Transfusion Medicine and Hemostasis (eBook)

Front Cover 1
Transfusion Medicine and Hemostasis: Clinical and Laboratory Aspects 4
Copyright Page 5
Contents 6
About the Editors 16
Contributors 18
Preface 22
Acknowledgments 24
PART I: Blood Banking and Transfusion Medicine 26
Introduction 28
Chapter 1 Blood Banking and Transfusion Medicine – the Field, the Discipline and the Industry 28
Blood Banking and Transfusion Medicine as a Discipline 28
Structure of Blood Banks and Transfusion Services 30
Blood Banking and Transfusion Medicine as a Medical Specialty 31
Oversight and Regulation of the Blood Industry 31
Oversight by Non-governmental Organizations 32
Recommended Reading 33
Chapter 2 Brief History of Blood Transfusion 34
Early Transfusion 34
Blood Groups 34
Blood Storage 34
Blood Derivatives 35
Blood Component and Derivative Therapy 35
Apheresis 35
Adverse Effects of Transfusion 35
Current Transfusion Medicine and Blood Banking 36
Recommended Reading 36
Chapter 3 Introduction to Quality Systems and Quality Management 38
Compliance versus Quality 38
Background 38
Quality System Essentials 39
Other Systems 41
Quality as a Philosophy and Culture 42
Additional and Related Terms 42
Facility Inspections 42
Recommended Reading 43
Chapter 4 The Role of the Physician in the Blood Center 44
Blood Center Table of Organization 44
Specific Roles in Blood Center Core Operations 44
Quality Systems and Laboratories 45
Clinical Services 47
Financial Issues and Confiict of Interest 48
Research and Advancement of the Field 48
Recommended Reading 48
Donation Process 50
Chapter 5 The Blood Donor, Donation Process and Technical Aspects of Blood Collection 50
Blood Donor 50
Blood Donation Process 51
Technical Aspects of Blood Donation 55
Donor Adverse Reactions 56
Recommended Reading 56
Chapter 6 Apheresis Blood Component Collections 58
Apheresis RBC Collections 58
Platelet Apheresis (Plateletpheresis) Collections 59
Plasmapheresis Collections 59
Recommended Reading 60
Chapter 7 Recipient-specific Blood Donations 62
Exceptional Medical Need 62
Directed Donation 62
Autologous Donation 63
Chapter 8 Adverse Donor Reactions 66
Complications of Whole Blood Donation 67
Complications of Apheresis Donations 68
Approach to the Donor and Donation Process 69
Recommended Reading 69
Component Manufacturing 70
Chapter 9 Component Preparation and Manufacturing 70
Whole Blood 70
Component Manufacturing 70
RBC Components 71
Plasma Components 72
Plasma Derivatives 73
Platelet Components 74
Granulocytes 75
Component Labeling 75
Recommended Reading 75
Donor Testing 76
Chapter 10 Serologic Testing of Donor Products 76
ABO Group Typing 76
D-antigen Phenotype 76
Antibody Screening for the Presence of Unexpected RBC Antibodies 77
Phenotyping RBC Products 77
Antibody Titer Anti-A, Anti-B 78
International 78
Recommended Reading 79
Chapter 11 Overview of Infectious Disease Testing 80
Background 80
Approach to Testing 80
Determination of Need and Requirement for Testing 81
Selection of a Testing Methodology 81
The Biology of an Infection, the Window Period and Testing Strategies 81
Recommended Reading 84
Chapter 12 HIV Screening of Donor Products 86
Description 86
Methods and Interventions to Ensure the Safety of the Blood Supply 87
Determination of Need and Requirement for Testing 89
Approach to Testing 89
International Considerations 90
Recommended Reading 91
Chapter 13 Hepatitis B Screening of Donor Products 92
Determination of Need and Requirement for Testing 92
Approach to Donor Testing 92
International Considerations 94
Recommended Reading 95
Chapter 14 Hepatitis C Screening of Donor Products 96
Determination of Need and Requirement for Testing 96
Approach to Testing 96
International Standards 97
Recommended Reading 98
Chapter 15 West Nile Virus Screening of Donor Products 100
Determination of Need and Requirement for Testing 100
Approach to Testing 101
International Considerations 101
Recommended Reading 101
Chapter 16 Syphilis, HTLV and Chagas Testing of Donor Products 102
Syphilis 102
Human T-cell Lymphotropic Virus 103
Chagas' Disease 105
Recommended Reading 106
Chapter 17 Bacterial Detection Methods 108
Methods to Avoid Bacterial Contamination 108
Methods to Reduce Bacterial Contamination 109
Methods to Inhibit or Inactivate Bacteria 109
Methods to Detect Contaminated Products 109
Future Considerations 111
Recommended Reading 111
Transfusion Medicine 112
Chapter 18 The Role of the Transfusion Service Physician 112
Organization Chart 112
Specific TS Physician Roles 112
TS Medical Direction within Small- to Medium-Sized Community Hospitals 117
Transfusion Medicine as a Career 117
Recommended Reading 117
Testing 118
Chapter 19 Pretransfusion Testing 118
Patient Identification 118
Specimen Requirements 119
Method 119
ABO Blood Type 121
D Type 122
Antibody Screen 122
Blood Component Selection 123
Crossmatch 124
Neonates 124
Labeling and Release of Blood Components 125
Causes of Unexpected Test Results 125
Quality Assurance 126
Recommended Reading 126
Chapter 20 Antibody Identification 128
Antibody Identification Panel 128
Indication 130
Specimen Requirements 130
Method 130
Blood Component Selection 134
Crossmatch 135
Neonates 135
Quality Assurance 135
Recommended Reading 135
Chapter 21 Direct Antiglobulin Test 136
Indication 137
Specimen Requirements 138
Method 138
Evaluation of a Positive DAT 138
False-negative DAT 139
False-positive DAT 139
Clinical Significance of a Positive DAT 139
Recommended Reading 139
Blood Groups 140
Chapter 22 ABO and H Blood Group Systems 140
Antigens 140
Expression 143
Antibodies 143
Antibody Titers 143
Typing Discrepancies 144
Recommended Reading 147
Chapter 23 Rh Blood Group System 148
Antigens 148
Expression 151
Antibodies 152
Recommended Reading 152
Chapter 24 Kell and Kidd Blood Group Systems 154
Kell Blood Group System 154
Kidd Blood Group System 156
Recommended Reading 157
Chapter 25 MNS and Duffy Blood Group Systems 158
MNS Blood Group System 158
Duffy Blood Group System 160
Recommended Reading 162
Chapter 26 Lewis, I and P Blood Group Systems 164
Lewis Blood Group System 164
Ii Antigens 166
P and GLOB Blood Group Systems 168
Recommended Reading 169
Chapter 27 Other Blood Group Systems, Collections and Antigens 170
Blood Group Systems 170
Blood Group Collections 173
High-incidence RBC Antigens 174
Low-incidence RBC Antigens 174
Blood Products 176
Chapter 28 Red Blood Cells and Related Products 176
Product Names 176
Description 176
RBC Storage Lesion 176
Indications 178
Contraindications 182
Processing and Storage 182
Preparation and Administration 182
Quality Assurance 183
Dose 183
Adverse Events 183
Alternatives and Future Considerations 183
International Considerations 184
Recommended Reading 184
Chapter 29 Plasma Products 186
Product Names 186
Description 186
Indications 187
Dosage 190
Compatibility 191
Adverse Events 191
Alternatives to Plasma Products 191
International Considerations 191
Recommended Reading 191
Chapter 30 Platelet Products 192
Product Names 192
Description 192
Indications 192
Preparation and Administration 193
Quality Assurance 196
Dose 196
Product Selection 197
Adverse Events 198
Alternatives and Future Considerations 198
International Standards 198
Recommended Reading 199
Chapter 31 Cryoprecipitate 200
Product Names 200
Description 200
Indications 200
Processing and Storage 202
Preparation and Administration 202
Quality Assurance 202
Dose 203
Adverse Events 203
International Standards 203
Recommended Reading 203
Chapter 32 Granulocyte Products 204
Description 204
Indications 204
Processing and Storage 206
Patient Selection, Dose Preparation, Administration and Toxicities 206
Quality Assurance 207
International Issues 207
Recommended Reading 208
Chapter 33 Albumin and Related Products 210
Indications 210
Contraindications 212
Adverse Effects 212
Cost and Usage 212
Manufacturing 213
Storage 213
Preparation and Administration 213
Albumin Dosing 214
Other Colloid Solutions 214
Recommended Reading 215
Chapter 34 Human Immunoglobulin Preparations 218
Intravenous Immune Globulin (IVIG) 219
Hyperimmune Globulin Products 227
Recommended Reading 227
Chapter 35 Rh Immune Globulin 230
Indications in the Prevention of Anti-D Formation 230
Indications in Idiopathic Thrombocytopenia Purpura 232
Preparation and Administration 232
Adverse Events 232
International Standards 232
Recommended Reading 232
Product Modifications 234
Chapter 36 Irradiation of Blood Products 234
Risk of TA-GVHD 234
Indications for Irradiated Products 234
Guidelines and Standards for Irradiation and Mitigation of TA-GVHD 234
Processing and Storage 237
Quality Assurance 237
Adverse Events 238
International Considerations 238
Recommended Reading 238
Chapter 37 Leukoreduction of Blood Products 240
Indications for Leukoreduction 240
Potential Indications 241
Controversial Indications 241
Contraindications 242
Methods of Leukoreduction 242
Quality Assurance 242
Pre-storage versus Bedside Leukoreduction 242
Universal versus Diagnosis-specific Leukoreduction 242
International Differences 242
Recommended Reading 242
Chapter 38 CMV-safe Blood Products 244
Description 244
Indications 244
Processing and Storage 245
Quality Assurance 246
Adverse Events 246
International Differences 246
Recommended Reading 247
Chapter 39 Frozen Blood Products 248
Cryopreservation of RBC Products 248
Cryopreservation of HPC Products 250
Recommended Reading 250
Chapter 40 Washed Blood Products 252
Washing of RBC Products 252
Washing of Platelet Products 252
Indications 252
Recommended Reading 254
Chapter 41 Volume-reduced Products 256
Red Blood Cell Products 256
Platelet Products 257
Hematopoietic Progenitor Cell Products 258
Recommended Reading 258
Specific Clinical Settings 260
Chapter 42 Neonatal and Pediatric Transfusion Medicine 260
Red Blood Cell Transfusions 260
Platelet Transfusions 262
Plasma Transfusions 263
Cryoprecipitate Transfusions 263
Granulocyte Transfusions 263
Recommended Reading 264
Chapter 43 Perinatal Transfusion Medicine 266
Hemolytic Disease of the Fetus and Newborn 266
Prenatal Testing 267
Intrauterine Transfusions 271
Neonatal Testing 272
Recommended Reading 273
Chapter 44 Autoimmune Hemolytic Anemias 276
Clinical Manifestations 276
Warm Autoimmune Hemolytic Anemia 277
Cold Agglutinin Disease 279
Combined Cold and Warm AIHA 281
Paroxysmal Cold Hemoglobinuria 281
Drug-induced Hemolytic Anemia 281
Recommended Reading 283
Chapter 45 Transfusion Management in Patients with Hemoglobinopathies 284
Sickle Cell Disease 284
& #946
Recommended Reading 291
Chapter 46 Transfusion of Patients Undergoing HPC and Solid-organ Transplantation 294
Transfusion of Patients Undergoing HPC Transplantation 294
Transfusion of Patients Undergoing Solid-organ Transplantation 297
Recommended Reading 299
Chapter 47 Transfusion of HIV-positive Patients 300
Pathophysiology 300
RBC Transfusion 301
Platelet Transfusion 302
Adverse Effects 302
Recommended Reading 303
Chapter 48 Management of Patients Who Refuse Blood Transfusion 304
Specific Circumstances 305
Documentation of Consent or Non-consent 307
Recommended Reading 307
Chapter 49 Platelet Transfusion Refractory Patients 308
Non-immune Refractoriness 308
Immune Refractoriness 309
Calculation of Refractoriness 309
Testing 310
Treatment of the Alloimmunized Patient 310
Bleeding, Platelet-refractory Patient 311
Prevention 311
Recommended Reading 311
Chapter 50 Massive Transfusion 312
Clinical Significance 312
Resuscitation Approaches 312
Complications of Massive RBC Transfusion 316
Recommended Reading 316
Chapter 51 Perioperative Blood Management 318
Factors Influencing the Risk of Transfusion 318
Blood Utilization Guidelines 320
Pharmaceutical Preparations 320
Autologous Blood 322
Controlled Hypotension 325
Recommended Reading 325
Transfusion Reactions 328
Chapter 52 Adverse Events and Outcomes Following Transfusion: an Overview 328
Transfusion Reactions 328
Posttransfusion Complications 328
Serious Hazards of Transfusion 329
Recommended Reading 331
Chapter 53 Febrile Non-hemolytic Transfusion Reactions 334
Incidence 334
Diagnosis, Differential Diagnosis and Evaluation 334
Pathophysiology 335
Management 335
Prevention 335
Recommended Reading 335
Chapter 54 Allergic, Anaphylactoid and Anaphylactic Reactions 336
Pathophysiology 336
Clinical Features 337
Diagnosis 337
Treatment 338
Prevention 338
Recommended Reading 340
Chapter 55 Acute Hemolytic Transfusion Reactions 342
Transfusion of Incompatible RBCs 342
Transfusion of Significant Amounts of Incompatible Plasma 346
Recommended Reading 347
Chapter 56 Delayed Hemolytic Transfusion Reactions 348
Incidence 348
Clinical Manifestations 348
Pathophysiology 348
Diagnosis 348
Management 349
Prevention 350
Hyperhemolytic Transfusion Reaction 350
Recommended Reading 351
Chapter 57 Transfusion-Associated Circulatory Overload 352
Incidence 352
Clinical Manifestations 352
Pathophysiology 352
Diagnosis 352
Management 353
Prevention 354
Recommended Reading 354
Chapter 58 Transfusion-Related Acute Lung Injury 356
Definition 356
Clinical Manifestations 356
Pathophysiology 356
Diagnosis 357
Management 358
Prevention 358
Recommended Reading 359
Chapter 59 Septic Transfusion Reactions 360
Incidence 360
Clinical Manifestations 361
Diagnosis 361
Treatment 361
Contamination Source 361
Prevention 362
Recommended Reading 363
Chapter 60 Metabolic, Hypotensive and Other Acute Reactions and Complications 364
Metabolic Complications of Transfusion 364
Hypotensive Reactions 365
Red Eye Syndrome 366
Back Pain 366
Recommended Reading 367
Chapter 61 Posttransfusion Purpura 368
Pathophysiology 368
Clinical Manifestations 368
Diagnosis 368
Treatment 369
Prevention 369
Recommended Reading 369
Chapter 62 Transfusion Associated Graft versus Host Disease 370
Graft versus Host Disease 370
Diagnosis, Treatment and Prevention of TA-GVHD 371
Blood Product Factors Contributing to the Risk of TA-GVHD 372
Patients at Increased Risk for TA-GVHD 373
Recommended Reading 376
Chapter 63 Microchimerism 378
Pathophysiology of TA-MC 378
Clinical Elements of TA-MC 378
Diagnosis 379
Prevention 379
Recommended Reading 379
Chapter 64 Transfusion Related Immunomodulation 382
Accepted TRIM Effects 382
Debated TRIM Effects 383
Proposed Mechanisms of TRIM 383
Recommended Reading 383
Chapter 65 Iron Overload 384
Pathophysiology 384
Clinical Manifestations 384
Diagnosis 384
Management 385
Recommended Reading 385
Chapter 66 Transfusion Transmitted Diseases 386
Hepatitis Viruses 387
Retroviruses 390
Herpesviruses 391
Other Viruses 393
Protozoa 394
Prions 395
Other Emerging Infections 396
Recommended Reading 396
Therapeutic Apheresis and Phlebotomy 398
Chapter 67 Overview of Therapeutic Apheresis 398
Methods 398
Volumes Exchanged 403
Calculation of Total Blood Volume, Total RBC Volume, and Total Plasma Volume 403
Total Extracorporeal Volume and Total RBC Extracorporeal Volume 404
Replacement Solutions 405
Vascular Access 405
Anticoagulation 405
Adverse Events 405
ASFA Indication Categories 406
Evaluation of a New Patient for the Initiation of TA 406
Recommended Reading 407
Chapter 68 Therapeutic Plasma Exchange 408
Pathophysiology 408
Methods 408
Volume Exchanged 408
Timing and Frequency 408
Replacement Fluids 408
Indications 409
Adverse Effects 420
Recommended Reading 421
Chapter 69 Therapeutic Erythrocytapheresis 424
Indications 424
Volume Exchanged 425
Replacement Fluids 425
End Hematocrit 426
Adverse Effects 426
Recommended Reading 426
Chapter 70 Therapeutic Thrombocytapheresis 428
Indications 428
Volume Exchanged 428
Recommended Reading 428
Chapter 71 Therapeutic Leukapheresis 430
Indications 430
Volume Exchanged 431
Timing 431
Replacement Fluids 431
Recommended Reading 431
Chapter 72 Extracorporeal Photopheresis 432
Pathophysiology 432
Methods 432
Indications 432
Adverse Effects 435
Recommended Reading 435
Chapter 73 LDL Pheresis 436
Indications 436
Methods 436
Adverse Effects 436
Recommended Reading 436
Chapter 74 Immunoadsorption 438
Indications 438
Methods 439
Adverse Effects 439
Recommended Reading 439
Chapter 75 Therapeutic Phlebotomy 440
Indications 440
Methods 441
Adverse Effects 441
Recommended Reading 441
Cellular Therapy and Tissue Banking 442
Chapter 76 HPC Products 442
Indications 443
Collection 443
Processing 445
Storage 448
Preparation and Infusion 448
Quality Assurance 449
Dose 449
Donor Lymphocyte Infusions 449
Recommended Reading 450
Chapter 77 Tissue Banking in the Hospital Setting 452
Tissue Suppliers and Hospital Tissue Services 452
Tissues Transplanted at Hospitals 452
Regulatory Agencies and Tissue Banking 453
Decentralized Tissue Services in Hospitals 454
Centralized Tissue Services in Hospitals 454
Recommended Reading 455
PART II: Coagulation 456
Introduction 458
Chapter 78 Overview of the Coagulation System 458
Platelet/Blood Vessel Interaction 458
The Role of Platelets in Blood Vessel Interaction 459
Formation of Thrombin 461
Recommended Reading 463
Clinical Coagulation 464
Chapter 79 Approach to the Bleeding Patient 464
History 464
Physical Examination 465
Laboratory Evaluation 466
Overview of Coagulation Testing 468
Recommended Reading 469
Neonatal Thrombocytopenia 470
Chapter 80 Congenital Thrombocytopenia 470
Differential Diagnosis 470
Management 470
Congenital Thrombocytopenias 470
Recommended Reading 475
Chapter 81 Neonatal Alloimmune Thrombocytopenia 478
Pathophysiology 478
Clinical Manifestations 478
Diagnosis 478
Management 479
The Future 480
Recommended Reading 480
Chapter 82 Acquired Neonatal Thrombocytopenia 482
Pathophysiology 482
Clinical Manifestations 483
Diagnosis 483
Management 484
Recommended Reading 486
Inherited Platelet Function Disorders 488
Chapter 83 Bernard-Soulier Syndrome and Other GPIb-IX-V Related Receptor Defects 488
Bernard-Soulier Syndrome 488
Benign Mediterranean Macrothrombocytopenia 489
Thrombocytopenia and Velocardiofacial (DiGeorge) Syndrome 489
Platelet-type von Willebrand Disease (Gain of Function Mutation of GPIb-IX-V) 489
Recommended Reading 490
Chapter 84 Glanzmann Thrombasthenia 492
Pathophysiology 492
Diagnosis 492
Management 493
Recommended Reading 493
Chapter 85 Platelet Storage-granule Defects 494
Diagnosis 494
Management 494
Other Granule Defects 495
Recommended Reading 496
Chapter 86 Failure to Release and Aspirin-like Defects 498
Pathophysiology 498
Examples of Failure of Granule Release and Aspirin-like Defects 498
Diagnosis 499
Management 499
Recommended Reading 499
Immune Thrombocytopenia 500
Chapter 87 Acute (Childhood) Immune Thrombocytopenic Purpura 500
Pathophysiology 500
Clinical Manifestations 500
Diagnosis 501
Management 502
Recommended Reading 503
Chapter 88 Chronic Immune Thrombocytopenic Purpura 506
Pathophysiology 506
Clinical Manifestations 507
Diagnosis 507
Management 508
Relapse 509
Recommended Reading 510
Chapter 89 Drug-induced Thrombocytopenia 512
Pathology 513
Clinical Manifestations 514
Diagnosis 514
Management 515
Recommended Reading 515
Chapter 90 Heparin-induced Thrombocytopenia 516
Pathophysiology 516
Clinical Manifestations 516
Diagnosis 517
Management 519
Recommended Reading 522
Chapter 91 Autoimmune Lymphoproliferative Syndrome 524
Pathophysiology 524
Clinical Manifestations 524
Diagnosis 524
Management 525
Recommended Reading 526
Immune-mediated Coagulopathies 528
Chapter 92 Hemolytic Uremic Syndrome 528
Pathophysiology 528
Clinical Manifestation and Laboratory Features 530
Diagnosis 530
Management/Prognosis 531
Recommended Reading 531
Chapter 93 Thrombotic Thrombocytopenic Purpura 534
Pathophysiology 534
Epidemiology 534
Clinical Manifestations 534
Diagnosis 535
Management 536
Recommended Reading 538
Chapter 94 Antiphospholipid Antibody Syndrome 540
Pathophysiology 540
Clinical Manifestations 541
Diagnosis 541
Management 541
Recommended Reading 542
Congenital Bleeding Disorders 544
Chapter 95 von Willebrand Disease 544
Pathophysiology 544
Classification 544
Clinical Manifestations 546
Diagnosis 547
Management 549
Recommended Reading 550
Chapter 96 Hemophilia A 552
Pathophysiology 552
Clinical Manifestations 552
Diagnosis 553
Management 553
Complications 555
Recommended Reading 556
Chapter 97 Hemophilia B 558
Pathophysiology 558
Clinical Manifestations 558
Diagnosis 559
Management 559
Complications 559
Recommended Reading 561
Chapter 98 Congenital Disorders of Fibrinogen 562
Pathophysiology 562
Clinical Manifestations 563
Diagnosis 564
Management 564
Recommended Reading 564
Chapter 99 Factor XIII, & #945
Pathophysiology 566
Clinical Manifestations 567
Diagnosis 568
Management 568
Recommended Reading 569
Chapter 100 Factor XI Deficiency 570
Pathophysiology 570
Clinical Manifestations 571
Diagnosis 571
Management 572
Recommended Reading 572
Chapter 101 Factor VII Deficiency 574
Pathophysiology 574
Diagnosis 574
Management 575
Recommended Reading 575
Chapter 102 Factor II, Factor V and Factor X Deficiencies 576
Pathophysiology 576
Diagnosis 577
Management 577
Recommended Reading 578
Acquired Bleeding Disorders 580
Chapter 103 Bleeding Disorders in Pregnancy 580
Congenital Disorders 580
Acquired Disorders 582
Recommended Reading 584
Chapter 104 Vascular Bleeding Disorders 586
Hereditary Vascular Malformations 586
Hereditary Connective Tissue Disorders 587
Acquired Vascular Disorders 587
Recommended Reading 588
Chapter 105 Bleeding Risks with Liver Disease 590
Pathophysiology 590
Clinical Manifestations 592
Diagnosis 592
Management 593
Recommended Reading 593
Chapter 106 Bleeding Risks with Vitamin K Deficiency 596
Pathophysiology 596
Clinical Manifestation 597
Diagnosis 598
Management 599
Recommended Reading 599
Chapter 107 Bleeding Risks with Cardiac Disease 602
Pathophysiology 602
Clinical Manifestations 603
Diagnosis and Differential Diagnosis of Bleeding Associated with CPB 603
Management 604
Recommended Reading 605
Chapter 108 Bleeding Risks with Renal Disease 606
Pathophysiology 606
Clinical Manifestations 607
Diagnosis 607
Management 607
Recommended Reading 608
Chapter 109 Bleeding Risks in Cancer 610
Clinical Manifestations 610
Diagnosis 611
Management 612
Recommended Reading 612
Chapter 110 Disseminated Intravascular Coagulopathy 614
Pathophysiology 614
Clinical Manifestations 615
Diagnosis 615
Management 616
Recommended Reading 618
Chapter 111 Acquired Coagulation Factor Inhibitors 620
Inhibitors of FVIII 620
Inhibitors of VWF 623
Inhibitors of FV 624
Inhibitors of Prothrombin and Thrombin 624
Recommended Reading 625
Laboratory Testing of Coagulation: Introduction 626
Chapter 112 Introduction to Coagulation Testing 626
Analysis of Proteins Involved in Coagulation 627
Analysis of Cellular Biology in Coagulation 628
Analysis of Therapeutic Interventions 629
Integration of Coagulation Labs with Patient Care 629
Screening Tests 632
Chapter 113 Prothrombin Time and Activated Partial Thromboplastin Time 632
Prothrombin Time 632
Activated Partial Thromboplastin Time 633
Interpretation of PT and PTT Tests 634
Chapter 114 Platelet Count 636
Methods 636
Sources of Error 636
Recommended Reading 638
Chapter 115 Global Tests of Primary Hemostasis 640
Bleeding Time 640
Platelet Function Analyzer 641
Recommended Reading 641
Laboratory Assessment of Platelet Disorders 642
Chapter 116 Platelet Aggregation Studies 642
Platelet Aggregation by Light-transmission Aggregometry (LTA) 642
Platelet Aggregation by Whole Blood Aggregometry (WBA) 642
Platelet Adenosine Triphosphate (ATP) Release 643
Interpretation of Results from LTA, WBA and ATP Release 644
Recommended Reading 645
Chapter 117 Laboratory Diagnosis of Genetic Platelet Function Defects 648
Platelet Aggregation Studies 648
Platelet Function Analyzer 648
Electron Microscopy 648
DNA Sequence Analysis 648
Interpretation of Results Based Upon Combined Application of the Above Lab Tests 650
Recommended Reading 651
Chapter 118 Laboratory Diagnosis of Acquired Platelet Function Defects 652
Anemia 652
Myeloproliferative Disorders 652
Hepatic Disease 653
Gammopathies 654
Autoimmunity to Platelet Proteins 654
Disseminated Intravascular Coagulopathy 654
Extracorporeal Membrane Oxygenation 654
Recommended Reading 654
Chapter 119 Laboratory Diagnosis of Immune Thrombocytopenic Purpura 656
Methods for Platelet Antibody Testing 656
Platelet Antibody Testing in Other Diseases 658
Recommended Reading 658
Chapter 120 ADAMTS13 Testing 660
ADAMTS13 Activity 660
Methods 660
ADAMTS13 Inhibitor 662
Recommended Reading 663
Chapter 121 Laboratory Diagnosis of Heparin-induced Thrombocytopenia 664
Laboratory Testing for HIT Antibodies 664
Antigen Assays 664
Platelet Activation (Functional) Assays 666
Recommended Reading 667
Laboratory Assessment of VWD 670
Chapter 122 Molecular Biology of von Willebrand Disease 670
DNA Sequence Analysis 671
Recommended Reading 672
Chapter 123 Laboratory Diagnosis of Inherited von Willebrand Disease 674
Ristocetin Cofactor 674
VWF Antigen 674
Factor VIII Coagulant Activity 675
Collagen Binding Assay 675
Ristocetin-induced Platelet Aggregation 675
VWF Multimers 675
VWF Inhibitor 675
VWF Binding to Platelets 676
Factor VIII Binding to VWF 676
DNA Sequencing 676
Diagnosis of VWD Types 676
Recommended Reading 677
Chapter 124 Laboratory Diagnosis of Acquired von Willebrand Syndrome 678
Recommended Reading 679
Chapter 125 Laboratory Assessment of Treatment of von Willebrand Disease 680
Treatment Modalities 680
Recommended Reading 681
Laboratory Assessment of Coagulation Factor Disorders 682
Chapter 126 Coagulation Factor Testing 682
Methods 683
Test Performance 684
Sources of Error 684
Quality Assurance 684
International Standards 684
Recommended Reading 684
Chapter 127 Mixing Studies 686
Method 686
Interpretation 686
Test Performance 687
Sources of Error 687
Quality Assurance 687
Recommended Reading 687
Chapter 128 Specific Factor Inhibitor Testing 688
Methods 688
Sources of Error 690
Recommended Reading 690
Laboratory Assessment of Fibrinogen and Fibrinolysis 692
Chapter 129 Laboratory Diagnosis of Dysfibrinogenemia and Afibrinogenemia 692
Description, Methods and Indications 693
Sources of Error 694
Genetic Testing for Fibrinogen Abnormalities 694
Recommended Reading 694
Chapter 130 Laboratory Assessment of Fibrinolysis 696
Laboratory Testing of Fibrinolysis 698
Sources of Error 699
Recommended Reading 700
Tests for Hypercoaguable State 702
Chapter 131 General Overview of the Hypercoaguable State 702
Pathophysiology 702
Specific Perturbations Leading to Hypercoaguability 703
Recommended Reading 704
Chapter 132 Antithrombin Testing 706
AT Activity 706
AT Antigen 707
Recommended Reading 707
Chapter 133 Proteins C, S and Z Testing 708
Protein C and Protein S 708
Protein Z 711
Chapter 134 Activated Protein C Resistance and Factor V Leiden Testing 714
Activated Protein C Resistance 714
Factor V Leiden 716
Recommended Reading 717
Chapter 135 Prothrombin Gene Mutation Testing 718
Prothrombin Gene Mutation Assay 718
Recommended Reading 719
Chapter 136 Laboratory Diagnosis of Hyperhomocysteinemia 720
Plasma Homocysteine Level 720
MTHFR Mutation 721
Recommended Reading 722
Chapter 137 Laboratory Diagnosis of Lupus Anticoagulant and Antiphospholipid Antibodies 724
Diagnosis 725
Lupus Anticoagulant 725
Antiphospholipid Antibodies 726
Recommended Reading 727
Chapter 138 Lipoprotein(a) Testing 728
Laboratory Test 728
Recommended Reading 728
Chapter 139 Laboratory Diagnosis of Factor Level Abnormalities Associated with Thrombosis 730
Association of Factor Level Abnormalities with Thrombosis 730
Recommendations for Testing Individual Factors 730
Current and Future Applications 731
Recommended Reading 731
Tests for Activation of the Coagulation System 732
Chapter 140 Laboratory Management of DIC 732
Laboratory Diagnosis of DIC 732
Monitoring of a Bleeding Patient in DIC 733
Monitoring of a Thrombotic Patient in DIC 733
Unique Laboratory Findings Associated with Certain Conditions of DIC 734
Recommended Reading 734
Laboratory Support for Anticoagulation 736
Chapter 141 Laboratory Support for Heparin Monitoring 736
PTT 736
Chromogenic Anti-Xa Activity Assay 737
Comparison of the PTT and Anti-Xa Activity Assay for Monitoring Heparin Therapy 737
PTT and Anti-Xa to Monitor Heparin Resistance 738
Recommended Reading 738
Chapter 142 Laboratory Support for Warfarin Monitoring 740
PT 740
Abnormal Warfarin Responsiveness 741
Recommended Reading 745
Coagulation Factor Concentrates 746
Chapter 143 Prothrombin Complex Concentrates 746
Products 746
Description 746
Indications 746
Storage and Stability 746
Dosage 747
Recommended Reading 748
Chapter 144 von Willebrand Factor Concentrates 750
Indications 751
Storage and Stability 752
Dosing 752
Adverse Reactions of FVIII/VWF Containing Products 752
Recommended Reading 753
Chapter 145 Factor VIII Concentrates 754
Factor VII Products 754
Indications, Dosing and Administration 756
Processing and Storage 756
FVIII Dosing and Administration 757
Complications of FVIII Therapy 757
Recommended Reading 758
Chapter 146 Factor IX Concentrates 760
Factor IX Products 760
Indications, Dosing and Administration 761
Complications of FIX Therapy 762
Recommended Reading 762
Chapter 147 Factor VII Concentrates 764
Manufacturing 764
Pathophysiology 764
Storage and Stability 764
Dosage 764
Adverse Reactions/Precautions 765
Recommended Reading 766
Chapter 148 Antithrombin Concentrates 768
Description 768
Indications 768
Dosing/Administration and Stability 769
Adverse Reactions/Precautions 770
Recommended Reading 770
Chapter 149 Protein C Concentrates 772
Indications 772
Dosage and Administration 773
Storage and Stability 773
Adverse Reactions 773
Recommended Reading 774
General Handbook References 776
Index 778
A 778
B 780
C 782
D 783
E 784
F 784
G 786
H 787
I 789
J 790
K 790
L 790
M 791
N 791
O 792
P 792
Q 795
R 795
S 796
T 797
V 799
W 800
X 800
Y 800