Non-S Sickling Hemoglobin Variants: Historical, Genetic, Diagnostic, and Clinical Perspectives.

Apart from hemoglobin-S (HbS), there are other Hb variants (non-S sickling Hb variants) that cause sickle cell disease. However, the profiles of these non-S sickling Hb variants have neither been collated nor harmonized. A literature search revealed 14 non-S sickling Hb variants (HbC-Harlem, HbC-Ziguinchor, HbS-Travis, HbS-Antilles, HbS-Providence, HbS-Oman, HbS-Cameroon, HbS-South End, Hb Jamaica Plain, HbC-Ndjamena, HbS-Clichy, HbS-San Martin, HbS-Wake, and HbS-São Paulo). Generally, the non-S sickling Hb variants are double mutants with the HbS mutation (GAG>GTG: ßGlu6Val) and additional ß-chain mutations. Consequently, non-S sickling Hb variants give positive solubility and sickling tests, but they differ from HbS with respect to stability, oxygen affinity, and electro-chromatographic characteristics. Similarities and discrepancies between HbS and non-S sickling Hb variants create diagnostic pitfalls that can only be resolved by elaborate electro-chromatographic and/or genetic tests. It is therefore imperative that tropical hematologists should have a thorough understanding of these atypical sickling Hb variants. Collated and harmonized appraisal of the non-S sickling Hb variants have not been previously undertaken. Hence, this paper aims to provide a comprehensive but concise historical, genetic, comparative, diagnostic, and clinical overview of non-S sickling Hb variants. The elaborate techniques often required for precise diagnosis of non-S sickling Hb variants are regrettably not readily available in low resource tropical countries, which paradoxically carry the heaviest burden of sickling disorders. We strongly recommend that tropical countries should upgrade their diagnostic laboratory facilities to avoid misdiagnosis of these atypical Hb mutants.

Correlating transcranial arterial Doppler velocities with haematologic parameters and haemolytic indices of Nigerian children with sickle cell anaemia.

INTRODUCTION: Cerebral vasculopathy, elevated transcranial Doppler velocities and stroke are linked to excessive intravascular haemolysis in sickle cell anaemia. This study determined the prevalence and pattern of abnormal blood flow velocities in children with sickle cell anaemia from Northern Nigeria using transcranial Doppler and to correlate transcranial Doppler velocities with haematological and biochemical markers of haemolysis. METHODS: Full blood count, reticulocyte count, fetal haemoglobin and some selected biochemical markers of haemolysis of 100 children with sickle cell anaemia were determined at steady state. The time-averaged mean of maximal velocities in four major intracranial blood vessels was measured using non-imaging transcranial Doppler, which were then classified according to the stroke prevention in sickle cell disease trial protocol. A simple linear correlation between time-averaged mean of maximal velocities in the four major intracranial vessels as the dependent variable and haematological and biochemical markers of haemolysis as independent variables was also determined at the significance level of 0.05. RESULTS: Abnormal transcranial Doppler velocities, classified as high risk, were found in 3% of the studied patients; 11% had intermediate risk while 84% had standard risk. Most high velocities were detected in the middle cerebral artery. The time-averaged mean of maximal velocities of middle cerebral artery positively correlated with total white blood cell count, absolute neutrophil count, platelet count, reticulocyte count, serum lactate dehydrogenase and total bilirubin, while it was negatively correlated with haematocrit and fetal haemoglobin levels. CONCLUSION: Our study showed low prevalence of abnormal transcranial Doppler velocities and low prevalence is unrelated to low markers of haemolysis in our study population.

Hematological parameters of human immunodeficiency virus positive pregnant women on antiretroviral therapy in Aminu Kano Teaching Hospital Kano, North Western Nigeria.

CONTEXT: Human immunodeficiency virus (HIV) scourge continues to affect young women within the reproductive age group and pregnancy is a recognized indication for the use antiretroviral (ARV) drugs among HIV-positive women. AIMS: The aim is to determine the combined effect of pregnancy, HIV and ARV drugs on the hematological parameters of the pregnant women. SETTINGS AND DESIGN: This was a comparative cross-sectional study conducted among 70 each of HIV-positive and negative pregnant women. SUBJECTS AND METHODS: Bio-demographic and clinical data were extracted from the client folder and 4 ml of blood sample was obtained from each participant. Full blood count was generated using Swelab automatic hematology analyzer while reticulocyte count and erythrocyte sedimentation rate (ESR) were conducted manually. STATISTICAL ANALYSIS USED: Data analysis was performed using SPSS version software 16 while P < 0.05 was considered statistically significant. RESULTS: Pregnant women with HIV had statistically significant lower hematocrit and white blood cell (WBC) and higher ESR than pregnant women without HIV (P < 0.000). There was no statistically significant difference between the two groups in terms of platelet and reticulocyte (P > 0.05). However, among HIV positive pregnant women, those with CD4 count <350/µL had statistically significant lower WBC and lymphocyte count than those with CD4 count ≥350/µL (P < 0.05), whereas, those on zidovudine (AZT)-containing treatment had statistically significant lower hematocrit and higher mean cell volume than those on non-AZT-containing treatment (P < 0.05), but there was no statistically significant difference in any of the hematological parameters (P > 0.050) between women on first- and second-line ARV regimens. CONCLUSIONS: There is a significant difference in terms of hematological parameters between HIV-positive and HIV-negative pregnant women in this environment.

The Pathophysiologic Basis of Anaemia in Patients with Malignant Diseases.

Cancer patients frequently present with anaemia that may result from the direct or indirect effects of the tumor or its treatment. Anaemia is an independent adverse prognostic factor that exerts negative influence on quality of life and survival of cancer patients. Anaemia in malignant disorders often arises from an interplay of multiple aetiological and pathophysiologic mechanisms. Understanding these mechanisms will help the oncologist identify and treat specific causes of the anaemia thereby minimizing the use of blood transfusion, which is associated with many adverse effects. This paper reviewed the various aetiological and pathophysiologic mechanisms of anaemia in cancer patients including direct and indirect tumour effects that lead to reduced red cell production or increased red cell destruction via a myriad of mechanisms ranging from marrow infiltration and cancer-associated acute myelonecrosis to chronic inflammation, blood loss, iron, folate, vitamin B12 and other nutrients deficiencies, malignancy related renal injury, pure red cell aplasia, hypersplenism, haemophagocytic syndrome, red cell autoantibody production, non-immune red cell fragmentation and cytotoxic therapy-induced erythroid cell apoptosis and eryptosis. Hence anaemia in cancer patients is attributable to a wide spectrum of aetiological factors with multiple and sometimes overlapping pathophysiologic mechanisms. It is therefore necessary for the oncologists to thoroughly investigate all cases of anaemia with the aim of identifying the actual causative factors in order to offer more sustainable cause-specific treatment modalities that will minimize the use of blood transfusion with its attendant adverse effects.

Impact of sickle cell trait on the thrombotic risk associated with non-O blood groups in northern Nigeria.

BACKGROUND: The non-O blood group is an established risk factor for deep vein thrombosis (DVT), while controversy surrounds the role of sickle cell trait (SCT) as a risk factor for DVT. We hypothesised that if SCT is a risk factor for DVT, individuals with non-O blood groups and SCT (Hb AS) would have a higher risk of DVT than their counterparts with non-O blood groups and normal haemoglobin phenotype (Hb AA). MATERIALS AND METHODS: We retrospectively analysed the prevalence of SCT and non-O blood groups among 148 DVT patients with control subjects in order to determine the role of SCT as a risk factor for DVT and its impact on the risk of DVT among patients with non-O blood groups. RESULTS: In comparison with control subjects, DVT patients had significantly higher prevalences of SCT (35.1% vs 27.7%, p=0.04) and non-O blood groups (68.9% vs 45.9%, p=0.02). The odds ratios for DVT due to SCT, non-O blood groups with normal Hb phenotype (Hb AA) and non-O blood groups with SCT (Hb AS) were 1.3, 2.4 and 3.5, respectively. DISCUSSION: These results suggest that SCT by itself is a weak risk factor for DVT but it has the potential of escalating the DVT risk among patients with non-O blood groups. The combined effects of elevated clotting factors (non-O group effect) and increased clotting factor activation (SCT effect) were responsible for the escalated DVT risk among patients with co-inheritance of non-O blood groups and SCT. Co-inheritance of SCT and non-O blood group is, therefore, an important mixed risk factor for DVT. This should be taken into account when assessing DVT risk profiles of patients in Africa and other parts of the world where the SCT is prevalent.

The role of infection in the pathogenesis of vaso-occlusive crisis in patients with sickle cell disease.

Sickle cell disease (SCD) is characterized by recurrent vaso-occlusive crisis (VOC). Patients with SCD have impaired immunity and are thus predispose to infections. The vast majority of SCD patients live in underdeveloped nations with high prevalence and transmission rates of infections. This makes the SCD patients prone to infections, which frequently precipitate VOC. We reviewed the role of infection in the pathogenesis of VOC, taking into consideration all potential mechanisms from previous studies and hypothetical perspectives. The potential mechanisms through which infections may lead to VOC involve several pathological changes including pneumonitis, pyrexia, acute phase reaction, hypercoagulability, neutrophilia, eosinophilia, thrombocytosis, bronchospasm, red cell cytopathic and membrane changes, auto-antibodies mediated red cell agglutination and opsonization, diarrhoea and vomiting, which may act singly or in concert to cause red cell sickling. These changes can induce sickling directly or indirectly through their adverse effects on Hb oxygenation and polymerization, hydration, blood viscosity, red cell metabolism, procoagulant activation, intercellular adherence and aggregation, culminating in VOC. There is therefore the need to ameliorate the burden of infection on SCD through immunization, prophylactic and therapeutic use of antimicrobials, barrier protection and vector control in communities with high prevalence of SCD.

A strategic approach to the problems of providing rhesus D-negative blood transfusion in geographic areas with low RhD negativity: a Nigerian perspective.

In contrast to the white prevalence, the frequency of rhesus D (RhD) negativity in the Nigerian population ranges from less than 1% to about 6% in the different ethnic population groups across the country. Consequently, there is often a severe scarcity of RhD-negative blood in Nigeria, leading to undue delay in transfusing RhD-negative patients. This situation has led to the prolongation of hospital stays as well as increased morbidity and mortality in affected patients. The problem is compounded by the general unavailability of donor RhD-negative blood, which is partially related to a suboptimal national blood transfusion service. This situation has thus relegated the responsibilities of donor recruitment and blood collection to individual hospital blood banks. This has led to the necessity of finding a variety of ways to mitigate the daunting problem of the provision of RhD-negative donor blood in Nigeria. In this article, we review the roles, advantages, and disadvantages of various methods including the use of autologous donations, D(u) testing, inter-blood bank transfers, voluntary RhD-negative donor recall, family donations, and cryopreservation to ameliorate the problem. The real need is nonetheless to optimize the functional capacity of the Nigerian National Blood Transfusion Service.

Hematological indices of sickle cell anaemia patients with pulmonary tuberculosis in northern Nigeria.

Nigeria has the fourth highest prevalence of TB and the highest prevalence of Sickle cell anaemia (SCA) in the world. SCA patients have impaired immunity and are vulnerable to TB. Hence, we studied the haematological indices of SCA patients with TB in Nigeria. A total of 23 SCA patients with TB were studied in parallel with equal number of age and sex matched SCA patients without TB. SCA patients with TB had significantly lower haematocrit, higher level of circulating sickle cells (CSCs) and similar level of reticulocyte count in comparison to patients without TB. SCA patients with TB had significantly higher mean WBC count associated with higher frequency of neutrophilia in comparison to those without TB. Monocytosis and eosinopenia were exclusively found in SCA patients with TB at frequencies of 52% and 65% respectively. Lymphocyte and basophil counts were normal in all patients with and without TB. Mean platelet counts were high in both patient groups but the frequency of thrombocytosis was significantly higher in patients with TB. SCA patients with TB had significantly higher mean ESR than their counterparts without the infection. The findings of this study revealed that TB in SCA patients was associated with rising level of CSCs, falling level of haematocrit, sub-optimal reticulocytosis, neutrophilia, monocytosis, thrombocytosis, eosinopenia and rising level of ESR. Hence, SCA patients presenting with these haematological indices should be investigated for TB.

Hematological parameters in sickle cell anemia patients with and without priapism.

BACKGROUND: Priapism was associated with certain hematological parameters in sickle cell anemia (SCA) patients in one report but not in another. We studied differences in haematological parameters between SCA patients with and without priapism. PATIENTS AND METHODS: Eighteen patients with SCA who presented with acute priapism during the years 2001-2004 were compared with age- and sex-matched SCA patients without priapism with respect to hematocrit, reticulocyte count, level of irreversibly sickled cells (ISC), percentage of haemoglobin F (Hb F), total leukocyte and platelet counts. RESULTS: SCA patients with priapism had a mean hematocrit of 0.28 L/L, which was significantly higher than the mean hematocrit value of 0.24 L/L (P<0.05) in patients without priapism. The mean reticulocyte count of 8% in patients with priapism was significantly lower than mean reticulocyte count of 12% (P<0.05) in patients without priapism. The level of ISC of 3% in patients with priapism was significantly lower than the level of 6.5% (P<0.05) in patients without priapism. There was no statistically significant difference in the mean levels of Hb F (7% vs. 6%). Patients with priapism had a mean leukocyte count and mean platelet count that did not significantly differ from values in patients without priapism. CONCLUSIONS: SCA patients with priapism had a lower rate of hemolysis, resulting in a higher hematocrit and greater blood viscosity, which increased the risk of corpora cavernosal sickling and blockade. Hence, a relatively high hematocrit is a risk factor for the development priapism in patients with sickle cell anemia.

Spontaneous coronary artery dissection.

Spontaneous coronary artery dissection (SCAD) should be considered as a cause of the acute coronary syndrome in young patients with few apparent risk factors for coronary artery disease, in females in the peripartum period, and in patients who are at a higher risk for this condition. SCAD can also present as sudden death and cardiogenic shock. Several mechanisms have been described in the pathophysiology of this condition. Urgent coronary angiography is indicated if SCAD is suspected. Percutaneous coronary artery stenting and coronary artery bypass grafting are the main treatment strategies.

Cardiac involvement in non-Hodgkin's lymphoma: with and without HIV infection.

AIDS has resulted in a significant increase in the incidence of both primary and secondary cardiac lymphomas. Prognosis of HIV associate cardiac non-Hodgkin's lymphoma is poor with very limited survival. Many cases of cardiac involvement in lymphoma remain undetected secondary to non-specific symptoms. Chemotherapy may produce remission in some cases. We report two cases of cardiac involvement with B-cell lymphoma. The first patient had a history of AIDS while the second had no evidence of HIV infection.