Diagnostic Accuracy of Immature Platelet Fraction (IPF) to Differentiate Between Thrombocytopenia due to Peripheral Destruction versus Bone Marrow Failure.

OBJECTIVE: To analyse the predictive value of immature platelet fraction (IPF) as an independent diagnostic marker to differentiate between hyperdestructive and hypoproductive thrombocytopenia. STUDY DESIGN: Cross-sectional observational study. Place and Duration of the Study: Armed Forces Institute of Pathology Rawalpindi, from February to July 2022. METHODOLOGY: A total of 164 samples were included in the study by non-probability consecutive sampling. Among these, 80 were obtained from normal individuals serving as control; 43 were obtained from patients having hyperdestructive thrombocytopenia (idiopathic thrombocytopenia, thrombotic thrombocytopenic purpura, disseminated intravascular coagulation); and 41 were obtained from those hypoproductive thrombocytopenia (acute leukaemia, aplastic anaemia, chemotherapy). Sysmex automated haematology analyzer, XN-3000 was used to determine the immature platelet fraction (IPF) of the patients. ROC curves analysis was done to ascertain area under curve. RESULTS: Immature platelet fraction (IPF %) was significantly higher in consumptive / hyperdestructive thrombocytopenia group i.e. median (IQR), 21% (14.4-26.2) as compared to 6.5% (4.6-8.9) in hypoproductive thrombocytopenia, and 2.6% (1.3-4.1) in normal control group (p <0.001). Cut-off value with the highest sensitivity and specificity for IPF vs. normal population was 7.95% with sensitivity of 97.7% and specificity of 86%. CONCLUSION: Immature platelet fraction (IPF of 7.95%) possesses high diagnostic accuracy, sensitivity and specificity for differentiation between hyperdestructive vs. hypoproductive thrombocytopenia. It can be used as a reliable marker to differentiate between the two entities. KEY WORDS: Immature platelet fraction, Thrombocytopenia, Bone marrow failure, Peripheral destruction.

Diagnostic Significance Of Bone Marrow Examination Amongst The Patients With Abnormal Haematological Parameters.

BACKGROUND: Bone Marrow examination is considered to be the most indispensable diagnostic tool for the evaluation of many neoplastic and non-neoplastic haematological disorders. After an initial assessment of suspicious cases on abnormal laboratory parameters along with the clinical presentation of the patient marrow examination is finally required for diagnosis as well as management of many haematological malignancies as it offers a clear cytological as well as histological picture of Bone Marrow aspirate and biopsy respectively. The Objective was to evaluate the significance of Bone Marrow examination in patients with abnormal haematological parameters. METHODS: A retrospective study conducted at the Pathology Department of Pak Emirates Military Hospital from (Jan-June 2022) On data from150 patients who were advised to undergo bone marrow examination due to abnormal lab parameters and peripheral smear findings after informed consent and approval from the ethics review committee, to find out the correlation of abnormal haematological parameters and aspirate findings which have led to a definitive diagnosis. Data comprising basic demographic variables (age, gender etc.), Abnormal Haematological Parameters (CBC), peripheral smear findings and Aspirate findings were analyzed using SPSS version 23.0. RESULTS: Out of 150 studied participants with abnormal haematological parameters 24 (16%) were diagnosed on bone marrow examination as acute leukaemia / Hodgkin's and Non-Hodgkin's lymphoma respectively, 13 (9%) cases of aplastic anaemia and Autoimmune HaemolyticAnaemia, 33 (22%)cases of hypersplenism, CML and multiple myeloma. While 22 (15%) cases were diagnosed with BME as CKD and reactive changes. Moreover, 22(15%) cases were found to have Iron Deficiency anaemia respectively. CONCLUSIONS: The study revealed that patients with abnormal haematological parameters should undergo bone marrow examination to ascertain the diagnosis for malignant as well as non-malignant conditions that could cause abnormal lab parameters.

Aberrant expression of myeloid antigens in patients of acute lymphoblastic leukaemia.

OBJECTIVE: To determine the immunophenotypic pattern and aberrant expression of myeloid antigens in newly diagnosed patients of acute lymphoblastic leukaemia(ALL). METHODS: This descriptive cross-sectional study was carried out in Haematology / Pathology department, Army Medical College, National University of Medical Sciences (NUMS) in collaboration with Immunology and Haematology departments of Armed Forces Institute of Pathology (AFIP), Rawalpindi from 1st January, 2019 to 31st December, 2019. Seventy-three (73) recently diagnosed patients of Acute Lymphoblastic leukaemia of all age groups and both genders were included in the study. A proforma was used to note demographic data. CBC, cytochemical stains and bone marrow examinations were carried out and assessed for morphology and percentage of blasts using a microscope. Flow cytometry was used to perform immunophenotyping on samples of peripheral blood and bone marrow, using a standard panel. RESULTS: The most commonly expressed markers were weak CD45, TdT, CD19, CD10 and HLA-DR. Weak CD45 was present in almost all blast cells and there was no remarkable difference in its positivity among various subtypes of ALL. Myeloid expression was observed in 13 (17.8%) cases. CD13 and CD33 were aberrantly expressed in 11 and 12.3 of all cases of ALL respectively. CONCLUSIONS: Expression of aberrant myeloid CD markers in acute lymphocytic leukaemia has prognostic significance and should be documented during lineage assignment of acute leukaemias while performing immunophenotyping.

Can disseminated intravascular coagulation scores predict mortality in COVID-19 patients?

OBJECTIVES: Complications related to coronavirus disease 2019 (COVID-19) may lead to disseminated intravascular coagulation (DIC), which has been reported to be among the known causes of mortality in such patients. This study aims to analyse the incidence of DIC in COVID-19 non-survivors and to assess the association between DIC and its comorbidities. METHODS: The medical records of 154 non-survivors of COVID-19, hospitalised between April 2020 and July 2020, were retrospectively analysed. The International Society on Thrombosis and Haemostasis (ISTH) criteria for DIC were applied to identify the occurrence of coagulopathy. The receiver-operating characteristic (ROC) analysis was used to assess the association between DIC and its comorbidities. RESULTS: Out of 154 non-survivors, non-overt DIC was observed in 94.8% of the patients, whereas only 5.2% fulfilled the overt criteria of DIC with a mean age 64.6 years. The mortality rate was 4.5 times higher among men than women. The D-dimer level was >250 ng/ml in 68.8% of the patients including 88.9% of the non-overt and 100% of the overt DIC patients. Prothrombin time (PT) in non-overt and overt DIC cases was 17.3 s and 24.4 s, respectively. Thrombotic event and chronic kidney disease were found to be the main predictors of DIC (p < 0.0001 and 0.03, respectively) followed by diabetes mellitus (DM) and hypertension (statistically insignificant). CONCLUSIONS: Our study concludes that the ISTH DIC score cannot predict mortality as the COVID-19 related DIC differs from the sepsis-induced DIC. Among the seriously ill, older patients with comorbidities, increased levels of D-dimer and prolonged PT are more reliable parameters among COVID-19 non-survivors.

Neutrophil-to-Lymphocyte Ratio, derived Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio and Lymphocyte-to-Monocyte Ratio as risk factors in critically ill COVID-19 patients, a single centered study.

BACKGROUND: A lot remains anonymous about the characteristics and laboratory findings that may evaluate poor outcomes in patients with Coronavirus disease 2019.The aim of this study was to determine the relationship of change in the peripheral blood factors of Neutrophil-to-Lymphocyte Ratio, derived-Neutrophil-to-Lymphocyte Ratio, Lymphocyte-to-Monocyte Ratio, and Platelet-to-Lymphocyte Ratio in hospitalized patients with COVID-19 and its severity. METHODS: Cross-sectional analytical study was performed at Department of Haematology in Pak Emirates Military Hospital affiliated with Army Medical College, Rawalpindi, Pakistan from March-July 2020. We included 735 patients confirmed by real-time reverse transcriptase polymerase-chain-reaction test for subacute respiratory syndrome corona virus-2 of all ages, irrespective of gender and were classified in groups of severe and non-severe groups. RESULTS: Data of blood and baseline characteristics were compared in between the two groups and found to be significant (p-value <0.001). The median age was 46.3 years, and 82 cases were only females. Receiver operator curve demonstrated larger area under the curve of NLR, d-NLR, and PLR and showed them as independent diagnostic biomarkers which were significantly associated with the severity of illness. Binary logistic regression performed in the form of forest plot also showed these factors were significantly linked with the severity (p-value <0.001). CONCLUSION: NLR, d-NLR, and PLR along with pre-existing co morbidities can be used as an independent biomarker for the poor clinical outcome of COVID-19 illness.

Post-transplant infections: single center experience from the developing world.

OBJECTIVE: To describe our experience of post-transplant infections in allogeneic stem cell transplants at the Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan. METHODS: From July 2001 to September 2006, patients with malignant and non-malignant hematological disorders having human leukocyte antigen (HLA)-matched sibling donors were selected for transplant. Pre-transplant infection surveillance was carried out, and strict prophylaxis against infection was observed. After admission to the hospital, patients were kept in protective isolation rooms, equipped with a HEPA filter positive-pressure laminar airflow ventilation system. Bone marrow and/or peripheral blood stem cells were used as the stem cell source. Cyclosporin and prednisolone were used as prophylaxis against graft-versus-host disease (GVHD). The engraftment was monitored with cytogenetic/molecular analysis and change of blood group. Survival was calculated from the date of transplant to death or last follow-up. RESULTS: One hundred and fifty-four patients received allogeneic stem cell transplants from HLA-matched siblings for various hematological disorders at the Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan between July 2001 and September 2006. Indications for transplant included aplastic anemia (n=66), beta-thalassemia major (n=40), chronic myeloid leukemia (n=33), acute leukemia (n=8), and miscellaneous disorders (n=7). One hundred and twenty patients were male and 34 were female. The median age of the patient cohort was 14 years (range 1 1/4-54 years). One hundred and thirty-six patients and 135 donors were cytomegalovirus (CMV) IgG-positive. One hundred and forty patients (90.9%) developed febrile episodes in different phases of post-transplant recovery. Infective organisms were isolated in 150 microbiological culture specimens out of 651 specimens from different sites of infections (23.0% culture positivity). Post-transplant infections were confirmed in 120 patients (77.9%) on the basis of clinical assessment and microbiological, virological, and histopathological examination. Mortality related to infections was 13.0%. Fatal infections included CMV disease (100% mortality, 6/6), disseminated aspergillosis (66.7% mortality, 4/6), pseudomonas septicemia (42.9% mortality, 9/21), and tuberculosis (25% mortality, 1/4). CONCLUSIONS: More than 90% of our patients developed febrile episodes with relatively low culture yield. The majority of infections were treated effectively, however CMV, aspergillosis, and pseudomonas infections remained problematic with high mortality.

Management of acute myeloid leukaemia--5 years experience at Armed Forces Bone Marrow Transplant Centre, Rawalpindi.

OBJECTIVE: To evaluate the outcome in denovo AML patients treated with different remission induction and consolidation chemotherapy regimens in our population. METHODS: A retrospective study on acute myeloid leukaemia (AML) patients was carried out at Armed Forces Bone Marrow Transplant Centre Rawalpindi Pakistan between July 2001 and June 2006. During 5 years period 46 patients received treatment for AML at our centre. Twenty nine patients were males and 17 were females. Median age of patients was 21 years (range: 7-56 years). These 46 patients were categorized into two groups on the basis of type of leukaemia and chemotherapy given. In group-I 40 patients (group Ia: 23 patients of M1-M6, less M3 group Ib: 17 patients of AML M3) received anthracycline and cytarabin based chemotherapy. In group-II, six patients (AML- M3) received all trans retinoic acid (ATRA) based chemotherapy. RESULTS: In group Ia, out of 23 patients, 14 patients (60.8%) achieved complete remission (CR) after remission induction chemotherapy, 10 patients remained in CR after 3rd and 4th consolidation. Eleven patients died and five patients relapsed during treatment and follow up. In this group overall CR, relapse rate (RR) and mortality was 30.4% (7/23), 21.7% (5/23) & 48% (11/23) respectively. In group Ib out of 17 patients, 9 patients (53%) achieved CR after remission induction. Eleven patients died during treatment while one patient relapsed in this group. Overall CR, RR & mortality was 29.4% (5/17), 6% (1/17) & 55% (11/17) respectively. In group II all patients achieved CR (100%) after 1st course of chemotherapy. Two of these patients unfortunately died of uncontrolled sepsis during 1st consolidation, while remaining 4 patients 66.6% are on maintenance chemotherapy and are still in CR. CONCLUSION: Overall CR, RR and mortality in all groups was 35% (16/46), 13% (6/46) and 52% (24/46) respectively at a median follow-up of 36 + 8 months. Survival in AML-M3 patients treated with ATRA based chemotherapy is significantly superior than anthracycline based chemotherapy (66.6% vs. 29.4%). Infection and chemotherapy toxicity being major causes of mortality.