Anaemia

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CLINICAL DESCRIPTION

Anaemia is defined as decreased concentration of haemoglobin for the age and sex of the individual (i.e., below 14 g/dL in adult males, 12 g/dL in adult females, 11 g/dL in children, and below 13.5 g/dL in the 1st week of life). Anaemia is not a diagnosis. It has a cause, which must be identified and properly managed. 

The cause must be investigated before initiating treatment. In an emergency, blood samples must be taken for investigations before blood transfusion.

Causes

  • Nutritional (micronutrient and vitamin deficiency) e.g., iron, folic acid, vitamin B12 deficiency
  • Bleeding e.g., heavy menstruation, haemorrhoids (piles), peptic ulcer, infestations (hookworm, bilharzia), solid organ malignant tumours e.g., colonic cancer, haematological malignancies: e.g., leukaemia
  • Haemolysis e.g., severe malaria, sickle cell disease, G6PD deficiency, hypersplenism, autoimmune, drugs
  • Bone Marrow Failure e.g., Disease infiltration e.g., leukaemia, lymphoma, tuberculosis, Aplasia - primary or secondary e.g., due to cytotoxics
  • Anaemia of Chronic Diseases
    • Common causes of anaemia of chronic disorder include malignancy, e.g., haematological or solid tumours, autoimmune disorders, e.g., rheumatoid arthritis, acute or chronic infections, e.g., HIV and TB, chronic kidney disease, and chronic rejection of solid-organ transplantation, etc.
  • Autoimmune Disease (SLE, Pernicious anaemia)

CLINICAL FEATURESSIGNS AND SYMPTOMS

General Symptoms

Easy fatigability, dizziness, shortness of breath on exertion, palpitations

Signs

  • Pale mucous membranes and palms, Angular stomatitis, "Spoon shaped" and ridged finger and toe nails (if iron deficiency), Spleen, liver and lymph nodes may be palpable (if infection or hematological malignancy), Signs of heart failure (in severe anaemia), Jaundice (in haemolysis), Petechiae and purpura (bone marrow failure), Hyperpigmentation of palms and soles of feet and Other Specific signs of the underlying disease.
INVESTIGATIONS
  • Also determined by suspected cause (see causes section)

TREATMENT

The objectives are to treat underlying cause of anaemia and restore haemoglobin levels to normal.

SICKLE CELL DISEASE

It is an inherited disease characterized by the possession of two abnormal hemoglobin, at least one of which is hemoglobin S.

CLINICAL FEATURES 

SIGNS AND SYMPTOMS
  • Suspect if patient is chronically anaemic and/or received previous blood transfusions and those with family history of siblings/relatives with multiple blood transfusions.
  • Suspect in children who have suffered from one or more of the presentations listed below.

Presentation

Age

Vaso-occlusive crisis -– painful hand and/or foot swelling early infancy

0.5 - 2 yr

Stroke/ CNS complications (reduced consciousness, seizures)

5-10yr

Bone lnfarct (painful, swollen limbs)

0.5- 10yr

Splenic sequestration (new or worsening splenomegaly, +/- pallor)

<3yr

Acute Chest (difficulty breathing, cough, desaturations)

0.5- 10yr

Bowel infarct /Abdominal crisis (abdominal pain and/or distention, vomiting)

 

Priapism- sudden painful onset of penis that fails to relax

6-20yrsr

Kidney infarct (abdominal pain, reduced urine output)

 

Skin Ulcers

>10yrs

Eye disorders

>10yrs
  • Crises are typically precipitated by: cold weather, dehydration, infection, physical exertion and mental stress.
  • For sickle cell test, refer for further investigations and management.

INVESTIGATIONS

  • FBC, sickling test, Hb electrophoresis, annual urine dipstick, annual ophthalmology review, transcranial Doppler and Other investigations as indicated in table above.

 

TREATMENT

Treatment objectives

  • To prevent the development of sickle cell crises
  • To relieve pain
  • To identify and manage the precipitating cause of crises
  • To maintain a good steady state hemoglobin
  • To prevent long term complications and organ damage
  • To manage sickle cell crises and complications once developed
 NON-PHARMACOLOGICAL TREATMENT
  • Adequate hydration always by drinking adequate water/fluids
  • Avoid common precipitating causes
  • Good nutrition
  • Client /parental/guardian education
  • Genetic counselling with voluntary family size restriction  
PHARMACOLOGICAL TREATMENT

If Severe Aneamia 

  • If shocked, consider splenic sequestration {20ml/kg normal saline -see shock protocol}
  • Transfuse in acute chest syndrome or stroke
    • Consider BTF program/ Hydroxyurea 15mg/kg q24h then increase by 5mg/kg every 12th week to max 35mg/kg daily.
    • To be managed at a central hospital, discuss patient with referral facility prior to referral.

For painful and vaso-occlusive crises

  • All children should be started on oxygen even if saturations are normal.
  • Give IV fluids at 1.5 times maintenance.
  • Give adequate analgesia according to the analgesic ladder.
  • For patients with frequent crises, discuss referral to tertiary facility for hydroxyurea.

Infection and fever

  • Patients with sickle cell disease have functional asplenia and therefore are at risk of encapsulated bacteraemia.
    • If concerns of sepsis or meningitis, give IV Ceftriaxone 100mg/kg q24h for 2 weeks.
    • Salmonella osteomyelitis: Ceftriaxone IV 100mg/kg q24h for 6 weeks)  then oral Ciprofloxacin (10mg/kg BD for 2 weeks)
    • Acute chest syndrome, give Ceftriaxone as for sepsis and Erythromycin 25mg/kg PO 6 hourly for 2 weeks

Others

  • Always check for malaria parasites
  • Cholelithiasis/Cholecystitis {>10yrs} AXR, needs abdominal ultrasound and surgical referral

Discharge and follow up 

  • Regular follow up in outpatient clinic
  • Malaria prophylaxis
    • Monthly Sulphadoxine pyrimethamine (SP)

Weight

Dose

3-6kg

¼ tablet

6-10kg

½ tablet

10-15kg

¾ tablet

15-20kg

1 tablet

20-29kg

1 ½ tablet

9-14yrs

2 tab

>14yrs

3 tab
  • Alternatively use weekly Chloroquine 5mg/kg
  • Folic acid 1-5mg q24h
  • Benzathine Penicillin {>6months} monthly IM
  • <30KG: 0.6MU
  • >30KG: 1.2MU
  • Pneumococcal vaccine {2 and 5yrs} if available
  • Consider Hydroxyurea for those with frequent painful crises

Do not give ferrous sulphate.

Educate patient and family to ensure early analgesics, and to promptly seek medical attention if

  • severe pain
  • fast breathing
  • looking much more pale than usual
  • high temperature
  • vomiting and diarrhoea

Referral criteria

  • Consider referral to a specialist in case of the following:
    • Bleeding into the eye, priapism, haematuria/renal disease, CNS events including stroke, osteomyelitis, aseptic necrosis of the hip, acute chest syndrome, persistent jaundice, unexplained high white cell/platelet counts (more than 15 and 500 x 109/L respectively), intractable morbid pain, repetitive crises or recurrent severe anaemia interfering with their lives.

APLASTIC ANAEMIA 

It is an abnormality in at least 2 blood cell lines with hypocellular bone marrow.

Causes 

Primary causes: Inherited (e.g., Fanconi anaemia) or idiopathic (acquired and accounts about 67% of aplastic anaemia cases)

Secondary causes: Chemicals (e.g., benzene, toluene, glue sniffing), drugs (e.g., chemotherapeutic drugs, chloramphenicol, gold, penicillamine, phenytoin, carbamazepine, azathioprine), insecticides, ionizing radiation, infections (e.g., HIV, EBV, Viral hepatitis, TB, Parvovirus B19), paroxysmal nocturnal haemoglobinuria and pregnancy.

CLINICAL FEATURES

SIGNS AND SYMPTOMS
  • Easy bruising, bleeding, blood blisters in the mouth
  • Pallor
  • Petechiae
  • Purpura
  • Bleeding
  • Frequent or severe infections
INVESTIGATIONS
  • FBC: Pancytopenia
  • PBF: Reduced blood cells and absence of reticulocytes
  • Bone marrow aspiration and trephine: hypocellular bone marrow
  • Other investigations: to exclude secondary causes (e.g., HIV, TB screen, Hepatitis B and C serology)
  • Refer to central hospital for further workup

TREATMENT

  • Treatment is largely supportive
  • Treat infections aggressively
  • If anaemic and/or bleeding, transfuse whole blood and/or platelets
  • If neutropenic and febrile: antibiotics

Referral Criteria

  • Discuss all cases of suspected aplastic anaemia with a haematologist/specialist.
  • Stabilise the patient, if necessary, with blood products before referral.

ANAEMIA OF CHRONIC DISEASE

Anaemia due to chronic inflammation. It is characteristically a normochromic, normocytic anaemia but can also be microcytic.

  • Common causes of anaemia of chronic disorder include:
    • Malignancy ( e.g. Haematological or solid tumours), 
    • Autoimmune disorders ( e.g. Rheumatoid arthritis,SLE)
    • Acute or chronic infections, e.g. HIV and TB
    • Chronic kidney disease

CLINICAL FEATURES

SIGNS AND SYMPTOMS 
  • Pallor and signs of underlying condition

INVESTIGATIONS:

  • Full blood count, specific tests to exclude causes , HIV test, Urea, electrolytes and creatinine, ESR, sputum for GeneXpert, chest xray

TREATMENT

  • Treat the underlying condition.
  • Transfusion is seldom necessary.
  • Do not treat with iron, folic acid or vitamin B12 unless there is a documented deficiency.

Referral Criteria

  • Patients not responding to treatment
  • Patients requiring further work up and treatment at tertiary centre

 

HAEMOLYTIC ANAEMIA

Anaemia due to increased destruction of red blood cells. Destruction may be due to extravascular or intravascular causes. Cause can be inherited or acquired.

CLINICAL FEATURES

SIGNS AND SYMPTOMS
  • Evidence of haemolysis: anaemia, reticulocytosis, decreased haptoglobin, increased lactate dehydrogenase {lDH} and unconjugated hyperbilirubinaemia.
INVESTIGATIONS
  • Coombs' test {direct antiglobulin} is usually positive with autoimmune haemolysis

TREATMENT

Efficacy of transfusion is limited by the shortened red cell survival due to haemolysis.

  • Supplement with folic acid, oral, 5 mg q24h given to all patients
  • For Autoimmune haemolytic anaemia, give Prednisolone, oral, 1-2 mg/ kg q24h, When a satisfactory response is obtained with recovery of the haemoglobin and a decrease in LDH serum concentrations, taper dose over a period of 4 weeks to 30mg q24h.
  • Thereafter reduction should be slower to prevent disease recurrence
  • Prednisone treatment can be stopped when the Coombs' reaction becomes negative.
  • If inadequate response add Azathioprine, oral, 2.5 mg/kg q24h. Titrate to Hb response. May be required for several months. Monitor for neutropenia.
  • Patients who fail medicine treatment should be considered for splenectomy.

Complications

  • Cholelithiasis
  • Iron overload
  • Transfusion related infections

Referral criteria

  • Suspected haemolytic anaemia
  • Patients requiring further work up at tertiary facility
  • No response to treatment

IRON DEFICIENCY ANAEMIA 

Anaemia due to iron deficiency. Common causes of iron deficiency are chronic blood loss or poor nutritional intake. Other causes are parasitic infestation (worms, schistosomiasis). This is usually hypochromic microcytic anaemia. 

CLINICAL FEATURES

SIGNS AND SYMPTOMS
  • Anaemia symptoms and signs
  • Nail spooning
INVESTIGATIONS
  • Full blood count: microcytic anaemia.
  • Iron studies (Iron level, ferritin level).
  • Stool microscopy: worms ova, Schistosoma ova.
  • Urine microscopy: Schistosoma ova.
  • Gastroscopy/colonoscopy if GIT blood loss.
  • Assess for a haematological response to Iron therapy.

 

TREATMENT

Treatment objectives

  • Identify and treat the cause
  • Dietary adjustment
PHARMACOLOGICAL TREATMENT

1st Line Treatment:

  • Ferrous sulphate (dried or anhydrous), oral

Adults: 

  • 200 mg (65 mg elemental iron) q8h for 3-6 months

Children:

> 10 years;

200 mg q12h for 3-6 months

8-10 years;

200 mg q24h for 3-6 months

5-7 years;

80-120 mg q8-12h for 3-6 months

1-4 years;

45-90 mg q8-12h for 3-6 months

< 1 year; 

30-60 mg q8-12h for 3-6 months

Alternatively

  • Ferrous sulphate 6mg/kg orally, q24h (can be given in 2 divided doses)
  • Continue for a minimum of 3 months after anaemia has been corrected to replenish iron stores.
  • Repeat Hb in 1 month.
  • If there is no response; then consider the following causes: no compliance, wrong dose prescribed, continued blood loss, wrong diagnosis; malabsorption, thalassemia, and concurrent folate or vitamin B12 deficiency or ferrous fumarate, oral,
    • Adults: 200 mg (65 mg elemental iron) q8h
    • Children: 3-6 mg elemental iron/kg per day for 3-6 months

2nd Line Treatment Parenteral Iron

  • Parenteral iron has no advantage over oral iron preparations
  • Parenteral iron indications include:
    • Malabsorption
    • Patients on hemodialysis and erythropoietin
    • Patients requiring repeated iron therapy
    • Patients who are not tolerating oral iron therapy
  • Where a once-off dose is required, give intramuscularly (if iron dextran). Minimum required dose is 250 mg of iron per gram of Hb below normal.
  • Use in consultation with a hematologist/specialist.

Adults: 

  • Iron sucrose (venofer), IV (as a slow bolus injection over 2-5 minutes)
  • 200 mg every 3 days for 5 doses

Children: 

  • Total dose = weight {kg} x [11 g/dl - actual Hb {g/dl}] x 2.4 + 200 mg.
  • Maximum daily dose: 200 mg.
  • Administer over 30 minutes in 200 ml

Alternatively 

Iron dextran, IV (as a slow bolus or IM by deep intramuscular) injection

Adults:

  • 25-100 mg q24h as needed

Children: Not recommended

  • Repeat every second day until the total dose is given.
  • Ensure that the correct formulation is given as some preparations can be given IM, or IV only, or both.
  • Resuscitation equipment should be ready to manage anaphylaxis.
  • Blood transfusion {see above section 1.2}

Deworming: 

  • Albendazole STAT dose 200mg if <10kg, 400mg if >10kg
NON-PHARMACOLOGICAL

Dietary advice:

  • Increase intake of vitamin C containing foods
  • Increase intake of iron rich foods, beans, liver, eggs, lentils, meat

Complications

  • Iron overload

Referral Criteria

  • No response to iron therapy after ensuring compliance and correct dose.

MEGALOBLASTIC ANAEMIA

  • Anaemia characterized by formation of unusually large, abnormal and immature red blood cells, called megaloblasts. It is caused by a deficiency of folate and/or vitamin B12.
  • Causes of vitamin B12 deficiency; poor diet intake (e.g., vegan), diseases affecting Vitamin B12 absorption in the gut e.g., pernicious anaemia, fish tapeworm, gastrectomy, ileum resection, Crohn’s disease, celiac disease.
  • Causes of folic acid deficiency; diet low in fresh fruits/vegetables/fortified cereals, diseases affecting folic acid absorption in the gut (e.g., Crohn’s disease, celiac disease, excessive alcohol intake), drugs (phenytoin, cotrimoxazole, methotrexate, sulfasalazine).

 

CLINICAL FEATURES

SIGNS AND SYMPTOMS
  • Fatigue, general body weakness, lethargy, dizziness, palpitation, shortness of breath
  • Numbness/burning sensation
  • Mood changes/psychosis (vitamin B12 deficiency)
  • Pallor
  • Red beefy tongue, hyperpigmented skin (vitamin B12 deficiency)
  • Cerebellar ataxia
  • hemiplegia
  • Decreased vibration and discriminative touch sensation Folate Deficiency
  • Glossitis
  • Neurotube defects (spina bifida) in neonates
INVESTIGATIONS
  • FBC: Elevated MCV {mean corpuscular volume} and MCH {mean corpuscular hemoglobin}.
  • Macro-ovalocytes on blood smear; poly-segmentation of neutrophils (hyper segmented neutrophils), thrombocytopenia with giant platelets.
  • Decreased serum vitamin B12 or red blood cell folate. Pancytopenia in severe cases.
  • Intrinsic factor antibodies and anti-parietal cell antibodies in vitamin B 12 deficiency due to pernicious anaemia.

TREATMENT

Treatment objectives

  • Dietary modifications to ensure adequate intake of folate and Vitamin B12.
  • Identify and treat the underlying cause, e.g., antibiotics for intestinal overgrowth with bacteria.
NON-PHARMACOLOGICAL TREATMENT

Dietary modification:

  • Include foods high in folic acid e.g., green leafy vegetables, broccoli, peas, chickpeas, kidney beans liver, breakfast cereals fortified with folic acid.
  • Foods high in Vitamin B12: Meat, Fish, Milk, Cheese, Eggs, fortified breakfast cereals.
PHARMACOLOGICAL TREATMENT
  • Start with Folic Acid and Vitamin B12. Take blood samples for RBC, folate and vitamin B12 levels before starting treatment.
  • Monitor serum potassium and replace if necessary.
  • Give vitamin B12 and folic acid together until the test results are available as giving folic acid alone in patients with a B12 deficiency may precipitate a permanent neurological deficit.
  • Adjust management according to results.
  • Folic acid deficiency:
    • Folic acid, oral, 5 q24h until hemoglobin returns to normal.
    • Prolonged treatment may be required for malabsorption states.
  • Vitamin B12 deficiency:
    • Vitamin B12, IM. 1 mg daily for 7 days, then weekly for a further 4 doses.
  • Follow with 1 mg every third month for life in patients with pernicious anaemia, except in patients with clearly modifiable nutritional deficiency.
  • The anemia is corrected within 1-2 months. As there is an increase in red blood cell production, short-term iron and folic acid supplementation is also recommended.
  • Consider the following if there is failure to respond: co-existing folate and/or iron deficiency, infection, hypothyroidism, myelodysplasia, incorrect diagnosis, and drug-induced, e.g., hydroxyurea and Zidovudine.
    • Prophylaxis. Vitamin B12 is indicated for patients after total gastrectomy or ileal resection. Give vitamin B12, IM, 1 mg every third month for life (4 times a year).
    • Indications for prophylactic folic acid: chronic inherited haemolytic anemia, sickle cell anaemia, thalassemia; myeloproliferative disorders; exfoliative skin disorders; increased demands, e.g.  pregnancy, chronic hemodialysis. Give Folic acid, oral, 5mg q24h