Comparing thrombin generation in patients with hemophilia A and patients on vitamin K antagonists
Essentials It is unknown if hemophilia patients with atrial fibrillation need anticoagulation. Endogenous thrombin potentials (ETP) in hemophilia patients and patients on coumarins were compared. Severe hemophilia patients had comparable ETP to therapeutic international normalized ratio (INR). In no...
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| Veröffentlicht in: | Journal of thrombosis and haemostasis 2017-05, Vol.15 (5), p.868-875 |
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| creator | Koning, M. L. Y. Fischer, K. Laat, B. Huisman, A. Ninivaggi, M. Schutgens, R. E. G. |
| description | Essentials
It is unknown if hemophilia patients with atrial fibrillation need anticoagulation.
Endogenous thrombin potentials (ETP) in hemophilia patients and patients on coumarins were compared.
Severe hemophilia patients had comparable ETP to therapeutic international normalized ratio (INR).
In non‐severe hemophilia, 33% had higher ETP than therapeutic INR and may need anticoagulation.
Click to hear Dr Negrier's perspective on global assays for assessing coagulation
Summary
Background
It is unknown whether patients with hemophilia A with atrial fibrillation require treatment with vitamin K antagonists (VKAs) to the same extent as the normal population.
Objective
To compare hemostatic potential in hemophilia patients and patients on VKAs using thrombin generation (TG).
Methods
In this cross‐sectional study, TG, initiated with 1pM tissue factor, was measured in 133 patients with severe (FVIII < 1%, n = 15) and non‐severe (FVIII 1–50%, n = 118) hemophilia A, 97 patients on a VKA with an international normalized ratio (INR) ≥ 1.5 and healthy controls. Endogenous thrombin potential (ETP) (nm*min) was compared according to FVIII level (< 1%, 1–19% and 20–50%) with healthy controls and patients with sub‐therapeutic INR (1.5–1.9) and therapeutic INR (≥ 2.0). Medians and interquartile ranges (IQRs) were calculated.
Results
Compared with healthy controls (898 [IQR 803–1004]), both hemophilia patients and patients on VKAs had lower median ETPs at 304 (196–449) and 176 (100–250), respectively. ETP was quite similar in severe hemophilia patients (185 [116–307]) and patients with a therapeutic INR (156 [90–225]). Compared with patients with therapeutic INR, ETP in patients with FVIII 1–19% and patients with FVIII 20–50% was higher at 296 (203–430) and 397 (219–632), respectively. All patients with therapeutic INR had an ETP < 400. Considering this threshold, 93% of severe hemophilia patients, 70% of patients with FVIII 1–19% and 52% of patients with FVIII 20–50% had an ETP < 400.
Conclusion
In severe hemophilia patients, TG was comparable to that in patients with a therapeutic INR. In one‐third of non‐severe hemophilia patients, TG was higher. These results suggest that anticoagulation therapy should be considered in a substantial proportion of non‐severe hemophilia patients. |
| doi_str_mv | 10.1111/jth.13674 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_1895084890</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1895084890</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3884-813b308da7783e1ae245f4826679c680d2ce2f3575d3f2202652cf75a91fea673</originalsourceid><addsrcrecordid>eNp1kE1PwzAMhiMEYmNw4A-gSpw4dOSjTZPjNAEDJnEZ5yhr0zXTmpQkY9q_J9ANTvhiW3782noBuEZwjGLcr0MzRoQW2QkYopywtGCEnh5rTsgAXHi_hhDxHMNzMMAMc4owHwI5tW0nnTarJDTOtkttkpUyysmgrUli18VKmeCTnQ5N0qjWdo3eaJlMEmmqv3GkP3WQbVx5jZMgV9ZoH_wlOKvlxqurQx6B98eHxXSWzt-enqeTeVoSxrKUIbIkkFWyiM8rJBXO8jpjmNKCl5TBCpcK1yQv8orUGENMc1zWRS45qpWkBRmB2163c_Zjq3wQa7t1Jp4UiPEcsoxxGKm7niqd9d6pWnROt9LtBYLi20wRzRQ_Zkb25qC4Xbaq-iWP7kXgvgd2eqP2_yuJl8Wsl_wCgcJ-Fg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1895084890</pqid></control><display><type>article</type><title>Comparing thrombin generation in patients with hemophilia A and patients on vitamin K antagonists</title><source>MEDLINE</source><source>Alma/SFX Local Collection</source><source>EZB Electronic Journals Library</source><creator>Koning, M. L. Y. ; Fischer, K. ; Laat, B. ; Huisman, A. ; Ninivaggi, M. ; Schutgens, R. E. G.</creator><creatorcontrib>Koning, M. L. Y. ; Fischer, K. ; Laat, B. ; Huisman, A. ; Ninivaggi, M. ; Schutgens, R. E. G.</creatorcontrib><description>Essentials
It is unknown if hemophilia patients with atrial fibrillation need anticoagulation.
Endogenous thrombin potentials (ETP) in hemophilia patients and patients on coumarins were compared.
Severe hemophilia patients had comparable ETP to therapeutic international normalized ratio (INR).
In non‐severe hemophilia, 33% had higher ETP than therapeutic INR and may need anticoagulation.
Click to hear Dr Negrier's perspective on global assays for assessing coagulation
Summary
Background
It is unknown whether patients with hemophilia A with atrial fibrillation require treatment with vitamin K antagonists (VKAs) to the same extent as the normal population.
Objective
To compare hemostatic potential in hemophilia patients and patients on VKAs using thrombin generation (TG).
Methods
In this cross‐sectional study, TG, initiated with 1pM tissue factor, was measured in 133 patients with severe (FVIII < 1%, n = 15) and non‐severe (FVIII 1–50%, n = 118) hemophilia A, 97 patients on a VKA with an international normalized ratio (INR) ≥ 1.5 and healthy controls. Endogenous thrombin potential (ETP) (nm*min) was compared according to FVIII level (< 1%, 1–19% and 20–50%) with healthy controls and patients with sub‐therapeutic INR (1.5–1.9) and therapeutic INR (≥ 2.0). Medians and interquartile ranges (IQRs) were calculated.
Results
Compared with healthy controls (898 [IQR 803–1004]), both hemophilia patients and patients on VKAs had lower median ETPs at 304 (196–449) and 176 (100–250), respectively. ETP was quite similar in severe hemophilia patients (185 [116–307]) and patients with a therapeutic INR (156 [90–225]). Compared with patients with therapeutic INR, ETP in patients with FVIII 1–19% and patients with FVIII 20–50% was higher at 296 (203–430) and 397 (219–632), respectively. All patients with therapeutic INR had an ETP < 400. Considering this threshold, 93% of severe hemophilia patients, 70% of patients with FVIII 1–19% and 52% of patients with FVIII 20–50% had an ETP < 400.
Conclusion
In severe hemophilia patients, TG was comparable to that in patients with a therapeutic INR. In one‐third of non‐severe hemophilia patients, TG was higher. These results suggest that anticoagulation therapy should be considered in a substantial proportion of non‐severe hemophilia patients.</description><identifier>ISSN: 1538-7933</identifier><identifier>ISSN: 1538-7836</identifier><identifier>EISSN: 1538-7836</identifier><identifier>DOI: 10.1111/jth.13674</identifier><identifier>PMID: 28296129</identifier><language>eng</language><publisher>England: Elsevier Limited</publisher><subject>Acenocoumarol - administration & dosage ; Acenocoumarol - adverse effects ; Adolescent ; Adult ; Aged ; Antagonists ; Anticoagulants - administration & dosage ; Anticoagulants - adverse effects ; atrial fibrillation ; Atrial Fibrillation - blood ; Atrial Fibrillation - diagnosis ; Atrial Fibrillation - drug therapy ; Blood Coagulation - drug effects ; Cardiac arrhythmia ; Case-Control Studies ; Coagulation ; coumarins ; Cross-Sectional Studies ; Drug Monitoring - methods ; factor VIII ; Female ; Fibrillation ; Hemophilia ; hemophilia A ; Hemophilia A - blood ; Hemophilia A - diagnosis ; Hemostasis - drug effects ; Humans ; International Normalized Ratio ; Kinetics ; Male ; Middle Aged ; Phenprocoumon - administration & dosage ; Phenprocoumon - adverse effects ; Severity of Illness Index ; Thrombin ; Thrombin - metabolism ; Tissue factor ; Vitamin K ; Vitamin K - antagonists & inhibitors ; Young Adult</subject><ispartof>Journal of thrombosis and haemostasis, 2017-05, Vol.15 (5), p.868-875</ispartof><rights>2017 International Society on Thrombosis and Haemostasis</rights><rights>2017 International Society on Thrombosis and Haemostasis.</rights><rights>Copyright © 2017 International Society on Thrombosis and Haemostasis</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3884-813b308da7783e1ae245f4826679c680d2ce2f3575d3f2202652cf75a91fea673</citedby><cites>FETCH-LOGICAL-c3884-813b308da7783e1ae245f4826679c680d2ce2f3575d3f2202652cf75a91fea673</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27915,27916</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28296129$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Koning, M. L. Y.</creatorcontrib><creatorcontrib>Fischer, K.</creatorcontrib><creatorcontrib>Laat, B.</creatorcontrib><creatorcontrib>Huisman, A.</creatorcontrib><creatorcontrib>Ninivaggi, M.</creatorcontrib><creatorcontrib>Schutgens, R. E. G.</creatorcontrib><title>Comparing thrombin generation in patients with hemophilia A and patients on vitamin K antagonists</title><title>Journal of thrombosis and haemostasis</title><addtitle>J Thromb Haemost</addtitle><description>Essentials
It is unknown if hemophilia patients with atrial fibrillation need anticoagulation.
Endogenous thrombin potentials (ETP) in hemophilia patients and patients on coumarins were compared.
Severe hemophilia patients had comparable ETP to therapeutic international normalized ratio (INR).
In non‐severe hemophilia, 33% had higher ETP than therapeutic INR and may need anticoagulation.
Click to hear Dr Negrier's perspective on global assays for assessing coagulation
Summary
Background
It is unknown whether patients with hemophilia A with atrial fibrillation require treatment with vitamin K antagonists (VKAs) to the same extent as the normal population.
Objective
To compare hemostatic potential in hemophilia patients and patients on VKAs using thrombin generation (TG).
Methods
In this cross‐sectional study, TG, initiated with 1pM tissue factor, was measured in 133 patients with severe (FVIII < 1%, n = 15) and non‐severe (FVIII 1–50%, n = 118) hemophilia A, 97 patients on a VKA with an international normalized ratio (INR) ≥ 1.5 and healthy controls. Endogenous thrombin potential (ETP) (nm*min) was compared according to FVIII level (< 1%, 1–19% and 20–50%) with healthy controls and patients with sub‐therapeutic INR (1.5–1.9) and therapeutic INR (≥ 2.0). Medians and interquartile ranges (IQRs) were calculated.
Results
Compared with healthy controls (898 [IQR 803–1004]), both hemophilia patients and patients on VKAs had lower median ETPs at 304 (196–449) and 176 (100–250), respectively. ETP was quite similar in severe hemophilia patients (185 [116–307]) and patients with a therapeutic INR (156 [90–225]). Compared with patients with therapeutic INR, ETP in patients with FVIII 1–19% and patients with FVIII 20–50% was higher at 296 (203–430) and 397 (219–632), respectively. All patients with therapeutic INR had an ETP < 400. Considering this threshold, 93% of severe hemophilia patients, 70% of patients with FVIII 1–19% and 52% of patients with FVIII 20–50% had an ETP < 400.
Conclusion
In severe hemophilia patients, TG was comparable to that in patients with a therapeutic INR. In one‐third of non‐severe hemophilia patients, TG was higher. These results suggest that anticoagulation therapy should be considered in a substantial proportion of non‐severe hemophilia patients.</description><subject>Acenocoumarol - administration & dosage</subject><subject>Acenocoumarol - adverse effects</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Antagonists</subject><subject>Anticoagulants - administration & dosage</subject><subject>Anticoagulants - adverse effects</subject><subject>atrial fibrillation</subject><subject>Atrial Fibrillation - blood</subject><subject>Atrial Fibrillation - diagnosis</subject><subject>Atrial Fibrillation - drug therapy</subject><subject>Blood Coagulation - drug effects</subject><subject>Cardiac arrhythmia</subject><subject>Case-Control Studies</subject><subject>Coagulation</subject><subject>coumarins</subject><subject>Cross-Sectional Studies</subject><subject>Drug Monitoring - methods</subject><subject>factor VIII</subject><subject>Female</subject><subject>Fibrillation</subject><subject>Hemophilia</subject><subject>hemophilia A</subject><subject>Hemophilia A - blood</subject><subject>Hemophilia A - diagnosis</subject><subject>Hemostasis - drug effects</subject><subject>Humans</subject><subject>International Normalized Ratio</subject><subject>Kinetics</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Phenprocoumon - administration & dosage</subject><subject>Phenprocoumon - adverse effects</subject><subject>Severity of Illness Index</subject><subject>Thrombin</subject><subject>Thrombin - metabolism</subject><subject>Tissue factor</subject><subject>Vitamin K</subject><subject>Vitamin K - antagonists & inhibitors</subject><subject>Young Adult</subject><issn>1538-7933</issn><issn>1538-7836</issn><issn>1538-7836</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kE1PwzAMhiMEYmNw4A-gSpw4dOSjTZPjNAEDJnEZ5yhr0zXTmpQkY9q_J9ANTvhiW3782noBuEZwjGLcr0MzRoQW2QkYopywtGCEnh5rTsgAXHi_hhDxHMNzMMAMc4owHwI5tW0nnTarJDTOtkttkpUyysmgrUli18VKmeCTnQ5N0qjWdo3eaJlMEmmqv3GkP3WQbVx5jZMgV9ZoH_wlOKvlxqurQx6B98eHxXSWzt-enqeTeVoSxrKUIbIkkFWyiM8rJBXO8jpjmNKCl5TBCpcK1yQv8orUGENMc1zWRS45qpWkBRmB2163c_Zjq3wQa7t1Jp4UiPEcsoxxGKm7niqd9d6pWnROt9LtBYLi20wRzRQ_Zkb25qC4Xbaq-iWP7kXgvgd2eqP2_yuJl8Wsl_wCgcJ-Fg</recordid><startdate>201705</startdate><enddate>201705</enddate><creator>Koning, M. L. Y.</creator><creator>Fischer, K.</creator><creator>Laat, B.</creator><creator>Huisman, A.</creator><creator>Ninivaggi, M.</creator><creator>Schutgens, R. E. G.</creator><general>Elsevier Limited</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope><scope>K9.</scope></search><sort><creationdate>201705</creationdate><title>Comparing thrombin generation in patients with hemophilia A and patients on vitamin K antagonists</title><author>Koning, M. L. Y. ; Fischer, K. ; Laat, B. ; Huisman, A. ; Ninivaggi, M. ; Schutgens, R. E. G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3884-813b308da7783e1ae245f4826679c680d2ce2f3575d3f2202652cf75a91fea673</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Acenocoumarol - administration & dosage</topic><topic>Acenocoumarol - adverse effects</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Antagonists</topic><topic>Anticoagulants - administration & dosage</topic><topic>Anticoagulants - adverse effects</topic><topic>atrial fibrillation</topic><topic>Atrial Fibrillation - blood</topic><topic>Atrial Fibrillation - diagnosis</topic><topic>Atrial Fibrillation - drug therapy</topic><topic>Blood Coagulation - drug effects</topic><topic>Cardiac arrhythmia</topic><topic>Case-Control Studies</topic><topic>Coagulation</topic><topic>coumarins</topic><topic>Cross-Sectional Studies</topic><topic>Drug Monitoring - methods</topic><topic>factor VIII</topic><topic>Female</topic><topic>Fibrillation</topic><topic>Hemophilia</topic><topic>hemophilia A</topic><topic>Hemophilia A - blood</topic><topic>Hemophilia A - diagnosis</topic><topic>Hemostasis - drug effects</topic><topic>Humans</topic><topic>International Normalized Ratio</topic><topic>Kinetics</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Phenprocoumon - administration & dosage</topic><topic>Phenprocoumon - adverse effects</topic><topic>Severity of Illness Index</topic><topic>Thrombin</topic><topic>Thrombin - metabolism</topic><topic>Tissue factor</topic><topic>Vitamin K</topic><topic>Vitamin K - antagonists & inhibitors</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Koning, M. L. Y.</creatorcontrib><creatorcontrib>Fischer, K.</creatorcontrib><creatorcontrib>Laat, B.</creatorcontrib><creatorcontrib>Huisman, A.</creatorcontrib><creatorcontrib>Ninivaggi, M.</creatorcontrib><creatorcontrib>Schutgens, R. E. G.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><jtitle>Journal of thrombosis and haemostasis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Koning, M. L. Y.</au><au>Fischer, K.</au><au>Laat, B.</au><au>Huisman, A.</au><au>Ninivaggi, M.</au><au>Schutgens, R. E. G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Comparing thrombin generation in patients with hemophilia A and patients on vitamin K antagonists</atitle><jtitle>Journal of thrombosis and haemostasis</jtitle><addtitle>J Thromb Haemost</addtitle><date>2017-05</date><risdate>2017</risdate><volume>15</volume><issue>5</issue><spage>868</spage><epage>875</epage><pages>868-875</pages><issn>1538-7933</issn><issn>1538-7836</issn><eissn>1538-7836</eissn><abstract>Essentials
It is unknown if hemophilia patients with atrial fibrillation need anticoagulation.
Endogenous thrombin potentials (ETP) in hemophilia patients and patients on coumarins were compared.
Severe hemophilia patients had comparable ETP to therapeutic international normalized ratio (INR).
In non‐severe hemophilia, 33% had higher ETP than therapeutic INR and may need anticoagulation.
Click to hear Dr Negrier's perspective on global assays for assessing coagulation
Summary
Background
It is unknown whether patients with hemophilia A with atrial fibrillation require treatment with vitamin K antagonists (VKAs) to the same extent as the normal population.
Objective
To compare hemostatic potential in hemophilia patients and patients on VKAs using thrombin generation (TG).
Methods
In this cross‐sectional study, TG, initiated with 1pM tissue factor, was measured in 133 patients with severe (FVIII < 1%, n = 15) and non‐severe (FVIII 1–50%, n = 118) hemophilia A, 97 patients on a VKA with an international normalized ratio (INR) ≥ 1.5 and healthy controls. Endogenous thrombin potential (ETP) (nm*min) was compared according to FVIII level (< 1%, 1–19% and 20–50%) with healthy controls and patients with sub‐therapeutic INR (1.5–1.9) and therapeutic INR (≥ 2.0). Medians and interquartile ranges (IQRs) were calculated.
Results
Compared with healthy controls (898 [IQR 803–1004]), both hemophilia patients and patients on VKAs had lower median ETPs at 304 (196–449) and 176 (100–250), respectively. ETP was quite similar in severe hemophilia patients (185 [116–307]) and patients with a therapeutic INR (156 [90–225]). Compared with patients with therapeutic INR, ETP in patients with FVIII 1–19% and patients with FVIII 20–50% was higher at 296 (203–430) and 397 (219–632), respectively. All patients with therapeutic INR had an ETP < 400. Considering this threshold, 93% of severe hemophilia patients, 70% of patients with FVIII 1–19% and 52% of patients with FVIII 20–50% had an ETP < 400.
Conclusion
In severe hemophilia patients, TG was comparable to that in patients with a therapeutic INR. In one‐third of non‐severe hemophilia patients, TG was higher. These results suggest that anticoagulation therapy should be considered in a substantial proportion of non‐severe hemophilia patients.</abstract><cop>England</cop><pub>Elsevier Limited</pub><pmid>28296129</pmid><doi>10.1111/jth.13674</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1538-7933 |
| ispartof | Journal of thrombosis and haemostasis, 2017-05, Vol.15 (5), p.868-875 |
| issn | 1538-7933 1538-7836 1538-7836 |
| language | eng |
| recordid | cdi_proquest_journals_1895084890 |
| source | MEDLINE; Alma/SFX Local Collection; EZB Electronic Journals Library |
| subjects | Acenocoumarol - administration & dosage Acenocoumarol - adverse effects Adolescent Adult Aged Antagonists Anticoagulants - administration & dosage Anticoagulants - adverse effects atrial fibrillation Atrial Fibrillation - blood Atrial Fibrillation - diagnosis Atrial Fibrillation - drug therapy Blood Coagulation - drug effects Cardiac arrhythmia Case-Control Studies Coagulation coumarins Cross-Sectional Studies Drug Monitoring - methods factor VIII Female Fibrillation Hemophilia hemophilia A Hemophilia A - blood Hemophilia A - diagnosis Hemostasis - drug effects Humans International Normalized Ratio Kinetics Male Middle Aged Phenprocoumon - administration & dosage Phenprocoumon - adverse effects Severity of Illness Index Thrombin Thrombin - metabolism Tissue factor Vitamin K Vitamin K - antagonists & inhibitors Young Adult |
| title | Comparing thrombin generation in patients with hemophilia A and patients on vitamin K antagonists |
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