Severe amlodipine toxicity: A medical dilemma managed with therapeutic plasma exchange.

Amlodipine poisoning is a nightmare for treating clinicians because of the intractable hypotension and bradycardia induced by the drug, which requires a balanced treatment algorithm. We encountered a case of severe Amlodipine toxicity (450 mg) who presented with complaints of nausea, multiple episodes of vomiting, and chest discomfort. On arrival at the EMD, the patient had significant hypotension (80/46 mmHg), bradycardia (40 beats/min), and a fall in oxygen saturation (75 %). He was symptomatically managed with inotropes, IV calcium, IV fluids, and oxygen supplementation. We decided to go forward with Therapeutic Plasma Exchange (TPE) in an attempt to remove the inciting agent. Two sessions of TPE were performed and the patient showed significant improvement post-procedure which led to the discharge of the patient within 10 days of admission. This case report highlights the noteworthiness of TPE in treating significantly high doses of drug poisoning.

Inherited thrombophilia in unprovoked venous thromboembolism: Is non 'O' blood group an additional culprit in Indian patients?

BACKGROUND: Venous thromboembolism (VTE) is a known situation of considerable mortality and morbidity and occurs due to the convergence of multiple acquired and genetic risk factors. METHODS: In this study, we have comprehensively analyzed the effect of ABO blood groups and inherited thrombophilia factors [Protein C (PC), Protein S (PS), Antithrombin III (AT III), Activated Protein C Resistance (APCR) and Homocysteine (Hcy)] on 150 unprovoked VTE patients, comparing with normal healthy controls. ABO phenotyping was done using gel cards and thrombophilia workup done using standard kits on coagulation autoanalyzer. RESULTS: Non O blood group was significantly more frequent among cases than controls (77.3% vs. 62.7%) and had higher odds of VTE (OR = 2.03, 95%CI: 1.22-3.37).Positivity for at least one marker of thrombophilia was more in cases (40%) than controls (16%), and led to significantly higher odds (OR = 3.5, 95%CI: 2.03-6.04) of VTE. Deficiency of PS was the commonest thrombophilia abnormality.Combination of non O group with positivity for thrombophilia markers was also more among cases (OR = 5.67, 95%CI: 2.76-11.65). Highest odds of VTE in cases were associated with non O group in combination with increased Homocystein (OR = 10.8, 95%CI: 2.27-51.5). CONCLUSION: The study results show non O blood group and positivity for factors of inherited thrombophilia in cases impart higher odds of VTE individually. Also combination of both non O blood group and positivity for factors of inherited thrombophilia in cases further increases the odds of VTE. This awareness could assist physicians in identifying those at higher risk of VTE and tailor-made the thromboprophylaxis accordingly.

Minimal residual disease detection using flow cytometry: Applications in acute leukemia.

Minimal residual disease (MRD) describes disease that can be diagnosed by methodologies other than conventional morphology, and includes molecular methods (like polymerase chain reaction (PCR)) or flow cytometry (FCM). Detection and monitoring of MRD is becoming the standard of care, considering its importance in predicting the treatment outcome. MRD aids in identifying high-risk patients and hence therapy can be intensified in them while deintensification of therapy can prevent long-term sequelae of chemotherapy in low-risk category. FCM is considered as a less labor-intensive and faster MRD technique as compared to PCR although it has its own share of disadvantages. Current immune-based methodologies for detection of MRD depend on establishing leukemia-associated aberrant immunophenotype (LAIP), at diagnosis or relapse and use this information at specified time points for detection of MRD, or apply a standardized panel of antibody combinations for all MRD cases, in a different-from-normal approach. This review highlights MRD detection by FCM and its application in acute leukemia.

Antiphospholipid syndrome: A diagnostic challenge.

The antiphospholipid syndrome (APS) is an acquired autoimmune thrombophilic disorder that is characterized by thrombosis (venous, arterial and microvascular) and obstetric morbidity due to a diverse family of antibodies against phospholipid-binding proteins present in plasma. The term antiphospholipid antibody is actually a misnomer as the antibodies are not against the phospholipid per se, but target the plasma protein co-factors, which bind to anionic PLs. The exact etiology has not been elucidated and is multifactorial. The initial guidelines for the diagnosis of APS were laid down in Sapporo, 1999, which were subsequently revised as the Sydney Consensus Conference criteria in 2006. Major changes were the inclusion of ß2GPI as independent laboratory criteria, addition of ischemic stroke and transient cerebral ischemia as established clinical criteria and the requirement of repeating the test after 12 weeks. The laboratory tests recommended are coagulation assays, which study the effect of lupus anticoagulant on the clotting time and immunological assays, mostly ELISAs to detect IgG and IgM antibodies against cardiolipin and/or ß2 glycoprotein I. For the diagnosis of APS, at least one clinical criterion and one laboratory criterion should be present. Limitations pertaining to the standardization, reproducibility and robustness of the currently recommended diagnostic tests still remain. Despite elaborate guidelines and syndrome defining criteria, the diagnosis of APS still remains a challenge. A greater interaction between the clinicians and the laboratory professionals is necessary for arriving at the correct diagnosis as a misdiagnosis of APS can have grave consequences.

To study the effects of gamma irradiation on single donor apheresis platelet units by measurement of cellular counts, functional indicators and a panel of biochemical parameters, in order to assess pre-transfusion platelet quantity and quality during the shelf life of the product.

BACKGROUND: The occurrence of transfusion associated graft versus host disease can be prevented by gamma irradiation of blood components. This study was undertaken to assess the effects of gamma irradiation on single donor platelet (SDP) concentrate units. METHOD: SDPs were collected by a continuous flow apheresis technique (n = 400). The SDPs from each donor were divided into two parts, one gamma-irradiated with 25 Gy and the other used as a non-irradiated control. Swirling and morphological features, cellular counts, biochemical parameters including blood gas analysis, and platelet activation levels (CD62P: p-selectin) by flow cytometry were analyzed on Day 1 and on Day 5. RESULTS: Swirling and morphology were maintained in all products, in both the groups throughout the shelf life. No significant change was seen in both groups, on the first and fifth day, as far as pO2, pCO2, Na(+), K(+), HCO3 (-) & Ca(2+) were concerned. However, lactate increased and glucose decreased significantly in irradiated products over 5-day storage period. A small but significant decrease in pH and platelet count was found in the irradiated PCs after 5-day storage. The mean proportion of platelets expressing CD62P over 5-day storage increased significantly. CONCLUSION: After an overall assessment of all our in vitro parameter results and observations, a few of which were significant, while most were not significant, we concluded that a well-preserved quality of gamma irradiated apheresis platelets is maintained throughout the entire 5-day shelf life of the platelet product, with minimal difference compared to non-irradiated platelets.

Point of care hemoglobin testing in plateletpheresis donors: Noninvasive versus invasive methods.

BACKGROUND: Predonation hemoglobin (Hb) for plateletpheresis donors is estimated by presently available invasive methods. Venous samples of only those donors whose Hb is more than 12.5 g/dl are screened for complete blood count and transfusion transmissible infections. There is a pressing need to substitute this invasive Hb test with noninvasive one to reduce donor discomfort and avoid further pricking the donor. We therefore went ahead with the aim of comparing a noninvasive Hb estimation method NBM 200 with the invasive method - Hemocue, taking SYSMEX KX-21 as a gold standard. METHODS: 500 voluntary consenting plateletpheresis donors qualifying the laid down criteria for platelet donation were included in the study. Hb readings obtained by the NBM 200 and Hemocue were compared to those obtained from the fully automated hematology analyzer SYSMEX KX-21. RESULTS: Coefficients of correlation were found to be statistically significant at <0.0001 level of confidence. Results of Friedman's test on the three methods also showed significant difference in means. Bland-Altman plots and mountain plots also confirm the same. NBM 200 was found to be more sensitive, specific, and precise than Hemocue in detecting ineligible donors. CONCLUSION: NBM 200 was found to be more sensitive, specific, and precise as compared to Hemocue for predonation screening of Hb in plateletpheresis donors and the prime benefit it offers is that it is 'noninvasive' thereby assisting in stemming the platelet donor pool. The onus lies on the blood transfusion services to make use of appropriately validated gadgets that reduce the donor discomfort.

Proportion of Rh phenotypes in voluntary blood donors.

BACKGROUND: The Rh system is the major blood group system besides ABO system. Even after proper blood grouping and cross matching there is a possibility of alloimmunization and antibody production in the recipients against the Rh or minor blood group antigens like Kell, MNSs, Duffy etc. Keeping in view the heavy financial burden of complete phenotyping of blood; the determination of only Rh phenotypes can play a major role in preventing alloimmunization and adverse events in multitransfusion cases. To determine the proportion of Rh phenotypes in voluntary blood donors with a view to generate blood bank data for constitution of panel of blood donors for multipurpose utilities. METHOD: Identification of Rhesus factors (Rh) was done by the antigen antibody agglutination test by the test tube method on 10,133 healthy voluntary donors. RESULTS: The phenotypic frequencies of Rh blood groups in the studied population were D-92.25%, C-87.55%, E-26.55%, c-51.06% and e-98.42%. Thus 'e' was the most common and E was the least common of all the Rh types. Phenotypically DCCee group was the most common phenotype and dccee was least common type. CONCLUSION: Determination of Rh phenotypes can play a major role in preventing alloimmunization and avoiding adverse events in multitransfusion cases.

Non Infectious Complications Related to Blood Transfusion: An 11 year Retrospective Analysis in a Tertiary Care Hospital.

In India transmission of transfusion transmissible infections (TTI) has shown a relative decrease as a result of mandatory screening of donated blood for TTI's. However, reducing the incidence of non infectious complications poses a major challenge, mainly due to the fact that a number of adverse reactions go unreported. Blood transfusion reaction, can be categorized based on the time interval between transfusion of blood products and the presentation of adverse reactions as acute i.e. those presenting during or within 24 h and as delayed i.e. those presenting anytime after 24 h. Transfusion reactions can further be classified as immune and non immune or infectious and non infectious based on the pathophysiology. In this retrospective study which was undertaken with an aim to determine the type and frequency of non infectious complications due to transfusion of blood and blood products recorded the incidence of febrile non hemolytic transfusion reactions (FNHTR) 51.40 %, allergic reactions 40.14 %, non immune hemolytic reactions 4.22 %, hypothermia 2.81 %, anaphylaxis 0.70 % and iron overload 0.70 %. FNHTR which was found to be the most common complication in this study can certainly be minimized, if not completely eliminated by adopting a policy of universal leucodepletion, the implementation of which solely depends on the financial and infrastructure resources available. This study also reiterates the importance of hemovigilance as a tool to improve the safety of blood transfusion.

A Comparative Assessment of Quality of Platelet Concentrates Prepared by Buffy Coat Poor Platelet Concentrate Method and Apheresis Derived Platelet Concentrate Method.

Many blood centres in country don't have costly apheresis technology and rely heavily on the platelet production from whole blood donation. We conducted this study with the aim to compare the quality of platelet concentrates (PC) prepared by Buffy Coat derived (BC-PC) and apheresis derived platelet concentrate (Apheresis-PC). Our objective was to collect data by analysis of platelet concentrates prepared by BC-PC methods and Apheresis-PC methods in respect of swirling, volume, platelet count, WBC count and pH of the PC units and elaborate on the quality parameters. Tertiary Care Hospital and Medical College. We assessed a total of 200 BC-PC and 200 Apheresis-PC for their in vitro quality by observing swirling, volume of PC, platelet count/unit, WBC count/unit and pH, to see if they satisfy the recommended quality criteria. Data was analyzed using appropriate statistical technique under the guidance of biostatistician. Apheresis-PC units showed better swirling than BC-PC units (Chi square test; P < 0.05). There was a significant difference in proportion of units satisfying the required volume QC between the two methods (Chi-square test; P < 0.05). Apheresis-PC showed better adherence to the physiological pH values (Student's unpaired t test; P < 0.05). The units of BC-PC and Apheresis-PC did not show significant difference in proportion of units satisfying the Platelet count per unit and residual WBC count per count (Chi square; P 0.203 and 0.617 respectively). There was comparable adherence to QC requirement for platelet count and WBC contamination in two methods. BC-PC were found to be adhering lesser to QC parameters for swirling, volume and pH, but found to be in required QC limits. BCPC can be used effectively in the majority of thrombocytopenic patients in resource poor setting.

Knowledge of Transfusion Medicine Among Resident Doctors in Clinical Specialities: A Cross-Sectional Study from a Tertiary Care Centre.

UNLABELLED: Knowledge of transfusion medicine (TM) has profound impact on transfusion outcomes. Variations from the standards in practices of TM may jeopardize patient care. We assessed the awareness of TM in resident doctors. Our aims was to assess the essential knowledge of TM among resident doctors. The study was carried in a tertiary care hospital. It was a descriptive cross- sectional study using a self-administered, questionnaire comprising of 35 items which was developed to assess the essential knowledge of TM for resident doctors. A total of 85 residents responded from various clinical specialties. STATISTICAL ANALYSIS USED: Results of correct response were put as Mean ± SD using SPSS. Survey revealed an overall mean score of 48.53 % for correct responses. Lowest knowledge score of 32.94 % was found for blood bank procedures. The differences between the knowledge of residents from various specialities were not statistically significant. Our study shows that majority of resident doctors have inadequate knowledge of TM. More studies are required from different parts of the country to create data on this issue. The implementation of two weeks training for all residents from clinical specialties in TM department will improve the situation and help to connect our clinician to TM better.

Evaluation of Random Donor Platelets Produced from Buffy Coat Stored for 24 h at Ambient Temperature: Should This be Implemented in India?

Whole blood derived platelets are made from platelet rich plasma (PRP) method or buffy coat (BC) method. In India majority of random donor platelets (RDPs) are prepared by PRP method. However, BC method offers the advantage of less platelet activation and fewer WBC contamination. Presently in India RDPs are prepared within 8 h of whole blood collection, whereas, in Europe this time limit is up to 24 h. Our aim was to evaluate the platelet count, WBC contamination, platelet CD62P expression, and biochemical parameters of RDPs prepared from BC within 8 h and within 24 h of collection. We prepared 40 units of RDP by the BC method from whole blood stored at room temperature within 8 h of collection (fresh BC), and another 40 units from BC stored at 22 °C for <24 h (stored BC). We analyzed the platelet counts, CD62P expression, WBC counts, glucose levels, pH, PO2, PCO2 in both the groups of RDPs, 24 h after respective preparation. The platelet counts from stored BC was higher in fresh BC. CD62P expression was low in stored BC compared to fresh BC. There were no differences of pH, pO2, pCO2 and glucose levels in fresh BC and stored BC. WBC contamination was more in fresh BC. Our study stored BC contained higher platelet counts, less WBC contamination and less platelet activation. We conclude that RDP prepared from stored BC is the better method for RDP production.

Prevalence of Alloimmunization to Human Platelet Antigen Glycoproteins and Human Leucocyte Antigen Class I in ß Thalassemia Major Patients in Western India.

Present management of ß thalassemia major by regular packed red blood cell (PRBC) transfusions poses risk of alloimmunization not only to red blood cell antigens, but also to human platelet antigens (HPA) and Human leucocyte antigens class I (HLA I). However data in this context is very limited in Indian population. The aim of the study was to determine the prevalence of alloimmunization to HPA and HLA I in ß thalassemia major patients who have received multiple PRBC transfusions over the years. A cross sectional study was performed at our tertiary care blood bank. ß thalassemia major patients of more than 6 years of age were included who were receiving fresh, leucoreduced and irradiated PRBC units regularly with annual requirement of more than ten PRBC transfusions. A total of 9 out of 80 (11.25 %) patients were found to be alloimmunized for HPA antigens of various specificity and 24 out of 80 (30 %) developed antibodies to HLA I. The awareness of development of alloimmunization to HPA and HLA antigens in multi PRBC transfused thalassemics, despite use of leucofilters will prompt us, to look for improvement in our current PRBC preparations to minimise platelet alloimmunisation. Further studies are required to validate the findings and build the base line data in this regard. This is of importance, especially in view of providing suitable cross-matched platelets when required in future especially when considering future haematopoietic stem cell transplantation (HSCT).