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9.1 Anaemias and some other Blood Disorders
9.1.1 Iron-deficiency anaemias
    Treat demonstrable iron-deficiency state only. Use prophylactically in some situations.
    Patients should be directed to purchase nutritional supplements (including iron) over the counter post bariatric surgery.
    See guideline Oral Iron
   Treatment needs 100-200mg elemental iron per day. Prophylaxis 50-100mg elemental iron per day.  When treating iron-deficiency
   anaemia, haemoglobin should rise by approximately 100-200mg/100ml (1-2g/litre) per day or 2g/100ml (20g/litre) over 3-4 
   weeks. Once it has reached reference range, treatment should be continued for a further 3 months in order to replenish iron 
   stores, and then stopped.
       GREEN      Ferrous sulphate tablets 200mg provide 65mg iron  
       GREEN      Ferrous fumarate tablets 210mg provide 68mg iron
       GREEN      Sodium feredetate elixir (Sytron®)** provides 27.5mg iron/5ml 
       GREEN      Ferrous fumarate syrup 140mg/5ml provides 45mg iron/5ml
   ** ELHT neonatal formulary recommends that babies started on Sytron® and/or Abidec® on the Neonatal Intensive Care Unit  
        (ELHT) should remain on the treatment for 1 year post birth. GPs in Primary care are requested to continue to prescribe these 
        products for neonates until the age of 1 year old.
   Modified release preparations give a reduced total daily dose of iron, and are less efficacious as they carry iron past the
   duodenum where absorption may be poor. They should therefore only ever be used for low dose prophylaxis, not for treatment       of  iron- deficiency states.
       GREEN      Ferrous sulphate modified release tablets 325mg (Ferrograd®) (provides 105mg iron (give once daily)
   Iron and folic acid
       GREEN      Pregaday® tablets provide 100mg iron + 350microgram folic acid Parenteral Iron
   The only valid reason for administering iron parenterally is non-tolerance of oral therapy, continuing blood loss or malabsorption.
   If oral preparations are taken reliably and are absorbed, the haemoglobin response is not significantly faster with the
   parenteral route. 
   CosmoFer® (iron dextran injection) has the advantage of being licensed for administration 
   as a single total dose infusion, and can also be given IM. Due to the association of administration of parenteral iron preparations
   with severe anaphylactoid reactions prescribers are reminded to test dose patients and have anaphylactic emergency kits 
   close to hand when giving either Cosmofer® or Venofer®.
   First Line
       AMBER     Iron dextran injection (CosmoFer®) 2ml provides 50mg/ml iron
   Second Line
       AMBER     Iron sucrose injection (Venofer®) 5ml provides 20mg/ml iron
       RED           Ferric Carboxymaltose (Ferinject®) 50mg/ml*
       * Can be considered as a cost effective option where IV iron is required - shorter infusion time , reduced adverse effects  
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 9.1.2 Drugs used in megaloblastic anaemias
   Megaloblastic anaemia is usually due to vitamin B12 or folate deficiency; the specific deficiency and underlying cause must be 
   identified. Treatment is usually only begun once a firm diagnosis is made. In emergencies, where delayed treatment may be
   dangerous, both folate and vitamin B12 may be required initially, until assay results are known. Folate must not be used alone
   in undiagnosed megaloblastic anaemia due to the risk of B12 deficiency leading to peripheral neuropathy. During pregnancy
   the prevention of a first occurrence of neural tube defects is with 400 microgram/day. A higher dose of folic acid at 5mg/day 
   is used for folate deficiency and prevention of recurrence of neural tube defects.  Both should be continued for the first 
   twelve weeks of pregnancy.
       GREEN      Folic Acid
                          tablets 5mg
                          tablets 400 microgram
                          syrup 2.5mg/5ml
       RED           Folic acid injection 15mg/ml (unlicensed)
       GREEN      Hydroxocobalamin injection 1mg/ml
   There is little place for use of low dose vitamin B12 orally. 
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9.1.3 Drugs used in hypoplastic, haemolytic and renal anaemias
   Epoetin for use in patients with renal disease will be supplied from the tertiary referral centre.  For all other indications supply 
   will usually be organised through a home delivery company.
       RED           Darbepoetin alfa (Aranesp®) Prefilled disposable SureClick™ devices
                         100micrograms, 150micrograms, 300micrograms, 500micrograms.
       RED           Epoetin alfa (Eprex®)
                         Vial 40 000unit/ml 1ml
                         Prefilled syringes 1000units, 2000units, 4000units, 5000units, 6000units, 8000units, 10,000units.
   NICE TA323 - replaces NICE TAG142
   Erythropoiesis-stimulating agents (epoetin and darbepoetin) are recommended, within their marketing authorisations, as options
   for treating anaemia in people with cancer having chemotherapy.          
   NICE TA807: Roxadustat for treating symptomatic anaemia in chronic kidney disease
                         Roxadustat is recommended as an option for treating symptomatic anaemia associated with chronic kidney disease 
                         (CKD) in adults only if:
                            > they have stage 3 to 5 CKD with no iron deficiency and
                            > they are not on dialysis at the start of treatment
                            > the company provides roxadustat according to the commercial arrangement
       RED              Roxadustat [Evrenzo] tablets 20mg, 50mg. 70mg, 100mg, 150mg
                                                                                                                                                                    ICB Commissioned, Blueteq required
   Iron Overload
   Iron overload is the result of many disorders and can lead per se to the development of organ damage and increased mortality. 
   In humans total body iron stores is maintained within the range of 200-1500 mg by adequate adjustment of intestinal iron
   absorption, since no excretory mechanisms exist. Frequent blood transfusions lead to excessive accumulation of iron with a toxic 
   accumulation in 3 to 10 years. The toxicity of iron results from two related events:
            1. excess iron deposits in various tissues of the body, particularly in liver, heart and
                endocrine organs with the consequence of liver diseases, diabetes mellitus and
                other complications, and
            2. free iron that catalyzes the formation of highly reactive hydroxyl radicals which 
                lead to membrane damage and denaturation of proteins.
   Once iron exceeds a certain level, these effects lead to significant morbidity and mortality. Without specific chelation therapy to
   remove the iron, in 3 to 10 years almost all regularly transfused patients will have acquired a toxic accumulation of iron.
   The main cause of death is due to cardiac complications. The management of established iron overload also  involves 
   venesection which is not always possible.  The subsequent aim is to make the iron as safe as possible by binding the toxic iron
   pools responsible for causing tissue damage. Iron chelation therapy reduces iron-related morbidity, reduces and retards liver 
   diseases, diabetes and other endocrine failures, normalizes growth and sexual development, prevents, and in some cases 
   reverses, cardiac insufficiency and improves quality of life. Consequently iron chelation therapy dramatically reduces mortality.

   Deferasirox should only be initiated and prescribed by a haematologist or paediatrician for the management of patients with 
   chronic iron overload.  It can be used as a first line therapy for all beta thalassaemia patients aged 6yrs and older requiring 
   frequent blood transfusions (>7 ml/kg/month packed red blood cells).  

   It should be used as a second or third line therapy in the following groups:
         >   patients  with beta thalassaemia major aged 2-5yrs, patients with beta thalassaemia requiring infrequent
              blood transfusions, or
         >   those patients with other rare anaemias where desferrioxamine (DFO) and/or deferiprone are contra-indicated, 
               not tolerated or insufficiently effective. 
   Deferasirox should only be used in those patients with myelodyslplastic syndrome (MDS) requiring long term blood transfusions 
   such as those with sideroblastic anaemia or 5q-- syndrome where concurrent immunosuppression prevents the use of DFO.
   Treatment should be regularly monitored by the specialist according to the SPC.  Desferasirox should be funded by the patients 
   CCG under ‘pass through’ funding.  Deferasirox requires intensive monitoring - consult the SPC.   

       RED           Deferasirox dispersible tablets 125mg, 250mg, 500mg (Exjade®)

   Desferrioxamine (deferoxamine) is given by sub-cutaneous infusion, usually over 12hrs for a certain number of days per week.  It 
   is an alternative to desferasirox, where this cannot be used.  Supplies are made direct to the patients home through a 
   homecare delivery service, funded by the patients CCG.  Contact pharmacy before prescribing.  Specialist use only.
       RED           Desferrioxamine mesilate 500mg, 2gram vial

   Deferiprone is only used in thalassaemia major where desferrioxamine is contra-indicated or is not tolerated.  Blood dyscrasias,
   particularly agranulocytosis have been reported with its use.  Specialist use only.
       RED           Deferiprone tablets 500mg
       RED           Deferiprone suspension 750mg/5ml (unlicensed special)
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 9.1.4 Drugs used in platelet disorders

   Idiopathic thrombocytopenic purpura
   Romiplostim is recommended by NICE TAG 221 for the treatment of adults with chronic immune (idiopathic) thromboycytopenic
           >     whose condition is refractory to standard active treatments and rescue  therapies or
           >     who have severe disease and a high risk of bleeding that needs frequent courses of rescue therapy and
           >     if the manufacturer makes romiplostim available with the discount agreed as part of the patient access scheme
       RED           Romiplostim (Nplate®) 250mcg vial     
   Eltrombopag is recommended as an option by NICE (TAG293) for treating adults with chronic immune (idiopathic)
   thrombocytopenic purpura, within its marketing authorisation (that is, in adults who have had a splenectomy and whose
   condition is refractory to other treatments, or as a second-line treatment in adults who have not had a splenectomy
   because surgery is contraindicated), only if:
           >     their condition is refractory to standard active treatments and rescue therapies, or
           >     they have severe disease and a high risk of bleeding that needs frequent courses of rescue therapies and 
           >     the manufacturer provides eltrombopag with the discount agreed in the patient access scheme
       RED            Eltrombopag (Revolade®) tablets 25mg, 50mg

   Essential thrombocythaemia
   In thrombocythaemia, Anagrelide is recommended to be initiated for patients who have failed two previous treatments to
   control platelet counts and who have one or more of the following features:
           >       >60 years of age, or
           >       a platelet count >1,000 x 109/l, or
           >       a history of thrombo-haemorrhagic events.
   Anagrelide treatment should be initiated by a clinician with experience in the management of essential thrombocythaemia.
        RED           Anagrelide capsules 500micrograms 

   Severe thrombocytopenia in adults with chronic liver disease (a platelet count of below 50,000 platelets per microlitre of blood)
       RED     Lusutrombopag  [Mulpleo tablets 3mg]                                                                                            NHS England Commissioned
   NICE TA617      Lusutrombopag is recommended, within its marketing authorisation, as an option for treating severe 
                          thrombocytopenia in adults with chronic liver disease having planned invasive procedures) 
       RED    Avatrombopag [Doptelet]
   NICE TA626    Avatrombopag is recommended, within its marketing authorisation, as an option for treating severe
                         thrombocytopenia in adults with chronic liver disease having a planned invasive procedure.
                                                                                                                                                                                            CCG Commissioned
   Acute Acquired Thrombotic Thrombocytopenic purpura [TTP] in adults
       RED  Caplacizumab 
   NICE TA667  Caplacizumab with plasma exchange and immunosuppression is recommended, within its marketing authorisation, as
                      an option for treating an acute episode of acquired thrombotic thrombocytopenic purpura in adults, and in young 
                      people aged 12 years and over who weigh at least 40kg. Treatment should be started and supervised by physicians 
                      experienced in managing thrombotic microangiopathies.                                                 NHS England Commissioned
   Refractory Chronic Immune Thrombocytopenia
       RED    Fostamatinib (Tavlesse)
   NICE TA835 Recommended as an option for treating refractory chronic immune thrombocytopenia (ITP) in adults, only if:
                            >  they have previously had a thrombopoietin receptor agonist (TPO‑RA), or a TPO‑RA is unsuitable
                            >  the company provides fostamatinib according to the commercial arrangement.
    This NICE TA updates and replaces NICE TA759                                                                                   ICB Commissioned, Blueteq form
   Primary Chronic Immune Thrombocytopenia
       RED    Avatrombopag (Doptelet)
   NICE TA853  Recommended, within its marketing authorisation, as an option for treating primary chronic immune 
                        thrombocytopenia (ITP) refractory to other treatments (for example, corticosteroids, mmunoglobulins) in adults. 
                        It is only recommended if the company provides it according to the commercial arrangement.
                                                                                                                                                                 ICB Commissioned, Blueteq form
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 9.1.6 Drugs used in neutropenia
   Single dose pegfilgrastim is to replace the use of daily filgrastim (G-CSF) to reduce chemotherapy induced neutropenia in cancer 
   patients who would normally receive 5 or more days of daily filgrastim (G-CSF) following chemotherapy (except chronic myeloid 
   leukaemia and myelodysplastic syndrome patients).
       RED           Pegfilgrastim prefilled syringe 6mg
   Pegfilgrastim is not licensed for the following indications: 
           >     Mobilisation of peripheral blood progenitor cells (PBPCs)
           >     To reduce duration of neutropenia post transplant of PBPCs
           >     To support weekly chemotherapy regimes
   Filgrastim will continue to be used for these three indications.      
       RED           Filgrastim
                         Injection 300micrograms 1ml vial
                         Prefilled syringes 300microgram, 480microgram

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