sickle cell disease

Sickle cell disease

Dr Moutasem Almashour

Definition Clinical Features of Sickle Cell Disease Pathophysiology Distribution of the sickle-cell(Epidemiology) Mortality/Morbidity Features of sickle-cell disease Factors That Can Cause Sickle Cell Crises Anesthetic Management Preoperative Preparation Transfusion Predictors of Postoperative SCD complications

What is Sickle Cell Anemia (SCA)?

Sickle-cell disease (SCD), or sickle-cell anaemia or drepanocytosis, is an autosomal co-dominant genetic blood disorder characterized by red blood cell that assume an abnormal, rigid, sickle shape.

+Recurrent episodes of painful crises, and

progressive end-organ damageThe American Society of Anesthesiologists© 2008 , Inc.ISSN

0363-471X

Normally, humans have

Of these, Haemoglobin A makes up around 96-97% of the normal haemoglobin in humans.

Haemoglobin

A two alpha two beta

A2 two alpha two delta

F two alpha two gamma

Common types of Sickle Cell DisordersType of anaemia

Hemoglobin variation

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Sickle Cell Anemia

Sickle haemoglobin (HbS) + Sickle haemoglobin

Most Severe – No HbA

Hemoglobin S-Beta thalassemia

Sickle haemoglobin (HbS) + reduced HbA

Mild form of Sickle Cell Disorder

Hemoglobin S-C disease

Sickle haemoglobin (HbS) + (HbC)

Mild form of Sickle Cell Disorder

Sickle Cell Trait Sickle haemoglobin (S) + Normal haemoglobin (A)

Sickle Cell Trait

Sickle haemoglobin (S) + Normal haemoglobin (A) in RBC

• Adequate amount of normal Hb (A) in red blood cellsRBC remain flexible CarrierDo Not have the symptoms of the sickle cell disorders, with exceptions:

Pain when Less Oxygen than usual (scuba diving, activities at high altitude (12,000ft), under general anaesthesia)

Minute kidney problems* *Gupta, Kirchner, Nicholson, Adams, Schechter, Noguchi, Steinberg, JCI 1991

Epidemiology

The highest frequency of sickle cell disease is found in tropical regions, particularly sub-Saharan Africa, India and the Middle-East.

AfricaThree quarters of sickle-cell cases occur in Africa. WHO report

2% of newborns affected by sickle cell anemia The carrier 2% and 40%

United KingdomIn United Kingdom, more than 200 babies are born annually with

SCD.Middle EastAbout 6,000 children are born annually with SCD, at least 50% of

these in Saudi Arabia.IndiaThe prevalence has ranged from 9.4 to 22.2% in endemic areas.

Features of sickle-cell disease in Bahrain

In 56198 Bahrainis, we found that2% of newborns have sickle-cell disease (SCD) and 18% have sickle-cell trait, while24% are carriers of the (thalassaemia gene).

It was also found that their haematological values are similar to those of patients from Eastern Province, Saudi Arabia, where the mild form of the disease predominates. .

In Qateef region of Saudi Arabia Hb F found at steady high level in sickle cell disease has been the rule rather than exception*.

Sheikha Al Arrayed ,Eastern Mediterranean Health Journal | Volume 1,1995

*Weatherall DJ. Some aspects of the haemoglobinopathies of particular relevance to Saudi Arabia and other parts of the Middle East. Saudi Med J 1988;9:107-15

Pathophysiology

Sickle-cell anaemia Is caused by a point mutation in the β-globin

chain of haemoglobin, causing the hydrophilic amino acid glutamic acid to be replaced with the hydrophobic amino acid valine at the sixth position.

Red blood cells typically live 90–120 days, but sickle cells only survive 10–20 days.

Quinn CT, et al.: Minor elective surgical procedures using general anesthesia in children with sickle cell anemia without pre-operative blood transfusion.

Pediatr Blood Cancer 2005; 45:43–7

Pathophysiology cont.

The induction of sickling in susceptible erythrocytes requires exposure to oxygen tensions less than 40 mmHg for 2 to 4 minutes. The de-oxygenation of hemoglobin S leads to polymerization of insoluble hemoglobin S strands

The initiation of polymerization may be incomplete and reversible if re-oxygenation occurs early in the process. Repetitive exposure to alternating de-oxygenated and oxygenated states can lead to membrane distortion, oxidative damage and irreversible sickling.

Marchant WA, Walker I: Anaesthetic management of the child with sickle cell disease. Paediatr Anaesth 2003; 13:473–89.

Anesthesiology Problem-oriented Patient Management, 6th ed. 2008, pp 980–92.

Red Blood Cells from Sickle Cell Anemia

Deoxygenation of SS erythrocytes leads to intracellular hemoglobin polymerization, loss of deformability and changes in cell morphology.

OXY-STATE DEOXY-STATE

Clinical Features of Sickle Cell Disease

HematologicalHemolytic anemia Typical baseline hemoglobin levels are 6–9 g/dl in SS disease.Acute aplastic anemia Parvovirus B19 infections trigger acute severe exacerbations of anemiaSplenic enlargement/fibrosis

OrthopedicOsteonecrosis 50 % of adultsOsteomyelitits.Dactylitis Early onset is a marker of disease severity

VascularLeg ulcers 20 % of SS adults

David C. Warltier, M.D., Ph.D., Editor,Anesthesiology 2004


NeurologicalPain crisis 70% of patientsStroke 10% of children; Cause of 20% deaths.Proliferative retinopathy 50% of SC adults; rare in SS homozygotesChronic pain syndrome A small subset of patients

PulmonaryAcute Chest Syndrome 40% of patients; mortality rate of 1.1% for children and 4.8% for adults.Airway hyperreactivity 35% of childrenRestrictive lung disease 10–15% of patients



ImmunologicalImmune dysfunction Increased susceptibility to infectionsErythrocyte auto/alloimmunization Increased incidence of transfusion

Hemolytic transfusion reactions ACS acute chest syndrome;

GenitourinaryChronic renal insufficiency 5–20% of adultsPriapism 10–40% of menGastrointestinal

Cholelithiasis 70% of adultsViral hepatitis from transfusion 10% of adultsLiver failure 2%.


Defective Urine Concentrating Ability in Sickle Cell anaemia

High osmolality and low O2 sat of the renal medulla are conditions that favor polymerization.

Hemoglobin polymerization correlates inversely with urine concentrating ability.

a-Thalassemia reduces %HbS, and polymerization potential.

Gupta, Kirchner, Nicholson, Adams, Schechter, Noguchi, Steinberg, JCI 1991

Clinical Features of Sickle Cell Disease in infants

History Anemia is universally present.

It is chronic and hemolytic in nature and usually very well tolerated.

While patients with an Hb level of 6-7 g/dL who are able to participate in the activities of daily life in a normal fashion are not uncommon, their tolerance for exercise and exertion tends to be very limited.

A serious complication is the aplastic crisis.

The spleen enlarges in the latter part of the first year of life. Occasionally, it undergoes a sudden very painful

enlargement due to pooling of large numbers of sickled cells. This phenomenon is known as splenic sequestration crisis.

The nonfunctional spleen is a major contributor to the immune deficiency that exists in these individuals.

Another problem occurring in infancy is hand-foot syndrome. This is a dactylitis presenting as painful swelling of the dorsum

of the hand and foot. The acute chest syndrome consists of chest pain, fever,

tachypnea, leukocytosis, and pulmonary infiltrates. This is a medical emergency and must be treated immediately. Fat embolism, resulting from bone marrow infarction, plays an

important etiological role in the pathogenesis of this syndrome. If not attended to promptly, it may lead to acute respiratory

distress syndrome (ARDS).

Factors That Can Cause Sickle Cell Crises

Infections Low oxygen tension Concomitant medical conditions (e.g., sarcoidosis,

diabetes mellitus, herpes) Dehydration* Acidosis Extreme physical exercise Physical or psychologic stress Alcohol Pregnancy Cold weather

*Firth PG, Head CA: Sickle cell disease and anesthesia. Anesthesiology 2004; 101:766–85.

Measures for Preventing Pain Crises in Patients with Sickle Cell Disease

Consuming adequate amounts of fluids to prevent dehydration (especially during febrile periods and hot weather)

Avoiding exposure to extreme cold, exercising to exhaustion or using drugs that can lead to acidosis (e.g., acetazolamide [Diamox])

Avoiding mountain climbing or air flights in an unpressurized cabin (noncommercial flights) above 10,000 feet

Avoiding hypoxemia in the perioperative period when general anesthesia is used or when a procedure involves hypertonic radiographic dyes

Preoperative anesthesia considerations for SCD

Patients with SCD show wide variation in the severity from mild disease to very complicated with organ damage.

The anesthesiologist should have full history and should search for evidence of end-organ damage in respiratory, cardiovascular, neurological, liver and renal.

Investigations requested depends on the patients condition and if there is any symptom or signs of end-organ damage. The minimal of full blood count, electrolytes, renal function test, liver function test and chest x-ray.

I.V. fluid should request during NPO period to avoid dehydration.

Hb should be > 7 mg/dl especially for the major surgery whine the bleeding is anticipated and to achieve Hb A 70% .

Inrtaoperative and postoperative, conditions can lead to acute sickling should be avoided dehydration, hypoxia, acidosis and low temperature

Preoperative Preparation

An elective surgical procedure should not proceed in a sickle cell patient with an on going infection such as urinary track infection or respiratory tract infection since these could lead to a painful crisis, ACS, or CVA.

Intravenous fluids should be administered while the

patient is fasting.

While the recommendation of an infusion rate of one and a half times maintenance fluid requirement of a balanced salt solution is frequently made, there is no evidence that excessive hydration is beneficial.

The goal of intravenous fluid therapy is to prevent dehydration throughout the peri-operative period.

Preoperative Preparation

Together the hematologist, anesthesiologist and surgeon can assess the patient’s perioperative risk and determine any special requirements.

In general the patient should be admitted to the

hospital the day before surgery to permit assessment by hematology, anesthesiology, and surgery.

NHS Sickle Cell Disease in Childhood: Standards and Guidelines for Clinical Care 14/10/2010

Investigations

It is important that sickle cell disease is written on the forms so that the appropriate investigations are performed. Blood tests required include:

FBC HPLC to determine percentages of HbS, HbF and HbAGroup and antibody screen

NHS Sickle Cell and Thalassaemia Screening Programme (2006) NHS Sickle Cell Disease in Childhood: Standards and Guidelines for Clinical Care

14/10/2010

Preoperative Transfusion

The need for and value of preoperative transfusion is one of the more controversial areas in managing patients with sickle cell disease.

The benefits cited are the past history of frequent complications, increased tissue oxygenation, reduced blood viscosity, and a "margin of safety". The most consistent benefit may result from prevention of the need to transfuse after surgery because of bone marrow suppression.

The disadvantages include induction of hyperviscosity, significant alloimmunization, delayed transfusion reactions, exposure to infectious disease, cost, and provision of a false sense of security.

Indications for transfusion therapy in sickle-cell diseaseAcute Acute on chronic anaemias: splenic sequestration

and severe or longlasting aplastic crises CNS: acute stroke Pulmonary: acute chest syndrome (with hypoxia or

chest radiography with multisegment involvement)

Acute multiple-organ-failure syndrome Preoperative (in select cases)

Sickle-cell disease Marie J Stuart, Ronald L Nagel Lancet 2004; 364: 1343–60

Fu T, et al.: Minor elective surgical procedures using general anesthesia in children with sickle cell anemia without preoperative blood transfusion. Pediatr Blood Cancer 2005.

28 children with hemoglobin SS undergoing a total of 38 minor surgical procedures The findings of the study showed the preoperative blood transfusions were not necessary for minor elective surgical procedures.

Vichinsky EP, et al.: A comparison of conservative and aggressive transfusion regimens in the perioperative management of sickle cell disease. N EnglJ Med 1995.

55 patients for a total of 60 surgical procedures The findings of the study showed the perioperative complication rate was the same for both groups; however, there were two deaths and twice as many transfusion-related complications in the aggressive group. The authors concluded a simple transfusion was as beneficial and less risky as an aggressive transfusion regimen.


National Institutes of Health’s 2002 publication on

“The Management of Sickle Cell Disease” recommends:

“In patients with SCD-SS and SCD-S β Thalassemia, simple transfusion to achieve a hemoglobin of 10g/dl should be performed before all but the lowest risk procedures.”


General vs. regional

study involving nearly 717 patients undergoing more than 1,000 surgical procedures revealed more sickle cell disease-related complications after surgery among patients with sickle cell disease having regional anesthesia as opposed to general anesthesia.Although regional anesthesia induces vasodilatation and increases capillary and venous oxygen tension in the anesthetized area, there is compensatory vasoconstriction and possible reduction in venous oxygen tension in the rest of the body.

The authors of the study qualified this finding by stating the obstetric population is inherently at higher risk for sickle cell-related complications.

Koshy et al.: Surgery and anesthesia in sickle cell disease. Cooperative Study of Sickle Cell Diseases. Blood 1995; 86:3676

Firth PG, Head CA: Sickle cell disease and anesthesia. Anesthesiology 2004; 101:766–85

Predictors of Postoperative SCD complications

Type of surgical procedure-Low, moderate or high risk

Increased age-Associated with disease progression

Frequency of recent complications-Current activity of disease state

Hospitalization-Marker of disease severity

Temporal clustering of ACS-Progression of lung disease

Abnormal lung fields on radiograph-Evidence of sickle chronic lung

disease

Pregnancy-Increased risk of maternal complications

Pre-existing infection-Triggering agent for ACS

Haplotype-African haplotypes have more severe disease than the

Asian haplotype

Anesthesiology, V 101, No 3, Sep 2004

Predictors of Postoperative SCD complications in the first two years of life

Early dactylitis (ie, pain and tenderness in the hands or feet occurring before the age of one year)

Hemoglobin concentration <7 g/dL Leukocytosis in the absence of infection

Powars DR, et al. Beta-S gene cluster haplotypes modulate hematologic and hemorheologic expression in sickle cell anemia. Use in predicting clinical severity. Am J Pediatr Hematol Oncol 1994; 16:55.

Mortality/Morbidity

Among children and adults with sickle cell anemia (homozygous for sickle hemoglobin), the median age at death was 42 years for males and 48 years for females.*

Historically, perioperative mortality rates as high as 10% and morbidity rates as high as 50% have been reported. More recent studies have reported a mortality of around 1%. **

*Orah S. Platt, N Engl J Med ;June 9, 1994**Sickle Cell Disease in Childhood: Standards and Guidelines for Clinical Care

14/10/2010

Postoperative Management

Most of the serious sickle cell disease related complications occur in the postoperative period. Vaso-occlusive crises are among the most frequent and include painful crisis, acute chest syndrome and stroke.

For these reasons the with the paradigm used in The Preoperative Transfusion in Sickle Cell Disease Study Group, which includes postoperative oxygen supplementation, hydration, and pulse oximeter monitoring.

This has obvious implications on the advisability of outpatient surgery for these patients.

Pregnant women with sickle cell disease

Anesthetic management of pregnant women with sickle cell disease - effect on postnatal sickling complications

Conclusion: Our study suggests that general anesthesia could be associated with postnatal sickling complications, even when the severity of illness was taken into account.

Julien Camous MD, CAN J ANESTH 2008 / 55: 5 / pp 276–283Firth PG, Head CA: Sickle cell disease and anesthesia. Anesthesiology 2004;

101:766–85

A randomized, controlled trial in 72 patients found no significant difference in perinatal outcome between the offspring of mothers with SCD treated with prophylactic transfusions and those who were not.

Morrison JC. Use of partial exchange transfusion preoperatively in patients with sickle cell hemoglobinopathies. Am J Obstet Gynecol 1978; 132:59.

Websiteshttp://www.sicklecellsociety.org/: Another Great Siteinformation, Counselling and Caring for those with Sickle Cell Disorders and their families: UK based

http://www.sicklecelldisease.org/: Sickle Cell Disease Association of America

The Human Genome Project Sickle Cell Education Site at http://www.massinteraction.org/html/genome/

http://www.ascaa.org/ American Sickle Cell Anemia AssociationASCAA was founded in 1971 and is the oldest sickle cell research, education, and social services organization in the United States.

http://www.ncd.gov/

http://www.painfoundation.org/

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