ABO compatible group if possible as with FFP. \200 Contains 80 \200\223100IU FVIIIC, 100 \200\223250mg Fgn, 50 \200\22360mg fi bronectin, and 40 \200\22370% of the original vWF. Should be used immediately for optimum replacement of Fgn and factor VIIIC. The adult dose is 2 pools of cryoprecipitate (each pool contains 5 units). Give when fi brinogen <1.5g/L. Reference 1. CRASH-2 Trial Collaborators (2010). Eff ects of tranexamic acid on death, vasc ular occlusive events, and blood transfusion in trauma patients with signifi cant hemorrhage (CR ASH-2): a randomized, placebo-controlled trial. Lancet, 376, 23 \200\22332. 661 MASSIVE BLOOD TRANSFUSION 662 CHAPTER 13 Hematological emergencies Paraparesis/spinal collapse May be due to tumor in the cord, spinal dura, or meninges or by exten- sion of a vertebral tumor into the spinal canal with compression of the cord or as a result of vertebral collapse. Spinal cord compression from vertebral collapse in a hematological patient is most commonly due to myeloma (in up to 20% of patients) but may occur in a patient with HL (3 \200\2238% ) or occasionally NHL. Spinal cord involvement by leukemia is most common in AML, less so i n ALL and CGL, and least common in CLL. Onset of paraplegia may be preceded for days or weeks by paraesthesia but in some patients the onset of paraplegia may follow initial symptoms by only a few hours. Symptoms suggestive of spinal cord compression require urgent assess- ment by CT or MRI and referral to a neurosurgical unit for assessment for surgical decompression. Where this is not possible, early radio- therapy may provide symptomatic improvement. However, if treatme nt is delayed until paraparesis has developed, this often proves to be irre- versible despi te surgery and/or radiotherapy. 663 LEUCOSTASIS Leucostasis Term is applied both to organ damage due to \200\230sludging \200\231 of leuco cytes in the capillaries of a patient with high circulating blast count and to the lodging and growth of leukaemic blasts, usually in AML, in the vascular tree eroding the vessel wal l and producing tumors and hemorrhage. Features \200 More common in AML and blast crisis of CML. \200 Leucostatic tumors are a ssociated with an exponential increase in blasts in the peripheral blood and, prior to the development of eff ective chemotherapy, hemorrhage from intracerebral tumors was not an unc ommon cause of death. Pulmonary or cerebral leucostasis are serious complications which may occur in patients who present with a blast count >50 \227 109/L. Leucocyte thrombi may cause plugging of pulmonary or cerebral capillaries. Vascular rupture and tissue infi ltration may occur. Less common manifestations are priapism and vascular insuffi ciency. \200 Pulmonary leuco stasis causes progressive dyspnoea of sudden onset associated with fever, tachypnoea, hypox aemia, diff use crepitations, and a diff use interstitial infi ltrate on CXR. Pulmonary hemorrhage and haemoptysis may occur. More common with monocytic leukaemias and t he microgranular variant of acute promyelocytic leukemia. Diff erentiation from bacterial o r fungal pneumonia may be diffi cult. Cerebral leucostasis may cause a variety of neurological abnormalities. Anemia may protect a patient with marked leucocytosis from the eff ects of i whole blood vi scosity. Transfusion of RBCs to correct anemia prior to chemotherapy may initiate leucostas is. Management Urgent leucapheresis is required for a patient with marked leucostasis (>200 \227 109/L) or in any patient in whom leucostasis is suspected. Chemotherapy may be commenc ed concomitantly to further reduce the leucocyte count but may be associated with a high in cidence of pulmo- nary and CNS hemorrhage. 664 CHAPTER 13 Hematological emergencies Thrombotic thrombocytopenic purpura De \201 nition Fulminant disease of unknown etiology characterized by i platelet aggregati on and occlusion of arterioles and capillaries of the microcir- culation. Considerable over lap in pathophysiology and clinical features with HUS \200\224fundamental abnormality may b e identical. Incidence Rare, 71 in 500,000 per year. \231\200: \231\202 = 2:1. HUS much commoner in chi l- dren, TTP commoner in adults \200\224peak age incidence is 40 years, and 90% of cases <6 0 years old. There is some case clustering. Clinical features \200 Classical description is of a pentad of features: \200 1. Microa ngiopathic haemolytic anemia. \200 2. Severe thrombocytopenia. \200 3. Neurological inv olvement. \200 4. Renal impairment. \200 5. Fever. In practice, few patients have the \200\230full Monty \200\231. 50 \200\22370% have renal abnor- malities (cf. nearly all with HUS) and they are less severe. Neurological involvemen t is more prevalent in TTP than HUS. 40% of TTP patients have fever. \200 Haemolysis \200 \224severe and intravascular causing jaundice. \200 Thrombocytopenia \200\224severe, muco sal hemorrhage likely and intracranial hemorrhage may be fatal. Neurological \200\224from mild depression and confusion l visual defects, coma and status epilepticus. Renal \200\224haematuria, proteinuria, oliguria and i urea and creatinine. HUS>TTP. Fever \200\224very variable, weakness and nausea common. \200 Other disease features: ser ious venous thromboses at unusual sites (e.g. sagittal sinus \200\224microthrombi in the br ain seen on MRI scan). Abdominal pain severe enough to mimic an acute abdomen is sometimes seen due to mesenteric ischaemia. Diarrhea is common, particularly bloody in HUS. Diagnosis and investigations \200 Made on the clinical features \200\224exclude other dis eases, e.g. cerebral lupus, sepsis with DIC. FBC shows severe anemia and thrombocytopenia. \200 Blood fi lm usually shows gross fragme ntation of red cells, spherocytes, and nucleated red cells with polychromasia. Reticulocytes ii. \200 LDH ii (>1000IU/L). \200 Clotting screen including Fgn and FDPs usually n (cf. DIC). \200 Serum haptoglobin low or absent. \200 Urinary haemosiderin +v e. \200 Unconjugated bilirubin i. 665 THROMBOTIC THROMBOCYTOPENIC PURPURA DAT \210\222ve. \200 BM hypercellular. \200 U&E show i (HUS>TTP). \200 Proteinuria a nd haematuria. \200 Renal biopsy shows microthrombi. \200 Stool culture for Escherichia coli 0157 +ve in most cases of HUS in children, less often in adult TTP. MRI brain scan shows microthrombi and occasional intracranial hemorrhage. 2Lumbar puncture \200\224do not proceed with LP unless scans clear and there is suspicion of infective meningitis. Look for evidence of viral infection. Association of syndrome with HIV, SLE, usage, and the 3rd trimester of pregnancy. Treatment is a hematological emergency \200\224seek expert help immediately 1 Unless antecu bital venous access is excellent, insert a large-bore central apheresis catheter (may need blood product support). 2 May need ITU level of care and ventilation. 3 Initiate plasmapheresis as soon as possible : Exchange 1 \200\2231.5 plasma volume daily until clinical improvement. May need 3 \200\2234 L exchanges. Replacement fl uid should be solely FFP. In the event of delayed access to cel l separator facilities, start IV infusions of FFP making intravascular space with diuretics if necessary. Once response achieved, d frequency of exchanges gradually. If no response o btained within 1 week, change FFP replacement to cryosupernatant (rationale: it lacks HMW m ultimers of vWF postulated in endothelial damage disease triggers). 4 Give RBC as necessary but reserve platelet transfusions for severe mucosal or intracrania l bleeding as reports suggest they may worsen the disease. 5 Cover for infection with IV broad-spectrum antibiotics including teicoplanin if necessary to preserve the apheresis catheter. 6 Start anticonvulsants if fi tting. 7 Most would start high-dose steroids (prednisolone 2m g/kg/d PO) with gastric protection although evidence is equivocal. 8 Aspirin/dipyridamole/heparin may be considered for non- responders. 9 Refractory patients (710%) should be considered for IV vincristine. 10 Still refractory p atients may achieve remission with splenectomy. 11 Response to treatment may be dramatic, e .g. ventilated, comatose patient watching TV in the afternoon after plasma exchange in the morning! Prognosis \200 90% respond to plasma exchange with FFP replacement. \200 730% will rela pse. Most respond again to further plasma exchange but leaves 15% who become chronic relapsers. Role of prophylaxis for chronic relapsers unclear. Intermittent FFP infusions or continuous low-dose aspirin may help individual cases. 666 CHAPTER 13 Hematological emergencies Sickle crisis Management 2Early and eff ective treatment of crises essential (hospital). 2Rest patient an d start IV fl uids and O2 (patients often dehydrated through poor oral intake of fl uid + e xcessive loss if fever). 2Start empirical antibiotic therapy (e.g. cephalosporin) if infect ion is suspected whilst culture results (blood, urine or sputum) are awaited. 2Analgesia us ually required \200\224e.g. IV opiates (diamorphine/morphine) especially when patients are fi rst admitted to hospital. Switch later to oral medication after the initial crisis abate s. 2Consider exchange blood transfusion (if neurological symptoms, stroke or visceral damag e). Aim to d HbS to <30%. 2Exchange transfusion if PaO2 <60mm on air ( 2chest syndrome). 2 -adrenergic stimulators for priapism. 2Seek advice of senior hematology staff . 2Consider regular blood transfusion if crises frequent or anemia is severe or patient has had CVA/abn ormal brain scan. 2Top-up transfusion if Hb <4.5g/dL (hunt for cause). Transfusion and splenectomy may be lifesaving in children with splenic sequestration. Management of acute chest syndrome \200 O2 supplementation. \200 Antibiotics (include c over for community-acquired organisms and atypicals). Monitor fl uid balance aiming for euvolaemia. \200 Implement pain management, avoid splin ting and oversedation. \200 Bronchodilator therapy. \200 Red cell transfusion if respir atory compromise or clinical deterioration. Further reading M www.bcshguidelines.com/pdf/SICKLE.V4_0802.pdf 667 Chapter 14 Supportive care Quality of life 668 Pain management 670 Psychological support 673 668 CHAPTER 14 Supportive care Quality of life In managing any disease problem a key objective is to improve the quality o f a patient \200\231s survival as well as its duration. Part of the clinical decision- maki ng process takes into account QoL in judging the most appropriate treatment. QoL is also ev aluated as an outcome in clinical trials parallel to conventional measures such as survival . Defi ning QoL precisely is not easy; it has been described as a measure of the diff erence at a particular time point between the hopes and expecta- tions of the individual and that individual \200\231s present experiences. QoL is multifaceted and can only be assessed by t he individual since it takes into account many aspects of that individual \200\231s life an d their current percep- tion of what, for them, is good QoL in their specifi c circumstance s. A clear distinction exists between performance scores (e.g. Karnofsky or WHO) which record functional status and assess independence; these are assessed by the physician according to pre-set criteria. They have erroneously been considered to be surrogate markers of QoL. Patient QoL as assessed by the treating physician has been shown to be unreliable in an onc ological setting. There is no single determinant of good QoL. A number of qualities which go to make up QoL a re capable of assessment; these include: ability to carry on normal physical activities, ab ility to work, to engage in normal social activities, a sense of general well-being, and a perception of health. Several validated instruments now exist to measure QoL; these mainly involve questionnaires completed by the patient. They are simple to complete and involve \200\230yes \200\231 or \200\230no \200\231 answers to specifi c questions, answers on a linear analog scale or t he use of 4- or 7-point Likert scales. Available QoL instruments include: \200 Functional Living Index \200\223Cancer (FLIC).1 \200 Functional Assessment of Cancer Therapy (FACT).2 \200 European Organization for Res earch and Treatment in Cancer (EORTC) Quality of Life Questionnaire C-30 (QLQ C30).3 Data from validated QoL questionnaires are now accepted as a require- ment and a clinical e nd point in many major clinical trials, especially in malignancies, particularly those wher e survival diff erences are minimal between contrasting therapy approaches. Where survivals are minimally aff ected it is essential to focus on treatments which will off er the best QoL. References 1 Schipper, H. et al. (1984). Measuring the quality of life of cancer patients: the Functional Living Index \200\223Cancer: development and validation. J Clin Oncol, 2, 47 2 \200\22383. 2 Cella, D.F. et al. (1993). The Functional Assessment of Cancer Therapy scal e: development and validation of the general measure. J Clin Oncol, 11, 570 \200\2239. 3 Aa ronson, N.K. et al. (1993). The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst, 85, 365 \200\22376. 669 QUALITY OF LIFE 670 CHAPTER 14 Supportive care Pain management Pain is a clinical problem in diverse hematological disorders, notably in s ickle cell disease, hemophilia, and myeloma. Acknowledgement of the need to manage pain eff ectively is an essential part of successful patient care and management in clinical hemato logy. Pain may be local or generalized. More than one type of pain may be present and causes may be multifactorial. It is most important to listen to the patient and give them the chance t o talk about their pain(s). Not only will this help determine an appropriate therapeutic st rategy, the act of listening and allowing the patient to talk about their pains and associ- ated anxieties is part of the pain management process. Engaging the patient in \200\230measuring \200\231 their pain is often helpful; it enables specifi c goals to be set and provides a means to assess the eff ective- ness of the analg esic strategy. A variety of scales have been employed, with simple numerical values ( \200 \230pain score out of ten \200\231) being the most common. These strategies must be tailore d to the individual patient \200\231s comprehension \200\224often young children are being assessed. Basic to the control of pain is to manage and remove the pathological process causing pain, wherever this is possible. Analgesia must be part of an integrated care plan which takes t his into account. Analgesic requirements should be recorded regularly as these form a valuable \200\230semi- quantitative \200\231 end point of pain measurement. Reduction in requirements, for example , is an indicator that attempts to remove or control the underlying cause are succeeding. Managing pain successfully involves patient and family/carer participation, a collaborative multidisciplinary approach in most categories of haema- tological disorder-related pain; m edication should aim to provide contin- uous pain relief wherever possible with a minimum o f drug-related side eff ects. Anticipating pain with the use of regular medications rather than a \200\230PRN \200\231 basis can be key to analgesic success. Treatment strategies ar e based on the WHO pain ladder, simple analgesics being used initially, in combination with opiates of i strength if pain is not relieved (Table 14.1). Table 14.1 Analgesics Paracetamol: 1g 4 \200\2236-hourly, oral as tablets or liquid; suppositories available Simple non-opioid analgesics No contraindication in liver disease; useful in mild-to-moderate pain Ibuprofen 800mg or diclofenac 75 \200\223100mg bd as slow release formulations can be syner gistic with other analgesics; combined formulations of diclofenac with misoprostol may redu ce risks of gastric irritation bleeding, or used with gastric acid suppressants; useful in combination with paracetamol or weak opioids Anti-in \202 ammatory drugs Caution should be exercised in renal impairment (notably in myeloma) 671 PAIN MANAGEMENT Table 14.1 Analgesics (continued) Codeine 30 \200\22360mg usually combined with paracetamol 1g as co-codamol 30/500 tablets; usual dosage is 2 tablets 6-hourly or dihydrocodeine 30 \200\22360mg up to 4-hourly provide eff ective analgesia for moderate pain Weak opioids Confusion, drowsiness may be associated with initial usage in some. Weak (and strong) opioi ds cause constipation; usually requires simple laxatives Morphine available as liquid or tablets commencing at 5 \200\22310mg and given 4-hourly is treatment of choice in severe pain Strong opioids Once daily requirements are established patients can be \200\230converted \200\231 to 12-h ourly slow release morphine preparations Breakthrough pain can be treated with additional doses of 5 \200\22310mg morphine. Diamorph ine preferred for parenteral usage. Highly soluble and suitable for use in a syringe driver for continuous administration or as a 4-hourly injection. Can be administered as a nasal s pray in children. Accumulation can occur with renal impairment Tramadol may be given orally Alternatives to opioids Fentanyl given as slow release transdermal patches may be a valuable alternative to slow re lease morphine for moderate-to-severe chronic pain. It is also available in \200\230lollip op \200\231 and sublingual tablets form for rapid relief Oxycodone is a newer synthetic opiate which has been successfully employed as an alternativ e to morphine where analgesia is inadequate or adverse eff ects intolerable For chronic pain give analgesia PO regularly, wherever possible. \200 Pain control is ver y specifi c to the individual patient, there is no \200\230correct \200\231 formula other than the combination of measures which alleviate th e pain. The clinician should work \200\230upwards \200\231 or \200\230downwards \200\231 through the levels of available analgesics to achieve control. Constipation due to analgesics should be managed appropriately. \200 Nausea or vomiting m ay occur in up to 50% patients with strong opiates; anti-emetics should be given to avoid n ausea or vomiting. Additional general measures include: Radiotherapy for localized cancer pain and lytic lesions in myeloma. \200 Physical method s, e.g. TENS or consideration of nerve root block. \200 Surgery, especially in myeloma wh ere stabilizing fractures and pinning will relieve pain and allow mobility. Encouraging/allowing patients to utilize \200\230alternative \200\231 approaches. includin g relaxation techniques, aromatherapy, hypnosis, etc. 672 CHAPTER 14 Supportive care Additional drug therapy: Antidepressants, e.g. amitriptyline may help in neuropathic pain. \200 Anticonvulsants, e .g. carbamazepine and gabapentin may be helpful in neuropathic pains especially in post-herpetic neuralgia. \200 Corticosteroids, particularly dexamethasone, to relieve leukaemic bone pain in late-stage disease. Very rarely can spinal anesthesia be used in acute pain problems 2 to myelomatous disease. This can be a bridge to a more defi nitive solution. Many hospitals also run specifi c pain clinics and have palliative care or pain control tea ms who can review in-patients and off er advice. The support and expertise available should be enlisted particularly for diffi cult prob- lems with persistent localized pain, e.g. po st-herpetic neuralgia. For long- term painful conditions it is essential to work with medic al and nursing colleagues in Primary Care and in Palliative Care so that the patient receiv es appropriate support in hospital as well as in the community setting. Physiotherapy care can also be appropriate, particularly with chronic joint damage (e.g. in haemophilic arthro pathy), and orthopedic referral is often useful. The severe acute pain in sickle crises often requires high and frequent doses of strong opi ates. Health professionals unused to caring for patients with these conditions are sometime s cautious about use of such high doses and fear that patients may become addicted. Situati ons can arise whereby the patients are not receiving appropriate care because of such fears . These can be generally resolved by good communication and education. Electronic note keep ing and databases can help in communi- cation. Psychological dependence on opiates is rare, and may be associ- ated with diffi cult psychosocial circumstances which makes care for su ch patients challenging. 673 PSYCHOLOGICAL SUPPORT Psychological support Many hematological disorders are long-term conditions; the spe- cifi c diagnosis can be seen to \200\230label \200\231 the patient as diff erent or ill and the refore will exert a profound infl uence on their life and that of their immediate family or carers. Patients (and their families) experience and demonstrate a number of reactions to their diagnosis, the clinical hae- matologist needs to have an awareness of this and respon d accordingly. Reactions to serious diagnosis include: \200 Numbness. \200 Denial. \200 Anger. \200 Guilt. \200 Depression. \200 Loneliness. Ultimately most patients come to acceptance of their condition; carers/ partners will also go through a similar range of reactions. The clinician needs to be aware of the way in whic h news of a diagnosis is likely to aff ect a patient and their family/carers and respond ap propriately. In the fi rst instance this will often involve the need to impart the diagnosi s, what it means, and what needs to be done clinically. There is no \200\230right way \200 \231 to impart bad or diffi cult news. It is very important to make and take time to tell t he patient of the diagnosis. Wherever possible this should be done in a quiet, private sett ing. The presence of an experienced Clinical Nurse Specialist is advised. Numbness at learn ing of a serious diagnosis often means that very little is taken in initially other than th e diagnostic label. The various reactions just listed may subsequently emerge during the ti me the patient comes to accept the diagnosis, what it means, and what is to be done clinica lly. Literature can be very useful to convey disease information. Within the hematological team there should be support available to the patient and family/c arers which can provide them with practical infor- mation about the disease and its managem ent. Simply knowing there is a sympathetic ear may be all that is required in the way of su pport; however, for some patients and families/carers more specialized support may be neede d, e.g. availability of formal counseling or access to psychological or psychiatric support . Children may experience a variety of hematological diseases requiring admission to hospital . They will have ongoing needs with regards to schooling and exams. Specialist professional s such as play therapists can help families through frightening and confusing experiences. Use can be made of local or national patient support groups; knowledge of others in similar predicaments can help diff use anger and loneliness. Support groups can also be a valuable resource in providing information and experience which patients and families/carers fi nd helpful. The most eff ective psychological support for hematological patients is to see the m as individuals and not \200\230diseases \200\231. Clinical nurse specialists play an abs olutely vital role and must where possible be involved in the patient \200\231s journey. This page intentionally left blank 675 Chapter 15 Protocols and procedures Acute leukemia: investigations 676 Platelet reactions and refractoriness 678 Prophylactic r egimen for neutropenic patients 680 Guidelines for use of IV antibiotics in neutropenic pat ients 682 Treatment of neutropenic sepsis: source unknown 684 Treatment of neutropenic seps is: source known/ suspected 686 Prophylaxis for patients treated with purine analogs 688 Tumor lysis syndrome 690 Administr ation of chemotherapy 692 Antiemetics for chemotherapy 694 Intrathecal chemotherapy 698 Man agement of extravasation 700 Specifi c procedures after extravasation of cytotoxics commonly used in hematology 702 Anticoagulation therapy: heparin 704 Oral anticoagulation with VKA 706 Oral anticoagulation with NOAC 707 Management of needlestick injuries 708 Chemotherapy protocols 710 ABVD 711 BEACOPP/escalated BEACOPP 712 BEAM/LEAM 714 Bortezomib/dexamethasone 716 CHOP 21 a nd CHOP 14 718 ChlVPP 720 CODOX-M/IVAC R 722 CTD and CTDa 726 DHAP R 728 ESHAP R 7 30 FC R 732 ICE R 733 Lenalidomide/dexamethasone 734 MPT 735 Mini-BEAM R 736 Nordi c schedule (R-maxi-CHOP and R-high-dose cytarabine for MCL) 737 PMitCEBO 738 R-Bendamustine 739 R-CHOP 740 R-CVP and CVP 741 Rituximab: monotherapy and mai ntenance therapy 742 Stanford V 743 Note Please check local protocols and guidelines since these may diff er to those outlined in this handbook. Local guidelines should be followed. 676 CHAPTER 15 Protocols and procedures Acute leukemia: investigations \200 FBC, blood fi lm, reticulocytes. \200 ESR & CRP. \200 Serum B12, red cell folate, and ferritin. \200 Blood group, antibody screen, and DA T/DCT. \200 Coagulation screen, PT, APTT, fi brinogen. \200 BM aspirate for morphology, cytogenetics, immunophenotype (type peripheral blood if relevant) plus additional samples if required by clinical trials. BM trephine biopsy recommended at diagnosis. Biochemistry \200 U&E, LFTs. \200 Ca2+, phosphate, random glucose. \200 LDH. Virology \200 Hepatitis & HIV serology. \200 CMV IgG and IgM. Immunology \200 Serum immunoglobulins. \200 Autoantibody screen profi le. \200 HLA ty pe \200\224class 1 always in case HLA matched platelets are required, class 1 and 2 if allogeneic transplant indicated. Bacteriology \200 Baseline blood cultures. \200 Throat swab. \200 MSU. \200 Stool f or fungal culture. \200 Swabs for MRSA. Cardiology \200 ECG. \200 Echocardiogram: if in cardiac failure, infective endocarditis , older patient, or suspected/signifi cant cardiac history. Radiology \200 CXR. \200 Other imaging as guided by clinical picture (chloromas). Other \200 If any evidence of severe dental caries or gum disease refer patient for dental assessment. Consider semen storage, or egg harvesting pre-chemo. 677 ACUTE leukemia: INVESTIGATIONS 678 CHAPTER 15 Protocols and procedures Platelet reactions and refractoriness Reactions to platelet transfusion are common and rang e from mild temperatures to rigors. The development of an urticarial rash is also frequentl y seen. Most reactions are 2 to plasma-proteins. When a transfusion reaction develops, th e following steps should be taken: \200 Stop the transfusion. \200 Give 10mg chlorphena mine IV and 1g of paracetamol PO. \200 Cover future transfusions with chlorphenamine and paracetamol 30min pre-transfusion. Hydrocortisone 100mg IV stat may be (sparingly) used for refractory reactions but not routinely recommended. Pethidine is a suitable alternative for severe reactions/rigors and is almost invariably ef f ective. Give 25mg IV stat with repeat dose if necessary. The possibility of generation of HLA and platelet-specifi c antibodies should also be considered. Platelet refractoriness More than 2/3 of patients receiving multiple transfusions with rand om platelets develop anti-HLA antibodies. Refractoriness is defi ned as failure of 2 consec utive transfusions to give corrected increment of >7.5 \227 109/L 1h after platelet transf usion in absence of fever, infec- tion, severe bleeding, splenomegaly, or DIC. See Box 15.1 for calculating platelet increment. The most common physical mechanism is of platelet circulatory half- life reduction caused b y concurrent sepsis or coagulopathy, e.g. DIC. Immunological causes include induction of an ti-HLA antibodies due to allo-sensitization from previous transfusions or generation of ant i-platelet antibodies such as in ITP. Investigation should be considered if platelet transf usions fail to maintain a platelet count >10 x 109/L at all times. Proceed as follows \200 Aim for group-specifi c platelet transfusions. \200 Check FBC p re-platelet infusion, 1h and 12h post-infusion to assess the rate of platelet count reduction. Failure to show a rise of platelet count by at least 10 \227 109/L at 1h or any rise after 12h post-infusion merits further testing. Samples should be sent to a blood transfusion center for HLA- antibody screening (10mL EDTA samples and 20mL serum). The patient \200\231s own HLA type should be checked. \200 If negative for HLA-antibodies , HPA-antibodies should be tested for. \200 If HLA or HPA antibodies are identifi ed, the provision of HLA or platelet antigen matched platelet products may improve the platelet transfusion responsiven ess. In emergencies random platelets can and should be used if no HLA- matched platelets are available. 679 PLATELET REACTIONS AND REFRACTORINESS Box 15.1 Calculating platelet increment [(P1 \210\222 P0) SA]/n P0 = platelet count pre-tr ansfusion ( \227 109/L) P1 = platelet count post-transfusion ( \227 109/L) SA = surface are a n = number of units of platelets transfused Corrected increment 60min after transfusion >7. 5 \227 109/L indicates successful platelet transfusion (P1 \210\222 P0). 680 CHAPTER 15 Protocols and procedures Prophylactic regimen for neutropenic patients Infective risk is related to the severity and duration of neutropenia. Higher risk is associated with concurrent immunological defects, e.g. hypogammaglobulinaemia in myeloma, T-cell defects, e.g. in HIV, addi- tional immunosup pressive agents, e.g. ciclosporin post-transplant, and older patients. Principal risk is fr om bacterial organisms but fungi and viruses, especially herpes (HSV, HZV) as well as CMV a re also seen in prolonged neutropenia. Generally prophylaxis is only recommended for patien ts with prolonged phases of neutropenia. Typical protocols include: \200 Isolation procedures: isolation rooms with +ve pressure f i ltered air. Strict hand washing by all patient contacts is the only isolation measure of universally pr oven benefi t. Others include visitor restriction, gloves, aprons, gowns, masks, and full r everse barrier nursing. Drinks: avoid mains tap water. Avoid unpasteurized milk and freshly squeezed fruit juice. Food: avoid cream, ice-cream, soft, blue, or ripened cheeses, live yogurt, raw eggs or derived foods, e.g. mayonnaise and souffl s, cold chicken, meat pat , raw fi sh/shellfi sh, unpeeled fresh vegetables/ salads, unpeeled fruit, uncooked herbs a nd spices. These are general guidelines, a realistic approach with common sense should prev ail. \200 General mouthcare: antiseptic mouthwash (e.g. chlorhexidine gluconate) 4-hourly, swish and spit. For generalized ulceration use 0.9% saline mouthwash hourly, swis h and spit. Oral antifungal prophylaxis could be with nystatin suspension 1mL 4-hourly swis h and spit or swallow. \200 Antibacterial prophylaxis: aim to alter fl ora and prevent ex ogenous colonization. Principal agents: ciprofl oxacin and co-trimoxazole. Prophylactic cip rofl oxacin during prolonged periods of neutropenia has shown a reduction on morbidity and in some studies mortality and is recommended. Local guidelines should be followed. Antifungal prophylaxis: a systemic azole compound is most routinely used. Fluconazole is in ferior to itraconazole liquid. Posaconazole has been shown to be superior to both and is be coming more commonly used. Local guidelines should be followed. Antiviral prophylaxis: aciclovir is the most useful drug at preventing viral infection (mai nly herpes reactivation). Generally 400mg BD is recommended throughout prolonged phases of neutropenia. Local guidelines should be followed. Additional prophylaxis for speci \201 c situations: history of, or radiological evidence o f, tuberculosis (TB). Consideration should be given to standard anti-TB prophylaxis, e.g. i soniazid for 6 months particularly if prolonged neutropenia is expected. Splenectomized pat ient \200\224 at i risk from encapsulated organisms particularly Streptococcus pneumoniae, Haemophilus infl uenza, and Neisseria meningitidis. Use phenoxymethylpenicillin 500mg od PO or erythromycin 250 mg bd PO if penicillin allergic as prophylaxis switching to high dose amoxicillin/cefotaxime if febrile. 681 PROPHYLACTIC REGIMEN FOR NEUTROPENIC PATIENTS 682 CHAPTER 15 Protocols and procedures Guidelines for use of IV antibiotics in neutropenic patients Urgent/immediate action required if neutropenic patient develops: \200 Single fever spike >38 C. \200 2 fever spikes >37.5 C 1h apart. \200 Symptoms or signs of sepsis or inf ection without fever (e.g. hypotension and tachycardia). Assessment \200 Search for localizing symptoms or signs of infection. \200 Full clinica l examination noting BP, pulse, RR, and oxygen saturations. Examination including oral exam ination, chest, perineum, line sites, skin, and fundi. O2 saturation (pulse oximetry). \200 FBC, U&E, creatinine, LFTs, CRP, PT, APTT, fi brinog en. \200 Perform a septic screen: Blood cultures (10mL per bottle optimizes organism recovery) if central line present, take paired peripheral and central samples. Single further blood culture set if non-response at 48 \200\22372h or condition changes. Repeat cultures every 24h if ongoing fever. Swab relevant sites: wounds, central line exit site, throat. \200 Sputum culture. \200 MSU. \200 Feces if symptomatic incl. C. diffi cile toxin. \200 Viral serology if clinic ally relevant. \200 CXR. \200 Other imaging as relevant, consider sinus CT. \200 Cons ider bronchoalveolar lavage if chest infi ltrates present. \200 Consider risk of invasive fungal infection: HRCT chest if high risk and unresponsive to antibiotics. Empirical treatment Start IV broad-spectrum antibiotics to provide adequate cover. Stop pro phylactic ciprofl oxacin. Local protocols are based on local experi- ence and epidemiology of infections and organism. Follow local protocol where available. One possible protocol is shown here: 1st line: piperacillin-tazobactam 4.5g tds plus gentamicin 5 \200\2237mg/kg OD. If patient has history of penicillin allergy use ceftazidime 2g tds instead of piperacillin-tazobactam . If suspected line infection (exit site infl ammation, symptoms typically after line-use) ad d vancomycin 1g bd and consider line removal. If there are signs of perianal sepsis, mucositis or intra-abdominal infec- tion or if C. di ffi cile is suspected add metronidazole 500mg tds IV/oral. \200 Patients on od gentamicin should have pre-dose level checked 24h after 1st dose then twice weekly if satisfactory. 683 GUIDELINES FOR USE OF IV ANTIBIOTICS Patients on vancomycin should have predose levels checked immediately before 3rd or 4th dose (2nd if renal impairment) then twice weekly if satisfact ory. Reassess at 48h If no response to antibiotics and \210\222ve blood cultures: \200 Consid er switching to 2nd-line antibiotics, e.g. meropenem 1g tds vancomycin (if central line in situ). Consider line removal. \200 Further imaging as clinically indicated. Reassess after further 48h If no response to antibiotics and \210\222ve blood cultures: If high risk for invasive fungal infection: Consider starting antifungal therapy if clinica lly suggestive or signs of invasive fungal infection on imaging (e.g. liposomal amphoterici n 3 \200\2235mg/ kg/d, including a 1mg test-dose). Stop prophylactic antifungal. Request HR CT and consider bronchoscopy with bronchio-alveolar lavage (BAL). If low risk for invasive fungal infection: Consider switching antibiotics after microbiolog y advice. Reassess after further 48 \200\22372h \200 Further management empirical and individual. D iscuss with microbiology. Sometimes switching antifungal agent might be indicated. Duration of therapy If fever responds and cultures are \210\222ve, continue anti-infective treatment until apyrexial for 48h or minimum 5d course. If still neutropenic restart proph ylactic anti-infectives. Antifungal therapy should be continued until complete response and neutrophil regeneration; no fi xed duration can be recommended; oral voriconazole or posac onazole can facilitate early discharge during this period. Wherever possible switching to o ral agents as soon as clinically possible is indicated. +ve cultures Antibiotic therapy may be changed on the basis of +ve cultures and sen- sitivi ties at any time. 684 CHAPTER 15 Protocols and procedures Treatment of neutropenic sepsis: source unknown 3 One of the most common haemato-oncologica l emergencies. \200 May be defi ned as the presence of symptoms or signs of infection in a patient with an absolute neutrophil count of <1.0 \227 109/L. In practice, the neutrophi l count is often <0.1 \227 109/L. Similar clinical picture also seen in neutrophil function disorders such as MDS despite n neutrophil numbers. Can occur without pyrexia, especially patients on steroids. \200 In neutropenic patients all new symptoms must be taken seriously and assessed for possible underlying infective cau ses. Known neutropenic patients or patients at risk of neutropenia must have easy and insta nt access to acute care/hospital admission. Immediate action 3 Urgent clinical assessment. See E Septic shock, p.636 for further detail s; summary: \200 Fluid resuscitation. \200 Insert central catheter if not in situ and m onitor CVP. \200 Start O2 by face mask if pulse oximetry shows saturations <95%. \200 P erform full septic screen. \200 Give 1st dose of 1st-line antibiotics immediately. Follow established protocols. Monitor fl uid balance chart/urine output. \200 If BP not restored with appropriate fl ui d resuscitation, consideration should be given to inotropes. If O2 saturations remain low despite 60% O2 delivered by rebreathing mask, consider (non-invasive) ventilation. \200 Discuss with senior colleague and alert I TU. Subsequent actions \200 Amend antibiotics according to culture results. \200 Follow neu tropenic sepsis protocol as outlined on E p.680. \200 Continue antibiotics for a minimum of 5d and often until neutrophil recovery. If cultures show central line to be source of sepsis, remove immediately if patient not responding. Consider central line removal at presentation if lines suspected source. 685 TREATMENT OF NEUTROPENIC SEPSIS: SOURCE UNKNOWN 686 CHAPTER 15 Protocols and procedures Treatment of neutropenic sepsis: source known/suspected Central indwelling catheters Very common. Organisms usually Staph. epidermidis but can be o ther Staph. spp. and even Gram \210\222ve organisms. Line might appear fi ne, but there ma y be erythema/exudate around entry or exit sites of line, ten- derness/erythema over SC tun nel or discomfort over line track. Suspect line if rigors/symptoms in period after line use /fl ush. Blood cultures must be taken from each lumen and peripherally. Add vancomycin 1g b d IV to neutropenic protocol. If no response or clinical deterioration, remove line immedia tely.