CLINICO-HEMATOLOGICAL STUDY OF ACUTE LYMPHOBLASTIC LEUKEMIA AND THEIR CORRELATION WITH INFLAMMATORY MARKERS IN SERUM.

SUMMARY: Acute lymphoblastic leukemia (ALL) is early childhood hematological malignancies. In present scenario immunophenotyping became an important tool for subtyping of ALL into B-ALL and TALL. In order to understand the mechanism of development of leukemia it is important to study the cytokine environment of malignant cells. OBJECTIVE: Aim of the present study was to evaluate clinical and hematological features in ALL and correlate serum levels of IL6 and IL-10 expression in ALL patients and their subtypes. MATERIALS & METHODS: A total of 68 ALL cases along with 20 healthy controls were included in the study between periods of 2015 to 2017. About 4 mL blood samples were collected from all cases for immunophenotyping and serum studies. Levels of IL6 and IL10 were determined in all cases by ELISA. RESULT: In the present study immunphenotyping was done in all cases of ALL, which showed 52 cases (76.5%) of B-ALL and 16 cases (23.5%) of T-ALL. T-ALL was mostly found in higher aged children than B-ALL. A male predominance was seen in all cases. No signicant differences in hemoglobin levels and platelet counts were found between T-ALL and B-ALL. A signicantly high percentage of T-ALL cases were having more than 50000 cells per microliter than B-ALL (56.2% vs. 23.1%). Almost similar clinical features were found in both subgroups, only bleeding manifestation was found signicantly higher in T-ALL than B-ALL (31.2% vs.11.5%). Acute lymphoblastic leukemia (ALL) patients were associated with signicantly elevated serum IL6 and IL10 level than the healthy control group. Mean levels of serum IL6 were 167.9±306.46 pg/mL in ALL, and 6.51 ± 2.27 pg/mL in healthy control group. Mean IL10 levels were 70.56±111.48 pg/mL in ALL and 29.39 ± 4.27 pg/mL in control group. There were no signicant differences found in IL-6 and IL-10 serum levels between T-ALL and B-ALL. CONCLUSION: Present study found elevated level of IL-6 and IL-10 in ALL patients which suggest possible role of these cytokines in disease transformation. Detection of IL-6 and IL-10 in newly diagnosed patient may predict disease outcome and possibly poor prognosis in patients

Dealing with hypodysfibrinogenemia during pregnancy with a successful outcome

Background: Fibrinogen is a protein playing pleiotropic role in human body. It is engaged in maintaining hemostasis. Congenital fibrinogen disorders comprise quantitative and qualitative fibrinogen anomalies. The symptoms range from bleeding, thrombosis to asymptomatic at all what is the most common case. Hypodysfibrinogenemia with lower level of fibrinogen of reduced activity, is the least common of all congenital fibrinogen disorders. Case report: A 31-year-old woman was reported at the 21 weeks of gestation, suffered from genital tract bleeding and there was a history of stillbirth. Clinical examination with no pathology, however laboratory tests revealed coagulation abnormalities due to prolonged thrombin test, decreased protein S and lower fibrinogen level (70 mg/dl). Autoimmune diseases were excluded and the diagnosis was widened with rotational thromboelastometry and genetic test for hypodysfibrinogenemia. The patient was treated with fibrinogen substitution and prophylactic dose of heparin throughout pregnancy and 2 weeks following labour. At 39 week of gestation Caesarean section was done, with no complications. Results: Genetic test revealed heterozygous mutation in fibrinogen gamma gene confirming hypodysfibrinogenemia. Due to bleeding manifestation in this patient of congenital fibrinogen disorders, fibrinogen substitution was implemented with heparin as a paranticoagulant prophylaxis, what turned out to be successful and enabled the patient to maintain the pregnancy. Conclusions: As hypodysfibrinogenemia symptoms are diverse the management is difficult and each patient’s therapy should be planned separately. Pregnancy may be the first time when congenital fibrinogen disorders reveal and it is especially challenging to prevent from obstetrical complications.

Evaluation of thrombocytopenia: A single-center experience

To evaluate the common etiologies and bleeding manifestations in patients of thrombocytopenia and its clinical presentation, methods of investigation, and impact of various modes of management. Total 104 patients with platelet count less than l00,000 per cu.mm. with age, more than 12 years admitted to hospital between January 2010 to October 2011 were included in this study. Platelet count on automated cell counter less than 100,000 per cu.mm. and confirmed in peripheral smear were included in the study. All EDTA samples were processed in Abacus junior 5 hematology Analyser. Peripheral blood smear review was done for all cases. Clinical history and physical examination were collected from patients and medical record files.The present study included 56 male patients and 48 female patients. The most common bleeding manifestation was petechial rash 8.6%, hemoptysis and traumatic bleeding account for 1.9 % each, whereas 74% of patients did not present with any bleeding issues. Total 66 patients presented with symptoms of fever, 73 had signs of pallor, 22 patients had splenomegaly, 16 patients had hepatomegaly. Total 37.5% of patients were diagnosed with malaria and 1 patient (0.96%) was diagnosed with plasma cell leukemia. Chronic liver disease, megaloblastic anaemia, ITP (Idiopathic thrombocytopenia) and chronic renal failure account for 9.6%, 13.4%, 5.7% and 3.8% respectively. Total 16 patients had platelet counts less than 20000/cu.mm. and 37 patients had platelet count between 60000-80000/cu.mm. Malaria (39 patients) was the major cause of thrombocytopenia. Out of 39 patients with malaria 10 patients had P. Falciparum, 27 had P. Vivax and 2 patients had both. Patients with a platelet count less than 100,000/cu.mm have very high chances of bleeding manifestation. Cutaneous bleed is the most common manifestation. Malaria can be present with signs of thrombocytopenia. Timely and accurate diagnosis is the key to the management of thrombocytopenia.

Post Transfusion Purpura - Red Alert to Clinician

A 45-year-old multiparous female was admitted 1 week back in Bapuji hospital attached to J J M medical college in view of iron deficiency anaemia and had underwent 3 pints of blood transfusion and was discharged with haematinics. Now after 5 days patient noted purpura and ecchymosis over her all four limbs which has increased from past 2 days. Patient also noticed epistaxis, subconjunctival haemorrhage in the last 1 day which brought her to Bapuji hospital in November 2019. Patient had no history of fever, bleeding per rectum, melena, joint pains, headache, blurring of vision, loss of consciousness, seizures. No past history of bleeding manifestations, blood transfusions and medications altering haemostasis in the family. Complete hemogram showed Hb : 11.1 g/dl, total count: 7210 cells/cumm, platelet count: 22000 cells/cumm. Peripheral smear showed normocytic normochromic anaemia with severe thrombocytopenia. LFT showed serum bilirubin: 2.5 mg/dl, indirect bilirubin: 1.9 mg/dl with normal liver enzymes. Coagulation profile and fever profile was done to rule out other causes of thrombocytopenia and was found to be normal. Serum LDH levels were 856 u/l. Direct and indirect coombs test is negative. ANA was negative. USG abdomen shows no splenomegaly. Patient was transfused with 4 pints of platelets and repeat platelet count after 12 hours shows 19000 cells/cumm. This clinical picture with bleeding manifestation with history of blood transfusion suggested post transfusion purpura, patient was transfused with aphaeretic blood and iv immunoglobulins at 500 mg/kg/day for 5 days and corticosteroid prednisolone was given at the dose of 1 mg/kg body weight. Patient platelet count improved significantly to 72,000 cells/cumm on 3rd day of admission. Patient did not have further bleeding manifestation. Patient’s platelet count improved to 1.60 lakhs/cumm at the time of discharge. Patient couldn’t get anti platelet antibodies and HPA genotyping due to financial constraints.

Ethylenediaminetetraacetic Acid‑Dependent Pseudothrombocytopenia in Patient Previously Treated as Dengue Fever

One of the most widely used anticoagulants for a complete blood count is ethylenediaminetetraacetic acid (EDTA). Pseudothrombocytopenia (PTCP) may be caused by EDTA, this condition may lead to inappropriate diagnosis and treatment. We report a 25-year-old female with unspecific headache and joint pain with very low platelet count since 1 month before hospital admission. She was diagnosed with Dengue fever infection and got some platelet transfusion from the previous secondary hospital. She was carried out for a blood test with another anticoagulant (sodium citrate) and bone marrow aspiration. The results showed that she had normal platelet count and bone marrow cellularity. When a patient was identified with thrombocytopenia without any bleeding manifestation, hematology disease, and family history, PTCP should be taken into consideration to prevent unnecessary intervention. Keywords: platelet, pseudothrombocytopenia, ethylenediaminetetraacetic acid, Dengue fever

New Developments in the Pathophysiology and Management of Primary Immune Thrombocytopenia

Immune thrombocytopenia (ITP) is an autoimmune disease that is characterized by a significant reduction in the number of circulating platelets and frequently associated with bleeding. Although the pathogenesis of ITP is still not completely elucidated, it is largely recognized that the low platelet count observed in ITP patients is due to multiple alterations of the immune system leading to increased platelet destruction as well as impaired thrombopoiesis. The clinical manifestations and patients' response to different treatments are very heterogeneous suggesting that ITP is a group of disorders sharing common characteristics, namely, loss of immune tolerance toward platelet (and megakaryocyte) antigens and dysfunctional primary hemostasis. Management of ITP is challenging and requires intensive communication between patients and caregivers. The decision to initiate treatment should be based on the platelet count level, age of the patient, bleeding manifestation, and other factors that influence the bleeding risk in individual patients. In this review, we present recent data on the mechanisms that lead to platelet destruction in ITP with a particular focus on current findings concerning alterations of thrombopoiesis. In addition, we give an insight into the efficacy and safety of current therapies and management of ITP bleeding emergencies.

Clinical Evaluation of Febrile Thrombocytopenia in Western Rajasthan - a Hospital-based Study

: A number of patients of febrile thrombocytopenia increase during monsoon and postmonsoon period. Diseases like dengue fever, malaria, chikungunya fever, etc. are responsible for the clustering of febrile thrombocytopenia cases during this period. The diagnosis of fever with thrombocytopenia cases can be challenging and physicians should be aware of the regional and endemic seasonal cause of this syndrome. Study Design: It is a prospective observational study. Material and Methods: The study included 103 consecutive patients. The patients admitted with acute febrile illness defined by a duration of less than 2 weeks with thrombocytopenia were evaluated. Results: The present study included 103 consecutive cases of febrile thrombocytopenia. Out of these, 71.84% were male and 28.16% were female. The most common etiology for febrile thrombocytopenia was dengue fever (44.66%) and malaria (31.06%). Among clinical evaluation of the cases, fever was the inclusion criteria. Myalgia was the most common symptom found after fever, which was observed in 83.5% of the patients. The most common bleeding manifestation was petechiae/ purpura (12.62%) followed by hematuria (6.80%). Renal dysfunction was present in all 8(100%) cases of sepsis, followed by 14(43.75%) cases of malaria. All sepsis cases also had liver dysfunction, followed by 91.3% cases in dengue fever and 90.62 % cases in malaria had liver dysfunction. Conclusion: The study showed that acute febrile thrombocytopenia is an important seasonal syndrome. The common causes are dengue fever and malaria. Early identification of these diseases and prompt treatment decreases complications and reduces mortality.

Prevalence of Haemarthrosis and Clinical Impact on The Musculoskeletal System in People With Haemophilia in The United Kingdom; Evaluation of UK National Haemophilia Database and Haemtrack Patient Reported Data.

Introduction; Severe haemophilia is a rare x-linked recessive genetic disorder characterised by bleeding into soft tissue and joints. Haemarthrosis is the most common bleeding manifestation in haemophilia, leading to haemarthropathy. The ankle joint has been reported as the most common site of bleeding, but it is unclear whether the ankle is most affected in terms of joint health status. Aims; To determine the prevalence of joint bleeding and musculoskeletal health status at an individual joint level of children and adults with severe haemophilia A and B without a current inhibitor.Methods; Application was made to the National Haemophilia Database (NHD) with a request for the following; Haemtrack patient reported treatment record and Haemophilia Joint Health Scores (HJHS) in children (<18y) and adults (≥18y) with severe haemophilia A (HA) and B (HB) (FVIII/FIX, <0.01 iu/ml) without a current inhibitor. Data were collated and reported for 1st January to 31st December 2018.Results; 2238 cases were identified, of which 273 were Haemtrack compliant with contemporaneous HJHS. The median (IQR) age of children was 10 (6-13) and adults 40 (29-50) years. Haemarthrosis prevalence in HA/HB children was 33% and 47%, respectively and 60% and 42%, respectively, in adults. The most common haemarthrosis site in children was the knee in HA and ankle in HB. In adults, the incidence of haemarthrosis at the ankles and elbows was equal. Median (IQR) total HJHS in HA/HB children were 0 (0;0). In adults with HA/HB, HJHS were 18 (6; 31) and 11 (5; 24), respectively. In adults with HA/HB, mean (SD) ankle HJHS of 3.8 (4.1) and median 4.0 (0.0; 8.0) were higher than the knee (mean 2.9 (4.1) and median 1.0 (0.0; 5.0) and elbow (mean 3.3 (4.1) and median 1.0 (0.0; 7.0) joints.Conclusion; During 2018, NHD prevalence data of haemarthrosis indicate only two-thirds of children and one-third of adults from a UK cohort compliant with prophylaxis were bleed free. HJHS of zero in children suggests joint health status is either unaffected during childhood or undetected by HJHS. In adults, higher HJHS are reported for the ankles indicating worse joint health.

Clinical profile of thrombocytopenia in tropical infectious diseases

Background: In an infant or child thrombocytopenia can occur due to large spectrum of illness ranging from tropical infection to malignancy or bone marrow failure. Management is decided by the severity of thrombocytopenia, associated risk factors and underlying illness. Children with thrombocytopenia may be asymptomatic – detected by complete blood count for some other clinical issue or symptomatic-presenting with mucosal and/or cutaneous bleeding and rarely central nervous system bleed. Aim of this research is to study the distribution of patients with thrombocytopenia, their grading according to platelet counts and etiology with special focus to infective causes, other complications in these infections and recovery from thrombocytopenia.Methods: This is an observational analytical retrospective study. 100 randomly selected pediatric patients (6 months to 12 years) admitted in pediatric ward with documented thrombocytopenia (platelet count <150,000/ul) on admission or at any point of time during hospitalisation are enrolled and analyzed.Results: 91% patients have thrombocytopenia associated with infective causes, of which 44% have dengue. 7 patients in study have bleeding manifestations and 3 required platelet transfusion. 50% patients with dengue with thrombocytopenia have leucopenia and 2% have pancytopenia. 57.1% patients with enteric fever with thrombocytopenia show elevated alanine aminotransferase (ALT) levels. Mean platelet recovery time is 2 to 4 days for various infections.Conclusions: Majority of patients do not have bleeding manifestations, and they are mainly seen with severe thrombocytopenia associated with infections. Requirement of platelet transfusion is not common and is seen only in patients with severe thrombocytopenia with significant bleeding manifestation.