infectious and non-infectious causes of aPL

Q: Which of the following parasites is so far known to cause positive antiphospholipid antibodies (aPL)?

A) Toxoplasma 

B) Malaria

C) Amoeba 

D) Giardia 

E) Cryptosporidium 

Answer: B

Many infectious and non-infectious conditions may cause aPL, which is usually IgM (aCL).

Infectious causes have some tendency to cause thrombosis, in contrast to medication-induced causes, which are usually transient and rarely associated with thrombosis. 

The long list of infectious and non-infectious causes of aPL is below:

• Bacterial sepsis
• leptospirosis
• syphilis
• Lyme disease (borreliosis)
• tuberculosis
• leprosy
• infective endocarditis
• post-streptococcal rheumatic fever
• Klebsiella 
• Hepatitis A and B
• mumps
• human immunodeficiency virus (HIV)
• human T-lymphotropic virus type 1 (HTLV-I)
• cytomegalovirus
• varicella-zoster
• Epstein-Barr virus (EBV)
• adenovirus; parvovirus; rubella
• severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
• COVID-19
•  Malaria
• Pneumocystis jirovecii
• visceral leishmaniasis (also known as kala-azar)
• phenothiazines (chlorpromazine)
• phenytoin
• hydralazine
• procainamide
• quinidine
• quinine
• ethosuximide
• alpha interferon
• amoxicillin
• chlorothiazide
• oral contraceptives
• propranolol 
• Solid tumors 
• Hodgkin disease and non-Hodgkin lymphoma
• MPNs (primary myelofibrosis, polycythemia vera)
• myeloid and lymphocytic leukemias 

#Rheumatology

References:

1. Smiyan S, Kuzmina G, Garmish O, Komorovsky R. Infection-Triggered Antiphospholipid Syndrome: A Critical Overview. Open Access Rheumatol. 2025 Aug 24;17:173-183. doi: 10.2147/OARRR.S541224. PMID: 40894518; PMCID: PMC12393084.

2. Sherer Y, Blank M, Shoenfeld Y. Antiphospholipid syndrome (APS): where does it come from? Best Pract Res Clin Rheumatol. 2007 Dec;21(6):1071-8. doi: 10.1016/j.berh.2007.09.005. PMID: 18068862.

3. Willis R, Pierangeli SS. Pathophysiology of the antiphospholipid antibody syndrome. Auto Immun Highlights. 2011 Mar 24;2(2):35-52. doi: 10.1007/s13317-011-0017-9. PMID: 26000118; PMCID: PMC4389016.

4. Jakobsen PH, Morris-Jones SD, Hviid L, Theander TG, Høier-Madsen M, Bayoumi RA, Greenwood BM. Anti-phospholipid antibodies in patients with Plasmodium falciparum malaria. Immunology. 1993 Aug;79(4):653-7. PMID: 8406592; PMCID: PMC1421917.