Donor-type bone marrow aplasia following hematopoietic stem cell transplantation in a child with a novel SAMD9L variant.

Pathogenic variants in the genes SAMD9 (sterile a-motif domain containing protein - 9) and SAMD9L (SAMD9-like) cause bone marrow failure with characteristic syndromic features. We report a case of a previously healthy, 3-year-old boy with no dysmorphology, who presented with severe aplastic anemia and a novel variant in the SAMD9L gene. His father, elder brother and sister who harbored the same variant were completely healthy. In the absence of a matched unrelated donor, he underwent a stem cell transplant from his sister, a 10/10 match. Almost 2 years later he developed donor type aplasia and succumbed to an invasive fungal infection after a failed haplograft from his mother. This case highlights the pathogenicity of this previously undescribed germline variation of uncertain significance in the SAMD9L gene and the value of comprehensive genetic testing for inherited bone marrow failures even in the absence of a positive family history or characteristic congenital abnormalities.

Hirudin versus citrate as an anticoagulant for ROTEM platelet whole blood impedance aggregometry in thrombocytopenic patients.

Citrate is widely used as an anticoagulant for platelet function tests (PFTs). Due to an intrinsic inhibitory effect of citrate on platelet function, hirudin is used as an alternative. However, studies comparing the effect of these anticoagulants on rotational thromboelastometry (ROTEM) platelet whole blood impedance aggregometry in thrombocytopenic patients are scant. Cross-sectional study was done in 105 patients who entered the critical phase of Dengue hemorrhagic fever with plasma leakage and severe thrombocytopenia (<100 × 109/L). Samples were collected on two consecutive days and considered as a combined data set for analysis, out of which 200 have been included in the data analysis. Platelet count was used from routine full blood count. ROTEM platelet used TRAPTEM assay, which was performed with 3.2% sodium citrate and 525 ATU/ml hirudin anticoagulated blood. Means of all the TRAPTEM parameters were significantly higher in hirudin, compared to citrate samples (p < .05). Significantly higher overall platelet aggregation was observed in hirudinized samples with a significant mean difference (p < .05) compared to citrate in each quartile of platelet count. Higher platelet aggregation was observed with hirudin compared to citrate in ROTEM platelet whole blood impedance aggregometry in thrombocytopenic patients elaborating the importance of using hirudin anticoagulation in PFTs, particularly in patients with severe thrombocytopenia.

Citrate is the most commonly used anticoagulant for coagulation studies including rotational thromboelastometry (ROTEM).Hirudin is an alternative option to be used as an anticoagulant for PFTs because of the inhibitory effect of citrate on platelet function.One study (Nissen et al. (2020)) reported higher precision and platelet aggregation with hirudinized blood of healthy individuals, over citrate using ROTEM platelet.However, none of the studies were performed in patients in actual clinical context.We evaluated the potential benefit of using hirudin anticoagulated blood over citrate in thrombocytopenic patients due to Dengue hemorrhagic fever using ROTEM platelet.We observed higher platelet aggregation with hirudin compared to citrate suggesting the importance of using hirudin anticoagulation in PFTs, particularly in patients with severe thrombocytopenia.

The use of rotational thromboelastometry parameters in understanding the coagulopathy following hump-nosed viper (Hypnale spp) bites: a preliminary study.

BACKGROUND: Hump-nosed vipers (HNV; Hypnale spp) are one of the medically important venomous snakes in Sri Lanka and South-Western regions of India. The haemostatic dysfunction due to HNV bites is poorly characterized by standard diagnostic tests performed to identify coagulopathy. We aimed to determine the usefulness of rotational thromboelastometry (ROTEM) parameters compared to 20-minute whole blood clotting test (WBCT20) and prothrombin time (PT) in understanding the coagulopathy of HNV bites. METHODS: Twenty-three HNV snakebite patients in a prospective study of 127 consecutive snakebites were recruited. After recording details of the clinical presentation, PT/international normalized ratio (INR), WBCT20 and ROTEM delta were performed at presentation. RESULTS: In this preliminary study, none of the patients had clinically apparent bleeding. Coagulopathy was detected by either WBCT20, INR or ROTEM in 13 HNV patients. Eleven had a coagulopathy detectable by ROTEM (either abnormal EXTEM-CT, INTEM-CT or FIBTEM-MCF) but with negative WBCT20. Of them, only two had prolonged INR values. Two patients had positive WBCT20 but with normal ROTEM and INR values. The remaining 10 patients did not show any coagulopathy either by INR, ROTEM or WBCT20. CONCLUSION: In this preliminary study with small number of sample size, ROTEM parameters appeared to be more sensitive to subtle changes in coagulation compared to WBCT20. The clinical utility of detecting these changes and their usefulness in managing snakebite should be explored further in a larger study.

Assessment of iron overload in a cohort of Sri Lankan patients with transfusion dependent beta thalassaemia and its correlation with pathogenic variants in HBB, HFE, SLC40A1, and TFR2 genes.

BACKGROUND: Iron overload (IO) is a complication in transfusion dependent beta thalassaemia (TDT). Pathogenic variants in genes involving iron metabolism may confer increased risk of IO. The objective of this study was to determine the magnitude of the cardiac and hepatic IO and determine whether pathogenic variants in HFE, SLC40A1 and TFR2 genes increase the risk of IO in a cohort of TDT patients in Sri Lanka. MATERIALS AND METHODS: Fifty-seven (57) patients with TDT were recruited for this study. Serum ferritin was done once in 3 months for a period of one year in all. Those who were ≥ 8 years of age (40 patients) underwent T2* MRI of the liver and heart. Fifty-two (52) patients underwent next generation sequencing (NGS) to identify pathogenic variants in HBB, HFE, SLC40A1 and TFR2 genes. RESULTS: The median age of the patients of this cohort was 10 years. It comprised of 30 (52.6%) boys and 27 (47.4%) girls. The median level of serum ferritin was 2452 ng/dl. Hepatic IO was seen in 37 (92.5%) patients and cardiac IO was seen in 17 (42.5%) patients. There was no statistically significant correlation between serum ferritin and hepatic or cardiac IO. Thirty-two (61.5%), 18 (34.6%), 2 (3.8%) of patients were homozygotes, compound heterozygotes and heterozygotes for pathogenic variants in the HBB gene. Eight (15.4%) and 1 (1.9%) patients were heterozygotes for pathogenic and likely pathogenic variants of HFE genes respectively. There were no pathogenic variants for the TfR2 and SLC40A1 genes. The heterozygotes of the pathogenic variants of the HFE were not at increased risk of IO. CONCLUSIONS: Cardiac T2* MRI helps to detect cardiac IO in asymptomatic patients. It is important to perform hepatic and cardiac T2* MRI to detect IO in patients with TDT. There was no statistically significant correlation between pathogenic variants of HBB and HFE genes with hepatic and cardiac IO in this cohort of patients.

Rotational thromboelastometry in critical phase of dengue infection: Association with bleeding.

Background: The critical phase of dengue carries a high risk of bleeding. Associations of coagulation test parameters and the risk of bleeding in the critical phase is unclear. This study examines the association of rotational thromboelastometry (ROTEM delta and ROTEM platelet) with bleeding risk of patients with dengue in the critical phase. Methods: A total of 105 patients with confirmed dengue in the critical phase were recruited, with two subsequent prospective time point analyses of ROTEM parameters and platelet count within 24 and 48 hours from the onset of the critical phase. Conventional coagulation tests were performed only at the initial time point. Results: Twenty of 105 patients developed bleeding after onset of the critical phase. Within the first 24 hours of critical-phase onset, platelet count, coagulation tests, and ROTEM delta were unable to differentiate patients with bleeding manifestations from those without (P < .05). Area under the curve of thrombin receptor activating peptide-6 assay of ROTEM platelet (TRAPTEM) discriminated patients with bleeding manifestations from those without, at a cutoff value of <12.5 Ω*min at a sensitivity and specificity of 73.7%, and 60.2%. In patients who developed bleeding, the maximum lysis of extrinsic pathway of ROTEM was significantly lower in patients with severe bleeding compared to those with mild to moderate bleeding. (4.3 ± 3.4% vs 9.4 ± 7.5%; P = .01). Conclusion: An association with bleeding manifestations and TRAPTEM suggest a potential role for defective platelet aggregation in the pathogenesis of bleeding in the critical phase of dengue.

A report of haploidentical allogeneic haematopoietic stem cell transplantation for inherited bone marrow failure in Sri Lanka.

Abstract: Bone marrow failure (BMF) in children can be idiopathic (70-80%) or inherited. Haematopoietic stem cell transplantation (HSCT) is the only cure for both causes. Allogeneic HSCT requires a suitable donor. Many children will not have a HLA matched sibling or unrelated donor. A haploidentical donor is available for all children as eaazch parent will have at minimum a 50% HLA match. This report of a 7-year old girl with BMF treated with a haplo-HSCT, the first in Sri Lanka, highlights the importance of developing a haploidentical HSCT programme as a potential cure for a disease with a dismal outcome.

A Sri Lankan girl with a new genetic variant in the PKLR gene causing pyruvate kinase deficiency: a case report.

BACKGROUND: Erythrocyte pyruvate kinase is expressed under the control of the PKLR gene located on chromosome 1q21. Pyruvate kinase catalyzes the final steps of the glycolytic pathway and creates 50% of the red cell total adenosine triphosphate. Pyruvate kinase deficiency is the commonest glycolytic defect causing congenital non-spherocytic hemolytic anemia inherited in an autosomal recessive trait in which homozygotes and compound heterozygotes are common. Over 200 mutations have been described in patients with pyruvate kinase deficiency. This case report identifies a new pathogenic variant in PKLR gene detected in a patient with severe pyruvate kinase deficiency. CASE PRESENTATION: A Sri Lankan Sinhalese girl who developed neonatal anemia and jaundice within 24 hours of birth with mild hepatomegaly. She was from a nonconsanguineous marriage and had two siblings who had no hematological disorders. She had repeated admissions due to similar illnesses and at the age of 8 years was found to have pyruvate kinase deficiency associated with a novel homozygous pathogenic variant c.507+1delG in the PKLR gene. CONCLUSIONS: A novel genetic variant in PKLR gene, consistent with pyruvate kinase deficiency, was detected in a Sri Lankan girl. This genetic variant may be specific to the Asian population and requires further studies.

Comparison of rotational thromboelastometry parameters with 20-minute whole blood clotting test as a predictor of envenoming in Russell's viper bite patients.

BACKGROUND: Coagulopathy is an important and common systemic clinical syndrome caused by snake envenoming. The major clinical effect of Russell's viper (RV) envenoming is haematotoxicity. The 20-min whole blood clotting test (WBCT20) is the standard test for identification of envenoming in resource-limited settings. However, its reliability as a diagnostic test has been questioned. Rotational thromboelastometry (ROTEM) assays different phases of clot formation from initiation to fibrinolysis. Our objective was to compare parameters of ROTEM with WBCT20 and the international normalized ratio (INR) as predictors of envenoming in RV bite patients. METHODS: Fifty-three patents with RV bite presenting to Anuradhapura Hospital, Sri Lanka were recruited. Epidemiological and clinical data were obtained. Venous blood samples were collected at admission for ROTEM, INR and WBCT20. RESULTS: A total of 46 of 53 patients with RV bites received antivenom serum (AVS); 74% had a non-clottable WBCT20. All 46 had at least one abnormal ROTEM parameter and 93% had a prolonged EXTEM clotting time (EXTEM-CT). The sensitivity of a prolonged INR was only 55%. CONCLUSIONS: EXTEM-CT is a better predictor of envenoming and the need for AVS than WBCT20 in RV bites (p=0.02). It provides a numerical value that can be used post-AVS to objectively assess the response and decide on further treatment.

Hemostatic derangement in leptospirosis: A prospective cross-sectional study.

CONTEXT: Coagulation abnormalities have been observed among leptospirosis patients. However, coagulopathy in severe leptospirosis has not been further characterized. AIMS: The aim of this study was to evaluate conventional coagulation and rotational thromboelastometry (ROTEM®) parameters in leptospirosis patients. SETTINGS AND DESIGN: This prospective cross-sectional comparative study included patients presenting to a tertiary hospital in Sri Lanka with clinically and serologically confirmed leptospirosis (14 severe and 6 mild), dengue (6), sepsis (5), and 6 healthy individuals. SUBJECTS AND METHODS: Blood samples were collected between the 3rd and 10th days of illness for prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), fibrinogen, lupus anticoagulant, factors VII and VIII, D-dimer, platelet count, and ROTEM. STATISTICAL ANALYSIS USED: ANOVA post hoc comparison using Bonferroni was applied to compare groups. RESULTS: PT and aPTT were prolonged in leptospirosis patients and were corrected with normal plasma. TT was not significantly prolonged in leptospirosis. Fibrinogen was significantly elevated in severe leptospirosis (P = 0.001) and sepsis (P = 0.001) compared with healthy controls and dengue. Thirty percent of leptospirosis patients had thrombocytopenia (17% in mild and 36% in severe). No significant differences were seen in inTEM clotting time (CT) and exTEM CT in leptospirosis when compared to the other three groups. inTEM clot formation time (CFT) and exTEM CFT in dengue were significantly higher compared to severe (P = 0.001) and mild (P = 0.005) leptospirosis. inTEM maximum clot firmness (MCF) (P = 0.001) and exTEM MCF (P = 0.001) were significantly lower in dengue than in leptospirosis. Only one patient with leptospirosis had bleeding manifestations. CONCLUSIONS: Abnormalities in conventional coagulation parameters occur in leptospirosis. However, ROTEM parameters in leptospirosis are not significantly altered.

Pharmacokinetic, pharmacodynamic, and pharmacogenetic assays to monitor clopidogrel therapy.

Clopidogrel is the most common and widely used antiplatelet agent for patients with coronary artery disease following confirmation by electrocardiographic studies. The nonresponsiveness of patients to clopidogrel and the possibility of testing for clopidogrel resistance by platelet function assays (PFA) are contentious issues. Light transmission aggregometry (LTA) is considered as the gold standard test among all PFA. In this review, the most commonly used PFA used for monitoring the effect of clopidogrel, LTA, vasodilator-stimulated phosphoprotein assay phosphorylation, rotational thromboelastometry (ROTEM) delta and ROTEM platelet, thromboelastography, PFA-100, VerifyNow P2Y12 assay, Multiplate analyzer, Plateletworks assay and pharmacogenetic studies, are comparatively discussed including their principles of action, advantages, and disadvantages. VerifyNow P2Y12 assay can be accepted as the ideal point of care test out of the discussed assays. However, modified assays are required which could overcome the limitations associated with currently available assays.

Immunophenotypic characterization of acute lymphoblastic leukemia in a flowcytometry reference centre in Sri Lanka.

BACKGROUND: Acute lymphoblastic leukemia (ALL), is a biologically heterogeneous disease where diagnosis, treatment and prognosis is heavily dependent on the correct characterization of the immunophenotype of each case. OBJECTIVES: To describe the immunophenotypic and laboratory features of a cohort of Sri Lankan children and adults with ALL and to compare them with those reported in other series. METHODS: Records of 229 patients who were suspected of having acute leukaemia and referred for flow cytometry to the Asiri Hospital Sri Lanka, between August 2009 and October 2013 were reviewed. Referrals were from across the country including the National Cancer Institute. RESULTS: Sixty seven percent were children below 12 years of age. 80% had B-lymphoblastic leukaemia (B-ALL), 20% T- lymphoblastic leukaemia (T-ALL). In children, the peak age of diagnosis was between 2-6 years in B-ALL (61%) and 3-6 years (43.7%) in T-ALL. Incidence was commoner in males in all age groups and subtypes except in the adult B ALL group where the incidence was equal. Ninety three percent of paediatric B-ALL and 67% adult B-ALL were CD10 positive common ALL. In T-ALL cytoplasmic expression of CD3 was 100%. nTdT was the most commonly expressed immature marker, in B-ALL - 91% and in T-ALL- 69%. At least one myeloid antigen was present in 34% of B-ALL cases and 60% of T-ALL cases. CONCLUSIONS: This study represents the first immunophenotype based description of ALL in Sri Lanka. Age, sex distribution, ALL subtypes and the immunophenotypic profile of each subtype mirrored those of previous studies.

Transient elevation of serum ferritin in a Sri Lankan with homozygosity for H63D mutation in the HFE gene: a case report.

INTRODUCTION: Hereditary hemochromatosis is an inherited disorder of iron metabolism, characterized by excessive iron deposition in major organs of the body, leading to multi-organ dysfunction. It is a genetically heterogeneous disease caused by mutations in one or more different genes, the most common being mutations in the HFE gene. HFE hereditary hemochromatosis is mostly found in Europeans and is almost always a result of two mutations: C282Y and H63D. The H63D mutation is not as penetrant as the C282Y mutation, but there are rare reported cases of hereditary hemochromatosis with homozygous H63D genotype. While the C282Y mutation is primarily confined to persons of Northern European origin, the H63D mutation is spread worldwide. Other types of hereditary hemochromatosis are rare and broadly defined as non-HFE hereditary hemochromatosis and include mutations in the hemojuvelin gene, hepcidin (HAMP gene), transferrin receptor 2 gene, and ferroportin gene. Hereditary hemochromatosis is commonly found in populations of European origin; in contrast, it is rare and less well understood in Asia. It can be masked by the presence of concurrent iron deficiency or secondary iron overload in thalassemias. CASE PRESENTATION: We report the case of a 42-year-old Sri Lankan man investigated for fatigue during a brief upper respiratory tract infection and found to have high liver transaminases and high serum ferritin, which persisted even after complete resolution of the infection. Homozygosity for H63D mutation in the HFE gene was detected. Liver enzymes, serum ferritin, and transferrin saturation normalized following venesections. CONCLUSION: This case adds to the literature on the importance of being vigilant and investigating patients suspected for iron overload, including genetic studies for hereditary hemochromatosis, even though it is a rare clinical entity in Asians.

Polyneuropathy, organomegaly, endocrinopathy, monoclonal band, and skin (POEMS) changes syndrome presenting with a pseudosensory level: a case report.

INTRODUCTION: Polyneuropathy is a key feature of polyneuropathy, organomegaly, endocrinopathy, monoclonal band, and skin changes syndrome, which is a paraneoplastic manifestation of an underlying lymphoproliferative neoplasm. We report the first case of polyneuropathy, organomegaly, endocrinopathy, monoclonal band, and skin changes syndrome presenting with a pseudosensory level. CASE PRESENTATION: A 59-year-old Tamil woman with long-standing diabetes mellitus and hypertension developed painless, progressive inguinal lymphadenopathy. A contrast-enhanced computed tomography scan showed mild hepatomegaly and intra-abdominal lymphadenopathy. A histological examination of an enlarged inguinal lymph node showed features of a plasma cell-type Castleman disease. She was treated with rituximab. Six months later, she developed gradually ascending numbness and weakness of both lower limbs. On examination, she had flaccid paraparesis (power 3/5) with a sensory level to pinprick at thoracic level 9. Joint position sense was preserved. Her cranial nerves and upper limbs were neurologically normal. Nerve conduction studies confirmed peripheral neuropathy with conduction slowing and a magnetic resonance imaging of her spine did not show cord or root compression. Serum protein electrophoresis showed a monoclonal band. A bone marrow biopsy showed a hypercellular marrow with 30% plasma cells. A repeat contrast-enhanced computed tomography scan showed sclerotic bony lesions involving multiple vertebrae in addition to mild hepatomegaly and intra-abdominal lymphadenopathy. Polyneuropathy, organomegaly, endocrinopathy, monoclonal band, and skin changes syndrome was diagnosed and she was treated with intravenously administered pulse therapy of dexamethasone and cyclophosphamide. After three cycles of treatment, she regained normal muscle power and sensation. CONCLUSIONS: Polyneuropathy in polyneuropathy, organomegaly, endocrinopathy, monoclonal band, and skin changes syndrome can present as a pseudosensory level.

Advances in hematopoietic stem cell transplantation in the Asia-Pacific region: the second report from APBMT 2005-2015.

Between 2005 and 2015, 138,165 hematopoietic stem cell transplantation (HSCT) were reported in 18 countries/regions in the Asia-Pacific region. In this report, we describe current trends in HSCT throughout the Asia-Pacific region and differences among nations in this region and various global registries. Since 2008, more than 10,000 HSCTs have been recorded each year by the Asia-Pacific Blood and Marrow Transplantation Group Data Center. Between 2005 and 2015, the greatest increase in the number of HSCTs was observed in Vietnam. Allogeneic HSCT was performed more frequently than autologous HSCT, and a majority of cases involved related donors. Regarding allogeneic HSCT, the use of cord blood has remained steady, especially in Japan, and the number of cases involving related HLA non-identical donors has increased rapidly, particularly in China. The incidence of hemoglobinopathy, a main indication for allogeneic HSCT in India, China, Iran, and Pakistan, increased nearly six-fold over the last decade. Among the 18 participating countries/regions, the transplant rate per population varied widely according to the absolute number of HSCTs and the national/regional population size. We believe that this report will not only benefit the AP region but will also provide information about HSCT to other regions worldwide.

Can findings on peripheral blood smear differentiate leptospirosis from other infections? A preliminary comparative study.

Background: Blood smear changes have never been investigated as a potential tool to aid in the diagnosis of leptospirosis. Methods: Blood smears prepared from patients with leptospirosis, dengue and sepsis within the first 5 days of illness were reported by haematologists blinded to the diagnosis. Results: A total of 20, 28 and 22 patients with leptospirosis, dengue and sepsis, respectively, were analysed. Neutrophil leucocytosis, toxic changes in neutrophils, left shift, reactive lymphocytes, target cells and thrombocytopaenia were seen in 60%, 70%, 40%, 70%, 50% and 65% of the leptospirosis patients, respectively. The combination of reactive lymphocytes with toxic neutrophils or neutrophil leucocytosis was highly suggestive of leptospirosis. Conclusions: Peripheral blood smear findings may be helpful in differentiating leptospirosis from other common acute febrile illnesses.

The role of haematological indices in predicting early iron deficiency among pregnant women in an urban area of Sri Lanka.

BACKGROUND: Early detection and treatment of iron deficiency during pregnancy is crucial for optimum pregnancy outcomes. Anaemia is a late indictor of iron deficiency measured as Hb < 11 g/dL, and is widely used as a proxy for iron deficiency. We aimed to evaluate the role of red cell indices as a screening tool for early detection of iron deficiency among pregnant women in an urban area of Sri Lanka. METHOD: A cross-sectional study was conducted among 110 apparently healthy pregnant women ≤12 weeks of gestation attending antenatal clinics in Colombo, Sri Lanka. Women already on nutritional supplements were excluded. Full blood count, serum ferritin (SF) and high sensitive C-reactive protein (hs-CRP) assessments were performed. The women with evidence of inflammation as indicated by hs-CRP > 10 mg/L were excluded (N = 20) from data analysis. Anaemia (Hb < 11 g/dL) and iron deficiency (SF < 30 µg/L) were defined according to WHO guidelines. Receiver operating characteristics curves were used to derive red blood cell indices that showed the optimal cut-offs in detecting early iron deficiency. RESULTS: Of the 90 women, 63 (70.0%) were iron deficient (SF < 30 µg/L), out of whom 10 (15.9%) were identified as having iron deficiency anaemia (Hb < 11 g/dL). A high sensitivity (> 70%) in the prediction of iron deficiency was obtained for the optimal cut-off values of Hb < 12.2 g/dL, MCV < 83.2 fl, MCH < 26.9 pg and MCHC 33.2 g/dL while maintaining a specificity > 40%. CONCLUSION: Iron deficiency can be predicted in early stages using Hb and red cell indices, which is much less expensive. This could be a useful method in areas with limited resources and a high prevalence of iron deficiency.

ATG vs thiotepa with busulfan and cyclophosphamide in matched-related bone marrow transplantation for thalassemia.

Matched-related bone marrow transplantation (BMT) may cure >80% of low-risk children with severe thalassemia (ST). Very long-term follow-up studies have shown how the standard busulfan-cyclophosphamide (BuCy) regimen may be associated with normalization of health-related quality of life, no second malignancies in the absence of chronic graft-versus-host disease, and fertility preservation in many patients. However, because BuCy may be associated with high rejection rates, some centers incorporate thiotepa (Tt) in busulfan- or treosulfan-based regimens, a combination that may increase the risk of permanent infertility. This study retrospectively compares matched-related BMT outcomes in 2 groups of low-risk ST patients conditioned with either Tt or anti-thymocyte globulin (ATG) in addition to BuCy. A total of 81 consecutive first BMTs were performed in 5 collaborating startup BMT centers in the Indian subcontinent between January 2009 and January 2016; 30 patients were transplanted after conditioning with Tt-BuCy between January 2009 and July 2013, whereas between August 2013 and January 2016, 51 patients received ATG-BuCy. All patients were <15 years and had no hepatomegaly (liver ≤2 cm from costal margin). Actuarial overall survival in the Tt-BuCy and ATG-BuCy groups was 87% and 94% and thalassemia-free survival was 80% and 85% at a median follow-up of 37 and 17 months, respectively, with no significant differences by log-rank statistics. Substituting Tt with ATG in the standard BuCy context seems safe and effective and may decrease transplant-related mortality. Higher fertility rates are expected for patients who received ATG-BuCy.

Rituximab in the treatment of autoimmune haemolytic anaemia.

Rituximab is a B-cell depleting monoclonal antibody that is gaining popularity as an effective therapy for many autoimmune cytopenias. This article systematically evaluates its therapeutic efficacy in the treatment of different types of autoimmune haemolytic anaemia. We conclude that there is sufficient evidence to recommend it as a second line therapy for warm autoimmune haemolytic anaemia (wAIHA) either as monotherapy or combined therapy. Evidence from a single randomized controlled trial suggests that it may also be more efficacious as first line therapy in combination with steroids than steroids alone. A fewer number of studies have assessed its role in cold autoimmune haemolytic anaemia (cAIHA) and cold agglutinin disease (CAD) with success rates varying from 45-66%. In the absence of alternative definitive therapy, rituximab should be considered for patients with symptomatic CAD and significant haemolysis. Case reports of its efficacy in mixed autoimmune haemolytic anaemias are available but evidence from case series or larger cohorts are nonexistent.

Klippel-Trenaunay syndrome presenting with acanthocytosis and splenic and retroperitoneal lymphangioma: a case report.

INTRODUCTION: Klippel-Trenaunay syndrome is a rare congenital mesodermal abnormality characterized by bone and soft tissue hypertrophy, extensive hemangioma and venous abnormalities. We report the case of a patient with two additional rare clinical manifestations in the background of Klippel-Trenaunay syndrome, namely, acanthocytosis and splenic and retroperitoneal lymphangioma. CASE PRESENTATION: A 24-year-old Sri Lankan man from North Central Province in Sri Lanka presented to our general medical unit with symptomatic anaemia. He had been diagnosed with Klippel-Trenaunay syndrome at the age of six years, with hemihypertrophy of his right lower limb and strawberry naevi over both lower limbs. His blood film results were positive for acanthocytes, which accounted for more than 20% of the red blood cell population. He was also found to have extensive splenic lymphangiomas and a large retroperitoneal lymphangioma encasing the mesentric vessels in the right para-aortic region. An extensive battery of tests to identify a secondary cause for the acanthocytosis failed to show any positive results. CONCLUSIONS: Retroperitoneal lymphangioma has been reported in association with Klippel-Trenaunay syndrome once before, but an association with acanthocytosis has never been reported. Given the rarity of all three conditions this is not surprising. The cause of acanthocytosis in this setting is currently unresolved. It is plausible that this may be a primary association with Klippel-Trenaunay syndrome, as an alternative aetiology was not found.