This article uses case-based discussion to review prevention and management of thrombotic problems in hospitalized patients that involve a clinical hematologist. There is variation in the clinical hematologist’s role in thrombosis practice throughout the world, and we discuss this where indicated. Hospital-associated venous thromboembolism (VTE), or hospital-associated thrombosis (HAT), is the term to cover VTE occurring during admission and for 90 days postdischarge and is a common patient safety problem. HATs are the most common cause of VTE accounting for 55% to 60% of all VTE, with an estimated 10 million occurring globally. VTE risk assessment alongside evidence-based thromboprophylaxis reduces this risk significantly. Many hospitalized patients, especially older patients, use direct oral anticoagulants (DOACs), mainly to prevent stroke in atrial fibrillation. DOACs require perioperative management and may need urgent reversal. Other complex interventions such as extracorporeal membrane oxygenation which require anticoagulation are also discussed. Lastly, those with uncommon high-risk thrombophilias, especially those with antithrombin deficiency, produce unique challenges when hospitalized.

1.
Virchow
R
. "Thrombose und Embolie. Gefässentzündung und septische Infektion". Gesammelte Abhandlungen zur wissenschaftlichen Medicin (in German). Frankfurt am Main: Von Meidinger & Sohn. In:
Matzdorff
AC
,
Bell
WR
, eds.
Thrombosis and Emboli (1846-1856)
.
Science History Publications
;
1998
. :
219
-
732
.
2.
Hunt
BJ
.
Preventing hospital associated venous thromboembolism
.
BMJ
.
2019
. ;
365
:
l4239
.
3.
Jha
AK
,
Larizgoitia
I
,
Audera-Lopez
C
,
Prasopa-Plaizier
N
,
Waters
H
,
Bates
DW
.
The global burden of unsafe medical care: analytic modelling of observational studies
.
BMJ Qual Saf
.
2013
. ;
22
(
10
):
809
-
815
.
4.
Wendelboe
AM
,
Langenfeld
H
,
Ageno
W
, et al
.
Current practices of standardized risk assessment for venous thromboembolism: Results from a global survey from the World Thrombosis Day steering committee
.
J Thromb Haemost
.
2022
. ;
20
(
2
):
532
-
535
.
5.
Machin
M
,
Younan
HC
,
Smith
S
,
Salim
S
,
Davies
AH
,
Shalhoub
J
.
Systematic review on the benefit of graduated compression stockings in the prevention of venous thromboembolism in low-risk surgical patients
.
Phlebology
.
2021
. ;
36
(
3
):
184
-
193
.
6.
Colilla
S
,
Crow
A
,
Petkun
W
,
Singer
DE
,
Simon
T
,
Liu
X
.
Estimates of current and future incidence and prevalence of atrial fibrillation in the U.S. adult population
.
Am J Cardiol
.
2013
. ;
112
(
8
):
1142
-
1147
.
7.
Bickford
A
,
Majercik
S
,
Bledsoe
J
, et al
.
Weight-based enoxaparin dosing for venous thromboembolism prophylaxis in the obese trauma patient
.
Am J Surg
.
2013
. ;
206
(
6
):
847
-
851
.
8.
World Health Organization /Health
.
Topics/ Obesity
. Accessed 17 February 2023. Available at: https://www.who.int/health-topics/obesity.
9.
Centers for Disease Control and Prevention
.
Adulty Obesity facts
. Accessed 17 February 2023. Available at: https://www.cdc.gov/obesity/data/adult.html.
10.
Giugliano
RP
,
Ruff
CT
,
Wiviott
SD
, et al
.
Mortality in Patients with Atrial Fibrillation Randomized to Edoxaban or Warfarin: Insights from the ENGAGE AF-TIMI 48 Trial
.
Am J Med
.
2016
. ;
129
(
8
):
850
-
857.e2
.
11.
Held
C
,
Hylek
EM
,
Alexander
JH
, et al
.
Clinical outcomes and management associated with major bleeding in patients with atrial fibrillation treated with apixaban or warfarin: insights from the ARISTOTLE trial
.
Eur Heart J
.
2015
. ;
36
(
20
):
1264
-
1272
.
12.
Lopez-Lopez
JA
,
Sterne
JAC
,
Thom
HHZ
, et al
.
Oral anticoagulants for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis, and cost effectiveness analysis
.
BMJ
.
2017
. ;
359
:
j5058
.
13.
van Es
N
,
Coppens
M
,
Schulman
S
,
Middeldorp
S
,
Buller
HR
.
Direct oral anticoagulants compared with vitamin K antagonists for acute venous thromboembolism: evidence from phase 3 trials
.
Blood
.
2014
. ;
124
(
12
):
1968
-
1975
.
14.
van Gorp
RH
,
Schurgers
LJ
.
New insights into the pros and cons of the clinical use of vitamin K antagonists (VKAs) versus direct oral anticoagulants (DOACs)
.
Nutrients
.
2015
. ;
7
(
11
):
9538
-
9557
.
15.
Bauer
KA
.
Pros and cons of new oral anticoagulants
.
Hematology Am Soc Hematol Educ Program
.
2013
. ;
2013
:
464
-
470
.
16.
Schulman
S
,
Angeras
U
,
Bergqvist
D
, et al
.
Definition of major bleeding in clinical investigations of antihemostatic medicinal products in surgical patients
.
J Thromb Haemost
.
2010
. ;
8
(
1
):
202
-
204
.
17.
Tomaselli
GF
,
Mahaffey
KW
,
Cuker
A
, et al
.
2020 ACC expert consensus decision pathway on management of bleeding in patients on oral anticoagulants: a report of the American College of Cardiology Solution Set Oversight Committee
.
J Am Coll Cardiol
.
2020
. ;
76
(
5
):
594
-
622
.
18.
Cuker
A
,
Siegal
DM
,
Crowther
MA
,
Garcia
DA
.
Laboratory measurement of the anticoagulant activity of the non-vitamin K oral anticoagulants
.
J Am Coll Cardiol
.
2014
. ;
64
(
11
):
1128
-
1139
.
19.
Henskens
YMC
,
Gulpen
AJW
,
van Oerle
R
, et al
.
Detecting clinically relevant rivaroxaban or dabigatran levels by routine coagulation tests or thromboelastography in a cohort of patients with atrial fibrillation
.
Thromb J
.
2018
. ;
16
:
3
.
20.
Tripodi
A
,
Ageno
W
,
Ciaccio
M
, et al
.
Position Paper on laboratory testing for patients on direct oral anticoagulants. A Consensus Document from the SISET, FCSA, SIBioC and SIPMeL
.
Blood Transfus
.
2018
. ;
16
(
5
):
462
-
470
.
21.
Samuelson
BT
,
Cuker
A
,
Siegal
DM
,
Crowther
M
,
Garcia
DA
.
Laboratory assessment of the anticoagulant activity of direct oral anticoagulants: a systematic review
.
Chest
.
2017
. ;
151
(
1
):
127
-
138
.
22.
Gosselin
RC
,
Adcock
DM
,
Bates
SM
, et al
.
International Council for Standardization in Haematology (ICSH) recommendations for laboratory measurement of direct oral anticoagulants
.
Thromb Haemost
.
2018
. ;
118
(
3
):
437
-
450
.
23.
Cuker
A
.
Laboratory measurement of the non-vitamin K antagonist oral anticoagulants: selecting the optimal assay based on drug, assay availability, and clinical indication
.
J Thromb Thrombolysis
.
2016
. ;
41
(
2
):
241
-
247
.
24.
Levy
JH
,
Ageno
W
,
Chan
NC
, et al
.
When and how to use antidotes for the reversal of direct oral anticoagulants: guidance from the SSC of the ISTH
.
J Thromb Haemost
.
2016
. ;
14
(
3
):
623
-
627
.
25.
Connolly
SJ
,
Crowther
M
,
Eikelboom
JW
, et al
.
Full study report of andexanet alfa for bleeding associated with factor Xa inhibitors
.
N Engl J Med
.
2019
. ;
380
(
14
):
1326
-
1335
.
26.
Pollack
CV
,
Reilly
PA
,
van Ryn
J
, et al
.
Idarucizumab for dabigatran reversal - full cohort analysis
.
N Engl J Med
.
2017
. ;
377
(
5
):
431
-
441
.
27.
Chaudhary
R
,
Singh
A
,
Chaudhary
R
, et al
.
Evaluation of direct oral anticoagulant reversal agents in intracranial hemorrhage: a systematic review and meta-analysis
.
JAMA Netw Open
.
2022
. ;
5
(
11
):
e2240145
.
28.
Gomez-Outes
A
,
Alcubilla
P
,
Calvo-Rojas
G
, et al
.
Meta-analysis of reversal agents for severe bleeding associated with direct oral anticoagulants
.
J Am Coll Cardiol
.
2021
. ;
77
(
24
):
2987
-
3001
.
29.
Heo
YA
.
Andexanet alfa: first global approval
.
Drugs
.
2018
. ;
78
(
10
):
1049
-
1055
.
30.
Frontera
JA
,
Bhatt
P
,
Lalchan
R
, et al
.
Cost comparison of andexanet versus prothrombin complex concentrates for direct factor Xa inhibitor reversal after hemorrhage
.
J Thromb Thrombolysis
.
2020
. ;
49
(
1
):
121
-
131
.
31.
Benz
AP
,
Xu
L
,
Eikelboom
JW
, et al
.
Andexanet alfa for specific anticoagulation reversal in patients with acute bleeding during treatment with edoxaban
.
Thromb Haemost
.
2022
. ;
122
(
6
):
998
-
1005
.
32.
Cuker
A
,
Burnett
A
,
Triller
D
, et al
.
Reversal of direct oral anticoagulants: guidance from the Anticoagulation Forum
.
Am J Hematol
.
2019
. ;
94
(
6
):
697
-
709
.
33.
Bauer
ME
,
Arendt
K
,
Beilin
Y
, et al
.
The Society for Obstetric Anesthesia and Perinatology Interdisciplinary consensus statement on neuraxial procedures in obstetric patients with thrombocytopenia
.
Anesth Analg
.
2021
. ;
132
(
6
):
1531
-
1544
.
34.
Tiede
A
,
Tait
RC
,
Shaffer
DW
, et al
.
Antithrombin alfa in hereditary antithrombin deficient patients: A phase 3 study of prophylactic intravenous administration in high risk situations
.
Thromb Haemost
.
2008
. ;
99
(
3
):
616
-
622
.
35.
Chaireti
R
,
Tronnhagen
I
,
Bremme
K
,
Ranta
S
.
Management and outcomes of newborns at risk for inherited antithrombin deficiency
.
J Thromb Haemost
.
2020
. ;
18
(
10
):
2582
-
2589
.
36.
Kietaibl
S
,
Ferrandis
R
,
Godier
A
, et al
.
Regional anaesthesia in patients on antithrombotic drugs: Joint ESAIC/ESRA guidelines
.
Eur J Anaesthesiol
.
2022
. ;
39
(
2
):
100
-
132
.
37.
Spyropoulos
AC
,
Hartaigh
BO
,
Cao
Z
, et al
.
Costs and healthcare resource utilization associated with idarucizumab or andexanet alfa oral anticoagulant reversal in patients hospitalized with life-threatening bleeds
.
Clin Appl Thromb Hemost
.
2022
. ;
28
:
10760296221110568
.
38.
Fanikos
J
,
Goldstein
JN
,
Lovelace
B
,
Beaubrun
AC
,
Blissett
RS
,
Aragão
F
.
Cost-effectiveness of andexanet alfa versus four-factor prothrombin complex concentrate for the treatment of oral factor Xa inhibitor-related intracranial hemorrhage in the US
.
J Med Econ
.
2022
. ;
25
(
1
):
309
-
320
.
39.
Lu
G
,
Conley
PB
,
Leeds
JM
, et al
.
A phase 2 PK/PD study of andexanet alfa for reversal of rivaroxaban and edoxaban anticoagulation in healthy volunteers
.
Blood Adv
.
2020
. ;
4
(
4
):
728
-
739
.
40.
Greenberg
SM
,
Ziai
WC
,
Cordonnier
C
, et al
.
2022 Guideline for the management of patients with spontaneous intracerebral hemorrhage: a guideline from the American Heart Association/American Stroke Association
.
Stroke
.
2022
. ;
53
(
7
):
e282
-
e361
.
41.
Ansell
J
,
Laulicht
BE
,
Bakhru
SH
, et al
.
Ciraparantag, an anticoagulant reversal drug: mechanism of action, pharmacokinetics, and reversal of anticoagulants
.
Blood
.
2021
. ;
137
(
1
):
115
-
125
.
42.
Ansell
J
,
Bakhru
S
,
Laulicht
BE
,
Tracey
G
,
Villano
S
,
Freedman
D
.
Ciraparantag reverses the anticoagulant activity of apixaban and rivaroxaban in healthy elderly subjects
.
Eur Heart J
.
2022
. ;
43
(
10
):
985
-
992
.
43.
Nederpelt
CJ
,
Naar
L
,
Krijnen
P
, et al
.
Andexanet alfa or prothrombin complex concentrate for factor Xa inhibitor reversal in acute major bleeding: a systematic review and meta-analysis
.
Crit Care Med
.
2021
. ;
49
(
10
):
e1025
-
e1036
.
44.
Doyle
AJ
,
Karunanithy
N
,
Hunt
BJ
.
Another nail in the coffin of vena cava filters
.
Br J Surg
.
2020
. ;
107
(
1
):
9
-
10
.
45.
Mismetti
P
,
Laporte
S
,
Pellerin
O
, et al
.
Effect of a retrievable inferior vena cava filter plus anticoagulation vs anticoagulation alone on risk of recurrent pulmonary embolism: a randomized clinical trial
.
JAMA
.
2015
. ;
313
(
16
):
1627
-
1635
.
46.
Young
T
,
Sriram
KB
.
Vena caval filters for the prevention of pulmonary embolism
.
Cochrane Database Syst Rev
.
2020
. ;
10
:
CD006212
.
47.
Stevens
SM
,
Woller
SC
,
Kreuziger
LB
, et al
.
Antithrombotic therapy for VTE disease: second update of the CHEST Guideline and Expert Panel Report
.
Chest
.
2021
. ;
160
(
6
):
e545
-
e608
.
48.
Baglin
TP
,
Brush
J
,
Streiff
M
;
British Committee for Standards in Haematology Writing Group
.
Guidelines on use of vena cava filters
.
Br J Haematol
.
2006
. ;
134
(
6
):
590
-
595
.
49.
Kaufman
JA
,
Barnes
GD
,
Chaer
RA
, et al
.
Society of Interventional Radiology clinical practice guideline for inferior vena cava filters in the treatment of patients with venous thromboembolic disease: developed in collaboration with the American College of Cardiology, American College of Chest Physicians, American College of Surgeons Committee on Trauma, American Heart Association, Society for Vascular Surgery, and Society for Vascular Medicine
.
J Vasc Interv Radiol
.
2020
. ;
31
(
10
):
1529
-
1544
.
50.
Sheehan
M
,
Coppin
K
,
O'Brien
C
, et al
.
A single center 9-year experience in IVC filter retrieval - the importance of an IVC filter registry
.
CVIR Endovasc
.
2022
. ;
5
(
1
):
15
.
51.
Kelkar
AH
,
Rajasekhar
A
.
Inferior vena cava filters: a framework for evidence-based use
.
Hematology Am Soc Hematol Educ Program
.
2020
. ;
2020
(
1
):
619
-
628
.
52.
Spyropoulos
AC
,
Brohi
K
,
Caprini
J
, et al
.
Scientific and Standardization Committee communication: guidance document on the periprocedural management of patients on chronic oral anticoagulant therapy: Recommendations for standardized reporting of procedural/surgical bleed risk and patient-specific thromboembolic risk
.
J Thromb Haemost
.
2019
. ;
17
(
11
):
1966
-
1972
.
53.
Douketis
JD
,
Spyropoulos
AC
,
Duncan
J
, et al
.
Perioperative management of patients with atrial fibrillation receiving a direct oral anticoagulant
.
JAMA Intern Med
.
2019
. ;
179
(
11
):
1469
-
1478
.
54.
Erdoes
G
,
Martinez Lopez De Arroyabe
B
,
Bolliger
D
, et al
.
International consensus statement on the peri-operative management of direct oral anticoagulants in cardiac surgery
.
Anaesthesia
.
2018
. ;
73
(
12
):
1535
-
1545
.
55.
Saja
K
;
Haemostasis and Thrombosis Taskforce of the British Society for Haematology
.
Addendum to the guideline on the peri-operative management of anti-coagulation and anti-platelet therapy
.
Br J Haematol
.
2022
. ;
197
(
2
):
188
-
189
.
56.
Douketis
JD
,
Spyropoulos
AC
,
Murad
MH
, et al
.
Perioperative management of antithrombotic therapy: an American College of Chest Physicians Clinical Practice Guideline
.
Chest
.
2022
. ;
162
(
5
):
e207
-
e243
.
57.
Fujikawa
T
,
Takahashi
R
,
Naito
S
.
Perioperative antithrombotic management of patients who receive direct oral anticoagulants during gastroenterological surgery
.
Ann Gastroenterol Surg
.
2020
. ;
4
(
3
):
301
-
309
.
58.
Tafur
AJ
,
Clark
NP
,
Spyropoulos
AC
, et al
.
Predictors of Bleeding in the Perioperative Anticoagulant Use for Surgery Evaluation Study
.
J Am Heart Assoc
.
2020
. ;
9
(
19
):
e017316
.
59.
McMichael
ABV
,
Ryerson
LM
,
Ratano
D
,
Fan
E
,
Faraoni
D
,
Annich
GM
.
2021 ELSO Adult and Pediatric Anticoagulation guidelines
.
ASAIO J
.
2022
. ;
68
(
3
):
303
-
310
.
60.
Levy
JH
,
Staudinger
T
,
Steiner
ME
.
How to manage anticoagulation during extracorporeal membrane oxygenation
.
Intensive Care Med
.
2022
. ;
48
(
8
):
1076
-
1079
.
61.
Protti
A
,
Iapichino
GE
,
Di Nardo
M
,
Panigada
M
,
Gattinoni
L
.
Anticoagulation management and antithrombin supplementation practice during veno-venous extracorporeal membrane oxygenation: a worldwide survey
.
Anesthesiology
.
2020
. ;
132
(
3
):
562
-
570
.
62.
Panigada
M
,
Cucino
A
,
Spinelli
E
, et al
.
A randomized controlled trial of antithrombin supplementation during extracorporeal membrane oxygenation
.
Crit Care Med
.
2020
. ;
48
(
11
):
1636
-
1644
.
63.
Doyle
AJ
,
Hunt
BJ
,
Sanderson
B
, et al
.
A comparison of thrombosis and hemorrhage rates in patients with severe respiratory failure due to Coronavirus disease 2019 and influenza requiring extracorporeal membrane oxygenation
.
Crit Care Med
.
2021
. ;
49
(
7
):
e663
-
e672
.
64.
Kovac
M
,
Mitic
G
,
Mikovic
Z
, et al
.
The influence of specific mutations in the AT gene (SERPINC1) on the type of pregnancy related complications
.
Thromb Res
.
2019
. ;
173
:
12
-
19
.
65.
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
.
66.
Bramham
K
,
Retter
A
,
Robinson
SE
,
Mitchell
M
,
Moore
GW
,
Hunt
BJ
.
How I treat heterozygous hereditary antithrombin deficiency in pregnancy
.
Thromb Haemost
.
2013
. ;
110
(
3
):
550
-
559
.
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