Sickle Cell Disease in Brazil Heloisa H.A. Gallo da Rocha; MD Laboratório Lâmina; Grupo de Trabalho da Vice Governadoria do Estado do Rio de Janeiro.

Sickle Cell Disease in BrazilSickle Cell Disease in Brazil

Heloisa H.A. Gallo da Rocha; MD

Laboratório Lâmina;

Grupo de Trabalho da Vice Governadoria do Estado do Rio de

Janeiro

Sickle cell disease and Fetal HbSickle cell disease and Fetal Hb

Studied 105 patients SCD- age groups;• 4 to 11 months (5 patients)-HbF: 13,8%• 2 to 5 years old(13 p.)- HbF: 12,3%• 5 to 10 years ( 12 p.) HbF: 8,7%• 10 to 20 years (24 p.) HbF: 7,5%• 20 to 30 years (18 p.) HbF :4,1%• 30 to 40 years (15 p) HbF: 8,4% • > 40 years (7 p.) HbF: 3,13%

ConclusionsConclusions

• Median of HbF is higher in SCP

• until 10 years there is a predominance for high HbF that goes decreasing

• there is an enhance in the group from 30 to 40 ys; it may be due that the people with high level of HbF lived more.

• Surprising the patients with more than 50 ys presented a lower level of HbF than the anterior group age

Sickle cell disease in BrazilSickle cell disease in Brazil

• According to the registers that we have we can say that the slaves that came to Rio de Janeiro were Bantu and the slaves that came to Bahia were Benin.

• According to haplotypes we could suspect that if these people had SCD they had the worst prognosis, but as far as we know nowadays:

Sickle cell diseaseSickle cell disease

• The association between the beta globin haplotypes and HbF levels becomes apparent if the influence of F cell production locus is removed, because it is the most important factor identified to date in determining HbF levels.

• FCP- 40% of HbF variability• beta globin haplotype- accounts for less than

10% of the variation

Sickle cell diseaseSickle cell disease• Data Local AS AC Btal SS N

• 10/99 UERJ 11,4% 105

• 11/99 Macuco 4,08% 1,02% 0% 0% 98

• 01/00 Lamina 14,8% 27

• 01/00 Carmo 0% 0% 0% 0% 23

• 02/00 Deodoro 4,75% 1,5% 1,5% 1,25%23

• 21/03 RIO 11% 2,7% 0% 0% 36

Prevalence of SC trait and AC in Prevalence of SC trait and AC in Rio de JaneiroRio de JaneiroIn Rio de Janeiro city :

• 9,4% (22/234)AS;AC:1,2% (3/234);SS Disease:0,4% (1/234);AT:0,4% (1/234)

In Rio de Janeiro State:

• 7,3% (26/355)AS;

• 1,12%(4/355)AC;

• 0,28%(1/355)SS;

• 0,28%(1/355)A T

OsteomyelitisOsteomyelitis

• In a serie of 228 patients with SCD in Rio de Janeiro;the prevalence of osteomyelitis was 5,7%; the mean age of onset14 years range 8 months- 42 years); the mean platelet account was 389.000/mm3 and hemoglobin value was 7,5 g/dl. There was no difference between those accounts from SC patients without osteomyelitis (p=NS)

Aplastic crisisAplastic crisis

• We studied the prevalence of antibodies anti- Parvovirus in patients with hereditary hemolytic anemia in 1994 ; 92 serum of those patients: 30 (32,6%) were considered immunized (IgG+) and 61 (66,3%) were susceptible (IgG-).

• In November 1994 we observed a child with hereditary spherocytosis that developed an aplastic crisis due to Parvovirus with IgM+.

Use of angiotensine converting enzyme Use of angiotensine converting enzyme inhibitor in sickle cell painful crisisinhibitor in sickle cell painful crisis

• According to the hypothesis that the SC painful crisis resulted from a centrally mediated reflex shunting of blood away from the bone marrow(Serjeant); this vasomotion alteration would render the local bone marrow ischemic and necrotic, resulting inflammatory response and increase in intramedullary pressure and impairing the blood flow to adjacent normal marrow.

Painful crisisPainful crisis

• Supposing this hypothesis was correct we thought that the use of a drug that broke this reflex vasomotion would prevent the painful crisis. Then we initiated a protocol using an angiotensine- converting enzyme inhibitor (fosinopril). The number of emergence room admissions for painful crisis were registered 12 months before and 13+/- 6 months after the beginning of the fosinopril.

Painful crisisPainful crisis• Statistical analysis of the results were performed by

using the Student “t”test to determine the significance of the differences between the pretreatment and treatment mean values of ratios variables. The mean age of the patients was 27 ys. One patient was excluded because symptomatic hypotension after the first dose of fosinopril. There were no statistical difference between hb,bilirrubin,HbF and LDH before and after the treatment.

Painful crisisPainful crisis

• The numbers of emergence room admission before the treatment were 6,6 +/- 2,3 and after 1,4 +/-1,4 (p<0,0001). We concluded that the use of fosinopril was beneficial in preventing recurrent painful crisis in SCA; probably this effect was due to the inhibition of reflex vasomotion phenomenon. This was a pilot study.

StrokeStroke

• We studied the incidence and risk factors for Stroke in 252 patients with SCD, prospectively from 1969 to 1994.We did a comparative study with the literature. The strokes occurred in 22/228(9,6%) SS patients; 81% of these events occurred before 15 years old. The recurrece rate was 30,3%. Patients with SBeta Thalassemia; SC and SD (24 patients)did not experienced strokes.

StrokesStrokes

• There was no difference between the levels of HbF, hemoglobin or platelet number when we compared the general sickle cell population with that who presented stroke. At the same time the author presents a clinical research by direct questioning 62 SC adult patients about another neurological symptoms.

AlloimmunizationAlloimmunization

• We performed a research getting to know the serological study of 22 patients with history of stroke and hypertransfusion; 20% of the patients developed alloimmunization (unpublished observations)

Infections due to transfusionInfections due to transfusion

• 228 patients with SCD were studied (unpublished observations):

• 12,7% had Hepatitis B

• 18,4% had Hepatitis C

• 7% had both Hepatitis.

Pregnancy and SCDPregnancy and SCD• We did a clinical research by questioning 33

women that were or had been pregnant before.

• 79% (26/33) had normal delivery

• 28% (9/33) had fetal wastage:neonatal deaths and stillbirths. One of the patients had 4 fetal wastage and another 2.

• 28% (9/33) had toxemia.2 had in 2 pregnancies; another died soon after the interview.

Pregnancy and SCD- conclusionPregnancy and SCD- conclusion

• The fetal wastage from stillbirths and neonatal deaths are increased here in Brazil/Rio de Janeiro.

• The maternal outcome is not different from US or Jamaica

The Liver and Gall bladderThe Liver and Gall bladder

• The Cholelithiasis occurs in 58% of the patients with SCD in Rio de Janeiro ( 258 patients studied prospectively from 1969 to 1994).36% of those patients were submitted to cholecystectomy;

• The age of diagnosis were 8- 18 years.

• Extreme hyperbilirubinemia: occurred in 5% of the patients (Gallo da Rocha, 1992)

Bone in SCDBone in SCD• 100 patients with SCD had radiological study of

the skull.1 patient(1%) had the “hair on end”appearance.

• Dactylitis: We did a clinical research by questioning mothers from 16 patients with SCD. We registered that 87,5% of their children had Dactylitis.The age of presentation varied from 4 months to 10 years old; 75% of the patients presented Dactylitis until 3 years old.

Bone and SCDBone and SCD

• 37,5% of the patients presented Dactylitis in hands and feet.(unpublished observations)

• There is a work that describes that there is medullar and internal cortex necrosis.These are responsible for the shortened deformed bones.

Bone and Sickle Cell DiseaseBone and Sickle Cell Disease

• 119 patients with SCD were submitted to radiological study of the hands. The age of the patients varied from 3 to 64 years; mean age: 22,3 years; 7/110 (5,8%) had shortened digits. We concluded that 5,8% of the patients presented severe bone infarction with or without osteomyelitis.(unpublished observations).

Bone and Sickle Cell DiseaseBone and Sickle Cell Disease

• We studied 255 SCD patients from IEHASC registered from 1969 to 1994.

• Age of Avascular Necrosis of Femoral Head (ANFH) in SCD :

Jamaica Nigeria Brazil (Rio)

20 years 13,7 years 25,6years

Avascular Necrosis of Femoral Avascular Necrosis of Femoral Head and SCD Head and SCD

• 15 years of age - 26% of the SCD patients had already had ANFH.

• The age period of greater prevalence was from 12 to 37 years old (89% of the cases was within this age group)

Genotype andGenotype and ANFH Prevalence ANFH Prevalence

• USA- 33/175 (19%)- SS

• USA-6/66(9%)- SCD

• USA-101/990 (10,2%) for SS (Sebes)

• USA-23/459 (5%) for SC

• Brazil- 19/230 (8,2%) for SS

• Brazil- 5/18 (27,7%) for SC

Avascular Necrosis of FH Avascular Necrosis of FH

• There was no difference between the Hb level or platelet number from those who developed or did not developed the ANFH. The pregnant women presented a tendency for the development of ANFH:

• 126 patients were women with SCD.• 8/101(7,9%) no pregnancy with ANFH• 5/25 (20%) had already been pregnant -ANFH

Kidney and SCDKidney and SCD

• 8/251 (3,18%) SC Patients had haematuria; 3 of those patients had renal insufficiency. The prevalence - when we study the medical literature, is unknown, but it is presumed to result from microinfarction of the renal pyramids by intravascular sickling.

• Proteinuria (++ or more): 9/110 patients (8,18%)- Brazil

• 9/38- patients (23,6%)Jamaica

Renal Failure and SCDRenal Failure and SCD

• 8/251(3,18%) patients presented renal failure:

• 6 men and 2 women(1 after eclampsia).• 4/8 (50%) presented arterial hypertension.• 2/8 (25%) presented with Cardiac

Insufficiency• 2/8 (25%)- was submitting to chronic

haemodialysis.

Renal Failure(RF) 3,18% of SC Renal Failure(RF) 3,18% of SC Patients:Patients:

• Mean Hb- 6,25 g/dl (R.F.)

• Mean Hb- 7,4 g/dl (without RF).

• Hypertransfusion and R.F.:

• 228/20(8,7%) were hypertransfunded- those patients had serum ferritin (Immunochemiluminescent Assay) above 800 ug/L-4/20(20%) had R.F. All of these patients had SS genotype.

Priapism and SCDPriapism and SCD

• Two works were done in SCPatients:

• 1- retrospective : 278 patients

• 2- clinical research by questioning 73 patients.

Firs work- retrospective:Firs work- retrospective:

• 21/278 patients (7,1%) had priapism.

• 4/21 (19%)- Impotence (All the 4 patients were done aspiration of corpora (aspiration combined with irrigation of the corpora with saline and heparin solution)

• 1/4 (25%)put prosthesis (semirigid device) .

• The age of beginning the episodes varied from 3 to 30 years; 43% of the patients had less than 10 years old.

Priapism- Prospective studyPriapism- Prospective study

• The mean age was- 13,5 years old.

• 90% of the patients were SS.

• Hb Fetal mean: 3,38%

• MCV mean: 92.4 f/dl

• Hb:7.6%

• Platelets: 370.000/mm3

Priapism: Second work- Priapism: Second work- ProspectiveProspective

• 73 patients with SCD:

• 25/73 (34%) prevalence of Priapism

• age of onset:mean: 19,8 years

• precipitating factor:spontaneous nocturnal erections. One patient(4%) reported the attack following intercourse;Jamaica- 16% of the patients.

Priapism- Prospective studyPriapism- Prospective study

• Emond described Hb F lower in this group of patients. Our patients also presented a lower level of fetal hemoglobin when we compare with the SCP that had no Priapism.

-mean Hb F (Priapism group)- 3,28%

-mean HbF Non Priapism group)- 7,4%

The level of platelet account from both groups did not showed difference; discordant with the Emond findings

Priapism - prospective studyPriapism - prospective study

• The prevalence of Priapism was 7,5% in the prospective study and 34% in the questioning study. In medical literature the prevalence was described from 2 and 6%; the prevalence between 38 and 42% have been ascertain among adults by direct questioning.

• The great majority of patients presented stuttering attacks.

Leg Ulcers in SCDLeg Ulcers in SCD

• Two studies were done:

• 1) retrospective- 252 patients

• 2) prospective study

Leg ulcersLeg ulcers• Prevalence of leg ulcers in SCD- Brazil - 19,5%;

SS patients: 21.4%(by direct questioning: 44%)• Jamaica: 75%.• Questioning- 90% of the cases had traumatic

cause(in some cases, local pruritus happened : 4% of the cases and insect bites : 6%)

• The age of onset was between 10 to 30 years, mean age:19,5 years; 98% were SS patients

Leg ulcersLeg ulcers

• Proportion male: female was 1,3.

• The patients with SC hemoglobinopathy did not presented leg ulcers

• S/ Thalassemia-1/6 (16%)patients.

• There was no difference between the SCD patients with or without leg ulcers in relation to the Hb,HbF,number of Platelets and MCH levels.

Leg Ulcers and SCPLeg Ulcers and SCP

• The ulcers were predominantly in medial and lateral malleoli.

• The ulcers did not occurred before 10 years of age.

• The micro organisms more common were Staphylococcus aureus and Psedomonas aeruginosa. The treatment with systemic or local antibiotic did not offered improvement just when there was cellulite (oral ant.)

Causes of DeathCauses of Death

• From 1987 June, to 1991, August:

• 24 deaths in patients with SCD in IEHASC : 33% was due to sepsis and splenic sequestration and 77% to Stroke .

Age and Death in SCDAge and Death in SCD

0

5

10

15

20

25

<7

anos

8 a

15

16 a

20

21 a

30

31 a

40

41 a

50

51 a

60

idadetotal

•Causes:

•AVC ; 5

•Sepsis: 4

•Spl. Seq: 4