condition is likely multifactorial and includes hypercoagulability related to nephrotic syndrome, positive LAC activity, medium to high levels of anticardiolipin antibodies, β₂ GPI antibody, and chronic inflammation of SLE. ⁸

It is unclear whether heparin, thrombolysis, high-intensity anticoagulation with warfarin with INR goal of 3-4, rituximab (anti-CD20 monoclonal antibody), or surgical excision is the best therapeutic approach.

In the prospective study by Turiel et al, 16% of primary APLS patients were found to have intracardiac thrombus, more often in the right heart. ⁹ Ten mainly female patients aged 30 to 40 were summarized in a literature review article with predominantly right atrial thrombus. One female teenager had APLS associated with SLE. ¹⁰

PubMed search has been done to include MeSH terms “APLS” and “RA thrombus.” Most of the cases were associated with the primary APLS with only few cases of secondary APLS; SLE was found to be the main culprit, females more than males (Table 1). The most frequent antibody positivity was dual positivity for LAC and aCL followed by isolated anti-β₂ GPI and finally least frequently triple positivity for all 3 aPL.

Table 1.

Summary of Patients With Antiphospholipid Syndrome With RA Thrombus. ¹¹

Authors	Primary/secondary	Sex	Secondary association	Heart involved	PTE	LAC	aCL	Anti-β2 GPI
1. Lawrence JL et al (Am J Med. 1989)	Primary	F	—	RA	−	+	+	−
2. Kjernsmo A et al (Tidsskr Nor Laegeforen. 1990)	Primary	F	—	RA	+	+	+	−
3. Villani R et al Minerva (Cardioangiol. 1994)	Primary	F	—	RA	+	+	+	−
4. Matos V et al (Acta Medica Portuguesa. 1994)	Primary	F	—	RA	+	+	−	−
5. Yeghen T et al (Am J Hematology. 1995)	Primary	M	—	RA	+	−	+	−
6. Granel B et al (Cardiology. 1999)	Primary	F	—	RA	−	+	+	+
7. Ghirarduzzi A et al (Ital Heart J Suppl. 2001)	Primary	F	—	RA	−	+	+	−
8. Latagliata R et al (Acta Haematol. 2002)	Secondary	F	AIHA	RA	−	+	+	+
9. Tamura K et al (Kyobu Geka. 2002)	Primary	F	—	RA	−	+	−	−
10. Lime et al (Internal Med J. 2004)	Secondary	F	SLE	RA	+	−	+	−
11. Cristina B et al (J Thorac Cardiovasc Surg. 2005)	Primary	F	—	RA	−	+	−	−
12. Morel O et al (Thrombosis J. 2005)	Primary	M	—	RA, RV	−	−	+	−
13. Zhong-Xuan Y et al (Circ J. 2005)	Primary	F	—	RA	+	−	+	−
14. Duman D et al (Heart Surg Forum. 2006)	Primary	M	—	RA	−	−	+	−
15. Guedes-Barbosa LS et al (Arthritis Rheum. 2007)	Primary	M	—	RA, LA, RV, LV	−	+	+	−
16. Tomas FC et al (Tex Heart Inst J. 2008)	Secondary	F	SLE	RA	+	+	−	−
17. Jose et al (Eur Heart J—Cardiovascular Imaging. 2009)	Primary	F	—	RV	−	+	+	−
18. Ashish A et al (J Am Soc Echocardiogr. 2010)	Primary	F	—	RA	−	−	+	+
19. Rawat SKS et al (Ann of Card Anaesthesia. 2010)	Primary	F	—	RA	+	+	−	−
20. Nadine A et al (Eur Heart J. 2012)	Primary	M	—	RA, LA, RV, LV	−	−	+	−

Abbreviations: F, female; M, male; RA, right atrium; SLE, systemic lupus erythematosus; LA, left atrium; RV, right ventricle; LV, left ventricle; PTE, pulmonary thromboembolism, LAC, lupus anticoagulant; aCL, anticardiolipin antibodies; anti-β₂ GPI, anti-β₂-glycoprotein I; AIHA, Autoimmune hemolytic anemia.

Conclusion

In summary, here, we report a case of newly diagnosed SLE with secondary APLS manifested earlier by lower extremity Deep vein thrombosis (DVT) and later by right atrial thrombosis despite anticoagulation with direct oral anticoagulants supporting need of warfarin use in APLS. We are, therefore, adding to the scant literature on right atrial thrombi in SLE and increasing awareness of readers of this potentially life-threatening presentation.