Hara Prasad Pati

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.

Turnaround Time (TAT): Difference in Concept for Laboratory and Clinician

Lab investigations are essential in patient management and qualities of the tests reports are emphasized. But there is another aspect of quality which is often overlooked and that is timeliness which is expressed as turnaround time (TAT). Mostly the laboratory services are directed at providing a rapid, reliable report at a reasonable cost. However, most laboratories put undue stress on only reliability, where as the clinician gives more stress on how soon (TAT) a report would be available to them. There is no clear definition of TAT, as to which period should be included in determining TAT for a specific test. For laboratory personnel, it would be from the time of receipt of sample in laboratory till report is generated. However, for a clinician, it would appropriate from the time of his/her requisition of a test till the report reaches him/her. The TAT would not be similar for routine tests versus in STAT/urgent tests. TAT would be different for ICU/emergency services. The causes of poor satisfaction level from lab users includes stat and routine test TAT and stat test TAT is considered by majority as the most important indicator of laboratories functioning. Hospital computerization with record of time from test request, sample collection, report generation and receipt of report by clinician would help in generating TAT. Analyzing outliers in TAT in a lab gives insight of causes delay in TAT and the areas need improvement. Laboratories in developing countries are yet to use TAT and analyze them for laboratory improvement.

Cytochemical, immunophenotypic and ultrastructural characterization of acute leukemias: A prospective study of fifty cases

Abstract Cytochemistry and immunophenotyping are established methods in the diagnosis of most leukemias but the role of electron microscopy in diagnosis, apart from understanding the cellular morphology is less studied. We present here 50 cases of acute leukemias that were studied for morphology, conventional cytochemistry, immunophenotyping and transmission electron microscopy (TEM), including ultrastructural cytochemistry using myeloperoxidase (MPO) and platelet peroxidase activity. TEM morphology using ultrastructural cytochemistry helped in definitive typing in one mixed lineage leukemia case, one AML-M5b, one AML-M6b and one microgranular variant of APML. Thus, ultrastructural studies may be useful in accurate diagnosis of biphenotypic leukemia and further classification of acute leukemias. Also, in cases with hypercellular marrow and with associated myelofibrosis, where the marrow aspirate gives low cell count, ultrastructural studies are a valuable aid to arriving at an accurate diagnosis.

Immunoglobulin free light chains: do they have a role in plasma cell leukemia?

Abstract The assay of serum free light chains (FLCs) is established in the diagnosis and prognosis of several plasma cell dyscrasias, but its significance in plasma cell leukemia (PCL) has not been reported so far. PCL is a rare and aggressive disease with a poor prognosis. The authors describe two cases of PCL with divergent clinical profiles where the serum FLC assay was available. Although both patients had greatly elevated serum β 2-microglobulin, one patient had much higher levels of serum FLCs and evidence of renal impairment, which were absent in the other; however, the latter, who had multisystem involvement, showed a more rapidly downhill course with early mortality.

Acute Traumatic Endotheliopathy in Isolated Severe Brain Injury and Its Impact on Clinical Outcome

Study design: Prospective observational cohort. Objective: To investigate the difference in plasma levels of syndecan-1 (due to glycocalyx degradation) and soluble thrombomodulin (due to endothelial damage) in isolated severe traumatic brain injury (TBI) patients with/without early coagulopathy. A secondary objective was to compare the effects of the degree of TBI endotheliopathy on hospital mortality among patients with TBI-associated coagulopathy (TBI-AC). Methods: Data was prospectively collected on isolated severe TBI (sTBI) patients with Glasgow Coma Scale (GCS) ≤8 less than 12 h after injury admitted to a level I trauma centre. Isolated sTBI patients with samples withdrawn prior to blood transfusion were stratified by conventional coagulation tests as coagulopathic (prothrombin time (PT) ≥ 16.7 s, international normalized ratio (INR) ≥ 1.27, and activated partial thromboplastin time (aPTT) ≥ 28.8 s) and non-coagulopathic. Twenty healthy controls were also included. Plasma levels of thrombomodulin and syndecan-1 were estimated by ELISA. With receiver operating characteristic curve (ROC) analysis, we defined endotheliopathy as a syndecan-1 cut-off level that maximized the sum of sensitivity and specificity for predicting TBI-AC. Results: Inclusion criteria were met in 120 cases, with subjects aged 35.5 ± 12.6 years (88.3% males). TBI-AC was identified in 50 (41.6%) patients, independent of age, gender, and GCS, but there was an association with acidosis (60%; p = 0.01). Following isolated sTBI, we found insignificant changes in soluble thrombomodulin (sTM) levels between patients with isolated TBI and controls, and sTM levels were lower in coagulopathic compared to non-coagulopathic patients. Elevations in plasma syndecan-1 (ng/mL) levels were seen compared to control (31.1(21.5–30.6) vs. 24.8(18.5–30.6); p = 0.08). Syndecan-1(ng/mL) levels were significantly elevated in coagulopathic compared to non-coagulopathic patients (33.7(21.6–109.5) vs. 29.9(19.239.5); p = 0.03). Using ROC analysis (area under the curve = 0.61; 95% Confidence Interval (CI) 0.50 to 0.72), we established a plasma syndecan-1 level cutoff of ≥30.5 ng/mL (sensitivity % = 55.3, specificity % = 52.3), with a significant association with TBI-associated coagulopathy. Conclusion: Subsequent to brain injury, elevated syndecan-1 shedding and endotheliopathy may be associated with early coagulation abnormalities. A syndecan-1 level ≥30.5 ng/mL identified patients with TBI-AC, and may be of importance in guiding management and clinical decision-making.

Early posttraumatic changes in coagulation and fibrinolysis systems in isolated severe traumatic brain injury patients and its influence on immediate outcome

OBJECTIVE/BACKGROUND Early coagulopathy in isolated severe traumatic brain injury occurs despite the lack of severe bleeding, shock, and fluid administration. We aimed to correlate coagulation activation/inhibition, thrombin generation and fibrinolysis with the development of acute trauma induced coagulopathy (TIC) and its effects on early mortality in isolated severe traumatic brain injury (iSTBI) patients. METHODS A prospective screening of iSTBI patients was done for two years. History of anticoagulants, liver disease, hypotension, extracranial injuries, transfusion, brain death were excluded. TIC was defined as international normalized ratio (INR) ≥ 1.27 and/or prothrombin time (PT) ≥ 16.7 seconds and/or activated partial thromboplastin Time (aPTT) ≥ 28.8 seconds on admission following iSTBI. Analysis of tissue factor (TF), tissue factor pathway inhibitor (TFPI), protein C (PC), protein S (PS), thrombin/antithrombin complex (TAT), soluble fibrin monomer (sFM), tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) was done. Cases were categorized as presence or absence of TIC and 20 healthy controls participants were included. RESULTS A total of 120 cases met the inclusion criteria, aged 35.7 ± 12.12 years, 96% males. TIC was identified in 50 (41.6%). TIC occurred independently of age, sex, Glasgow coma scale (GCS) but was associated with acidosis (60%; p = .01). Following iSTBI significant decline was seen in coagulation activation. Thrombin generation and fibrinolysis were markedly increased. TF, TFPI, PC and PS were low in TIC compared with control. Significant depletion of PS was seen in TIC versus No-TIC. TBI patients with depleted PS had an odds ratio (OR) of 7.10 (1.61-31.2) for TIC. Receiver operating characteristic curve (ROC) analysis depicted area under the curve (AUC) of 0.73 (95% confidence interval [CI] 0.63-0.84) with a cut-off of ≥74 of PS (specificity 63.9%, sensitivity 72.7%). In-hospital mortality was higher in TIC group (44%) compared with no-TIC (20%) with OR of 4.73 (95% CI 1.68-13.3) and hazard ratio [HR] of 2.8 (95 % CI 1.2-6.4). CONCLUSION Incidence of TIC in iSTBI is 41.6%, with 4.7 times odds for mortality. Traumatic brain injury causes enhanced coagulation activation, inadequate inhibition, exacerbation of thrombin generation, and subsequent increased fibrinolysis. ROC curve analysis revealed a cut-off of PS ≤ 74 with specificity 63.8%, sensitivity 72.7% for development of TIC.

PRCA with myelofibrosis: an unusual case report

The association of PRCA and myelofibrosis is very rare with only two such cases reported in the literature. Leukemic transformation in myelofibrosis is known but the progression of PRCA to acute leukemia is very rare. We present an unusual case of PRCA with myelofibrosis which after 14 months of transfusion dependent anemia transformed to acute monocytic leukemia.