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 Table of Contents  
CASE REPORT
Year : 2020  |  Volume : 6  |  Issue : 1  |  Page : 75-77

Antiphospholipid antibody syndrome presenting as pulmonary embolism in a young male


1 Department of Rheumatology and Immunology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
2 Department of Cardiology, Dayanand Medical College and Hospital, Unit . Hero DMC Heart Institute, Ludhiana, Punjab, India

Date of Submission11-Nov-2019
Date of Decision10-Feb-2020
Date of Acceptance24-Feb-2020
Date of Web Publication17-Apr-2020

Correspondence Address:
Vikas Gupta
Department of Rheumatology and Immunology, Dayanand Medical College and Hospital, Ludhiana - 141 001, Punjab
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jpcs.jpcs_66_19

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  Abstract 


Antiphospholipid syndrome (APS) is a prothrombotic condition seen more commonly in females. APS may be primary or secondary to an underlying connective tissue disease like systemic lupus erythematosus (SLE), which is also more common in females. We report an 18-year-old male who presented with deep venous thrombosis (DVT) and pulmonary embolism and was later diagnosed as SLE with secondary APS. This case highlights a rare presentation of DVT with pulmonary embolism as the presenting manifestation of SLE with secondary APS in a young male. It also highlights the importance of recognizing this hypercoagulable state as the cause of pulmonary embolism since it has important therapeutic implications.

Keywords: Antiphospholipid syndrome, hypercoagulable state, pulmonary embolism, systemic lupus erythematosus


How to cite this article:
Gupta V, Singla T, Singh B, Mohan B. Antiphospholipid antibody syndrome presenting as pulmonary embolism in a young male. J Pract Cardiovasc Sci 2020;6:75-7

How to cite this URL:
Gupta V, Singla T, Singh B, Mohan B. Antiphospholipid antibody syndrome presenting as pulmonary embolism in a young male. J Pract Cardiovasc Sci [serial online] 2020 [cited 2020 Aug 4];6:75-7. Available from: http://www.j-pcs.org/text.asp?2020/6/1/75/282809




  Introduction Top


Antiphospholipid syndrome (APS) is a prothrombotic condition characterized by vascular thrombosis (arterial or venous) or pregnancy morbidity in association with antiphospholipid antibodies.[1] Seen more commonly in females, APS may occur in isolation (primary APS) or association with a systemic autoimmune disease like systemic lupus erythematosus (SLE) (secondary APS).[2] We report an 18-year-old male who presented with deep venous thrombosis (DVT) and pulmonary embolism and was later diagnosed as SLE with secondary APS. Pulmonary thromboembolism is an uncommon presenting manifestation of SLE with secondary APS in a male.[2] It is important to recognize this hypercoagulable condition since it has important therapeutic implications with regard to the choice of anticoagulant agents. Our case highlights this rare presentation and the importance of recognizing this condition.


  Case Report Top


An 18-year-old male student presented with complaints of left calf pain for 7 days and left calf swelling for 5 days. He also complained of mild occasional breathlessness on exertion for the past 3 months. He did not complain of any fever, cough, or hemoptysis. There was no history of surgery, immobilization, or long-haul air travel. He did not give any history of recurrent oral or genital ulcers. There was no history of any thrombotic events in the family. General physical examination was remarkable for the presence of nonpitting edema over the left lower limb and an erythematous rash over malar eminences.

Color Doppler ultrasound of the left lower limb showed an echogenic thrombus in distal part of the left superficial femoral vein and left popliteal vein with no blood flow on Doppler, suggesting acute DVT. Chest X-ray was normal, and electrocardiogram showed right bundle branch block with sinus tachycardia. Two-dimensional (2D) echocardiography showed dilated right atrium and right ventricle (RV) with mild RV systolic dysfunction and pulmonary artery systolic pressure (PASP) of 62 mmHg. Computed tomography pulmonary angiography showed thrombosis of the right pulmonary artery with nonopacification of its segmental and subsegmental branches [Figure 1], suggestive of pulmonary embolism. Blood samples were drawn for thrombophilia work-up, and the patient was started on low molecular weight heparin (LMWH). LMWH was overlapped with oral Vitamin K antagonists (VKA) (Acitrom) titrated to target International Normalized Ratio (INR) between 2.0 and 3.0.
Figure 1: Computed tomography pulmonary angiography showing filling defect in the basal trunk of pulmonary artery suggestive of pulmonary embolism.

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Complete hemogram showed a low normal platelet count of 108,000/mm3. Hemoglobin, total leucocyte count, renal, and liver function tests were within normal limits. The patient's activated partial thromboplastin time was high (77.4 s, ratio − 2.76; normal 22.0–40.0 s). Further, lupus anticoagulant (LA) came out to be positive by dilute Russell viper venom test (dRVVT). In addition, anti-beta 2 glycoprotein-1 (β 2GP1) IgG and IgM were significantly raised (both > 200 RU/mL). Anti-cardiolipin antibodies (aCL) had equivocal titers. Other thrombophilia work-up was negative. Hence, the patient was suspected to be having APS. Further, he was evaluated for SLE in view of the presence of malar rash and to rule out secondary APS. Antinuclear antibody (ANA) by immunofluorescence was 3 + nuclear homogenous at dilution of 1:80. Anti-double stranded DNA (anti-dsDNA) titers were >200 IU/mL. Complement C3 and C4 levels were normal. The patient fulfilled SLE International Collaborating Clinics (SLICC) criteria for classification for SLE. The patient was started on hydroxychloroquine with a diagnosis of SLE with secondary APS. LMWH was continued along with oral anticoagulants until two consecutive INR values ranged between 2.0 and 3.0. He improved with treatment and was discharged on oral anticoagulants. The patient is currently on treatment with oral anticoagulants with INR in therapeutic range and is doing well. 2D echocardiography was done after 1 month of discharge from the hospital and showed a fall in PASP to 45 mmHg. Antiphospholipid antibody (aPL) profile was repeated after 12 weeks and was found to be again positive for LA (by dRVVT) and anti-beta 2 glycoprotein-1 IgG (150.39 RU/mL). Persistent antiphospholipid antibody positivity after 12 weeks confirmed the diagnosis of APS.


  Discussion Top


This young male patient presented to us with DVT and pulmonary thromboembolism, cause of which was found to be APS secondary to SLE. APS is a syndrome characterized by vascular thrombosis (arterial or venous) or pregnancy morbidity in association with antiphospholipid antibodies.[1] APS occurs more commonly in females with a female: male ratio of 3:1.[2] APS could be primary when it occurs as an isolated disease or secondary to a rheumatic disease like SLE. SLE is a systemic autoimmune disease with a strong gender bias and a female: male ratio of 9:1.[3] Pulmonary thromboembolism, though one of the predominant manifestations in primary APS male patients, is an uncommon presenting manifestation of SLE with secondary APS in a male.[2]

Our patient had malar rash as the only clinical manifestation of SLE. Among the serologic manifestations, he had ANA 3+ (nuclear homogeneous at dilution 1:80), antibodies to anti-dsDNA, and antiphospholipid antibodies and hence, fulfilled the 2012 SLICC classification criteria for SLE. However, our patient did not fulfill the 1997 American College of Rheumatology criteria for SLE.[4] Persistent positivity of both anti-β2GP1 and LA more than 12 weeks apart confirmed the diagnosis of APS. While initial testing for antiphospholipid antibodies was done prior to starting anticoagulants, follow-up testing was done while the patient was on oral VKA therapy. While testing for anti-β2GP1 (and aCL) is not affected by anticoagulation, testing for LA by dRVVT is considered reliable even if the patient on oral VKA therapy.[5] It may be argued whether this patient had primary APS, secondary APS with Lupus-like disease, or SLE with secondary APS.[6] An intermediate APS group with lupus-like disease has been classified by some authors. This group includes patients who do not differ from primary APS in any clinical or laboratory features except for the presence of antibodies to dsDNA and extractable nuclear antigen.[7] Our patient with the presence of malar rash and anti-dsDNA antibodies would be best classified as SLE with secondary APS.

Antiphospholipid antibodies (aPLs) are frequently found in patients with SLE. Lupus anticoagulant (LA) is found in about one-third of SLE patients, aCL in about one-fourth to half, and anti-beta 2 GP1 in about 20% of SLE patients.[8] aPLs are strongly associated with thromboembolism in SLE patients. Thromboembolic events have been reported in 53% of SLE patients with LAC positivity.[9] The risk of thrombotic events correlates with number of aPL antibody positivity with triple aPL positivity (LAC/aCL/β2GP1) associated with the highest risk of thrombosis in most studies.[10] However, a recent study found double aPL positivity of LAC + β2GP1 to be associated with the highest risk of venous thrombosis (Odds ratio [OR] = 5.5) or any thrombosis (OR = 4.1), more than that of triple aPL positivity.[11] The same double aPL positivity (LAC + β2GP1) was found in our patient.

The treatment of acute thromboembolism in APS is anticoagulation. This generally includes heparin overlapped with a Vitamin K antagonist like warfarin. This is followed by long-term, usually indefinite, warfarin therapy to prevent recurrent thrombotic events, maintaining an INR of 2.0–3.0 in venous thrombosis. Arterial thrombosis is treated with a higher intensity oral anticoagulation (INR >3.0) or low-dose aspirin plus standard-intensity oral anticoagulation (INR 2.0–3.0).[12] Although direct oral anticoagulants (DOAC) seem an attractive option since laboratory monitoring is not required during their use, the data to support the efficacy and safety of DOAC in APS are lacking.[13] Hence, it is important to recognize APS as the cause of hypercoagulable state leading to pulmonary embolism and treat these patients with VKA rather than DOAC for secondary thromboprophylaxis.

In a patient with first, unprovoked venous thromboembolism (VTE), testing for heritable thrombophilia (Protein C deficiency [PC], Protein S deficiency [PS], antithrombin deficiency CASE REPORT, factor V Leiden mutation [FVL] and Prothrombin gene mutation [PG]), following the acute episode, is not useful since it will not change the initial management of VTE.[14] However, as mentioned above, testing for aPLs might be useful to guide the choice of anticoagulant therapy since VKA is preferred to DOAC for secondary thromboprophylaxis in APS.[13],[15] If aPLs are positive, testing should be repeated after 12 weeks to demonstrate persistent positivity (and hence, classify as definite APS).[15] aPLs may, however, be transiently lowered during acute thrombosis, particularly in patients with SLE.[16] Hence, if the aPLs are negative, or not tested, during the acute episode, aPL testing may be considered later if it is being planned to stop anticoagulation.[14],[17] Testing for heritable thrombophilia (PC, PS, AT, FVL, and PG) may be considered in young patients (<50 years) with unprovoked VTE who have first-degree female relative of childbearing age since it might affect the decision about estrogen use or pregnancy management in these family members.[14],[18] Testing for heritable thrombophilia should be done at least 3 months after the acute episode and when the anticoagulation has been withheld for 2–4 weeks (for PC, PS, and AT).[18]


  Conclusion Top


This case highlights the importance of suspecting APS in young male patients presenting with VTE and also evaluating them further to rule out an underlying connective tissue disease since it has important therapeutic implications.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Ethics clearance

As per the institute's guidelines, ethics clearance is not required for case reports. However, the authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Gómez-Puerta JA, Cervera R. Diagnosis and classification of the antiphospholipid syndrome. J Autoimmun 2014;48-49:20-5.  Back to cited text no. 1
    
2.
Medina G, Vera-Lastra O, Barile L, Salas M, Jara LJ. Clinical spectrum of males with primary antiphospholipid syndrome and systemic lupus erythematosus: A comparative study of 73 patients. Lupus 2004;13:11-6.  Back to cited text no. 2
    
3.
Hughes GR. Systemic lupus erythematosus. Postgrad Med J 1988;64:517-21.  Back to cited text no. 3
    
4.
Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997;40:1725.  Back to cited text no. 4
    
5.
Olteanu H, Downes KA, Patel J, Praprotnik D, Sarode R. Warfarin does not interfere with lupus anticoagulant detection by dilute Russell's viper venom time. Clin Lab 2009;55:138-42.  Back to cited text no. 5
    
6.
Grossman JM. Primary versus secondary antiphospholipid syndrome: Is this lupus or not? Curr Rheumatol Rep 2004;6:445-50.  Back to cited text no. 6
    
7.
Weber M, Hayem G, De Bandt M, Seifert B, Palazzo E, Roux S, et al. Classification of an intermediate group of patients with antiphospholipid syndrome and lupus-like disease: Primary or secondary antiphospholipid syndrome? J Rheumatol 1999;26:2131-6.  Back to cited text no. 7
    
8.
Laskin CA, Clark CA, Spitzer KA. Antiphospholipid syndrome in systemic lupus erythematosus: Is the whole greater than the sum of its parts? Rheum Dis Clin North Am 2005;31:255-72, vi.  Back to cited text no. 8
    
9.
Love PE, Santoro SA. Antiphospholipid antibodies: Anticardiolipin and the lupus anticoagulant in systemic lupus erythematosus (SLE) and in non-SLE disorders. Prevalence and clinical significance. Ann Intern Med 1990;112:682-98.  Back to cited text no. 9
    
10.
Forastiero R. Trends in the antiphospholipid syndrome criteria. J Hematol Thromboembolic Dis 2013;1:1-2.  Back to cited text no. 10
    
11.
Petri M Goldman D. predictive value for thrombosis of double or triple positivity in secondary APS depends on the component assays and the type of thrombosis. Arthritis Rheumatol 2017;69 Suppl 10. Available from. https://acrabstracts.org/abstract/predictive-value-for-thrombosis-of-double-or-triple-positivity-in-secondary-aps-depends-on-the-component-assays-and-the-type-of-thrombosis/. [Last accessed on 2019 Jan 11].  Back to cited text no. 11
    
12.
Ruiz-Irastorza G, Cuadrado MJ, Ruiz-Arruza I, Brey R, Crowther M, Derksen R, et al. Evidence-based recommendations for the prevention and long-term management of thrombosis in antiphospholipid antibody-positive patients: Report of a task force at the 13th International Congress on antiphospholipid antibodies. Lupus 2011;20:206-18.  Back to cited text no. 12
    
13.
Dufrost V, Risse J, Zuily S, Wahl D. Direct oral anticoagulants use in antiphospholipid syndrome: Are these drugs an effective and safe alternative to warfarin? A systematic review of the literature. Curr Rheumatol Rep 2016;18:74.  Back to cited text no. 13
    
14.
Connors JM. Thrombophilia testing and venous thrombosis. N Engl J Med 2017;377:1177-87.  Back to cited text no. 14
    
15.
Tektonidou MG, Andreoli L, Limper M, Amoura Z, Cervera R, Costedoat-Chalumeau N, et al. EULAR recommendations for the management of antiphospholipid syndrome in adults. Ann Rheum Dis 2019;78:1296-304.  Back to cited text no. 15
    
16.
Gómez-Pacheco L, Villa AR, Drenkard C, Cabiedes J, Cabral AR, Alarcón-Segovia D. Serum anti-beta2-glycoprotein-I and anticardiolipin antibodies during thrombosis in systemic lupus erythematosus patients. Am J Med 1999;106:417-23.  Back to cited text no. 16
    
17.
National Clinical Guideline Centre. Venous Thromboembolic Diseases: The Management of Venous Thromboembolic Diseases and the Role of Thrombophilia Testing. National Clinical Guideline Centre (Uk). London: Royal College of Physicians; 2012.  Back to cited text no. 17
    
18.
Stevens SM, Woller SC, Bauer KA, Kasthuri R, Cushman M, Streiff M, et al. Guidance for the evaluation and treatment of hereditary and acquired thrombophilia. J Thromb Thrombolysis 2016;41:154-64.  Back to cited text no. 18
    


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