HLA match likelihoods for Indian patients seeking unrelated donor transplantation grafts: a population-based study.

BACKGROUND: For patients who do not have a suitable human leukocyte antigen (HLA)-matched family donor, unrelated donor registries of adult volunteers and banked umbilical cord blood (UCB) units provide the potential for successful haemopoietic stem-cell transplantation. The size and genetic composition of such registries determines the proportion of patients who will be able to find a suitable match. We aimed to assess the proportion of positive matches for Indian patients. METHODS: Using HLA data from ten existing donor and UCB registries and clinical transplant centres in India, we built population-based genetic models for 14 Indian regions to model Indian registry growth to predict the likelihood of identifying a suitable donor-either an adult donor or UCB-for Indian patients. We computed ranking tables of the top ten haplotypes in each regional group and compared these with four US samples from the National Marrow Donor Program (NMDP) registry. FINDINGS: The mean proportion of individuals who would have a 10/10 adult donor match within India ranged from 14·4% with a registry size of 25 000 to 60·6% with a registry size of 1 000 000. Only when donor registries increased to 250 000 did the match rate within India exceed that found by searching the US-NMDP registry combined with an Indian registry of 25 000 donors. The proportion of matches increased logarithmically with increased registry size (R(2)=0·993). For a UCB registry size of 25 000, 96·4% of individuals would find a 4/6 match; however, only 18·3% would have a 6/6 match. INTERPRETATION: Serial match modelling and follow-up comparisons can identify the relative and progressively greater value of an India-based donor registry and UCB banking network to serve the Indian population. Understanding regional HLA haplotype diversity could guide registry growth and maximise benefit to patients. Similar modelling could guide planning for the needs of other ethnically distinct populations. FUNDING: University of Minnesota and the Indian Council for Medical Research.

Budd-Chiari syndrome following laparoscopic cholecystectomy.

Patients with thrombophilic disorder while undergoing intra-abdominal surgery may develop splanchnic vein thrombosis which can have dire consequences. Here we report a case of a 38-year-old female who developed acute Budd-Chiari syndrome after a laparoscopic cholecystectomy. She had polycythemia vera which was not diagnosed before surgery. In this report we want to highlight presurgical evaluation of routine biochemical tests and ultrasonography suggestive of myeloproliferative disorders were missed which led to the Budd-Chiari syndrome. We recommend a meticulous look at the routine evaluation done prior to cholecystectomy is essential.

Portal hypertension and ascites in extramedullary hematopoiesis.

Myeloproliferative diseases (MPD) are clonal stem cell disorders which mainly include polycythemia vera (PV), essential thrombocythemia (ET), and idiopathic myelofibrosis (IMF). They are characterized by leucocytosis, thrombocytosis, erythrocytosis, splenomegaly, and bone marrow hypercellularity. This might also result in extramedullary hematopoiesis. Abdominal manifestation has been recognized as a feature of these disorders. Splenomegaly and hepatomegaly are fairly common as opposed to ascites which is rare. The MPDs mainly affect the hepatic circulatory systems. The common hepatic manifestations are Budd-Chiari syndrome (BCS), portal vein thrombosis (PVT), and nodular regenerative hyperplasia. A few other features seen in MPDs are caused by extramedullary hematopoiesis, increased hepatic blood flow, and secondary hemosiderosis from multiple blood transfusions. Portal hypertension is found in up to 7% of patients. We report a case of portal hypertension with ascites in a patient with extramedullary hematopoiesis treated with transjugular intrahepatic portocaval shunt (TIPS).

Prevalence of JAK29V617F) mutation in intra-abdominal venous thrombosis.

BACKGROUND AND AIM: Myeloproliferative disorders (MPD) (like polycythemia vera, essential thrombocythemia and primary myelofibrosis) are responsible for 50% cases of Budd-Chiari syndrome (BCS) and 35% cases of portal venous thrombosis (PVT) in western series. A point mutation at Val617Phe of Janus kinase 2 tyrosine kinase gene (JAK2(V617F) mutation) occurs in high proportion with MPD. This may be useful in diagnosing overt and latent form of MPD in intra-abdominal venous thrombosis (IAVT), consisting of BCS and PVT. METHODS: In a 4 year prospective study from 2006 to 2009, JAK2 mutations were assessed in all patients diagnosed with MPD and IAVT attending our institution. Twenty three healthy individuals and 31 patients with non-MPD hematological disorders served as controls. All patients of idiopathic IAVT were tested for the mutation. Test for JAK2(V617F) mutation was carried out by allele specific polymerase chain reaction. RESULTS: JAK2(V617F) mutation was significantly more common in MPD patients (76%) than in non-MPD hematological disorders (0%) and healthy controls (0%). There was no statistical difference in presence of JAK2(V617F) mutation in patients of MPD with or without thrombosis (80% vs. 74%). In 58 patients with IAVT, the JAK2(V617F) mutation was present in 40% with BCS, 14% with PVT and 100% combined BCS+PVT). CONCLUSIONS: The JAK2(V617F) mutation occurs at high frequency in patients with MPD and IAVT. All idiopathic IAVT patients must be screened for JAK2(V617F) mutation to detect latent MPD. Detection of latent MPD by JAK2(V61F) mutation in BCS may change treatment strategy and outcome.

Prenatal diagnosis in a family at risk for beta-thalassemia and hemophilia A: an uncommon association.

beta-Thalassemia (thal) is an autosomal recessive disorder with a prevalence of 2-3% in Indians, while hemophilia A is X-linked with a prevalence of 1 in 5,000-10,000 male births. The chances of both these disorders being present together is extremely rare (1 in 250,000). We report an interesting consanguineous family from Western India with a combination of these two disorders, which was referred to us for prenatal diagnosis.