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  1. Article ; Online: Thrombotic Thrombocytopenic Purpura: Beyond Empiricism and Plasma Exchange.

    Tsai, Han-Mou

    The American journal of medicine

    2019  Volume 132, Issue 9, Page(s) 1032–1037

    Abstract: For many years after its first description in 1924, thrombotic thrombocytopenic purpura was an intriguing puzzle for clinicians and researchers, not only for its unique pathology, perplexing changes in von Willebrand factor multimers, and high rate of ... ...

    Abstract For many years after its first description in 1924, thrombotic thrombocytopenic purpura was an intriguing puzzle for clinicians and researchers, not only for its unique pathology, perplexing changes in von Willebrand factor multimers, and high rate of rapid fatality but also for its dramatic response to plasma infusion or exchange. The discovery of ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats member-13) and its deficiency in patients with thrombotic thrombocytopenic purpura, due to inhibitory autoantibodies or genetic mutations, provides a mechanistic scheme for understanding its pathogenesis. This new knowledge quickly led to the use of rituximab to promote its remission and prevent recurrence. Recombinant ADAMTS13 is also under development to replace plasma infusion as the therapy for hereditary thrombotic thrombocytopenic purpura. Recently, caplacizumab, a bivalent nanobody targeting the glycoprotein 1b binding epitope of von Willebrand factor A1 domain, was approved as an addition to the current regimen of plasma exchange and immunomodulation for adult patients of acquired thrombotic thrombocytopenic purpura. This review discusses how the new treatment may improve patient outcomes and its potential pitfalls.
    MeSH term(s) ADAMTS13 Protein/deficiency ; ADAMTS13 Protein/genetics ; ADAMTS13 Protein/immunology ; Empiricism ; Fibrinolytic Agents/therapeutic use ; Hemorrhage/chemically induced ; Humans ; Immunologic Factors/therapeutic use ; Plasma Exchange ; Platelet Aggregation/drug effects ; Purpura, Thrombotic Thrombocytopenic/blood ; Purpura, Thrombotic Thrombocytopenic/genetics ; Purpura, Thrombotic Thrombocytopenic/therapy ; Randomized Controlled Trials as Topic ; Rituximab/therapeutic use ; Single-Domain Antibodies/therapeutic use ; Thrombosis/prevention & control ; von Willebrand Factor/antagonists & inhibitors
    Chemical Substances Fibrinolytic Agents ; Immunologic Factors ; Single-Domain Antibodies ; von Willebrand Factor ; caplacizumab (2R27AB6766) ; Rituximab (4F4X42SYQ6) ; ADAMTS13 Protein (EC 3.4.24.87) ; ADAMTS13 protein, human (EC 3.4.24.87)
    Language English
    Publishing date 2019-03-28
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 80015-6
    ISSN 1555-7162 ; 1873-2178 ; 0002-9343 ; 1548-2766
    ISSN (online) 1555-7162 ; 1873-2178
    ISSN 0002-9343 ; 1548-2766
    DOI 10.1016/j.amjmed.2019.03.009
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Stomatitis and Bone Marrow Suppression Followed by Leukoerythroblastosis in a Patient on Long-Term Low-Dose Methotrexate Therapy.

    Lien, Yeong-Hau H / Tsai, Han-Mou

    The American journal of medicine

    2022  Volume 135, Issue 11, Page(s) e423–e424

    MeSH term(s) Humans ; Methotrexate/adverse effects ; Bone Marrow ; Bone Marrow Diseases ; Stomatitis
    Chemical Substances Methotrexate (YL5FZ2Y5U1)
    Language English
    Publishing date 2022-07-23
    Publishing country United States
    Document type Case Reports
    ZDB-ID 80015-6
    ISSN 1555-7162 ; 1873-2178 ; 0002-9343 ; 1548-2766
    ISSN (online) 1555-7162 ; 1873-2178
    ISSN 0002-9343 ; 1548-2766
    DOI 10.1016/j.amjmed.2022.07.007
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Atypical Hemolytic Uremic Syndrome: Beyond Hemolysis and Uremia.

    Tsai, Han-Mou

    The American journal of medicine

    2018  Volume 132, Issue 2, Page(s) 161–167

    Abstract: Atypical hemolytic uremic syndrome commonly presents with the triad of microangiopathic hemolytic anemia, thrombocytopenia, and renal function impairment without an antecedent hemorrhagic diarrhea. Less known are extrarenal complications due to abnormal ... ...

    Abstract Atypical hemolytic uremic syndrome commonly presents with the triad of microangiopathic hemolytic anemia, thrombocytopenia, and renal function impairment without an antecedent hemorrhagic diarrhea. Less known are extrarenal complications due to abnormal vascular permeability, although these are a major cause of morbidity and mortality for the patients. Furthermore, it is increasingly recognized that the disease may present with hypertension or renal function impairment with no or mild thrombocytopenia and microangiopathic hemolytic anemia. Awareness of the full spectrum of atypical hemolytic uremic syndrome may facilitate its diagnosis and treatment before serious complications or death occurs.
    MeSH term(s) Atypical Hemolytic Uremic Syndrome/diagnosis ; Atypical Hemolytic Uremic Syndrome/pathology ; Complement Activation ; Hemolysis ; Humans ; Purpura, Thrombotic Thrombocytopenic/diagnosis ; Uremia/etiology ; Uremia/pathology
    Language English
    Publishing date 2018-08-24
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 80015-6
    ISSN 1555-7162 ; 1873-2178 ; 0002-9343 ; 1548-2766
    ISSN (online) 1555-7162 ; 1873-2178
    ISSN 0002-9343 ; 1548-2766
    DOI 10.1016/j.amjmed.2018.08.011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Does Anticomplement Therapy Have a Role in the Management of Malignant Hypertension?

    Tsai, Han-Mou

    Journal of clinical hypertension (Greenwich, Conn.)

    2015  Volume 18, Issue 4, Page(s) 359–360

    MeSH term(s) Blood Pressure/drug effects ; Complement Inactivator Proteins/therapeutic use ; Humans ; Hypertension, Malignant/drug therapy ; Hypertension, Malignant/physiopathology ; Male ; Middle Aged
    Chemical Substances Complement Inactivator Proteins ; anticomplement
    Language English
    Publishing date 2015-09-11
    Publishing country United States
    Document type Case Reports ; Letter
    ZDB-ID 2077222-1
    ISSN 1751-7176 ; 1524-6175
    ISSN (online) 1751-7176
    ISSN 1524-6175
    DOI 10.1111/jch.12664
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Measurement of ADAMTS13.

    Tsai, Han-Mou

    International review of thrombosis

    2015  Volume 1, Issue 4, Page(s) 272–280

    Abstract: ADAMTS13, encoded on chromosome 9q34, is a member of the ADAMTS (a disintegrin and metalloprotease with thrombospondin type 1 motif) metalloprotease family, containing the common domain structure of (from the amino terminus) signal peptide, propeptide, ... ...

    Abstract ADAMTS13, encoded on chromosome 9q34, is a member of the ADAMTS (a disintegrin and metalloprotease with thrombospondin type 1 motif) metalloprotease family, containing the common domain structure of (from the amino terminus) signal peptide, propeptide, reprolysin type metalloprotease, thrombospondin type 1 motif, cysteine-rich region, and spacer domain. ADAMTS13 cleaves von Willebrand factor (VWF) in a shear stress dependent manner. Deficiency of the enzyme causes the platelet aggregation of thrombotic thrombocytopenic purpura (TTP). Inhibitory antibodies of ADAMTS13 are detected in patients with acquired TTP, while homozygous or double heterozygous mutations of the ADAMTS13 gene cause the hereditary form of the disease 1. Targeting of the ADAMTS13 gene by recombinant technology has reproduced the phenotype of human TTP in ADAMTS13-null mice 2. Despite these advances, intense controversy and confusion persist regarding the role of ADAMTS13 assays in the diagnosis of TTP. This brief review highlights some of the contentious issues and proposes steps to improve the diagnostic value of ADAMTS13 assays.
    Language English
    Publishing date 2015-01-03
    Publishing country Japan
    Document type Journal Article
    ISSN 1880-8549
    ISSN 1880-8549
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: A mechanistic approach to the diagnosis and management of atypical hemolytic uremic syndrome.

    Tsai, Han-Mou

    Transfusion medicine reviews

    2014  Volume 28, Issue 4, Page(s) 187–197

    Abstract: Until recently, atypical hemolytic uremic syndrome (aHUS), conventionally defined in the pediatric literature as a syndrome of the triad of renal failure, microangiopathic hemolytic anemia, and thrombocytopenia without a prodrome of hemorrhagic diarrhea, ...

    Abstract Until recently, atypical hemolytic uremic syndrome (aHUS), conventionally defined in the pediatric literature as a syndrome of the triad of renal failure, microangiopathic hemolytic anemia, and thrombocytopenia without a prodrome of hemorrhagic diarrhea, has received little attention in adult practice because the patients are commonly given the diagnosis of thrombotic thrombocytopenic purpura (TTP) or TTP/HUS and treated as TTP with plasma exchange, augmented in refractory cases with rituximab and sometimes even splenectomy. Molecular studies have shown that the regulation of the alternative complement pathway is defective in many patients with conventionally defined aHUS. With this new knowledge and the findings of ADAMTS13 autoinhibitors or mutations in TTP, it is time to redefine aHUS as a disorder with propensity to the development of thrombotic microangiopathy due to defective regulation of the alternative complement pathway and TTP as a disorder with propensity to arteriolar and capillary thrombosis due to ADAMTS13 deficiency. This new definition provides a clear distinction of aHUS from TTP, encompasses patients without all 3 components of the triad, and provides the rationale for management with anticomplement therapy.
    MeSH term(s) ADAM Proteins/genetics ; ADAMTS13 Protein ; Adult ; Antibodies, Monoclonal, Humanized/therapeutic use ; Antibodies, Monoclonal, Murine-Derived/therapeutic use ; Atypical Hemolytic Uremic Syndrome/diagnosis ; Atypical Hemolytic Uremic Syndrome/therapy ; Comorbidity ; Complement System Proteins ; Diagnosis, Differential ; Gene Deletion ; Hematopoietic Stem Cells/cytology ; Humans ; Mutation ; Purpura, Thrombotic Thrombocytopenic/diagnosis ; Rituximab ; Splenectomy ; Treatment Outcome
    Chemical Substances Antibodies, Monoclonal, Humanized ; Antibodies, Monoclonal, Murine-Derived ; Rituximab (4F4X42SYQ6) ; Complement System Proteins (9007-36-7) ; eculizumab (A3ULP0F556) ; ADAM Proteins (EC 3.4.24.-) ; ADAMTS13 Protein (EC 3.4.24.87) ; ADAMTS13 protein, human (EC 3.4.24.87)
    Language English
    Publishing date 2014-09-03
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 639107-2
    ISSN 1532-9496 ; 0887-7963
    ISSN (online) 1532-9496
    ISSN 0887-7963
    DOI 10.1016/j.tmrv.2014.08.004
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  7. Article ; Online: In Reply.

    Tsai, Han-Mou / Kuo, Elizabeth

    Obstetrics and gynecology

    2016  Volume 128, Issue 3, Page(s) 657–658

    Language English
    Publishing date 2016-05-20
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 207330-4
    ISSN 1873-233X ; 0029-7844
    ISSN (online) 1873-233X
    ISSN 0029-7844
    DOI 10.1097/AOG.0000000000001611
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  8. Article ; Online: Myocardial Infarction with Limb Arterial and Venous Thrombosis in a Patient with Enoxaparin-Induced Thrombocytopenia.

    Singh, Navdeep / Singh Lubana, Sandeep / Tsai, Han-Mou

    The American journal of case reports

    2020  Volume 21, Page(s) e922498

    Abstract: BACKGROUND Heparin, often used as an anticoagulant, acts by binding to antithrombin III. Indeed, heparin binds to a variety of proteins other than antithrombin III. Among them, platelet factor 4 can bind and neutralize the anticoagulant activity of ... ...

    Abstract BACKGROUND Heparin, often used as an anticoagulant, acts by binding to antithrombin III. Indeed, heparin binds to a variety of proteins other than antithrombin III. Among them, platelet factor 4 can bind and neutralize the anticoagulant activity of heparin. Upon binding with heparin, platelet factor 4 undergoes a conformational change and expresses immunogenic neo-epitopes that induce the generation of antibodies of the platelet factor 4 heparin complex. This immune reaction may lead to thrombocytopenia and venous, arterial, or microvascular thrombosis. However, the risk of such complications is quite variable, as it is affected not only by the source and dose of heparin and the clinical condition (e.g., cardiovascular surgery and orthopedic surgery) of the patient, but also the molecular size of the heparin formulation. Venous, arterial, and small-vessel thrombosis can lead to leg swelling, pulmonary embolism, stroke, skin necrosis, or gangrene requiring limb amputation or intestinal resection. Myocardial infarction due to coronary thrombosis also occurs, although it is less common and can be readily recognized. CASE REPORT Heparin-induced thrombocytopenia (HIT) is a potentially life-threatening complication of heparin therapy. We report the case of a 67-year-old woman who developed ST-segment elevation myocardial infarction and thrombocytopenia within 10 days of prophylactic enoxaparin therapy after undergoing bilateral total knee replacement surgery. She also had peripheral arterial and venous thrombosis. With thrombolysis and argatroban anticoagulation therapy, she recovered without residual sequelae. CONCLUSIONS Thrombocytopenia with coronary and other vascular thrombosis is a potentially serious complication of heparin therapy. A trend of decreased platelet count, decreased platelet count by 30% or more, and/or occurrence of any type of thrombosis should raise the suspicion of HIT. This case demonstrates that early recognition and prompt treatment of HIT can be life-saving.
    MeSH term(s) Aged ; Antithrombins/therapeutic use ; Arginine/analogs & derivatives ; Arginine/therapeutic use ; Enoxaparin/adverse effects ; Factor Xa Inhibitors/therapeutic use ; Female ; Humans ; Pipecolic Acids/therapeutic use ; Pyrazoles/therapeutic use ; Pyridones/therapeutic use ; ST Elevation Myocardial Infarction/chemically induced ; ST Elevation Myocardial Infarction/diagnosis ; ST Elevation Myocardial Infarction/drug therapy ; Sulfonamides/therapeutic use ; Thrombocytopenia/chemically induced ; Thrombocytopenia/diagnosis ; Thrombocytopenia/drug therapy ; Thrombosis/chemically induced ; Thrombosis/diagnosis ; Thrombosis/drug therapy
    Chemical Substances Antithrombins ; Enoxaparin ; Factor Xa Inhibitors ; Pipecolic Acids ; Pyrazoles ; Pyridones ; Sulfonamides ; apixaban (3Z9Y7UWC1J) ; Arginine (94ZLA3W45F) ; argatroban (IY90U61Z3S)
    Language English
    Publishing date 2020-05-29
    Publishing country United States
    Document type Case Reports ; Journal Article
    ZDB-ID 2517183-5
    ISSN 1941-5923 ; 1941-5923
    ISSN (online) 1941-5923
    ISSN 1941-5923
    DOI 10.12659/AJCR.922498
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Thrombotic thrombocytopenic purpura and the atypical hemolytic uremic syndrome: an update.

    Tsai, Han-Mou

    Hematology/oncology clinics of North America

    2013  Volume 27, Issue 3, Page(s) 565–584

    Abstract: Since the last review in 2007 of thrombotic thrombocytopenic purpura (TTP) and microangiopathic hemolytic anemia in the Clinics, further understanding of the nature of TTP and atypical hemolytic uremic syndrome (aHUS) has led to increasing use of ... ...

    Abstract Since the last review in 2007 of thrombotic thrombocytopenic purpura (TTP) and microangiopathic hemolytic anemia in the Clinics, further understanding of the nature of TTP and atypical hemolytic uremic syndrome (aHUS) has led to increasing use of rituximab in the treatment of TTP and the approval in 2011 of eculizumab for the treatment of aHUS. With this new armamentarium, distinction of aHUS from TTP has become more critical than ever. This article updates the new knowledge, highlights the difference between aHUS and TTP, and presents a scheme for their diagnosis and management.
    MeSH term(s) ADAM Proteins ; ADAMTS13 Protein ; Adult ; Animals ; Atypical Hemolytic Uremic Syndrome ; Diagnosis, Differential ; Female ; Hemolytic-Uremic Syndrome/diagnosis ; Hemolytic-Uremic Syndrome/etiology ; Hemolytic-Uremic Syndrome/therapy ; Humans ; Male ; Middle Aged ; Purpura, Thrombotic Thrombocytopenic/diagnosis ; Purpura, Thrombotic Thrombocytopenic/etiology ; Purpura, Thrombotic Thrombocytopenic/therapy
    Chemical Substances ADAM Proteins (EC 3.4.24.-) ; ADAMTS13 Protein (EC 3.4.24.87) ; ADAMTS13 protein, human (EC 3.4.24.87)
    Language English
    Publishing date 2013-04-09
    Publishing country United States
    Document type Case Reports ; Journal Article ; Review
    ZDB-ID 93115-9
    ISSN 1558-1977 ; 0889-8588
    ISSN (online) 1558-1977
    ISSN 0889-8588
    DOI 10.1016/j.hoc.2013.02.006
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  10. Article ; Online: Untying the knot of thrombotic thrombocytopenic purpura and atypical hemolytic uremic syndrome.

    Tsai, Han-Mou

    The American journal of medicine

    2013  Volume 126, Issue 3, Page(s) 200–209

    Abstract: Patients presenting with microangiopathic hemolysis and thrombocytopenia are often given the diagnosis of thrombotic thrombocytopenic purpura and treated with plasma exchange until the acute episode is over. Recent findings have shown that acquired ... ...

    Abstract Patients presenting with microangiopathic hemolysis and thrombocytopenia are often given the diagnosis of thrombotic thrombocytopenic purpura and treated with plasma exchange until the acute episode is over. Recent findings have shown that acquired thrombotic thrombocytopenic purpura is a chronic autoimmune disease with inhibitory antibodies of a disintegrin and metalloprotease with thrombospondin repeat, member 13 and are at risk of relapses that may be preventable. Furthermore, many of the patients given the diagnosis of thrombotic thrombocytopenic purpura really have atypical hemolytic uremic syndrome due to defective complement regulation that can be more effectively treated to prevent death and end-stage renal failure with eculizumab, a humanized monoclonal antibody of complement C5. These advances indicate that an accurate differential diagnosis of microangiopathic hemolysis is essential for optimal patient management.
    MeSH term(s) Atypical Hemolytic Uremic Syndrome ; Complement Activation/physiology ; Diagnosis, Differential ; Hemolytic-Uremic Syndrome/diagnosis ; Hemolytic-Uremic Syndrome/etiology ; Hemolytic-Uremic Syndrome/physiopathology ; Hemolytic-Uremic Syndrome/therapy ; Humans ; Purpura, Thrombotic Thrombocytopenic/diagnosis ; Purpura, Thrombotic Thrombocytopenic/etiology ; Purpura, Thrombotic Thrombocytopenic/physiopathology ; Purpura, Thrombotic Thrombocytopenic/therapy
    Language English
    Publishing date 2013-03
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 80015-6
    ISSN 1555-7162 ; 1873-2178 ; 0002-9343 ; 1548-2766
    ISSN (online) 1555-7162 ; 1873-2178
    ISSN 0002-9343 ; 1548-2766
    DOI 10.1016/j.amjmed.2012.09.006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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