Amyloidosis Presenting as Severe Bleeding Diathesis

Bleeding is one of the rare presentations of Amyloidosis. The mechanism behind spontaneous or peri- interventional bleeding in patients of amyloidosis is complex and involves multiple co-existing factors like coagulation factor deficiency, abnormal synthesis of coagulation factors due to advanced liver dysfunction, acquired Von Willebrand disease, platelet dysfunction, amyloid angiopathy and other unknown mechanisms. We present a case of middle aged female, presenting with spontaneous retroperitoneal haemorrhage, on further investigations was found to have systemic amyloidosis and secondary severe factor X deficiency (2.7 % of normal by one stage factor assay method). Factor X deficiency (both inherited and acquired) is known to present with the most severe bleeding phenotype. The management option for such acute spontaneous haemorrhage is limited and mostly supportive in nature. Definitive treatment is directed towards the primary pathology and requires chemotherapy and hematopoietic stem cell transplantation.

A 60-year-old lady with leonine facies: A rare diagnosis.

Systemic mastocytosis is a rare clonal disorder characterized by mast cell infiltration of one or more organs, with or without skin involvement. Leonine facies is a rare presentation and corresponds to the morphologic manifestation of diffuse dermal infiltration of the face as a result of long standing disease. Bone marrow aspiration and biopsy findings in a 60-year-old woman, who had extensive cutaneous infiltration due to systemic mastocytosis, resulting in 'leonine facies,' are described, and causes of leonine facies are discussed.

Platelet enzyme abnormalities in leukemias.

Aim of the Study: The aim of this study was to evaluate platelet enzyme activity in cases of leukemia. Materials and Methods: Platelet enzymes glucose-6-phosphate dehydrogenase (G6PD), pyruvate kinase (PK) and hexokinase (HK) were studied in 47 patients of acute and chronic leukemia patients, 16 patients with acute myeloid leukemia (AML)(13 relapse, three in remission), 12 patients with acute lymphocytic leukemia (ALL) (five in relapse, seven in remission), 19 patients with chronic myeloid leukemia (CML). Results: The platelet G6PD activity was significantly low in cases of AML, ALL and also in CML. G6PD activity was normalized during AML remission. G6PD activity, although persistently low during ALL remission, increased significantly to near-normal during remission (P < 0.05) as compared with relapse (P < 0.01). Platelet PK activity was high during AML relapse (P < 0.05), which was normalized during remission. Platelet HK however was found to be decreased during all remission (P < 0.05). There was a significant positive correlation between G6PD and PK in cases of AML (P < 0.001) but not in ALL and CML. G6PD activity did not correlate with HK activity in any of the leukemic groups. A significant positive correlation was however seen between PK and HK activity in cases of ALL remission (P < 0.01) and CML (P < 0.05). Conclusions: Both red cell and platelet enzymes were studied in 36 leukemic patients and there was no statistically significant correlation between red cell and platelet enzymes. Platelet enzyme defect in leukemias suggests the inherent abnormality in megakaryopoiesis and would explain the functional platelet defects in leukemias.

Hairy cell leukemia: Clinical, pathological and ultrastructural findings in Asian-Indians.

Background: Hairy-cell leukemia (HCL), lymphoproliferative disease of older age, is characterized by projections from surface of abnormal cells. Aim: The aim was to study the clinical presentation and ultrastructural changes in hairy cells (HCs) following cladribine treatment. Settings and Design: Clinical presentation, peripheral smear, bone marrow aspiration and biopsy of HCL cases diagnosed over a period of three years were reviewed. Materials and Methods: Consecutive HCL cases in Hematology clinic of a tertiary care center were enrolled. Tartarate-resistant acid phosphatase (TRAP) test was done to detect HCs and electron microscopy was done to demonstrate initial ultrastructural changes and alterations following cladribine therapy. Results: Fifteen cases of HCL, aged 32-57 years (median 47 years) were studied. The clinical presentation included splenomegaly in 15 (100%), fever in 10 (67%), hepatomegaly and pain abdomen in eight (53%), fatigue in nine (60 %) cases. The commonest laboratory features were monocytopenia in 13 (87%), neutropenia in 12 (80%), anemia in 10 (67 %) and pancytopenia in nine (60%). All patients showed symptomatic improvement on cladribine therapy. Electron microscopy after treatment (three months) showed loss of the finger like projections, characteristic bald lymphocytes, loss of ribosomal lamellar complexes, as well as decrease in mitochondria and vacuoles. Conclusions: Indian patients with HCL are younger. Cladribine is an effective therapy for these patients and leads to complete response in most of the patients. There is a significant improvement in the ultrastructural features following cladribine therapy.

AML1-ETO positive AML: first report from India.

Translocation (8;21) is associated with few typical morphological features and favorable prognosis. All patients of AML and MDS with increased blasts (N = 35) according to FAB criteria, presenting (between Jan 2004 to June 2005) to the Department of Hematology, AIIMS were studied. RT-PCR was done for the AML1-ETO fusion transcript in all cases. Overall incidence of AML1-ETO was 28.57% and no correlation was found between AML1-ETO positivity and clinical or hematological parameters except for a direct correlation with absolute blast count (ABC) (a lower ABC in the AML1-ETO positive cases). Interestingly, 1/3 MDS cases were positive for the same fusion transcript and thus, it appears worthwhile to look for AML1-ETO in all cases of MDS with increased blasts. Objective morphological evaluation using a scoring system based on morphological features was not helpful in predicting positivity for AML1-ETO. The effect of this translocation on long-term survival could not be determined by the present study.

Erythrocyte enzyme abnormalities in leukemias.

Red cell enzymes were assayed in a total of 67 patient including 24 patients with AML (19 relapse, 5 remission), 16 patients with ALL (10 relapse, 6 remission), 22 patients with CML and 5 patients with blastic CML. Diagnosis of leukemia was based on clinical presentation, peripheral blood smear and bone marrow examination (as per FAB classification). PK activity was significantly high in case of CML and blastic CML (p<0.01). Red cell HK was high in all leukemia subtypes. There was no alteration in red cell G6PD. Notably there was no PK deficiency in AML or G6PD deficiency in ALL. Activities of G6PD and PK could be correlated in cases of CML, AML, (p<0.05) and ALL (p<0.01) i.e. when there was increased activity of G6PD, PK activity also tended to be higher. HK activity showed a positive correlation with PK and G6PD activity in cases of CML (p<0.05), however in acute leukemia there was no such correlation. Alteration of enzyme activities among red cells in leukemia occurred only during relapse. At the time of remission there has been no significant alteration in any of the enzyme activities. It would therefore, appear that enzyme alterations seen in leukemia patients is due to abnormal pluripotent stem cell that has given to a leukemia cell. The fact that enzyme alterations have primarily occurred at the time of relapse would further substantiate that abnormalities of red cell enzymes may be the result of a derivation some circulating red cells from the abnormal pluripotent stem cell. With the recovery of normal stem cells function during remission, enzyme abnormalities tend to become normal.

Disseminated Langerhans cell histiocytosis-an interesting case report with concise review of literature.

A 2-year-old boy presented with fever, recurrent infections and multiple skin lesions. He had anemia, eczematous skin lesions, cervical lymph node enlargement, hepatomegaly and lytic lesions on skull x-ray. The skin infiltrates were CD 68, CD 1a positive and S100 positive. He was diagnosed as disseminated langerhans cell histiocytosis. The occurrence of histiocytosis is reviewed and possible treatment is discussed.

Deferiprone, efficacy and safety.

OBJECTIVE: Deferiprone (L1), the new oral iron chelator has been studied in several countries for its efficacy and toxicity with some conflicting observations. Toxicity involving joints has been reported more frequently in Indian patients. The authors planned to include larger number of Indian thalassemics in studying safety and efficacy of Deferiprone. METHODS: Seventy five thalassemic children (4-14 yr) were studied for one year with various investigations done periodically. Thirty patients (group A) received 50 mg/kg dose and 21 others (group B) received 75 mg/kg dose of Deferiprone. Rest of the patients were followed up without any chelator. RESULTS: The serum ferritin levels reduced significantly in both groups (P < 0.01 each); more in 75 mg/kg than the 50 mg/kg group. Arthropathy appeared in 15 (50%) patients in Group A and 6 (28.6%) of Group B after 1-12 (mean 6) months of L1 treatment; however, only one patient needed withdrawal of L1. Eleven patients needed indomethacin for pain relief. Seropositivity for antinuclear factor and rheumatoid factor had no relation to dose or duration of L1 therapy, arthropathy or the serum ferritin level. Twelve patients developed leucopenia (< 3.0 x 10(9)/L) and neutropenia (0-1.8 x 10(9)/L) after 2-11 months of L1 therapy and was not related to the dose or duration of therapy. The drug was restarted in 10 patients and only one of them developed a second episode of neutropenia. CONCLUSION: Deferiprone is an effective iron chelator, but arthropathy and neutropenia are very frequent side effects and need strict monitoring during therapy. Most of the neutropenia are neither very severe nor recur with re-challenge with the drug. Similarly, arthropathy does not need withdrawal of drug in majority of patients.

Management of idiopathic thrombocytopenic purpura.

Idiopathic thrombocytopenic purpura is not an uncommon bleeding disorder with a prevalence of 40-80 per million children per year. Over the last six decades, the subject of ITP has attracted the attention of pediatricians and hematologists. It is one of the subjects which has many controversies because of its unpredictable course heralded by remission relapses, and chronicity with mortality in less than 1% of cases. In the present review only the controversies in the management of acute and chronic ITP have been reviewed as it interests most pediatricians. Management of intracranial hemorrhage (ICH), severe gastrointestinal hemorrhage and menorrhagia continues to still remain a challenge in spite of newer therapies.

Hematological responses to hydroxyurea therapy in multitransfused thalassemic children.

Fifteen multi-transfused thalassemic children between 3-6 years of age (seven boys and eight girls) were administered hydroxyurea for 5 days and three such cycles were repeated at 15 days interval. Rise in hemoglobin levels was observed in 13, 8 and 7 cases, while rise in mean hemoglobin F was seen in 8, 11 and 10 cases following 1st, 2nd and 3rd course of hydroxyurea therapy respectively. Rise in hemoglobin level was associated with transient rise in fetal hemoglobin level. Though the changes in mean hemoglobin levels and hemoglobin F levels were statistically insignificant, a definite trend of rise in hemoglobin and hemoglobin F was observed.

Resistance to activated protein C (APC) in Indian patients of thrombophilia.

In a pilot study, 28 consecutive patients with thrombosis and 23 age and sex matched healthy normal controls were investigated with normalised APC sensitivity ratio (n-APC-SR) to know the defect exists and if so its prevalence in India. Six of the 28 (21.4%) thrombotic patients had n-APC-SR of < 0.76 (range 0.55 to 0.74) as compared to the normal control value (0.97 +/- 0.105). Our study shows APC resistance defect in a significant proportion (21.4%) of Indian patients with thrombotic disorders.

Clinico-hematological spectrum of auto-immune hemolytic anemia: an Indian experience.

Twenty-one patients of autoimmune hemolytic anemia (AIHA), aged 2 months to 57 years were analyzed. The common presenting feature was pallor (89%), fever (38%), Jaundice (43%) and hepatomegaly and splenomegaly was seen in 76% and 81% respectively. Fifteen cases were of idiopathic etiology and in 6 cases the etiology could be identified as systemic lupus erythematosus, systemic sclerosis, pregnancy, maternal AIHA, typhoid fever and myelodysplastic syndrome (one each). Hemoglobin level ranged between 1.9 to 11.7 gm/dl (mean 6.8 gm/dl) and reticulocyte counts between 6% to 42% (mean (20.2%). Four patients had thrombocytopenia. Direct antiglobulin test (DAT) was positive in 19 and indirect antiglobulin test (IAT) in 7 cases. There was no correlation between DAT positivity and severity of anemia. All patients had warm antibodies of IgG type. Ten of fourteen patients responded to steroid therapy. Patients with secondary AIHA had a significantly poorer prognosis compared to the idiopathic group.