Coagulation in cancer

Coagulation in cancer

  • نوع فایل : کتاب
  • زبان : انگلیسی
  • مؤلف : David Green; Hau C Kwaan
  • ناشر : New York ; London : Springer
  • چاپ و سال / کشور: 2009
  • شابک / ISBN : 9780387799629

Description

NOTE: The page numbers with letter ‘f ’ denote figures and with letter ‘t’ denote tables. A Abdominal vein thrombosis (AVT), 162 Acquired von Willebrand syndrome (AvWS), 169, 299 See also Von Willebrand factor (VWF) Activated partial thromboplastin time (APTT), 143, 243, 317 Activated protein C (APC), 234 Activated prothrombin complex concentrate, 320–321 Acute leukemia, 54 Acute lymphoblastic leukemia (ALL), 141, 143, 146, 210, 225, 229–230, 232–234 Acute monoblastic leukemia, 141 Acute myeloid leukemia (AML), 141, 143, 162, 286 Acute promyelocytic leukemia (APL), 54, 146 ADAMTS13, 115, 117, 118t–119t, 120–121, 281–282 AI, see Aromatase inhibitors (AI) Allogeneic hematopoietic stem cell transplantation (ASCT), 169–170 ALL, see Acute lymphoblastic leukemia (ALL) Amino-terminal fragment (ATF), 46 AML, see Acute myeloid leukemia (AML) Amplification phase, 4–6 Amyloid fibrils, 296 Amyloidosis, 295–297, 298, 300 Angiogenesis anticoagulation and, 72–74 L-selectin, 268–270 platelets, 23–24 P-selectin, 268–270 tissue factor, 69–70 tumor, 53 Angiopoietin (ANG), 23 Angiostatin, 44, 53, 72 ANG, see Angiopoietin (ANG) Annexin II, 46, 54 Anthracyclines, 104 Antiangiogenic therapy, 74–75 Anticoagulants, heparins angiogenesis, 268 beneficial effects, 261–363, 362t chemotherapeutic agents, 260–261, 260t experimental studies, 265–266 heparanase, 267 P-selectin, L-selectin, 268–270, 269t survival impact, 259 TF, 267 thrombin generation inhibition, 266–267, 269t tumor growth and metastasis models, 265, 269t UFH, LMWH, 259–265, 264t, 270 VEGF, 266–267 Anticoagulation, angiogenesis and, 72–74 Antifibrinolytic agents, 318–319 Anti-JAK2 investigational therapy, 170–171 Antithrombin (AT), 5f, 18, 99, 143, 182, 183f, 227 APC, see Activated protein C (APC) APL, see Acute promyelocytic leukemia (APL) Apoptosis, 52, 141 Aprotinin, 310 APTT, see Activated partial thromboplastin time (APTT) Arachidonic acid, 158 327 Arg-560, 44 Arg92-Ala93 bond, 50 Argatroban, 283 Arimidex, Tamoxifen Alone or in Combination (ATAC) trial, 184 Aromatase inhibitors (AI), 105 therapy-associated thrombosis, breast cancer, 184 Arsenic, 122 ASCT, see Allogeneic hematopoietic stem cell transplantation (ASCT) Asparaginase, 86, 104 Aspirin, 24–25, 103, 164, 168–169 Astrocytomas, 35 AT, see Antithrombin (AT) ATAC trial, see Arimidex, Tamoxifen Alone or in Combination (ATAC) trial ATF, see Amino-terminal fragment (ATF) ATRA therapy, 54, 139 Aurora kinase inhibitors, 170 AVT, see Abdominal vein thrombosis (AVT) AvWS, see Acquired von Willebrand syndrome (AvWS) B B16a, 20 B16F10, 22 Basic fibroblast growth factor (bFGF), 68, 267 Basophils, 192 BC, see Buffycoat method (BC) BCL-2, 49 Bevacizumab (Avastin), 74, 86, 104, 122, 124–126, 181, 190–191 bFGF, see Basic fibroblast growth factor (bFGF) Billroth, A.T., 84 Bioactive lipids, 24 Bivalirudin, 283 Bleeding management, 301 activated prothrombin complex concentrate, 320–321 antifibrinolytic agents, 318–319 cancer invasion, 305–306 cancer patients, bleeding causes, 305–306, 305t coagulation abnormalities, 307 desmopressin, 316–317 diathesis, 308–321 dysproteinemias, 308 endoscopy, 310–311 general measures, 308 local measures, 309 packing, 309–310 palliative embolization, 311 patients with cancer, 309t patients at risk, 308t plasma products, 314–315 platelet dose, 313 platelet products, 312 platelet transfusions, 311–314, 314t platelet transfusions, expected response, 313–314 platelet transfusions, refractoriness, 314 radiation therapy, 310 recombinant factor VIIa, 319–320 systemic interventions, 309t, 311 thrombocytopenia, 306–307 topical hemostatics, 310, 311 transfusion indications, 312–313 treatment associated bleeding, 307–308 use of drugs, 307 Vitamin K, warfarin effect reversal, 316 Bleomycin, 104, 122 Bone marrow suppression, 285–286 treatment-related, 286–287 Bortezomib, 301 Brain cancer, 103 Brain metastasis, 90 Breast cancer, 55t, 84, 141, 183 therapy-associated thrombosis, 182–185 Buffycoat method (BC), 312 Busulfan, 170 C CAA, see Cerebral amyloid angiopathy (CAA) Calcineurin inhibitors, 122 Calcium chloride, 310 California Patient Discharge data sets, 100 Cancer hypercoagulation activation markers, 18 laboratory findings, 18 VTE diagnosis, 18 Cancer procoagulant (CP), 139 Cancer procoagulant A (CPA), 84, 85f Cancer-specific thromboembolic syndromes, 90–91 Cancer therapy aspirin, 24–25 bevacizumab, 74, 87, 124–126 direct anticoagulation, 37 FOLFOX chemotherapy, 74 LMWH compounds, 37 TF targeting, coagulation intermediates, 35–37, 36f 328 Index Cathepsin, 22 CD33, 193 CD39, 24 CD226, 19 Central venous catheter (CVC), 97, 106 CVDRT, 208–210, 210t indwelling, 225 pediatric hemostatic system, 225, 230, 232 thrombotic complications, 207–209 Central venous catheter-related deep vein thrombosis (CVDRT) anticoagulation therapy, 214–215 catheter removal, 215–216 diagnosis, 208–210, 210t management strategies, 214–216 prophylaxis, 212–214 risk factors, 210–212 superior vena cava vein filters, 216 Central venous catheters (CVC), 88 Cerebral amyloid angiopathy (CAA), 296 Certoparin, 262 Cervical cancer, 58t, 103 Chemoimmunotherapy, 36t Chemotherapy, 233–234 Chronic myeloid leukemia (CML), 91, 126, 281, 282 Cisplatin, 122, 188–189, 194 Cisplatinum, 104 Clinical trials, 24–25 Clinique medicale de l’Hoˆtel-Dieu de Paris (Trousseau), 83 Clot retraction, 298 CLOT trial, 73, 247, 249 CMF, see Cyclophosphamide-methotrexate- 5-fluorouracil (CMF) CML, see Chronic myeloid leukemia (CML) Coagulation altered TF, 9 amplification phase, 4–6 antiangiogenic therapy, 74–75 cascade activation, 34f dysregulations, 7, 8 inflammatory cells, 11 initiation phase, 4 intact vessel, 5f localization phase, 6–7 model, 3–8, 4f other, 11 platelet activation on endothelium, 12 propagation phase, 6 TF cancer cells, 5f TF on endothelium, 5f, 9 TF expression, tumor cells, 9 TF on microparticles, 5f, 9–11, 9f thrombomodulin down regulation, 12 treatment-associated abnormalities, 300–301 See also Hemostasis; Hypercoagulability COALL protocol, 234 Cochrane Collaboration, 213 COLO205, 20 Colorectal cancer (CRC), 35, 84, 191 plasminogen-plasmin system in, 56t Computerized tomography (CT), 84 Corticosteroids, 123, 124, 193, 234 COX-2, see Cyclooxygenase-2 (COX-2) CP, see Cancer procoagulant (CP); Cryoprecipitate (CP) CPA, see Cancer procoagulant A (CPA) CRC, see Colorectal cancer (CRC) Creatinine, 89 Cross-linked fibrin (xLF), 139 Cryoprecipitate (CP), 315 CT, see Computerized tomography (CT) CT26 colon carcinoma, 19, 20 Cushing’s disease, 234 CVC, see Central venous catheters (CVC) CVDRT, see Central venous catheter-related deep vein thrombosis (CVDRT) CXCL 12, 268 CXCR 4, 268 Cyclooxygenase-2 (COX-2), 33, 34f, 38 Cyclophosphamide, 194 Cyclophosphamide-methotrexate-5- fluorouracil (CMF), 58 Cyclosporine, 122, 128 TMA associated with, 128–129 Cysteine, 53 Cytarabine, 122 Cytokines, 85, 188 DIC, 140 D Daclizumab, 128 Dalteparin, 247, 248t, 249–250, 249f, 254, 263, 266 Danazol, 170 Darbepoetin, 191 Daunorubicin, 122 D-dimer, 86, 281 Deep vein thrombosis (DVT), 95, 98t Defibrotide, 128 Deoxycoformycin, 122 Deoxyuridine monophosphate, 190 Desmopressin, 301, 316–317 Index 329 Dexamethasone, 83, 104, 185, 188, 194, 195, 234 DIC, see Disseminated intravascular coagulation (DIC) Disseminated intravascular coagulation (DIC), 18, 33, 99, 279–281 acute, 143, 145t associated cancers, 142t chemotherapy, 145–146 chronic, 142, 145t concept, 138 CP, 139 cytokines, 140 diagnosis, 141–143, 142t, 145t fibrin, 138 fibrinolytic activities, 139–140 heparin treatment, 146–147 ISTH scoring system, 143, 144t management, 145–146 non-overt scoring system, 144t other therapeutic modalities, 147–150 overt scoring system, 144t PAI-1, PAI-2, 140 pathophysiology, cancer-associated, 138 procoagulant mediators, 138–139 replacement therapy, 147 TF, 138–139 therapeutic approaches, 148t–149t thrombocytopenia and, 279–281 tPA, uPA, 139–140 underlying malignancy treatment, 145–146 VTE and, 137 warfarin treatment, 147 Doxorubicin, 104, 185, 194, 195 DVT, see Deep vein thrombosis (DVT) Dysfibrinogenemia, 307 Dysproteinemia, 308 Dysregulation, see Coagulation, dysregulations E E-cadherin-mediated cell-cell adhesion, 22 ECLAP, see European Collaboration on Low-Dose Aspirin in Polycythemia Vera (ECLAP) study ECM, see Extracellular matrix (ECM) Edg-1, see Endothelial differentiation gene (Edg)-1 EEC, see Endogenous erythroid colony (EEC) EGR-1, 37 EMH, see Extramedullary hematopoiesis (EMH) Endocarditis, non-bacterial thrombotic, 90 Endogenous erythroid colony (EEC), 168 Endometrial cancer, 58t Endoscopy, 310–311 Endothelial differentiation gene (Edg)-1, 24 Endothelial growth factor, 49 Endothelium inflammatory cells, 11 intact vessel, 5f platelet activation on, 11 procoagulant factor, 9f TF and, 5f, 9–11 thrombomodulin down regulation, 11 Enoxaparin, 194, 236, 261, 263, 266 Eosinophils, 192 Epidermal growth factor, 23, 68 Epinephrine, 298, 301 EPO, see Erythropoietin (EPO) Epsilon amino-caproic acid, 45 ERK, 69 Erythromelalgia, 159 Erythropoiesis stimulating agents (ESAs), 170 Erythropoietin (EPO), 159, 191–192 ESAs, see Erythropoiesis stimulating agents (ESAs) E-selectin, 185 Esophageal cancer, 57t Essential thrombocythemia (ET), 103, 157, 196 See also Myeloproliferative neoplasms (MPN) Etoposide, 194 ET, see Essential thrombocythemia (ET) European Collaboration on Low-Dose Aspirin in Polycythemia Vera (ECLAP) study, 103, 164 Extracellular matrix (ECM), 34f, 45, 52, 267 Extramedullary hematopoiesis (EMH), 162–163 F Factor I, 99 Factor II, 99, 189, 260, 316 Factor V, 7, 70, 143 Factor V Leiden, 87, 99–100, 105, 211 Factor Va, 4, 5f, 140 Factor VII, 10, 35, 147, 150, 189, 192, 230, 316 Factor VIIa, 6, 36, 267 recombinant, 319–320 330 Index Factor VIII, 70, 99, 143, 189, 192, 295, 298 Factor VIIIa, 6, 140 Factor IX, 4, 5f, 99, 189, 233, 260, 316 Factor IXa, 6 Factor X, 4, 5f, 6, 84, 189, 260, 296, 316 Factor Xa, 5f, 10, 31, 38 Factor XI, 6, 70, 99, 189, 192, 233 Factor XII, 260 Factor XIII, 70, 233, 310 FAMOUS study, 73, 262 FEIBA, 320–321 FGF, see Fibroblast growth factor (FGF) Fibrin, 8, 45, 73, 85, 138, 207, 266 cross-linked, 139 formation, 17 Fibrinogen, 143, 310 Fibrinogen gamma, 99 Fibrinolysis, 50, 54, 227–228, 299–300, 307 Fibrinopeptide-A, 18, 25, 143 Fibrinopeptide-B, 143 Fibrin split products (FSP), 143 Fibroblast growth factor (FGF), 23, 188 Fibronectin, 21f, 52 First-trimester miscarriages, 169 5-Fluorouracil (5-FU), 104, 146, 190 FOLFOX chemotherapy, 74 Fondaparinux, 244, 266 Fresh frozen plasma, 124, 315, 316 G Gamma irradiation, 163 Gastric cancer, 56t Gastrointestinal malignancies, 306 G-CSF, see Granulocyte colony-stimulating factor (G-CSF) Gemcitabine, 123–124 Gemtuzumab ozogamicin, 193 Genetic models, 23 Germ cell tumors, 193 Glioblastoma multiforme, 35, 57t Glioma, 57t Glomerular podocytes, 125 Glutathione, 53, 193 Glycoprotein Ib/IX/V complex, 4 Glycoprotein VI, 4 Glycosyl-phosphatidylinositol (GPI), 47 GM-CSF, see Granulocyte-macrophage colony-stimulating factor (GM-CSF) GPIIb-IIIa, 22 GPI, see Glycosyl-phosphatidylinositol (GPI) Graft-versus-host disease (GVHD), 127, 308 Granulocyte colony-stimulating factor (G-CSF), 105, 192 Granulocyte-macrophage colonystimulating factor (GM-CSF), 67, 192 GVHD, see Graft-versus-host disease (GVHD) H Head and neck cancer, 305 Helicobacter pylori, 50 Hematogenous metastasis, 68 Hematopoietic growth factors, 105 Hematopoietic progenitor cell transplantation (HPCT), 307 Hematopoietic stem cell transplantation (HSCT), 127–130, 127t allogenic, 169 Hemolytic-uremic syndrome (HUS), 115 Hemostasis phases, 4f, 5f, 7–8 primary, 226–227, 298–299 secondary, 227, 299–300 Hemostatic envelope, 4 Heparanase, 267 Heparan sulfate-glycoaminoglycans (HS-GAGs), 265 Heparan sulfate-proteoglycans (HSPGs), 265 Heparin, 21, 88 binding domain, 36 unfractionated, 71, 73, 236, 244–245, 259 See also Low molecular weight heparin (LMWH) Heparinase, 37 Heparin-induced thrombocytopenia (HIT), 253, 283–285 Hepatic veno-occlusive disease (VOD), 90–91 Hepatocellular carcinoma, 306 Hepatocyte growth factor (HGF), 23, 34f Hepatocyte scatter factor (HSF), 34f Hepatoma, 141 Hereditary thrombophilia, 98t HES, see Hypereosinophilic syndrome (HES) HGF, see Hepatocyte growth factor (HGF) HIT, see Heparin-induced thrombocytopenia (HIT) HLA antibodies, 314 Hodgkin lymphoma, 102, 124, 225 Homocystinuria, 99 Hormone therapy, 98, 100 Index 331 HPCT, see Hematopoietic progenitor cell transplantation (HPCT) HSCT, see Hematopoietic stem cell transplantation (HSCT) HSF, see Hepatocyte scatter factor (HSF) HS-GAGs, see Heparan sulfateglycoaminoglycans (HS-GAGs) HSPGs, see Heparan sulfate-proteoglycans (HSPGs) HUS, see Hemolytic-uremic syndrome (HUS) Hydroxyurea, 158, 163, 169, 170 Hypercoagulability, 31, 33 Hypereosinophilic syndrome (HES), 126 Hyperfibrinogenemia, 44 Hyperhomocysteinemia, 99 Hypofibrinogenemia, 315 Hypoxia, 34 Hypoxia-inducing factor, 49 I Idraparinux, 250–251 IGF, see Insulin-like growth factor (IGF) IgG, see Immunoglobulin G (IgG) IgM, see Immunoglobulin M (IgM) IL-1, see Interleukin-1 (IL-1) IL-2, see Interleukin-2 (IL-2) IL-6, see Interleukin-6 (IL-6) Immune mediated thrombocytopenia (ITP), 282–283 Immunoglobulin G (IgG), 121, 295, 298, 300 Immunoglobulin M (IgM), 299 Immunotoxins, 32 Inflammatory bowel disease, 99 Inflammatory cells, 11 Inhibitory proteins, 227 Initiation phase, 4 INR, see International Normalized Ratio (INR) Insulin-like growth factor (IGF), 23 Interleukin-1 (IL-1), 67, 141, 183f Interleukin-2 (IL-2), 211 Interleukin-6 (IL-6), 67 International Breast Cancer Intervention Study, 183 International Normalized Ratio (INR), 193, 316 International Society of Thrombosis and Hemostasis Scoring Systems (ISTH), 143, 144t Invasion, tumor cell, 53 Iowa State Surveillance, Epidemiology, and End Results SEER, 103 ISTH, see International Society of Thrombosis and Hemostasis Scoring Systems (ISTH) ITP, see Immune mediated thrombocytopenia (ITP) IVIG, 121 J Janus kinase 2 mutation (JAK2V617F), 91, 104, 157–159, 162f, 163f, 164f anti-JAK2 investigational therapy, 170–171 L Lactate dehydrogenase (LDH), 117, 280 Lambda dimer, 299 Laminin, 21 Laryngeal cancer, 57t L-asparaginase, 189–190, 233 LDH, see Lactate dehydrogenase (LDH) LDLR, see Low density lipoprotein receptor (LDLR) Lenalidomide, 170, 181, 188, 193, 195 Lepirudin, 283 Leucovorin, 190–191 Leukemia acute, 54 acute lymphoblastic, 141, 143, 146, 210, 225, 229–230, 232–234 acute monoblastic, 141 acute myeloid, 141, 143, 162, 286 acute promyelocytic, 54, 146 chronic myeloid, 91, 126, 281, 282 promyelocytic, 50 Leukocytes, 21 Leukocytosis, 170 Leukoerythroblastic anemia, 285 Liver cancer, 57t Liver disease, 307 Liver metastases, 90 LMWH, see Low molecular weight heparin (LMWH) Localization phase, 6–7 Low density lipoprotein receptor (LDLR), 47, 48 Low molecular weight heparin (LMWH), 37, 73–74, 86, 88–90, 89t, 213, 243, 254–255, 259–265, 265t antineoplastic potential of, 254–255 daily dosing, 245 LPA, see Lysophosphatidic acid (LPA) 332 Index LS174HT, 20 L-selectin, 21, 185 angiogenesis, 268–270 Lung cancer, 57t, 84 Lymphoma, 196 Hodgkin, 102, 124, 225 non-Hodgkin, 102, 225 Lymphoproliferative disorders, 317 Lys-77, 38 Lys-78, 38 Lysophosphatidic acid (LPA), 24 M Magnetic resonance imaging (MRI), 84, 225 MAHA, see Microangiopathic hemolytic anemia (MAHA) MALT, 254 MAPK activity, 70 Matrigel model, 69 Matrix metalloproteinases (MMPs), 68, 71 Mayo Clinic, 128, 188 MCMRP, see Minnesota Case-Mix- Review-Program (MCMRP) MDA-BO2, 24 MDS, see Myelodysplastic syndrome (MDS) MEDENOX study, 106 MEGA, see Multiple Environmental and Genetic Assessment (MEGA) Megakaryocytes, 283 Melanoma, 58t Melphalan, 170 Mesenchymal cells, 22 Metastasis, 44 brain, 90 experimental models, 265 hematogenous, 68 liver, 90 plasminogen-plasmin system, 51–53 platelets in, 19–20 MF, see Myelofibrosis (MF) MGUS, see Monoclonal gammopathy of unknown significance (MGUS) Microangiopathic hemolytic anemia (MAHA), 115, 125 Microparticles, 8–10, 9f, 10 Microvesicles, 10 Migration, tumor cell, 53 Minnesota Case-Mix-Review-Program (MCMRP), 102 Mitomycin, 104 Mitomycin-C, 122–123 MM, see Multiple myeloma (MM) MMPs, see Matrix metalloproteinases (MMPs) Monoclonal gammopathy of unknown significance (MGUS), 184, 295, 298, 393 MPD, see Myeloproliferative disorders (MPD) MPN, see Myeloproliferative neoplasms (MPN) MPS, see Myeloproliferative syndromes (MPS) MRI, see Magnetic resonance imaging (MRI) Mucins, 85f Multiple Environmental and Genetic Assessment (MEGA), 102 Multiple myeloma (MM), 102, 300 lenalidomide, 188 thalidomide, 185, 188 therapy-associated thrombosis, 184–185 treatment, 186t–187t Myelodysplastic syndrome (MDS), 286 Myelofibrosis (MF), 91, 169–170 Myeloproliferative disorders (MPD), 104, 317 Myeloproliferative neoplasms (MPN) anti-JAK2 investigational therapy, 170–171 ASCT, 169–170 AvWS, 169 classification, 157 clinical features, 159, 162–163, 164f diagnosis, 159, 160t–161t, 164f, 165t ET treatment, 167t, 168–169 first-trimester miscarriages, 169 hydroxyurea, 169, 170 JAK2V617F, 157–159, 162f, 163f, 164f, 170–171 MF drug therapy, 170 MF treatment, 169–170 pathogenesis, 157–158 pipobroman, 169 PMF drug therapy, 170 PMF treatment, 167t, 169–170 prognosis, 163–164, 168 PV treatment, 167t, 168–169 RIC strategies, 169–170 splenomegaly, 170 symptomatic anemia, 170 treatment, 167t, 168–171 Myeloproliferative syndromes (MPS), 91 Myocardial infarction, 196 Index 333 N Nadroparin, 261, 264–265, 266 National Comprehensive Cancer Network (NCCN), 216 National Hospital Discharge Survey, 101 Natural killer cells, 20, 188 N-cadherin, 24 NCCN, see National Comprehensive Cancer Network (NCCN) Nephrotic syndrome, 99 Neutrophils, 192 New England Journal of Medicine, 216 NF-E2, see Nuclear factor-erythroid 2 (NF-E2) Nitric oxide (NO), 190 Non-bacterial thrombotic endocarditis, 88, 90 Non-Hodgkin lymphoma, 102, 225 Northwick Park Heart Study, 25 Nuclear factor-erythroid 2 (NF-E2), 23 O Oklahoma TTP-HUS Registry, 116–117, 120 Oral contraceptives, 98, 99 Ovarian cancer, 57t P p38, 70 Pacemaker, transvenous, 97 Packing, 309–310 PAIs, see Plasminogen activator inhibitors (PAIs) Palliative embolization, 311 Pancreatic adenocarcinoma, 263–264 PAR, see Protease activated receptors (PAR) Paraproteins, 300 PARKAA study, 232 Partial prothromboplastin time (PTT), 295 PC-3, 52 PD-ECGF, see Platelet-derived endothelial cell growth factor (PD-ECGF) Pediatric hemostatic system, 226t chemotherapy role, 233–234 CVCs, children with cancer, 230, 232 fibrinolysis, 227–228 inhibitory proteins, 226–227 primary hemostasis, 226–227 procoagulant properties, 229–230 prothrombotic state, 228–229, 229f secondary hemostasis, 226–227 thrombophilia, 230, 231t See also Thromboembolic events Pentasaccharides, 250–251 Peripheral destruction, 279–285 Peripheral smear, 288–290 PE, see Pulmonary embolism PET, see Positron emission tomography Phlebotomy, 163 Phosphatidylserine (PS), 227 Phosphoglycerate kinase, 53 PI 3-kinase, 69 Pipobroman, 169 Plasmapheresis, 124, 128 Plasma products, 314–315 Plasmin/angiostatin, 72 Plasminogen activator, 45–47 Plasminogen activator inhibitors (PAIs), 33, 34f, 38, 85, 140, 228, 280 PAI-1, 43, 47–49, 48t PAI-1 regulation, 49, 49t PAI-2, 49–50 TAFI, 50–51 TAFIa, 50 Plasminogen-plasmin system acute leukemia and, 54 Annexin II, 43 biologic processes, 43–44 breast cancer in, 55t cervical cancer, 58t clinical observations, 55, 56t–58t, 58–59 colorectal cancer, 56t description, 44–45, 44f endometrial cancer, 58t esophageal cancer, 57t gastric cancer, 56t glioblastoma, 57t glioma, 57t historical background, 44 inhibitors, 47 laryngeal cancer, 57t liver cancer, 57t lung cancer, 57t melanoma, 58t ovarian cancer, 57t PAIs, 43, 47–52, 48t, 49t pathophysiologic role, 59 plasminogen activators, 45–47 prognostic significance, 58–59 prostate cancer, 57t renal cell cancer, 58t thrombotic complications in cancer, 53–54 tPA, uPA expression, 43, 46 tumor angiogenesis, 53 tumor cell migration, invasion, 53 334 Index tumor cell proliferation, apoptosis, 52 tumor growth, metastasis, 51–53 uPA, uPAR, 43, 46–47, 52–53 Platelet-derived endothelial cell growth factor (PD-ECGF), 23 Platelet-derived growth factor (PDGF), 68 Platelet derived microparticles (PMPs), 69 Platelet-rich plasma (PRP), 312 Platelet(s) activating factor, 183f activation, 11 alpha-granules, 68 angiogenesis, 23–24, 67–69 bioactive lipids, 24 bleeding management, 311–314 clinical trials and, 24–25 dose, 313 functions, 17 genetic models, 23 in metastasis, 19–20 plug, 17 plug formation, 17 products, 312 thrombin and, 21f, 22–23 transfusions, 311–314, 314t transfusions, expected response, 313–314 transfusions, refractoriness, 314 tumor microenvironment and, 17 PMF, see Primary myelofibrosis PMPs, see Platelet derived microparticles Polycythemia vera (PV), 91, 104, 157 See also Myeloproliferative neoplasms (MPN) Positron emission tomography (PET), 84 Prednisone, 170 Prekallikrein, 227 Primary hemostasis, 226–227 abnormalities, 298–299 Primary myelofibrosis (PMF), 157 See also Myeloproliferative neoplasms (MPN) Procoagulant factor, 4, 8, 38 endothelium, 9f Procoagulant mediators, 138–139 Progesterone, 98 Promyelocytic leukemia, 50 acute, 54 Propagation phase, 6 PROSORBA, see Protein A absorbent resin (PROSORBA) Prostacyclin, 20, 190 Prostaglandins, 310 Prostate cancer, 57t, 147 Protease activated receptors (PAR), 4, 24, 31, 38, 68, 268 expression, 22 Protein A absorbent resin (PROSORBA), 121 Protein C, 5f, 18, 99, 182, 189, 191, 227, 316 activated, 234 Protein S, 99, 182, 189, 191, 227, 316 Prothrombin, 6, 99–100, 105, 228 Prothrombin activation fragments, 25 Prothrombin time (PT), 143, 189, 295 PRP, see Platelet rich plasma (PRP) PRV-1, 168 PS, see Phosphatidylserine (PS) P-selectin, 21, 22, 158, 267 angiogenesis, 268–270 P-selectin glycoprotein ligand (PSLG), 21f, 24 PSLG, see P-selectin glycoprotein ligand (PSLG) PT, see Prothrombin time (PT) PTEN, 34, 35 PTT, see Partial prothromboplastin time (PTT) PTTM, see Pulmonary tumor thrombotic microangiopathy (PTTM) Pulmonary embolism (PE), 95, 98t, 259 Pulmonary tumor thrombotic microangiopathy (PTTM), 117 PV, see Polycythemia vera (PV) Q Quality of life, 254 R Radiation therapy, 310 Raloxifene, 98 Reactive oxygen species, 49 Recombinant factor VIIa, 319–329 Reduced intensity conditioning (RIC), 169–170 Renal cell cancer, 58t, 84 Revimid, see Lenalidomide RIC, see Reduced intensity conditioning (RIC) Rituximab, 128 Russel’s viper venom tie (RVVT), 297 RVVT, see Russel’s viper venom tie (RVVT) Index 335 S S1P, see Sphingosine 1-phosphate (S1P) Schistocytes, 284 SDF-1, 24 Secondary hemostasis abnormalities, 299–300 Second Northwick Park Heart Study, 25 SEER, see Iowa State Surveillance, Epidemiology, and End Results SEER Selective estrogen receptor modulator (SERM), 182 Serine protease inhibitor (SERPIN), 47, 84 SERM, see Selective estrogen receptor modulator (SERM) Serotonin, 71 SERPIN, see Serine protease inhibitor (SERPIN) Sphingosine 1-phosphate (S1P), 24 Splenomegaly, 170 Src kinase, 69 Stasis, 33 Streptokinase, 73 Strontium-89, 286 SU5416, 74–75 Sunitinib, 104, 125 Superior vena cava, 216 Symptomatic anemia, splenomegaly, 170 Systemic lupus erythematosus, 99 T T241, 20 Tacrolimus, 122 TMA associated with, 129–130 TAE, see Transcutaneous arterial embolization (TAE) TAFI, see Thrombin activatable fibrinolysis inhibitor (TAFI) Tamoxifen, 58, 83, 98, 105, 182–184, 183 TAT, see Thrombin-antithrombin complex (TAT) TE, see Thromboembolism (TE) TEE, see Thromboembolic events (TEE) TF, see Tissue factor (TF) TFPI, see Tissue factor pathway inhibitor (TFPI) Thalidomide, 74, 83, 87, 170, 181, 184–185, 188, 193, 194 Therapeutic plasma exchange (TPE), 120, 123 Thrombin, 6, 10, 23, 70–71, 84 clotting time, 143 inhibition, 266–267 PAR-1 expression, 22 platelets and, 21f, 22–23 tumor dormancy, 25–26 Thrombin activatable fibrinolysis inhibitor (TAFI), 50–51, 54, 99 Thrombin-antithrombin complex (TAT), 143, 229 Thromboangiitis obliterans, 99 Thrombocytopenia, 18, 68, 90, 306–307 abnormal peripheral smear, 288–289 bone marrow suppression, treatment-related, 286–287 bone marrow suppression, tumor involvement, 285–286 by decreased production, 285–288 diagnostic evaluation, 288–290, 289t DIC, 279–281 disseminated intravascular coagulation, 279–281 HIT, 253, 283–285 ITP, 282–283 normal peripheral smear, 289–290 peripheral destruction, 279–285 peripheral smear, 288–290 treatment, decreased production, 287–288 TTP and, 281–282 Thrombocytosis, 18, 170 Thromboembolic events (TEE), 223 age distribution, children, 224, 224f chemotherapy role, 233–234 CVC, 225 general pediatric population, 223–224 pediatric cancer patients, 224–226, 225f Thromboembolic syndromes, 90–91 Thromboembolism (TE), 31, 86, 91 myeloproliferative syndromes, 91 Thrombogenesis, 140–141 Thrombomodulin, 7, 50, 230 downregulation of, 11 Thrombophilic clonal stem cell diseases, see Myeloproliferative neoplasms (MPN) Thrombopoietin (TPO), 67 Thrombosis, 7 age distribution, 224, 224f chemotherapy role, 233–234 corticosteroids, 234 CVCs, 230, 232 diagnosis, 86 epidemiology, 223–226 general pediatric population incidence, 223–224 LMWH, 236 336 Index prophylaxis, treatment, 235–237, 235t symptoms, 86 thrombophilia, 230, 231t Thrombosis, thrombophilia, 18 acquired, 97t children with cancer, 230, 231t hereditary, 98t mechanisms, 33 molecular pathogenesis, oncogenesis, 33–35, 34f screening, 87 secondary, 97t Virchow’s triad, 33 Thrombospondin, 21, 24, 70 Thrombotic microangiopathy (TMA) bevacizumab, 124–126 cyclosporine-associated, 128–129 HSCT, 127–130, 127t imatinib therapy, 126 immunoadsorption, 121 interferon therapy, 126 quinine exposure, 126–127 tacrolimus-associated, 129–130 transplant associated, 127t, 128 types, 115 vWF, 120 Thrombotic microangiopathy (TMA), cancer-associated, 116–121 ADAMTS13 activity, 117, 118t–119t, 120–121 clinical presentation, 117 epidemiology, 116–117 pathophysiology, 117–120 therapy, 120–122 Thrombotic microangiopathy (TMA), drug-associated, 122–127, 122t gemcitabine, 123–124 mitomycin-C, 122–123 other medications, 126–127 VEGF inhibitors, 124–126 Thrombotic thrombocytopenic purpura (TTP), 99, 115–116, 120–121, 281–282 thrombocytopenia and, 281–282 Thromboxane, 71 Thymidine monophosphate, 190 Tinzaparin, 250, 266 Tissue factor pathway inhibitor (TFPI), 18, 70, 267 Tissue factor (TF), 319 altered, 8 angiogenesis, 69–70 anticoagulants, heparins, 267 DIC, 138–139 endothelium, 6f, 8, 9 expression, 8 microparticles, 6f, 8–10, 9–11, 9f, 10 microvesicles, 10 secretion of, 84 targeting, coagulation intermediates, 35–37, 36f VTE, 84 Tissue plasminogen activator (t-PA), 85, 227, 228, 280 TMA, see Thrombotic microangiopathy (TMA) TNF-, see Tumor necrosis factor alpha (TNF-) Topical hemostatics, 310 t-PA, see Tissue plasminogen activator (t-PA) TPE, see Therapeutic plasma exchange (TPE) TPO, see Thrombopoietin (TPO) TRALI, see Transfusion-related lung injury (TRALI) Tranexamic acid, 45, 318 Transcutaneous arterial embolization (TAE), 311 Transfusion-related lung injury (TRALI), 121, 315 Transvenous pacemaker, 97 Treatment-related bone marrow suppression, 286–287 Trousseau, Armand, 67, 83, 259 Trousseau’s syndrome, 18, 33, 83, 142 TTP, see Thrombotic thrombocytopenic purpura (TTP) Tumor angiogenesis, 53 Tumor cell invasion, 53 migration, 53 tissue factor expression on, 8 Tumor cell adhesion, 20–22, 21f adhesive ligands, 21 P-selection and, 21 VWF, 20 Tumor-derived endothelial-like cells, 8 Tumor dormancy, 25–26 Tumor lysis syndrome, 141 Tumor necrosis factor alpha (TNF-), 139, 185, 188, 281 U UFH, see Unfractionated heparin (UFH) Ultrasonography, 209 UMCL, 22 Index 337 Unfractionated heparin (UFH), 73, 236, 244–245, 259 uPA, see Urokinase plasminogen activator (uPA) Urokinase plasminogen activator (uPA), 85, 139–140, 228, 280 V Val-561, 44 Vascular endothelial growth factor (VEGF), 23, 24, 31, 52, 68–71, 83–84, 85, 86, 183, 188, 190–191, 267, 281 expression of, 37 heparin-binding domain, 36 inhibitors, 124–126 neuropilin, 36 receptor, 36, 125 Vascular injury, 33 VCAM-1, 185 VEGF, see Vascular endothelial growth factor (VEGF) Venography, 210 Venous stasis, 211 Venous thromboembolism (VTE), 18, 33, 67 cancer chemotherapy, 86 cancer-specific risk factors, 100–106 central venous catheters, 88 CVC, 105 DIC, 137 epidemiology, 84 EPO, 191–192 factor V Leiden, 99 genetic risk factors, 99–100 heparin, 88 history, 83 immune-mediated pathways, 85 incidence, by cancer type, 101t lenalidomide, 188 LMWH, 88–90, 89t MPD, 104 pathophysiology, 84–86, 85f prophylaxis, 88 risk factors, 96–101, 97t symptoms, diagnosis, 86–87, 97f TF, 84 therapy, 89–90 Venous thromboembolism (VTE), cancer associated 5-FU, 101t ATAC trial, 184 bevacizumab, 190–191 breast cancer, therapy-associated thrombosis, 182–185 cancer-specific risk factors, 100–106 cisplatin-based regimens, 189 corticosteroids, 193 EPO, 191–192 G-CSF, GM-CSF, 192–193 hematopoietic growth factors, 191–192 incidence, by cancer type, 101t L-asparaginase, 189–190 lenalidomide, 188 leucocyte growth factors, 192–193 LMWH, 254–255 MGUS, 184 MM, 184–185, 186t–187t MM prophylaxis, 194–196 morbidity, 181–182 MPD prophylaxis, 194–196 other associated anti-neoplastic agents, 189–191 pathogenesis, 182 pathophysiology, 182, 183f patient quality of life, 254 patients with bleeding treatment, 251–252 predictive model, 196–197 prevention, 193–196 recurrent VTE treatment, 252–254 risk, by cancer type, 102t solid tumors prophylaxis, 193–194 thalidomide, 185, 188 treatment challenges, 251–254 Venous thromboembolism (VTE), treatment anticoagulants, 244–245 CLOT trial, 247, 249 dalteparin, 247, 248t, 249–250, 249f fondaparinux, 244 HIT, 253 idraparinux, 250–251 initial therapy, 243–245 LMWH, 244–245, 246–247, 248t long-term therapy, 246–247, 247f, 247t, 248t, 249–251, 249f pentasaccharides, 250–251 tinzaparin, 250 treatment duration, 251 UFH, 244–245 VKA, 246, 247t, 249t warfarin therapy, 246, 250 Vincristine, 121, 194, 195 Virchow, Rudolf, 83 Virchow’s triad, 33 Vitamin A, 298 Vitamin E, 298 338 Index Vitamin K agonists, 72, 89 Vitamin K antagonists, 246, 247t, 249t Vitronectin, 21, 52, 53 VOD, see Hepatic veno-occlusive disease (VOD) Von Willebrand factor (VWF), 4, 5f, 20, 21f, 68, 115, 120, 123, 189, 227, 234, 281, 282, 298–299 See also Acquired von Willebrand syndrome (AvWS) VTE, see Venous thromboembolism (VTE) VWF, see Von Willebrand factor (VWF) W Waldenstro¨m macroglobulinemia, 296–298 Warfarin, 72, 147, 193–195, 212, 215–216, 246, 250 reversal, 316 Wegener’s granulomatosis, 99 Werner, J., 83 WHO, see World Health Organization (WHO) World Health Organization (WHO), 157, 159, 313
Part I. Alterations in hemostasis due to cancer --

Dysregulation of hemostasis by cancer / Dougald M. Monroe and Maureane Hoffman --

Effect of cancer on platelets / David L. Green and Simon Karpatkin --

Activation of clotting factors in cancer / Frederick R. Rickles and Anna Falanga --

The role of plasminogen-plasmin system in cancer / Hau C. Kwaan and Brandon McMahon --

The coagulation system and angiogenesis / Gurinder Sidhu and Gerald A. Soff --

Part II. Thrombotic disorders associated with cancer --

Overview of cancer and thrombosis / Axel C. Matzdorff and David Green --

Risk factors for thrombosis in cancer patients / Aneel A. Ashrani and John A. Heit --

Thrombotic microangiopathy syndromes / Anaadriana Zakarija --

Disseminated intravascular coagulation (DIC) in cancer / Hussain I. Saba, Genevieve A. Morelli, and Rashid E. Saba --

Myeloproliferative neoplasms: thrombophilic clonal stem cell diseases / Ayalew Tefferi --

Chemotherapy-associated thrombosis / Aneel A. Ashrani and S. Vincent Rajkumar --

Catheter-related thrombosis / César O. Freytes --

Thrombosis in childhood cancer / Geoffrey A. Allen and Rukhmi Bhat --

Treatment of venous thrombosis / Agnes Y.Y. Lee --

Effects of anticoagulants on cancer: heparins / Graham F. Pineo and Russell D. Hull --

Part III. Bleeding disorders associated with cancer --

Thrombocytopenia and cancer / Elizabeth A. Eklund --

Bleeding disorders associated with cancer dysproteinemias / Maurizio Zangari, F. Elice, G. Tricot, and L. Fink --

Control of bleeding in cancer / Jaime Pereira.
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