786 CHAPTER 18 Rare diseases Niemann \200\223Pick disease Rare metabolic disorder; type of sphingolipidosis. Autosomal r ecessive disorder. Often fatal in infants; some patients with milder course live into their teens or early adulthood. Mutations in the SMPD1 gene (Type A/B) lead to no sphingomyelina se production; mutations in NPC1 and -2 (Type C) lead to abnormalities in the lipid-transpo rtation proteins. Incidence 1:250,000 (1:40,000 in Ashkenazi Jews). Genetic counseling and pre- natal diagnosis is possible. Pathophysiology Sphingomyelin defi ciency leads to accumulation of sphingomyelin in the lys osomes, leading to organ and tissue accumulation and dysfunction. Classi \201 cation \200 Type A: classic infantile. \200 Type B: visceral type. \200 Type C: subacute/juvenile. Most common form. Clinical \200 Hepatosplenomegaly. \200 Lung symptoms. \200 CNS: ataxia, dysarthria, d ysphagia. \200 Mental retardation. \200 BM deposition can lead to pancytopenia. Diagnosis: \200 Blood tests. \200 Raised cholesterol often seen. \200 BM: foam cells (due to multiple vacuoles) on aspirate: lipid-laden macrophages in the marrow and \200\230sea-blue histiocytes \200\231 on pathology. Sphingomyelin assay. Treatment \200 Statins to control cholesterol. \200 Supportive measures. \200 BMT/PBS CT can be considered in rare cases. \200 Enzyme replacement therapy though results poor. Further reading Vanier, M.T. (2013). Niemann \200\223Pick diseases. Handb Clin Neurol, 113, 1717 \200\22321. 787 NIEMANN \200\223PICK DISEASE 788 CHAPTER 18 Rare diseases Castleman disease Synonyms: giant or angio-follicular lymph node hyperplasia. A rare lymphoproliferative disorder which can present with local or widespread disease. It is not considered a malignancy although there is a hyperproliferation of B lymphocytes. Ove r-secretion of interleukin-6 (Il-6) and HHV-8 (human herpes virus-8) infection are implicat ed in its etiology. It is more often seen in HIV patients. The obvious diff eren- tial diag nosis includes lymphoma and other cancers, as well as reactive causes of lymphadenopathy. D iagnosis is made on excision biopsy; diag- nosis can be diffi cult and repeat biopsy might be required. Castleman disease is also seen in POEMS syndrome and implicated in a signifi c ant number of patients with paraneoplastic pemphigus. Unicentric and polycentric Castleman disease have been described. Unicentric Castleman disease (UCD) \200 Single-site disease, with often only local sympto ms. \200 Good prognosis. \200 Hyaline vascular variant (80%): etiology unknown; associa ted symptoms rare; associated diagnoses include paraneoplastic pemphigus and TTP. Treatment with surgery or radiotherapy. \200 Plasma cell variant (20%): etiology HHV-8 related; us ually more systemic symptoms and associated cytopenias. Associated diagnoses include amyloidosis and r enal insuffi ciency. Most treated with surgery, but radiotherapy, ganciclovir, chemotherapy , or Il-6 antibody might all be needed. Multicentric Castleman disease (MCD) \200 Plasma cell variant only. \200 Lymphadenopath y at multiple sites. Often unwell. \200 Raised ESR/CRP and cytopenias common. \200 Etio logy HHV-8 related. Associated diagnoses include POEMS syndrome, HIV infection, Kaposi sarcoma and amyloidosis. Treatments include ganciclovir (if HHV-8 positive) and rituximab. Steroids, combination che motherapy, Il-6 monoclonal antibodies and immunemodulators (thalidomide) have been used wit h varying success. In HIV patients HAART should be commenced or optimized. \200 High relapse rates. Further reading Dispenzieri, A. et al. (2012) The clinical spectrum of Castleman \200\231s disease. Am J Hematol, 87(11), 997 \200\2231002. Ramasamy, K. et al. (2012). Rituximab and thalidomide combination therapy for Castleman disease. Br J Haematol, 158(3), 421 \200\2233 . Roca, B. (2009). Castleman \200\231s disease. A Review. AIDS Rev, 11(1), 3 \200\2237. Tal at, N. et al. (2011). Castleman \200\231s disease: systematic analysis of 416 patients from the literature. Oncologist, 16(9), 1316 \200\22324. Uldrick, T.S. et al. (2012). Recent ad vances in Kaposi sarcoma herpesvirus-associated multicentric Castleman disease. Curr Opin O ncol, 24(5), 495 \200\223505. 789 KIKUCHI DISEASE Kikuchi disease Synonyms: Kikuchi \200\223Fujimoto disease (KFD), histiocytic necrotizing l ym- phadenitis, subacute necrotizing lymphadenitis. A rare disease aff ecting young adults typically presenting with cervical lymphadenopathy. Main prevalence in Japan though isolated cases else- where reported. Diff erential diagnosi s with malignancies (lymphoma), infective/reactive lymphadenitis (TB, sarcoidosis) and auto -immune dis- orders. Diagnosis is made on excision biopsy. If the diagnosis is in doubt a r epeat biopsy might be required. Pathophysiology Kikuchi disease is caused by a non-specifi c hyperimmune reaction. Many dif f erent aetiologies have been described, including auto-immune disor- ders (SLE, antiphosph olipid syndrome), infective agents (bacterial, viral) and genetic predisposition. Symptoms \200 Self-limiting disease with most lymphadenopathy resolved by 6 months. Recurrence in 3 \200\2235%. Fever. \200 Cervical lymphadenopathy: often tender. \200 Hepatosplenomegaly rare. \200 Skin rashes rare. \200 Headaches. \200 Aseptic meningitis has been decribed. \200 M ortality very rare. Management \200 Supportive: self-limiting disease. \200 NSAIDs and antipyretics. Further reading Veer, V. et al. (2012). Kikuchi \200\223Fujimoto disease: a case report and literature review. Case Rep Otolaryngol, 2012, 497604. Weiss, L.M. et al. (2013). Benign l ymphadenopathies. Mod Pathol, 26(Suppl. 1), S88 \200\22396. 790 CHAPTER 18 Rare diseases The porphyrias Rare inherited or acquired group of disorders, seen in all races. Over 200 m utations have been described. If the genetic defect is known, family screening and antenata l screening is possible. The acquired por- phyrias are 2 to liver disease, mercury or ars enic poisoning. Pathophysiology Porphyrins are the precursors of haem, essential for the production of hemo globin. In the porphyrias enzymatic defects lead to an insuffi cient production of haem and deposition of toxic porphyrin. Each particular enzymatic defect leads to diff erent porphy rins, which depending on their chemical properties deposit in diff erent locations. Some po rphy- rins induce photosensitivity. The subtype of porphyrias is dependent on what enzyme i s defi cient. Pathophysiologically porphyrias are divided into hepatic or erythropoietic, b ased on the site of haem deposition. Signs and symptoms Symptomatically the porphyrias are divided into acute or cutaneous proph yrias. Precipitating factors for acute attacks are stress, infections, barbiturates, some a ntibiotics (sulfonamides), surgery, and low caloric intake. All toxic intermediates can tri gger a haemolytic anemia. Acute porphyrias \200 Hepatic porphyria (neurovisceral). \200 Aff ects the nervous syst em: abdominal pain, vomiting, muscle weakness, neuropathy, arrhythmias, constipation/diarrhea, seizures and mental disturbances (anxiety, depression, hallucinations). Acute attacks can be fatal. i risk of hepatocellular carcinoma. \200 Variants: ADP: Ala-dehydratase porphyria; AIP: a cute intermittent porphyria; HCP: hereditary coproporphyria; VP: variegate porphyria (mixed porphyria), the o nly porphyria with both skin lesions and neurological symptoms. More common and dominant inheritance (AIP, HCP, and VP). Cutaneous porphyrias \200 Erythropoietic porpyrias. Symptoms due to complement activation . \200 Skin: photosensitiity, blisters, itch, skin necrosis, lichenifi cation, erythema. \200 i hair-growth (hypertrichosis). \200 No neurological symptoms. \200 Variants: CE P: congenital erythropoietic porphyria; PCT: porphyria cutanea tarda; EPP: erythropoietic p roto-porphyria; HEP: hepato- erythropoietic porphyria. Diagnosis \200 Biochemical analysis of blood, urine or stool sample. Protect samples from light. i porphobilinogen (a precursor) in urine: i precursor production through feedback mechanism. Raised in almost all acute porphyrias (not in acquired porphyri a). Testing should be done on samples during an acute attack otherwise false negatives are common. 791 THE PORPHYRIAS Treatment of acute porphyria \200 Avoid precipitating factors: drugs, stress, hormone rep lacement, infections, surgery, low carbohydrate diet. Glucose 10% infusion if severe porphyria attack is suspected. \200 Symptom control: pain relief (opiates), antiemetics. \200 Neurological and psychiatric problems: treat chronic neuropathic pain, gut dysmotility, chronic pain, and depression. Seizures: most antiepileptics can exacerbate acute attacks. Barbiturates must be avoided. Treat underlying liver disease (in acquired porphyria). \200 Treatment of iron overload. \200 Hormone treatment: oral contraceptives can be used to modify hormonal fl uctuations if this is triggering attacks. Specifi cally for erythropoietic porphyria: avoid sunlight; chloroquine to increase porphyrin secretion. For neurovisceral attacks (acute, hepatic prophyrias): haem supplementation: haematin (US) or haem arginate (UK). Should be given as soon as an attack starts; proven to reduce duration and intensity of attacks. Haem supplementation inhibits A LA-synthase and eliminates the feedback on precursor production. Preventative heme can be g iven every 10 \200\22314 days. In CEP, HEP, EPP: reduction of erythropoiesis can help prevent attacks: hydroxycarbamide, v enesections, hypertransfusion. Further reading Balwani, M. et al. (2012). The porphyrias: advances in diagnosis and treatm ent. Hematology Am Soc Hematol Educ Program, 2012, 19 \200\22327. Stein, P. et al. (2013). Best practice guidelines on clinical management of acute attacks of porphyria and their com plications. Ann Clin Biochem, 50(Pt 3):217 \200\22323. 792 CHAPTER 18 Rare diseases Retroperitoneal \201 brosis Synonym: Ormond \200\231s disease. This condition is a descriptive term; a proliferation of fi brous tissue is seen in the ret roperitoneum, mainly around the aorta. Causes Many aetiologies have been proposed. There is an association with auto- immune condi tions, previous radiotherapy, malignancy, certain drugs (hydralazine, beta-blockers) and in fections. Symptoms \200 Back pain. \200 Hydronephrosis and renal impairment. \200 Hypertension. \200 VTE. \200 Peripheral oedema 2 to obstruction. \200 Malaise and weight loss. Diagnosis Imaging can be diagnostic on its own (confl uent mass surrounding the aorta). If in doubt a biopsy is required. Treatment \200 Immune suppression has reported responses in 20 \200\22350%. \200 Surger y might be required. \200 Steroids have been used with varying success. Further reading Ormond, J.K. (1965). Idiopathic retroperitoneal fi brosis: a discussion of the etiology. J Urol, 94 (4), 385 \200\22390. Vaglio, A. et al. (2006). Retroperitoneal fi brosis. Lancet, 367(9506), 241 \200\22351. van Bommel, E.F. (2002). Retroperitoneal fi bros is. Neth J Med, 60(6), 231 \200\22342. 793 LANGERHANS CELL HISTIOCYTOSIS Langerhans cell histiocytosis Synonyms: histocytosis X; dendritic cell histiocytosis; eosin ophilic granu- loma (older term, a misnomer); Hand \200\223Sch ller \200\223Christian dise ase if mul- tiple lesions; Letterer \200\223Siwe disease if disseminated. Clonal proliferation of Langerhans cells (myeloid lineage-derived den- dritic cells). Gener ally considered to be a malignancy. Uni- or multifocal disease. The BRAF mutation (activati ng mutation of a proto-oncogen) is seen in 760% of cases. Disease most frequently seen in c hildren. Prognosis poor if multiple organs involved and young age. Solitary lesions and lim ited disease can regress spontaneously. Clinical \200 Unifocal: solitary lesions (skull, mandible, soft tissue). \200 Multifoca l unisystem: Hand \200\223Christian \200\223Sch ller disease: fever, bone lesions, and dif f use skin lesions (mainly scalp). Triad of diabetes insipidus, exophthalmos, and lytic les ions. Multifocal multisystem: Lettere \200\223Siwe disease: disseminated. \200 Constitutional s ymptoms: fever, lethargy, weight loss. \200 Lymphadenopathy and pancytopenia due to BM di sease. \200 Endocrine glands involved: diabetes insipidus most common. \200 Rare: lung, GI, or CNS. Diagnosis mainly on biopsy \200 Eosinophilic micro-abscesses and necrosis. Langerhans cel ls are seen (oval cells without dendritic processes). CD1a+, Langerin (CD207)+, S100+, CD68+, CD163+, lysosyme+, CD45+. Haemophagocytosis often seen. \200 Langerin induces the formation of Birbeck granules. \200 Other: radiology for staging. Treatment: \200 Solitary lesions: surgery or limited radiotherapy. \200 Chemotherapy fo r systemic disease: schedules including prednisolone, vinca-alkaloids, 6-mercaptopurine and etoposide have been used. Cladribine al so has shown activity. Further reading Donadieu, J. et al. (2013). Medical management of Langerhans cell histiocyt osis from diagnosis to treatment. Expert Opin Pharmacother, 13(9), 1309 \200\22322. Haupt, R. et al. (2013). Langerhans cell histiocytosis (LCH): guidelines for diagnosis, clinical w ork-up, and treatment for patients till the age of 18 years. Pediatr Blood Cancer, 60(2), 1 75 \200\22384. Hirasaki, S. et al. (2012). Multifocal Langerhans cell histiocytosis in an a dult. Intern Med, 51(1), 119 \200\22320. 794 CHAPTER 18 Rare diseases Osteopetrosis Synonym: marble bone disease; Albers \200\223Sch nberg disease. Rare inherited disorder whereby the osteoclast function is impaired (number of osteoclasts variable). This leads to impaired bone resorption with ongoing bone formation leading to ha rdened bones. Despite this, patients with osteopetrosis have an i risk of fractures and oth er bone problems. Etiology is unknown. Can occur at any age. Symptoms \200 Impaired growth. \200 Bone deformities. \200 Pathological fractures. \200 Bone expansion leads to BM replacement which leads to extramedullary haematopoiesis: hepatosplenomegaly, pancytopenia. \200 Blindness, deafness , and facial nerve palsies due to nerve compression. Diff erential diagnosis \200 Hypoparathyroidism. \200 Paget \200\231s disease: a diseas e of excessive bone breakdown and formation leading to enlarged and malformed bones. Metastatic cancer: prostate, breast. \200 Myelofi brosis. \200 Multiple myeloma. \200 Sickle cell/thalassaemia (extramedullary haematopoiesis). Treatment \200 BMT/PBSCT is the only possible curative option. \200 Vitamin D. \200 I nterferon has been used with varying results. \200 Supportive: analgesia. 795 Appendix 1 Hematology online Hematology online 796 796 APPENDIX 1 Hematology online Hematology online There are many Internet resources available for hematology, including org anizations, journals, atlases, conference proceedings, and news- groups. The main diffi cul ty with Internet resources is that they change so frequently and they are constantly being updated and outdated. It would be impossible to list every known site, and we have provided only URLs for those we think are of most value. General websites Bloodline M www.bloodline.net BloodMed M www.bloodmed.com Breaking Barriers M www.liv.ac.uk/breakingbarriers Clinical Leaders of Thrombosis (C.L.O.T.) M www.clotuk.com Congenital Dyserythropoietic Anemia Research Initiative Oxford M www.imm.ox.ac.uk/congenita l-dyserythropoietic-anemia-cda Elimination of Leukemia Fund M www.leukaemiafund.org.uk Free Medline Searching M www.ncbi.nlm.nih.gov/PubMed/ Health News \200\224The Media Medical Agency M www.health-news.co.uk/ International Medical News M www.internationalmedicalnews.com Lymphoma Forum M www.lymphoma.org.uk lymphoma-net.org M www.lymphoma-net.org MPD Voice M www.mpdvoice.org.uk Medical Matrix M www.medmatrix.org/Index.asp Meducation M www.meducation.com MRC Molecular Hematology Unit M www.imm.ox.ac.uk/mrc-molecular-hematology-unit Myeloma Forum M www.ukmf.org.uk/guidelines.shtml 797 hematology ONLINE National Library of Medicine M www.nlm.nih.gov NIH Consensus Conferences M http://odp.od.nih.gov/consensus Oncolink M www.oncolink.com Pharmaceutical Technology M www.pharmaceutical-technology.com Reuters Health News M www.reutershealth.com RD Direct M www.rddirect.org.uk WebPath M http://library.med.utah.edu/WebPath/ Atlases Atlas of Genetics and Cytogenetics in Oncology and Hematology M http://atlasgenetic soncology.org Atlas of Hematology M http://www.hematologyatlas.com/ Atlas of Hematology (Nagoya) M http://pathy.med.nagoya-u.ac.jp/atlas/doc/atlas.html The Crookston Collection, University of Toronto M www.thecrookstoncollection.com Journals and books ASH Education Book M www.asheducationbook.org Blackwell Publishing M www.blackwellpublishing.com Blood M www.bloodjournal.org Blood Book.com M www.bloodbook.com Blood Cells, Molecules and Disease M www.scripps.edu/bcmd British Journal of Hematology M www.blackwellpublishing.com/journals/bjh British Medical Journal M www.bmj.com Cancer M http://www.onlinelibrary.wiley.com/journal/10.3322/(ISSN)1542-4863 798 APPENDIX 1 Hematology online Haematologica M www.haematologica.org Hematological Oncology M www.interscience.wiley.com/journal/hon Journal of Clinical Investigation M www.jci.org Journal of Clinical Oncology M www.jco.ascopubs.org Lancet M www.thelancet.com Leukemia M www.Nature.com/leu Leukemia and Lymphoma M www.informahealthcare.com/journal/lal Nature M www.nature.com New England Journal of Medicine M www.nejm.org Oxford University Press M www.oup.com Science M www.sciencemag.org Societies and organizations American Association of Blood Banks (AABB) M www.aabb.org Ameri can Association for Cancer Research (AACR) M www.aacr.org American Cancer Society M www.can cer.org Association of Clinical Scientists M www.assclinsci.org American Medical Association M www.ama-assn.org American Society of Clinical Oncology M www .asco.org American Society of Hematology M www.hematology.org American Society of Pediatric Hematolog y/Oncology (ASPHO) M www.aspho.org Anticoagulation.org.uk M www.anticoagulation.org.uk 799 hematology ONLINE Aplastic Anemia Foundation of America & MDS International Foundation M www.aamds.org/ Association of Pediatric Oncology Nurses (APON) M www.apon.org Bloodline M www.bloodline.net British Blood Transfusion Society (BBTS) M www.bbts.org.uk British Committee for Standards in Hematology M www.bcshguidelines.com British Society of Blood and Marrow Transplantation M www.bsbmt.org British Society for Hematology M www.b-s-h.org.uk British Society for Haemostasis & Thrombosis (BSHT) M www.bsht.bham.ac.uk Centers for Disease Control (CDC), Atlanta, USA M www.cdc.gov European Bone Marrow Transplant Association www.embt.org European Hematology Association M www.ehaweb.org European Society of Pediatric Hematology and Immunology M www.esphi.eu Imperial Cancer Research Fund M www.cancerresearchuk.org Institute of Biomedical Science M www.ibms.org International Histiocytosis Organization (Hi stiocytosis Association of America) M www.histio.org International Hospital Federation M www.hospitalmanagement.net/ International Myeloma Foundation UK M www.myeloma.org.uk Leukemia and Lymphoma Society M www.leukemia-lymphoma.org Leukemia Research Fund M www.lrf.org.uk Leukemia Society of America M www.leukemia.org 800 APPENDIX 1 Hematology online Medical Research Council M www.mrc.ac.uk National Blood Service M www.blood.co.uk National Cancer Institute M www.cancer.gov National Children \200\231s Leukemia Foundation M www.leukemiafoundation.org National Guidelines Clearinghouse M www.guidelines.gov National Heart, Lung, and Blood Institute M www.nhlbi.nih.gov National Institutes of Health M www.nih.gov NHS Center for Reviews and Dissemination M www.york.ac.uk/inst/crd NHS Professionals M www.nhsprofessionals.nhs.uk Royal College of Pathologists M www.rcpath.org Royal College of Physicians M www.rcplondon.ac.uk Royal Society of Medicine M www.roysocmed.ac.uk Sickle Cell Information Center Home M www.scinfo.org Society for Hematopathology (Dartmouth College) M www.sh-eahp.org The Cochrane Library M www.thecochranelibrary.com/view/0/index.html UK NEQAS Schemes M www.ukneqas.org.uk UK CLL support association M www.cllsupport.org.uk Wellcome Trust M www.wellcome.ac.uk World Federation of Hemophilia M www.wfh.org World Health Organization M www.who.int/en 801 hematology ONLINE Guidelines, trials, and evidence-based practice British Committee for Standards in Hematolo gy (BCSH) M www.bcshguidelines.com Cochrane Library (The) M www.cochrane.org Clinical trials: hematology (CenterWatch) M www.centerwatch.com Comprehensive Sickle Cell Center at Grady Health System M www.scinfo.org National Center for Biotechnology Information M www.ncbi.nlm.nih.gov National Guideline Clearinghouse (Agency for Health Care Policy and Research (AHCPR)) M www .guidelines.gov National Library of Medicine M www.nlm.nih.gov Patient-Reported Health Instruments M http://phi.uhce.ox.ac.uk Transfusionguidelines.org.uk M www.transfusionguidelines.org.uk This page intentionally left blank 803 Appendix 2 Charts and nomograms Karnofsky performance status 804 WHO/ECOG performance status 804 WHO hematological toxicity scale 805 Body surface area nomogram 806 Gentamicin dosage nomogram 807 The Sokal Score fo r CML prognostic groups 808 804 APPENDIX 2 Charts and nomograms Karnofsky performance status Table A2.1 Karnofsky performance status Normal, no complaints; no evidence of disease 100% Able to carry on normal activity; minor signs or symptoms of disease 90% Normal activity with eff ort; some signs or symptoms of disease 80% Cares for self; unable to carry on normal activity or to do active work 70% Requires occasional assistance but is able to care for most of his/her needs 60% Requires considerable assistance and frequent medical care 50% Disabled; requires special care and assistance 40% Severely disabled; hospitalization is indicated although death not imminent 30% Very sick; hospitalization necessary 20% Moribund; fatal processes progressing rapidly 10% Dead 0% WHO/ECOG performance status Table A2.2 WHO/ECOG performance status 0 Fully active; able to carry on all pre-disease performance without restriction 1 Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature, e.g. light housework, offi ce work 2 Ambulatory and capable of all self-care but unable to carry out any work activities; up and about more than 50% of waking hours 3 Capable of only limited self-care, confi ned to bed or chair more than 50% of waking hours 4 Completely disabled; cannot carry on any self-care; totally confi ned to bed or chair Further reading Oken, M.M. et al. (1982). Toxicity and response criteria of the Eastern Coo perative Oncology Group. Am J Clin Oncol, 5, 649. 805 WHO hematological TOXICITY SCALE WHO hematological toxicity scale Table A2.3 WHO hematological toxicity scale Parameter Grade 0 Grade 1 Grade 2 Grade 3 Grade 4 Hemoglobin (g/dL) \211 11.0 9.5 \200\22310.9 8.0 \200\2239.4 6.5 \200\2237.9 <6.5 Leucocytes ( \227 109/L) \211 4.0 3.0 \200\2233.9 2.0 \200\2232.9 1.0 \200\2231.9 <1.0 \211 2.0 1.5 \200\2231.9 1.0 \200\2231.4 0.5 \200\2230.9 <0.5 Granulocytes ( \227 109/L) \211 100 75 \200\22399 50 \200\22374 25 \200\22349 <25 Platelets ( \227 109/L) Hemorrhage None Petechiae Mild Gross blood loss Debilitating blood loss blood loss 806 APPENDIX 2 Charts and nomograms Body surface area nomogram Fig. A2.1 Body surface area nomogram. Reproduced with permission from Ramrakha, P. and Moor e, K. (1997). Oxford Handbook of Acute Medicine, 2e. Oxford University Press, Oxford. 807 GENTAMICIN DOSAGE NOMOGRAM Gentamicin dosage nomogram Fig. A2.2 Gentamicin dosage nomogram. Reproduced with permission from Longmore, M. et al. ( 2007). Oxford Handbook of Clinical Medicine, 7e. Oxford University Press, Oxford. 808 APPENDIX 2 Charts and nomograms The Sokal Score for CML prognostic groups Table A2.4 The Sokal Score for CML prognostic groups Score = Exp[0.0116 (age \200\22443.4)] + 0.0345 (spleen size[cm] \200\2247.51) + 0.188 ([platelet s(109/L)/700]2 \200\2240.563) + 0.0887 (blasts[%] \200\2242.1) Low risk <0.8 Intermediate risk = 0.8 \200\2231.2 High risk >1.2 809 Appendix 3 Normal ranges Adult normal ranges 810 Pediatric normal ranges 812 810 APPENDIX 3 Normal ranges Adult normal ranges Table A3.1 Hematology ( \231\202) ( \231\200) ( \231\202) ( \231\200) ( \231\202) ( \231\200) Hemoglobin 130 \200\223180g/L 115 \200\223165g/L 0.40 \200\2230.52 0.36 \200\2230.47 4.5 \200\2236.5 \227 1012/L 3.8 \200\2235.8 \227 1012/L 77 \200\22395fL 27.0 \200\22332.0pg 32.0 \200\2233 6.0g/dL 4.0 \200\22311.0 \227 109/L 2.0 \200\2237.5 \227 109/L 1.5 \200\2234.5 \227 109/ L 0.04 \200\2230.4 \227 109/L 0.0 \200\2230.1 \227 109/L 0.2 \200\2230.8 \227 109/L 150 \200\223400 \227 109/L 0.5 \200\2232.5% (or 50 \200\223100 \227 109/L) 2 \200\22312mm/1st hour (Westergren) 25 \200\22335mL/kg 20 \200\22330mL/kg 150 \200\223700ng/L 2.0 \200\22311 .0mcg/L 150 \200\223700mcg/L 15 \200\223300mcg/L (varies with sex and age) 14 \200\223200mc g/L (premenopausal \231\200) 0.8 \200\2231.2 12.0 \200\22314.0sec 0.8 \200\2231.2 26.0 \200\22333.5sec 2.0 \200\2234.0g/L 3sec of control <250mcg/L <500ng/mL 50 \200\223150IU/ dL Haematocrit RCC MCV MCH MCHC WBC Neutrophils Lymphocytes Eosinophils Basophils Monocytes Platelets Reticulo cytes ESR Red cell mass ( \231\202) ( \231\200) Serum B12 Serum folate Red cell folate Serum ferritin INR PT APTT ratio APTT Fibrinogen Thrombin time XDPs D-dimer Factors II, V, VII, VIII, IX, X, XI, XII RiCoF vWF: Ag Protein C Protein S Antithrombin III APCR Bleeding time 45 \200\223150IU/dL 50 \200\223150IU/dL 80 \200\223135U/dL 80 \200\223135U/dL 80 \200\22312 0U/dL 2.12 \200\2234.0 3 \200\2239min 811 ADULT NORMAL RANGES Table A3.2 Biochemistry and immunology 3.0 \200\2236.5mmol/L 11.5 \200\22316.5g/dL 60 \200\223125 micromol/L 135 \200\223145mmol/L 3.5 \200\2235.0mmol/v 32 \200\22350g/L <17micromol/L 100 \200\223300IU/L 2.15 \200\2232.55 mmol/L 200 \200\223450IU/L 0.7 \200\2231.5mmol/L 63 \200\22380g/L 0.18 \200\2230.42mmol/L 1 0 \200\22346IU/L 14 \200\22333mcmol/L 11 \200\22328mcmol/L 45 \200\22375mcmol/L 5 \200\2234 2IU/L 5 \200\22342IU/L 9 \200\22324pmol/L 0.35 \200\2235.5mU/L Serum urea Serum creatinine Serum sodium Serum potassium Serum albumin Serum bilirubin Serum alk phos Serum calcium Serum LDH Serum phosphate Serum total protein Serum urate Serum -GT Serum i ron ( \231\202) ( \231\200) Serum TIBC Serum ALT Serum AST Serum free T4 Serum TSH Immunology 5.3 \200\22316.5g/L 0.8 \200\2234.0g/L 0.5 \200\2232.0g/L IgG IgA IgM Complement: 0.89 \200\2232.09g/L 0.12 \200\2230.53g/L 0.11 \200\2230.36g/L 80 \200\223120% C3 C4 C1 esterase CH50 C-reactive protein Serum 2-microglobulin CSF proteins: <6mg/L 1.2 \200\2232.4mg/L IgG Albumin 0.013 \200\2230.035g/L 0.170 \200\2230.238g/L Urine proteins: Total protein Albumin (24h) <150mg/24h <20mg/24h 812 APPENDIX 3 Normal ranges Pediatric normal ranges Table A3.3 Full blood count Age Hb (g/L) MCV (fL) Neuts Lymph Platelets Birth 149 \200\223237 100 \200\223125 2.7 \200\22314.4 2 \200\2237.3 150 \200\223450 2 weeks 134 \200\223198 88 \200\223110 1.5 \200\2235.4 2.8 \200\2239.1 170 \200\223500 2 months 94 \200\223130 84 \200\22398 0.7 \200\2234.8 3.3 \200\22310.3 210 \200\223650 6 months 100 \200\223130 73 \200\22384 1 \200\2236 3.3 \200\22311.5 210 \200\223560 1 year 101 \200\223130 70 \200\22382 1 \200\2238 3.4 \200\22310.5 200 \200\223550 2 \200\2236 years 115 \200\223138 72 \200\22387 1.5 \200\2238.5 1.8 \200\2238.4 210 \200\223490 6 \200\22312 years Adult \231\202 Adult \231\200 111 \200\223147 76 \200\22390 1.5 \200\2238 1.5 \200\2235 170 \200\223450 121 \200\223166 77 \200\22392 1.5 \200\2236 1.5 \200\2234.5 180 \200\223430 121 \200\223151 77 \200\22394 1.5 \200\2236 1.5 \200\2234.5 180 \200\223430 Neuts, neutrophils; lymph, lymphocytes and platelets (all \227 109/L) Table A3.4 Haemostasis Parameter Neonate Adult level 150 \200\223400 \227 109/L Few sec longer than adult Up to 25% increase As adult Up to 1 week By 2 \200\2239 months As adult As adult As adult Platelet count Prothrombin time APTT Thrombin time Bleeding time Fibrinogen 2 \200\22310min 2.0 \200\2234.0g/L Vit K factors: Up to 6 months By 1 month Up to 6 months Up to 6 months 30 \200\22350% adult level 30 \200\22350% adult level 20 \200\22350% adult level 30 \200 \22350% adult level Factor II Factor VII Factor IX Factor X As adult Factor V Factor VIII vW factor Variable: 50 \200\223200% adult level Usually raised (up to 3 \227 adult level) 20 \200 \22350% adult level 20 \200\22350% adult level 50 \200\223100% adult level 6 \200\22312 months 3 \200\2236 months 1 month Factor XI Factor XII Factor XIII By 7 days 6 \200\22312 months Up to 24 months 3 \200\2236 months Up to twice adult level 50 \200\22380% adult level 30 \200\22350% adult level 30 \200\22350 % adult level FDP/XDP AT Protein C Protein S Plasminogen 30 \200\22380% adult level 2 weeks 813 Index A AA amyloid 386 A- -lipoproteinaemia 97 ABO haemolytic disease of AIDS-related Kaposi sarcoma 554, 557 peripheral blood fi lm 32, 33 AL amyloidosis 380 \200\2236, 393 Albers \200\223Sch nberg disease (osteopetrosis) 395, 59 8, 794 pernicious 46, 47 pregnancy 26 prematurity 570 refractory 230, 624 refractory with excess the newborn 579 ABVD 711 acanthocytes 33 acanthocytosis 41, 83, 97 acenocoumarol 515 acholuric jaundice 574 acrocyanosis 100 activated partial albumin (4.5%) 563 alcoholic anemia 41 aldolase defi ciency 92 allergic reactions 638, 640 allogeneic stem cell blasts 230, 231, 624 \200\2235 refractory with excess blasts in transformation 230, 624 \200\2235 transplantation 389, 398 \200\223400, 448 refractory with ringed thromboplastin time 458 all-trans-retinoic acid 135 AmBisome 442 \200\2233, 687 amegakaryocytic sideroblasts 230, 231, 242, 243 acute chest syndrome renal disease 34 \200\2235 sickle cell 56 \200\22360, 81 spur cell 41 starvation 51 unexpla ined 8 \200\2239 vitamin A defi ciency 51 vitamin B6 (pyridoxine) 57, 666 thrombocytopenia 596 acute fat embolism syndrome 58 acute haemolytic with absent radii (TAR syndrome) 486, 596 amphotericin, liposomal transfusion reaction 638, 640 442 \200\2233 amyloidosis 25 acute lymphoblastic AA 386 AL 380 \200\2236, 393 hereditary 386 defi ciency 51 leukemia 138 \200\22345, 392, 395, 414, 612 \200\22314, 755 vitamin B12 defi ciency 46 \200\2237 vitamin C defi ciency 51 vitamin E defi ciency 51 acute myeloblastic anemia leukemia 124 \200\22335, 225, 392, 395, 414, 620 \200\2232, 755 alcoholics 41 anorexia nervosa 51 aplastic 102 \200\2233, 393, analgesics 670 \200\2231 anaphylactic reactions 638 anaplastic large cell acute promyelocytic leukemia 135 395, 414 lymphoma 199, 201 autoimmune haemolytic androgens 36 angio-follicular lymph node hyperplasia (Castleman disease) 364, 788 ADAMTS13 538 adenosine deaminase defi ciency 546 adrenal disorders 36 adult T-cell leukemia - 98 \200\2239 of chronic disorders 38 congenital dyserythropoietic 588 \200\2239 Cooley \200\231s 76 \200\2237 Diamond \200\223Blackfan 395, angio-immunoblastic T-cell lymphoma 199, 201 aniline dye poisoning 634 ankylostoma 633 Ann Arbor staging 216, 217 anorexia nervosa 51 anticoagulation therapy 467, 514 \200\22317, 536 , 704 \200\2237 lymphoma 167, 178 \200\22380, 755 adult-type chronic 590 \200\2231 myeloid (granulocytic) leukemia 626 drug-related 38, 40, 50, 94, 102 afi brinogenaemia 482 \200\2233 agammaglobulinaemia, endocrine disease 36 Fanconi 395, 415, 594 \200\2235 folate defi ciency 26, 41, X-linked 548 age-adjusted IPI 187 aggressive lymphomas anti-D 422, 578, 579 antiemetics 694 \200\2236 antifungals 442 \200\2234, 687 antiphospholi pid syndrome 48 \200\2239 gastrointestinal disease 40 iron defi ciency 42 \200\2235 joint disease 38 \200\2239 leucoe rythroblastic 101 liver disease 41 megaloblastic 46, 48, 50 microangiopathic 198 \200\223208 aggressive NK-cell large granular lymphocyte leukemia 176 aggressive systemic 534, 535 antiretrovirals 556 antithrombin defi ciency 530, 531 mastocytosis 312, 319 aplastic anemia 102 \200\2233, aggressive T-cell large haemolytic 96, 576 neonatal haemolytic 572, 393, 395, 414 granular lymphocyte leukemia 175 aprotinin 470 argatroban 655 arsenic trioxide 135 574, 576 neonates 568 \200\2239 AIDS 552 \200\2233 814 INDEX transfusion-associated massive blood loss 508 neonates 585 surgery 28 \200\2239, 467, 506 \200\2237 therapeutic pr oducts aspergillosis 442 \200\2234 aspirin 502 asymptomatic GvHD 775 transfusion haemosiderosis 77, 110 \200\22311 (smoldering) myeloma 25, 332 \200\2234 470 \200\2231 transfusion-related acute thrombolytic therapy overdose 651 blood and blood products bacterial contamination ataxia telangiectasia 548 ATRA syndrome 135 atypical chronic lung injury 638 transfusion transmitted infections 774 \200\2235 see also blood and blood lymphocytic leukemia 161 638 products CMV-negative blood atypical chronic myeloid leukemia 252, 253 \200\2234 atypical mycobacteria 687 Auer rods 12 5, 126, 621 autoantibody mediated Bloom syndrome 595 body surface area nomogram 806 bone fractures 23 bone marrow fi brosis 2 95 harvesting 388, 408 \200\2239 mastocytosis 319 bone tumors 608 bortezomib/ products 420, 563, 765 irradiated products 776 issue and administration 763 haemolysis 94 autohaemolysis test 85 autoimmune disorders stem cell transplantation 420 \200\2232 see also specifi c products 394, 396 and blood transfusion blood counts 560 \200\2231, 746, autoimmune haemolytic anemia 98 \200\2239 dexamethasone 716 \200\22317 812 autoimmune neutropenia brain tumors 396, 608 breast cancer 393 bruising 20 \200\2231 Bruton tyrosine kinase defi c iency 548 B-symptoms 185 Burkitt cell leukemia 144 Burkitt-like lymphoma 616 Burkitt lympho ma 200, 201, 206, 393, 616, 618, 755 blood fi lm 746 blood-grouping 762 blood loss, see bleeding blood products, see blood and b lood products blood transfusion 759 \200\22381 15, 601 autologous stem cell transplantation 389, 402, 449 azo compound poisoning 634 acute transfusion reactions 638 \200\22340, 641 Better Blood Transfusion B babesiosis 82 basopenia 120 basophilia 120 basophilic stippling 33 basophils 120 B cells 118 BCR-ABL+ acute initiatives 764 burns 82 burr cells 33, 35 children 562 \200\2234 consent for 764 delayed transfusion reaction 642 C Candida infections 442, history 2 HLA-related issues 757 hospital transfusion committee 764 lymphoblastic leukemia 144 444, 549 cardiac haemolysis 82 cardiopulmonary bypass hospital transfusion policy BEACOPP/escalated BEACOPP 712 BEAM/LEAM 714 \200\22315 benign familial neutropenia 763 502 hospital transfusion team cardioversion 536 caspofungin 443, 444 Castleman disease 364, 788 Castleman-like disease 36 4 CD number 752 central indwelling catheters 764 intra-operative cell salvage 777 15 -lactam antibiotics 502 Better Blood Transfusion issue and administration blood and blood products 763 Jehovah \200\231s Witnesses initiatives 764 B-fi ndings 316 bilirubin 582 Binet staging 162 bird-headed dwarfi sm 598 bite cells 33 Bla ckfan \200\223Diamond 686 central nervous system, 780 \200\2231 see CNS laboratory requests 762 massive 468, 658 \200\22360 maximum surgical blood ordering schedul e 778 post-transfusion purpura C-fi ndings 316 \200\22317 Chediak \200\223Higashi syndrome 486, 603 chemotherapy anemia, see Diamond \200\223 Blackfan anemia administration 692 \200\2233 emesis and antiemetics 492, 643 bleeding 466 \200\2238 sickle-modifying therapy anticoagulant-induced 694 \200\2236 62 467, 515 extravasation 700 \200\2233 intrathecal 698 \200\2239 traceability 763 transfusion-associated circulatory overload 639 heparin-induced 510 \200\22311, 704 chemotherapy protocols laboratory investigations 710 \200\22344 ABVD 711 469 815 INDEX Crohn \200\231s disease 394 cross-matching 762 Crow \200\223Fukase syndrome 364 cryoglobuli naemia 363 cryoprecipitate 658, 660, chronic neutrophilic leukemia 304 chronic NK-cell large BEACOPP/escalated BEACOPP 712 BEAM/LEAM 714 \200\22315 bortezomib/ granular lymphocyte leukemia 176 \200\2237 dexamethasone 716 \200\22317 ChlVPP 720 CHOP (21 and 14) 771 chronic renal failure 34 \200\2235, cryopreserved stem cells 498 412, 416 \200\22317 CTD/CTDa 726 \200\2237 Cushing \200\231s syndrome 36 cutaneous mastocyt osis chronic severe lymphopenia 15 718 \200\22319 chronic thromboembolic CODOX-M/IVAC R pulmonary hypertension 518 722 \200\2234 312, 313 \200\22315 CTD/CTDa 726 \200\2237 DHAP R 728 \200\2239 ESHAP R 730 \200\2231 FC R 732 ICE R 733 lenalidomide/ cyanotic congenital heart ciclosporin 424 \200\2236 cirrhosis 109 cladribine 688 classical Hodgkin disease 632 cyclical neutropenia 15, 116, 600 cytogenetics 754, 755 cytomegalovirus (CMV) blood products 420, lymphoma 214 \200\22315, 221 \200\2233 CLL-score 160 clonality assessment 753 Clostridium p erfringens 82 clot formation 456 clotting factor concentrates dexamethasone 734 mini-BEAM R 736 MPT 735 NORDIC schedule 737 PMitCEBO 738 R-Bendamustine 739 R-CHOP 740 R -CVP and CVP 741 R-high-dose cytarabine 563, 765 neutropenic sepsis 687 transplant patients 446 \200\2237 470 D dabigatran 516 \200\22317, 707 dactylitis 57 danaparoid 655 Darier \200\231s sign 313 D-d imer assay 518, 519 deep vein thrombosis clotting tests 458 \200\22360 CMV, see cytomegalovirus CNS 737 leukemia 135, 144 lymphoma 212 \200\22313 coagulation system 456, rituximab monotherapy and maintenance therapy 742 R-maxi-CHOP 737 Stanford V 743 \200\2234 457, 459, 461 coagulation tests 458 \200\22360 codeine 671 CODOX-M/IVAC R 518 \200\22321 children, see pediatrics chloroma 135, 622 ChlVPP 720 CHOP (21 and 14) 718 \200\22319 Chris tmas disease 476 chronic benign neutropenia deferasirox 77, 111, 245 deferiprone 77, 111, 245 dendritic cell histiocytosis 722 \200\2234 cold antibody induced haemolysis 98 (Langerhans cell) 628 \200\2239, 793 cold haemagglutinin disease desferrioxamine 77, 110, 100 combined 15, 600 245 chronic eosinophilic desmopressin 470 dexrazoxane 701 DHAP R 728 \200\2239 diabetes mellitus 36 Diamond \200 \223Blackfan anemia immunodefi ciency disorders 546 \200\2238 leukemia, not otherwise categorized 308 \200\2239 chronic granulomatous disease 395, 603 common variable immunodefi ciency 549 compatibility testing 762 complement defi ciency 603 conditioning 389, 399, chronic idiopathic neutropenia 15 chronic infl ammatory demyelinating polyneuropathy 394 395, 590 \200\2231 diamorphine 671 diclofenac 670 diff use cutaneous 414 \200\22315 reduced intensity 389, mastocytosis 313 415 chronic lymphocytic diff use large B-cell congenital amegakaryocytic thrombocytopenia 596, 598 leukemia 158 \200\22365, 166, 392, 755 lymphoma 198, 201, 204, 392, 617, 618 DiGeorge syndrome 548 dihydrocodeine 671 dimorphic re d blood chronic mucocutaneous congenital candidiasis 549 dyserythropoietic anemia 588 \200\2239 chronic myeloid leukemia 148 \200\22356, 392, 395, 414, 755, 808 cells 33 congenital intrinsic factor Diphyllobothrium latum defi ciency 50