9.1 ANAEMIAS AND SOME OTHER BLOOD DISORDERS

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

9.1.1.1 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

9.1.1.2 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

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.

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

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. A new drug review is available

online - click here to access it.

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

Desferrioxamine

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

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)

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

purpura:

> 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

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