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Article ; Online: The dos, don'ts, and nuances of thrombophilia testing.

Chiasakul, Thita / Bauer, Kenneth A

Hematology. American Society of Hematology. Education Program

2023 Volume 2023, Issue 1, Page(s) 593–599

Abstract: Considerable progress has been made in elucidating genetic and biologic risk factors for venous thromboembolism (VTE). Despite being able to identify heritable defects in a substantial proportion of patients with VTE, testing has not, in general, proven ... ...

Abstract	Considerable progress has been made in elucidating genetic and biologic risk factors for venous thromboembolism (VTE). Despite being able to identify heritable defects in a substantial proportion of patients with VTE, testing has not, in general, proven useful in management. Despite efforts to reduce inappropriate testing, it often falls to the hematologist to consult on patients having undergone thrombophilia testing. Through a series of cases, we discuss how D-dimer testing can be helpful in VTE recurrence risk stratification in younger women as well as how to approach patients with persistently elevated D-dimer levels in the absence of thrombosis. While elevated factor VIII coagulant activity levels are a significant risk factor for a first episode of VTE, its biologic basis is not fully understood, and studies have not shown it to be a useful predictor of recurrence. Abnormal results of genetic tests for methylene tetrahydrofolate reductase or plasminogen activator 1 promoter polymorphisms may be encountered, which carry little if any thrombotic risk and should never be ordered. We also discuss protein S deficiency, the most difficult of the hereditary thrombophilias to diagnose due to a wider "normal" range in the general population as compared with protein C, the presence of both free and bound forms in plasma, and the characteristics of the various assays in use. We also present a rare type of protein C deficiency that can be missed by functional assays using an amidolytic rather than a clotting end point.
MeSH term(s)	Humans ; Female ; Venous Thromboembolism/diagnosis ; Venous Thromboembolism/genetics ; Thrombophilia/diagnosis ; Thrombophilia/genetics ; Thrombosis/diagnosis ; Thrombosis/genetics ; Thrombosis/complications ; Risk Factors ; Biological Products
Chemical Substances	Biological Products
Language	English
Publishing date	2023-12-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	2084287-9
ISSN	1520-4383 ; 1520-4391
ISSN (online)	1520-4383
ISSN	1520-4391
DOI	10.1182/hematology.2023000491
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Article ; Online: Development of factor IX inhibitor in an adult with severe haemophilia B following COVID-19 vaccination: A case report.

Chiasakul, Thita / Kessler, Craig M

Haemophilia : the official journal of the World Federation of Hemophilia

2022 Volume 28, Issue 3, Page(s) e83–e85

MeSH term(s)	Adult ; COVID-19/prevention & control ; COVID-19 Vaccines/adverse effects ; Factor IX/therapeutic use ; Hemophilia A ; Hemophilia B/complications ; Hemophilia B/drug therapy ; Humans ; Vaccination
Chemical Substances	COVID-19 Vaccines ; Factor IX (9001-28-9)
Language	English
Publishing date	2022-03-08
Publishing country	England
Document type	Case Reports ; Letter
ZDB-ID	1229713-6
ISSN	1365-2516 ; 1351-8216 ; 1355-0691
ISSN (online)	1365-2516
ISSN	1351-8216 ; 1355-0691
DOI	10.1111/hae.14542
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Article ; Online: Laboratory Monitoring of Heparin Anticoagulation in Hemodialysis: Rationale and Strategies.

Chiasakul, Thita / Mullier, François / Lecompte, Thomas / Nguyen, Philippe / Cuker, Adam

Seminars in nephrology

2024 , Page(s) 151477

Abstract: Unfractionated heparin (UFH) and low-molecular-weight heparins (LMWHs) are commonly used to prevent clotting of the hemodialysis extracorporeal circuit and optimize hemodialysis adequacy. There is no consensus on the optimal dosing for UFH and LMWHs ... ...

Abstract	Unfractionated heparin (UFH) and low-molecular-weight heparins (LMWHs) are commonly used to prevent clotting of the hemodialysis extracorporeal circuit and optimize hemodialysis adequacy. There is no consensus on the optimal dosing for UFH and LMWHs during hemodialysis. In clinical practice, semiquantitative clotting scoring of the dialyzer and venous chamber may help to guide UFH and LMWH dose adjustment. Laboratory monitoring has not been shown to improve clinical outcomes and is therefore not routinely indicated in most hemodialysis patients. It might, however, be considered in select patients, such as those with extremes of body weight or history of repeated clotting or bleeding. Methods for laboratory monitoring include the activated partial thromboplastin time, activated clotting time, and antifactor Xa assays for UFH and antifactor Xa assay for LMWHs. Target ranges for anticoagulation in hemodialysis have been suggested but not clearly defined. When utilizing these tests, issues such as availability, standardization, interfering factors, and interpretation must be considered. In this narrative review, we discuss the rationale and methods of monitoring anticoagulation in hemodialysis.
Language	English
Publishing date	2024-01-29
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	604652-6
ISSN	1558-4488 ; 0270-9295
ISSN (online)	1558-4488
ISSN	0270-9295
DOI	10.1016/j.semnephrol.2023.151477
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Article ; Online: Four-factor prothrombin complex concentrate for the treatment of oral factor Xa inhibitor-associated bleeding: a meta-analysis of fixed versus variable dosing.

Chiasakul, Thita / Crowther, Mark / Cuker, Adam

Research and practice in thrombosis and haemostasis

2023 Volume 7, Issue 2, Page(s) 100107

Abstract: Background: The optimal dosing strategy of four-factor prothrombin complex concentrate (4F-PCC) to treat oral factor Xa (FXa) inhibitor-associated bleeding has not been established.: Objectives: To evaluate the effectiveness and safety of fixed ... ...

Abstract	Background: The optimal dosing strategy of four-factor prothrombin complex concentrate (4F-PCC) to treat oral factor Xa (FXa) inhibitor-associated bleeding has not been established. Objectives: To evaluate the effectiveness and safety of fixed versus variable 4F-PCC dosing for the management of FXa inhibitor-associated bleeding. Methods: A systematic literature search and meta-analysis of clinical studies was performed using PubMed, Embase, and Cochrane databases from inception to January 2022. The primary outcomes included hemostatic effectiveness, mortality, and thromboembolic events. Secondary outcomes included 4F-PCC usage, total length of stay in hospital and in intensive care units, and time to 4F-PCC administration. The pooled incidence or mean was calculated using a random-effects model and compared between the 2 dosing strategies. Results: Twenty-five studies were included and data from 1,760 patients (fixed dosing, n = 228; variable dosing, n = 1,532) were analyzed. There were no significant differences in hemostatic effectiveness, thromboembolic events, or mortality rates between the dosing strategies. Hospital length of stay was significantly longer in the fixed-dosing group, with a mean stay of 7.4 days (95% CI: 3.6-11.1) compared to 5.9 days (95% CI: 5.5-6.3) in the variable-dosing group ( Conclusions: A fixed-dosing strategy appears to be a safe and effective alternative to variable weight-based dosing and was associated with lower 4F-PCC usage. However, direct comparative studies are needed to confirm these results.
Language	English
Publishing date	2023-03-10
Publishing country	United States
Document type	Journal Article
ISSN	2475-0379
ISSN (online)	2475-0379
DOI	10.1016/j.rpth.2023.100107
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Article ; Online: The Pitfalls of Global Hemostasis Assays in Myeloproliferative Neoplasms and Future Challenges.

Tiu, Andrew / Chiasakul, Thita / Kessler, Craig M

Seminars in thrombosis and hemostasis

2023 Volume 50, Issue 2, Page(s) 213–223

Abstract: Venous and arterial thromboembolism are major complications of myeloproliferative neoplasms (MPNs), comprising polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Global hemostasis assays, including thrombin ... ...

Abstract	Venous and arterial thromboembolism are major complications of myeloproliferative neoplasms (MPNs), comprising polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Global hemostasis assays, including thrombin generation assay (TGA), rotational thromboelastometry (ROTEM), and thromboelastography (TEG), have been proposed as biomarkers to assess the hypercoagulability and thrombotic risk stratification in MPNs. We performed a systematic literature review on the parameters of TGA, ROTEM, and TEG and their association with thrombotic events and treatment strategies in MPNs. Thirty-two studies (all cross-sectional) were included, which collectively enrolled 1,062 controls and 1,608 MPN patients. Among the 13 studies that reported arterial or venous thrombosis, the overall thrombosis rate was 13.8% with 6 splanchnic thromboses reported. Out of the 27 TGA studies, there was substantial heterogeneity in plasma preparation and trigger reagents employed in laboratory assays. There was a trend toward increased peak height among all MPN cohorts versus controls and higher endogenous thrombin potential (ETP) between ET patients versus controls. There was an overall trend toward lower ETP between PV and PMF patients versus. controls. There were no substantial differences in ETP between JAK2-positive versus JAK2-negative MPNs, prior history versus negative history of thrombotic events, and among different treatment strategies. Of the three ROTEM studies, there was a trend toward higher maximum clot firmness and shorter clot formation times for all MPNs versus controls. The three TEG studies had mixed results. We conclude that the ability of parameters from global hemostasis assays to predict for hypercoagulability events in MPN patients is inconsistent and inconclusive. Further prospective longitudinal studies are needed to validate these biomarker tools so that thrombotic potential could be utilized as a primary endpoint of such studies.
MeSH term(s)	Humans ; Thrombin ; Cross-Sectional Studies ; Myeloproliferative Disorders/complications ; Myeloproliferative Disorders/diagnosis ; Polycythemia Vera/complications ; Thrombosis/etiology ; Thrombosis/complications ; Thrombocythemia, Essential ; Hemostasis ; Biomarkers ; Thrombophilia/complications ; Janus Kinase 2
Chemical Substances	Thrombin (EC 3.4.21.5) ; Biomarkers ; Janus Kinase 2 (EC 2.7.10.2)
Language	English
Publishing date	2023-04-17
Publishing country	United States
Document type	Systematic Review ; Journal Article
ZDB-ID	196901-8
ISSN	1098-9064 ; 0094-6176
ISSN (online)	1098-9064
ISSN	0094-6176
DOI	10.1055/s-0043-57010
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Article ; Online: Four-factor prothrombin complex concentrate for the treatment of oral factor Xa inhibitor-associated bleeding: a meta-analysis of fixed versus variable dosing

Chiasakul, Thita / Crowther, Mark / Cuker, Adam

Research and Practice in Thrombosis and Haemostasis. 2023 Feb., v. 7, no. 2, p. 100107

2023 , Page(s) 100107

Abstract: The optimal dosing strategy of four-factor prothrombin complex concentrate (4F-PCC) to treat oral factor Xa (FXa) inhibitor-associated bleeding has not been established. To evaluate the effectiveness and safety of fixed versus variable 4F-PCC dosing for ... ...

Abstract	The optimal dosing strategy of four-factor prothrombin complex concentrate (4F-PCC) to treat oral factor Xa (FXa) inhibitor-associated bleeding has not been established. To evaluate the effectiveness and safety of fixed versus variable 4F-PCC dosing for the management of FXa inhibitor-associated bleeding. A systematic literature search and meta-analysis of clinical studies was performed using PubMed, Embase, and Cochrane databases from inception to January 2022. The primary outcomes included hemostatic effectiveness, mortality, and thromboembolic events. Secondary outcomes included 4F-PCC usage, total length of stay in hospital and in intensive care units, and time to 4F-PCC administration. The pooled incidence or mean was calculated using a random-effects model and compared between the 2 dosing strategies. Twenty-five studies were included and data from 1,760 patients (fixed dosing, n = 228; variable dosing, n = 1,532) were analyzed. There were no significant differences in hemostatic effectiveness, thromboembolic events, or mortality rates between the dosing strategies. Hospital length of stay was significantly longer in the fixed-dosing group, with a mean stay of 7.4 days (95% CI: 3.6-11.1) compared to 5.9 days (95% CI: 5.5-6.3) in the variable-dosing group (P < 0.001). The mean initial 4F-PCC dose was significantly higher with variable dosing than fixed dosing (38 IU/kg; 95% CI: 32-44 vs. 27 IU/kg; 95% CI: 26-28, P < 0.001). A fixed-dosing strategy appears to be a safe and effective alternative to variable weight-based dosing and was associated with lower 4F-PCC usage. However, direct comparative studies are needed to confirm these results.
Keywords	hemostasis ; hospitals ; meta-analysis ; mortality ; prothrombin ; research ; statistical models ; thrombosis ; anticoagulants ; anticoagulation reversal ; factor Xa inhibitors ; prothrombin complex concentrates
Language	English
Dates of publication	2023-02
Size	p. 100107
Publishing place	Elsevier Inc.
Document type	Article ; Online
Note	Use and reproduction
ISSN	2475-0379
DOI	10.1016/j.rpth.2023.100107
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: The impact of warfarin on overall survival in cancer patients.

Chiasakul, Thita / Zwicker, Jeffrey I

Thrombosis research

2021 Volume 213, Issue Suppl 1, Page(s) S113–S119

Abstract: Venous thromboembolism (VTE) is a common complication in patients with cancer. Warfarin has largely been replaced by low-molecular-weight heparin (LMWHs) and direct oral anticoagulants (DOACs) as the standard of care in cancer-associated VTE. The ... ...

Abstract	Venous thromboembolism (VTE) is a common complication in patients with cancer. Warfarin has largely been replaced by low-molecular-weight heparin (LMWHs) and direct oral anticoagulants (DOACs) as the standard of care in cancer-associated VTE. The survival benefit of these anticoagulants over warfarin in the cancer population was not demonstrated in clinical trials, possibly due to insufficient sample size and limited follow-up duration. There are emerging population-based studies suggesting that warfarin may be associated with improved overall survival in cancers and may have a protective effect against certain types of cancers. Warfarin may exert its anti-neoplastic properties through both coagulation pathway -dependent and -independent mechanisms, the latter of which are mediated by inhibition of the Gas6-AXL signaling pathway. Further research should emphasize on identifying clinical and laboratory predictors of beneficial effects of warfarin. In this review article, we summarize and update the current evidence regarding the potential impact of warfarin on the overall survival of cancer patients and incidence of cancer, as well as review the potential mechanism of such effect and future perspectives.
MeSH term(s)	Anticoagulants/adverse effects ; Heparin, Low-Molecular-Weight/therapeutic use ; Humans ; Neoplasms/complications ; Neoplasms/drug therapy ; Venous Thromboembolism/drug therapy ; Venous Thromboembolism/etiology ; Warfarin/adverse effects
Chemical Substances	Anticoagulants ; Heparin, Low-Molecular-Weight ; Warfarin (5Q7ZVV76EI)
Language	English
Publishing date	2021-11-14
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	121852-9
ISSN	1879-2472 ; 0049-3848
ISSN (online)	1879-2472
ISSN	0049-3848
DOI	10.1016/j.thromres.2021.11.004
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Article ; Online: Thrombolytic therapy in acute venous thromboembolism.

Chiasakul, Thita / Bauer, Kenneth A

Hematology. American Society of Hematology. Education Program

2020 Volume 2020, Issue 1, Page(s) 612–618

Abstract: Although anticoagulation remains the mainstay of treatment of acute venous thromboembolism (VTE), the use of thrombolytic agents or thrombectomy is required to immediately restore blood flow to thrombosed vessels. Nevertheless, systemic thrombolysis has ... ...

Abstract	Although anticoagulation remains the mainstay of treatment of acute venous thromboembolism (VTE), the use of thrombolytic agents or thrombectomy is required to immediately restore blood flow to thrombosed vessels. Nevertheless, systemic thrombolysis has not clearly been shown to improve outcomes in patients with large clot burdens in the lung or legs as compared with anticoagulation alone; this is in part due to the occurrence of intracranial hemorrhage in a small percentage of patients to whom therapeutic doses of a thrombolytic drug are administered. Algorithms have been developed to identify patients at high risk for poor outcomes resulting from large clot burdens and at low risk for major bleeding in an effort to improve outcomes in those receiving thrombolytic therapy. In acute pulmonary embolism (PE), hemodynamic instability is the key determinant of short-term survival and should prompt consideration of immediate thrombolysis. In hemodynamically stable PE, systemic thrombolysis is not recommended and should be used as rescue therapy if clinical deterioration occurs. Evidence is accumulating regarding the efficacy of administering reduced doses of thrombolytic agents systemically or via catheters directly into thrombi in an effort to lower bleed rates. In acute deep venous thrombosis, catheter-directed thrombolysis with thrombectomy can be used in severe or limb-threatening thrombosis but has not been shown to prevent postthrombotic syndrome. Because the management of acute VTE can be complex, having a rapid-response team (ie, PE response team) composed of physicians from different specialties may aid in the management of severely affected patients.
MeSH term(s)	Acute Disease ; Adult ; Algorithms ; Female ; Fibrinolytic Agents/adverse effects ; Fibrinolytic Agents/therapeutic use ; Humans ; Postthrombotic Syndrome/etiology ; Postthrombotic Syndrome/mortality ; Postthrombotic Syndrome/prevention & control ; Pulmonary Embolism/mortality ; Pulmonary Embolism/therapy ; Thrombolytic Therapy ; Venous Thromboembolism/mortality ; Venous Thromboembolism/therapy
Chemical Substances	Fibrinolytic Agents
Language	English
Publishing date	2020-12-04
Publishing country	United States
Document type	Case Reports ; Journal Article ; Review
ZDB-ID	2084287-9
ISSN	1520-4383 ; 1520-4391
ISSN (online)	1520-4383
ISSN	1520-4391
DOI	10.1182/hematology.2020000148
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Article ; Online: Communication from the ISTH SSC Subcommittee on Hemostasis and Malignancy: a meta-analysis to assess the risk of bleeding and thrombosis following chimeric antigen receptor T-cell therapy.

Bindal, Poorva / Patell, Rushad / Chiasakul, Thita / Lauw, Mandy N / Ko, Amica / Wang, Tzu-Fei / Zwicker, Jeffrey I

Journal of thrombosis and haemostasis : JTH

2024

Abstract: Background: Chimeric antigen receptor T-cell (CAR T-cell) therapy is increasingly utilized for treatment of hematologic malignancies. Hematologic toxicities including thrombosis and bleeding complications have been reported. Accurate estimates for ... ...

Abstract	Background: Chimeric antigen receptor T-cell (CAR T-cell) therapy is increasingly utilized for treatment of hematologic malignancies. Hematologic toxicities including thrombosis and bleeding complications have been reported. Accurate estimates for thrombotic and bleeding outcomes are lacking. Objectives: We performed a systematic review and meta-analysis in patients who received CAR T-cell therapy for an underlying hematologic malignancy with the objective to: a) assess the thrombosis and bleeding risk associated with CAR T-cell therapy, b) assess the impact of CRS and ICANS on the risks of thrombosis and bleeding, and c) assess the safety of anticoagulant or antiplatelet use in the period following treatment with CAR T-cell therapy. Methods: We searched MEDLINE, EMBASE, and Cochrane CENTRAL up to February 2022 for studies reporting thrombotic or bleeding outcomes in patients receiving CAR T-cell therapy. Pooled event rates were calculated using a random-effects model. We performed subgroup analyses stratified by follow-up duration, CAR T-cell target antigen, and underlying hematologic malignancy. Results: We included 47 studies with a total of 7040 patients. High heterogeneity between studies precluded reporting of overall pooled rates of thrombotic and bleeding events. In studies with follow-up duration of ≤6 months, the pooled incidence of venous thrombotic events was 2.4% (95% CI, 1.4%-3.4%; I Conclusion: The risk of both thrombosis and bleeding following CAR T-cell therapy appears to be highest in the initial months following infusion.
Language	English
Publishing date	2024-04-02
Publishing country	England
Document type	Journal Article
ZDB-ID	2112661-6
ISSN	1538-7836 ; 1538-7933
ISSN (online)	1538-7836
ISSN	1538-7933
DOI	10.1016/j.jtha.2024.03.021
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Article: The Pitfalls of Global Hemostasis Assays in Myeloproliferative Neoplasms and Future Challenges

Tiu, Andrew / Chiasakul, Thita / Kessler, Craig M.

Seminars in Thrombosis and Hemostasis

(Editorial Compilation - Part XIV)

2023 Volume 50, Issue 02, Page(s) 213–223

Series title	Editorial Compilation - Part XIV
Abstract	Venous and arterial thromboembolism are major complications of myeloproliferative neoplasms (MPNs), comprising polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Global hemostasis assays, including thrombin generation assay (TGA), rotational thromboelastometry (ROTEM), and thromboelastography (TEG), have been proposed as biomarkers to assess the hypercoagulability and thrombotic risk stratification in MPNs. We performed a systematic literature review on the parameters of TGA, ROTEM, and TEG and their association with thrombotic events and treatment strategies in MPNs. Thirty-two studies (all cross-sectional) were included, which collectively enrolled 1,062 controls and 1,608 MPN patients. Among the 13 studies that reported arterial or venous thrombosis, the overall thrombosis rate was 13.8% with 6 splanchnic thromboses reported. Out of the 27 TGA studies, there was substantial heterogeneity in plasma preparation and trigger reagents employed in laboratory assays. There was a trend toward increased peak height among all MPN cohorts versus controls and higher endogenous thrombin potential (ETP) between ET patients versus controls. There was an overall trend toward lower ETP between PV and PMF patients versus. controls. There were no substantial differences in ETP between JAK2-positive versus JAK2-negative MPNs, prior history versus negative history of thrombotic events, and among different treatment strategies. Of the three ROTEM studies, there was a trend toward higher maximum clot firmness and shorter clot formation times for all MPNs versus controls. The three TEG studies had mixed results. We conclude that the ability of parameters from global hemostasis assays to predict for hypercoagulability events in MPN patients is inconsistent and inconclusive. Further prospective longitudinal studies are needed to validate these biomarker tools so that thrombotic potential could be utilized as a primary endpoint of such studies.
Keywords	global hemostatic assays ; myeloproliferative neoplasms ; thrombin generation assay ; rotational thromboelastometry ; thromboelastography
Language	English
Publishing date	2023-04-17
Publisher	Thieme Medical Publishers, Inc.
Publishing place	Stuttgart ; New York
Document type	Article
ZDB-ID	196901-8
ISSN	1098-9064 ; 0094-6176
ISSN (online)	1098-9064
ISSN	0094-6176
DOI	10.1055/s-0043-57010
Database	Thieme publisher's database

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