HOMOZYGOUS DELETION ALFA-THALASSEMIA AND HEREDITARY PERSISTENCE OF FETAL HEMOGLOBIN, TWO GENETIC FACTORS PREDICTIVE THE REDUCTION OF MORBIDITY AND MORTALITY DURING PREGNANCY IN SICKLE CELL PATIENTS . A REPORT FROM DEMOCRATIC REPUBLIC OF CONGO ALPHA THALASSEMIA AND HEREDITARY PERSISTENCE OF FETAL HEMOGLOBIN REDUCE MORBIDITY DURING PREGNANCY IN SICKLE CELL PATIENTS
Main Article Content
Keywords
alpha-thal, HPFH, morbidity, pregnancy, sickle cell disease
Abstract
FHb and alpha-thal are two genetic factors that modulate the clinical expression of sickle cell disease.
Objective: to determine the beneficial role of FHb and alpha-thal on fetal and maternal morbidity during pregnancy in sickle cell patients.
This is a documentary and analytical study that included 960 deliveries of homozygous sickle cell patients. The deliveries were divided into three genotype subgroups: Hb-SS / alpha-thal, HbSS / HPFH and HbSS. The diagnosis of SCD and the quantification of FHb were performed by the capillary electrophoresis technique. The diagnosis of SCD has been confirmed by the molecular test. The diagnosis of alpha-thal was made by the multiplex ligation dependent probe amplification (MLPA) technique. Sickle cell pregnancies were followed according to the protocol of care in force in our service. The variables of interest were: hematological variables, sickle cell crises during pregnancy, maternal and fetal complications. Statistical analyzes were performed with SPSS 20.0 software. Means and standard deviations were compared with the Student's t and Annova tests. The value of p <0.05 was considered the significance level.
The Hb-SS / alpha-thal and HbSS / HPFH genotypes were observed in 101 and 121 women respectively. Otherwise 758 women had the HbSS genotype. The morbidity related to sickle cell complications in the mother and fetus, were less frequent in the Hb-SS / alpha-thal and HbSS / HPFH groups. The statistical differences were statistically significant.
This study showed a significant protective effect of alpa-thal and HPFH during pregnancy in sickle-cell pregnant women.
FHb and alpha-thal are two genetic factors that modulate the clinical expression of sickle cell disease.
Objective: to determine the beneficial role of FHb and alpha-thal on fetal and maternal morbidity during pregnancy in sickle cell patients.
This is a documentary and analytical study that included 960 deliveries of homozygous sickle cell patients. The deliveries were divided into three genotype subgroups: Hb-SS / alpha-thal, HbSS / HPFH and HbSS. The diagnosis of SCD and the quantification of FHb were performed by the capillary electrophoresis technique. The diagnosis of SCD has been confirmed by the molecular test. The diagnosis of alpha-thal was made by the multiplex ligation dependent probe amplification (MLPA) technique. Sickle cell pregnancies were followed according to the protocol of care in force in our service. The variables of interest were: hematological variables, sickle cell crises during pregnancy, maternal and fetal complications. Statistical analyzes were performed with SPSS 20.0 software. Means and standard deviations were compared with the Student's t and Annova tests. The value of p <0.05 was considered the significance level.
The Hb-SS / alpha-thal and HbSS / HPFH genotypes were observed in 101 and 121 women respectively. Otherwise 758 women had the HbSS genotype. The morbidity related to sickle cell complications in the mother and fetus, were less frequent in the Hb-SS / alpha-thal and HbSS / HPFH groups. The statistical differences were statistically significant.
This study showed a significant protective effect of alpa-thal and HPFH during pregnancy in sickle-cell pregnant women.
Downloads
Abstract 9632
PDF Downloads 730
HTML Downloads 131
References
normal human and sickle cell anemia hemoglobin. Nature, 1956; 178:
792-4.
https://doi.org/10.1038/178792a0
PMid:13369537
2. Ingram VM. Abnormal hemoglobin. The chemical difference between
normal and sickle cell hemoglobins. Biochim - Biophys Acta, 1959; 36:
402-411.
https://doi.org/10.1016/0006-3002(59)90183-0
www.mjhid.org Mediterr J Hematol Infect Dis 2019; 11; e2019039 Pag. 6 / 6
3. Perutz MF, Mitchison JN. State of hemoglobin in sickle cell anemia.
Nature, 1950; 166: 677-679.
https://doi.org/10.1038/166677a0
4. Serjeant GR - Sickle cell disease. Lancet, 1997; 350: 725-730.
https://doi.org/10.1016/S0140-6736(97)07330-3
5. Serjeant GR. The Natural History of Sickle Cell Disease. Cold Spring
Harb Perspect Med, 2013; 3:a011783
https://doi.org/10.1101/cshperspect.a011783
PMid:23813607 PMCid:PMC3784812
6. Hendrickse JPdeV, Harrison KA, Watson-Williams EJ, Luzzatto L,
Ajabor LN. Pregnancy in homozygous sickle-cell anemia. J Obstet
Gynecol Br Com- monw 1972;79:396-409.
https://doi.org/10.1111/j.1471-0528.1972.tb14177.x
7. Baum KF, Dunn DT, Maude GH, Serjeant GR. The painful crisis of
homozygous sickle cell disease. A study of risk factors. Arch Intern Med
1987;147:1231-4.
https://doi.org/10.1001/archinte.1987.00370070045007
PMid:3606281
8. Koshy M, Burd L. Management of pregnancy in sickle cell syndrome.
Hematol Oncol North Am 1991;5(3):585-96.
https://doi.org/10.1016/S0889-8588(18)30433-7
9. Powars DR, Sandhu M, Niland-Weiss J et al. Pregnancy in SSD. Obstet
Gynecol 1986; 67:217-28.
https://doi.org/10.1097/00006250-198602000-00012
PMid:3945432
10. Sun PM, Wilburn W, Raynor D et al. SSD in pregnancy: twenty years of
experience at Grady Memorial Hospital, Atlanta, Georgia. Am J Obstet
Gynecol 2001;184:112-30.
https://doi.org/10.1067/mob.2001.115477
PMid:11349177
11. Serjeant GR, Loy LL, Crowther M et al. Outcome of pregnancy in
homozygous SSD. Obstet Gynecol 2004;103(6):1278-85.
https://doi.org/10.1097/01.AOG.0000127433.23611.54
PMid:15172865
12. Nagel RL, Bookchim RM, Johnson J et al. Structural bases of the
inhibitory effects of hemoglobin F and hemoglobin A2 on the
polymerization of hemoglobin S. Proc Natl Acad Sci USA, 1982;76: 670
- 2.
https://doi.org/10.1073/pnas.76.2.670
PMid:284392 PMCid:PMC383012
13. Cannas G, Poutrel S, Thomas X. Hydroxycarbamine: from an Old Drug
Used in Malignant Hemopathies to a Current Standard in Sickle Cell
Disease. Mediterr J Hematol Infect Dis. 2017 Feb 15;9(1):e2017015.
doi: 10.4084/MJHID.2017.015. eCollection 2017. Review.
https://doi.org/10.4084/mjhid.2017.015
PMid:28293403 PMCid:PMC5333733
14. Higgs DR, Aldridge BE, Lamb J et al. The interaction of alphathalassemia and homozygous sickle cell disease. N Engl J Med., 1982;
306: 1441 - 6.
https://doi.org/10.1056/NEJM198206173062402
PMid:6176865
15. Mikobi TM, Lukusa PT, Aloni MN, et al. Association between sickle
cell anemia and alpha thalassemia reveals a high prevalence of the ?3.7
triplication in congolese patients than in worldwide series. J Clin Lab
Anal. 2017;00:e22186.
https://doi.org/10.1002/jcla.22186
PMid:28276593
16. Mikobi TM, Lukusa Tshilobo P, Aloni MN, Akilimali PZ, MvumbiLelo G, and Mbuyi-Muamba JM. Clinical phenotypes and the biological
parameters of Congolese patients suffering from sickle cell anemia: A
first report from Central Africa. J Clin Lab Anal. 2017;00:e22140.
https://doi.org/10.1002/jcla.22140
PMid:28116772
17. Jit BP, Mohanty PK, Purohit P, Patel S, Meher S, Mohanty JR, Sinha S,
Behera RK, Das P. Association of fetal hemoglobin level with frequency
of acute pain episodes in sickle cell disease (HbS-only phenotype)
patients. Blood cells Mol Dis. 2019 Mar;75 :30-34. Epub 2018 Dec 20.
https://doi.org/10.1016/j.bcmd.2018.12.003
PMid:30597429
18. Yacobovich J, Tamary H : Thalassemia major and sickle cell disease in
adolescents and young adults. Acta Haematol. 2014;132(3-4) :340-7.
Epub 2014 Sep 10.
https://doi.org/10.1159/000360235
PMid:25228560
19. Chang JN, Magann EF, Novotny SA, Cooley CE, Gauss CH, Parrish
MR, Morrison JC. Maternal/Perinatal Outcome in Women with Sickle
Cell Disease: A Comparison of Two Time Periods. South Med J. 2018
Dec;111(12) :742-745.
https://doi.org/10.14423/SMJ.0000000000000900
PMid:30512127
20. Silva-Pinto AC, de Oliveira Domingues Ladeira S, Brunetta DM, De
Santis GC, de Lucena Angulo I, Covas DT. Sickle cell disease and
pregnancy: analysis of 34 patients followed at the Regional Blood
Center of Ribeirão Preto, Brazil. Rev Bras Hematol Hemoter. 2014 SepOct;36(5):329-33. Epub 2014 Jul 16.
https://doi.org/10.1016/j.bjhh.2014.07.002
PMid:25305164 PMCid:PMC4318372
21. Sokolova A, Mararenko A, Rozin A, Podrumar A, Gotlieb V. Hereditary
persistence of hemoglobin F is protective against red cell sickling. A
case report and brief review. Hematol Oncol Stem Cell Ther. 2017 Oct
16. pii: S1658-3876(17)30115-2.
https://doi.org/10.1016/j.hemonc.2017.09.003
PMid:29079125
22. Resende Cardoso PS, Lopes Pessoa de Aguiar RA, Viana MB. Clinical
complications in pregnant women with sickle cell disease: prospective
study of factors predicting maternal death or near miss. Rev Bras
Hematol Hemoter. 2014 Jul-Aug; 36(4):256-63. Epub 2014 May 29.
https://doi.org/10.1016/j.bjhh.2014.05.007
PMid:25031164
23. Cardosa D, Ridout A, Nanda S, Howard J, Robinson SE, Oteng-Ntim E.
Maternal sickle cell disease and twin pregnancy: a case series and
review of the literature. Hematology. 2019 Dec;24(1):148-158. Epub
2018 Oct 21.
https://doi.org/10.1080/10245332.2018.1535534
PMid:30345909
24. Chambers J, Smith N, Sehring M, Chittivelu S. Acute Chest Syndrome
Progressing to ARDS in a Patient of 25-Week Gestation. Case Rep Crit
Care. 2018 Jan 30;2018:4243569. eCollection 2018.
https://doi.org/10.1155/2018/4243569
PMid:29666710 PMCid:PMC5831955
25. Burgos Luna JM, Páez Rúa DM, Ruiz Ordoñez I, Fernández PA,
Escobar Vidarte MF. Description of criteria for near miss in highcomplexity obstetric population with sickle cell anemia: an
observational study. J Matern Fetal Neonatal Med. 2018 Sep 19:1-6.
https://doi.org/10.1080/14767058.2018.1510912
PMid:30231783
26. McGann PT, Williams AM, Ellis G, McElhinney KE, Romano L,
Woodall J, Howard TA, Tegha G, Krysiak R, Lark RM, Ander EL,
Mapango C, Ataga KI, Gopal S, Key NS, Ware RE, Suchdev PS.
Prevalence of inherited blood disorders and associations with malaria
and anemia in Malawian children. Blood Adv. 2018 Nov 13;2(21):3035-
3044.
https://doi.org/10.1182/bloodadvances.2018023069
PMid:30425067 PMCid:PMC6234379
27. Maier AG, Matuschewski K, Zhang M, Rug M. Plasmodium falciparum.
Trends Parasitol. 2018 Dec 27. pii: S1471-4922(