Seema Tyagi

Human parvovirus B19‐induced acquired pure amegakaryocytic thrombocytopenia

Acquired pure amegakaryocytic thrombocytopenic purpura is a relatively rare bone marrow failure disorder characterized by severe thrombocytopenia with total absence or marked reduction of bone marrow megakaryocytes in the absence of other haematological abnormalities (Hoffman, 1991). We report a case of acquired pure amegakaryocytic thrombocytopenia secondary to parvovirus infection, which was treated with intravenous immunoglobulin. A 9-month-old male child was noticed to have skin purpura in late November 2003, of 2 weeks duration, followed by epistaxis and haematochezia. He had developed a cough a week prior to the other symptoms. The child developed an intracerebral bleed and was found to have a platelet count of less than 10 · 10/l. Blood counts: Hb 10.9 g/dl, reticulocyte counts 0.4%, white blood cells (WBC) 9.8 · 10/l, neutrophils 44%, absolute neutrophil count (ANC) 4.31 · 10/l, platelet counts 9 · 10/l. Bone marrow examination showed the absence of megakaryocytes with a prominence of lymphoid cells and a large number of haematogones with normal erythroid and myeloid precursors. Treatment was started with steroids and intravenous immunoglobulin (IVIG). Further investigations showed a positive Parvovirus B19 serology for both IgG and IgM by enzyme-linked immunosorbent assay (ELISA) and the bone marrow was positive for parvo DNA by polymerase chain reaction (PCR). Haemoglobin electrophoresis showed : Hb F 1.7%, Hb A2: 2.8%, Hb A 85.2%. Glucose-6-phosphate dehydrogenase was normal. A peripheral blood smear showed normocytic normochromic red cells, no spherocytes or fragmented cells and no evidence of haemolysis. Immunoglobulin levels were normal. Screening for human immunodeficiency virus (HIV) type 1 and 2, toxoplasma, rubella, herpes simplex virus 1 and 2, and cytomegalovirus (IgM) were negative. Repeat bone marrow in January 2004 showed few megakaryocytes with a platelet count of 450 · 10/l and normal Hb and WBC count but parvovirus serology and PCR were still positive. Oral steroids were stopped and IVIG was continued once in 3 weeks for five cycles. The blood counts remained normal. In June 2004, bone marrow aspiration showed a normal population of megakaryocytes. The parvovirus B19 DNA was negative by PCR in both bone marrow and serum, while serology (IgM) was negative by ELISA. IVIG was stopped and the child was well at the last follow-up. Blood counts in September 2004 were: Hb 11.7 g/dl, reticulocytes 0.9%, WBC 11.8 · 10/l; neutrophils 35%, ANC 4.13 · 10/l, lymphocytes 60%, monocytes 3%, eosinophils 2%, platelets 180 · 10/l. The association of thrombocytopenia with parvovirus infection is uncommon, and is usually combined with other cytopenias or associated with aplastic crises of haemolytic anaemias (Saunders et al, 1986). There is one case report of transient erythroblastopenia of childhood with megakaryocytopenia associated with parvovirus B19 infection, which resolved spontaneously (Nagai et al, 1992). To our knowledge, no case of human parvovirus-induced pure amegakaryocytic thrombocytopenia has been reported so far in the literature. Our case is unique as there was no underlying haematological abnormality or immunocompromised state. The diagnostic criteria of parvovirus infection are PCR positivity and IgM positivity in serology (Gallinella et al, 2003, Young & Brown, 2004), both of which were present in our patient. On follow-up, the negative PCR and fall in IgM suggest that the virus was eradicated, with a possible role for IVIG. Parvoviruses have a remarkable tissue tropism for erythroid elements in the bone marrow and are known to cause transient aplastic crisis in patients with various haemolytic anaemias (Young & Brown, 2004) but their relationship to platelets is not well documented. In vitro exposure of human bone marrow cells to parvovirus has been shown to significantly suppress megakaryocyte colony formation (Srivastava et al, 1990). This may be the mechanism of amegakaryocytic thrombocytopenic purpura secondary to parvovirus. Parvovirus should be considered as a possible aetiological agent in amegakaryocytic thrombocytopenia, and IVIG may be of benefit.

Secondary myelofibrosis in children.

Myelofibrosis is a rare childhood myeloproliferative disorder. It has been reported as an associated complication of certain hematologic malignancies or as an isolated idiopathic process. We describe clinical course of 6 children diagnosed over 6 years. One child each responded well to steroid and treatment of the underlying condition. Three children died because of underlying conditions and 1 child was lost to follow up. A thorough search should be made for underlying disease when myelofibrosis is first diagnosed. Trephine biopsy though giving useful information, does not have a prognostic significance.

Clinico-haematological Profile of HbE Syndrome in Adults and Children

Abstract Haemoglobin E beta thalassemia (HbE β thalassemia) has a remarkable variability in clinical expression ranging from a mild form of thalassemia intermedia to a transfusion dependent condition. An overlap between the mild variety of HbE beta thalassemia and homozygous HbE disease is common, however, differentiation is required for early institution of therapy and for predicting the later clinical course. Fifty cases of Hb E syndrome comprising of 43 cases of Hb E beta thalassemia and 7 cases of homozygous HbE disease were studied. Their clinico- haematological features and results of high performance liquid chromatography (HPLC) were analysed.

An Unusual Cause of Eosinophilia in AML-M4 without the Inv(16) Abnormality

Copyright:

Feasibility and outcome of CT-guided lung biopsy in patients with hematological diseases and suspected fungal pneumonia.

INTRODUCTION Fungal pneumonia is a major cause of morbidity and mortality in immunocompromised patients with hematological diseases. This study is aimed to evaluate the feasibility and outcome of computed tomography (CT) guided lung biopsy or fine needle aspiration cytology (FNAC) in the diagnosis of fungal pneumonia in patients with hematological diseases. METHODOLOGY Seven hundred and seventy six consecutive patients with febrile neutropenia were evaluated prospectively over the period of three years. Patients with suspected fungal pneumonia, based on typical CT scan findings, were considered for lung biopsy. RESULTS Of the 776 patients evaluated for fever, 235 (30.3%) showed CT scan findings consistent with fungal pneumonia. Of the 235 patients, CT-guided lung biopsy/FNAC was recommended for 178 patients but could be performed in only 34 (19.1%) patients. Fungal pneumonia was proven in 15 (44%) out of 34 patients (aspergillus in 12; mucormycosis in 3 patients). Lung biopsies could not be performed for a number of reasons. These included thrombocytopenia, nodules being too small, infection improving with empiric treatment and patient recovering clinically, and the patient being too sick to undergo intervention. The median absolute neutrophil count (ANC) of patients at the time of lung biopsy was 0.41 x 10⁹/l in patients whose lung biopsy/FNAC showed fungal pneumonia, compared to 2.10 x 10⁹/l in patients whose biopsy/FNAC showed necrotizing pneumonitis. CONCLUSION CT-guided lung biopsy/FNAC can allow the definitive diagnosis of fungal pneumonia in selected patients with various hematological diseases and should be attempted whenever clinically indicated and radiologically feasible.

Double heterozygous hemoglobin Q India/hemoglobin D Punjab hemoglobinopathy: Report of two rare cases.

Cation exchange high performance liquid chromatography (CE HPLC) provides an excellent tool for accurate and reliable diagnosis of various hemoglobin (Hb) disorders. HbQ India is a rare alpha chain variant that usually presents in the heterozygous state. Its presence in double heterozygous state with HbD Punjab is extremely rare. The double heterozygosity for α and β chain variants leads to formation of abnormal heterodimer hybrids, which can lead to diagnostic dilemmas. We report two rare cases of double heterozygous HbQ India/HbD Punjab where the hybrid Hb was seen to elute at retention time similar to HbC on CE HPLC. The first case had unconjugated hyperbilirubinemia at presentation; while, the second case was asymptomatic.

Evaluation of the Diagnostic Performance of Fibrin Monomer in Comparison to d-Dimer in Patients With Overt and Nonovert Disseminated Intravascular Coagulation.

Introduction: Disseminated intravascular coagulation (DIC) is a thrombohemorrhagic disorder characterized by hyperactivation of coagulation and secondary fibrinolysis. Aim: The primary aim of this prospective study was to evaluate and compare the diagnostic performance of fibrin monomer (FM) and d-dimer (DD) for the preemptive diagnosis of DIC in the early stages. Materials and Methods: The patients were categorized into 3 groups: overt DIC, nonovert DIC, and non-DIC based on the International Society of Thrombosis and Hemostasis scoring for overt DIC and the modified nonovert-DIC criteria. Coagulation tests were performed on freshly obtained plasma. Quantitative determination of FM and DD was done by immunoturbidimetric assay. Results: Median DD and FM levels in patients with overt DIC were significantly higher in comparison to the other 2 groups. Interestingly, unlike DD, the difference in FM levels was also found to be statistically significant between patients with nonovert DIC and non-DIC patients (P = .0001). At receiver–operator characteristic curve-generated cutoff values, FM had higher specificity and negative predictive value than DD for predicting onset of overt DIC. Multivariate analysis showed that only FM was as an independent predictive factor useful in differentiating patients with overt DIC from non-DIC patients (odds ratio [OR]: 43.3; confidence interval [CI] 4.61-406.68; P value = .001) as well as in distinguishing nonovert DIC from non-DIC patients (OR:18.3; CI 3.45-97.19; P value = .001). Conclusion: Fibrin monomer is a better indicator than DD in distinguishing patients with overt and nonovert DIC from non-DIC patients, raising the possibility for its diagnostic utility as a marker for impending overt DIC, aiding in early diagnosis and prompt therapeutic intervention.

Primary myelodysplastic syndrome in children—clinical, hematological and histomorphological profile from a tertiary care centre in India

Abstract We describe the clinical, hematological and histomorphological features in children of primary myelodysplastic syndrome (MDS) seen at the All India Institute of Medical Sciences over three years (Jan 2001–Jan 2004). Twenty-one patients of primary MDS aged 17 year or less were classified using the latest proposed WHO classification for Pediatric MDS. The median age was 9 years with male predominance (80%). Pallor was present in all the cases while fever and bleeding diathesis was present in more than 50% of the cases. Morphological assessment of the peripheral blood showed macrocytosis in 50%, pancytopenia in 15% and blast cells in 45% of cases. A complete analysis of clinical features in conjunction with the bone marrow profile revealed 8 cases of refractory cytopenia (RC), 3 cases of refractory anemia with excess blasts (RAEB), 5 cases of refractory anemia with excess blasts in transformation (RAEB-T), 4 cases of Juvenile myelomonocytic leukemia (JMML) and a solitary cases of acute myeloid leukemia (AML) in Downs syndrome. These children were followed up from 1–36 months (mean 15 months). Three patients of RAEB-T progressed to AML within 3–4 months. RC had the best prognosis and all are alive and under regular follow up. The solitary case of AML of Downs syndrome died 1.5 months after initial diagnosis. All 3 cases of RAEB are under regular follow-up and doing well. Three cases of RAEB-T died (all had progressed to AML); the remaining 2 cases were lost to follow up. Of the 4 cases of JMML 1 died within 6 months of diagnosis; the other 3 cases are under regular follow up of whom 1 has a progressively increasing blast count. We conclude that the latest proposed WHO classification for Pediatric MDS can be successfully applied to all cases of primary MDS.

Hairy cell leukemia: A decade long experience of North Indian Hematology Center.

Introduction: Hairy cell leukemia is a rare chronic B-cell disorder that follows an indolent but progressive course. This disorder is characterized by pancytopenia, splenomegaly, bone marrow fibrosis and the presence of atypical lymphoid cells with hairy projections in peripheral blood, bone marrow and spleen. Treatment is mainly with nucleoside analog cladribine, which induces complete remission in up to 85% cases. Materials and Methods: This is a retrospective analysis of Hairy cell Leukemia cases diagnosed and treated in the Department of Hematology, All India Institute of Medical Sciences, New Delhi between 2002 and 2013. Various parameters such as clinical features, laboratory parameters including complete blood cell count, bone marrow findings, cytochemistry, immunophenotyping by flowcytometry or immunohistochemistry, treatment protocol and complications secondary to treatment and relapse were reviewed. Results: A total of 35 cases were diagnosed during this period of 12 years of which 27 received cladribine and went in to remission. Median follow-up duration was 26 months. 5 (18%) cases had a relapse and all relapsed cases achieved second remission with cladribine; however, there was no case of second malignancy in our cohort. Conclusion: Cladribine has emerged as the treatment of choice for hairy cell leukemia given that the overwhelming majority of patients achieve long-lasting complete remissions. Upon relapse, these patients could be successfully salvaged with cladribine retreatment.

Unusual Presentation of Hairy Cell Leukemia: A Case Series of Four Clinically Unsuspected Cases

Hairy cell leukemia (HCL) is characterized by pancytopenia and usually associated with massive splenomegaly, however the same may not be true in the clinical settings. Here we report four cases of HCL and all of them were without the classical clinical feature of splenomegaly. This is an observational study conducted between January 2013 to March 2014 where we could diagnose ten cases of HCL in Department of Hematology, All India Institute of Medical Sciences, New Delhi. Of these, four cases attracted attention because of absence of classical clinical features of HCL. Of the four cases, three presented with weakness/fatigability while fourth patient presented with recurrent respiratory tract infection. Surprising finding in these cases was absence of splenomegaly, both clinically and on imaging which demerit the suspicion of HCL clinically. All four had bi/pancytopenia and bone marrow examination coupled with immunophenotypic analysis confirmed the diagnosis of HCL. Three patients received chemotherapy with cladribine and achieved complete hematological remission. One patient did not receive chemotherapy due to poor general condition and was subsequently lost to follow up. To conclude, HCL can and do present without splenomegaly and this should not restrain one from suspecting HCL based on histomorphology which needs to be further confirmed by ancillary techniques. This finding in our series could be because these cases were picked early in their natural course of the disease. A high index of suspicion is essential for diagnosing and appropriately managing such cases.