CLINICAL CASE REPORT OF TRANSFUSION-DEPENDENT HEREDITARY HEMOLYTIC ANEMIA DUE TO ABNORMAL UNSTABLE HEMOGLOBIN ALESHA/BRISTOL

Qualitative hemoglobinopathies caused by the presence of abnormal unstable hemoglobins are a group of rare hemolytic anemia that create great difficulties in diagnosis. The use of modern methods of examination, including genetic ones, allows to avoid diagnostic errors. The article contains a detailed analysis of clinical manifestations in patients with abnormal unstable hemoglobins with the example of Hb Alesha/Bristol.

The rare hemoglobin variant Hb Mizuho: report of a Swiss family and literature review

Hb Mizuho is a very rare unstable hemoglobin; here, we describe the clinical history of three Swiss family members with Hb Mizuho together with a systematic review of the previously six published cases. The clinical history of the adult woman we report here is unique since this is the first Hb Mizuho presenting with Moyamoya complications and the first case reported with long-term erythrocyte exchange. The literature review showed that Hb Mizuho was mainly reported as a de novo mutation, with the exception of children descended from known cases. All published patients with this unstable hemoglobin showed severe hemolytic anemia with the exception of one; all were regularly transfused. Patients with higher HbF levels might require fewer transfusions. All patients underwent splenectomy at a median age of 4 years and had variable clinical improvement; some achieved complete resolution of transfusion dependency after splenectomy. Iron overload in Hb Mizuho patients seems to be mainly attributed to transfusions and has less to do with ineffective erythropoiesis. Diagnosis might be challenging; a normal hemoglobin electrophoresis should not rule out the diagnosis of unstable hemoglobin in patients with otherwise unexplained hemolytic anemia. This series shows the enormous utility of using molecular techniques for diagnosis.

Spectrin Interactome under normal and HbE-disease conditions

ABSTRACTSpectrin, the major component of the erythrocyte membrane skeleton is a key player in red cell biology. It has a significant role in signalling pathways and as such knowledge of spectrin interactors becomes crucial. Here we report the cytosolic interactome of human erythroid spectrin (ProteomeXchange id: PXD021525). This is to the best of our knowledge the first report of the interactome of human erythroid spectrin. We have further investigated the spectrin interactome under HbE disease conditions. Our findings indicate that there is no difference in the identity of the proteins interacting with spectrin between normal and disease conditions. However relative abundance of the interacting partners is seen to change. Very interestingly the interacting chaperone proteins, heme-containing proteins and redox active proteins are seen to be up-regulated in HbE disease state. This is consistent with our previous observation that presence of oxidation prone hemoglobin variants leads to an increase of redox regulators and chaperones in the red cell proteome. Spectrin can also interact with horse radish peroxidase and oxidatively crosslink hemoglobin, which has possible implications in oxidative stress management. Since a large fraction of spectrin interacting proteins are chaperones and redox active proteins, it is possible that spectrin may have a broader role in redox regulation, especially in cases where there are unstable hemoglobin variants present.

An « unorthodox » pathophysiology of severe cases of COVID-19 The « weak heme » hypothesis

Important amount of severe cases is the main concern in COVID-19 pandemic. It could be the running cause of the burn out of the health system in many countries. The aim of this paper is to suggest a pathophysiologic hypothesis to explain the main characteristics of severe cases of COVID-19 and its underlying conditions. In fact, the clinical and biological picture of severe cases of COVID-19 can easily be explained by free heme toxicity exceeding the endogenous antioxidant systems. Severe cases of COVID-19 are comparable to acute porphyria. On the other hand, the geographical distribution of severe cases of COVID-19 is directly associated to how fresh or polluted the air is. Finally, the relatively low rate of severe cases of COVID-19 could be explained by the presence of an unstable hemoglobin variant highly sensitive to the intrinsic conditions resulting from the acute pneumonia secondary to SARS-CoV2 infection. The combination of air pollution and free heme toxicity, resulting from the interaction between an unstable hemoglobin variant and SARS-CoV2 infection, seems to be the best scheme to explain clinical and biological manifestations in severe COVID-19. The arguments to support this hypothesis are detailed. We also propose some strategies to verify the concordance of our hypothesis with the reality and the implications it could have, if verified, either for scientists and decision makers.

Family case hemolytic anemia due to abnormal unstable hemoglobin with low oxygen affinity (Hb Cheverly)

Hereditary hemolytic anemia caused by unstable hemoglobin is a rare pathology, characterized by variability of clinical manifestations. This disease is characterized by the hemolytic crises, which are frequently associated with infections or taking drugs that cause hemolysis. Age of debut depends on which of the globin chains mutation occurs. Among these diseases, hemolytic anemia associated with the presence of a structurally abnormal unstable hemoglobin with low oxygen affinity in the erythrocytes is a special group. With this type of abnormal hemoglobin, pulse oximetry demonstrates falsely low oxygen saturation of the blood, with increased oxygen delivery to the tissues. It is important to identify unstable hemoglobin in order to avoid the misinterpretation of low oxygen saturation during the pulse oximetry in emergency cases, surgeries or intensive therapy. The article presents an analysis of the family with hereditary hemolytic anemia due to unstable hemoglobin Cheverly. The main clinical and diagnostic markers of the disease are described in detail. Parents gave their permission for using personal data for clinical research and publications.