Cover......Page 1
Copyright......Page 2
Dedication......Page 6
Contributors......Page 8
Preface......Page 14
General Information......Page 16
The Consultative Process......Page 17
Comprehensive Consultation......Page 18
The Curbside Consultation......Page 19
Other Third Parties......Page 20
Inappropriate Consultations......Page 21
Duties of the Referring Physician and the Consultant......Page 22
Role of the Clinical Laboratory......Page 23
Concerns......Page 24
Consultant Assumes Primary Care of the Patient......Page 25
Duration of Consultation......Page 26
When a Diagnosis Is Not Forthcoming......Page 27
When Should A Consultant Request Consultation?......Page 28
References......Page 29
The Clinical Evaluation......Page 31
Have you ever experienced excessive vaginal bleeding during pregnancy or immediately after childbirth or perineal bleeding.........Page 32
Have you ever developed hemarthrosis, retroperitoneal hematoma, or soft tissue hematoma in the absence of major trauma?......Page 33
Do you have any known medical problems?......Page 34
Objective Findings on the Physical Examination......Page 35
Basic Laboratory Evaluation of Coagulation and Hemostasis......Page 36
Basic Laboratory Tests to Distinguish Between Platelet and Coagulation Defects......Page 38
Laboratory Assessment of the Procoagulant System......Page 41
Tests for Lupus Anticoagulants (LA)......Page 43
Formulation of Treatment Strategies for the Management of Acute Hemorrhagic Episodes: How To Use Data From the Coagulation Lab......Page 45
References......Page 47
Phylogeny......Page 49
Input-Output Device......Page 50
Endothelial Functions......Page 51
Endothelium and Hemostasis......Page 52
Diagnosis......Page 54
References......Page 55
Hemorrhagic Processes......Page 57
Prenatal Diagnosis/Carrier Testing......Page 59
Postnatal Diagnosis......Page 60
Intra-articular Bleeding: Hemarthroses and Hemophilic Arthropathy......Page 61
Hematuria......Page 62
Laboratory Characteristics......Page 63
Hemophilia Treatment Centers......Page 64
Clotting Factor Replacement Therapy With Coagulation Factor Concentrates......Page 65
Fibrin Glues or Sealants......Page 68
Inhibitors......Page 69
Gene Therapy......Page 71
References......Page 72
Clinical Manifestations......Page 75
Diagnosis......Page 76
Treatment......Page 77
Diagnosis......Page 78
Pathogenesis and Genetics......Page 79
Treatment......Page 80
Differential Diagnosis......Page 81
Clinical Manifestations......Page 82
Diagnosis......Page 83
Clinical Manifestations......Page 84
Factor XII Deficiency......Page 85
Clinical Manifestations......Page 86
Diagnosis......Page 87
Differential Diagnosis......Page 88
Protein Z Deficiency......Page 89
References......Page 90
Inhibitor Specificity......Page 95
Quantitative Assays of Coagulation Factor Inhibitors......Page 96
Concomitant Conditions......Page 97
Management of Acute Bleeding......Page 99
Recombinant Activated Factor VII......Page 100
Intravenous Immune Globulin......Page 101
Inhibitors of Factor IX......Page 102
Inhibitors of Factor V......Page 103
Final Considerations......Page 104
References......Page 105
Physiology and Structure-Function Relationships......Page 111
Platelet-Related Functions of von Willebrand Factor......Page 112
von Willebrand Factor Levels in Health and Disease......Page 113
Laboratory Assays for von Willebrand Factor......Page 114
Pitfalls in Making the Diagnosis of VWD......Page 115
Type 1......Page 116
Type 2N......Page 117
Inherited VWD......Page 118
DDAVP......Page 119
Practical Considerations for Therapy......Page 120
References......Page 121
Introduction......Page 125
Relation of Bleeding Risks to Platelet Count......Page 126
The Biology of Platelet Production......Page 127
Causes of Thrombocytopenia......Page 128
Medical History......Page 129
Laboratory Investigations......Page 130
When should prophylactic platelet transfusions be given?......Page 131
Enhanced Hemostatic Function......Page 132
References......Page 133
Pathogenesis......Page 137
Evaluation of a Patient Who Presents with Isolated Thrombocytopenia......Page 138
Differential Diagnosis of ITP......Page 140
Drug-Induced Thrombocytopenia......Page 141
Congenital Thrombocytopenias......Page 142
Initial Management of ITP in Children......Page 143
Initial Treatment of Adult Patients who Present with Severe Thrombocytopenia and Symptomatic Purpura......Page 144
Splenectomy......Page 145
Glucocorticoids......Page 146
Vinca Alkaloids......Page 147
Management of ITP in Pregnant Women and their Newborn Infants......Page 148
References......Page 149
Does the Patient Have a Platelet-Related Bleeding Disorder?......Page 153
Medication-Related Disorders......Page 155
Hypersplenism......Page 156
Congenital platelet disorders with a normal platelet count......Page 157
Glanzmann thrombasthenia......Page 158
Other receptor defects......Page 159
Cheacutediak-Higashi syndrome......Page 160
Wiskott-Aldrich Syndrome/X-linked Thrombocytopenia......Page 161
Congenital Amegakaryocytic Thrombocytopenia......Page 162
GP-Ib/IX/V Receptor Defects (Bernard-Soulier Syndrome, Mediterranean Macrothrombocytopenia, and Velocardiofacial [DiGeorge] Syndrome......Page 163
MYH9-Related Thrombocytopenia (May-Hegglin, Sebastian, Fechtner, and Epstein Syndromes)......Page 164
GATA1-Related Thrombocytopenia......Page 165
Treatment of Patients With platelet-related bleeding (general guidelines)......Page 166
Conclusions......Page 167
References......Page 168
Macrovascular Disruption......Page 173
Ehlers-Danlos Syndrome......Page 174
Marfan Syndrome and Cystic Medial Degeneration......Page 175
Arteriovenous Malformations/Hemangiomas......Page 176
Hereditary Hemorrhagic Telangiectasia......Page 177
Historical Perspective......Page 179
Purpura Not Associated with Known Microvascular Pathology......Page 180
Psychogenic Purpura......Page 181
Progressive Pigmented Purpura......Page 182
Purpura Associated With Abnormal Platelet Function......Page 183
Cutaneous Vasculitis......Page 184
Hypercortisolism......Page 186
Amyloidosis......Page 187
Warfarin Skin Necrosis......Page 188
Fat Embolism Syndrome......Page 189
Blue Toe Syndrome, Purple Toe Syndrome, and Cholesterol Emboli Syndrome......Page 190
Livedo Reticularis......Page 191
Consultation Considerations......Page 192
References......Page 193
Physiology and Pathophysiology......Page 197
Initiation of Disseminated Intravascular Coagulation......Page 199
Closed Head Injury......Page 200
Placental Abnormalities......Page 201
Diagnosis of Disseminated Intravascular Coagulation......Page 202
Differential Diagnosis of Disseminated Intravascular Coagulation......Page 203
Consequences of Disseminated Intravascular Coagulation......Page 207
Treatment of Patients With Disseminated Intravascular Coagulation......Page 208
Consultation Considerations......Page 209
References......Page 210
General Aspects of Primary Hemostasis, Coagulation, and Fibrinolysis......Page 213
Endothelial Activation and its Effects on Coagulation during Inflammation......Page 214
Inflammatory Networks in Gram-Negative Sepsis......Page 215
Early and Late Effects Merge in Models ofΒSepsis and DIC......Page 216
Gram-Positive Bacteria......Page 217
Fungal and Parasitic Infections......Page 218
Restoration of Anticoagulant Pathways......Page 219
References......Page 220
Thrombotic Processes......Page 226
Indications for Thrombophilia Testing: Why should I test for thrombophilia?......Page 227
Counseling and Screening Asymptomatic Family Members......Page 228
Primary Prevention of Incident Venous Thromboembolism......Page 229
Secondary Prevention of Recurrent VTE......Page 231
Suggested Revised Recommendations......Page 232
Diagnostic Thrombophilia Testing: For what should I test?......Page 233
Arterial Thrombosis......Page 235
Acute Therapy......Page 236
Secondary Prophylaxis......Page 237
Antithrombin III Deficiency......Page 238
Protein C Deficiency......Page 239
Protein S Deficiency......Page 240
Deficiencies of Other Natural Anticoagulants (TFPI, Protein Z, Z-Dependent Protease Inhibitor, and Heparin Cofactor II)......Page 241
Increased Prothrombin (Factor II) Level/Prothrombin 20210 Mutation......Page 242
Increased Factors VII, VIII, IX, X, and XI, and von Willebrand Factor......Page 243
Increased Homocysteine (Homocystinuria; Hyperhomocysteinemia)/Methylene-Tetrahydrofolate Reductase (MTHFR)......Page 244
Activated Protein C Resistance/Factor V Leiden......Page 246
Increased Factor XIII Activity/Factor XIII Polymorphisms......Page 247
Paroxysmal Nocturnal Hemoglobinuria......Page 248
References......Page 250
Venous Ultrasonography......Page 259
Clinical Evaluation......Page 260
Screening With Blood Tests......Page 261
Echocardiography......Page 262
Echocardiography......Page 263
Low Molecular Weight Heparin......Page 264
Embolectomy......Page 265
Acute PE......Page 266
Optimal Duration of Anticoagulation......Page 267
References......Page 268
Importance To The Patient And The Clinician......Page 271
Overview......Page 272
Causes......Page 273
Overview......Page 274
Causes/Signs and Symptoms......Page 275
Treatment......Page 276
Treatment......Page 277
Causes......Page 278
Treatment......Page 279
Diagnosis......Page 280
Treatment......Page 281
Causes......Page 282
Causes......Page 283
Treatment......Page 284
Causes......Page 285
Diagnosis......Page 286
Adrenal Gland......Page 287
Consultation Considerations......Page 288
References......Page 289
Pathophysiology......Page 295
Symptoms......Page 297
Risk Factors......Page 298
Intravascular Ultrasound......Page 299
Venography......Page 300
Prevention......Page 301
Ligation and Stripping and Flush Ligation......Page 302
Surgical Treatment for Patients with VenousΒObstruction......Page 303
Venous Bypass Procedures......Page 304
References......Page 305
Familial Or Hereditary Thrombocytosis......Page 309
Essential Thrombocythemia......Page 310
Pathogenesis of Essential Thrombocythemia......Page 311
Criteria for the Diagnosis of Essential Thrombocythemia......Page 312
Coagulation Laboratory Features of Essential Thrombocythemia: The Paradox of.In Vivo Platelet Activation and Impaired Platelet Function......Page 314
Clinical Features and Thrombohemorrhagic Complications......Page 316
Treatment of Patients with Essential Thrombocythemia......Page 319
Hydroxyurea Therapy......Page 320
Anagrelide Therapy......Page 322
Recombinant Interferon-alpha......Page 324
Alkylating Agents and Radiophosphorus......Page 325
Pregnancy and Essential Thrombocythemia......Page 326
References......Page 327
beta2-Glycoprotein I (beta2GPI)......Page 333
Triggers for Hematologic Consultation......Page 335
Antiphospholipid Syndrome: Clinical Diagnosis......Page 336
Neurologic Manifestations of Antiphospholipid Syndrome......Page 337
Antiphospholipid Antibodies and Cardiac Dysfunction......Page 338
Bleeding Complications and Antiphospholipid Syndrome......Page 340
Lupus Anticoagulant......Page 341
Immunoassays......Page 342
APLA Presenting as a Laboratory Abnormality......Page 343
Treatment of Patients Who Have the Antiphospholipid Syndrome......Page 344
Oral Anticoagulation Intensity......Page 345
Cost Containment and Medical-Legal Aspects of Testing for Lupus Anticoagulant and Antiphospholipid Syndrome......Page 346
References......Page 347
Platelets......Page 353
Coronary Arterial Thrombogenesis......Page 354
Activation of Coagulation Factors......Page 355
Idling Coagulation: Setting the Stage for Thrombotic Events......Page 356
Platelet-Directed Therapies......Page 357
Pharmacokinetics......Page 359
Secondary Prevention of Vascular Events......Page 360
Clopidogrel......Page 361
Percutaneous Coronary Stenting......Page 362
Clopidogrel Response Variability......Page 363
Clinical Experience......Page 364
Pharmacodynamics......Page 365
Agent-Specific Characteristics......Page 366
Clinical Experience......Page 367
Unfractionated Heparin......Page 368
Adverse Effects......Page 369
Synthetic Pentasaccharide......Page 370
Clinical Experience......Page 371
LMWH and Platelet GP-IIb/IIIa Receptor Antagonist Combination Therapy......Page 372
Clinical Use......Page 373
Comparative Benefits of Direct Thrombin Inhibitors......Page 374
Atheromas of the Ascending Aorta......Page 375
An Evolving View of Blood Transfusion......Page 376
Defining Hemorrhagic Risk......Page 378
References......Page 379
C-Reactive Protein......Page 385
Total Plasma Homocysteine......Page 387
Fibrinolysis......Page 389
References......Page 390
Vascular Laboratory and Imaging......Page 393
Cardiovascular Risk Reduction Therapies......Page 395
Smoking Cessation......Page 396
Antiplatelet Drug Therapy......Page 397
Angioplasty......Page 398
Conclusions......Page 400
References......Page 401
Idiopathic Venous Thromboembolism and Occult Cancer......Page 403
Incidence of Thrombosis in Patients with Malignancy......Page 404
Increased Risk of Venous Thromboembolism in Patients With Cancer Subjected to Surgery......Page 407
Tumor Procoagulants......Page 408
Medical Patients......Page 409
Secondary Prophylaxis......Page 410
Secondary Prevention-Best Choice of Anticoagulant and Appropriate Duration of Therapy......Page 411
Central Vein Thrombosis......Page 412
Anticoagulation Therapy and Survival in Cancer......Page 413
References......Page 414
Historical Review......Page 419
Types of Thrombotic Thrombocytopenic Purpura......Page 420
von Willebrand Factor, ADAMTS13, and Thrombotic Thrombocytopenic Purpura......Page 421
Other Observations......Page 425
Distinction Between Thrombotic Thrombocytopenic Purpura and Hemolytic-Uremic Syndrome......Page 426
Treatment of Patients With Thrombotic Thrombocytopenic Purpura......Page 428
New Approaches To Therapy......Page 430
References......Page 431
Pathogenesis......Page 435
Clinical Features......Page 437
Severity of Thrombocytopenia......Page 438
Venous Thrombosis......Page 439
Microvascular Thrombotic Complications of Warfarin......Page 440
Neurologic Syndromes......Page 441
Clinical Scoring System......Page 442
Washed Platelet Activation Assays......Page 443
Fluid Phase Enzyme Immunoassays......Page 444
Lepirudin......Page 445
Argatroban......Page 447
Direct Thrombin Inhibitor-Warfarin Overlap......Page 449
Danaparoid......Page 450
Adjunctive Treatments......Page 451
Treatment of Patients With Isolated Heparin-Induced Thrombocytopenia......Page 452
Cardiac Surgery......Page 453
Hemodialysis......Page 454
References......Page 455
Further Reading......Page 459
Therapeutic Measures......Page 462
Administration and Monitoring......Page 463
Indications......Page 464
Reversal of Oral Anticoagulation......Page 465
Heparin Resistance......Page 466
Indications......Page 467
Mechanism and Pharmacology......Page 468
Clinical Uses......Page 469
Choice of Heparin Versus LMWH......Page 470
Mechanism and Pharmacology......Page 471
Reversal of Effect......Page 472
References......Page 473
Traditional Blood Components......Page 475
Platelets......Page 476
Fresh Frozen Plasma......Page 477
Adverse Effects of Blood Transfusion Therapy......Page 478
Commercial Plasma Fractions......Page 479
Mechanism of Action......Page 480
Dose and Administration......Page 481
Indications......Page 482
Background......Page 484
Mechanisms of Action and Tachyphylaxis......Page 485
Indications......Page 486
Background......Page 488
Indications......Page 489
Aprotinin......Page 491
Mechanism of Action, Dose, and Administration......Page 492
Indications......Page 493
Toxicity......Page 495
Estrogens......Page 496
Management of patients who refuse or are refractory to blood transfusion therapy......Page 497
References......Page 498
Direct fibrinolytic agents......Page 505
Direct Thrombin Inhibitors and Platelet Glycoprotein-IIb-IIIa Antagonists......Page 506
Plasma proteolytic ("lytic") state......Page 507
Allergy and Embolism......Page 508
Deep Venous Thrombosis......Page 509
Pulmonary Embolism......Page 510
Myocardial Infarction......Page 511
References......Page 512
Collagen-Based Materials......Page 517
Gelatin-Based Materials......Page 518
Commercially Prepared Fibrin Sealants......Page 519
References......Page 521
Automated Apheresis......Page 523
Programming and Input of Patient Values......Page 524
Evaluation and Care of the Patient......Page 525
Rationale for TPE......Page 526
Thrombotic Microangiopathies Other Than Idiopathic TTP and TPE......Page 528
Rapidly Progressive Glomerulonephritis......Page 529
Use of TPE......Page 530
Rationale for Plateletpheresis......Page 531
Erythrocytapheresis (Red Blood Cell Exchange)......Page 532
Protozoan Infection......Page 533
Complications......Page 534
Hypocalcemia and Citrate Toxicity......Page 535
Photopheresis......Page 536
References......Page 537
Historical Perspective......Page 545
Permanent Filters......Page 546
Nonpermanent Filters......Page 547
Studies on the Efficacy of Inferior Vena Caval Filters......Page 549
Permanent Filters......Page 553
Should patients with permanent vena caval filters receive prophylactic anticoagulation?......Page 555
Failure of anticoagulant therapy......Page 556
Trauma......Page 558
Patients with Cancer......Page 559
Other Indications......Page 560
References......Page 561
Catheter Occlusion......Page 567
Occlusive Venous Thrombosis......Page 568
Superior Vena Cava Occlusion......Page 569
Prophylaxis against Venous Access Device-Related Thrombosis......Page 570
References......Page 571
Ginseng......Page 575
Glucosamine......Page 576
Coumarin-Containing Plants......Page 577
Miscellaneous Supplements......Page 578
References......Page 579
Issues Specific to Women......Page 582
Basic Science......Page 583
Stroke......Page 584
Hormonal Contraception and Thrombophilia......Page 585
Hormone Replacement Therapy and Thrombosis......Page 586
Hormone Replacement Therapy and Cardiovascular Disease......Page 587
Hormone Replacement Therapy and Stroke......Page 588
Hormone Replacement Therapy and Venous Thromboembolic Disease......Page 589
Selective Estrogen Receptor Modulators/Selective Estrogen Receptor Down-Regulators, Aromatase Inhibitors, and Thrombosis......Page 590
References......Page 592
von Willebrand Disease......Page 595
Therapy During Labor and Delivery......Page 596
Therapy During Prenatal Diagnostic Testing and for Anesthesia......Page 597
Hemophilias......Page 598
Preconception Counseling......Page 599
Thrombocytopenia......Page 600
Diagnosis......Page 601
Impact of Maternal Immune Thrombocytopenic Purpura on Fetal Platelet Count......Page 602
The HELLP Syndrome......Page 603
References......Page 604
Thrombophilia and Venous Thromboembolism During Pregnancy......Page 607
Diagnosis of Venous Thromboembolism During Pregnancy......Page 608
Osteoporosis......Page 609
Other Antithrombotic Agents......Page 610
Primary Prophylaxis of Venous Thromboembolism in Asymptomatic Women......Page 611
Delivery......Page 612
Antiphospholipid Antibodies and the Antiphospholipid Syndrome......Page 613
Secondary Prophylaxis in Women with PriorΒThrombosis......Page 614
Pregnancy-Associated Stroke......Page 615
Thrombophilia and Obstetric Complications......Page 616
Screening for Thrombophilia......Page 618
References......Page 619
Special Issues......Page 626
Surgery for Patients With Congenital Hemostatic Defects......Page 627
Thrombotic Signals as a Result of Surgery......Page 629
Cardiopulmonary Bypass Surgery......Page 630
Orthotopic Liver Transplantation......Page 632
Screening for Hemostatic Defects......Page 633
Invasive Procedures in Patients With Abnormal Coagulation Tests......Page 635
Esophagogastroduodenoscopy and Colonoscopy......Page 636
Central Venous Access Devices......Page 637
Invasive Procedures for Patients On Anticoagulant Therapy......Page 638
Consultation On Patients With Intraoperative Or Postoperative Hemorrhage......Page 639
References......Page 643
Patients with a Mechanical Prosthetic Heart Valve......Page 649
Patients with Venous Thromboembolism......Page 650
Risk of Bleeding Associated with Type of Surgery or Procedure......Page 651
Patients with a Mechanical Prosthetic Heart Valve......Page 652
Management Recommendations......Page 654
Discontinuation of Antiplatelet Therapy......Page 655
Role of Prophylactic Inferior Vena Cava Filter Placement......Page 656
Patients with Renal Insufficiency......Page 657
References......Page 658
Procoagulant Factors......Page 661
Platelets......Page 662
Disorders of the Fibrinolytic System......Page 663
Assessment of the Risk of Thrombosis and Anticoagulation......Page 664
Invasive Procedures......Page 665
Coagulation During Infection andΒSepsis......Page 666
Therapy of Hemostatic Abnormalities in Liver Disease......Page 667
Anhepatic Phase......Page 668
References......Page 669
Pharmacokinetics and Pharmacodynamics......Page 675
Warfarin and Drug Interactions......Page 676
Initiation and Maintenance Dosing......Page 678
Management of Nontherapeutic International Normalized Ratios......Page 679
Management of Oral Anticoagulation During Invasive Procedures......Page 680
Diagnostic Evaluation of Bleeding......Page 681
Anticoagulation Management Services......Page 682
References......Page 683
Overview of Hemostatic Point-of-Care Testing......Page 687
VerifyNow (Ultegra) Instrument......Page 689
PFA-100 Platelet Function Analyzer......Page 690
Home PT Testing Systems......Page 691
INRatio......Page 692
Multitest Systems: PT, PTT, ACT......Page 693
Hemochron Jr. Signature/Signature+......Page 694
Hepcon HMS Hemostasis Management System......Page 695
References......Page 696
Treatment of Venous Thromboembolism in Stroke Patients......Page 699
Prophylaxis......Page 700
Prophylaxis......Page 701
Treatment......Page 702
References......Page 703
Physiopathology and Rationale for Ultra-Early Hemostatic Therapy......Page 705
Consultation Strategies......Page 706
Reversal of Warfarin-Induced Coagulopathy......Page 707
GIIb/IIIaβInduced Coagulopathy......Page 709
Cerebral Sinus Venous Thrombosis......Page 710
Prevention of Rebleeding......Page 711
Consultation Strategies......Page 712
Miscellaneous Coagulopathic States......Page 714
References......Page 715
Stroke risk......Page 719
Diagnostic testing......Page 720
Treatment......Page 721
References......Page 722
Endothelial Injury......Page 725
Thrombosis......Page 726
Investigations......Page 727
Pulmonary Thromboendarterectomy for CTEPH......Page 728
References......Page 729
Pathogenesis......Page 731
Clinical Presentation......Page 732
Use of Factor VIIa for Post-injury Coagulopathy......Page 733
Thrombocytopenia......Page 734
References......Page 735
Additional References......Page 736
Leukocytes......Page 737
Inflammation......Page 738
Hemostatic Changes......Page 739
Pathogenesis......Page 740
Thrombophilic DNA Mutations......Page 741
Etiology and Pathophysiology......Page 742
Pathophysiology......Page 743
Stroke......Page 744
References......Page 745
Atrial Fibrillation......Page 751
Mechanical Prosthetic Heart Valves......Page 752
When is it Appropriate to Restart Anticoagulation after Serious Bleeding?......Page 753
Epidural Hematomas......Page 754
Pregnancy and Valves......Page 755
The Patient on Warfarin Who Desires to Become Pregnant......Page 756
References......Page 757
Index......Page 761