Clinical and molecular findings of chronic granulomatous disease in Oman: family studies.

Chronic granulomatous disease (CGD), a rare inherited disorder of the innate immune system, results from mutations in any one of the five genes encoding the subunits of the nicotinamide adenine dinucleotide phosphate-oxidase (NADPH) oxidase enzyme, and is characterized by recurrent life-threatening bacterial and fungal infections. Molecular analysis of 14 Omani CGD patients from 10 families, diagnosed to have CGD on clinical (recurrent infections) and biochemical grounds (positive for both the nitroblue tetrazolium (NBT) test and the dihydrorhodamine (DHR-1,2,3 assay), revealed that only one patient had X-linked CGD, with a large deletion involving both the gp91-phox gene (CYBB) and the McLeod gene (XK). The remaining 13 patients were all homozygotes from a previously described c.579G>A (p.Trp193X) mutation in the NCF1 gene on chromosome 7, responsible for autosomal recessive CGD (AR-CGD). Although X-linked CGD is the most common type of CGD disorder in most population groups, AR-CGD is the most prevalent type in Oman.

Clinical and Laboratory Features of Sickle Cell Disease S/D Punjab: Impact of HbF and Hydroxyurea.

Background: Sickle cell disease (SCD) is a major public health issue worldwide with high morbidity and mortality. SCD SD Punjab is the third most common genotype of SCD in Oman and is associated with several serious complications. The aim of the study is to establish the clinical and laboratory features of SCD patients with SD double heterozygotes and study the impact of haemoglobin F, hydroxyurea, and other modulators on the disease severity. Methods: We analysed the electronic medical records of 52 consecutive SCD patients who were diagnosed as double heterozygote SD Punjab between 2006 and 2022. The study was approved by the local medical research and ethics committee. The data captured included SCD-related complications and current clinical and laboratory indices. Data from other studies on other SCD genotypes were used as historical controls. Results: 52 patients (31 males, 21 females) who formed this cohort had a median age of 32 years with an interquartile range (IQR) of 21-39.8 years. 37(71.2%) had <3 VOC per year, whereas 15 (28.8%) patients had ≥3 vasooclusive (VOC) episodes per year. SCD-related complications included Acute Chest Syndrome (ACS) (48%), Gall stones (26.9%), Avascular necrosis (AVN) (28.8%), Stroke (13.5%) and splenic sequestration (7.7%), whereas 5 (9.6%) patients of this cohort died. Surgical and Autosplenectomy were seen in 18 (34.6%). These findings were similar to other SCD genotypes in this community. 19 (57.6%) were taking Hydroxyurea (HU) amongst the 33 patients who were prescribed HU. Haematological parameters showed a median (IQR) Hb (g/dl), MCV (fl), Retic count (%), WBC count(×109/L) and Platelet count(×109/L) of 9.7 (8.5-11.3), 74.9 (68.4-79.8), 4 (3.2-5.7), 9.9 (8.1-12.6) and 309 (239-428) respectively. The haemoglobin electrophoresis showed an elevated HbF, whereas serum bilirubin and LDH were elevated amongst the biochemical parameters. The use of hydroxyurea showed no impact on VOC, ACS, AVN, Stroke or mortality. Conclusion: SD Punjab is the third most common SCD genotype in Oman and was associated with recurrent VOC, ACS, AVN, and gall stones comparable to other SCD genotypes. Patients with > 3 VOC/year had significantly increased incidence of Stroke, AVN, and gallstones. However, HU was not associated with improved prognosis and better survival in this cohort of patients.

Correlation of Transient Elastography with Liver Iron Concentration and Serum Ferritin Levels in Patients with Transfusion-Dependent Thalassemia Major from Oman.

Aims: In a longitudinal study, we aimed to assess the correlation between ultrasound transient elastography (TE), serum ferritin (SF), liver iron content (LIC) by magnetic resonance imaging (MRI) T2* along with the fibrosis-4 (FIB-4) score as a screening tool to detect significant liver fibrosis among chronically transfusion-dependent beta-thalassemia (TDT) patients. Methods: The study was conducted at a tertiary health center treating TDT patients. Transient elastography was performed within 3 months of Liver MRI T2* examinations at the radiology department over a median of one-year duration. T-test for independent data or Mann-Whitney U test was used to analyze group differences. Spearman correlation with linear regression analysis was used to evaluate the correlation between TE liver stiffness measurements, Liver MRI T2* values, and SF levels. Results: In this study on 91 patients, the median age (IQR) of the subjects was 33 (9) years, and the median (IQR) body mass index was 23.8 (6.1) kg/m2. Median (IQR) TE by fibroscan, MRI T2*(3T), Liver iron concentration (LIC) by MRI Liver T2*, and SF levels were 6.38 (2.6) kPa, 32.4 (18) milliseconds, 7(9) g/dry wt., and 1881 (2969) ng/mL, respectively. TE measurements correlated with LIC g/dry wt. (rS =0.39, p=0.0001) and with SF level (rS =0.43, P=0.001) but not with MRI T2* values (rS =-0.24; P=0.98). Conclusion: In TDT patients, liver stiffness measured as TE decreased significantly with improved iron overload measured as LIC by MRI and SF levels. However, there was no correlation of TE with the fibrosis-4 (FIB-4) score.

The Effects of Terrain Properties Upon the Small Crater Population Distribution at Giordano Bruno: Implications for Lunar Chronology.

The distribution of impact craters on the ejecta of Giordano Bruno, a recent (<10 Ma) 22-km diameter crater within the lunar highlands, exhibits substantial variations. We surveyed craters D ≥ 10 m across a 1,323 km2 area of Giordano Bruno's ejecta and compared the distribution of craters with variations in thermophysical properties derived from the Lunar Reconnaissance Orbiter Diviner instrument. We used Diviner-derived rock abundance and nighttime regolith temperatures along with thermal model-predicted surface temperatures for a diversity of terrains to identify and isolate areas of the ejecta based on thermophysical properties such as bulk density and thermal conductivity. We found that thermophysical properties of the ejecta vary considerably both laterally and vertically, and consistently differ from typical regolith, indicating the presence of higher thermal inertia materials. Crater-size frequencies are significantly lower in areas with terrain properties exhibiting higher: rock abundance, nighttime temperatures, and/or modeled thermal inertia. This discrepancy in crater distribution increases for craters smaller than ∼25 m. These thermophysical variations indicate changes in the mechanical properties of the target materials. We suggest that these variations-specifically, terrain-dependent crater scaling variations and impactor-scale heterogeneities in material properties such as the presence or absence of large boulders-may influence crater diameters or inhibit crater production altogether in Giordano Bruno's ejecta; furthermore, these factors are size-dependent.

Safety Warning for ChAdOx1 nCov-19 Vaccine in Patients with Sickle Cell Disease.

Vaccines against acute respiratory syndrome Coronavirus 2(SARS-CoV2) are critical weapons to control the spread of the deadly Coronavirus 2019(COVId-19) virus worldwide. Although these vaccines are generally safe, their widespread use has produced reports of rare complications, including vaccine-induced immune thrombotic thrombocytopenia (VIITT), particularly in connection with ChAdOx1 nCov-19. We have identified three cases of sickle cell disease (SCD) experiencing a severe vaso-occlusive crisis (VOC) shortly after the vaccine. Despite being stable for a long time, they had fever with tachycardia, along with a significant rise in WBC, liver enzymes, particularly alkaline phosphate, with a remarkable drop in hemoglobin, and platelets and one of them had probably a fatal TTP like syndrome. Given these findings, physicians and patients should exercise caution when taking this type of vaccine and be aware of these safety concerns.

Impact of COVID-19 on vasooclusive crisis in patients with sickle cell anaemia.

OBJECTIVES: The study aimed to assess COVID-19 impact on the morbidity and mortality of vasooclusive crisis (VOC) in sickle cell anaemia (SCA) patients. METHODS: A prospective cohort study of 100 SCA patients; 50 with COVID-19 (COVID group) and 50 without (non-COVID group). All patients signed written informed consent. RESULTS: The COVID group had a significantly higher VOC episode median per year; 3 (IQR,1-6) vs 2 (IQR,2-12) (P < 0.05). The need for hospitalisation was similar in both groups. The non-COVID group had more history of culture-proven infection (P = 0.05). The COVID-group had more osteonecrosis (P < 0.05), splenic sequestration, splenomegaly and hepatic crisis (P = 0.05, 0.006, 0.02; respectively) and significantly higher (P < 0.05) symptoms of fever, cough, fatigue, abdominal pain and anosmia. Mean haemoglobin, lymphocyte subset, platelets, and reticulocytes were reduced in both groups, while lactate dehydrogenase and ferritin levels were significantly elevated. In the COVID group, the rise in white blood cell count, reticulocyte percentage, platelets and ferritin was subdued (P < 0.05). Two patients in the COVID group and 3 in the non-COVID group died; there was no statistically significant difference in mortality. CONCLUSIONS: Although COVID-19 may have triggered the onset of VOC, it did not significantly influence VOC-related morbidity or mortality in this SCA cohort.

Acquired pericentric inversion of chromosome 9 in acute myeloid leukemia.

Pericentric inversion of chromosome 9 involving the qh region is relatively common as a constitutional genetic aberration without any apparent phenotypic consequences. However, it has not been established as an acquired abnormality in cancer. Among the three patients reported so far in the literature with acquired inv(9), only one had acute myeloid leukemia (AML). Here we describe an unique case where both chromosomes 9 presented with an acquired pericentric inversion with breakpoints at 9p13 and 9q12 respectively, in a AML patient with aberrant CD7 and CD9 positivity. Additionally, one der(9) also showed short arm deletion at 9p21 to the centromeric region and including the p16 gene. The constitutional karyotype was normal. This is probably the first report describing an acquired inv(9) involving both chromosomes 9 in AML. The possible significance of this inversion is discussed.

The Use of HPLC as a Tool for Neonatal Cord Blood Screening of haemoglobinopathy: A Validation Study.

BACKGROUND: Newborn cord blood screening identifies infants with underlying haemoglobinopathies before they develop the characteristic symptoms or sequelae. AIMS: This study was performed to validate the interpretation high-performance chromatography (HPLC) along with complete blood count (CBC) results as a tool for universal neonatal screening of hemoglobin disorders in Oman. METHODS: HPLC and CBC data on subjects who participated in the National Neonatal screening program at birth were obtained from archival records. The results recorded at birth were compared with a second study performed on the same subjects, after approval from the local medical research and ethics committee. RESULTS: Only 290 subjects from amongst the original cohort of 3740 newborns could be recalled between April 2010 to March 2011, to repeat HPLC and CBC, as well as perform confirmatory DNA studies, wherever necessary. All these subjects had been documented to show an initial abnormal result. 31 cases who had no HbA at birth on HPLC were confirmed as either homozygous ß-thalassaemia major (n=5 subjects) or homozygous sickle cell anemia (n=26 subjects) by appropriate DNA analysis. Additionally, amongst 151 subjects, 72 subjects were studied in the initial study by Hb Bart's quantitation using the alpha thalassaemia short program at birth. In this cohort, 42 subjects with Hb Bart's >1% at birth could be confirmed as having either deletional or non-deletional thalassaemia by GAP PCR studies. No case of HbH was detected in this cohort. Further, carrier status for structural hemoglobin variants (HbS, HbC, HbD, HbE) (n=67) and beta thalassaemia allele with low HbA at birth (n=29 out of 41) were confirmed by relevant molecular studies. CONCLUSIONS: The study validated the earlier observation by 100% concordance with the results of CBC and HPLC. Presence of Hb Bart's at birth does not always mean the presence of alpha thalassemia, as subjects with Hb Bart's below 1% by quantitation, were shown to be normal by molecular studies.

Hematopoietic stem cell transplantation in Oman.

Hematopoietic SCT (HSCT) is an integral part of the management of patients with hematologic disorders. The Sultanate of Oman, with a population of 2.3 million, has an HSCT program based in the Sultan Qaboos University (SQU) hospital. Initiated in 1995, this two-bed unit continues to be the only program in the country. Between June 1995 and August 2006, a total of 128 patients underwent HSCT in this center, averaging about 10-12 transplants per year. The median age of these patients was 11 years (2 months to 45 years). Hematologic malignancies (49%) and inherited disorders (42%) constituted the major transplant indications, whereas BM failure accounted for the remaining. The majority of transplants carried out so far have been HLA-matched sibling-donor allogeneic HSCTs. Among the inherited disorders, homozygous beta-thalassemia and primary immunodeficiency are important transplant indications in this center. The approximate cost of an uncomplicated transplant in this center is US$50,000. The success of this program has now led to the initiation of a new and larger HSCT complex to provide the opportunity for more patients to benefit from this treatment modality within the country.

Recombinant factor XIII A-subunit in a patient with factor XIII deficiency and recurrent pregnancy loss.

Essentials Inherited factor XIII deficiency is a very rare bleeding disorder. We used recombinant factor XIII-A in a pregnant patient with factor XIII-A subunit deficiency. The patient had a successful pregnancy outcome with no pregnancy related complications. The dose of recombinant factor XIII-A was minimized by using frequent trough level monitoring. SUMMARY: Inherited factor XIII deficiency is a very rare bleeding disorder, and is one of the causes of recurrent pregnancy loss. The use of plasma-derived FXIII to improve pregnancy outcomes has been reported. We report a 26-year-old woman with FXIII A-subunit (FXIII-A) deficiency who was treated with recombinant FXIII-A and had a successful pregnancy outcome with no pregnancy-related complications. Our case illustrates that the dose of recombinant FXIII-A can be minimized and adjusted on the basis of frequent trough level monitoring.

Bleeding score in Type 1 von Willebrand disease patients using the ISTH-BAT questionnaire.

BACKGROUND: Bleeding assessment tools have evolved in the last decade to standardize the assessment of the severity of bleeding symptom in a consistent way. In 2010, the International Society on Thrombosis and Hemostasis-Bleeding Assessment Tool (ISTH-BAT) was developed and validated. AIMS: Our aim was to administer ISTH-BAT questionnaire to the Omani patients with type 1 VWD and obtain the bleeding score (BS). We also studied the severity of their bleeding symptoms and correlated it with the BS as well as with the laboratory parameters. METHODS: Forty-eight type I VWD index cases and 52 normal subjects were interviewed and the ISTH-BAT questionnaire administered. The BS was calculated based on a history of bleeding symptoms from 12 different sites according to the standard ISTH-BAT questionnaire. Laboratory parameters were obtained from patient's medical records. RESULTS: The mean age of this cohort was 27 years (range, 6-49) with 60% being females. The median time to administer this questionnaire was 10 minutes with an interquartile range (IQR) from 8 to 17 minutes. Overall, the median BS was 7 (IQR; 2,11) although individual scores ranged between 0 and 36. The BS was negatively correlated with VWF: Ag, VWF: RCo, and VWF: CB and the Spearman's correlation coefficient "rho" was, respectively, -0.15, -0.08, and -0.22. CONCLUSION: The ISTH-BAT BS is designed to reflect the severity of bleeding. Our results demonstrate the inherent variability of this bleeding pattern. We also found that the ISTH-BAT BS significantly correlated with VWF: Ag and VWF: CB.

Bleeding score in type 1 von Willebrand disease patients using the condensed MCMDM-1 vWD validated questionnaire.

BACKGROUND: Assessment of the severity of bleeding symptom has led to the evolution of bleeding assessment tools which are now validated. AIMS: To administer the condensed molecular and clinical markers for the diagnosis and management of type 1 von Willebrand disease VWD (MCMDM-1 vWD) questionnaire to the Omani type 1 vWD patients and correlate it with the laboratory parameters. METHODS: Patients and controls were personally interviewed and the condensed MCMDM-1 vWD questionnaire administered by a single investigator. Bleeding score (BS) was calculated, based on the presence or absence of the bleeding symptoms according to a standard validated questionnaire in both the patients and the controls. RESULTS: The median age of the patient cohort was 27 (range, 7-49) years with 60.87% of females. The median time to administer condensed MCMDM-1 BS questionnaire was 11 minutes (interquartile range-IQR;7,16). Overall, bleeding from the oral cavity was the most predominant symptom (63%). The median BS was 5 (IQR;1,8) although individual scores ranged between 0 and 29. However, there was no statistically significant difference in BS between genders (males: median 4; IQR 1,6 and females: median 5, IQR 1,10) (P > .05, Kruskal-Wallis test) The Spearman's correlation value of BS was weak with FVIII:C levels and von Willebrand Ristocetin co-factor activity; very weak with von Willebrand Antigen level, and moderate with vonWillebrand Collagen Binding activity being -0.29, -0.28, -0.14 and -0.43, respectively. CONCLUSION: The BS reflects the severity of bleeding among the vWD patients. Although the BS was abnormal, it did not correlate significantly with the surrogate laboratory parameters [P > .05].

Follicular dendritic cell hyperplasia in plasma cell variant of Castleman's disease with interfollicular Hodgkin's disease.

We report a case of a multicentric plasma cell (PC) variant of Castleman's disease (CD) in association with interfollicular type of classic Hodgkin's disease (HD), both diseases identified in the same lymph node. The histologic features of CD were the classic ones, with hyperplastic and atrophic follicles, some with prominent mantle zones, hyalinzed vessels, and a very rich polyclonal proliferation of PCs in the interfollicular region. The presence of LCA-negative, but CD30- and CD15-positive typical and atypical Reed-Sternberg (RS) cells in the interfollicular region confirmed the presence of HD. In addition, many of the RS cells stained positive for EBV. CD35- and CD21-positive follicular dendritic cell (FDC) hyperplasia was a striking feature, a finding that has not been well documented in the PC variant of CD.

Increased Vasoocclusive Crises in "O" Blood Group Sickle Cell Disease Patients: Association with Underlying Thrombospondin Levels.

OBJECTIVES: To explore the incidence of vaso-occlusive crisis (VOC) in Blood Group "O" sickle cell disease (SCD) patients, and correlate it with the blood group and thrombospondin (TSP) levels. METHODS: In 89 consecutive SCD patients, blood samples were obtained for von Williebrand factor (vWF:Ag) antigen, collagen binding activity (CBA), ristocetin binding activity (RCo), blood group typing, C-reactive protein (CRP), high performance liquid chromatography (HPLC), Serum TSP 1 and TSP 2 levels, complete blood counts (CBC), lactic dehydrogenase (LDH) levels, liver function (LFT) and renal function tests (RFT) during VOC episodes and in steady state conditions. RESULTS: In steady state SCD patients (n=72), "O" blood group patients (n=37) showed a significantly higher median serum TSP 1 and TSP 2 levels as compared to non-O blood group patients [n=35] [p <0.05, Mann-Whitney test]; with an inverse relation between vWF:Ag, Factor VIII:C and TSP levels. Furthermore, the serum TSP 1 and TSP 2 levels were significantly higher in patients presenting with acute VOC [n=17], as well as in those with repeated VOC's (group 1, n=16), especially amongst blood group "O" patients [p, <0.05, Mann-Whitney test]. CONCLUSIONS: The study demonstrates an inverse relation between TSP and vWF levels, in blood group "O" SCD patients, with an upregulation of the TSP levels. Expectedly, during active VOC crisis, the TSP 1 and TSP 2 levels were significantly elevated.

First report of the spectrum of δ-globin gene mutations in Omani subjects - identification of novel mutations.

INTRODUCTION: Both coinheritance of thalassemic δ-globin mutation and coexistence of iron deficiency anemia (IDA) tend to decrease HbA2 (α2 δ2 ) level and thereby poses a diagnostic conundrum in ß-thalassemia trait. METHODS: We retrospectively studied 78 Omani subjects, presenting with low HbA2 level by high-performance liquid chromatography (HPLC), and their DNA was sequenced for the presence of mutations in the δ-globin gene (HBD). In these subjects, their serum ferritin levels allowed evaluation of the degree of iron deficiency. RESULTS: Overall, six different δ-globin gene mutations were observed in 40 study subjects (51.3%) and IDA in 33 subjects, with the remaining five subjects showing normal HBD sequence and serum ferritin level. Among the subjects with δ-globin gene mutations, seven had an associated IDA confirmed by significantly low serum ferritin levels. Heterozygosity for the delta (+) cd27G-->T mutation (HbA2 -Yialousa; HBD: c.82G>T) was the most common abnormality observed (n = 26, 66.6%) followed by heterozygosity for HBD c.-118C->T (d -68 C->T) (n = 6, 15.4%), for cd16G-->C (n = 4, 10.3%), for cd98G-->A (n = 2, 5.1%), for cd142G-->C (n = 1, 2.6%), and for cd147G-->T (n = 1, 2.6%). CONCLUSIONS: These delta mutations exhibit low HbA2 either due to a shift in the HPLC position or due to their bona fide thalassemic feature. Two mutations, namely cd142 G-->C (GCC to CCC, Ala to Pro) and stop codon cd147 G-->T (stop to Leu with elongation of 15 amino acids), herein first reported are novel. Coexistence of IDA could lead to erroneous diagnostic interpretation unless it is specifically looked for.

Dose-ranging studies on liposomal amphotericin B (L-AMP-LRC-1) in the treatment of visceral leishmaniasis.

Efficacy and tolerability of liposomal amphotericin B (L-AMP-LRC-1; developed in India by the Liposome Clinical Pharmacology Centre, Mumbai, and the Liposome Research Centre, New Delhi) were assessed in 63 patients suffering from visceral leishmaniasis at centres in Mumbai and Patna. Patients were treated with different daily dose schedules ranging from 1 mg/kg for 21 days to 3.0 mg/kg for 7 days. L-AMP-LRC-1 was well tolerated by all 63 patients. Two patients on the 3.0 mg/kg dose developed bronchospasm on 4 occasions which reversed with standard treatment and could be prevented by increasing the duration of infusion to 3 h. Forty-three patients were freshly diagnosed cases while 20 were unresponsive to standard treatment. All 42 assessable freshly diagnosed cases responded completely to L-AMP-LRC-1 (1 patient died owing to pulmonary infection before completion of treatment), but 5 patients required additional doses for parasitological cure. All 20 patients unresponsive to standard therapy responded completely, but 3 patients required additional doses. The regimen of 2 mg/kg daily for 10 days was 100% effective; 3 mg/kg daily for 5 days was efficacious in 90.9% freshly diagnosed patients, and 3 mg/kg daily for 7 days was effective in 100% of the unresponsive cases of visceral leishmaniasis. L-AMP-LRC-1 is thus found to be safe and effective in freshly diagnosed as well as unresponsive cases of visceral leishmaniasis at dose schedules of shorter duration than used for conventional amphotericin B.

Deferiprone (L1) as an adjuvant therapy for Plasmodium falciparum malaria.

BACKGROUND & OBJECTIVES: Mortality due to Plasmodium falciparum infection remains high in India, hence any modality of treatment which can improve the outcome of this disease is worth exploring. The present study was undertaken to see whether addition of an oral iron chelator, deferiprone (L1) to the conventional treatment regime for P. falciparum infection improves the clinical course and final outcome. METHODS: In this prospective, randomised double blind trial, 45 consecutive patients with P. falciparum infection were randomised into two groups. Patients in Group I (control group, 21 patients) received standard quinine and doxycycline therapy along with supportive therapy and placebo capsules for 10 days. Patients in Group II (24 patients) received the same treatment as Group I but in place of placebo capsule received deferiprone capsules 75 mg/kg/day in 12 hourly divided doses. The parameters evaluated included the time taken in resolution of parasitaemia, fever and coma, differences in final outcome i.e., death or other severe complications, and side effects and deferiprone tolerance. RESULTS: Four patients in Group I and two in Group II died (P > 0.05). The resolution of fever and coma was significantly faster in Group II (P < 0.05) and parasitaemia cleared 24 h earlier in this Group. The drug was well tolerated and had no side effects. INTERPRETATION & CONCLUSION: Deferiprone (L1) seems to be a promising agent as an adjuvant in the treatment for severe P. falciparum malaria infection.

Transfusion transmitted diseases in haemophilics from western India.

BACKGROUND & OBJECTIVES: Transfusion related human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) infections have been a major cause for morbidity and mortality in the haemophilic population in the west. The prevalence of these markers of transfusion transmitted viral diseases in severe and moderate haemophilia patients was studied. METHODS: The seropositivity for these viral markers was evaluated in 400 haemophilics (323 severe and 77 moderate) in a 5-year survey starting from 1995. First 188 of these patients were also tested for HCV. Serological tests for HIV, HBsAg and HCV were done by third generation ELISA; positive samples were also confirmed by Western blot. RESULTS: Fifteen of the 400 patients were found to be HIV positive (3.8%), 24/400 were HBsAg positive (6%) and 45/188 (23.9%) were positive for HCV (28 for both non-structural and core antigen, 13 for core only and 4 for non-structural antigen only). The lowest age of HIV positivity was 12 yr and that of HCV positivity was 8 yr. INTERPRETATION & CONCLUSION: The above study shows a reduction in blood product related HIV transmission in severe and moderately affected haemophilics but more stringent policy for blood product usage, universal hepatitis C screening, hepatitis B vaccination and continuous awareness programmes for medical staff, general public and patients is needed to reduce the incidence of these diseases in haemophilics.

Venous thromboembolism in young patients from western India: a study.

The goal of this article is to study the association of known markers of thrombophilia with venous thrombosis in young patients (< 45 years) from the Western part of India. A prospective study of 432 patients (252 males and 180 females, age 1-45 years) was conducted between 1994 and 2000 (6 years). The diagnosis was confirmed in all the patients by ultrasound with Doppler or by a computed tomograph (CT) scan of the brain with or without contrast depending on the case. Detailed clinical examination, and family history was taken to establish recurrent thrombosis and familial occurrence of thrombosis. The markers studied were protein C, protein S, antithrombin (AT) III, factor V Leiden mutation, prothrombin gene G20210A polymorphism, and the thermolabile MTHFR variant C677T polymorphism, using appropriate techniques. Lupus inhibitor was tested in the first 72 patients using Dilute Russel Viper Venom Time (DRVVT) test, and anticardiolipin antibodies were tested by enzyme-linked immunosorbent assay. Protein C, protein S, and AT III deficiency was detected in 9.5%, 6.5%, and 2.6%, respectively, among the patients. Anticardiolipin antibody was present in 9.9% of the patients, whereas lupus anticoagulant was present in 8.3% of patients; factor V Leiden mutation was detected in 3% of patients; thermolabile variant of MTHFR C677T polymorphism was present in 14.9% of patients with 1.2% homozygotes. Prothrombin G20210A polymorphism was not detected in any sample in this population. One hundred and four patients of 432 (24.9%) had recurrent attacks of thrombosis without any proximate precipitating cause, whereas 7.5 % of the patients had another close member of the family with a history of deep venous thrombosis. Eighty-six members from 28 families (out of 32 families giving family history of thrombosis) were investigated and found to have protein C and protein S deficiency in seven each; factor V Leiden was present in 6, and MTHFR C677T polymorphism was present in 5 cases. Hence, 25 of 86 members (28%) from the family of patients with familial history deep venous thrombosis had positive markers for thrombophilia. Thus, we could show that in young patients presenting with thrombosis, at least 34% of them had a demonstrable cause for thrombophilia. Prothrombin gene polymorphism G20210A seems to be nonexistent in our population and AT III deficiency also appears to be low compared to other markers of thrombophilia. There is a high prevalence of variant MTHFR C677T in our series, but the incidence of MTHFR C677T in our general population is also high. Hence, the significance of this finding in our cases of deep venous thrombosis remains to be seen, but we did not see any homozygotes when we tested 70 randomly selected asymptomatic persons, whereas in the present series, 1.8% of the patients had homozygosity for the MTHFR C677T polymorphism.