Good practice statements for antithrombotic therapy in the management of COVID-19: Guidance from the SSC of the ISTH.

Despite the emergence of high quality randomized trial data with the use of antithrombotic agents to reduce the risk of thromboembolism, end-organ failure, and possibly mortality in patients with coronavirus disease 2019 (COVID-19), questions still remain as to optimal patient selection for these strategies, the use of antithrombotics in outpatient settings and in-hospital settings (including critical care units), thromboprophylaxis in special patient populations, and the management of acute thrombosis in hospitalized COVID-19 patients. In October 2021, the International Society on Thrombosis and Haemostasis (ISTH) formed a multidisciplinary and international panel of content experts, two patient representatives, and a methodologist to develop recommendations on treatment with anticoagulants and antiplatelet agents for COVID-19 patients. The ISTH Guideline panel discussed additional topics to be well suited to a non-Grading of Recommendations Assessment, Development, and Evaluation (GRADE) for Good Practice Statements (GPS) to support good clinical care in the antithrombotic management of COVID-19 patients in various clinical settings. The GPS panel agreed on 17 GPS: 3 in the outpatient (pre-hospital) setting, 12 in the hospital setting both in non-critical care (ward) as well as intensive care unit settings, and 2 in the immediate post-hospital discharge setting based on limited evidence or expert opinion that supports net clinical benefit in enacting the statements provided. The antithrombotic therapies discussed in these GPS should be available in low- and middle-income countries.

Association of the ABO blood group with SARS-CoV-2 infection in a community with low infection rate.

BACKGROUND AND OBJECTIVES: Reports on the association of the ABO phenotypes with infection by the SARS-CoV-2 virus have mostly come from countries with high infection rates. This study examined the possible association between SARS-CoV-2 infection and the ABO phenotype in Black Africa. MATERIALS AND METHODS: This report is from a single centre where both asymptomatic and symptomatic patients were quarantined. At the time of this report, Oyo State, Nigeria had carried out 15 733 tests of which 3119 were positive for the virus with 1952 recoveries and 37 deaths. The ABO distribution of patients was compared with that of a blood donor population. RESULTS: Of the 302 participants, 297 (98%) had their blood group determined, asymptomatic and symptomatic individuals were 123 (40·7%) and 179 (59·3%) respectively. Blood group O was significantly less represented among the patients (P < 0·01) while blood groups B and AB were significantly more represented (P < 0·01, P = 0·03 respectively). Patients with anti-B (groups A and O) were significantly less represented than those without anti-B (B and/or AB): B and AB (P < 0·001), B (P = 0·002), AB (P = 0·01). There was no difference in the blood group distribution of symptomatic and asymptomatic patients (χ2 (3, N = 302) = 2·29; P = 0·51), but symptomatic patients with anti-A (groups B and O) were more represented than asymptomatic patients with anti-A (χ2 4·89; P = 0·03). CONCLUSION: The higher prevalence of blood group O and more potent beta haemolysins (anti-B antibodies) are likely reasons for the lower infectivity by the SARS-CoV-2 virus and severity of COVID-19 disease in the community.

Acute leukemia in sickle cell disease patients in a tertiary health facility in Nigeria: a case series.

BACKGROUND AND OBJECTIVES: Sickle cell disease(SCD) is a disorder of red cells resulting from the co-inheritance of haemoglobin S (HbS) with another abnormal haemoglobin. The diagnosis of acute leukaemia is uncommon in our patients with sickle cell disease more so the patients have high morbidity and mortality due to the sickling process. Acute leukemia is a malignant clonal disorder of haemopoietic precursor cells resulting in accumulation of immature blood cells in the bone marrow and blood. The objective of the case series was to highlight the challenges of diagnosis and management of SCD patients with acute leukaemia, the importance of peripheral blood film review and propound a possible risk factor. METHODS: Records of 58 patients diagnosed and managed for acute leukaemia over a 7 year period at the University College Hospital, Ibadan were reviewed. The diagnosis of acute leukaemia was based on clinical features in addition to peripheral and bone marrow smears findings. Microsoft excel version 2013 was used for statistical analysis. RESULTS: Five (8.6%) of the patients with acute leukaemia also had sickle cell disease: 3 males and 2 females were described. Recurrent fever and anaemia were the most consistent presenting features in the patients. All the patients were not on any routine medications meant for SCD patients and had poor history of clinic attendance prior to the diagnosis of acute leukaemia. The diagnosis of acute leukaemia was not made until the patients were seen by a haematologist. The principal tool of diagnosis in all the patients was peripheral blood film review. Two patients were discharged against medical advice. The treatment period ranged between one month and one year in the remaining three patients. CONCLUSION: SCD patients are not exempted from developing acute leukaemias and the diagnoses of the two conditions overwhelms the social and economic support of patients and care givers. The study also underscores the relevance of high level of suspicion and prompt review of peripheral blood film of SCD patients particularly when patients present with unremitting symptoms associated with anaemia and fever.

The effect of the coinheritance of Glucose-6-phosphate dehydrogenase deficiency on the severity of sickle cell disease.

BACKGROUND: Sickle cell disease (SCD) and glucose-6-phosphate dehydrogenase (G6PD) deficiency are inherited disorders associated with chronic haemolysis. Therefore, coinheritance of both disorders could worsen haemolysis in the former and compound a haemolytic crisis. This study compared clinical and laboratory features of deficient and non-deficient SCD patients and the G6PD activities of SCD patients and apparently healthy controls. MATERIALS AND METHODS: This is a case-control study of 175 SCD patients and 166 non-SCD controls. G6PD assay was carried out on haemolysate from washed red cells. The G6PD activity was measured by spectrophotometry. RESULTS: The mean age of patients and controls was 27.3 ± 9.4 and 35.9 ± 9.7 years, respectively, with 75 (46.2%) and 87 (52.4%) being males, respectively. G6PD activity was similar in cases and controls (6.7 ± 3.3 vs. 6.9 ± 3.0 IU/gHb), respectively (P = 0.6). The prevalence of G6PD deficiency was higher in patients than controls (28.6% vs. 22.3%, P = 0.18), and SCD patients were twice more likely to have enzyme activities below 3.0 IU/gHb. No significant difference was observed in the clinical parameters between deficient and non-deficient patients. Deficient patients were more likely to have lower haematocrit (22.8 ± 3.9% vs. 24.5 ± 5%, P = 0.04) and non-significantly higher bilirubin and reticulocyte counts. Furthermore, in patients, severe deficiency resulted in higher bilirubin than in those with mild deficiency (60.5 vs. 21.7 IU/L, P < 0.001). G6PD activity correlated positively with haematocrit (r = 0.91, P = 0.01) and mean corpuscular haemoglobin concentration (r = 0.17, P = 0.02). CONCLUSIONS: Coinheritance of both disorders could worsen haemolysis in SCD patients, and care should, therefore, be taken in the choice of drugs in deficient SCD patients.

Sickle Cell Disease Clinical Trials and Phenotypes.

Sickle cell disease, one of the world's most common genetic disorders is prevalent in sub-Saharan Africa. The trans-Atlantic slave trade accounted for the gene movement from Africa to the Caribbean and United States of America and lately, migration has resulted in the introduction of the gene to the United Kingdom and other parts of Europe. Different haplotypes exist, however the differences in these haplotypes are not sufficient to explain the different clinical variations within the same region or different settings.

Effect of tranexamic acid on coagulation and fibrinolysis in women with postpartum haemorrhage (WOMAN-ETAC): a single-centre, randomised, double-blind, placebo-controlled trial.

Background: Postpartum haemorrhage (PPH) is a leading cause of maternal death. The WOMAN trial showed that tranexamic acid (TXA) reduces death due to bleeding in women with PPH. We evaluated the effect of TXA on fibrinolysis and coagulation in a sample of WOMAN trial participants. Methods: Adult women with a clinical diagnosis of PPH were randomised to receive 1 g TXA or matching placebo in the WOMAN trial. Participants in the WOMAN trial at University College Hospital (Ibadan, Nigeria) also had venous blood taken just before administration of the first dose of trial treatment and again 30 (±15) min after the first dose (the ETAC study).  We aimed to determine the effects of TXA on fibrinolysis (D-dimer and rotational thromboelastometry maximum clot lysis (ML)) and coagulation (international normalized ratio and clot amplitude at 5 min). We compared outcomes in women receiving TXA and placebo using linear regression, adjusting for baseline measurements. Results: Women (n=167) were randomised to receive TXA (n=83) or matching placebo (n=84). Due to missing data, seven women were excluded from analysis. The mean (SD) D-dimer concentration was 7.1 (7.0) mg/l in TXA-treated women and 9.6 (8.6) mg/l in placebo-treated women (p=0.09). After adjusting for baseline, the D-dimer concentration was 2.16 mg/l lower in TXA-treated women (-2.16, 95% CI -4.31 to 0.00, p=0.05). There was no significant difference in ML between TXA- and placebo-treated women (12.3% (18.4) and 10.7% (12.6), respectively; p=0.52) and no significant difference after adjusting for baseline ML (1.02, 95% CI -3.72 to 5.77, p=0.67).  There were no significant effects of TXA on any other parameters. Conclusion: TXA treatment was associated with reduced D-dimer levels but had no apparent effects on thromboelastometry parameters or coagulation tests. Registration: ISRCTN76912190 (initially registered 10/12/2008, WOMAN-ETAC included on 22/03/2012) and NCT00872469 (initially registered 31/03/2009, WOMAN-ETAC included on 22/03/2012).

Haematological and fibrinolytic status of Nigerian women with post-partum haemorrhage.

BACKGROUND: Early treatment with tranexamic acid reduces deaths due to bleeding after post-partum haemorrhage. We report the prevalence of haematological, coagulation and fibrinolytic abnormalities in Nigerian women with postpartum haemorrhage. METHODS: We performed a secondary analysis of the WOMAN trial to assess laboratory data and rotational thromboelastometry (ROTEM) parameters in 167 women with postpartum haemorrhage treated at University College Hospital, Ibadan, Nigeria. We defined hyper-fibrinolysis as EXTEM maximum lysis (ML) > 15% on ROTEM. We defined coagulopathy as EXTEM clot amplitude at 5 min (A5) < 40 mm or prothrombin ratio > 1.5. RESULTS: Among the study cohort, 53 (40%) women had severe anaemia (haemoglobin< 70 g/L) and 17 (13%) women had severe thrombocytopenia (platelet count < 50 × 109/L). Thirty-five women (23%) had ROTEM evidence of hyper-fibrinolysis. Based on prothrombin ratio criteria, 16 (12%) had coagulopathy. Based on EXTEM A5 criteria, 49 (34%) had coagulopathy. CONCLUSION: Our findings suggest that, based on a convenience sample of women from a large teaching hospital in Nigeria, hyper-fibrinolysis may commonly occur in postpartum haemorrhage. Further mechanistic studies are needed to examine hyper-fibrinolysis associated with postpartum haemorrhage. Findings from such studies may optimize treatment approaches for postpartum haemorrhage. TRIAL REGISTRATION: The Woman trial was registered: NCT00872469; ISRCTN76912190 (Registration date: 22/03/2012).

Phenotyping and genotyping of CYP2C19 using comparative metabolism of proguanil in sickle-cell disease patients and healthy controls in Nigeria.

Polymorphic expression of metabolic enzymes have been identified as one of the key factors responsible for the interindividual/ethnic/racial variability in drug metabolism and effect. In Nigeria, there is a disproportionately high incidence of sickle-cell disease (SCD), a condition characterized by painful crisis frequently triggered by malaria. Proguanil, a substrate of the polymorphic CYP2C19, is a chemoprophylactic antimalarial drug widely used among SCD patients in Nigeria. This study aimed to conduct a comparative CYP2C19 phenotyping among SCD patients and healthy controls and to compare the results with those previously reported. One hundred seventy-seven unrelated subjects comprising 131 SCD patients and 46 non-SCD volunteers were phenotyped. This was carried out by collecting pooled urine samples over 8 h following PG administration. Proguanil and its major CYP2C19-dependent metabolites were measured by high-performance liquid chromatography. Metabolic ratios (MRs) were computed and employed in classifying subjects into poor or extensive metabolizers. Among SCD group, 130 (99.2%) were extensive metabolizers (EMs) and 1 (0.8%) was poor metabolizer (PM) of PG, while 95.7 and 4.3% non-SCDs were EMs and PMs, respectively. MRs ranged from 0.02 to 8.70 for SCD EMs and from 0.22 to 8.33 for non-SCD EMs . Two non-SCDs with MRs of 18.18 and 25.76 and the SCD with MR of 16.77 regarded as PMs had earlier been genotyped as CYP2C19*2/*2. Poor metabolizers of proguanil in SCD patients are reported for the first time. Regardless of clinical significance, a difference in metabolic disposition of proguanil and CYP2C19 by SCDs and non-SCDs was established.

Sickle Cell Trait: A Benign State?

BACKGROUND: Sickle cell trait (SCT) is the heterozygous form of sickle cell disease and expectedly should be a benign state with no complications ascribed to it. There are numerous reports challenging its being a benign condition, though this is controversial. METHODS AND RESULTS: A review of the results of the accompanying investigations done on some of the patients show that beta thalassemia may be responsible for many of the ascribed symptoms and complications. These patients may therefore have sickle cell beta thalassemia, a compound heterozygous form of sickle cell disease. CONCLUSION: It is important to screen for beta thalassemia using red cell indices and quantitation of the different hemoglobin fractions before attributing any symptoms to SCT. DNA analysis, though useful in ascertaining the presence of the sickle cell gene, is not sufficient. There is the need to exclude the presence of mutations for beta thalassemia, which often is geographical region-specific.

Effect of tranexamic acid on coagulation and fibrinolysis in women with postpartum haemorrhage (WOMAN-ETAC): protocol and statistical analysis plan for a randomized controlled trial.

Background: Postpartum haemorrhage (PPH) is a leading cause of maternal death. Tranexamic acid has the potential to reduce bleeding and a large randomized controlled trial of its effect on maternal health outcomes in women with PPH (The WOMAN trial) is ongoing. We will examine the effect of tranexamic acid on fibrinolysis and coagulation in a subset of WOMAN trial participants. Methods. Adult women with clinically diagnosed primary PPH after vaginal or caesarean delivery are eligible for inclusion in the WOMAN trial. In a sub-group of trial participants, blood samples will be collected at baseline and 30 minutes after the first dose of tranexamic acid or matching placebo.  Our primary objective is to evaluate the effect of tranexamic acid on fibrinolysis. Fibrinolysis will be assessed by measuring D-dimers and by rotational thromboelastometry (ROTEM). Secondary outcomes are international normalized ratio (INR), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, haemoglobin and platelets. We aim to include about 180 women from the University College Hospital, Ibadan in Nigeria. Discussion:  This sub-study of WOMAN trial participants should provide information on the mechanism of action of tranexamic acid in women with postpartum haemorrhage. We present the trial protocol and statistical analysis plan. The trial protocol was registered prior to the start of patient recruitment. The statistical analysis plan was completed before un-blinding. Trial registration: The trial was registered: ClinicalTrials.gov, Identifier NCT00872469 https://clinicaltrials.gov/ct2/show/NCT00872469; ISRCTN registry, Identifier ISRCTN76912190 http://www.isrctn.com/ISRCTN76912190 (Registration date: 22/03/2012).

Autopsy findings and pattern of mortality in Nigerian sickle cell disease patients.

INTRODUCTION: Sickle Cell Disease (SCD) has a high mortality rate in the environment where we practice. There is lack of contemporal autopsy studies describing causes of death among SCD patients at our centre. METHODS: This is a retrospective study of SCD patients who died between January 1991 and December 2008 and that had autopsy examination to confirm the cause of death in a Nigerian teaching hospital. The clinical data, including the age, gender, Hb genotype, and the major autopsy findings and cause of death were obtained for each patient from the complete autopsy reports that included histopathological examination. Multiple causes of death were entertained. RESULTS: A total of 52 autopsies were performed. The mean age at death was 21.3 years (range, 1-47 years) and a male/female ratio of 1.3:1. HbS+C patients lived longer than HbS patients (21.0 years Vs 24.0 years) and peak mortality was in the 2nd and 3rd decades of life. The commonest causes of death as a single entity or in combination included infections in 78% of cases, fatal thrombotic/embolic events (37%) making acute chest syndrome a leading cause of death. This was followed closely by anemia alone or in combination with acute sequestration crises in 31% of patients. CONCLUSION: Infections are the commonest causes of death in Nigerian SCD patients, efforts to reduce infection especially early in life through prophylaxis or vaccination will impact on the overall survival of these patients.

Guidelines for the diagnosis of the haemoglobinopathies in Nigeria.

The haemoglobinopathies are prevalent genetic disorders in Nigeria, it is therefore imperative that diagnosis is made accurately and promptly so that affected individuals can seek timely medical help. There is no structured modality for the investigation of the haemoglobinopathies in the country. Haemoglobin electrophoresis at alkaline pH is solely relied upon by both the secondary and tertiary health centres in the diagnosis of the haemoglobinopathies. It is also necessary to know and understand the various diagnostic tests available for this genetic disorder and to interpret the results correctly. This review discusses the different diagnostic tests appropriate for the different levels of health care in the country.

Molecular and contextual markers of hepatitis C virus and drug abuse.

The spread of hepatitis C virus (HCV) infection involves a complex interplay of social risks, and molecular factors of both virus and host. Injection drug abuse is the most powerful risk factor for HCV infection, followed by sexual transmission and additional non-injection drug abuse factors such as co-infection with other viruses and barriers to treatment. It is clearly important to understand the wider context in which the factors related to HCV infection occur. This understanding is required for a comprehensive approach leading to the successful prevention, diagnosis, and treatment of HCV. An additional consideration is that current treatments and advanced molecular methods are generally unavailable to socially disadvantaged patients. Thus, the recognition of behavioral/social, viral, and host factors as components of an integrated approach to HCV is important to help this vulnerable group. Equally important, this approach is key to the development of personalized patient treatment - a significant goal in global healthcare. In this review, we discuss recent findings concerning the impact of drug abuse, epidemiology, social behavior, virology, immunopathology, and genetics on HCV infection and the course of disease.

Beta thalassaemia trait in western Nigeria.

BACKGROUND: Genes for thalassaemia, haemoglobin S, Glucose-6-phosphate dehydrogenase which confer resistance to malaria are found in high frequencies in Nigeria, 25% of the population being carriers of the sickle cell trait while another 25% are hemizygous for the G6PD gene. The frequency of alpha thalassaemia is equally high among Nigerians but there is little information on beta thalassaemia in this population. A recent study however suggest a high prevalence of beta thalassaemia in the same population, hence the need for this study. METHODS: Haemoglobin A(2) and HbF were determined in healthy adults who have haemoglobin A genotype by elution after electrophoresis and alkaline denaturation methods respectively. RESULTS: The mean HbA(2) among the subjects was 3.3% (range 2.0-5.6%) while the mean HbF was 2.6% (range 0.4-8.8%). Twenty-six percent of the subjects had HbA(2) values higher than 3.9% while 86% had HbF values greater than 1%, twenty-four percent had elevated HbA(2) and HbF. The mean HbA(2) value was 2.7% among those with HbF <1%, 3.6% among those with HbF 1-3% and 3.1% among those with HbF >3%. CONCLUSION: These findings confirm that the frequency of beta thalassaemia in western Nigeria is higher than previously thought and that many of the individuals studied may be silent carriers of the beta thalassaemia trait. Its presence may also have been masked by the high prevalence of alpha thalassaemia in the same environment. It is therefore important to consider beta thalassaemia trait as a differential diagnosis in patients who present with haemolytic anaemia in this environment.

Beta thalassaemiatriat in Western Nigeria

Background: Genes for thalassaemia; haemoglobin S; Glucose-6-phosphate dehydrogenase which confer resistance to malaria are found in high frequencies in Nigeria; 25of the population being carriers of the sickle cell trait while another 25are hemizygous for the G6PD gene. The frequency of alpha thalassaemia is equally high among Nigerians but there is little information on beta thalassaemia in this population. A recent study however suggest a high prevalence of beta thalassaemia in the same population; hence the need for this study. Methods: Haemoglobin A2 and HbF were determined in healthy adults who have haemoglobin A genotype by elution after electrophoresis and alkaline denaturation methods respectively. Results: The mean HbA2 among the subjects was 3.3(range 2.0-5.6) while the mean HbF was 2.6(range 0.4-8.8). Twenty-six percent of the subjects had HbA2 values higher than 3.9while 86had HbF values greater than 1; twenty-four percent had elevated HbA2 and HbF. The mean HbA2 value was 2.7among those with HbF 1; 3.6among those with HbF 1-3and 3.1among those with HbF 3. Conclusion: These findings confirm that the frequency of beta thalassaemia in western Nigeria is higher than previously thought and that many of the individuals studied may be silent carriers of the beta thalassaemia trait. Its presence may also have been masked by the high prevalence of alpha thalassaemia in the same environment. It is therefore important to consider beta thalassaemia trait as a differential diagnosis in patients who present with haemolytic anaemia in this environment

Trends in transfusion-transmitted viral infections from 2001 to 2006 in Ibadan, Nigeria.

OBJECTIVE: Screening of blood before transfusion is an effective strategy to reduce transfusion-transmitted viruses. However, reports on viral marker trends among the donor population are scarce. This study looked at trends in the seroprevalence of hepatitis B (HBV) and C (HCV) and human immunodeficiency virus (HIV). METHOD: This is a retrospective study among blood donors at a tertiary hospital in Nigeria. We used the blood bank records to calculate yearly seroprevalence rates for HBV, HCV and HIV per 100 donations from 2001 to 2006. RESULTS: A total of 33,682 prospective donors were screened, of which 13.2% were positive for HBsAg. The overall seroprevalence rates for HIV and HCV were 7.66% and 3.69%, respectively. HIV seroprevalence rose from 4.25% in 2001 to peak at 12.64% in 2003, before a steep drop to 6.35% in 2004 and a gradual decline to 5.70% in 2006 (p < 0.05). CONCLUSION: The seroprevalence rates for HIV and HBsAg fluctuated greatly during the study period while the seroprevalence of HCV was consistent. The screening kits used may be partly responsible for these fluctuations. Innovative programs for donor education, with the use of a formal questionnaire in donor selection, are recommended to ensure a safe donor population.

Hodgkin lymphoma in a child with sickle cell anemia.

There are reports of patients with sickle cell disease who developed hematological malignancies but the relationship between these malignancies and sickle cell disease (SCD) is not yet defined. The co-existence of a hematological malignancy with SCD poses certain challenges for the management of each condition. We describe a 7-year-old boy with sickle cell anemia who developed Hodgkin's lymphoma and the challenges of management. He presented with a 4-year history of bilateral neck swelling and a 2-month history of weight loss and high-grade fever. Histology of a lymph node biopsy was consistent with mixed cellularity Hodgkin's lymphoma. He was treated with five cycles of Cyclophosphamide, Vincristine, Procarbazine and Prednisolone (COPP) and had complete clinical response. Chemotherapy was associated with an increase in frequency of painful crises and complicated by septicaemia. Blood transfusion needs were minimal; apart from the transfusion preceding the first cycle of chemotherapy, there was no need for further transfusion. Myelosuppression was not a problem in the patient; he responded well to antibiotics during the two episodes of septicemia without the use of hemopoetic growth factor. Patients with sickle cell anaemia who develop Hodgkin's lymphoma can be successfully treated with chemotherapy along with supportive management for crises and infections.

When the inheritance of two heterozygote states become a diagnostic problem: misdiagnosis of the sickle cell trait.

BACKGROUND: The sickle cell trait is a benign asymptomatic condition that should not ordinarily be associated with clinical manifestations of a haemoglobinopathy. METHOD: This is a case control study of sickle cell trait patients who presented with symptomatology of a haemoglobinopathy. HbA2, HbF and HbS levels as well as the haematocrit and the peripheral film pictures of 10 symptomatic individuals (patients) with the sickle cell trait were compared with those of 20 asymptomatic individuals (controls) with the sickle cell trait. RESULTS: The mean HbA, of the cases was 4.9% compared to the mean of 2.2% for the controls (p < 0.0001). Nine of the patients and none of the controls had a raised HbA, (> 3.5%). The mean HbF of the patients was 5.6% with a range of 1.2-14.0% while the mean of the control was 2.0% and a range of 0. 7-8.4% (p = 0.006). Six (30%) of the controls had normal HbF level (<1%) while none of the patients had a normal HbF level. The mean haematocrit of the patients and controls were 0.33 and 0.37 respectively (p = 0.009). HbS level was below 40% in both groups. Pregnancy did not significantly affect the mean HbF, the mean HbF for pregnant and non-pregnant cases were 2.1% and 3.8% respectively. CONCLUSION: These findings suggest that the prevalence of the thalassaemia trait may be higher among Nigerians than previously thought with the clinical severity masked by the co-inheritance of other genes like thalassaemia that occur frequently in the same population.

When the Inheritance of two Heterozygote States become a Diagnostic Problem : Misdiagnosis of the Sickle Cell Trait

BACKGROUND : The sickle cell trait is a benign asymptomatic condition that should not ordinarily be associated with clinical manifestations of a haemoglobinopathy. METHOD : This is a case control study of sickle cell trait patients who presented with symptomatology of a haemoglobinopathy. HbA2; HbF and HbS levels as well as the haematocrit and the peripheral film pictures of 10 symptomatic individuals (patients) with the sickle cell trait were compared with those of 20 asymptomatic individuals (controls) with the sickle cell trait. RESULTS : the mean HbA2 of the cases was 4.9compared to the mean of 2.2 for the controls (p0.0001). Nine of the patients and none of the controls had a raised HbA2 ( 3.5). The mean HbF of the patients was 5.6 with a range of 1.2-14.0 while the mean of the control was 2.0 and a range of 0.7-8.4 (p=0.006). Six (30) of the controls had normal HbF level (1) while none of the patients had a normal HbF level. The mean haematocrit of the patients and controls were 0.33 and 0.37 respectively (p

Liver dysfunction in steady state sickle cell disease.

The liver is one of the organs involved in the multiorgan failure that occurs in sickle cell disease, the pathophysiology of liver disease in this condition is complex because of the interrelated multifactorial causes. Liver dysfunction was assessed in both paediatric and adult sickle cell disease patients in the steady state. The transaminases and alkaline phosphatase were analysed by automation while coagulation studies were done manually. The mean (range) of Alanine transaminase (ALT), Aspartate transaminase (AST) and alkaline phosphatase (ALP) were 23.0 (2-77) IU, 48.5 (15-120) IU, 227.5 (37-1200) IU respectively. ALT and AST levels were less than 100 IU in over 95% of the patients. The gender or age of the patients did not significantly affect the level of these three enzymes. There was close association between the liver size and elevation of the liver enzymes except for alkaline phosphatase (ALT=.017, AST=.009, ALP=.056). Twenty-five percent of the patients had normal enzymes while 13% had derangement of the three enzymes, 19%, 50% and 74% had abnormal ALT, AST and ALP respectively. Only 22% and 5% had deranged PT and APTT respectively. In conclusion minimal elevation of the tramsaminases which is not gender or age dependent were observed in steady state sickle cell disease, higher levels of alkaline phosphatase may be due to associated vasoocclussive crises involving the bones rather than a pathology of the liver.