Hereditary persistence of hemoglobin F is protective against red cell sickling. A case report and brief review

Abstract

Fetal hemoglobin (HbF) is a physiologic protein tetramer that is crucial for a developing fetus to survive in utero. Maternal hemoglobin has a relatively lower affinity for oxygen, and thus allows for an efficient transfer of oxygen from maternal to fetal blood. In addition to fulfilling a critical physiologic role, HbF is also known to alleviate symptoms of sickle-cell disease (SCD). The concentration of HbF depends on several factors. HbF is elevated in inherited conditions, such as hereditary persistence of HbF, hereditary spherocytosis, and thalassemia. The level of HbF is also increased in acquired states, such as pregnancy, aplastic anemia, thyrotoxicosis, hepatoma, myeloproliferative disorders, or hypoplastic myelodysplastic syndrome. It has been identified that some genetic loci have significant influence on HbF levels. The XmnI polymorphism, the HMIP locus, and the BCL11A gene are responsible for 45% of variations in HbF levels. Although SCD has been well described in the subpopulations of Africa, it is less common in the subpopulations of India. We describe a case of SCD, in which a patient with high HbF level presented at a very late age (27 years old). We presume the patient's inherently elevated HbF levels were able to compensate for the hypoxic episodes associated with SCD. The onset of symptoms was delayed as a result of elevated HbF levels.

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

“…However, the group with the HbSS genotype was more exposed to cesarean section than the other two. The protective effect of HbF and alpha-thal observed in our series, is similar to that reported by other authors in the associations S/β(0) thalassemia, S/β(+) thalassemia,21 or other major sickle cell syndromes like SC, SD.…”

“…Our study showed a significant difference in weight gain in favor of the HbSS / PHHF and HbSS / alpha-thal genotypes. The observed difference could be associated with the protective effects of HbF21 and alpha-thal 22. From the hematological variables, the HbSS genotype has a high number of WBCs, reticulocytes, and platelets.…”

Periferik Kanında 100 HbF Bulunan Talasemi İntermedia Olgusu

“…HbF'in %50 doygunluğa ulaştığ pO 2 değeri yaklaşık olarak 19 mmHg iken, HbA'nın ise 27 mmHg'dır. Bu özelliği nedeni ile HbF oksijenin anneden fötüse taşınmasını kolaylaştırdığı için intrauterin dönemin en önemli hemoglobinidir(2).Gestasyonel Yüksek HbF düzeyi -Uğur Kurtoğlu et al Genel Tıp Derg 2021;31(2)180-181…”

Εξατομίκευση Της Θεραπείας Με Υδροξυουρία Ασθενών Με Β-Αιμοσφαιρινοπάθειες

“…Για το λόγο αυτό γίνεται προσπάθεια αύξησης των επιπέδων της HbF στους ασθενείς, η οποία έχει φανεί ότι ασκεί προστατευτική δράση έναντι της δρεπάνωσης των ερυθροκυττάρων. Πιο ειδικά, φαίνεται ότι η HbF (α2γ2) λόγω της παρουσίας των δυο γ-αλυσίδων, παρέχει υψηλότερη συγγένεια για το οξυγόνο απ' ό,τι η HbA ή η HbS αναστέλλοντας με αυτόν τον τρόπο τον πολυμερισμό της αποξυγονωμένης HbS και κατ'επέκταση τη δρεπάνωση των κυττάρων (Sokolova et al, 2017). Η πλέον ευρέως χρησιμοποιούμενη θεραπεία των ασθενών αυτών είναι η λήψη υδροξυουρίας (HU).…”

“…Το σύνδρομο της κληρονομικής παραμονής της εμβρυϊκής αιμοσφαιρίνης (Hereditary Persistence of Fetal Hemoglobin -HPFH syndrome) αποτελεί μια ασυμπτωματική κατάσταση κατά την οποία δεν συμβαίνει η δεύτερη μεταστροφή των σφαιρινών, με αποτέλεσμα η σύνθεση της HbF να μη σταματά μετά τη γέννηση, όπως συμβαίνει φυσιολογικά αλλά να συνεχίζει σε ποσοστό >2% και κατά την ενήλικο ζωή. Στο σύνδρομο αυτό τα επίπεδα της HbA2 συνήθως είναι μειωμένα ενώ τα ερυθροκύτταρα παρουσιάζουν μια φυσιολογική μορφολογία (Patrinos & Antonarakis, 2010, Sokolova et al, 2017. Τα HPFH σύνδρομα αποτελούν αντικείμενο μελέτης και έρευνας εδώ και αρκετές δεκαετίες, προκειμένου να διαλευκανθούν ο/οι μηχανισμοί που εμπλέκονται στη μεταστροφή των εμβρυϊκών αιμοσφαιρινών σε αυτές των ενηλίκων και κατ΄επέκταση η συνεχιζόμενη παραγωγή της HbF στο ενήλικο στάδιο.…”