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.

[Subpectoral tenodesis of the long head of the biceps tendon with an interference screw and a cortical button : Clinical and cosmetic results after 1 year]. / Subpektorale Tenodese der langen Bizepssehne mittels Interferenzschraube und Cortical-Button : Klinische und kosmetische Ergebnisse nach einem Jahr.

BACKGROUND: Pathologies of the long head of biceps tendon (LHB) can cause anterior shoulder pain. Surgical treatment includes tenotomy and tenodesis (TD), however TD causes fewer cosmetic deformities and less cramping of the biceps muscle. To date, numerous techniques for TD have been described but the "gold standard" has not yet been established. OBJECTIVES: The purpose of this study is to evaluate the functional and cosmetic outcome following subpectoral biceps TD with an interference screw and a cortical-button (STLHB-IC) after 1 year. MATERIALS AND METHODS: 35 patients (10 female, 25 male) with an average age of 57.4 ± 7 years were examined after STLHB-IC with a follow up of 12.8 ± 1.2 months. The constant score (CS), the long head of biceps score (LHBS) and the subjective shoulder value (SSV) were assessed. Furthermore, the cosmetic result was evaluated by the patient and the examiner, and the elbow flexion strength (EFS) was measured. RESULTS: The CS (82.5 ± 17.2), LHBS (90.1 ± 11.5) and SSV (83.2 ± 17.7) showed good and excellent results. The SSV increased significantly pre vs. postoperatively (40.6 ± 19.7 vs. 83.2 ± 17.7). The CS (82.5 ± 17.2) and the LHBS (90.1 ± 11.5), as well as the EFS (17.5 ± 4.8 kg) of the affected shoulder revealed no significant differences compared with the non-affected shoulder (CS: 91.8 ± 11.3, LHBS: 99.1 ± 11.5; EFS: 19.7 ± 4.8). Severe Popeye deformities (measured by LHBS) were found in 6% of the cases, however if they occurred patients (13.4 ± 3.8) evaluated them as significantly less disadvantageous than the examiners (11.9 ± 4.7). There were no neurovascular injuries, infections or fractures. CONCLUSION: STLHB-IC is a safe, reproducible technique with convincing functional and cosmetic results that provides high patient satisfaction.

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.

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.

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.

[Stent graft of the thoracic aorta]. / Stentversorgung der thorakalen Aorta.

Considering the demographic changes in our society and the proliferation of imaging-based improved diagnostics, both acute and chronic aortic diseases attract increasing attention and require dedicated care. Cardiac as well as vascular surgery used to represent the gold standards for therapeutic management of pathologies of the ascending aorta and the arch; however, the technological evolution of endoluminal strategies has had a serious impact on the treatment of the descending aorta, the aortic arch in combination with vascular debranching or bypass, and in selected cases even on managing pathologies of the ascending aorta. Although several case series and meta-analyses of published observations hint towards superiority of endografting in comparison to open surgical repair, the affected usually multimorbid patients with highly complex aortic disease should be subjected to an individual evaluation by a team of cardiologists, cardiac and vascular surgeons as well as imaging specialists; a dedicated individualized treatment concept in highly experienced centers of excellence is likely to provide the best results for such challenging patients.

Enhanced mobilization of the bone marrow-derived circulating progenitor cells by intracoronary freshly isolated bone marrow cells transplantation in patients with acute myocardial infarction.

Autologous bone marrow cell transplantation (BMCs-Tx) is a promising novel option for treatment of cardiovascular disease. We analysed in a randomized controlled study the influence of the intracoronary autologous freshly isolated BMCs-Tx on the mobilization of bone marrow-derived circulating progenitor cells (BM-CPCs) in patients with acute myocardial infarction (AMI). Sixty-two patients with AMI were randomized to either freshly isolated BMCs-Tx or to a control group without cell therapy. Peripheral blood (PB) concentrations of CD34/45(+) - and CD133/45(+)-circulating progenitor cells were measured by flow cytometry in 42 AMI patients with cell therapy as well as in 20 AMI patients without cell therapy as a control group on days 1, 3, 5, 7, 8 and 3, 6 as well as 12 months after AMI. Global ejection fraction (EF) and the size of infarct area were determined by left ventriculography. We observed in patients with freshly isolated BMCs-Tx at 3 and 12 months follow up a significant reduction of infarct size and increase of global EF as well as infarct wall movement velocity. The mobilization of CD34/45(+) and CD133/45(+) BM-CPCs significantly increased with a peak on day 7 as compared to baseline after AMI in both groups (CD34/45(+): P < 0.001, CD133/45(+): P < 0.001). Moreover, this significant mobilization of BM-CPCs existed 3, 6 and 12 months after cell therapy compared to day 1 after AMI. In control group, there were no significant differences of CD34/45(+) and CD133/45(+) BM-CPCs mobilization between day 1 and 3, 6 and 12 months after AMI. Intracoronary transplantation of autologous freshly isolated BMCs by use of point of care system in patients with AMI may enhance and prolong the mobilization of CD34/45(+) and CD133/45(+) BM-CPCs in PB and this might increase the regenerative potency after AMI.

Second- and third-generation drug-eluting coronary stents: progress and safety.

Drug-eluting stents (DES) have revolutionized the treatment of coronary artery disease by reducing the rate of in-stent restenosis from 20-40% with bare-metal stent (BMS) to 6-8% with DES. However, with widespread use of DES, safety concerns have risen due to the observation of late stent thrombosis. With this in mind and better understanding of mechanism and pathophysiology of stent thrombosis, the technological platform, especially innovative anti-restenotic agents, polymeric coatings, and stent platforms, improved with newer DES. Two second-generation DES, the Endeavor zotarolimus-eluting stent (ZES) and the Xience-V everolimus-eluting stent (EES), have provided promising results in both randomized controlled trials (SPIRIT and ENDEAVOR) and registries (E-Five, COMPARE) compared with bare-metal stents (BMS) and first-generation DES. Newer third-generation stent technology, especially biodegradable polymers, polymer-free stents, and biodegradable stents on the basis of poly-L-lactide (PLLA) or magnesium, has been evaluated in preclinical and initial clinical trials. However, despite encouraging initial results, long-term data of large-scale randomized trials as well as registries comparing them to currently approved first- and second-generation DES are still lacking.

Microalbuminuria: An inexpensive, non invasive bedside tool to predict outcome in critically ill patients.

This study was conducted to evaluate whether microalbuminuria on admission and after 24 hrs of admission to intensive care unit (ICU) predicts outcome as well as the Acute Physiology and Chronic Health Evaluation (APACHE) II severity illness score, the current accepted method of doing so. The study was carried out in a 20 bed mixed medical-surgical ICU of a tertiary care hospital. Of 525 consecutive adult patients with ICU stay of more than 24 hrs, 238 were included for the study. Patients with pregnancy, menstruation, anuria, macroscopic hematuria, urinary tract infection, marked proteinuria due to renal and post-renal structural diseases, were excluded. Spot urine samples were collected on admission to ICU and 24 hrs thereafter. Urine albumincreatinine ratio (ACR) was measured on ICU admission (ACR1) and after 24 hrs (ACR2) and expressed in mg/g. Patient demographics were noted on admission. For disease severity scoring, APACHE II scores were calculated. Each patient was followed up throughout their ICU stay for a maximum of 28 days and the following outcome data were obtained: ICU length of stay and ICU mortality. Of the 238 patients, 196 survived while 42 patients died in the ICU. Non-survivors had a significantly higher median ACR2 [162.7 mg/g (IQR 69.5-344.3)] in comparison to the survivors who had a median ACR2 = 54.4 mg/g (IQR 19.0-129.1) (P< 0.0001). The median ACR1 [161.0 mg/g (IQR 29.0-369.3)] of non-survivors was higher than the median ACR1 [80.4 mg/g (IQR 35.1-167.6)] of survivors but failed to reach statistical significance (P= 0.0948). In a receiver operating characteristic curve (ROC) analysis, ACR2 emerged as the best indicator of mortality [(area under curve (AUC) of ACR2 = 0.71 > AUC (ACR1) =0.58 > AUC (ΔACR) =0.55] similar to the currently used APACHE II scores (AUC = 0.78) (P=0.3). At a cutoff of 101 mg/g, ACR2 had a sensitivity of 69%, specificity of 67%, positive predictive value of 31% and a negative predictive value of 91% for predicting mortality in the critically ill patients. Absence of significant microalbuminuria at 24 hrs of ICU admission may help to predict survival in the ICU.

Assessment of vibration exposure and physiological responses of crew members during Infantry Combat Vehicle (ICV) operation: a pilot study.

BACKGROUND: Operation of infantry combat vehicle (ICV) influences the cardiorespiratory responses as well as the risk of vibration exposure on the crew members which adversely affect their performance and health. AIM: To assess the effect of stress factors, that is, ICV's compartmental temperature, relative humidity (RH) and vehicular vibration on the physiological parameters (heart rate (HR), respiratory frequency (RF), estimated core body temperature (ECT)) of the crew members during the ICV operation. METHODS: A 1 hour run trial of the ICV operation was conducted with its crew members at their respective positions. Compartmental temperature and RH were monitored at an interval of every 15 min during the run trial. Physiological parameters were monitored continuously during the run trial. Whole body vibration (WBV) and hand-arm vibration (HAV) of the crew members were also measured during the run trial time. RESULTS: The findings showed a strong positive correlation (p<0.05) between the increasing compartmental temperature and RH with its run trial time. Significant changes were observed in the physiological parameters (p<0.05) along with the increasing run trial time. Additionally, the physiological parameters showed a strong positive correlation with compartmental temperature and RH, respectively (p<0.05). Also, a significant increase (p<0.05) in the muscle strength was recorded after their exposure to ICV operation. The study also confirmed high level of WBV exposure of the crew members during the ICV operation. CONCLUSION: Increase in HR, RF and ECT along with increase in temperature and RH is a predictive indicator of physiological stress. Moreover, high levels of vibration exposure of various operations may bring deleterious effect on soldiers' health as well as their performance. Proper ergonomic intervention can reduce exposure to vibration, physiological stress and increase comfort which may ultimately ensure an optimum performance of soldiers and successful completion of mission.

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.

Dengue: A Clinicohaematological Profile.

BACKGROUND: Fifty cases of fever, clinically suspected to be dengue were studied. METHODS: Complete clinical, haematological evaluation and IgM capture assay was done. RESULT: 54% of patients clinically suspected to have dengue were positive for IgM antibodies by enzyme-linked immunosorbent assay (ELISA). The commonest clinical feature was fever with rash (85%). Thrombocytopenia was seen in 19% of patients only. One patient died of dengue shock syndrome (DSS). CONCLUSION: Out of the 27 cases of seropositive dengue there was one death due to dengue shock syndrome. Thrombocytopenia may not always be a feature of dengue.

Serological aspects of Dengue fever and its correlation with clinical features in a recent febrile outbreak.

The study was done to assess correlation between serology and clinical features of Dengue fever at Burdwan Medical College, where after clinical examination, blood samples were processed by E.I.A. Of 139 cases, mostly between 1 to 20 years, Male-Female ratio was 80:59. Bleeding manifestation was observed only in 3 cases, and Lymphadenopathy, Myocarditis were uncommon features. Few patients have biphasic temperature. Fever and severity of symptoms did not have correlation. Patients' blood was examined for Dengue viruses, with only 44.6% positivity. Correlation exists between illness duration and antibody titer. [r = 0.41; (P < 0.01)]. Fever other, than Dengue also exhibited similar symptoms, but optical density in EIA test was less. As high fever with similar symptoms may be due to causes other than Dengue, thorough search for other viral infection namely Chikungunya should be done in endemic areas also.

Percutaneous transcatheter closure of patent foramen ovale.

In presence of a patent foramen ovale (PFO) with cryptogenic cerebral embolism, traditional therapy consists of oral anticoagulation or antiplatelet therapy. Surgery was considered only in case of recurrence. Transcatheter closure of PFO is currently performed. The availability of new user friendly devices and the increasing knowledge of pathophysiology, epidemiology, and follow-up of these patients has broadened the indications and marked reduced morbidity related to interventional PFO closure. This review presents the current knowledge and our own data concerning transcatheter closure of PFO.

Angiogenesis in myelodysplastic syndromes (MDS) in Indian patients.

Angiogenesis plays an important role in the pathogenesis of haematological neoplasms and may be correlated with the prognosis. We recently evaluated the microvessel densities in trephine biopsy sections of seventeen patients of myelodysplastic syndromes (MDS). Of the 17 cases, 2 were RAEB-t, 3 were RAEB, one was RARS and 11 were of the subtype RA (FAB subtyping). The microvessel counts were measured in the bone marrow biopsy sections by immunohistochemical staining, using CD34 reactive monoclonal antibodies. MVD was significantly higher in the cases of RAEB and RAEB-t as compared to the cases of RA. The average MVD per x400 in the cases of RA was 5.7 +/- 4.7 with a median value of 4.65 (range 19) whereas it was 45.4 +/- 10.0 and 44.0 (range 27.3) respectively in RAEB and RAEB-t (p <.001), the 95% confidence interval being (2.94, 8.5) and (36.6, 54.3), for the two groups respectively. This finding may imply that subtypes of MDS with a higher tendency for converting to acute leukaemia are associated with increased angiogenesis as compared to other subtypes where the risk of progression to acute leukaemia is much lower.

Disseminated Langerhans cell histiocytosis-an interesting case report with concise review of literature.

A 2-year-old boy presented with fever, recurrent infections and multiple skin lesions. He had anemia, eczematous skin lesions, cervical lymph node enlargement, hepatomegaly and lytic lesions on skull x-ray. The skin infiltrates were CD 68, CD 1a positive and S100 positive. He was diagnosed as disseminated langerhans cell histiocytosis. The occurrence of histiocytosis is reviewed and possible treatment is discussed.

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.