Clinico-Haematological Profile Of Chronic Lymphoproliferative Disorders In Patients Presenting With Lymphocytosis.

Objectives: To assess the spectrum and clinico-haematological profile of chronic lymphoproliferative disorders in patients presenting with lymphocytosis. METHODS: The cross-sectional, retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised data related to cases of bone marrow aspirate and trephine from January to November 2020. Patients for whom the bone marrow was done for lymphocytosis were studied for the presence of lymphoproliferative disorders, sub-types and patients'characteristics. The diagnosis and classification were based on the World Health Organisation criteria for tumours of haematopoietic and lymphoid tissues. Data was analysed using SPSS 21. RESULTS: Of the 3,334 bone marrow specimenstested, 103(3%) were related to lymphocytosis. Of these, 84(82%) were diagnosed with lymphoproliferative disorders, while diagnosisremained undetermined in 19(18%) cases. Male:female ratio was 3.6:1 and median age was 60 years (range: 21-85 years). Constitutional symptoms were found in 61(73%) patients. Median absolute lymphocyte count was 45x109/L (range: 5.3-480). All 84(100%) patients were classified as B-cell lymphoproliferative disorder. Chronic lymphocytic leukaemia wasthe most common form, 61(73%), and 31(51%) of them presented with advanced stage disease. CONCLUSIONS: A huge majority of patients presenting with lymphocytosis had underlying lymphoproliferative disorders of which B-cell chronic lymphocytic leukaemia was found to be the most common.

Paediatric Thrombosis: A Five-Year Experience From A Tertiary Care Center Of Pakistan.

BACKGROUND: Advances in imaging techniques and longer survival of chronic medical conditions contribute to the increase in paediatric thrombosis. We aim to determine the incidence, underlying risk factors, management and clinical outcome of paediatric thrombosis at a multidisciplinary facility of Pakistan. METHODS: A retrospectively analysis of the medical records of patients in the paediatric age group admitted at the Aga Khan University hospital from January 2013-September 2018 was performed. Site of thrombosis, associated risks factors, management options and outcome of thrombotic event were evaluated. RESULTS: Of the 22,320 paediatric hospitalization, 35 paediatric patients were diagnosed with thrombosis (15 cases per 10,000 admissions). The median age of the study group was 15 years and twenty patients (57%) were male. The commonest site of thrombosis was in lower limb venous 11 (31%), followed by upper limb venous thrombosis 6 (17%), abdominal vein thrombosis 7 (20%), cerebral venous thrombosis 5 (14%), pulmonary embolism and arterial thrombosis 3(9% each). Eighty three percent had underlying clinical condition including central venous catheter [CVC] (26%), malignancy and infection (14% each), antiphospholipid antibody syndrome (9%), inherited thrombophilia (9%), congenital heart disease (6%), while thrombotic thrombocytopenic purpura and autoimmune disorder (3% each). Twelve (34%) patients were treated with heparin only, 8 (23%) received heparin followed by warfarin while warfarin as a single agent was given in 2 (5.7%) patients. One patient died of pulmonary embolism while 9 (25%) had persistence or recurrence of thrombosis. CONCLUSIONS: Incidence of paediatric thrombosis was 0.15%. CVC placement was the most common associated risk factor. Warfarin and heparin both were found to be safe anticoagulation option. Recurrence rate was found to be high.

Different Shapes Of Megakaryocytes In Essential Thrombocythemia.

Essential thrombocytopenia is the myeloproliferative neoplasm associated with the JAK2/CALR/MPL mutation. It is characterized by an increase in thrombocytes and abnormal megakaryocytes. WHO established the diagnostic criteria for diagnosing the myeloproliferative disorder, which is the combination of molecular, clinical, and histological findings. The appearance of megakaryocytes on bone marrow biopsy is the distinguishing feature to identify myeloproliferative neoplasm, and this short review would like to emphasize the presentation of megakaryocytes in bone marrow biopsy.

Seroprevalence of Hepatitis B, Hepatitis C, Human Immunodeficiency Virus, syphilis, and malaria among blood donors at tertiary care hospital blood bank.

OBJECTIVE: To ascertain the frequency of markers of transfusion-transmitted infections among blood donors in a tertiary care setting. METHODS: The retrospective cross-sectional descriptive study, was conducted in the Blood Bank section of the Department of Pathology at the Dow University of Health Sciences, Karachi, and comprised data of blood donors from January 2013, to October 2018. All blood donors had been screened for hepatitis B, hepatitis C, human immunodeficiency virus I and II, syphilis through electrochemiluminescence and malaria using immunochromatography. Data was analyzed using SPSS 21. RESULTS: Of the 29,732 donors, 29,712(99.93%) were males and 20(0.06%) were females; 12(0.04%) were volunteers and 29,720(99.95%) were exchange donors. Overall, 2587(8.7%) donors were positive for an infectious disease; 908(3%) hepatitis C virus, 887(2.9%) hepatitis B, 620(2%) syphilis, 168(0.5%) human immunodeficiency virus and 4(0.02%) malaria. CONCLUSIONS: Hepatitis C and B were the most frequent infections, followed by syphilis in the sample.

Precursor Lymphoblastic Lymphoma in the Extramedullary Tissue: A Rare Manifestation of Chronic Myeloid Leukemia in Blast Crisis.

Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by immature granulocytes in peripheral blood and bone marrow. In 95% of cases, it is always due to the presence of Philadelphia chromosome characterized by the presence of reciprocal translocation between chromosome 9 and 22. However, in 7% -17% of individuals, extramedullary proliferation also occurs, either in skin, lymph nodes, bone or central nervous system (CNS), which could be either myeloid, lymphoid or mixed progenitor in origin. The present case is of a 23-year-old male who presented with lower limb weakness, bowel and urinary incontinence. His complete blood count (CBC) findings showed a raised white blood count (WBC) of 408 X 10E9/L. Peripheral film, bone marrow biopsy and immunohistochemistry showed findings consistent with CML in chronic phase. Bone marrow cytogenetic revealed the presence of Philadelphia chromosome. Simultaneously, magnetic resonance imaging (MRI) was done which revealed extradural mass at L1-L3 level; histopathological and immunohistochemistry findings showed features compatible with precursor B cell lymphoblastic lymphoma. His cerebrospinal fluid (CSF) cytology revealed similar blast cells. This extramedullary presence of lymphoid blast cells in the CNS put the patient in the rare entity of CML in blast crisis. He was started on tablet nilotinib and also received multiple cycles of intrathecal chemotherapy with cytosar, methotrexate and hydrocortisone. He also underwent radiotherapy of extradural mass. His lower limb weakness improved dramatically. However, after receiving the fourth cycle of intrathecal therapy, the patient died consequent to neutropenic sepsis. Extramedullary blast crisis in CML has a poor prognosis. Any patient with CML, presenting with CNS symptoms or lymph node enlargement should be thoroughly investigated for extramedullary blast crisis, as there is a considerable change in management and prognosis from the prototype CML in chronic phase.

Congenital Thrombotic Thrombocytopenic Purpura With a Novel ADAMTS13 Gene Mutation.

Congenital thrombotic thrombocytopenic purpura (TTP) is an autosomal recessive disorder characterized by thrombocytopenia, microangiopathic hemolytic anemia (MAHA), and thrombosis. Congenital TTP should also be considered while investigating neonatal hyperbilirubinemia, hemolytic anemia, or isolated thrombocytopenia. This case is of an 8-year-old male child who presented with prolonged and recurrent history of thrombocytopenia and MAHA, first identified when he was seven weeks of age preceding neonatal hyperbilirubinemia. Peripheral blood smear examination showed thrombocytopenia and schistocytes. He then went through a series of laboratory investigations until at the age of seven years, when the ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) antigen level was performed and found to be low: 40 ng/ml (630-850). Subsequently, he received a trial of steroids and rituximab which were found to be ineffective and associated with complications. In this case, a definitive diagnosis was delayed until the age of eight years when a novel homozygous pathogenic frameshift variant ADAMTS13 c.3033delC, p.Cys1012AlafsX109 in exon 23 was identified. After receiving regular plasma infusions, thrombocytopenia and hemolysis improved. Congenital TTP should be considered in every neonatal hyperbilirubinemia, thrombocytopenia or hemolytic anemia to avoid delay in diagnosis. Early diagnosis through analysis of the ADAMTS13 gene is crucial for optimal management as well as for genetic counselling.

Extensive iron overload in bone marrow: A cause of pancytopenia in a thalassemia major patient - A case report.

Iron overload-associated organ damage in transfusion-dependent anemias is a well-known phenomenon. Here, we discuss a case of 28-year-old, poorly chelated thalassemia major patient, whose blood workup revealed pancytopenia and moderately raised serum ferritin levels. His bone marrow examination was performed which revealed massive iron overload. Aggressive iron chelation led to successful recovery of peripheral blood counts in his patient. This case focuses on the importance of early detection and timely management of reversible iron overload toxicities. Serum ferritin although is convenient marker to asses iron overload, but it should not be relied upon to assess the severity of iron overload. Hence, organ-specific diagnostic modalities must be used along with serum ferritin to assess the severity of iron overload to prevent long-term complications in patients with regular blood transfusions.

Reporting transfusion-related acute lung injury cases.

BACKGROUND: Transfusion-related acute lung injury (TRALI) is a rare but potentially fatal complication of blood product transfusion. It is felt worldwide that TRALI is an underrecognized and underreported entity because of lack of awareness. AIM: The purpose of this study was to report all cases of TRALI diagnosed in a tertiary care hospital over a 5-year period. MATERIALS AND METHODS: This is a retrospective review of all TRALI cases reported from January 2011 to December 2015. All TRALI cases were identified from a manual review of reported transfusion reaction forms. For detailed information of all TRALI cases, medical record charts of patients were reviewed. The record of donors implicated in TRALI cases was derived from blood bank system. STATISTICAL ANALYSIS USED: The rate of TRALI cases per 1000 blood products transfused was computed by dividing the transfusion reactions by total number of all blood units transfused. RESULTS: Total number of transfusions during the study was 291,041. Six cases of TRALI were reported during this period. Rate of TRALI per 1000 units transfused was 0.02%. The mortality associated with TRALI was 33.3%. TRALI occurred following the transfusion of fresh-frozen plasma in one patient, packed red blood cells in two patients, and a mixture of blood components in three patients. In all cases, the donors were male. CONCLUSION: The rate of TRALI reported to our blood bank was found to be 0.02%, which is very low as compared to international data. This is the first comprehensive study on TRALI from the country and a step forward to create awareness about the importance of diagnosing and reporting TRALI.

Use of ISTH bleeding assessment tool to predict inherited platelet dysfunction in resource constrained settings.

BACKGROUND: The International Society of Thrombosis & Hemostasis (ISTH) bleeding assessment tool (ISTH-BAT) is used to record bleeding symptoms in patients with possible bleeding disorders. AIM: To investigate the utility of the ISTH-BAT in predicting platelet dysfunction in individuals with suspected inherited platelet function disorders. METHOD: Individuals with clinical evidence of bleeding and suspected inherited platelet function disorder and healthy volunteers were included in the study. The ISTH-BAT questionnaire was applied prior to light transmission aggregometry (LTA). RESULTS: A total of 261 participants were included (100 healthy volunteers, and 161 with suspected inherited platelet function disorders). The ISTH-BAT score in participants with suspected inherited platelet function disorders (median 2; interquartile range [IQR] 5-1) was significantly higher than in healthy volunteers (median 0; IQR 2-0). There was also a significant difference between participants with suspected inherited platelet function disorders with a platelet defect detected by LTA (median 4; IQR 8-3) and those with normal platelet function (median 2; IQR 3-1) (p < 0.001). The ISTH-BAT score was associated with a demonstrable platelet defect on platelet function testing (area under the receiver operating characteristic curve = 0.8 [95% confidence interval 0.72-0.87, p = < 0.001] and odds ratio 3.25 [95% confidence interval 2.13-4.37, p = < 0.001]). CONCLUSION: The ISTH-BAT is a useful tool for documenting bleeding symptoms and the score obtained is also predictive of the presence of a platelet defect on LTA in patients with suspected inherited platelet dysfunction.