A. K. Saraya

Multilineage hempoietic stem cell defects in Budd Chiari syndrome

Abstract Background/Aims: Erythropoietin-independent endogenous growth of erythroid colony from bone marrow cells has been shown in many patients with Budd Chiari syndrome in earlier studies. In another report, increased megakaryocyte colony growth has also been documented in this disease. However, defects in granulocyte-macrophage cell lines in Budd Chiari syndrome have yet to be reported in the literature. Methods: Both in vitro erythroid and granulocyte-macrophage colony cultures from peripheral blood mononuclear cells with and without erythropoietin or granulocyte-macrophage colony stimulating factor, respectively, were studied in 32 patients with Budd Chiari syndrome, along with 20 normal healthy controls and ten patient controls with portal hypertension (five patients each with noncirrhotic portal fibrosis and liver cirrhosis). In 18 patients the occlusion was only in the inferior vena cava, in five patients only in hepatic veins, and in nine patients both inferior vena cava and hepatic veins were blocked. Result: Endogenous erythroid or granulocyte-macrophage colony growth was not observed in any of the normal healthy controls or in patient controls with portal hypertension. However, 22 of the 32 (68.8%) patients showed endogenous erythroid colony growth. Moreover, four of them also showed endogenous growth of granulocyte-macrophage colony, not previously reported in Budd Chiari syndrome. Conclusion: It may be inferred that stem cell defects affecting all three hemopoietic cell lines (erythroid, megakaryocyte and granulocyte-macrophage) occur in Budd Chiari syndrome, which may be the primary defect responsible for the pro-thrombotic state causing venous thrombosis in them.

Disseminated intravascular coagulation in post-dysenteric haemolytic uraemic syndrome

ABSTRACT. Coagulation studies were carried out in 14 children with haemolytic araemic syndrome that followed acute dysentery. Stool cultures showed Shigella dysenteriae in 3 cases and were sterile in the remainder. Prolongation of the prothrombin time, activated partial thromboplastin time and thrombin time and raised levels of fibrinogen degradation products were found in 12 cases, indicating the presence of disseminated intravascular coagulation. Renal histologic examination showed cortical necrosis in 7 cases, which was extensive in S and patchy in 2. Disseminated intravascular coagulation may have a role in the pathogenesis of haemolytic uraemic syndrome associated with acute dysentery.

Platelet aggregation in iron deficiency anemia

In-vitro platelet aggregation with ADP, adrenaline and collagen was studied in pediatric patients with iron deficiency before and after iron therapy, and in normal controls. Hyporeactivity of platelets to all agonists was seen in the untreated patients. This returned to normal following correction of anemia by iron therapy. There was a significant correlation between hemoglobin or serum iron and transferrin saturation on the one hand, and parameters of platelet aggregation on the other (P<0.001). Results of zero order correlation coefficient however, showed that platelet reactivity was actually dependent on the hemoglobin levels rather than the iron parameters per se. This may explain the prolonged bleeding time in patients with iron deficiency, particularly those associated with thrombocytopenia. Anemic individuals may be protected against thrombotic disorders due to this reduced platelet reactivity.

Asymptomatic visceral leishmaniasis in a child with acute lymphoblastic leukaemia

Visceral leishmaniasis was detected incidentally in a patient with acute lymphoblastic leukaemia in remission, during maintenance therapy. Absence of fever, a normal haemogram, normal serum globulins, a negative serology and testicular involvement were the hallmarks of the case. Treatment with sodium stibogluconate (20 mg/kg for 55 days) failed. Subsequent therapy with pentamidine resulted in complete parasite clearance. Prolonged therapy with pentavalent antimony compounds or a higher dose of second line drugs such as pentamidine are recommended for complete clearance.

Megaloblastic anemia—etiology and management

The term megaloblastic anemia refers to a characteristic morphology and functional abnormalities of erythrocytes, leucocytes, platelets and their precursors in the blood and bone marrow due to disturbed synthesis of deoxyribonucleic acid (DNA) resulting in anemia. The term megaloblast coined by Ehrlich in 1980 l to describe the abnormal erythroid wecursors of pernicious anemia (PA) is now used in general to denote abnormal erythroid precursors of megaloblastio anemia.

Camurati-Engelmann disease with recurrent bone marrow hypoplasia

A one year old girl with Camurati-Engelmann disease suffered from recurrent episodes of anemia and mucocutaneous bleeding, following upper respiratory or diarrheal infections. On two of such occasions, the bone marrow trephine biopsy showed hypoplastic marrow. Each time she showed complete hematological recovery, after corticosteroid therapy.

Increased ratio of thromboxane B2 and 6-keto PGF1α in patients of hepatic venous outflow obstruction

To the Editor: The etiology of hepatic venous outflow obstruction (HVOO) is poorly recognized and various hematologic and nonhematologic causes have been suggested (1). In Asian and African patients membranous obstruction of inferior vena cava (based on radiologic findings) has been considered a major etiologic factor and is believed to be congenital in origin (2-4). Recently, however, an autopsy study (5) and a prospective follow-up study (6) have shown that these membranous lesions are more likely to be acquired in origin, secondary to organized thrombus. Platelet function abnormality based on aggregation studies has been documented in HVOO patients (7). Altered transmission electron microscopic morphology of platelets and increased plasma beta-thromboglobulin levels, suggesting an in vivo platelet activation in these patients, has been reported recently by us (8). However, the pathogenetic mechanism for platelet activation in this disease has not yet been evaluated. An increased ratio of thromboxane A, (TxA,, a platelet aggregant) to prostacyclin (PGI,, a platelet antiaggregant) is an important component causing thrombogenic state (9,lO). This ratio was evaluated in the present study. Twenty-five patients (13 males and 12 females) of HVOO and 20 ageand sex-matched healthy controls were studied. The diagnosis of HVOO was based on ultrasonography, upper gastrointestinal endoscopy, liver biopsy and inferior venacavography with pressure measurements. All the patients were studied in the chronic phase. The duration of illness varied between 2 and 276 months (mean 33 months, median 24 months). Three of the 25 patients had an increased hematocrit (49-55%) and hemoglobin level (160-187 g/ L). Tests for lupus anticoagulant and paroxysmal nocturnal hemoglobinuria were negative in all these patients. None of the subjects had taken any antiplatelet agents for at least 10 d prior to the study. The plasma levels of TxA, were indirectly estimated by measuring its stable metabolite TxB, using an enzyme immunoassay kit (Amersham, UK). Similarly the plasma level of PGI, was estimated by measuring its stable metabolite 6-keto PGF,, using a radio-immuno assay kit (DuPont, USA). Venous blood sample was collected using a 21 G needle for venipuncture. Tourniquet was removed after locating the vein before blood collection. Initially 1-2 ml blood was collected for hemogram and then 900 p1 of blood was collected in a prechilled siliconized tube containing 100 pl of EDTA-indomethacin anticoagulant (indomethacin was added to inhibit the in vitro production of prostaglandins in platelets). The blood was centrifuged within 5 min of collection at 3500 g for 15 min at 4°C and plasma was immediately separated and stored in 2 aliquots at -70°C. Platelet aggregation was studied in 16 of the 25 patients and in 20 normal controls using an aggregometer (Chronolog, USA), as per Born (11). Adenosine diphosphate (2.5 and 1.25 pmol/l), adrenaline (20 pmol/l), collagen (1.0 pg/ml) and arachidonic acid (1.0 mmol/L) were used as agonists. Blood was collected in siliconized tubes in 3.8% sodium citrate anticoagulant (v : v, 9 : 1 ratio). Platelet rich plasma (PRP) was prepared by centrifugation at 250 g for 15 min. The aggregation studies were completed within 2 h of blood collection. The plasma levels of TxB, in the 20 normal healthy controls were between 10 and 160 pg/mL (meanf SD 70.0f54.0 pg/mL). The TxB, levels in all the patients were above 500 pg/mL (values above 500pg/mL were not readable from the standard curve) and were significantly higher (when each taken as 500 pg/mL) than the normal control values (p<O.OOl). The levels of 6-keto PGF,, were also significantly higher in patients (mean f SD 390.1 f 260.4 pg/mL, range 75-940 pg/ mL, p<O.Ol) than the normal controls (meanf SD 75.9f103.4 pg/mL, range 5.0 -360 pg/mL). The ratio of TxB, to 6-keto PGF,, was significantly