|Year : 2020 | Volume
| Issue : 1 | Page : 75-77
Antiphospholipid antibody syndrome presenting as pulmonary embolism in a young male
Vikas Gupta1, Tanvi Singla2, Bhupinder Singh2, Bishav Mohan2
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 Submission||11-Nov-2019|
|Date of Decision||10-Feb-2020|
|Date of Acceptance||24-Feb-2020|
|Date of Web Publication||17-Apr-2020|
Department of Rheumatology and Immunology, Dayanand Medical College and Hospital, Ludhiana - 141 001, Punjab
Source of Support: None, Conflict of Interest: None
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 2021 May 15];6:75-7. Available from: https://www.j-pcs.org/text.asp?2020/6/1/75/282809
| Introduction|| |
Antiphospholipid syndrome (APS) is a prothrombotic condition characterized by vascular thrombosis (arterial or venous) or pregnancy morbidity in association with antiphospholipid antibodies. 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). 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. 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|| |
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|| |
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. APS occurs more commonly in females with a female: male ratio of 3:1. 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. 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.
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. 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. It may be argued whether this patient had primary APS, secondary APS with Lupus-like disease, or SLE with secondary APS. 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. 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. aPLs are strongly associated with thromboembolism in SLE patients. Thromboembolic events have been reported in 53% of SLE patients with LAC positivity. 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. 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. 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). 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. 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. 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., If aPLs are positive, testing should be repeated after 12 weeks to demonstrate persistent positivity (and hence, classify as definite APS). aPLs may, however, be transiently lowered during acute thrombosis, particularly in patients with SLE. 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., 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., 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).
| Conclusion|| |
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.
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.
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Conflicts of interest
There are no conflicts of interest.
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