Anticoagulation is central to the management of antiphospholipid syndrome (APS), an acquired thrombo-inflammatory disorder characterized by thrombosis (venous, arterial, or microvascular) or pregnancy morbidity, in association with persistent antiphospholipid antibodies (aPL; ie, 1 or more of lupus anticoagulant [LA], anticardiolipin, anti-beta-2- glycoprotein I, IgG, or IgM antibodies). The mainstay of anticoagulation in patients with thrombotic APS is warfarin or an alternative vitamin K antagonist (VKA) and, in certain situations, low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH). Accurate assessment of anticoagulation intensity underpins optimal anticoagulant dosing for thrombus treatment or primary/secondary prevention. In patients with APS on warfarin, the international normalized ratio (INR) may not be representative of anticoagulation intensity due to an interaction between LA and the thromboplastin reagent used in the INR determination. In this review, we summarize the use of warfarin/VKA in patients with APS, along with venous and point-of-care INR monitoring. We also discuss the role and monitoring of LMWH/UFH, including in the anticoagulant refractory setting and during pregnancy.

1.
Barbhaiya
M
,
Zuily
S
,
Naden
R
, et al
;
ACR/EULAR APS Classification Criteria Collaborators
.
The 2023 ACR/EULAR antiphospholipid syndrome classification criteria
.
Arthritis Rheumatol
.
2023
;
75
(
10
):
1687
-
1702
.
2.
Devreese
KMJ
,
Ortel
TL
,
Pengo
V
,
de Laat
B
;
Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies
.
Laboratory criteria for antiphospholipid syndrome: communication from the SSC of the ISTH
.
J Thromb Haemost
.
2018
;
16
(
4
):
809
-
813
.
3.
Petri
M.
Update on anti-phospholipid antibodies in SLE: the Hopkins’ Lupus Cohort
.
Lupus
.
2010
;
19
(
4
):
419
-
423
.
4.
Tektonidou
MG
,
Andreoli
L
,
Limper
M
, et al.
EULAR recommendations for the management of antiphospholipid syndrome in adults
.
Ann Rheum Dis
.
2019
;
78
(
10
):
1296
-
1304
.
5.
Legault
K
,
Schunemann
H
,
Hillis
C
, et al.
McMaster RARE-Bestpractices clinical practice guideline on diagnosis and management of the catastrophic antiphospholipid syndrome
.
J Thromb Haemost
.
2018
;
16
(
8
):
1656
-
1664
.
6.
Garcia
D
,
Akl
EA
,
Carr
R
,
Kearon
C.
Antiphospholipid antibodies and the risk of recurrence after a first episode of venous thromboembolism: a systematic review
.
Blood
.
2013
;
122
(
5
):
817
-
824
.
7.
Kearon
C
,
Parpia
S
,
Spencer
FA
, et al.
Antiphospholipid antibodies and recurrent thrombosis after a first unprovoked venous thromboembolism
.
Blood
.
2018
;
131
(
19
):
2151
-
2160
.
8.
Tektonidou
MG
,
Andreoli
L
,
Limper
M
,
Tincani
A
,
Ward
MM
.
Management of thrombotic and obstetric antiphospholipid syndrome: a systematic literature review informing the EULAR recommendations for the management of antiphospholipid syndrome in adults
.
RMD Open
.
2019
;
5
(
1
):
e000924
.
9.
Cohen
H
,
Isenberg
DA
.
How I treat anticoagulant-refractory thrombotic antiphospholipid syndrome
.
Blood
.
2021
;
137
(
3
):
299
-
309
.
10.
Cervera
R
,
Boffa
M-C
,
Khamashta
M-A
,
Hughes
G-R
.
The Euro-Phospholipid project: epidemiology of the antiphospholipid syndrome in Europe
.
Lupus
.
2009
;
18
(
10
):
889
-
893
.
11.
Khairani
CD
,
Bejjani
A
,
Piazza
G
, et al.
Direct oral anticoagulants vs vitamin K antagonists in patients with antiphospholipid syndromes: meta-analysis of randomized trials
.
J Am Coll Cardiol
.
2023
;
81
(
1
):
16
-
30
.
12.
Zuily
S
,
Cohen
H
,
Isenberg
D
, et al.
Use of direct oral anticoagulants in patients with thrombotic antiphospholipid syndrome: guidance from the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis
.
J Thromb Haemost
.
2020
;
18
(
9
):
2126
-
2137
.
13.
Woller
SC
,
Stevens
SM
,
Kaplan
DA
, et al.
Apixaban for the secondary prevention of thrombosis among patients with antiphospholipid syndrome: study rationale and design (ASTRO-APS)
.
Clin Appl Thromb Hemost
.
2016
;
22
(
3
):
239
-
247
.
14.
Mittal
P
,
Gafoor
R
,
Sayar
Z
, et al.
Rivaroxaban for stroke patients with antiphospholipid syndrome (RISAPS): protocol for a randomized controlled, phase IIb proof-of-principle trial
.
Res Pract Thromb Haemost
.
2024
;
8
(
5
):
102468
.
15.
Dorgalaleh
A
,
Favaloro
EJ
,
Bahraini
M
,
Rad
F.
Standardization of prothrombin time/international normalized ratio (PT/INR)
.
Int J Lab Hematol
.
2021
;
43
(
1
):
21
-
28
.
16.
Tripodi
A
,
de Laat
B
,
Wahl
D
, et al
;
Subcommittees on Control of Anticoagulation and Lupus Anticoagulant/Antiphospholipid Antibodies
.
Monitoring patients with the lupus anticoagulant while treated with vitamin K antagonists: communication from the SSC of the ISTH
.
J Thromb Haemost
.
2016
;
14
(
11
):
2304
-
2307
.
17.
Tripodi
A
,
Chantarangkul
V
,
Clerici
M
,
Negri
B
,
Galli
M
,
Mannucci
PM
.
Laboratory control of oral anticoagulant treatment by the INR system in patients with the antiphospholipid syndrome and lupus anticoagulant. Results of a collaborative study involving nine commercial thromboplastins
.
Br J Haematol
.
2001
;
115
(
3
):
672
-
678
.
18.
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
(
7
):
736
-
745
.
19.
Christensen
TD
,
Larsen
TB
.
Precision and accuracy of point-of-care testing coagulometers used for self-testing and self-management of oral anticoagulation therapy
.
J Thromb Haemost
.
2012
;
10
(
2
):
251
-
260
.
20.
Witt
DM
,
Nieuwlaat
R
,
Clark
NP
, et al.
American Society of Hematology 2018 guidelines for management of venous thromboembolism: optimal management of anticoagulation therapy
.
Blood Adv
.
2018
;
2
(
22
):
3257
-
3291
.
21.
Taylor
JR
,
Richter
C
,
Lindamood
C
,
Liu
X
,
Zumberg
M
,
Fletcher
B.
Accuracy of CoaguChek XS in patients with antiphospholipid syndrome
.
Point Care
.
2017
;
16
(
4
):
161
-
163
.
22.
Isert
M
,
Miesbach
W
,
Schüttfort
G
, et al.
Monitoring anticoagulant therapy with vitamin K antagonists in patients with antiphospholipid syndrome
.
Ann Hematol
.
2015
;
94
(
8
):
1291
-
1299
.
23.
Jennings
I
,
Kitchen
D
,
Keeling
D
,
Fitzmaurice
D
,
Heneghan
C
;
BCSH Committee
.
Patient self-testing and self-management of oral anticoagulation with vitamin K antagonists: guidance from the British Committee for Standards in Haematology
.
Br J Haematol
.
2014
;
167
(
5
):
600
-
607
.
24.
Efthymiou
M
,
Lawrie
AS
,
Mackie
I
, et al.
Thrombin generation and factor X assays for the assessment of warfarin anticoagulation in thrombotic antiphospholipid syndrome
.
Thromb Res
.
2015
;
135
(
6
):
1191
-
1197
.
25.
Bick
RL
,
Rice
J.
Long-term outpatient dalteparin (fragmin) therapy for arterial and venous thrombosis: efficacy and safety–a preliminary report
.
Clin Appl Thromb Hemost
.
1999
;
5
(
suppl 1
):
S67
-
S71
.
26.
Vargas-Hitos
JA
,
Ateka-Barrutia
O
,
Sangle
S
,
Khamashta
MA
.
Efficacy and safety of long-term low molecular weight heparin in patients with antiphospholipid syndrome
.
Ann Rheum Dis
.
2011
;
70
(
9
):
1652
-
1654
.
27.
Carrier
M
,
Le Gal
G
,
Cho
R
,
Tierney
S
,
Rodger
M
,
Lee
AY
.
Dose escalation of low molecular weight heparin to manage recurrent venous thromboembolic events despite systemic anticoagulation in cancer patients
.
J Thromb Haemost
.
2009
;
7
(
5
):
760
-
765
.
28.
Gajic-Veljanoski
O
,
Phua
CW
,
Shah
PS
,
Cheung
AM
.
Effects of long-term low-molecular-weight heparin on fractures and bone density in non- pregnant adults: a systematic review with meta-analysis
.
J Gen Intern Med
.
2016
;
31
(
8
):
947
-
957
.
29.
American College of Obstetricians and Gynecologists' Committee on Practice Bulletins—Obstetrics
.
ACOG Practice Bulletin No. 196: thromboembolism in pregnancy
.
Obstet Gynecol
.
2018
;
132
(
1
):
e1
-
e17
.
30.
Kourlaba
G
,
Relakis
J
,
Kontodimas
S
,
Holm
MV
,
Maniadakis
N.
A systematic review and meta-analysis of the epidemiology and burden of venous thromboembolism among pregnant women
.
Int J Gynaecol Obstet
.
2016
;
132
(
1
):
4
-
10
.
31.
Royal College of Obstetricians and Gynaecologists
. Green-top Guideline No. 37a.
Reducing the Risk of Thrombosis and Embolism During Pregnancy and the Puerperium
. RCOG;
2015
.
32.
Lamy
C
,
Hamon
JB
,
Coste
J
,
Mas
JL
.
Ischemic stroke in young women: risk of recurrence during subsequent pregnancies. French Study Group on Stroke in Pregnancy
.
Neurology
.
2000
;
55
(
2
):
269
-
274
.
33.
Liu
S
,
Rouleau
J
,
Joseph
KS
, et al.
Epidemiology of pregnancy-associated venous thromboembolism: a population-based study in Canada
.
J Obstet Gynaecol Can
.
2009
;
31
(
7
):
611
-
620
.
34.
Skeith
L.
Preventing venous thromboembolism during pregnancy and postpartum: crossing the threshold
.
Hematology Am Soc Hematol Educ Program
.
2017
;
2017
(
1
):
160
-
167
.
35.
Rodríguez-Pintó
I
,
Moitinho
M
,
Santacreu
I
, et al
;
CAPS Registry Project Group (European Forum on Antiphospholipid Antibodies)
.
Catastrophic antiphospholipid syndrome (CAPS): descriptive analysis of 500 patients from the International CAPS Registry
.
Autoimmun Rev
.
2016
;
15
(
12
):
1120
-
1124
.
36.
Garcia
DA
,
Baglin
TP
,
Weitz
JI
,
Samama
MM
.
Parenteral anticoagulants: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines
.
Chest
.
2012
;
141
(
2 Suppl
):
e24S
-
e43S
.
doi: 10.1378/chest.11-2291
. Erratum in: Chest. 2012;141(5):1369. Dosage error in article text. Erratum in: Chest. 2013;144(2):721. Dosage error in article text.
37.
Bates
SM
,
Rajasekhar
A
,
Middeldorp
S
, et al.
American Society of Hematology 2018 guidelines for management of venous thromboembolism: venous thromboembolism in the context of pregnancy
.
Blood Adv
.
2018
;
2
(
22
):
3317
-
3359
.
38.
Fouda
UM
,
Sayed
AM
,
Abdou
A-M
,
Ramadan
D-I
,
Fouda
I-M
,
Zaki
M-M
.
Enoxaparin versus unfractionated heparin in the management of recurrent abortion secondary to antiphospholipid syndrome
.
Int J Gynaecol Obstet
.
2011
;
112
(
3
):
211
-
215
.
39.
Sammaritano
LR
,
Bermas
BL
,
Chakravarty
EE
, et al.
2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases
.
Arthritis Rheumatol
.
2020
;
72
(
4
):
529
-
556
.
40.
Fischer-Betz
R
,
Specker
C
,
Brinks
R
,
Schneider
M.
Pregnancy outcome in patients with antiphospholipid syndrome after cerebral ischaemic events: an observational study
.
Lupus
.
2012
;
21
(
11
):
1183
-
1189
.
41.
Stone
S
,
Hunt
BJ
,
Khamashta
MA
,
Bewley
SJ
,
Nelson-Piercy
C.
Primary antiphospholipid syndrome in pregnancy: an analysis of outcome in a cohort of 33 women treated with a rigorous protocol
.
J Thromb Haemost
.
2005
;
3
(
2
):
243
-
245
.
42.
Royal College of Obstetricians and Gynaecologists
. Green-top Guideline No. 37b.
Thrombosis and Embolism During Pregnancy and the Puerperium: Acute Management
.
RCOG, London
(
2015
).
43.
Yelnik
CM
,
Lambert
M
,
Drumez
E
, et al.
Bleeding complications and antithrombotic treatment in 264 pregnancies in antiphospholipid syndrome
.
Lupus
.
2018
;
27
(
10
):
1679
-
1686
.
44.
Robertson
L
,
Strachan
J.
Subcutaneous unfractionated heparin for the initial treatment of venous thromboembolism
.
Cochrane Database Syst Rev
.
2017
;
2
(
2
):
CD006771
.
45.
Cuker
A
,
Arepally
GM
,
Chong
BH
, et al.
American Society of Hematology 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia
.
Blood Adv
.
2018
;
2
(
22
):
3360
-
3392
.
46.
Konstantinides
SV
,
Meyer
G
,
Becattini
C
, et al
;
ESC Scientific Document Group
.
2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS)
.
Eur Heart J
.
2020
;
41
(
4
):
543
-
603
.
47.
Shore-Lesserson
L
,
Baker
RA
,
Ferraris
VA
, et al.
The Society of Thoracic Surgeons, The Society of Cardiovascular Anesthesiologists, and The American Society of ExtraCorporeal Technology: clinical practice guidelines-anticoagulation during cardiopulmonary bypass
.
Ann Thorac Surg
.
2018
;
105
(
2
):
650
-
662
.
48.
Kitchen
S
,
Gray
E
,
Mackie
I
,
Baglin
T
,
Makris
M
;
BCSH Committee
.
Measurement of non-coumarin anticoagulants and their effects on tests of haemostasis: guidance from the British Committee for Standards in Haematology
.
Br J Haematol
.
2014
;
166
(
6
):
830
-
841
.
49.
Greaves
M
;
Control of Anticoagulation Subcommittee of the Scientific and Standardization Committee of the International Society of Thrombosis and Haemostasis
.
Limitations of the laboratory monitoring of heparin therapy. Scientific and standardization committee communications: on behalf of the Control of Anticoagulation Subcommittee of the Scientific and Standardization Committee of the International Society of Thrombosis and Haemostasis
.
Thromb Haemost
.
2002
;
87
(
1
):
163
-
164
.
50.
Devreese
KM
,
Verfaillie
CJ
,
De Bisschop
F
,
Delanghe
JR
.
Interference of C-reactive protein with clotting times
.
Clin Chem Lab Med
.
2015
;
53
(
5
):
e141
-
e145
.
51.
Mehta
TP
,
Smythe
MA
,
Mattson
JC
.
Strategies for managing heparin therapy in patients with antiphospholipid antibody syndrome
.
Pharmacotherapy
.
2011
;
31
(
12
):
1221
-
1231
.
52.
Cohen
H
,
Efthymiou
M
,
Devreese
KMJ
.
Monitoring of anticoagulation in thrombotic antiphospholipid syndrome
.
J Thromb Haemost
.
2021
;
19
(
4
):
892
-
908
.
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