Journal of Applied Hematology and Blood Transfusion

Hyperhemolytic Syndrome Due to Hemoglobinopathy in Sub-Saharan Africa

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Published Date: June 05, 2020

Hyperhemolytic Syndrome Due to Hemoglobinopathy in Sub-Saharan Africa

Alphonsus O. Ogbuabor1*, Peter U. Achukwu2, Silas A. Ufelle1,2, and Daniel C. Ogbuabor1,3

1Department of Hematology and Blood Transfusion, Blood Bank   Unit, Enugu State University of Science and Technology Teaching Hospital, Parklane, Enugu, Enugu State, Nigeria

2Department of Medical Laboratory Sciences, Faculty of Health Sciences and Technology, College of Medicine, University of Nigeria

1,3Department of Health Administration and Management, Faculty of Health Sciences and Technology, University of Nigeria

*Corresponding author: Alphonsus Ogbonna Ogbuabor, Department of Hematology and Blood Transfusion, Blood Bank   Unit, Enugu State University of Science and Technology Teaching Hospital, Parklane, Enugu, Enugu State, Nigeria, E-mail:

Citation: Ogbuabor AO, Achukwu PU, Ufelle SA, Ogbuabor DC (2020) Hyperhemolytic Syndrome Due to Hemoglobinopathy in Sub-Saharan Africa. J App Hem Bl Tran 2(1): 104




Globally, hemoglobinopathies remains a common genetic disorder of blood with highest prevalence recorded in the developing countries particularly those of the sub-Saharan Africa. Although there is progress towards a permanent cure, life-long transfusion therapy remains a life-saving option for patients. While the safety of blood to patients are established in the developed countries, adverse reaction from  blood transfusion are  recurrent in developing countries with transfusion reactions rendering blood safety a major public health issue. While transfusion reactions could be a result of infectious or non-infectious agents the majority of blood transfusion reactions are nonetheless non-infectious with   outcomes ranging from mild, adverse effects to death. We present an overview of hyperhemolytic syndrome for patients with hemoglobinopathies in Sub-Saharan Africa.

Keywords:  Hemoglobinopathies; Hyperhemolysis Syndrome; Sub-Saharan Africa




Hemoglobinopathies are genetic hemopathies caused by mutations in the α- globulin and/or β-globulin genes of the haemoglobulin molecule which results in either quantitative and/or qualitative abnormality of the globulin molecule [1,2]. They ranges from asymptomatic to symptomatic conditions with the different symptomatic conditions such as α-and-β thalassemia, Sickle cell disease, HbE disease and HbC disease requiring a life-long blood transfusion therapy [3,4]. They have been reported to be more prevalent in the malaria endemic regions of the world such as the Mediterranean, Asia and sub-Saharan African due to natural selection [5]. This paper presents an overview on hyperhemolytic syndrome, hemovigilance and management for patients with hemoglobinopathies in the Sub-Saharan Africa.


Hyperhemolysis Syndrome is a Common Complication in Hemoglobinopathies


Life-long dependent blood transfusions are currently a major therapeutic option for patients with hemoglobinopathies in sub-Saharan Africa. Regardless of the associated adverse effects, pre-transfusion tests for blood and blood products in most countries in this region involves only ABO, Rhesus D grouping and cross-matching without Red Blood cell antibody screening [6,7]. A major complication of transfusion therapy in patients with hemoglobinopathies is an alloimmune response to Red Blood Cell antigens. This leads to the development of a life-threatening type of delayed transfusion reaction referred to as hyperhaemolytic syndrome [8,9]. Hyperhemolysis results in the destruction of transfused Red Blood Cells within 1-2 weeks post transfusion at extra vascular sites due to agglutination, opsonization and/or subsequent phagocytosis buy macrophages [10]. Studies have reported an alloimmunization rates of 20-50% in patients with hemoglobinopathies [11]. Currently, the International Society of Blood Transfusion (ISTB) recognizes about more than 300 blood group antigens that can be identified serologically which corresponds to more than 30 genetically different blood group systems. Antibodies against these antigens have equally been identified which can cause Red Blood Cell destruction along with the corresponding antigen [12].


Mechanism of Hyperhemolysis in Patients with Hemoglobinopathies


Although the pathophysiology has not been clearly defined, hyperhemolytic syndrome is suggested to be a result of much aetiology due to its consumptive effect. Among the proposed aetiologies are (i) acute generation of oxygen radicals due to oxidative stress (ii) immune complexes and complement activation priming autologous cells for phagocytosis (Bystander hemolysis) and (iii) suppression of erythropoiesis. These mechanisms  has been proposed due to increased destruction of Red Blood Cells by activated macrophages, expression of phosphatidylserine and a secondary immune response induced by the production of atypical antibodies [13,14,15].


Clinical Manifestations of Hyperhemolysis Syndrome


Although could be asymptomatic in a few patients, most patients with hyperhemolysis syndrome presents with fever, chills, rigors, hives, flushing, itching, back pain, chest pain and unexplained discomfort occurring days to weeks following transfusion [16,17]. Many patients may develop jaundice while hemoglobinuria may be observed as red urine due to hemolysis that is primarily extravascular. In some cases, acute renal failure or disseminated intravascular coagulation may occur. Transfusion- associated graft- versus-host disease occurs rarely but mostly in immune compromised patients with symptoms of rash, fever and diarrhea. Patients could also present with purpura.


Laboratory Investigations for Hyperhemolysis Syndrome


Investigative approach to a suspected case of hyperhemolytic syndrome involves a differential diagnostic tests to rule out other forms of delayed hemolytic transfusion reactions. This gives an insight into a definitive diagnosis for confirmation of the syndrome. The routine differential laboratory investigations  includes (i) Direct Anti-human globulin Test (ii) Antibody screening Tests (iii) Complete Blood Count (iv) Blood culture (v) Hemolysin Test (vi) Renal Function Test (vii) Coagulation Test (viii) Urinalysis (ix) HLA typing of recipient and donor (x) Skin Biopsy [18].

Transfusion associated graft –versus-host-disease may be identified by skin biopsy of the affected area which is confirmed with platelet antibody screening .The D-dimer, Prothrombin time test and Activated Partial Thromboplastin Time may be elevated particularly with Disseminated Intravascular Coagulation. An elevated lactate dehydrogenase concentrations, elevated bilirubin concentration, low serum haptoglobin and presence of free hemoglobin in urine support the diagnosis of hemolysis. A reduced post- transfusion hemoglobin below the pre-transfusion concentrations, markedly elevated lactate dehydrogenase, indirect hyperbilirubinemia and hemoglobinuria in the presence of reticulocytopenia in contrast to other types of hemolytic reactions characterized by reticulocytosis is confirmatory for hyperhemolytic syndrome [14,19].


Management of Hyperhemolysis Syndrome


Depending on the severity of reaction, the first line treatment involves some supportive care to address the patient’s cardiac, respiratory and renal functions as well as providing symptomatic therapy [20]. Further management strategies depend on the degree of anemia and severity of hemolysis. In the case of mild hemolysis, additional transfusion is avoided with oral prednisolone (1-2mg/kg/day) given. In an event of rapid severe hemolysis, additional transfusion is given with intravenous immunoglobin steroid-based therapy since the additional transfusion may precipitate further hemolysis. Intravenous immunoglobin in a low-dose regime of 0.4g/kg/day for 5days with intravenous methylprednisolone 0.5g/day (adults) and 4mg/kg (pediatric) for two days is recommended [18].


The Situation in Sub-Saharan Africa


It is currently a few countries that operate a functional hemovigilance system in the region despite the WHO guidelines on the safety of blood and blood products to patients. The WHO guideline defined hemovigilance as the fulcrum of its quality management system. It therefore recommended that each country establish an effective national, regional and local hemovigilance system. A functional hemovigilance system involves proper monitoring of the whole chain of events of blood transfusion to patients, documenting any undesirable effects and introducing measures to addressing them as well as preventing future recurrence.




Hyperhemolytic syndrome is a well-documented complication in patients with haemoglobinopathies. It is the main cause of morbidity and mortality in patients with hemoglobinopathies in the sub-Saharan Africa. Hemovigilance are indispensable in sub-Saharan Africa due to the current high prevalence of hemoglobinopathies. There is an urgent need to review its policy guidelines and implementation for this region.




  1. Lee YK, Kim HJ, Lee K, Park SH, Song SH, Seong MW, et al. Recent progress in laboratory diagnosis of thalassemia and haemoglobinopathy: a study by the Korean red blood cell disorder working party of the Korean Society of Hematology. Blood Res. 2019;54:17-22.
  2. Shabbier S, Nadeem M, Satter A, Ara I, Saqib A, Farzana T, et al. Type and frequency of haemoglobinopathies, diagnosis in the area of Karachi in Pakistan. Cogent Med. 2016;3:1-7
  3. Priyaranjan C, Kundu S, Saha TN, Chattyerjee K. Study of haemoglobinopathies at a referral laboratory in a western district of west Bengel among the antennal women and pre-marital men and women: a 2 year study. Int J Contemporary Med Res. 2019;6(6):f24-f27.
  4. Ademola SA, Obieche JC. Hypertransfusion therapy in sickle cell disease in Nigeria. Adv Haematol. 2014;923593:1-9.
  5. Goonasekera HW, Pathiniqe CS, Dissanayake VHW. Population screening for haemoglobinopathesis. Annu Rev Genom Hum Genet. 2018;19:358-80.
  6. Lilian AB, Alian MN, Imelda B, Henk S. Red blood cell alloimmunization in transfused patients with sickle cell disease in sub-Saharan Africa: a systematic review and meta-analysis. Transfus Med Rev. 2019;3(3):162-169.
  7. Boateng LA, Schonewille H, Sackey B, Owusu-Ofori S, Afriyie E. Prevalence of red blood cell antibodies among transfused patients at Komfo Anokye Teaching Hospital (KATH). Ghana J Sci Tech. 2014;34(3),27-34.
  8. Win S, Thida A, June MA, Kyaw TA, Swe ZO, Lwin H, et al. Hyperhaemolysis with haemoglobin H disease. Haematol Transfus Int J. 2017;5(3):250-252.
  9. Vagace JM, Cardesa R, Corbacho A, Vazguez T, Maya MDD, Gonzalez FA, et al. Etiopathological mechanisms and clinical characteristics of hyperhaemolytic syndrome in Spanish patients with thalassemia. Ann Haematol. 2016;95:1419-1427.
  10. Maria EG, Natalia BS, Mario SAN, Flavia CMA. Hyperhemolysis syndrome in a patient with sickle cell anemia: a case report. Brazillian J Hematol Hemother. 2015;37(4):266-268.
  11. Surapon T. Impact of alloimmunization on transfusion-dependent patients. Ann Adv Chem. 2017;1:070-082.
  12. Hart S, Gazdewich CNC, Mecluskey SA. Red cell transfusion and the immune system. Anaesthesia. 2015;70(suppl 1),38-45.
  13. Brand A. Immunological complications of blood transfusion. Curr Question Transfus Med. 2016;45(7):e313-e324.
  14. Banks M, Shirkle J. Hyperhemolysis syndrome in patients with sickle cell disease. Arch Pathol Lab Med. 2018;142:1425-1427.
  15. Win N. Hyperhemolysis syndrome in sickle cell disease. Ann Haematol Oncol. 2019;6(7):12-58.
  16. Parashar R, Bundas S, Sharma A, Meena BS, Pamendra P, Sharma S. Retrospective evaluation of adverse transfusion reactions following blood product transfusion from SMS Hospital Jaipur. J Med Sci Edu. 2019;6(2):64-69.
  17. Negi G, Gaur DS, Kaur R. Blood transfusion safety: a study of adverse reactions at the blood bank of a tertiary care center. Adv Biomed Res. 2015;4:237.
  18. Win N. Hyperhemolysis syndrome in sickle cell disease. Expert Rev Hematol. 2009;2(2):111-115.
  19. Zoe B, Anna C, Kontekaki E, Athanasios AG, Spyros PI, Menexiduo H, et al. Hyperhemolytic syndrome complicating a delayed hemolytic transfusion reaction due to anti-PI alloimmunization in a pregnant woman with Hbo-Arab/β-Thalassemia. Mediterr J Hematol Infect Dis. 2016;8(1):e053.
  20. Delaney M, Wendel S, Rachael SB, Joan C, Cohn C, Dunbar NM, et al. Transfusion reactions: prevention, diagnosis and treatment. Lancet. 2016;15:1-13.


Copyright: © 2020 Ogbuabor AO, et al.. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.