• Users Online: 115
  • Print this page
  • Email this page

 Table of Contents  
Year : 2023  |  Volume : 3  |  Issue : 3  |  Page : 134-137

Recurrent bleeding in a healthy child-A case of lupus anticoagulant-hypoprothrombinemia syndrome: A case report with review of literature

Department of Pediatrics, MGM Medical College, Kishanganj, Bihar, India

Date of Submission06-Feb-2023
Date of Decision09-May-2023
Date of Acceptance09-May-2023
Date of Web Publication14-Aug-2023

Correspondence Address:
Dr. Sudesh Kumar
I Block, Doctor's Quarters, MGM Medical College, Kishanganj - 855 107, Bihar
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ipcares.ipcares_32_23

Rights and Permissions

Background: Although lupus anticoagulant (LA) is known to be associated with an increased risk of thrombosis and obstetric complications, typically seen in antiphospholipid syndrome, the presentation of LA-hypoprothrombinemia syndrome (LA-HPS) is different with bleeding manifestations more common than thrombosis. We report such a rare disorder in an otherwise healthy boy, who presented with subcutaneous bleeding and was treated successfully. Clinical Description: A 9-year-old boy presented with acute-onset swelling in the popliteal fossa region of the left leg and left great toe. History of fever, trauma, drug intake, joint pain, epistaxis, or melena was absent. Since 6 months of age, he had recurrent episodes of multiple, painful joint, and soft-tissue swellings and ecchymotic patches which subsided spontaneously. Examination showed a tense, shiny bluish patch over the left popliteal fossa and a swollen tender left great toe, without any lymphadenopathy, hepatosplenomegaly, or arthritis. Management and Outcome: Routine hemogram and liver function tests were normal. Furthermore, antinuclear antibody and rheumatoid factor were within normal limits. Coagulation studies showed prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT), though bleeding and coagulation times were normal. Administration of Vitamin K and fresh frozen plasma (FFP) showed no improvement. Further investigations revealed normal values of von Willebrand Factor collagen binding, Factor VIII, Factor XIII, and fibrinogen, whereas prothrombin levels were reduced. The partial thromboplastin time-LA specific was high (170.10), suggesting a diagnosis of LA-HPS. The symptoms responded to prednisolone therapy, and there was complete recovery. Conclusion: A recurrent bleeding disorder with increased PT/APTT, not responding clinically to FFP transfusion, should raise suspicion of LA-HPS and appropriate tests need to be done. The prognosis of this disorder is good with corticosteroid therapy.

Keywords: Antiphospholipid syndrome, hypoprothrombinemia, lupus anticoagulant, venous thrombosis

How to cite this article:
Kumar S, Bhattacharya P, Gautam S, Chattopadhyay N. Recurrent bleeding in a healthy child-A case of lupus anticoagulant-hypoprothrombinemia syndrome: A case report with review of literature. Indian Pediatr Case Rep 2023;3:134-7

How to cite this URL:
Kumar S, Bhattacharya P, Gautam S, Chattopadhyay N. Recurrent bleeding in a healthy child-A case of lupus anticoagulant-hypoprothrombinemia syndrome: A case report with review of literature. Indian Pediatr Case Rep [serial online] 2023 [cited 2023 Sep 30];3:134-7. Available from:

Lupus anticoagulant-hypoprothrombinemia syndrome (LA-HPS) is a rare acquired disorder in which there is acquired Factor II deficiency associated with LA.[1] The disease may be transient during viral infections, or persistent, when associated with autoimmune diseases, such as systemic lupus erythematosus (SLE) or antiphospholipid syndrome (APS). Although LA is known to be associated with an increased risk of thrombosis and obstetric complications, typically seen in APS, the presentation of LA-HPS is different with bleeding manifestations more common than thrombosis.[2] We report this rare disorder in a boy who was treated successfully.

  Clinical Description Top

A 9-year-old boy was admitted to the pediatric ward with a complaint of an acute onset of swelling in the region of the left popliteal fossa, developing over 13 days. In addition, the child also complained of swelling of the left great toe, over the previous 3 days. There was no recent history of fever, cough, trauma, or drug intake. There was no present or past history of facial rash, oral mucosal lesion, or dactylitis. The boy had a history of recurrent painful joint swellings, since 6 months of age, along with ecchymotic skin patches, which subsided spontaneously. However, he had no history of epistaxis, melena, or any requirement for transfusion of blood products.

On examination, the child was afebrile, had a stable general condition, was afebrile, with no pallor or lymphadenopathy. His height was 132.2 cm and body mass index 18.32 which were within the normal range, as per age. He had a pulse rate of 90/min, a respiratory rate of 21/min, and a blood pressure of 110/60 mmHg. On systemic examination, there was no hepatosplenomegaly or any signs of arthritis. The left popliteal fossa appeared tense with a shiny bluish patch of around 3 cm × 4 cm on the overlying skin [Figure 1]. Furthermore, his left great toe was swollen with tenderness [Figure 2]. On the basis of the above clinical picture, we considered the differential diagnosis of a bleeding disorder, or sickle cell disease, or a connective tissue disorder, or systemic juvenile rheumatoid arthritis.
Figure 1: Swelling and ecchymosis in the left popliteal fossa

Click here to view
Figure 2: Swelling of the left great toe with splinter hemorrhage

Click here to view

  Management and Outcome Top

Laboratory investigations showed hemoglobin 9.8 mg/dL, total leukocyte count 11500/cmm, platelets 2.62 lakh/cmm, C-reactive protein 3 mg/L, and erythrocyte sedimentation rate 10 mm/h. The total serum bilirubin was 0.9 mg/dL, serum glutamic-pyruvic transaminase 42 IU/L, serum glutamic-oxaloacetic transaminase 28 IU/L, blood urea 30 mg/dL, and serum creatinine 0.6 mg/dL. Viral serologies for HIV and hepatitis B were nonreactive. He had prolonged prothrombin time (PT) of 15.4 s (11–13.5 s) and activated partial thromboplastin clotting time (APTT) of 39.8 s (23–32.4 s) [Table 1], but bleeding time and clotting time were normal. D-dimer and high-performance liquid chromatography results were normal. Antinuclear antibody, anti-double-stranded deoxyribonucleic acid, and rheumatoid factor (RA) were negative. Ultrasonography of the left knee joint showed subcutaneous bleed. Xray of left knee was normal. On the basis of the clinical features and investigations, the diagnosis of a bleeding diathesis (common pathway clotting factor deficiency or its inhibitor) was considered. The child was treated with injection Vitamin K 5 mg intravenous single injection and fresh frozen plasma (FFP) 10 mL/kg, but the swelling increased with the development of further petechial rash.
Table 1: Findings of coagulation studies done at presentation and later

Click here to view

The next line of investigations showed von Willebrand factor collagen binding of 123 (normal range: 50–194 U/dL) and normal values for Factor VIII, Factor XIII, and fibrinogen levels [Table 1]. The prothrombin level (29%, range: 70%–120%) was found to be low. However, we could not check Factor II activity in high dilutions of the patient's plasma. The partial thromboplastin time-LA specific (PTT-LA) (electromechanical clot detection) was high (170.10 s, range: 28.4–38.1 s). Anticardiolipin antibody and anti-beta-2-glycoprotein 1 antibody levels could not be tested, due to nonavailability in our hospital.

Thus, the clinical presentation of bleeding with normal count and prolonged PT, APTT, not responding to Vitamin K and FFP infusions, associated with low prothrombin levels and the presence of LA antibody, suggested a possibility of LA-HPS. The child was treated with prednisolone 2 mg/kg for 1 week and tapered over the next 2–3 weeks, resulting in complete recovery. Following recovery, repeat testing after 3 weeks of starting treatment showed PT – 12 s, APTT – 28 s, and PTT-LA – 38.5 s, which were all within normal limits.

After 3 months, the boy presented again with fresh petechial patches over the right thigh and trunk. Investigations revealed raised PT – 15.8 s, APTT – 42 s, and PTT-LA – 77.80 s. Another course of prednisolone was given, leading to the resolution of the lesions. The child was thus diagnosed with persistent primary LA-HPS.

  Discussion with Review of Literature Top

The clinical features and investigations described in the 9-year-old boy, as described above, are consistent with a diagnosis of LA-HPS. As all investigations related to associated conditions such as lupus were found to be negative, the boy had primary LA-HPS.

LA-HPS, a disorder in which there is an association of acquired factor II deficiency with LA, is a rare disease that is different from the APS, as the affected individuals are predisposed not only to thrombosis but also to severe bleeding. The disorder most commonly occurs in children and young adults, with a female-to-male sex ratio of 1.4. Nearly 90% of cases manifest with bleeding manifestations, with arterial and/or venous thrombosis being less common.[1] Bleeding symptoms may range from mild mucocutaneous bleeding to life-threatening intracranial hemorrhage. Gastrointestinal bleeding, epistaxis, and muscular and adrenal hemorrhage have been reported.[3]

Since its original description by Rapaport et al., in 1960,[4] in an 11-year-old girl with SLE having bleeding with LA associated with hypoprothrombinemia, there have been similar reports trickling in over the years. Bajaj et al. proposed that in acquired LA-HPS, hypoprothrombinemia results from the clearance of prothrombin-antiprothrombin antibody complexes from the circulation.[5]

Secondary LA-HPS occurs in autoimmune disorders such as SLE and acute infectious diseases such as adenoviral and streptococcal infection and can also occasionally be associated with lymphoma or can be drug induced.[1],[6],[7],[8],[9]

A brief review of the literature describing the cases of LA-HPS reported so far is shown in [Table 2].
Table 2: Review of the literature showing published articles of lupus anticoagulant-hypoprothrombinemia syndrome in children with bleeding manifestations

Click here to view

The first-line therapy for this condition is glucocorticoids. If patients with LA-HPS do not improve with glucocorticoids, then other immunosuppressive agents such as cyclophosphamide, azathioprine, or rituximab may be used.[2]

  Conclusion Top

Bleeding manifestations in children can rarely be due to LA-HPS. Awareness about this condition will enable pediatricians to do appropriate tests such as prothrombin levels and LA and thereby diagnose this condition.

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.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


  References Top

Mazodier K, Arnaud L, Mathian A, et al. Lupus anticoagulant-hypoprothrombinemia syndrome: Report of 8 cases and review of the literature. Medicine (Baltimore) 2012;91:251-60.  Back to cited text no. 1
Mulliez SM, De Keyser F, Verbist C, et al. Lupus anticoagulant-hypoprothrombinemia syndrome: Report of two cases and review of the literature. Lupus 2015;24:736-45.  Back to cited text no. 2
Sakamoto A, Ogura M, Hattori A, et al. Lupus anticoagulant hypoprothrombinemia syndrome associated with bilateral adrenal haemorrhage in a child: Early diagnosis and intervention. Thromb J 2021;19:19.  Back to cited text no. 3
Rapaport SI, Ames SB, Duvall BJ. A plasma coagulation defect in systemic lupus erythematosus arising from hypoprothrombinemia combined with antiprothrombinase activity. Blood 1960;15:212-27.  Back to cited text no. 4
Bajaj SP, Rapaport SI, Fierer DS, et al. A mechanism for the hypoprothrombinemia of the acquired hypoprothrombinemia-lupus anticoagulant syndrome. Blood 1983;61:684-92.  Back to cited text no. 5
Amiral J, Aronis S, Adamtziki E, et al. Association of lupus anticoagulant with transient antibodies to prothrombin in a patient with hypoprothrombinemia. Thromb Res 1997;86:73-8.  Back to cited text no. 6
Anderson AK, Mohan U, Liesner R. Transient lupus anticoagulant: An unusual cause of bruising in children. Emerg Med J 2003;20:E6.  Back to cited text no. 7
Ayoub O, Aljurf M, Al Nounou R, et al. Systemic lupus erythematosus presenting with haemorrhagic manifestation. Clin Lab Haematol 1999;21:413-6.  Back to cited text no. 8
Clauser S, Fischer AM, Darnige L. Quinidine-induced lupus anticoagulant, hypoprothrombinemia, and antiprothrombin antibodies. Am J Hematol 2007;82:330.  Back to cited text no. 9
Fujiwara K, Shimizu J, Tsukahara H, et al. Lupus anticoagulant-hypoprothrombinemia syndrome and immunoglobulin-A vasculitis: A report of Japanese sibling cases and review of the literature. Rheumatol Int 2019;39:1811-9.  Back to cited text no. 10
Pilania RK, Suri D, Jindal AK, et al. Lupus anticoagulant hypoprothrombinemia syndrome associated with systemic lupus erythematosus in children: Report of two cases and systematic review of the literature. Rheumatol Int 2018;38:1933-40.  Back to cited text no. 11


  [Figure 1], [Figure 2]

  [Table 1], [Table 2]


Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  In this article
Clinical Description
Management and O...
Discussion with ...
Article Figures
Article Tables

 Article Access Statistics
    PDF Downloaded124    
    Comments [Add]    

Recommend this journal