Management Of Oral Maxillofacial Surgery Patients With Anaemia
As a reduction below normal in the volume of packed red cells as measured by the hematocrit or reduction in the Hb conc of blood.
In physiological terms it is defined as a reduction in the O2 transport capacity of the blood.
SYMPTOMS AND SIGNS
- Breathlessness on exertion
- Throbbing in head n ears
- Dimness of vision
- Paresthesia in fingers n toes
- Pallor of :-
- Mucous membranes
- Palms of hand
- Cardiac dilatation
- Systolic flow murmurs
IRON DEFICIENCY ANAEMIA
Iron deficiency is the most common cause of anaemia in the world affecting almost 500 million people.
Causes of iron deficiency are :
- Increased iron utilization
- Adolescent growth spurts
- Postnatal growth spurts
- Physiologic iron loss
- Pathologic iron loss
- Genitourinary bleeding
- Gastrointestinal bleeding
- Pulmonary hemosiderosis
- Intravascular hemolysis
- Decreased iron intake
- Cereal-rich, meat-poor diets
- Elderly and indigent
- Food faddists
- Brittle nails
- Spoon shaped nails (koilonychia)
- Atrophy of the papillae of the tongue
- Angular stomatitis
- Brittle hair
- Plummer-Vinson syndrome
- Hb level Variably reduced
- MCV Reduced
- Erythrocyte count Normal or reduced
- Blood film Hypochromia, Microcytosis, Oval & elliptical cells poikilocytes in more severe cases
- DLC Normal
- Platelet Count Normal or raised
- Bone marrow iron stores Empty
- Plasma Transferrin Raised
- Plasma iron Reduced
- Serum ferritin Reduced
MANAGEMENT OF IRON DEFICIENCY ANAEMIA
Oral iron is all that is required in most cases. Best preparation is ferrous sulphate (200 mg tablet contains 60 mg elemental iron) which is given every 8th hourly.
Absorption is much better if the iron preparations are taken in empty stomach.
If the patient has side effects like nausea, diarrhea or constipation. Taking tablets with food or reducing the dose may reduce the symptoms. Dose is reduced by using preparation with less iron like ferrous gluconate (35mg elemental iron per 300mg tablet)
Parenteral iron therapy is indicated only when :
- Oral iron is not tolerated.
- Failure to absorb oral iron.
- Non-compliance to oral iron.
- In presence of severe deficiency with chronic bleeding.
For parenteral iron therapy firstly we have to calculate the total iron requirement of the patient.
Iron requirement (mg) = 4.4 × body weight (kg) × Hb deficit (g/dl)
Iron dextran colloidal solution having 50 mg elemental iron/ml. It can be given i.v and i.m.
Iron-sorbital-citric acid complex having 50 mg elemental iron/ml. It can be given only i.m
Intramuscular injection is given by the Z track technique. Iron dextran is given 2ml/day or on alternate days.
Intravenous : After a test dose of 0.5ml iron-dextran injected i.v over 5-10 mins, 2ml can be injected per day. Alternatively the total calculated dose is diluted in 500ml of glucose/saline and infused iv over 6-8hrs under constant observation. Injection should be terminated if the patient complains of giddiness, paresthesias or constriction of chest.
The megaloblastic anaemias are disorders caused by impaired DNA synthesis.
Megaloblastic anaemia is chrd. by the presence in the bone marrow of erythroblasts with delayed nuclear maturation coz of defective DNA synthesis (megaloblasts).
Megaloblasts are large and have large immature nuclei.
Megaloblastic changes occur in :
Vit B12 deficiency or abnormal Vit B12 metabolism.
Folic acid deficiency or abnormal folate metabolism.
Other defects of DNA synthesis, such as congenital enzyme deficiencies in DNA synthesis or resulting from therapy with drugs interfering with DNA synthesis.
- Hb often reduced, may be very low.
- MCV raised.
- Erythrocyte count is low for degree of anemia.
- Blood film oval macrocytosis, poikilocytosis, red cell fragmentation and neutrophil hyper segmentation.
- Reticulocyte count low for degree of anemia.
- Leukocyte count normal or reduced.
- Platelet count normal or reduced.
- Bone marrow increased cellularity, megaloblastic changes in erythroid series, giant metamyelocytes, dysplastic megakaryocytes, increased iron in stores.
- Serum iron elevated.
- Iron binding capacity increased saturation.
- Serum ferritin elevated.
- Plasma LDH elevated, often markedly.
- Vitamin B12
- Cyanocobalamin and hydroxycobalamin are complex cobalt containing compounds present in diet and referred to as vit. B12.
- Dietary sources – liver, fish, kidney, egg yolk, meat, cheese are the main vit. B12 containing constituents of diet. The only vegetable source is legumes (pulses).
- Daily requirement – 1-3 µgms. During pregnancy and lactation – 3-5 µgms.
CAUSES OF VITAMIN B12 DEFICIENCY
- Low dietary intake :
- Impaired absorption :
- Stomach :
- Pernicious anemia
- Congenital deficiency of intrinsic factor.
- Small bowel :
- Ileal disease or resection
- Bacterial overgrowth
- Tropical sprue
- Fish tapeworm (diphyllobothrium latum)
- Abnormal metabolism:
- Congenital transcobalamin ll deficiency
- Nitrous oxide (inactivates B12)
The most common cause of vit. B12 deficiency in adults is pernicious anemia.
It is a condition in which there is atrophy of the gastric mucosa with consequent failure of intrinsic factor production and vit. B12 malabsorption.
There is an association with other autoimmune diseases, particularly thyroid disease, Addison’s disease and vitiligo.
Parietal cell antibodies are found in 90% of patients with pernicious anemia.
Intrinsic factor antibodies are found in about 50% of the patients and are specific for this diagnosis. There are two types of intrinsic factor antibodies :
Blocking antibody: it inhibits binding of intrinsic factor to vit. B12
Precipitating antibody: it inhibits the binding of B12 – intrinsic factor complex to its receptor site in the ileum.
A red sore tongue (glossitis) and angular stomatitis are sometimes present.
Anorexia with moderate weight loss also maybe evident, possibly accompanied by diarrhea and other gi symptoms.
The neurologic manifestations are the most worrisome. They begin with demyelination , followed by axonal degeneration and eventual neuronal death
Patients present with symmetrical paraesthesiae in the fingers and toes, early loss of vibration sense and proprioception, and progressive weakness and ataxia. Paraplegia may result. Dementia and optic atrophy may also occur.
MANAGEMENT OF VITAMIN B12 DEFICIENCY
Preparations available are:
Cyanocobalamin available as 35µgm/5 ml liq. 100, 500, 1000µgm injection.
Hydroxycobalamin available as 1000µgm injection.
Methylcobalamin available as 0.5mg tab.
Hydroxycobalamin is preferred for parenteral use coz of better retention.
When B12 deficiency is due to lack of intrinsic factor hydroxycobalamin is given by i.m. or deep s.c. injection. Initially 30-100µgm/day is given for 10 days followed by 100µgm/weekly and then 100µgm monthly as life long maintenance therapy.
In other types of deficiencies 10-30µgm/day may be used orally.
Folic acid is chemically Pteroyl glutamic acid.
Dietary sources – liver, green leafy vegetables, egg, meat, milk.
Daily requirement – for adults is 0.1mg but dietary allowance of 0.2mg/day is recommended. During pregnancy/lactation or any condition of high metabolic activity 0.8mg/day is appropriate.
Causes of folate deficiency :
- Poor intake Poor intake due to anorexia
- Old age G.I. disease ( eg. Partial
- Poor social conditions gastrectomy, coelic disease
- Starvation Crohn’s disease)
- Alcohol excess Cancer
Antifolate drugs :
Excess utilization :
Hematological disease with excess red cell production. (eg. hemolysis)
Malignant disease with increased cell turnover.
Metabolic diseases. (eg. Homocystinuria)
Haemodialysis or peritoneal dialysis.
MANIFESTATIONS AND MANAGEMENT OF FOLIC ACID DEFICIENCY
Manifestations are :
- Megaloblastic anemia like that caused by vit. B12 deficiency.
- Epithelial damage : glossitis, enteritis, diarrhea, steatorrhoea.
- General debility, weight loss, sterility.
Preparations available are :
- Folic acid 5mg tab, liquid oral preparations and injectables also available.
- Folinic acid available as 3mg/ml inj.
- Treatment with 5mg/day oral dose of folic acid is sufficient. 5mg weekly is sufficient for maintenance.
Folic acid must never be given, other than with vit. B12 in pernicious anemia or other vit. B12 deficiency anemia, because of the risk of aggravating or precipitating neurological features of vit. B12 depletion.
Aplastic anemia is defined as pancytopenia with hypocellurality of the bone marrow.
Aplastic anemia occurs due to reduction in the number of pluripotential stem cells together with a fault in those remaining or an immune reaction against them so that they are unable to repopulate the bone marrow.
Causes of aplastic anemia :
- Congenital (eg. Fanconi’s anemia)
- Idiopathic acquired
- Chemicals (eg. Benzene)
- Idiosyncratic reactions
- Ionizing radiation
- Viral (eg. hepatitis, EBV, HIV, Parvovirus)
Other (eg. tuberculosis)
Paroxysmal nocturnal haemoglobinuria
The clinical manifestations of marrow failure from any cause are anemia, bleeding and infection.
Bleeding is often the predominant initial presentation of aplastic anemia with bruising with minimal trauma or blood blisters in the mouth.
Physical findings may include ecchymosis, bleeding gums and epistaxis.
Mouth infections are common.
- Red blood cells normocytic normochromic, sometimes macrocytic
- Blood film pancytopenia, absolute granulocyte count low
- Reticulocyte count very low
- Bone marrow tap may yield a dry tap
- Bone marrow biopsy reveals severely hypocellular or aplastic marrow with replacement by fat.
- Serum iron level elevated
MANAGEMENT OF APLASTIC ANEMIA
The treatment depends on providing supportive care while awaiting bone marrow recovery and specific treatment to accelerate bone marrow recovery.
The main danger is infection and any suspicion of infection in a severely neutropenic patient should lead to immediate institution of parenteral antibiotics.
Supportive care including transfusions of red cells and platelets should be given as necessary.
The cause of the aplastic anemia should be eliminated if possible.
Bone marrow transplant is the treatment of choice for patients who have an HLA-identical sibling donor.
Immunosuppressive therapy is given to patients without an HLA-identical sibling donor. Antilymphocyte globulin and ciclosporin are used alone or in combination.
Androgens ( eg. oxymethalone, fluoxymesterone) are sometimes useful in patients not responding to immunosuppression and in patients with moderate severe anemia. Response may occur 3-6 months after initiating therapy.
It is inherited in an autosomal dominant manner.
Affected individuals have congenital hemolysis arising from a defect in one of the proteins in the red cell membrane leading to a decreased ratio of surface area to volume and consequently spherocytes.
As spherocytes are more rigid and less deformable than normal red cells they are unable to pass through the splenic microcirculation and they die.
DIAGNOSTIC FEATURES :
- Blood film spherocytes, reticulocytes and anisocytosis
- MCV slightly reduced
- MCHC increased
- Osmotic fragility of red cells is increased.
- Haemolysis is evident (eg. The serum bilirubin and urinary urobilinogen will be raised).
MANIFESTATIONS AND MANAGEMENT
The major clinical features of HS are anemia, splenomegaly and jaundice.
Chronic hemolysis leads to formation of pigment gallstones.
Chronic leg ulcers may also be present.
Splenectomy results in striking and usually permanent improvement both in the symptoms and in the anemia and should be advised when :
The anemia causes persistent impairment of health.
Severe hemolytic or aplastic crises have occurred.
Other members of the family have died from the disease.
Evidence of cholecystitis and cholelithiasis are present.
The splenectomy should be performed during periods of remission, in young childern it should be deferred until they are as old as possible and should be preceded by vaccination against pneumococcal and Hemophilus influenzae infection.
Splenectomy is followed by lifelong pencillin therapy. 250mg penicillin V, 12 hourly.
Severe hemolytic crises require treatment by blood transfusion.
Folic acid, 5mg daily orally is prescribed to support the increased erythropoiesis.
Thalassaemia is an inherited impairment of Hb production, in which there is partial or complete failure to synthesize a specific type of globin chain.
Two types of thalassaemias are seen.
- Alpha (a)-thalassaemia – impaired production of á-chains.
- Beta (B)-thalassaemia – impaired production of â-chains.
Alpha thalassaemia :
Normal individuals inherit two-á chain genes from each parent so total of four á chain genes. Alpha thalassaemia occurs because of gene deletions & presents in various ways.
One gene is deleted the blood picture is normal.
Two genes are deleted there is microcytosis with or without mild anemia.(alpha-thalassaemia trait)
Beta thalassaemia :
Three genes are deleted – moderate anemia, microcytic hypochromic RBCs including target cells, Heinz bodies are seen and splenomegaly.
Four genes are deleted – baby is still born. (hydrops fetalis)
Clinically Beta-thalassaemia can be divided as following :
- Beta-thalassaemia minor
- Beta-thalassaemia major
Beta thalassaemia minor :
This is the carrier state. Anemia is mild or absent.
RBCs are hypochromic, microcytic.
MCV is low.
MCHC is normal.
Blood film occasional target cells, cigar-shaped cells, a moderate amount of basophilic stippling.
Reticulocyte count is normal.
These patients don’t require much treatment just reassurance.
Beta thalassaemia major : (Cooley’s anemia)
Most children affected by this disease present during the first year of life with :
Failure to thrive and recurrent bacterial infections.
Severe anemia from 3-6 months when the switch from ã- to â-chain production should normally occur.
Extramedullary haemopoiesis that soon leads to heptosplenomegaly and bone expansion, giving rise to the classical thalassaemic facies. (Chipmunk facies)
Chronic blood transfusions lead to significant hemosiderosis.
Patients invariably have cardiomegaly, marked hepatomegaly and splenomegaly are also seen.
RBCs hypochromic, microcytic cells.
Hemolysis is evident.
Peripheral blood smear marked variations in size and shape of RBCs including target and stippled cells, as well as teardrop- and cigar-shaped cells.
Increased amount of Hb F.
Variable amounts of Hb A.
Bone marrow transplantation in young patients with HLA-matched siblings is the definitive treatment.
In others the aims of treatment are to suppress ineffective erythropoiesis, prevent bony deformities and allow normal activity and development.
Long term folic acid supplements are given.
Blood transfusions are required to maintain Hb level above 10g/dl.
If transfusion requirements increase splenectomy should be considered preceded by prophylaxis against infection.
In cases of iron overload desferrioxamine therapy should be instituted to chelate the iron.
Desferrioxamine is given as an overnight s.c infusion on 5-7 nights in a week.
Ascorbic acid 200mg is given along with desferrioxamine as it increases the rate of urinary excretion of iron in response to desferrioxamine.
SICKLE CELL ANEMIA
Sickle cell disease is a genetically derived disorder.
It results from a point mutation that leads to substitution of valine for glutamic acid at the 6th position of the beta-globin chain. The resultant Hb is designated as HbS.
On deoxygenation the HbS molecules undergo aggregation and polymerization. This converts Hb from freely flowing liquid to a viscous gel leading to distortion of red cells which acquire a sickle shape.
The sickling is reversible on oxygenation but repeated episodes of sickling leaves the RBCs irreversibly sickled.
Sickling is precipitated by infection, dehydration, cold, acidosis or hypoxia.
Sickling can produce:
Shortened red cell survival
Impaired passage of cells through the microcirculation leading to obstruction of small vessels and tissue infarction.
- Hb level is low 5-9g/dl
- Blood film normochromic, normocytic RBCs, sickled RBCs, Howell-jolly bodies, siderocytes.
- RBC survival time is markedly decreased.
- Reticulocyte count is markedly increased. (5%-25%)
- Platelet count can be normal or slightly raised.
- WBC count is increased.
- Hemolysis is evident.
Sickled RBCs are the cause of end organ pathology in the sickle cell disease.
Cardiopulmonary, renal ,CNS, bone and extremity, and ophthalmic complications are the result of repeated micro infarcts.
Long term problems in these patients are :
Susceptibility to infections.
Chronic leg ulcers, due to ischemia.
Gallstones : pigment stones from persistent hemolysis.
Aseptic necrosis of bone : particularly long bones.
Blindness, due to retinal detachment
Chronic renal disease.
Osteomyelitis of the long bones and mandible.
Steady state anemia requires no treatment.
Acute attacks require supportive therapy with i.v. fluids, oxygen, antibiotics and adequate analgesia.
Repeated transfusions are done before elective surgery or in pregnancy to reduce proportion of circulating HbS to less than 20%.
Before any emergency surgery exchange transfusions are recommended.
Hydroxycarbamide has been widely used in treatment. It acts by increasing the conc. of HbF.
Bone marrow transplantation is used to treat SCD. Young adults and adolescents under age of 16 who have identical HLA-matched donor are the best candidates for transplantation.
The SCD patient who requires treatment for minor dentoalveolar problems can be managed safely in the ambulatory setting if the disease is stable.
Specific measures should be taken to prevent dehydration, hypoxia, acidosis and infection.
Adequate hydration should be maintained by infusion of i.v fluids.
Supplemental oxygen should be provided to prevent hypoxia.
The likelihood of respiratory acidosis should be avoided by using medications such as narcotics, which suppress the respiratory drive.
Prophylactic antibiotics are recommended for all surgical procedures. Pencillin V, 2gm orally 1 hour before and I gm 6 hours later or clindamycin 300mg orally 1 hour before and 150mg 6 hours later are appropriate choices.
The principles of management of the inpatient are the same as in the ambulatory setting.
In addition, hypothermia must be avoided during general anesthesia to prevent reflex vasoconstriction. This can be accomplished by warming i.v fluids and using a warming blanket.
ANEMIA DUE TO GLUCOSE-6-PHOSPHATE DEHYDROGENASE DEFICIENCY
The normal RBC is well endowed to protect itself against oxidant stress.
Upon exposure to offending agent the amount of glucose metabolized via the HMP shunt is increased manifold.
In this way reduced glutathione is regenerated protecting the sulfhydryl groups of Hb and the RBC membrane form oxidation.
Individuals with an inherited defect in the HMP shunt are unable to maintain adequate amounts of reduced glutathione in their RBCs. This leads to oxidation of the Hb sulfhydryl groups which leads to precipitation of the Hb within the RBC.
Several 100 G6PD genetic variants have been described.
Two variants G6PD A ¯ and G6PD Mediterranean lead to significant hemolysis.
In the G6PD A ¯ deficiency the activity of the enzyme is normal in reticulocytes, there is no defect in synthesis. The enzyme is unstable having half life of 13 days.
In the Mediterranean variant the deficiency is far more severe bec. there is both impaired synthesis and reduced enzyme stability.
Clinical presentation :
Clinical problems arise when the affected individual is subjected to some type of environmental stress, viral or bacterial infections or to drugs and toxins which pose an oxidant threat to RBCs.
Patients may experience an acute hemolytic crises within hours of exposure to the oxidant stress.
- Blood count normal between attacks.
- During an attack blood film may show irregularly contracted cells, bite cells, blister cells, Heinz bodies and reticulocytosis.
- Hemolysis is evident.
- Hematocrit level – decreased.
- Plasma haptoglobin – decreased.
- Unconjugated bilirubin – increased.
- Attention should be directed towards prevention of hemolytic episodes.
- Removal of the toxic agent.
- Any offending drug should be stopped.
- Underlying infections should be treated.
- These patients should be warned of risks from oxidant drugs.
- If anemia is severe may require blood transfusion.
AUTOIMMUNE HEMOLYTIC ANAEMIAS
Autoimmune hemolytic anaemias are acquired disorders resulting from increased red cell destruction due to red cell autoantibodies.
AIHA is divided into ‘warm’ and ‘cold’ types depending on whether the antibody attaches better to red cells at body temperature or at lower temperatures.
CAUSES AND MAJOR FEATURES OF AUTOIMMUNE HAEMOLYTIC ANAEMIAS
Temperature at which Antibody attaches best to red cells
|37°C||Lower than 37°C|
|Type of antibody||IgG||IgM|
|Direct Coomb’s test
|Causes of Primary Condition||Idiopathic||Idiopathic|
|Causes of Secondary Condition||Autoimmune disorders
other viral infections (EBV)
|Drugs eg: methyl dopa|
AIHA – WARM ANTIBODY TYPE
Large fraction of patients have a chronic mild anaemia and splenomegaly.
In other cases the disorder may be more severe, with Hb levels less than 7gm/dl and reticulocyte counts of 30% or higher. Spherocytosis is usually marked.
In its most severe form it presents with fulminant overwhelming hemolysis associated with hemoglobinemia, hemoglobinuria, and shock.
Associated findings include hyperbilirubinemia, decreased or absent haptoglobin levels, splenomegaly and occasionally hepatomegaly.
Patients with mild degree of anaemia usually require no therapy.
In patients with clinically significant hemolysis.
Initial therapy consists of glucocorticoids. (eg. Prednisone 1.0mg/kg per day)
Prednisone is continued until the Hb level has risen to normal values and thereafter it is tapered over the course of several months.
Second line of therapy is splenectomy. It is recommended in patients who cannot tolerate or fail to respond to steroid therapy.
Patients who are refractory to steroid therapy and to splenectomy can be treated with immunosuppressive drugs. Best experience is with azathioprine and cyclophosphamide.
AIHA – COLD ANTIBODY TYPE
The clinical manifestations elicited by the antibody are of two sorts :
Acrocyanosis is the marked purpling of the extremities, ears, and nose when the blood becomes cold enough to agglutinate in the veins. It clears on warming.
Hemolysis is usually not severe and is manifested by a mild reticulocytosis and agglutination on the blood film.
- The degree of hemolysis depends on :
- Antibody titer
- Thermal amplitude of the antibody.
- Environmental temperature.
The underlying cause should be treated.
The cutaneous manifestations of this disorder are best treated by maintaining the patient in a warm environment.
Patients should avoid exposure to cold.
Harrison’s principles of internal medicine – Kurt J. Isselbacher, Eugene Braunwald et al.
Davidson’s principles and practice of medicine. By Christopher Haslett, Edwin R. Chilvers et al
Robbins pathologic basis of disease. By Cotran, Kumar and Robbins
Textbook of medical physiology. By Guyton and Hall
Clinical medicine. By Kumar and Clark
Management of oral and maxillofacial surgery patient with sickle cell disease and related hemoglobinopathies. Joseph J. Sansevere and Manno Milles JOMS 1993 Vol 51 pages 912 – 916.