Sickle cell anemia

Dr.Fedaa Shaher Dr.Yasmeen Fayez

Hassan Qasim 19 year old Palestinian male … a known case of sickle cell anemia diagnosed at the age of 13 month at Ajman hospital. He received blood transfusion twice in Ajman on diagnosis at 13 months & 19 months.

He was first seen Al Wasl Hospital at age 19 months on 1991, when he presented to A\E because of jaundice & pallor of 6 months duration since then has been followed up at the Dubai thalassemia center.

Birth history:

Full term , NVD in Ajman hospital.

vaccination:

Pneumococcal vaccine in Nov 1991.

H.Influenza vaccine in May 1992.

HB vaccine 3 rd dose in Jan 1993.

He has getting penicillin prophylaxis regularly.

Family history:

Parents are 1 children.

st cousin. He is one of the 6 Mother sickle cell trait.

Father sickle cell trait.

DNA study showed:

Beta globin gene analysis: CD6 (GAG GTG) \CD6 (GAG GTG) Alpha gobin gene analysis:

α α \ α α

Patient was kept on regular blood transfusion from April 1996.

Hassan used to have mild painful episode once or twice per year.

On several occasions he had hemolytic crises needed blood transfusion.

In Nov 1995 he developed stroke preceded by febrile illness & manifested by left sided hemi paresis, headache & deterioration of his level of consciousness.

He was managed accordingly with blood transfusion and parietal exchange transfusion.

His condition improved & he was discharged to be followed up in thalassemia center.

Since then he was put on regular blood transfusion & regular chelating therapy with desferal.

In April 1996 he developed an afebrile seizure hence was put on Na valporate.

1 st exchange transfusion was done on 23\4\2007 in Rashid hospital when he presented to A\E with history of chest pain & breathing difficulties.

Investigation

FBC on 4\11\08: WBC 8.1

RBC 2.95

HGB 9.9

MCV 101.9

MCH 33.6

RDW 25.8

PLT 97

Hb electrophoresis

On 21\10\08 HBA 36.4

HBF 9.6

HBS 50.4

HBA2 3.6

Haemoglobinopathy

Inherited disorders of hemoglobin structure e.g. HbS, HbE, HbC, or its production e.g. thalassemia

Globin fraction

–

4 peptides

HbA

– two alpha & two beta chains α

2 β 2

HbF - two alpha & two gama chains α

2 γ 2

HbA2 - two alpha & two sigma chains α2δ2 α chain – β chain – 141 amino acids 146 amino acids

Sickle cell disease

Produces by replacement of glutamic acid by valine at position 6 of the β-chain

Symptoms

1-Anemia

Hb electrophoresis:

SS no Hb A only Hb S & Hb F HbF 5 - 20% or more the higher the level of Hb F, the milder the disease

2-Episodes of pain 3-Hand-foot syndrome: swollen hand & feet caused by sickle shaped red cells blocking blood flow out of the hand & feet.

4-Jaundice 6-Vision problems: Some people with sickle cell anemia experience vision problems. Tiny blood vessels that supply your eyes may become plugged with sickle cells. This can damage the retina.

5-Frequent infection

Infectious complications

Increased susceptibility to aggressive infections due to loss of splenic function.

1-Strep. Pneumoniae – 2-H. Influenzae – most common cause second common 3-Meningitis – risk > 300 times that in gen pop.

4-Salmonella osteomyelitis – on infarcted bone (Risk significantly reduced by vaccination and prophylactic penicillin).

Other complications

Cerebrovascular events – TIA, stroke Pulmonary hypertension Cardiac complications: cardiomegaly & transfusion iron overload.

Priapism: Abnormally persistent erection of the penis in the absence of sexual desire occur in persons with sickle cell anemia.

Renal complications: hematuria, papillary necrosis & CRF.

Treatments and drugs Antibiotics:

Children with sickle cell anemia usually begin taking the antibiotic penicillin when they're about 2 months of age and continue until they're 5 years old. Doing so helps prevent infections, such as pneumonia, which can be life-threatening to an infant or child with sickle cell anemia. Antibiotics may also help adults with sickle cell anemia fight certain infections

Pain-relieving medications:

To relieve pain during a sickle crisis.

Hydroxyurea:

This prescription drug, normally used to treat cancer , may be helpful for adults with severe disease. When taken daily, it reduces the frequency of painful crises and may reduce the need for blood transfusions. It seems to work by stimulating production of fetal hemoglobin that helps prevent the formation of sickle cells.

There is some concern about the possibility that long-term use of this drug may cause tumors or leukemia in certain people

Blood transfusions.

Supplemental oxygen.

Exchange transfusion.

Bone marrow transplant.

BMT for Sickle Cell Disease

The first BMT for sickle cell disease was reported in 1984. The patient had both sickle cell anemia and acute leukemia. Subsequently, a handful of other patients who had both sickle cell disease and another blood disorder underwent successful BMTs, and it was observed that their sickle cell disease was eliminated.

Three large clinical trials--one in Belgium , another in France and a third in the US - have reported results of BMT for 116 patients with sickle cell disease.

Of the 116 patients, 91 (78 %) and disease-free BMT.

were alive 2 to 4 years following An additional 16 were alive, but had rejected the donor marrow or cord blood (graft rejection), and continued to have symptoms of sickle cell disease.

Neurological problems such as bleeding in the brain developed in about 25% of patients following BMT.

Patients who had experienced a stroke prior to BMT developed neurological complications more often than those who had not.

Who's a Good Candidate ?

it is difficult to predict how the disease will progress in each individual. Some patients with sickle cell disease have few symptoms for many years. Others experience repeated episodes of extreme pain, lung problems and/or other organ damage.

The unpredictable course of the disease has made it difficult to determine the best time to offer BMT to patients. Most patients with sickle cell disease survive the first 10 years of their life without major complications.

While BMT can cure patients with sickle cell disease, some will die as a result of the treatment and some survivors will have long-term problems that affect their quality of life to varying degrees.

BMT considered only for children younger than 16 who have: 1 Severe sickle cell disease complications, including repeat strokes , episodes of acute chest syndrome , and painful events . 2 An available donor (a healthy brother or sister who has matching bone marrow). 3 No significant damage to major organs. About 1% of people with sickle cell disease meet the criteria for bone marrow transplant.

Description : -

Chemotherapy agent that allows sickled shaped

–

blood cells to assume the shape and characteristics of fetal hemoglobin by becoming larger and less adherent, thus allowing travel through the blood vessels to occur easier.

Shown to

reduce frequency of painful crises

and to

reduce need for blood transfusions

in patients with recurrent moderate-to-severe painful crises episodes

Drug Category : Cytoreductive agent Adult Dose : 15-20 mg/kg/d PO qd initially; may increase by 5 mg/kg/d q12wk until maximum tolerated dose achieved; not to exceed 35 mg/kg/d Pediatric Dose : Not established; data suggest to administer as in adults

Contraindications : Patients who have a sensitivity to hydroxyurea Interactions : Coadministration with fluorouracil can increase neurotoxicity; coadministration with didanosine or stavudine may cause fatal pancreatitis and hepatotoxicity; immunization with live-virus vaccine may cause severe or fatal infection in immunocompromised patient

Precautions

:

Monitor blood count q2wk and adjust dose accordingly (ie, disconatinue if hematologic toxicity occurs, then resume after recovery by reducing dose associated with hematologic toxicity by 2.5 mg/kg/d .

hematologic toxicity is defined as : neutrophils <2000/mL, platelets <80,000/mL, hemoglobin<4.5 g/dL, reticulocytes <80,000/mL (if Hbg <9 g/dL); caution with renal impairment, may cause dysfunction .

renal tubular

Transfusion In Sickle Cell (Controversy!)

Used correctly : transfusion can prevent organ damage and the lives of sickle cell disease patients.

Used unwisely : transfusion therapy can result in serious complications.

Transfusion In Sickle Cell

Simple transfusion

: give blood. Partial exchange transfusion : Remove blood and give blood .

Erythrocytapheresis : use apheresis to maximize blood exchange .

When to use each method?

Transfusion In Sickle Cell

In severely anemic patients, simple transfusions should be used.

- Acute splenic sequestration. - Transient red cell aplasia.

- Hyperhemolysis (infection, acute chest syndrome, malaria).

- If the patient is stable and the reticulocyte count high, transfusions can (and should) be deferred.

Transfusion in Sickle Cell

…In general, patients should be transfused if there is sufficient physiological derangement to result in heart failure, dyspnea, hypotension, or marked fatigue.

…Tends to occur during an acute illness or when hemoglobin falls under 5 g/dL.

Transfusion in Sickle Cell (exchange transfusion)

An

exchange transfusion

is a medical treatment in which apharesis is used to remove one person's red blood cells or platelets and replace them with tranfused blood products exchange transfusion is used in the treatment of a number of diseases, including:

Transfusion in Sickle Cell (exchange transfusion)

Except in severe anemia, exchange transfusion offers many benefits and is our first choice .

Phenotypically matched, leukodepleted packed cell are the blood product of choice .

A posttransfusion hematocrit of 36 percent or less is recommended .

Avoid hyperviscosity , which is dangerous to sickle cell patients .

Transfusion in Sickle Cell (exchange transfusion)

Exchange transfusion

…Bleed one unit (500 ml), infuse 500 ml of saline : …Bleed a second unit and infuse two units.

…Repeat. If the patient has a large blood mass, do it again.

Transfusion in Sickle Cell (exchange transfusion)

... A comprehensive transfusion protocol should include accurate records of the patient’s red cell phenotype, alloimmunization units rechistory, number of eived, serial Hb S percentages , and results of monitoring for diseinfectious ases and iron overload.

…Transfusions are used to raise the oxygen-carrying capacity of blood and decrease the proportion of sickle red cells.

Transfusion in Sickle Cell (exchange transfusion) Transfusions usually fall into two categories :

…episodic, acute transfusions to stabilize or reverse complications.

…long-term, prophylactic transfusions to prevent future complications.

Transfusion in Sickle Cell (exchange transfusion)

… episodic, acute transfusions to stabilize or reverse complications. Limited studies have shown that aggressive transfusion (get Hgb S < 30%) may help in sudden severe illness.

May be useful before general anesthesia.

Transfusion in Sickle Cell (chronic transfusion therapy)

Stroke Chronic debilitating pain Pulmonary hypertension Setting of renal failure and heart failure

Transfusion in Sickle Cell (chronic transfusion therapy) Controversial uses :

..Prior to contrast media exposure ..Sub-clinical neurological damage ..Priapism

..Ulcers

..Pregnancy

Erythrocytapheresis thus has the advantage of controlling iron accumulation in patients with sickle cell disease who undergo long term transfusion, and the ability to achieve adequate Hb and HbS concentrations without exceeding the normal concentration.

This precision is achieved because the computer in the pheresis machine is able to use various physiologic parameters such as height, weight, and Hb level to compute expected amount of packed RBCs required to obtain a specific hemoglobin level.

Further, erythrocytapheresis requires the

least amount of time

when compared to using similar blood volumes on patients receiving simple blood transfusions.

Although erythrocytapheresis is more expensive than simple transfusion, if the cost of chelation and organ damage due to iron overload is considered, erythrocytapheresis without chelation costs less than simple transfusion programs.

Central venous access devices

be used for long-term can safely erythrocytapheresis in patients with sickle cell disease with a low rate of complications.

Transfusion in Sickle Cell

Inappropriate uses of transfusion:

..Chronic steady-state anemia ..Uncomplicated pain episodes ..Infection

..Minor surgery ..Uncomplicated pregnancies ..Aseptoic necrosis

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