Antiphospholipid Antibody Syndrome During Acute Q Fever: a Cross-Sectional Study of The

Antiphospholipid Antibody Syndrome during Acute Q fever: A Cross-Sectional Study of the French National Referral Center for Q Fever

Matthieu Million et al.

Supplemental Digital Content 1. Table which reports the detailed characteristics of patients with acute Q fever and thrombosis reported in the literature

Reference / Country
Age/Sex
Risk factor for thrombosis / Thrombosis
(technical diagnosis) / Type of Coxiella burnetii infection
(microbiological confirmation) / Lupus anticoagulant and antiphospholipid antibodies work-up / Treatment and outcome
Venous thrombosis (n= 14)
Cerebrospinal venous thrombosis (n= 2)
Stevens, 20001 / France
44/M / Cerebral venous thrombosis
(CT scan) / Acute Q fever
(IFA serology: seroconversion to 256) / NA / Doxy 21d, subcutaneous heparin, recovered
Gomes, 20142 / Portugal
47/M / Cerebral venous thrombosis
(CT scan) / Acute Q fever
(IFA serology: phase II IgG 800 IgM 800) / Negative / Doxy 18m, enoxaparin then warfarin 12m, alive
Pulmonary embolism with or without DVT (n = 5)
Brown, 19483 / USA
43/M / Pulmonary embolism with DVT
(autopsy) / Acute Q fever
(guinea pig inoculation) / NA / Died
Marmion, 19534 – case 1 / UK
45/M / Massive pulmonary infarction / Acute Q fever
(serology: 1024) / NA / Died (day 23 of symptoms onset)
Spinelli, 19815 / USA
NA / Pulmonary embolism / NA / NA / Died
Cuenca Luque, 19906 / Spain
27/F / Pulmonary embolism (VP scintigraphy) with bilateral iliac DVT (phlebography) / Acute Q fever
(IFA serology: increase from 320 to 2560) / Normal aPTT
Positive IgG aCL 5* / Sodic heparin, alive
Janowski, 19957 / France
33/M
smoking / Bilateral pulmonary embolism (VP scintigraphy) with DVT (Doppler US) / Acute Q fever
(serology: phase II IgG 1280 IgM 640, no phase I) / Prolonged aPTT (60/30 (2.0))
Lupus anticoagulant (antiprothrombinase)
Positive IgG aCL 1.24 (< 0.8) / Doxy 3m, prolonged anticoagulation due to antiprothrombinase activity persistence up to 1 year, cured
del Arco, 20018 / Spain
33/NA / Pulmonary embolism (VP scintigraphy†) with inferior limb proximal thrombus (Doppler US and phlebography) / Acute Q fever
(serology: phase II IgM 1024 IgG 512) / Negative lupus anticoagulant
Positive IgG aCL 132 (<23)
Positive IgM aCL 71 (<11) / Doxy 200 mg/d and ciprofloxacin 750mg bid 14d, heparin then coumarin for 6m, cured
Other deep vein thrombosis without pulmonary embolism (n= 7)
Michon, 19589 / France
39/F / Thrombosis of the inferior vena cava with myocarditis (autopsy) / Acute Q fever
(serology: agglutination 80) / NA / Died
Wolf, 197610 / Germany
15/M / Deep left leg and pelvic venous thrombosis (phlebography) / Acute Q fever / NA / Operated (surgical thrombosis removal), alive
Marrie, 199011 / Canada
NA/NA / DVT / Acute Q fever / NA / NA
Galvez, 199712 / Spain
42/M / Left iliac and femoral DVT / Acute Q fever
(IFA serology: seroconversion to phase II IgG 512) / Thrombocytopenia
Normal aPTT
Negative lupus anticoagulant
Positive IgG aCL 782 (<23)
Positive IgM aCL 337 (<11) / IV heparin then coumarin for 3m, alive
Ben abdelghani, 200013 / France
53/F
DVT history / Femoral DVT / Granulomatous hepatitis
(serology: phase I IgG 1600) / Thrombocytopenia
Prolonged aPTT 44/32 (1.37)
Positive IgG aCL 24 (<12) / IgG aCL disappearance with doxycycline and ofloxacine, alive
Fernandez-Guerrero, 200414 / Spain
39/M / Migratory thrombophlebitis (Trousseau’s syndrome) / Acute Q fever
(serology CF 512 - IFA phase I IgG 512, IgM 64, phase II IgG >2,048, IgM 256) / Thrombocytopenia
Prolonged aPTT
Positive IgG aCL 95 (<22)
Positive IgM aCL 19 (<10) / No specific anti C. burnetii treatment, subcutaneous heparin and diclofenac, alive
Vidal, 200515 / France
55/M / Bilateral thrombophlebitis / Acute Q fever
(serology: phase II IgG 1600 IgM 50) / Thrombocytopenia
Prolonged aPTT (ratio 1.7)
Positive lupus anticoagulant
Positive IgG aCL >200 (N < 11)
Positive IgM aCL > 200 (<10)
Positive IgG antiβ2GP1 28 (N < 20)
Positive IgM antiβ2GP1 92 (N < 10)) / Doxycycline 15d, anticoagulation for 3m, cured
Arterial thrombosis (n = 6)
Marrie, 199011 / Canada
NA/NA / Myocardial infarction / Acute Q fever pneumonia / NA / NA
Turtle, 199916 / Australia
22/M / Multiple splenic infarcts (CT scan) / Acute Q fever
(serology: IgM positive, phase II 1024) / Thrombocytopenia
Prolonged aPTT 44/26 (1.7)
Positive lupus anticoagulant
Positive IgG aCL > 64 (<10)
Positive IgM aCL 49 (<10) / No specific treatment, cured
Fernandez-Ruiz, 201017 / Spain
62/M
Smoking, positive hepatitis C virus serology / Left atrial thrombus / Persistent infection with renal and splenic involvement, normal cardiac valves
(serology: phase I ≥ 2560 Phase II ≥ 1280, Thrombus positive by PCR, IHC and electronic microscopy) / NA / Doxy 12 m, cured
Pers, 200918 / France
43/M
Smoking / Left renal infarction
(CT scan) / Acute Q fever
(serology: phase II IgG 3200) / Thrombocytopenia
Prolonged aPTT 48/33 (1.45)
Positive lupus anticoagulant
Positive IgG aCL >300 (< 20)
Positive IgM aCL > 300 (<20) / Doxycycline, IV heparin, IVIG – continuation of oral anticoagulation up to 1 year after diagnosis (aCL persistence) then aspirin
Newcombe, 201319 / Australia,
9/M / Splenic infarction
(CT scan) / Acute Q fever
(serology: CFT and EIA) / Negative IgG aCL < 7 (<9)
Positive IgM aCL 18 (<9) / Doxy 14d, cured
Cebrian, 201620 / Spain
30/M / Splenic infarction
(Doppler US and CT scan) / Acute Q fever
(serology) / Prolonged aPTT
Positive antiphospholipid antibodies

aPL, anti-phospholipid antibodies; aPTT, activated partial thromboplastin time; CFT, complement fixation test; CT scan, computed tomography scanner; d, days; Doxy, doxycycline; DVT, deep vein thrombosis; EIA, enzyme immunoassay; G, giga; IgG aCL, anticardiolipin antibodies of the IgG isotype in GPLU units if not indicated (Normal value for this laboratory); IgM aCL, anticardiolipin antibodies of the IgM isotype in MPLU units if not indicated (normal threshold); IFA, indirect immunofluorescence assay; IHC, immunohistochemistry; IV, intravenous; IVIG, intravenous immunoglobulins; LA, lupus anticoagulant; m, months; NA, not available; PCR, polymerase chain reaction; US, ultrasound; VP scintigraphy, ventilation perfusion scintigraphy. *Considered positive by the authors but the serum was collected long after the thrombosis event. †CT scan was negative for pulmonary embolism.

Supplemental Digital Content 2. Table which reports the detailed characteristics of patients with acute Q fever and thrombosis reported in this study

Patient number, year of diagnosis / Country (region)
Age/Sex
Risk factor for thrombosis / Thrombosis
(technical diagnosis) / Type of Coxiella burnetii infection
(microbiological criteria*) / Lupus anticoagulant and antiphospholipid antibodies work-up† / Treatment and outcome
Patient 1,2014 / France (Provence-Alpes-Côte d’Azur)
58/M
DVT history / Bilateral pulmonary embolism with lung infarction (CT scan) one month after splenic infarction (CT scan) / Acute Q fever
(seroconversion and positive blood PCR) / Thrombocytopenia
Prolonged aPTT
Positive lupus anticoagulant
Positive IgG aCL 13,000 / IV heparin then fluindione, progression to possible endocarditis (A0B1C221) treated by 18m DOHCQ, cured at 25m
Patient 2, 2011 / France (Nouvelle Aquitaine)
67/M
Smoking, DVT history with long-term anticoagulation / Bilateral pulmonary embolism with lung infarction (CT scan) with bilateral lower limb DVT / Acute Q fever
(seroconversion) / Long-term anticoagulation
Positive IgG aCL 310
Positive IgM aCL 52 / Heparin then long-term warfarin, doxy 21d, cured at 17m
Patient 3, 2012 / France (Provence-Alpes-Côte d’Azur)
87/M / Pulmonary embolism (CT scan) / Acute Q fever
(serology: 800, 100, 25/1600, 200, 50) / Prolonged aPTT 53/31 (1.7)
Positive IgG aCL 652 / Enoxaparine then fluindione for 6m, doxy 9m, cured at 17m but grade II persistent dyspnea with long-term oxygenotherapy
Patient 4, 2012 / France (Auvergne-Rhône-Alpes)
43/M / Pulmonary embolism (CT scan) / Acute Q fever
(seroconversion) / Thrombocytopenia
Normal aPTT
Positive lupus anticoagulant
Positive IgG aCL 98
Positive IgM aCL 150
Positive IgM anti-β2GP1 10 (N < 8) / LMWH then rivaroxaban for 6 m, doxy 21d, cured at 6m
Patient number, year of diagnosis / Country (region)
Age/Sex
Risk factor for thrombosis / Thrombosis
(technical diagnosis) / Type of Coxiella burnetii infection
(microbiological criteria*) / Lupus anticoagulant and antiphospholipid antibodies work-up† / Treatment and outcome
Patient 5, 2008 / France (Provence-Alpes-Côte d’Azur)
38/M / Lower limb DVT / Acute Q fever
(serology: 25, 800, 0/50, 1600, 0) / Thrombocytopenia
Negative IgG aCL 9 / Unknown anticoagulation, doxy 21d, cured at 5m
Patient 6, 2008 / French Guiana, Cayenne
17/F / Extensive left superior member DVT
(Doppler US) / Acute Q fever
(serology: 200, 50, 0/400, 100, 0) / Thrombocytopenia
Positive IgG aCL 46 / NA (lost of follow-up at 1m)
Patient 7, 2012 / France (Occitanie)
56/M
Smoking / Lower limb DVT (Doppler US) / Acute Q fever
(serology 200, 100, 0/400, 200, 0) / Thrombocytopenia
Prolonged aPTT (ratio 1.98)
Positive lupus anticoagulant (anti-prothrombinase)
Positive IgG aCL 64
Positive IgM aCL >80
Positive IgM anti-β2GP1 12 UI/ml (<5) / Enoxaparine, doxy 21d then progression to definite endocarditis in 3m (A0B2C121), 18 m DOHCQ treatment, cured at 23m
Patient 8, 2014 / France (Provence-Alpes-Côte d’Azur)
65/M / Lower limb DVT (doppler US) / Acute Q fever
(serology 3200, 200, 0/3200, 200, 0) / Prolonged aPTT 61.4/32 (1.9)
Positive lupus anticoagulant
Positive IgG aCL 494
Negative extensive coagulation check-up / Heparin then long-term fluindione, doxy 21d, uveitis during follow-up (addition of ofloxacin), progression to possible chronic endocarditis (A0B0C321) with 12m treatment, cured at 17m
Patient number, year of diagnosis / Country (region)
Age/Sex
Risk factor for thrombosis / Thrombosis
(technical diagnosis) / Type of Coxiella burnetii infection
(microbiological criteria*) / Lupus anticoagulant and antiphospholipid antibodies work-up† / Treatment and outcome
Patient 9, 2009 / France (Auvergne-Rhône-Alpes)
52/M
Smoking / Stroke (CT scan) with left hemiparesia and dysarthria
PFO/ASA at TEE / Acute Q fever
(serology 100, 100, 100/200, 200, 200) / Negative lupus anticoagulant
Positive IgG aCL 88 / Heparin then fluindione for 3m, doxy 21d, persistent right thermoalgic hypoesthesia, cured ad integrum at 39m
Patient 10, 2012 / France (Auvergne-Rhône-Alpes)
65/M
Smoking / Left axillar and sub-clavian artery thrombosis with left upper arm acute ischemy
(Doppler US + CT scan) / Acute Q fever
(serology: 50, 800, 100/100, 1600, 200) / Thrombocytopenia 102
Positive IgG aCL 652
Positive IgM aCL 75 / Heparin IV, doxy 21d, cured at 47m
Patient 11, 2011 / France (Occitanie)
54/F / Splenic infarction
(CT scan) / Acute Q fever
(serology: 1600, 100, 200/3200, 200, 400) / Thrombocytopenia 70
Positive IgG aCL 1380 / NA (lost of follow-up at 2m)
Patient 12, 2011 / France (Nouvelle-Aquitaine)
59/M / Splenic infarction (CT scan) / Acute Q fever
(serology: 200, 50, 50/400, 100, 100) / Positive IgG aCL 1020
Positive IgM aCL 134 / Progression to focal vasculitis (periduodenal artery) diagnosed by PET-scan, prolonged DOHCQ, cured at 48m
Patient 13, 2015 / France (Provence-Alpes-Côte d’Azur)
52/M
Smoking and alcohol abuse, arteriopathy of lower limb without thrombosis in a recent CT scan / Right iliac and femoral and left femoral artery thrombosis (CT scan), superficial phlebitis of right and left upper arms / Acute Q fever
(serology 1600, 0, 100/3200, 0, 200) / Prolonged aPTT 47/32 (1.46)
Positive lupus anticoagulant
Positive IgG aCL 36
Positive IgM aCL 54 / Acetylsalicylic acid,
lost to follow-up (2m)

aPTT: activated partial thromboplastin time, CT scan: computed tomography, d: day, DOHCQ: doxycycline and hydroxychloroquine treatment, Doxy: doxycycline, DVT: Deep vein thrombosis, IgG aCL: anticardiolipin antibodies of the IgG isotype, IgM aCL: anticardiolipin antibodies of the IgM isotype, IV: intravenous, LMWH: Low molecular weight heparin, m: months, NA: Not available, PCR: polymerase chain reaction, PET-scan: 18F-fluorodeoxyglucose positron emission tomography / computed tomography, PFO/ASA: patent foramen ovale associated with atrial septum aneurysm, TEE: transesophageal echocardiography, US: ultrasound. *Phase 1: IgG, IgM, IgA; phase 2: IgG, IgM, IgA. †Cutoff value for the presence of IgG aCL was 22 GPLU. Cutoff value for the presence of IgM aCL was 10 GPLU.

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