Treatment of Manifestations

- Hb Bart Syndrome
• Hb Bart syndrome was previously considered a universally fatal
condition, however, its prognosis is shifting because of prenatal
diagnosis, intrauterine blood transfusions, improved transfusion
strategies, and (rarely) curative hematopoietic stem cell transplant
[Pecker et al 2017]. Although the Thalassemia International Guidelines
recommend a transfusion strategy similar to β-thalassemia for these
individuals; however, no reports on optimal transfusion management
exist [Amid et al 2016]. Because few children with Hb Bart syndrome
survive, clinical trials to assess these treatment approaches are lacking.

• The advances in intrauterine and postnatal therapy have resulted in

ethical dilemmas for the family and health care provider.
Alpha-Thalassemia.
Origa R, Moi P.
Editors In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH, Stephens K, editors. Source
GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2016. 2005 Nov 1 [updated 2016 Dec 29].

https://www.ncbi.nlm.nih.gov/books/NBK1435/
 Treatment of Manifestations
- HbH disease
• Most individuals with HbH disease are clinically well and survive without any treatment.
• Occasional red blood cell transfusions may be needed if the hemoglobin level suddenly
drops because of hemolytic or aplastic crises.
• Chronic red blood cell transfusions should be considered in selected individuals only.
Clear indications for red blood cell transfusions are severe anemia affecting cardiac
function and massive erythroid expansion, resulting in severe bone changes and
extramedullary erythropoiesis. Note: These events are quite rare in HbH disease.
• Iron chelation therapy may be needed in individuals with iron loading caused by regular
blood transfusion, inappropriate iron therapy, or abnormal iron absorption.
• Splenectomy should be performed only in individuals with massive splenomegaly or
hypersplenism; the associated risks for severe, life-threatening sepsis and venous
thrombosis should be considered.
• Other complications, such as gallstones and leg ulcers, require appropriate medical or
surgical treatment.

Alpha-Thalassemia.
Origa R, Moi P.
Editors In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH, Stephens K, editors. Source
GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2016. 2005 Nov 1 [updated 2016 Dec 29].
https://www.ncbi.nlm.nih.gov/books/NBK1435/
 Iron Overload in Thalassemia
Blood transfusion is a comprehensive source of iron loading for β-thalassemia patients.

Nevertheless, iron overload occurs also in patients who have not received transfusions
such as patients suffering from thalassemia intermedia. Decreased levels of hepcidin in
these patients explain this paradoxical feature.

• If hepcidin expression would be correctly regulated, it should be increased in β-

thalassemia patients in order to decrease intestinal iron absorption. However, the
opposite effect is observed

• Indeed, 2 hepcidin erythroid regulators have been reported: the growth differentiation
factor 15 (GDF15) and the twisted gastrulation protein homolog 1 (TWSG1) -high
concentrations of both proteins, members of the TGF-β superfamily, were evidenced in β-
thalassemia serum compared to normal human serum. These proteins downregulate
hepcidin secretion by hepatocytes .

The Scientific World Journal Volume 2013 (2013), Article ID 394295, http://dx.doi.org/10.1155/2013/394295
Review Article Ineffective Erythropoiesis in β-Thalassemia
Jean-Antoine Ribeil,Jean-Benoit Arlet,Michael Dussiot,Ivan Cruz Moura,Geneviève Courtois,and Olivier Hermine
 CMV causing Hydrops fetalis
Given the diversity of potential etiologies, the investigation of non-
immune hydrops fetalis requires a multidisciplinary approach.
Infectious pathogens acquired in utero represent an important
category of the identifiable causes of hydrops fetalis among which
parvovirus B19 is the most common agent. Among the other viral
etiologies of hydrops fetalis, cytomegalovirus (CMV) infection,
although uncommon, is important to identify, since specific
antiviral therapy is available.

Nonimmune Hydrops Fetalis and Fulminant Fatal Disease Due to Congenital

Cytomegalovirus Infection in a Premature Infant
Venkatesh Sampath MD, Vivek Narendran MD, Edward F Donovan MD, Jerzy Stanek PhD and Mark R Schleiss MD
Journal of Perinatology (2005) 25, 608–611. doi:10.1038/sj.jp.7211357
 Epstein-Barr Virus Infectious Mononucleosis in a
Splenectomized Patient
Junwa Kunimatsua, Riri Watanabea, Atsuto Yoshizawaa
Journal of Medical Cases, Volume 4, Number 6, June 2013, pages 353-356
ISSN 1923-4155 print, 1923-4163 online, Open Access

• IM is a common clinical syndrome. However, little attention has been paid to

the clinical picture of IM in a splenectomized patient. Indeed, the clinical
features in splenectomized patients with IM have not yet been fully described.

• Although rare, several reports of CMV-IM in splenectomized patients have

been published. Han et al reported two cases with post-splenectomy CMV
mononucleosis. In their report, the clinical features highlighted were prolonged
fever, marked lymphocytosis in the peripheral blood, an impaired IgM response
to CMV, and clonal T-cell proliferation, with T-cell receptor γ gene
rearrangements. Furthermore, based on a literature review, Han et al argued
that post-splenectomy CMV mononucleosis was a distinct clinicopathological
syndrome because they noticed that CMV-IM in an asplenic state had some
unique clinical characteristics
Harlem Hosp Bull. 1954 Dec;7(3):101-4.
Sickle cell anemia complicated by infectious
mononucleosis.
BEDELL H, PALEY SS.
PMID: 14366472 [PubMed - indexed for MEDLINE]
The direct antiglobulin (Coombs) test is used to determine whether RBC-binding antibody
(IgG) or complement (C3) is present on RBC membranes. The patient's RBCs are incubated
with antibodies to human IgG and C3. If IgG or C3 is bound to RBC membranes,
agglutination occurs–a positive result.

False positive:
• If patient received a transfusion in the last 3 months
• Alloantibodies to transfused RBCs (usually seen in acute or delayed hemolytic reaction)
• Drug-dependent or drug-induced antibodies against RBCs
 Isolated IgA Deficiency
• Most common of all primary immune deficiencies (1 in 700 whites)
• Recurrent sino-pulmonary infections and diarrhea (Giardia)
• Significant, but unexplained association with autoimmune diseases
• Block in terminal differentiation of IgA-secreting B cells to plasma cells