519© Springer Nature Switzerland AG 2019H. M. Lazarus, A. H. Schmaier (eds.), Concise Guide to Hematology, https://doi.org/10.1007/978-3-319-97873-4

Index

AAberrant myeloid antigen expression, 269ABL proteins, 313Abnormal fetomaternal cell traffic

ANN, 230HDN, 229, 230NAIT, 230

Abnormal hematopoiesisanemia, 11blood cells production, 11CHIP, 12leukopenia, 10low number of white blood cells, 10lymphopenia, 10multilineage cytopenias, 11neutropenia, 10, 11thrombocytopenia, 11

Abnormal liver function tests, 169Abnormal protein molecule, 89Absolute counting, 261Absolute reticulocyte count (ARC), 68Acalabrutinib, 404ACE inhibitors, 421Acquired amegakaryocytic thrombocytopenia, 138Acquired bleeding disorders

consumption coagulopathy, 118–120diagnosis

bleeding history, 111global coagulation tests, 112medical history, 111physical examination, 111prolonged aPTT, 112prolonged PT, 112screening coagulation tests, 111

impaired fibrin formationdue to anticoagulants, 116–118coagulation factor deficiency, 115coagulation factor inhibitors, 115, 116

platelet, 113–115Acquired hemolytic anemia

causes, 70–71clinical characteristics, 67definition, 67external toxins, 77immune-mediated hemolytic anemia (see Immune-mediated

hemolytic anemia)laboratory evaluation

bilirubin, 69bone marrow aspirate and biopsy, 70cold agglutinin titer, 70complete blood count,with reticulocyte count, 68direct antiglobulin test, 69

Donath-Landsteiner antibody test, 70haptoglobin, 69indirect antiglobulin test, 69lactate dehydrogenase, 69peripheral blood flow cytometry, 70peripheral blood smear, 68plasma-free hemoglobin, 69serum and RBC folate, 69serum aspartate aminotransferase, 69serum iron, TIBC, ferritin, 69urine hemoglobin and hemosiderin, 69urine urobilinogen, 69

paroxysmal nocturnal hemoglobinuriacauses/underlying disorders, 78clinical and laboratory findings, 78pathophysiology, 78treatment, 79

spur cell anemia, 78traumatic hemolytic anemia

due to DIC, 76external impact, 75HUS, 76, 77macrovascular defects-prostheses, 76microangiopathic hemolytic anemia, 76microvascular abnormalities, 77thrombotic microangiopathy, 76thrombotic thrombocytopenic purpura, 76

Acquired immunodeficiency syndrome (AIDS), 221Acquired impaired fibrin formation

due to anticoagulants, 116–118coagulation factor deficiency, 115coagulation factor inhibitors, 115, 116

Acquired platelet disordersqualitative defects, 114, 115quantitative defects, 113, 114

Acquired von Willebrand factor (vWF) deficiency, 114Activated partial thromboplastin time (aPTT)

diagnosis, 98to monitor anticoagulation, 92screening tests, 90

Acute hemolytic reactions, 75Acute hemolytic transfusion reactions

(AHTRs), 474, 475Acute intravascular hemolysis, 68Acute leukemia

acute myeloid leukemia, 343–348acute lymphoblastic leukemia, 348–352acute promyelocytic leukemia, 348flow cytometry, 271lineage assignment for, 270, 271stains, 249supportive care, 352–353

520

Acute lymphatic leukemia of the B cell line (B-ALL), 432Acute lymphatic leukemia of the T cell line (T-ALL), 290, 433Acute lymphoblastic leukemia (ALL), 348, 424

B-cell ALL, 288BCR-ABL1 (Ph)-like B-cell ALL, 290hyperdiploid, 289hypodiploid, 289iAMP21, 289t(1;19)/E2A/TCF3 fusion, 289t(4;11)/AFF1/KMT2A fusion and KMT2A/MLL

translocations, 289t(8;14)/MYC/IGH fusion, 289t(9;22)/BCR/ABL1 fusion, 289t(12;21)/ETV6/RUNX1 fusion, 288, 289

chemical diagnosisbone marrow involvement, 434CNS involvement, 434testicular involvement, 434

chemotherapy, 435chromosomal and molecular changes, 349, 350clinical features, workup, and diagnosis, 348, 349clinical symptoms

bone marrow involvement, 433CNS involvement, 433testicular involvement, 434

cytochemistry, 432cytology, 432definition, 430diagnosis, 431immune phenotyping, 349, 432, 433initial evaluation for, 349initial patient admission, 434, 435morphology, 432MRD, 435, 436pathogenesis, 431prevalence, 430prognosis, 431relapse, 435risk stratification

adults, 351children, adolescents, and young adult patients, 351

structural chromosomal aberrations, 431supportive care

blood product support, 353coagulopathy, 352leukostasis, 352menses, fertility and suppression of, 353opportunistic infections and neutropenic fever, 353TLS, 352

T-ALL, 290treatment

anti-CD20 therapy, 352cellular therapy, 352CNS prophylaxis, 351consolidation, 351induction, 351maintenance, 351tyrosine kinase inhibitor therapy, 352

WHO classification, 350Acute myeloid leukemia (AML), 270, 281, 343

APL, 348classification, 270, 345–346clinical symptoms, 443, 444clinical features, workup and diagnosis, 343, 345cytogenetic typing, 440, 443, 444definition, 436

diagnosis, 437differential diagnosis, 437gene mutations in, 287, 288hyperleukocytosis and leukostasis, 444immune phenotyping, 438, 443incidence, 436initial evaluation, 345massive chromosomal imbalances, complex karyotype,

and clonal heterogeneity in, 284morphology and cytochemistry, 437, 439, 440, 443pathogenesis, 437prognosis, 436prognostic significance, 281relapse, 445response criteria, 347risk stratification, 345, 346supportive care

blood product support, 353coagulopathy, 352leukostasis, 352menses, fertility and suppression of, 353opportunistic infections and neutropenic fever, 353TLS, 352

therapy, 444, 445treatment

CNS disease, 347consolidation, 347induction, 346, 347

Acute promyelocytic leukemia (APL), 270, 282, 348Acute transient hemolytic anemia, 63Acyclovir, 516Adenosine deaminase deficiency (ADA), 221Adjuvant therapy, 100Aerolysin, 261Age-adjusted international prognostic index (age-adjusted IPI), 390Aggregation, 123Aggressive B-cell lymphoma subtypes

Burkitt lymphomadiagnostic considerations, 394first-line treatment, 395prognostic factors, 394, 395relapsed/refractory treatment, 395

DLBCLDHL, 392, 393diagnostic considerations, 389, 390first-line therapy, 390–392prognostic factors, 390relapsed and refractory disease, 390, 392

MCLdiagnostic considerations, 393frontline treatment, 393, 394prognostic factors, 393relapsed/refractory MCL, 394

transformed lymphoma, 395clinical presentation, 395diagnosis, 395epidemiology, 395treatment, 395

Aggressive lymphomaaggressive B-cell lymphoma subtypes

Burkitt lymphoma, 394, 395DLBCL (see Diffuse large B-cell lymphoma)MCL, 393, 394transformed lymphoma, 395, 396

aggressive mature peripheral T-cell lymphomasanaplastic large cell lymphoma, 396

Index

521

angioimmunoblastic T-cell lymphoma, 396mature peripheral T-cell lymphomas, 397PTCL-NOS, 396

clinical presentation, 387, 388CNS treatment and prophylaxis, 397diagnosis, 388epidemiology and classification, 387initial workup and staging, 388, 389investigational/emerging therapies, 397

Aggressive mature peripheral T-cell lymphomasanaplastic large cell lymphoma, 396angioimmunoblastic T-cell lymphoma

diagnostic considerations, 396prognostic factors, 397

mature peripheral T-cell lymphomas, 397PTCL-NOS, 396

Aggressive NK and NK-like T cell leukemia/lymphoma, 362Alcohol-induced thrombocytopenia, 138Alemtuzumab, 403Alkylating agents, 402Allele-specific oligonucleotide PCR (ASO-PCR), 301, 302Allergic transfusion reactions (ATRs), 475Allogeneic hematopoietic cell transplantation (allo-HCT), 382

AML (see Hematopoietic cell transplantation (HCT), allogeneic)CLL, 406PMF, 327

Alloimmune hemolytic anemia, 23Alloimmune neonatal neutropenia (ANN), 230Alloimmune thrombocytopenia, 143

NAIT, 143passive alloimmune thrombocytopenia, 143platelet transfusion refractoriness, 144posttransfusion purpura, 143transplantation-associated alloimmune thrombocytopenia, 144

Allopurinol therapy, 428All-trans retinoic acid (ATRA), 348Alpha-1-antitrypsin PITTSBURGH, 93Alpha-2-antiplasmin deficiency, 92α0-mutation, 54α−thalassemia, 55, 64

α0-mutation, 54clinical consequences, 54clinical presentation, 55epidemiology, 54HbCS, 56HbH disease, 56hydrops fetalis, 56prognosis, 55silent carrier/α−thalassemia trait, 56treatment, 56

Amotosalen, 482Amplification refractory mutation system (ARMS), see Allele-specific

oligonucleotide PCRAmyloid cardiomyopathy, 412Amyloidosis, 420, 421Anagrelide, 326Anaplastic large cell lymphoma (ALCL), 361, 396Anaplastic large T-cell lymphoma (ALTCL), 292, 293Androgen danazol, 328Anemia

acute blood loss, 21definition, 11, 67destruction

alloimmune hemolytic anemia, 23autoimmune hemolytic anemia, 23hemoglobinopathy, 22

mechanical causes of hemolysis, 23red blood cell enzyme defects, 23red blood cell membrane defects, 23

inadequate productionbone marrow replacement, 22endocrine, 22folate deficiency, 22inflammation, 21iron deficiency, 21pure red cell aplasia, 22renal disease, 21sideroblasts, 22vitamin B12 deficiency, 22

of inflammation, 35laboratory diagnosis

MCV, 24, 25, 27peripheral blood smear, 25RDW, 24, 25, 27reticulocyte count, 24, 25

normal range, 21, 22red blood cell parameters, 22symptoms/signs, 24, 67

Anemia of chronic disease, see Anemia of inflammationAnemia of inflammation, 21, 35–36Angioimmunoblastic T-cell lymphoma, 361

diagnostic considerations, 396prognostic factors, 397

Anisocytosis, 25Ann Arbor staging system, 374, 380

Lugano modification of, 389Anopheles, 481Antibody-drug conjugates (ADC), 377, 430Anti-CD19 chimeric antigen receptor T-cells

(CAR T-cells), 352Anti-CD20 therapy, 352Anti-CD22 antibody-drug conjugate inotuzumab

ozogamicin, 352Anticoagulation system, 82, 86, 87Anti-factor IIa chromogenic assay, 113Anti-factor Xa assay, 116Antifibrinolytics, 473Antifungal prophylaxis, 427, 511Antigens, 259Antiphospholipid syndrome (APS), 157Antiplatelet therapy

aspirindosing, 197efficacy and safety, 197indications, 197–199mechanism of action, 196pharmacodynamics, 197pharmacokinetics, 197resistance, 198

cilostazol, 205DAPT

duration, 202, 203therapeutic oral anticoagulation, 202

dipyridamole, 204glycoprotein IIb/IIIa inhibitors, 203P2Y12 antagonists

cangrelor, 201, 202clopidogrel, 199, 200mechanism of action, 198prasugrel, 200ticagrelor, 200, 201ticlopidine, 198

Index

522

Antiplatelet therapy (cont.)pathophysiology

cerebrovascular disease, 195coronary artery disease, 195peripheral artery disease, 196pharmacologic targets, 196in venous thrombosis, 196

vorapaxar, 204Antithrombin (AT) deficiency, 153Antithrombin anticoagulation system, 87Anti-thymocyte globulin (ATG), 499Aplastic anemia, 11, 52Array, 307, 308Array comparative genomic hybridization (aCGH) technique, 307Arterial thrombosis

etiology, 155occurrence, 149pathogenesis, 155risk factors

CRP, 157Lp (a), 157plasma homocysteine, elevation of, 155–157

Aspergillus-specific lateral-flow device, 512Aspirin

dosing, 197efficacy and safety, 197indications, 197–199mechanism of action, 196pharmacodynamics, 197pharmacokinetics, 197resistance, 198

Atypical hemolytic uremic syndrome (aHUS), 66, 76Auer bodies, 453Autoaggression syndrome, 491Autofluorescence, 257Autoimmune disorders, 140Autoimmune hemolytic anemia, 23Autoimmune heparin-induced thrombocytopenia, 145Autologous GvHD, 491, 492Autologous hematopoietic cell transplant (AHCT), 382, 416

Hodgkin lymphoma, 376, 377See also Hematopoietic cell transplantation (HCT), autologous

Autosomal dominant thrombocytopeniaACTN1, 128ANKRD26, 128gray platelet syndrome, 127HOXA11, 128macrothrombocytopenia, 127MECOM, 128MYH9-related thrombocytopenia syndromes, 126Paris-Trousseau platelet disorder, 127RUNX1, 127TUBB1, 128Velocardiofacial/DiGeorge Syndrome, 128

Autosomal recessive thrombocytopeniaBernard-Soulier syndrome, 128congenital amegakaryocytic thrombocytopenia, 128TAR, 128

Axicabtagene ciloleucel, 430

BBabesia microti, 481Babesia spp., 481Band, 241Banti’s syndrome, 139

Basophilic erythroblast, 242Basophilic stippling, 16Basophils, 2, 217B-cell acute lymphoblastic leukemia

BCR-ABL1 (Ph)-like B-cell ALL, 290hyperdiploid, 289hypodiploid, 289iAMP21, 289t(1;19)/E2A/TCF3 fusion, 289t(4;11)/AFF1/KMT2A fusion and KMT2A/MLL translocations,

289t(8;14)/MYC/IGH fusion, 289t(9;22)/BCR/ABL1 fusion, 289t(12;21)/ETV6/RUNX1 fusion, 288, 289

B cell clonality, 264B cell development, 266B cell leukemia, 430B cell lymphoblastic leukemia/lymphoma, 273B cell neoplasms, 267, 268B-cell lymphocytes, 219, 220BCL-2 inhibitor, 405BCR-ABL inhibitors, 429BCR-ABL tyrosine kinase inhibitors, 352BCR-ABL1, 313, 316Bendamustine, 377, 382, 402Benzene, 425Bernard-Soulier syndrome (BSS), 128, 129β−thalassemia, 57, 64β1-tubulin macrothrombocytopenia, 138Bilirubin, 69Biological products, 463Blasts, 243, 328Bleeding disorders

activated partial thromboplastin timeto monitor anticoagulation, 92screening tests, 90

AML, 444clinical presentation, 89coagulation cascade hypothesis, 90coagulation protein defects, 89differential diagnosis

isolated prolonged aPTT, 91isolated PT prolongation, 91prolonged activated partial thromboplastin time, 91prothrombin time, 91

plasma protein defect, 89platelet abnormality, 89platelet-endothelial cell interactions, 89screening tests, 90

bleeding time, 90plasma coagulation assays, 90platelet count, 90prothrombin time, 90, 91thrombin clotting time, 90, 91

Bleeding time, 90Bloodstream infections, 503Bone

biology, 233cellular components, 233medullary cavity, 233structure, 233

Bone marrow, 488ancillary tests, 249, 250aspirate clot, 248aspiration, 236, 238, 239biopsy, 236, 238, 239

Index

523

chlorhexidine, 237complications, 237consenting process, 237core biopsy, 246cytogenetic and molecular testing, 251differential count, 245, 246flow cytometry, 250hematopoietic cells, 236iron stain, 248medical practitioner, 237morphologic examination

aspiration, 240band, 241blasts, 243erythroid precursors, 242granulocytes, 240lymphocytes, 244macrophages, 245mast cells, 245megakaryocytes, 243metamyelocyte, 241monocytes, 244myelocyte, 241non-hematopoietic elements, 245plasma cells, 244promyelocyte, 241segmented form, 242slide preparations, 239, 240

myeloid/erythroid ratio, 246prepacked bone marrow diagnostic kit, 237procedural preparation, 237sedation, 237sterile gloves, 237stroma, 235therapeutic intent, 239touch imprint, 248trained laboratory assistant, 237vasculature, 235

Bone marrow failure, 493Bone marrow harvesting, 489Bone marrow replacement, 22Bone marrow stroma, 235Bortezomib, 394Bosutinib, 319Breakpoint cluster regions (BCRs), 307Breast implant anaplastic large cell lymphoma (BIA-ALCL), 361Brentuximab, 377Bruton’s agammaglobulinemia, 220Bruton’s tyrosine kinase (Btk), 420BTK inhibitors, 404Burkitt lymphoma

diagnostic considerations, 394first-line treatment, 395prognostic factors, 394, 395relapsed/refractory treatment, 395t(8;14)/IGH/MYC fusion, 292

CCalcineurin inhibitors, 497, 500Candidemia, 510Candidiasis, 500CAR T cell therapy, 430Cardiac disease, 420Cardiopulmonary bypass (CPB), 140Cardiovascular disease, 116, 155, 160

antiplatelet therapy (see Antiplatelet therapy)Cather-related bloodstream infection (CRBSI), 508CD10, 267, 269, 273, 349CD11b, 270CD13, 270CD15, 372CD16, 270CD19, 272, 352, 430CD20, 261, 349CD23, 267CD30, 361, 363, 372CD34 enumeration method, 261CD34 hematopoietic stem cells

determining concentration, 263ISHAGE method, 262

CD38, 267CD45, 258, 272CD5, 266, 267, 272, 356CD56, 271–273CD79a, 349CD117, 272Cellular therapy, 352Central nervous system (CNS)

disease, 347prophylaxis, 351, 425radiotherapy

long-term effects of, 426pCRT, 425side effects, 426tCRT, 426

treatment and prophylaxis, 397CEPBA, 287Cerebral folate deficiency, 43Cerebrovascular disease, 195Chediak-Higashi syndrome (CHS), 215Chemoimmunotherapy (CIT), 402–404Chemotherapy

Hodgkin lymphoma, 374, 375neoplastic hematologic disorders

DIC, 428peripheral neuropathy, 428thrombophilia, 428tumor lysis syndrome, 427, 428

Chemotherapy-induced nausea and vomiting (CINV), 426Chickenpox, 515Chimeric antigen receptor T-cells (CAR T-cells), 352, 405Christmas disease, see FIX deficiencyChromogenic anti-factor Xa assay, 184Chromogenic factor assay, 98Chromosomal analysis, 277, 304, 305

applications, 306cytogenetic technique, 305, 306

Chromosome abnormalities, 277ALL

B-cell ALL, 288–290T-ALL, 290

AML, 281, 284APL, 282CBF leukemia, 281CHIP, 288chromosomal analysis, 277clinical diagnostics, 278, 279CLL, 293, 294clonality, definition of, 279CML and and t(9;22)/Philadelphia chromosome, 280cytogenetic terms and definition, 279, 280

Index

524

Chromosome abnormalities (cont.)detection of, 277, 27911q23/KMT2A (MLL) translocations, 282FISH, 278genomic microarray testing, 278Hodgkin lymphoma, 293

cHL, PDL1/PDL2 amplification/gain, 293CIITA abnormalities in, 293

inv(3)/t(3;3)/MECOM/EVI1 fusion, 282, 284mature B- and T-cell NHL and Hodgkin lymphoma, 290–292MDS, 286, 287

and AML, gene mutations in, 287−7/del(7q), 287Del(5q) and 5q- syndrome, 287t-AML/MDS, 287, 288

multiple myeloma and plasma cell neoplasms, 294, 295NGS analysis, 278NHL

i(7q), 292inv(14)/t(14;14)/TRAD/TCL1 fusion, 292t(2;5)/ALK/NPM1 fusion, 292t(8;14)/IGH/MYC fusion, 292t(11;14)/IGH/CCND1 fusion, 292t(11;18)/API1/MALT1 fusion and MALT1 fusion, 292t(14;18)/IGH/BCL2 fusion, 292

t(1;22)/RBM15/MKL1 fusion, 284t(6;9)/DEK/NUP214 fusion, 284in T-cell NHL, 291types and abbreviations, 305

Chronic eosinophilic leukaemia (CEL), 329Chronic granulomatous disease (CGD), 215Chronic lymphocytic leukemia (CLL), 268, 293, 294, 401

allo-HCT, 406autoimmune complications of, 406biology, 401clinical features, 402epidemiology, 401hypogammaglobulinemia, 406laboratory features and diagnosis, 402mature B cell neoplasms, 356, 357novel targeted therapies, 404

BCL-2 inhibitor, 405BTK inhibitors, 404CAR T cell therapy, 405lenalidomide, 405PI3-K inhibitors, 405

prognosis, 402Richter transformation, 406treatment

chemoimmunotherapy, 403, 404first-line therapy, 404indications for, 402monoclonal antibodies, 403MRD, 404purine analogues and alkylating agents, 402

Chronic myeloid leukemia (CML), 280, 323accelerated phase/blast crisis, treatment, 317, 318chronic phase, treatment

initial therapy, failure of, 316, 317monitoring therapy, 315, 316TKI selection, 314, 315

clinical symptoms, 453cytogenetic typing, 453definition, 313, 452diagnosis, 313, 314, 453differential diagnosis, 453

immune phenotyping, 453incidence, 452long-term effects and follow-up, 454medications

bosutinib, 319dasatinib, 318–319imatinib, 318nilotinib, 318omacetaxine, 320ponatinib, 319, 320

morphology and cytochemistry, 453, 454pathogenesis, 452pathophysiology, 313prognosis, 314, 452relapse, 453treatment, 453

Chronic myeloproliferative diseases, 452CML

clinical symptoms, 453cytogenetic typing, 453definition, 452diagnosis, 453differential diagnosis, 453immune phenotyping, 453incidence, 452long-term effects and follow-up, 454morphology and cytochemistry, 453, 454pathogenesis, 452prognosis, 452relapse, 453treatment, 453

essential thrombocythemiacytogenetic typing, 455definition, 454diagnosis, 455differential diagnosis, 455long-term effects and follow-up, 456morphology and cytochemistry, 455pathogenesis, 455prognosis, 454therapy, 455–456

PMFclinical symptoms, 456, 457cytogenetic typing, 456definition, 456diagnosis, 456differential diagnosis, 456incidence, 456long-term effects and follow-up, 457, 458morphology and cytochemistry, 456, 457pathogenesis, 456prognosis, 456therapy, 457

polycythemia veraclinical symptoms, 459cytogenetic typing, 459definition, 458diagnosis, 458differential diagnosis, 458incidence, 458long-term effects and follow-up, 460morphology and cytochemistry, 458pathogenesis, 458prognosis, 458therapy, 460

Chronic NK lymphocytosis (CNKL), 219

Index

525

Chronic visceral organ dysfunction, 492Cilostazol, 205Cladribine, 331Classic drug-induced immune thrombocytopenic purpura (D-ITP),

144, 145Classic hemophilia, see FVIII deficiencyClassical Hodgkin lymphoma (cHL), 371, 372

CIITA rearrangement, 293H&E stain of, 372histology subtypes of, 373PDL1/PDL2 amplification/gain in, 293PTLD, 366

Classical NK cell deficiency (CKND), 218Clonal eosinophilias, 329Clonal hematopoiesis of indeterminate potential (CHIP), 12, 288Clonality (BCR/TCR rearrangement) analysis, 302Clonality

B cells, 264definition of, 279plasma cells, 273T cells, 269

Coagulation cascade hypothesis, 89–90Coagulation disorders, 428Coagulation factor deficiency, 115Coagulation protein defects, 89Coagulation protein system

factor V (proaccelerin), 83factor VIII (antihemophilic factor), 83fibrinogen, 83high-molecular-weight kininogen, 83in infants and childhood, 227, 228phospholipid-bound proenzymes, 82physiology, 84, 85prothrombinase assembly, 84surface-bound proenzymes, 82tenase assembly, 83thrombin generation, 84tissue factor, 83

Coagulopathy, 352Coagulopathy of trauma, 473Cobalamin, see Vitamin- B12 deficiencyCold agglutinin disease (CAD), 72, 73Cold agglutinin disease/syndrome (CAD/CAS)

causes/underlying disorders, 73clinical and laboratory findings, 73pathophysiology, 72treatment, 73

Cold agglutinin titer, 70Collagen-binding assay (vWF:CBA), 104Colony-forming units (CFUs), 8Common lymphocyte progenitor cells (CLP), 220Compensation, 255Complete hematologic response (CHR), 315Complex karyotype, 279Congenital amegakaryocytic thrombocytopenia, 128, 137Congenital bleeding disorders

clinical symptoms, 107diagnosis, 107hemophilia (see Hemophilia)inhibitors, 107RBD

clinical manifestation, 106definition, 106diagnosis, 107epidemiology, 106management, 107–109

treatment, 110von Willebrand disease

antigen assay, 102clinical presentation, 102, 103clinical subtypes, 103–105definition, 101diagnostic assays, 104factor VIII activity, 104function analysis, 102genetics, 102multimer analysis, 104specialized assays, 104structure, 102synthesis, 102therapeutic DDAVP challenge, 104treatment, 105, 106

Congenital dyserythropoietic anemias (CDAs), 66Congenital heart disease, 140Congenital hemolytic anemias

atypical hemolytic uremic syndrome, 66CDAs, 66clinical and family history, 59hemolytic enzyme disorder

enzyme defects, 64G6PD deficiency, 62, 63PK deficiency, 63pyrimidine 5′ nucleotidase deficiency, 63

hemolytic hemoglobinopathiesalpha-thalassemias, 64β-thalassemia, 64, 65Hb H disease, 64thalassemias, 64

laboratory studies, 59red blood cell membrane disorders

hereditary elliptocytosis, 61hereditary spherocytosis, 59, 61hereditary pyropoikilocytosis, 61

sickle cell diseaseclinical presentation, 65definition, 65epidemiology, 65laboratory diagnosis, 65pathophysiology, 65treatment, 65

unstable Hbs, 66Consolidation, 347, 351Consumption coagulopathy, 118–120Contact activation system, 82Coombs’ test, 70Core-binding factor (CBF) leukemias, 281Coronary artery bypass graft (CABG), 470Coronary artery disease (CAD), 195Corticosteroids, 497C-reactive protein (CRP), 157Cryoprecipitated antihemophilic factor (AHF), 469, 470Cryopreservation, 489Cutaneous gamma-delta T cell lymphoma, 362Cutaneous mastocytosis (CM), 330Cutaneous T cell lymphoma, 362Cyclin D1, 356Cyclosporine, 497Cytarabine, 347Cytogenetic abnormalities, 288Cytogenetic response (CyR), 315Cytogenetic scoring system, 335, 338Cytogenetics, 277

Index

526

Cytokine, allogeneic HCT, 499Cytokine release syndrome (CRS), 430Cytomegalovirus (CMV), 471Cytopenias, 328, 334Cytoreduction, allogeneic HCT, 499Cytotoxic T cells, 220

DDaratumumab, 267Dasatinib, 319Daunorubicin, 347−7/del(7q), 287Del(5q), 287Del(17p/TP53), 294, 295Delayed hemolytic reactions, 75Delayed hemolytic transfusion reactions (DHTRs), 477δ-storage pool deficiency (δ-SPD), 130Dense tubular system, 123Dexamethasone-rituximab-cyclophosphamide (DRC), 385Diapedesis, 210Diffuse alveolar hemorrhage, 491Diffuse large B-cell lymphoma (DLBCL)

DHL, 392, 393diagnostic considerations, 389, 390first-line therapy

advanced stage disease, 390limited stage disease, 390–392relapsed and refractory disease, 390, 392

mature B cell neoplasms, 359, 360prognostic factors, 390t(8;14)/IGH/MYC fusion, 292t(14;18)/IGH/BCL2 fusion in, 292

Digital PCR, 304Dimethyl sulfoxide (DMSO), 488, 489Dipyridamole, 204Direct antiglobulin test (DAT), 69, 70Direct Coombs’ test, see Direct antiglobulin testDirect oral anticoagulants (DOACs), 116–118

andexanet alfa, 186apixaban, 184ciraparantag, 186dabigatran etexilate, 183dosing, 185drug–drug interactions, 186edoxaban, 184idarucizumab, 186invasive procedures, 185monitoring therapy, 184patient selection, 184qualitative and quantitative assays, 184, 185rivaroxaban, 183, 184transitions of Care, 187vs. warfarin, 187warfarin’s drawbacks, 182

Direct oral anti-Xa agents, 117Direct thrombin inhibitor (DTI)

adverse effect, 176argatroban, 173, 175bivalirudin, 173, 175clinical indications, 174frequency of monitoring, 175HIT, 174initiation, titration, and maintenance, 174managing invasive procedures, 175mechanism of action, 173

pharmacodynamics, 173pharmacokinetics, 173site of action, 164transition from, 175transition to anticoagulants, 175

Disseminated intravascular coagulation (DIC), 118, 120, 139, 343, 428

Disseminated juvenile xanthogranuloma (DJXG), 367, 368DNA library, 311DOACs, see Direct oral anticoagulantsDonath-Landsteiner antibody test, 70Donor T cells, 495Dot plots, 256Double-hit lymphoma (DHL), 392, 393Double-negative (DN) thymocytes, 220Drug intolerance, 316Dual antiplatelet therapy (DAPT)

duration, 202, 203therapeutic oral anticoagulation, 202

Dual platform method, 261Duffy antigen receptor complex (DARC), 214Duodenal-type follicular lymphoma, 383, 384Dutcher bodies, 359Dyserythropoiesis, 334Dysmegakaryopoiesis, 334Dysplasia, 334Dysproteinemias, see Plasma cell disorders

EEDTA-induced pseudothrombocytopenia, 146Embden-Meyerhof pathway, 20Embryonic hematopoiesis, 225Endocrine anemia, 22Endonuclease, 302Engraftment, 491

allogeneic HCT, 495Engraftment syndrome, 491, 492Enteropathy-associated TCL (EATL), 362Eosin-5-maleimide (EMA) binding test, 61Eosinopenia, 217Eosinophilia, 217

investigation of, 329, 330management, 329presentation and differential diagnosis, 328

chronic eosinophilic leukaemia and clonal causes, 328, 329PDGFRA, PDGFRB, FGFR1 or PCM1-JAK2, 328

Eosinophils, 2, 216, 217Epinephrine, 475Epstein-Barr virus (EBV), 366, 516Erdheim-Chester disease (ECD), 368Erythrocyte, 2, 26Erythrocyte alloantibodies

neonatal alloimmune hemolysis, 74, 75posttransfusion hemolytic reactions, 75

Erythrocyte autoantibodiesCAD/CAS, 72, 73PCH, 73, 74w-AIHA, 71, 72

Erythrocytosisinvestigation of, 325management, 324, 325presentation and investigation, 324

Erythroferrone production, 15Erythropoiesis, 15Erythropoietin (EPO), 9, 15, 226

Index

527

Essential thrombocythemia (ET)cytogenetic typing, 455definition, 454diagnosis, 455differential diagnosis, 455long-term effects and follow-up, 456management, 326morphology and cytochemistry, 455pathogenesis, 455presentation and investigation, 325, 326prognosis, 454therapy, 455, 456

Euro score, 314EUTOS score, 314Extracorporeal photopheresis (ECP), 498Extramedullary hematopoiesis, 225Extranodal T cell lymphoma, 361, 362

FFactor replacement therapy, 98–100Factor V Leiden (FVL), 152Factor VIII deficiency, 469Factor XIII deficiency, 92, 107Fanconi anemia, 11Febrile nonhemolytic transfusion reactions (FNHTRs), 476Felty’s syndrome, 139Fertility, 353Fetal hematopoiesis, 225Fibrinolytic protein system, 82, 85, 86Fibroblast growth factor receptor 1 (FGFR1), 328Fibroblastic reticular cell tumors (FRCT), 367Filters, 255FIX deficiency, 95Florescence in situ hybridization (FISH), 306Florid follicular hyperplasia PTLD, 366Flow cytometer, 253

advantages, 258, 259applicability, 260–262data display, 256–258electronics, 255, 256IHC vs., 259, 260instrument, 254, 255limitations, 260, 261neoplasia, assessment methods, 263, 264, 267–270optical system, 255platelet disorders, testing for, 262, 263specimen processing, 253, 254

Flow cytometry, 253, 388crossmatch, 262in hematopoietic neoplasia, 260in immunodeficiency, 261sample preparation and technical operations of, 254

Fluidics system, 255Fluorescence, 253Fluorescent “spillover”, 256Fluorescent aerolysin (FLAER), 261Fluorescent in situ hybridization (FISH), 277, 278, 306

applications, 307, 308technique, 306, 307

Fluorochromes, 255Fluoroquinolones, 503Folate deficiency, 22

beneficial effects, 38bone marrow examination, 46causes, 47

classification, 41clinical presentation, 44diagnostic approach, 45drug dosage, 47incomplete response, 47laboraory tests

megaloblastosis, 45peripheral smear, 45

metabolite levels, 46nutrition, 37pathogenesis

chronic tropical sprue, 44drugs, 44nutritional causes, 43pregnancy and infancy, 43–44tropical sprue, 44

physiologyconsequences, 43intracellular metabolism, 42normal folate absorption, 42normal folate transport, 42renal conservation, 43vitamin B12-folate interactions, 42

prognosis, 47systems abnormalities, 44treatment, 47

Folate receptor autoantibodies, 43Follicular dendritic cell sarcoma (FDCS), 367Follicular lymphoma

mature B cell neoplasms, 358pathology, 380t(14;18)/IGH/BCL2 fusion in, 292treatment, 380–382

Fondaparinuxadministeration, 172adverse effect, 173clinical dosing, 172clinical indications, 172managing invasive procedures, 172mechanism of action, 171monitoring, 172pharmacodynamics, 172pharmacokinetics, 172transition from anticoagulants, 173transition to anticoagulants, 173

Formalin-fixed and paraffin-embedded (FFPE) tissue, 278, 291Forward angle light scatter (FSC), 255Fragment analysis technique, 302Fresh-frozen plasma (FFP), 468Fungal infections, 509–514Fusariosis, 513FVIII deficiency, 95

GGalactomannan (GM) antigen test, 512Gap-PCR technique, 303Gating, 257, 258G-banded karyotypes, 305Gene expression profiling (GEP), 308, 389Gene mutations, 277

chromosomal analysis, 277clinical diagnostics, 279FISH, 278genomic microarray testing, 278NGS analysis, 278

Index

528

Gene therapy, 101Genetic mutations, 17Gestational thrombocytopenia, 138GI tract injury, 500Giant metamyelocyte, 38Glanzmann thrombasthenia, 129Global coagulation tests, 112Globin gene disorders, 53Glucose-6-phosphase dehydrogenase deficiency (G6PD)

blackwater fever, 63clinical features, 63geographic distribution, 62hemolysis, risk of, 63pathophysiology, 63variants, 63

Glycoprotein IIb/IIIa inhibitors, 203Glycosyl-phosphatidyl-inositol (GPI) moieties, 260Graft rejection, 492Graft-versus-host disease (GvHD), 495

acuteclinical grading of, 497pathophysiology of, 496, 497prevention of, 497, 498treatment of, 498

chronic, 498, 499pathophysiology of, 496types, 496

Graft-versus-leukemia effect, 495Graft-versus-tumor (GvT) effect, 488Granulocyte-macrophage colony stimulating factor

(GM-CSF), 209Granulocyte-monocyte progenitor cells (GMPs), 209Granulocytes, 240, 471

administration, 471contraindications/adverse events, 471evidence, 471indications, 471

Granulopoiesis, 209Gray platelet syndrome (GPS), 127, 131

HHaematocrit (HCT), 324Hairy cell leukemia (HCL), 359Hans algorithm, 389Haploidentical transplants, 495Haptoglobin, 69HBH disease, 64HELLP syndrome, 141Hemagglutination assay (TPHA), 480Hemarthrosis, 97Hematogones, 244Hematologic malignancies, 277Hematology

blood, physical states, 3lymphocyte system, 3molecular testing (see Molecular testing)mononuclear phagocyte system, 3myeloid system, 2origins of, 1

Hematopoiesisabnormal

anemia, 11blood cells production, 11CHIP, 12leukopenia, 10low number of white blood cells, 10

lymphopenia, 10multilineage cytopenias, 11neutropenia, 10, 11thrombocytopenia, 11

allogeneic HCT, 493hierarchical organization

erythroid compartment, 8hematopoietic stem cell, 6hematopoietic stressors, 8HPCs, 8mature blood cells, 8, 9mature polymorphonuclear neutrophil, 8myeloid precursors, 8

ontogenyadult, 5definitive, 5, 6extramedullary, 6hemoglobin switches, 6myelophthisic anemia, 6primitive RBCs, 5, 6

regulationbone marrow niches, 9extracellular matrix, 9growth factors, 9hereditary/acquired GM-CSF deficiency, 10

Hematopoietic cell transplantation (HCT), 317, 318, 382, 487abbreviations, 488acute, clinical grading of, 497allogeneic, 492, 493

aggressive supportive care, 499bone marrow failure, 493cytoreduction, 499GI tract injury, 500hematopoiesis, 493HLA system, 494immune system, 500immunosuppression, 499infections, 499, 500infusing donor T cells, benefits of, 495infusing donor T cells, disadvantages of, 495–499late effects, 500, 501liver dysfunction, 500lung injury, 500malignancy, 493outcomes, 501storage diseases, 493suitable donor, finding, 494, 495TA-TMA, 500transplant, 499

autologous, 488, 489advantages, 492conditioning, 489, 490cryopreservation and reinfusion of cells, 489disadvantages, 492diseases treated, 489engraftment syndrome and autologous GvHD, 491harvesting, 489hematopoietic growth factors, 490high-dose chemoradiation therapy, consequences, 490idiopathic pneumonia syndrome and diffuse alveolar

hemorrhage, 491outcomes, 491–492peri-transplant complications, 490regimen-related toxicity/organ dysfunction syndromes,

490, 491supportive care during recovery, 490VOD/SOS, 491

Index

529

CLL, 406graft sources, definitions for, 487neoplastic hematologic disorders, 435types, 487

Hematopoietic cells, 236Hematopoietic growth factors, 15Hematopoietic neoplasia, 260Hematopoietic stem cell (HSC) transplantation, 6, 449Hemoglobin (Hb)

forms, 17function, 17oxygenation, 17structure, 16, 17

Hemoglobin constant spring (HbCS), 56Hemoglobinopathies, 493

α−thalassemiaclinical consequences, 54clinical presentation, 55epidemiology, 54HbCS, 56HbH disease, 56hydrops fetalis, 56prognosis, 55silent carrier/α−thalassemia trait, 56treatment, 56α0-mutation, 54

β−thalassemia, 57globin gene mutations, 49peripheral blood smear, 50SCD, 49

clinical presentation and complications, 51, 52diagnosis, 54epidemiology, 51pathophysiology, 51, 52prognosis, 51treatment, 53

Hemoglobinopathy, 22, 36Hemolysis

definition, 67symptoms/signs, 68

Hemolytic disease of the fetus and newborn (HDFN), 474

Hemolytic disease of the newborn (HDN)clinical features, 229laboratory findings, 229management and prevention, 229, 230pathophysiology, 229

Hemolytic enzyme disorderenzyme defects, 64G6PD deficiency, 62, 63PK deficiency, 63pyrimidine 5′ nucleotidase deficiency, 63

Hemolytic hemoglobinopathiesalpha-thalassemias, 64β-thalassemia, 64β-thalassemia major, 65Hb H disease, 64thalassemias, 64

Hemolytic uremic syndromes (HUS)causes/underlying disorders, 76clinical and laboratory findings, 77pathophysiology, 76treatment, 77

Hemolytic-uremic syndrome (HUS), 141, 142Hemophagocytic lymphohistiocytosis (HLH), 219Hemophilia

bleeding manifestations

hemarthrosis, 97hemophilic arthropathy, 97life-threatening, 97muscle bleeding, 97recommended dosing regimens, 97, 100soft tissue bleeding, 97

characteristics, 97clinical classification, 96coagulation factor, inhibitors of, 100–101definition, 95diagnosis, 98epidemiology, 95FIX deficiency, 95FVIII deficiency, 95gene therapy, 101genetics, 96management

acute bleeding episode, 100adjuvant therapy, 100factor replacement therapies, 98–99hemostatic rebalancing therapy, 99substitution therapy, 99

non-factor replacement products, 100Hemophilia A, see FVIII deficiencyHemophilia B, see FIX deficiencyHemophilic arthropathy, 97Hemostasis, 81, 95

adhesion, 123aggregation, 123procoagulant activities, 124secretion, 123

Hemostatic rebalancing therapy, 99Hemostatic system, 227

anticoagulation system, 82, 86, 87blood coagulation proteins, 82cohesive hypothesis, 87, 88components, 81fibrinolytic protein system, 82, 85regulation, 81

Heparin, 113Heparin-induced thrombocytopenia (HIT), 114, 135

argatroban, 174autoimmune, 145bivalirudin, 174clinical features, 145laboratory testing, 146LMWH, 171pathophysilogy, 145repeat heparin exposure, 146treatment, 146

Heparin-induced thrombocytopenia and thrombosis (HITT), 158

Hepatitis B virus (HBV), 516Hepatitis C virus (HCV), 517Hepatosplenic gamma-delta TCL, 362Hepatosplenic T-cell lymphoma (HSTL), 292Hepatosplenomegaly, 229Hereditary elliptocytosis (HE), 61Hereditary folate malabsorption, 43Hereditary immunodeficiency syndromes, 221Hereditary non-spherocytic hemolytic anemia, 20Hereditary pyropoikilocytosis (HPP), 61Hereditary spherocytosis (HS)

clinical manifestations, 61laboratory evaluation, 61pathophysiology, 60treatment, 61

Index

530

Hereditary stomatocytosis, 18Hereditary syndromes, 350Hereditary thrombocytopathic disorders, 138Herpes simplex virus (HSV), 490Herpesviruses, 515Hexose monophosphate shunt, 20HIDAC, 347High resolution melting (HRM) analysis, 302High-dose chemotherapy, 376Histamine receptor (H1 and H2) antagonists, 331Histiocytic and dendritic cell neoplasms, 366Histiocytic sarcoma, 367Histiocytosis X, 366Histogram plots, 256Hodgkin lymphoma (HL), 290–293, 355, 363, 371

CHL, 363, 364clinical evaluation, 373, 374epidemiology, 371long-term sequelae of, 375pathology, 371–373prognostic factors, 364radiation field designs used in, 374treatment, 374

chemotherapy, 374, 375clinical prognostic factors, 376combined therapy, 375–376NLPHL, 376radiation therapy, 374relapsed/refractory, 376, 377

Homocysteine, 153Hormonal therapy, 155Howship’s lacunae, 233H. Pylori eradication (HPE), 383Human hematopoietic system, 225Human leukocyte antigen (HLA) system, 262, 494, 495Hydrodynamic focusing, 255Hydroxycarbamide, 325Hydroxyethyl starch (HES), 471Hyperdiploid clones, 289, 294, 295Hyperhomocysteinemia, 153, 155, 156Hyperleukocytosis, 444Hypersplenism, 77, 138, 139Hypodiploid, 289Hypogammaglobulinemia, 406Hypomegakaryocytic, 137Hypothermia, 139Hypothyroidism, 106

IIbrutinib, 382, 394, 404, 420Idelalisib, 405Idiopathic hypereosinophilia, 329Idiopathic pneumonia syndrome, 491IGH translocations, 294Ig-like transcripts (ILTs), 218IgM MGUS, 411Imatinib, 279, 315, 316, 318IMiDs, 421Immature (precursor) B- and T-cell neoplasms, 387Immune checkpoint inhibition drugs, 382Immune dysregulation, polyendocrinopathy, enteropathy,

X-linked (IPEX), 221Immune hemolytic transfusion reactions, 75Immune system, allogeneic HCT, 500Immune thrombocytopenia (ITP), 113, 262

adults, 141childhood, 141drug-induced autoimmune thrombocytopenia, 143

Immune-checkpoint inhibitors, 418Immune-mediated hemolytic anemia

erythrocyte alloantibodiesneonatal alloimmune hemolysis, 74posttransfusion hemolytic reactions, 75

erythrocyte autoantibodiesCAD or CAS, 72, 73drug-induced AIHA, 74paroxysmal cold hemoglobinuria, 73, 74warm antibody autoimmune hemolytic anemia, 71, 72

hypersplenism, 77Immune-mediated heparin-induced thrombocytopenia

(HIT), 168Immunochemotherapy, 381, 383, 385Immunodeficiency, 261Immunofixation electrophoresis, 411Immunoglobulin heavy chain variable (IGHV) gene, 401Immunoglobulin light chain amyloidosis, 420, 421Immunohistochemistry (IHC)

DLBCL, 389flow cytometer, 259

Immunophenotyping, 388Immunosuppression, 499Immunothrombosis, 158, 159In situ follicular neoplasia, 383Increased platelet consumption

bacteremia, 140cardiovascular disorders, 140DIC, 139fungemia, 140parasitemia, 140TMA, 140

Increased platelet destructionalloimmune thrombocytopenia, 143D-ITP, 145HIT, 145, 146ITP, 141

Indeterminate dendritic cell tumor/sarcoma, 367Indirect antiglobulin test, 69Indirect Coombs’ test, see Indirect antiglobulin testIndolent lymphomas

clinical presentationslymphadenopathy, 379pathology, 380staging, 380

epidemiologic factors, 379treatment

duodenal-type follicular lymphoma, 383, 384follicular, 380–382in situ follicular neoplasia, 383nodal marginal zone lymphoma, 384, 385splenic marginal zone lymphoma, 384

types and frequencies of, 379Induction, 346, 347, 351Infections

allogeneic HCT, 499, 500AML, 444CRBSI, 508fungal, 509–514HCT, 490neutropenic fever, 503, 504, 506pneumonia, 506–508prevention of, 503, 504

Index

531

typhlitis, 508, 509viral

CMV, 515community-acquired respiratory viruses, 516detection, 514EBV, 516epidemiology, 514hepatitis, 516, 517herpesviruses, 514VZV, 515, 516

Infectious mononucleosis PTLD, 366Inflammation, anemia of, 21, 35–36Inflammatory bowel disease (IBD), 154–155Inherited afibrinogenemia, 129Inherited disorders

allogeneic HCT, 493, 494platelet function

activation, 132adhesion, 128aggregation, 129classification, 128granules, 130, 131inherited platelet function defects, 132procoagulant activities, 132secretion, 130transcription factors, 132

plateletsassociated with decreased platelet number, 125bleeding time, 125impaired platelet function, 125in vitro studies, 125, 126peripheral smear, 125platelet count and size, 125

Inherited platelet function defects, 132Inherited thrombocytopenia

autosomal dominantACTN1, 128ANKRD26, 128gray platelet syndrome, 127HOXA11, 128macrothrombocytopenia, 127MECOM, 128MYH9-related thrombocytopenia syndromes, 126Paris-Trousseau platelet disorder, 127RUNX1, 127TUBB1, 128Velocardiofacial/DiGeorge Syndrome, 128

autosomal recessiveBernard-Soulier syndrome, 128congenital amegakaryocytic thrombocytopenia, 128TAR, 128

classification, 126diagnosis, 126gene implication, 126X-linked disorders, 128

Integrins, 210Interdigitating dendritic cell sarcomas, 367Interferon-alfa, 326, 331International prognostic index (IPI), 390International prognostic scoring system (IPSS), 335, 338Intracellular antigens, 254Intracellular epitopes, 259Intrachromosomal amplification of chromosome 21

(iAMP21), 289inv(14)(q11.2q32), 292inv(16)/CBFB/MYH11 fusion, 283

Invasive aspergillosis (IA), 511–513Invasive Candida infections, 510–512Inverse shifting-PCR (IS-PCR), 303Iron cycle

cellular iron uptake and distribution, 31intestinal iron absorption, 30iron excretion, 31

Iron deficiencyanemia, 21anemia of inflammation, 35causes

GI blood loss, 32in infancy, 32in women, 32

depletion, 31hemoglobinopathy, 36laboratory diagnosis

bone marrow aspiration, 34complete blood count, 33peripheral smear, 33serum ferritin, 33sTfR, 34

metabolismbody iron distribution, 29body iron exchange, 29iron cycle, 30, 31

prevalence, 31sideroblastic anemia, 36signs, 33symptoms, 33thalassemia major or minor, 36treatment, 34, 35

Iron depletion or repletion, 138Iron overload, 467, 479Iron-chelating agents, 479Irradiated cellular products, 472Irradiation, transfusion medicine, 472Isavuconazole, 353Ischemic stroke, 52ISHAGE method, 262Isochromosome of the long arm of chromosome 7 [i(7)(q10)], 292Ixodes, 481

JJacobsen syndrome, 127Jak1/2 inhibitors, 323, 328, 429Juvenile myelomonocytic leukemia (JMML)

clinical symptoms, 451definition, 450diagnosis, 450differential diagnosis, 450–452immune phenotyping, 451incidence, 450long-term effects and follow-up, 452pathogenesis, 450prognosis, 450relapse, 452therapy, 451

KKaryogram, 304Karyotyping, see Chromosomal analysisKiller cell immunoglobulin-like receptors (KIR), 218KMT2A methylates histone H3 lysine 4 (H3K4), 282

Index

532

LLactate dehydrogenase (LDH), 69Lactic acidosis, 427Langerhans cell histiocytosis, 366Langerhans cell sarcomas, 367Lasers, 255Lenalidomide, 382, 394, 405Leptomeningeal disease, 347Letermovir, 515Leucoerythroblastic pattern, 6, 327Leukemia, 424Leukemic T cell lymphoma, 362Leukocyte adhesion deficiency, 215Leukocyte reduction, 471, 472Leukocytes, 151

cellular components, 81physiological roles

basophils and mast cells, 217eosinophils, 216–217lymphocytes, 218–221monocytes, 217–218myeloid cells, 209–212neutrophils, 212–216

subsets, 209Leukopenia, 10Leukostasis, 352, 444Light and heavy chain deposition diseases, 421Light chain MGUS (LC-MGUS), 414Lipoprotein(a) (LP (a)), 153, 157Liver dysfunction, 500Low-molecular-weight heparin (LMWH)

administration, 170clinical dosing, 170dalteparin, 170enoxaparin, 170heparin-induced thrombocytopenia, 171managing bleeding and reversal, 171managing invasive procedures, 171mechanism of action, 169monitoring, 170pharmacokinetic, 169transition from anticoagulants, 171transition to anticoagulants, 171

Lumbar puncture (LP), 347, 434, 437Lung injury, allogeneic HCT, 500Lymph node biopsy, 356Lymphadenopathy, 379Lymphocyte function-associated antigen 1 (LFA1), 210Lymphocyte system, 3Lymphocyte-depleted CHL, 364Lymphocyte-predominant (LP) cells, 364Lymphocyte-rich CHL (LRCHL), 364Lymphocytes, 244

B lymphocytes, 219, 220natural killer cells

CKND, 218CNKL, 219hemophagocytic lymphohistiocytosis, 219mechanisms, 218ontogeny, 218tumor surveillance, 218

T cellsactivated T cells, 220AIDS, 221cytotoxic T cells, 220double-negative thymocytes, 220

FOXP3, 221hereditary immunodeficiency syndromes, 221IPEX, 221Omenn syndrome, 221Treg cells, 221

Lymphoid antigens, aberrant expression of, 270Lymphoid cell subsets, enumeration of, 261Lymphomas, 355

classification, 355REAL, 355WHO, 355, 356

diagnosis, 356mature B cell neoplasms, 356–360mature T and NK cell neoplasms, 360–362

histiocytic and dendritic cell neoplasms, 366DJXG, 367, 368Erdheim-Chester disease, 368FDCS, 367FRCT, 367histiocytic sarcoma, 367indeterminate dendritic cell tumor/sarcoma, 367interdigitating dendritic cell sarcomas, 367Langerhans cell histiocytosis, 366Langerhans cell sarcomas, 367

Hodgkin lymphoma, 363CHL, 363, 364prognostic factors, 364, 365

PTCL treatment and prognosis, 362, 363PTLD, 365, 366

classical Hodgkin, 366florid follicular hyperplasia, 366infectious mononucleosis, 366monomorphic, 366plasmacytic, 366polymorphic, 366

Lymphomatoid papulosis (LP), 362Lymphopenia, 10Lymphoplasmacytic lymphoma (LPL), 359, 384, 419

MMacrocytosis, 447Macroglossia, 420Macrophage-1 antigen (Mac-1), 210Macrophages, 245Malaria, 23, 43, 46, 51, 140, 481Malignancy, allogeneic HCT, 493Mantle cell lymphoma, 292, 356Mantle cell lymphoma (MCL)

diagnostic considerations, 393frontline treatment, 393, 394prognostic factors, 393relapsed/refractory MCL, 394

Marrow cellularity, 236Massive transfusion protocol (MTP), 473Mast cells, 217, 245Mastocytosis, 323

diagnosis, 330management, 331presentation, 330

Matched unrelated donor (MUD) graft, 492Mature B- and T-cell NHL, 290–292Mature B cell neoplasms, 356, 357

CLL, 356, 357DLBCL, 359, 360follicular lymphoma, 358

Index

533

HCL, 359LPL/Waldenström Macroglobulinemia, 359mantle cell, 356marginal zone/MALT, 358MBL, 357

Mature blood cells, 8, 9Mature peripheral T-cell lymphomas, 387

first line treatment, 397relapsed and refractory disease, 397

Mayo Stratification for multiple myeloma and risk-adapted therapy (mSMART), 419

Mean corpuscular volume (MCV), 24, 27Medullary hematopoiesis, 225Megakaryocytes, 243, 248Megaloblastic anemia, 8, 37, 38, 137Meningeosis leucaemica, 435Menses, fertility and suppression of, 353Mepacrine, 263Mesenchymal stromal cells (MSCs), 498Metabolic syndrome, 154Metamyelocyte, 241Metaphase chromosomes, 305Methemoglobin reduction pathway, 20Methotrexate (MTX), 497Microangiopathic hemolytic anemia (MAHA), 23, 76Microarray, 277, 278Microthrombocytopenia, 137Minimal residual disease (MRD), 273

AML, 347CLL, 404diagnosis, 435, 436neoplastic hematologic disorders, 429

Minipool (MP), 480Mixed cellularity HL, 364Mixed phenotype acute leukemias (MPAL), 349Mobilized blood cell harvesting, 489Mobilized blood progenitor cells, 489Molecular assays, 299Molecular immunohematology, 474Molecular response, 315Molecular testing

array, 307, 308chromosomal analysis, 304, 305

applications, 306cytogenetic technique, 305, 306

digital PCR, 304FISH, 306

applications, 307, 308technique, 306, 307

Gap-PCR, 303HRM analysis, 302IS-PCR, 303MLPA, 303, 304molecular assays, material for, 299PCR, 299, 300qPCR, 301

allele-specific oligonucleotide PCR/ARMS, 301, 302applications, 301design, 301multiplex PCR, 301post-PCR fragment analysis/sizing assay, 302

RFLP, 302RT-PCR, 300sequencing, 308–310

NGS, 309–311Sanger sequencing, 309, 310

STR analysis, 303types of, 311

Monoclonal antibodies, 253, 267, 403based regimens, 417neoplastic hematologic disorders, 429, 430

Monoclonal B-cell lymphocytosis (MBL), 12, 357Monoclonal gammopathy of undetermined significance (MGUS), 294,

411, 414Monoclonal gammopathy of unknown significance (MGUS), 12Monoclonal Ig, 411Monocytes, 2, 217, 244Monocytic leukemia, 441Monocytopenia, 217Monocytosis, 217Monomethyl auristatin E (MMAE), 377Monomorphic PTLD, 366Mononuclear phagocyte system, 3Monosomal karyotypes, 279M-spike, 411Mucormycosis, 513Mucosa-associated lymphoid tissue (MALT) lymphoma, 383, 384

mature B cell neoplasms, 358t(11;18)/API1/MALT1 fusion and MALT1 fusion, 292

Mucositis, prophylaxis and therapy of, 426, 427Multilineage cytopenias, 11Multiple myeloma, 294, 295Multiple myeloma (MM)

clinical manifestations and workup, 416epidemiology, 414, 415pathophysiology, 415, 416risk stratification systems in, 418treatment of, 416, 417, 419

Multiplex ligation-dependent probe amplification (MLPA), 303, 304

Multiplex PCR, 301Mycophenolate mofetil (MMF), 498Mycophenolic acid, 498Mycosis fungoides, 362Myeloblasts, 263, 265Myelocyte, 241Myelodysplastic syndromes (MDS), 286, 287, 424

and AML, gene mutations in, 287classification, 446

FAB, 334WHO, 334–337

clinical presentation, 333clinical symptoms, 448cytogenetic and molecular characteristics, 335cytogenetic typing, 448definition, 445Del(5q) and 5q- syndrome, 287−7/del(7q), 287diagnosis, 446differential diagnosis, 446epidemiology, 333evaluation and differential diagnosis, 334HCT, 449immune phenotyping, 448incidence, 446IPSS, 335, 338long-term effects and follow-up, 450morphology and cytochemistry, 447pathogenesis, 333, 446pathologic features, 334prognosis, 446relapse, 450

Index

534

Myelodysplastic syndromes (MDS) (cont.)t-AML/MDS, 287, 288treatment

higher-risk MDS, 339, 340lower-risk MDS, 338, 339

Myelofibrosis, 327Myeloid cells

absolute number, 209automated cell counter, 209basophils, 217differential cell count, 209eosinophils, 216, 217mast cells, 217monocytes, 217neutrophils

elimination, 212integrins, 210NETosis, 212PAD4, 212production, 209qualitative neutrophil defects, 215, 216quantitative neutrophil defects, 212, 215sterile inflammatory stimuli, 212

subsets, 209variations, 209

Myeloid lineage cells, 15Myeloid system, 2Myelomonocytic leukemia, 441Myelophthisis, 22Myelopoiesis, 227Myeloproliferative neoplasms (MPNs), 8, 158, 323

diagnosis, 323eosinophilia

investigation, 329management, 329presentation and differential diagnosis, 328, 329

erythrocytosis and polycythaemia veramanagement, 324, 325presentation and investigation, 324

investigations, 323mastocytosis

diagnosis, 330mediator-release symptoms, 331presentation, 330reducing mast cell burden, 331

molecular abnormalities, 324PMF

diagnosis, 327management, 327, 328presentation, 326, 327prognosis, 327

thrombocytosis and essential thrombocythaemiamanagement, 326presentation and investigation, 325

World Health Organization classification, 323MYH9-associated macrothrombocytopenia, 137MYH9-related thrombocytopenia syndromes, 126

NNatural killer (NK) cells

CKND, 218CNKL, 219hemophagocytic lymphohistiocytosis, 219mechanisms, 218ontogeny, 218tumor surveillance, 218

NCCN-International Prognostic Index (NCCN-IPI), 390Neonatal alloimmune hemolysis

clinical and laboratory findings, 74pathophysiology, 74treatment, 75

Neonatal alloimmune thrombocytopenia (NAIT), 230Neonatal autoimmune hemolytic anemia, 231Neonatal autoimmune neutropenia, 231Neonatal autoimmune thrombocytopenia (NITP), 231Neoplasia, assessment methods, 263, 264, 267, 268Neoplastic hematologic disorders, children and adolescents, 424

acute complications during chemotherapyDIC, 428peripheral neuropathy, 428thrombophilia, 428tumor lysis syndrome, 427, 428

ALLchemical diagnosis, 434chemotherapy, 435clinical symptoms, 433, 434cytochemistry, 432cytology, 432definition, 430, 431diagnosis, 431immune phenotyping, 432, 433initial patient admission, 434–435morphology, 432MRD, 435, 436pathogenesis, 431prevalence, 430prognosis, 431relapse, 435

AMLclinical symptoms, 443, 444cytogenetic typing, 440, 443, 444definition, 436diagnosis, 437differential diagnosis, 437hyperleukocytosis and leukostasis, 444immune phenotyping, 438, 443incidence, 436morphology and cytochemistry, 437, 439, 440, 443pathogenesis, 437prognosis, 436relapse, 445therapy, 444, 445

chronic myeloproliferative diseases, 452CML, 452–454essential thrombocythemia, 454–456PMF, 456–458polycythemia vera, 458–460

epidemiology, 424JMML

clinical symptoms, 451definition, 450diagnosis, 450differential diagnosis, 450–452immune phenotyping, 451incidence, 450long-term effects and follow-up, 452pathogenesis, 450prognosis, 450relapse, 452therapy, 451

MDSclassification, 446clinical symptoms, 448

Index

535

cytogenetic typing, 448definition, 445diagnosis, 446differential diagnosis, 446HCT, 449immune phenotyping, 448incidence, 446long-term effects and follow-up, 450morphology and cytochemistry, 447pathogenesis, 446prognosis, 446relapse, 450

pediatric neoplasia, causes of, 424, 425supportive care, 426

antiemetic prophylaxis and therapy, 426antifungal prophylaxis, 427blood components, substitution of, 427mucositis, prophylaxis and therapy of, 426, 427Pneumocystis jirovecii prophylaxis, 427

targeted therapy, 428CAR T cell therapy, 430monoclonal antibodies, 429, 430TKI, 428, 429

therapyCNS prophylaxis, 425CNS radiotherapy, 425, 426consolidation phase, 425induction phase, 425maintenance therapy, 425re-induction phase, 425

Neoplastic T cells, 268NETosis, 212Neutropenia, 10, 11, 212, 503Neutropenic fever, 353

algorithm, management, 506empirical antimicrobial treatment of, 505infections, 503, 504, 506

Neutrophil dysplasia, 334Neutrophilia, 215Neutrophils, 2

elimination, 212integrins, 210NETosis, 212PAD4, 212production, 209qualitative neutrophil defects, 215, 216quantitative neutrophil defects

artificial surfaces, 215autoimmune diseases, 214drugs, 215hypersplenism, 215infections, 215medications, 214myelophthisis, 214sepsis, 215

sterile inflammatory stimuli, 212Next-generation sequencing (NGS), 309

applications, 310technique, 277, 278, 310, 311

Nilotinib, 315, 316, 318, 319, 429NK subtype mucosal PTCL, 362NK/T cell neoplasms, 360

cutaneous T cell lymphoma, 362diagnosis, 360extranodal T cell lymphoma, 361, 362leukemic T cell lymphoma, 362nodal T cell lymphoma

AITL, 361ALCL, 361BIA-ALCL, 361peripheral T cell lymphoma, 360, 361

Nodal marginal zone lymphoma, 384Nodal T cell lymphoma

AITL, 361ALCL, 361BIA-ALCL, 361peripheral T cell lymphoma, 360, 361

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), 364, 365, 372, 376

Nodular sclerosing CHL (NSCHL), 364Non-factor replacement products, 100Non-hematopoietic elements, 245Non-Hodgkin lymphoma (NHL), 290–292, 355, 379, 387

inv(14)/t(14;14)/TRAD/TCL1 fusion, 292t(2;5)/ALK/NPM1 fusion, 292t(11;14)/IGH/CCND1 fusion, 292t(11;18)/API1/MALT1 fusion and MALT1 fusion, 292t(14;18)/IGH/BCL2 fusion, 292

Non-IgM MGUS, 411Nonimmune hemolytic transfusion reactions, 75Nonneoplastic hematologic processes, flow cytometry, 260NOTCH1 mutations, 294NT-ProBNP, 421Nuclear hyposegmentation, 334Nucleic acid test (NAT), 480Nutrient artery, 235

OObinutuzumab, 382, 403Obstetrics, 473, 474Occlusive vascular disease, 44Ocular lymphoma, 384Ofatumumab, 403Omacetaxine, 320Omenn syndrome, 221Ontogeny

adult, 5definitive, 5, 6extramedullary, 6hemoglobin switches, 6myelophthisic anemia, 6primitive RBCs, 5, 6

Opportunistic infections, 353Oral anticoagulants

direct oral anticoagulantsandexanet alfa, 186apixaban, 183, 184ciraparantag, 186dabigatran etexilate, 183dosing, 185drug–drug interactions, 186idarucizumab, 186invasive procedures, 185monitoring therapy, 184patient selection, 184qualitative and quantitative assays, 184, 185rivaroxaban, 184transitions of care, 187vs. warfarin, 187

vitamin K antagonistadverse events, 181, 182anticoagulation management, 182clinical indications, 178

Index

536

Oral anticoagulants (cont.)cssation of therapy, 182dose maintenance, 178drug interactions, 180frequency of monitoring, 179initiation of therapy, 178invasive procedures, 180mechanism of action, 176out-of-range INR, 179pharmacodynamics, 177, 178pharmacokinetics, 177, 178

Organ dysfunction syndromes, 490, 491Orthochromic erythroblast, 242Orthostatic hypotension, 421Oscillatory or turbulent non-unidirectional shear stress, 159Osmotic fragility test, 61Osteoblasts, 233, 245Osteoclasts, 233, 234, 245Osteocytes, 234Osteomyelofibrosis, 456Osteonecrosis of the jaw (ONJ), 419Osteopetrosis, 493Osteoporosis, 169Ovarian leukemic relapse, 435

PPancytopenia

acquired disorder, 136bone marrow injury, 137congenital/hereditary disorder, 136infiltration, 136nutritional disorders, 137

Panniculitis subcutaneous T cell lymphoma alpha-beta subtype, 362

Parenteral anticoagulantsdirect thrombin inhibitor

adverse effect, 176argatroban, 173, 175bivalirudin, 173, 175clinical indications, 174frequency of monitoring, 175HIT, 174initiation of therapy, 174initiation, titration, and maintenance, 174managing invasive procedures, 175mechanism of action, 173pharmacodynamics, 173pharmacokinetics, 173site of action, 164transition from, 175transition to anticoagulants, 175

fondaparinuxadministeration, 172adverse effect, 173clinical dosing, 172managing invasive procedures, 172mechanism of action, 171monitoring, 172pharmacodynamics, 172pharmacokinetics, 172transition from anticoagulants, 173transition to anticoagulants, 173

indirect thrombin and/or Xa inhibitors, 163low- molecular- weight heparin

administration, 170clinical dosing, 170dalteparin, 170enoxaparin, 170heparin-Induced thrombocytopenia, 171managing bleeding and reversal, 171managing invasive procedures, 171mechanism of action, 169monitoring, 170pharmacodynamic, 169transition from anticoagulants, 171transition to anticoagulants, 171

unfractionated heparinabnormal liver function tests, 169bleeding and reversal, 168clinical indications, 164frequency of monitoring, 168immune-mediated HIT, 168initiation of therapy, 165invasive procedures, 168maintenance dosing and titration, 168mechanism of action, 163osteoporosis, 169pharmacodynamics, 164pharmacokinetics, 164transition from anticoagulants, 169transition to anticoagulants, 169

Paris-Trousseau platelet disorder, 127Paroxysmal cold hemoglobinuria (PCH)

causes/underlying disorders, 73clinical and laboratory findings, 74pathophysiology, 73treatment, 74

Paroxysmal cold hemoglobinuria (PCH), 73, 74Paroxysmal nocturnal hemoglobinuria (PNH), 23, 67, 158, 260

causes/underlying disorders, 78clinical and laboratory findings, 78pathophysiology, 78treatment, 79

Passive alloimmune thrombocytopenia (PAT), 143Patient blood management (PBM) programs, 465Patient hemovigilance, 482PCM1-JAK2, 328PD-1 inhibitors, 377Pediatric hematology

abnormal fetomaternal cell trafficANN, 230HDN, 229, 230NAIT, 230

coagulation system, 227, 228embryonic and fetal hematopoiesis, 225erythropoietin, after birth, 226hemoglobin synthesis, 226human hematopoietic system, 225myelopoiesis, 227placental insufficiency, 228platelet count, 227transplacental transfer of maternal autoantibodies, 230

Pediatric neoplasia, causes of, 424, 425Peptidylarginine deiminase 4 (PAD4), 212Peripheral artery disease (PAD), 196Peripheral neuropathy, 428Peripheral T cell lymphoma (PTCL), 360, 361Peripheral T-cell lymphoma, not otherwise specified

(PTCL-NOS), 396

Index

537

Permeabilization, 254Phenotypic aberrancy, 273Philadelphia chromosome, 314, 315Philadelphia chromosome (Ph1), 425Phospholipid-bound proenzymes, 82Photomultiplier tube (PMT), 255PI3-K inhibitors, 405Plasma, 468, 469Plasma cell disorders (PCD), 411

characteristic, 412–413immunoglobulin light chain amyloidosis, 420, 421MGUS, 411, 414multiple myeloma

clinical manifestations and workup, 416epidemiology, 414, 415pathophysiology, 415, 416treatment of, 416, 417, 419

POEMS, 421tests and procedures, 417treatment, antineoplastic medications, 418Waldenstrom Macroglobulinemia, 419, 420

Plasma cell dyscrasias, see Plasma cell disordersPlasma cell myeloma, 267, 272Plasma cell neoplasms, 294, 295Plasma cells, 244, 265, 271Plasma coagulation assays, 90Plasma protein defect, 89Plasmacytic hyperplasia PTLD, 366Plasma-free hemoglobin, 69Plasminogen activated inhibitor-1 (PAI-1), 85, 154Plasminogen activator inhibitor-1 deficiency, 93Plasmodium spp., 481Platelet abnormality, 89Platelet count, 90Platelet disorders, testing for, 262, 263Platelet function

in hemostasisadhesion, 123aggregation, 123procoagulant activities, 124secretion, 123

inherited disordersactivation, 132adhesion, 128aggregation, 129classification, 128granules, 130inherited platelet function defects, 132procoagulant activities, 132secretion, 130transcription factors, 132

Platelet function analyzer (PFA-100), 126Platelet satellitism, 147Platelet transfusion refractoriness, 144Platelet-derived growth factor receptor alpha (PDGFRA), 328Platelet-derived growth factor receptor beta (PDGFRB), 328Platelets, 2, 334, 470

activating mechanisms, 125administration, 470, 471bacterial contamination, 480contraindications/adverse event, 470elaborate channel system, 123evidence, 470indications, 470inherited disorders

associated with decreased platelet number, 125bleeding time, 125impaired platelet function, 125in vitro studies, 125, 126peripheral smear, 125platelet count and size, 125

inherited thrombocytopeniaautosomal dominant, 126–128autosomal recessive, 128classification, 126diagnosis, 126gene implication, 126X-linked disorders, 128

number, 125structure, 123

Platelets dense tubular system, 123Platelets open canalicular system, 123Platelets organelles, 123Ploidy, 431Pluripotent hematopoietic stem cells (HSC), 15Pneumocystis jirovecii pneumonia (PCP), 513Pneumocystis jirovecii prophylaxis, 427Pneumonia

diagnostic tests in, 507etiology of, 505infections, 506–508

Poikilocytosis, 25Polychromatophilic erythroblast, 242Polycythemia vera (PV)

clinical symptoms, 459cytogenetic typing, 459definition, 458diagnosis, 458differential diagnosis, 458long-term effects and follow-up, 460management, 324, 325morphology and cytochemistry, 458pathogenesis, 458presentation and investigation, 324prognosis, 458therapy, 460

Polymerase chain reaction (PCR), 299, 300Polymorphic PTLD, 366Polyneuropathy, organomegaly, endocrinopathy, monoclonal

gammopathy, and skin (POEMS), 421Ponatinib, 316, 319, 320Popcorn cells, 372Posaconazole, 353Positron emission tomography with contrast-enhanced computed

tomography (PET/CT), 389Postpartum hemorrhage (PPH), 473Post-PCR fragment analysis/sizing assay, 302Posttransfusion purpura (PTP), 143, 478, 479Posttransplant lymphoproliferative disorder

(PTLD), 365, 366, 500classical Hodgkin, 366florid follicular hyperplasia, 366infectious mononucleosis, 366monomorphic, 366plasmacytic, 366polymorphic, 366

Posttransplantation cyclophosphamide (PTCY), 498Pregnancy, 473Pretransfusion testing, 464Primary cutaneous acral CD8-positive TCL, 362

Index

538

Primary cutaneous anaplastic large cell lymphoma and lymphomatoid papulosis, 362

Primary cutaneous small/medium CD4-positive T cell lymphoproliferative disorder, 362

Primary hemostasis, 111qualitative defects, 114, 115quantitative defects, 113, 114

Primary myelofibrosis (PMF)clinical symptoms, 456, 457cytogenetic typing, 456definition, 456diagnosis, 327, 456differential diagnosis, 456incidence, 456long-term effects and follow-up, 457, 458management, 327

allogeneic hematopoietic cell transplantation, 327blast phase, 328constitutional symptoms, 328cytopenias, 328splenomegaly, 327, 328

morphology and cytochemistry, 456, 457pathogenesis, 456presentation, 326, 327prognosis, 327, 456therapy, 457World Health Organization criteria, 327

Primary neutrophilia, 215Prions, 481Proerythroblast, 242Progenitor cells, 489Prognostic Index for AITL (PIAI), 361Progressive cerebral vasculopathy, 52Promyelocyte, 241, 282Prophylactic CNS radiotherapy (pCRT), 425Protease-activated receptor 1 (PAR-1) antagonists, 204Protein C/protein S system, 86Prothrombin complex concentrates (PCCs), 117, 473Prothrombin time (PT), 90, 91Pseudothrombocytopenia, 146, 147Pulmonary embolism, 140Pulmonary marginal zone lymphoma, 383Pure red cell aplasia, 22Purine analog drugs, 402, 478P2Y12 antagonists

cangrelor, 201, 202clopidogrel, 199, 200mechanism of action, 198prasugrel, 200ticagrelor, 200, 201ticlopidine, 198

Pyrimidine 5′ nucleotidase (P5N) deficiency, 63Pyruvate kinase (PK) deficiency, 63

Q5q-syndrome, 6111q23/KMT2A (MLL) translocations, 282Quality-adjusted life year (QALY), 483Quantitative PCR (qPCR), 301Quebec platelet disorder (QPD), 131

RRadiation therapy (RT), 382, 383

Hodgkin lymphoma, 374Rapamycin, 498

Rapid plasma reagin (RPR) assays, 480Rapoport-Luebering pathway, 20Rare bleeding disorders (RBD)

bleeding manifestation, 106definition, 106diagnosis, 107epidemiology, 106management, 107–109

Rare connective tissue disorders, 92Red blood cell membrane defects, 23Red blood cell membrane disorders

hereditary elliptocytosis, 61hereditary spherocytosis

clinical manifestations, 61laboratory evaluation, 61pathophysiology, 60treatment, 61

Red blood cells (RBCs), 466–468development stages, 16early development, 15Embden-Meyerhof pathway, 20enzyme defects, 23hexose monophosphate shunt, 20membrane, 18membrane defects, 23methemoglobin reduction pathway, 20oxyhemoglobin dissociation curve, 17parameters, 22regulation of growth, 15

Red cell distribution width (RDW), 24, 27Reduced-intensity conditioning (RIC), 493Reed-Sternberg cells, 377Regimen-related toxicity/organ dysfunction

syndromes, 490, 491Relapse

CML, 453MDS, 450

Relapsed and refractory disease, 390, 395, 397Relapsed/refractory Hodgkin lymphoma, 375–377Relapsing-remitting multiple sclerosis (RRMS), 221Renal disease, 21, 414Restriction fragment length polymorphism (RFLP), 302Reverse transcription PCR (RT-PCR), 300Revised international prognostic scoring system (IPSS-R)

classification, 338, 339Ribonucleotide reductase inhibitor, 325Richter transformation, 406Ring sideroblasts, 249, 334Risk-based decision-making (RBDM), 482, 483Ristocetin cofactor assay (vWF:RCo), 102Ristocetin-induced platelet aggregation (RIPA), 104Rituximab, 381, 383, 403, 406RNA microarray, 308Ruxolitinib, 429

SSalvage chemotherapy, 375, 376Sanger sequencing technique, 309Schilling test, 47SCID-repopulating capacity (SRC), 6Secondary erythrocytosis

acquired, 458causes of, 324

Selective IgA deficiency, 220Selective serotonin release inhibitors (SSRI’s), 115Sepsis, 111

Index

539

Sequencing, 308, 309NGS, 309

applications, 310technique, 310, 311

Sanger sequencing, 309, 310Serious Hazards of Transfusion (SHOT), 478, 482Serotonin release assay (SRA), 146Serum aspartate aminotransferase (AST), 69Serum concentration of transferrin receptor (sTfR), 34Serum protein electrophoresis (SPEP), 411, 414Severe combined immunodeficiency, 493Severe combined immunodeficiency (SCID), 10Sezary syndrome, 268, 362SF3B1 gene, 294Sheath fluid, 255Short arm of chromosome 17, 285Short tandem repeat (STR) analysis, 303Sickle cell anemia (SCA), 49Sickle cell disease (SCD)

clinical complications, 51, 52clinical presentation, 51, 52, 65definition, 65diagnosis, 54epidemiology, 51, 65laboratory diagnosis, 65pathophysiology, 65prognosis, 51subtypes, 51treatment, 53, 65

Side angle light scatter (SSC), 255, 258Sideroblastic anemia, 22, 36Sideroblasts, 34, 249Single nucleotide polymorphism (SNP)

microarray technique, 308probes, 278

Single platform method, 262Sinusoidal obstruction syndrome (SOS), 491, 500Sirolimus, 498, 500Sizing assay, 302Sokal score, 314Spirochetes, 480Splenic marginal zone lymphomas (SMZL), 358, 384Splenomegaly, 327, 328St. Jude’s staging system, 395Staining, 253Staphylococcus spp., 480Stem cell enumeration, 261Steroids, 406Storage diseases, 493Stromal cells, 9, 233, 235, 245Substitution therapy, 99Syndromic hypomegakaryocytic thrombocytopenia, 137Syngeneic, 488, 494Syphilis, 480Systemic mastocytosis (SM), 328, 330

diagnosis, 330diagnostic criteria in, 331management, 331presentation, 330

TTacrolimus, 497T cell histiocyte-rich LBCL (THRLBCL), 364, 365T cell large granular lymphocytic leukemia

(T-LGL), 362T cell leukemia, 430

T cell lymphocytesactivated T cells, 220AIDS, 221cytotoxic T cells, 220double-negative thymocytes, 220FOXP3, 221hereditary immunodeficiency syndromes, 221IPEX, 221Omenn syndrome, 221Treg cells, 221

T cell lymphomas, 268T cell lymphoproliferative disorders, 269T cell malignancies, 270T cell neoplasia, 265T cell prolymphocytic leukemia (T-PLL), 292, 362T cell receptor (TCR), 268T-cell depletion, 498T-cells with chimeric antigen receptors (CAR-T), 418Terminal deoxynucleotide transferase (TDT), 267Thalassemia, 49Therapeutic CNS radiotherapy (tCRT), 426Therapy-related myeloid neoplasia (t-AML/MDS), 288Therapy-related myeloid neoplasm, 288Thrombin clotting time (TCT), 90, 91Thrombin generation time (TGT) curve, 84Thrombin-activable fibrinolysis inhibitor (TAFI), 154Thrombocytopenia, 11, 113, 474

classification, 135, 136clinical feature, 135, 136, 144decreased platelet production

isolated thrombocytopenia, 137–138pancytopenia, 136–137

hemodilution, 138hypersplenism, 138, 139hypothermia, 139increased platelet consumption

bacteremia, 140cardiovascular disorders, 140DIC, 139fungemia, 140parasitemia, 140TMA, 140

increased platelet destructionalloimmune thrombocytopenia, 143D-ITP, 145HIT, 145, 146ITP, 141

platelet count, 135pseudothrombocytopenia, 146, 147

Thrombocytopenia with absent radii (TAR), 128Thrombocytopenia-absent radius (TAR)

syndrome, 131, 137Thrombocytosis

investigation of, 326management, 326presentation and investigation, 325, 326

Thromboembolism, 149Thrombophilia, 188, 428Thrombosis

arterialetiology, 155occurrence, 149pathogenesis, 155risk factor, 155–157

causes, 149combined thrombosis

antiphospholipid syndrome, 157

Index

540

Thrombosis (cont.)HITT, 158immunothrombosis, 158, 159molecular regulators, 159, 160myeloproliferative neoplasms, 158PNH, 158TMAs, 158

pathogenetic features, 150platelets vs. fibrin clots, 150risk factors, 149venous

acquired risk factors, 154–155complications, 152components, 151endothelial dysfunction or damage, 151inherited-risk factors, 152–154intravital microscopy imaging techniques, 151occurrence, 149pathogenesis, 151vessel wall injury, 151

Thrombotic microangiopathy (TMA), 76, 113, 140, 158Thrombotic thrombocytopenic purpura (TTP), 76, 140Ticlopidine, 198Time delay integration, 256Tisagenlecleucel, 352Tisagenlecleucel (B-ALL) l, 430Tissue factor pathway inhibitor (TFPI), 87Tranexamic acid (TXA), 328, 473Transformed lymphoma, 395Transfusion medicine, 463

adverse events and side effectsAHTRs, 474, 475ATRs, 475DHTRs, 477FNHTRs, 476iron overload, 479PTP, 478, 479TACO, 477TA-GVHD, 477, 478TRALI, 476, 477TRIM, 479

AHF, 469, 470blood bank policies and procedures

blood utilization/transfusion committees, 465pretransfusion testing, 464transfusion administration and monitoring, 464, 465

CMV-serology testing, 472delayed adverse events/side effects, 477donors, 463, 464granulocytes, 471immediate adverse events and side effects, 475immunized patients, 474irradiation, 472leukocyte reduction, 471, 472massive transfusion, 473neonates/pediatrics, 474obstetrics, 473, 474plasma, 468, 469platelet, 470, 471RBCs, 466–468safety considerations

health economics and cost-effectiveness, 482, 483pathogen reduction, 481, 482patient hemovigilance, 482platelets, bacterial testing of, 482RBDM, 482, 483

transfusion/mitigation measures, 472, 473TTI, 479, 480

bacteria, 480, 481blood donor screening and blood testing approaches, 480parasites, 481pathogen reduction technologies, 480prions, 481viruses, 480

volume reduction, 472washing, 472whole blood, 465, 466

Transfusion-associated cardiac overload (TACO), 472Transfusion-associated circulatory overload (TACO), 467, 477Transfusion-associated graft-versus-host disease

(TA-GVHD), 477, 478Transfusion-related acute lung injury

(TRALI), 469, 476, 477Transfusion-related immunomodulation (TRIM), 479Transfusion-transmitted infection (TTI), 479, 480

bacteria, 480, 481blood donor screening and blood testing approaches, 480parasites, 481pathogen reduction technologies, 480prions, 481viruses, 480

Transmissible spongiform encephalopathies (TSEs), 481Transplantation-associated alloimmune thrombocytopenia, 144Transplantation-associated thrombotic microangiopathy

(TA-TMA), 500Transthyretin amyloidosis (ATTR), 420Traumatic hemolytic anemia

due to DIC, 76external impact, 75HUS, 76, 77macrovascular defects-prostheses, 76microangiopathic hemolytic anemia, 76microvascular abnormalities, 77thrombotic microangiopathy, 76thrombotic thrombocytopenic purpura, 76

T-regulatory cells (Tregs), 221Trephine, 326Treponema pallidum, 480Trisomy 21, 424Troponin T, 421True protein deficiency, 89Trypanosoma cruzi, 481TTP-mimicking disorders, 140, 141Tumor lysis syndrome (TLS), 352, 395, 427, 428Typhlitis, 508, 509Tyrosine kinase inhibitors (TKI), 314

ALL, 352CML, 314, 315ELN definition of response, 315, 316neoplastic hematologic disorders, 428, 429

BCR-ABL inhibitors, 429Jak1/2 inhibitors, 429side effects, 429

UUmbilical cord blood (UCB) graft, 225, 487, 492, 494Unfractionated heparin (UFH), 116

abnormal liver function tests, 169bleeding and reversal, 168clinical indications, 164frequency of monitoring, 168

Index

541

immune-mediated HIT, 168initiation of therapy, 165invasive procedures, 168maintenance dosing and titration, 168mechanism of action, 163osteoporosis, 169pharmacodynamics, 164pharmacokinetics, 164transition from anticoagulants, 169transition to anticoagulants, 169

Unstable hemoglobins (Hbs), 66Upshaw-Shulman syndrome, 66Uratoxidase, 428Urine protein electrophoresis (UPEP), 411UV light process, 482

VValaciclovir, 516Valvular heart disease, 140Vancomycin, 504, 506, 508Varicella zoster virus (VZV), 427, 515, 516Varicella zoster virus postexposure prophylaxis, 427Vascular endothelial growth factor (VEGF), 421Vascular malformations, 67, 106Vasculitic disorders, 141Velocardiofacial/DiGeorge syndrome, 128Venetoclax, 382, 405Veno-occlusive disease (VOD), 491, 500Venous thromboembolism (VTE), 328

oral antocoagulants (see Oral antocoagulants)parenteral anticoagulants (see Parenteral anticoagulants)treatment

breastfeeding, 188cancer, 188duration of, 190extremes of weight, 188indications, 189, 190inherited or acquired thrombophilia, 188pediatrics, 189pregnancy, 187renal impairment, 188

Venous thrombosisacquired risk factors

age, 154cancer, 155cardiac disease, 154IBD, 154obesity/metabolic syndrome, 154oral contraceptives, 155pregnancy, 155surgery, 154trauma, 154

complications, 152components, 151endothelial dysfunction or damage, 151inherited high-risk factors

antithrombin deficiency, 153epidemiology, 152factor V Leiden, 152protein C deficiency, 152protein S deficiency, 153prothrombin gene mutation, 152

inherited low-risk factorscoagulation factors, 154fibrinogen, 153

homocysteine, 153Lp(a), 153plasminogen activator inhibitor-1, 154thrombin-activable fibrinolysis inhibitor, 154

intravital microscopy imaging techniques, 151occurrence, 149pathogenesis, 151vessel wall injury, 151

Viral infectionsallogeneic HCT, 500CMV, 515community-acquired respiratory viruses, 516detection, 514EBV, 516epidemiology, 514hepatitis, 516, 517herpesviruses, 514VZV, 515, 516

Vitamin B12 deficiency, 22beneficial effects, 38bone marrow examianiton, 46causes, 47classification, 40–42clinical presentation, 44components and mechanism, 40diagnostic approach, 45drug dosage, 47epidemiology, 37incomplete response, 47laboraory tests, 45metabolite levels, 46physiology

components and mechanism, 39normal absorption and transport, 39normal cellular processing, 39poor intake vs. malabsorption, 39prophylaxis, 39

prognosis, 47supplementation, 44“systems” abnormalities, 44treatment, 47

Vitamin K antagonist (VKA), 117adverse events, 181, 182anticoagulation management, 182clinical indications, 178cessation of therapy, 182dose maintenance, 178drug interactions, 180frequency of monitoring, 179initiation of therapy, 178invasive procedures, 180mechanism of action, 176out-of-range INR, 179pharmacodynamics, 177, 178pharmacokinetics, 177, 178

Vitamin K deficiency, 112Vitamin K epoxide reductase complex subunit

1 gene (VKORC1), 117Vitamin K-dependent coagulation factors,

106, 112, 115, 117, 176, 177von Willebrand disease (vWD), 92

acquired abnormalities, 106antigen assay, 102clinical presentation, 102, 103clinical subtypes, 103–105definition, 101

Index

542

von Willebrand disease (vWD) (cont.)diagnostic assays, 104factor VIII activity, 104function analysis, 102genetics, 102multimer analysis, 104specialized assays, 104structure, 102synthesis, 102therapeutic DDAVP challenge, 104treatment, 105, 106

von Willebrand factor (vWF), 66, 154function analysis, 102multimer analysis, 104

von Willebrand factor propeptide (vWFpp), 104Vorapaxar, 204vWD, see von Willebrand diseasevWF antigen (vWF:Ag) assay, 102

WWaldenström macroglobulinemia (WM), 359, 384, 419, 420Warfarin therapy, 177–180, 182, 186, 187, 473Warm antibody autoimmune hemolytic anemia (w-AIHA)

causes/underlying disorders, 71clinical and laboratory findings, 71pathophysiology, 71treatment considerations, 72

WHIM syndrome (WHIM), 212Whole blood (WB), 465, 466Wilm’s tumor, 106Wiskott-Aldrich syndrome (WAS), 128, 137, 493

XX-linked agammaglobulinemia, 220X-linked macrothrombocytopenia with dyserythropoiesis, 128X-linked thrombocytopenia, 128, 137

Index