Karuna Rameshkumar

Significance of preoperative thrombocytosis in epithelial ovarian cancer.

BACKGROUND Reactive thrombocytosis is reported in a variety of solid tumors. A few studies have documented preoperative thrombocytosis in ovarian cancer and identified it as a marker of aggressive tumor biology. AIM To study the incidence of preoperative thrombocytosis (platelets greater than 400x10) in epithelial ovarian cancer and its association with other clinicopathologic factors. MATERIALS AND METHODS Sixty-five patients with invasive ovarian epithelial cancer were retrospectively reviewed and analyzed for the association preoperative thrombocytosis with other clinical and histopathological prognostic factors. Means were analyzed by Students t test; proportions were determined by Chi-square analysis. RESULTS Twenty of 65 (37.5%) patients had thrombocytosis at primary diagnosis. Patients with preoperative thrombocytosis were found to have lower hemoglobin (P < 0.0002), more advanced stage disease (P < 0.05) and higher grade tumors (P < 0.02). Patients with thrombocytosis had greater likelihood of subpotimal cytoreduction. CONCLUSIONS Preoperative thrombocytosis is a frequent finding in ovarian carcinomas and their association with advanced stage disease and higher grade denotes that platelets play a role in the tumor growth and progression.

Red blood cell antibody screening in pregnancy

Sir, Hemolytic disease of newborn (HDN) is defined as neonatal anemia and hyperbilirubinemia caused by an incompatibility between maternal and fetal red blood cells (RBCs).[1] In 98% cases it is caused due to ABO and Rh incompatibility and antibodies to other blood group antigens (Kell, c, E, C, Kidd, Duffy, M, and so on) are causative in remaining 2%.[2] More than 43 different RBC antigens have been reported to be associated with HDN.[3] Red cell antibody screening (RCAS) is a valuable tool in the detection of alloantibodies to other blood group systems (other than ABO and Rh) in the serum of patients during pregnancy or prior to transfusion. Red cell antibody identification (RCAI) should then be carried out on a larger panel of RBCs to precisely identify the antibody. In a prospective study carried out on 624 antenatal cases, RCAS was done using a 3-cell panel from Diamed, Switzerland. RCAI was carried out on cases that were positive for RCAS. RCAS was positive in 9 out of 624 cases—1.4% (excluding the 3 cases who had autoantibodies). After RCAI these were identified as anti-D antibody (6 cases, 66%), anti-D with anti-C antibody (2 cases, 22%), and anti-M antibody (1 case, 11%). The most common antibody identified remained anti-D. In 2 cases of Rh negative pregnancy, the RCAS was suggestive of anti-D. RCAI done, however, showed a combination of anti-D and anti-C. One case of anti-M was detected in a G2P1L1D1 lady. The first pregnancy was full-term normal delivery at home, however, the baby died after birth. The mother’s and baby’s blood group was O positive. RCAS done during second pregnancy was suggestive of anti-Duffy (Fya) or anti-M antibody. RCAI done showed anti-M antibody with dosage effect. The second pregnancy was postdated with Intrauterine growth retardation (IUGR,) and Lower segment caesarean section(LSCS) was done for fetal distress. The baby had hyperbilirubinemia and was Direct Coombs test (DCT) positive requiring phototherapy. Rh incompatibility continues to be a common cause for HDN. Patients with no prior history of sensitization can also develop anti-D as seen in 3 of our cases probably due to naturally occurring anti-Rh antibodies or antepartum hemorrhage. Despite the use anti-D immunization, 1%–2% of the cases are still sensitized. Anti-D immunization resulted in a favorable fetal outcome in the study. Anti-D complicated with anti-C presents with more severe HDN as seen in 1 patient who had a previous stillbirth and a hydrops baby despite receiving anti-D. Anti-C antibodies resulting in HDN requiring exchange transfusion have been reported.[4] Anti-M as a cause of HDN is rare as they are usually complete cold antibodies (IgM). However, it can be IgG type resulting in HDN.[3] HDN due to anti-M antibody can be mild to severe with stillbirth and cases requiring exchange transfusion have been reported.[5] Anti-M causing blood group discrepancy and crossmatch incompatibility has been reported in the Indian literature.[6] Antenatal detection of the non-anti-D causes of HDN requires RCAS. If RCAS is positive, the following steps are to be taken. RCAI should be done to identify the antibody. The spouse has to be screened for the presence of offending antigen and the pediatrician has to be alerted about delivery of a potentially sensitized infant. The blood bank should find a suitable antigen-negative donor for transfusion to baby and mother.

Polycythemia vera and essential thombocythemia - A single institution experience

Background: In myeloproliferative disorders, occurrence of Janus kinase 2 [JAK2] mutation is a significant factor in pathogenesis in polycythemia rubra vera (PRV) and Essential thrombocythemia (ET). We studied the frequency of JAK2 mutation in patients with PRV and ET and to compare clinical and laboratory features of patients positive and negative for mutation. Patients and Methods: Clinical and laboratory features of PRV and ET patients (WHO criteria) from 1997 to 2004 were included. After morphological diagnosis, presence or absence of JAK 2 mutation was done during follow up and follow up details were recorded. Results: A cohort of 39 patients (ET-17, PRV -14, ET- PRV-8) were identified .The mean age of entire cohort was 55.5+14.5 years. Comparison of clinical and laboratory features showed JAK2 positive patients were older by a decade, had higher frequency of splenomegaly and higher values for hemoglobin (16.5+2.6 gm/dl) and neutrophil counts (14.5+4.8 thousand/μl).During the course of follow up (6 to 106 months; mean 25.5+28.6 months) frequency of thrombotic events in both groups (p value >0.05) was same, though time for occurrence for thrombotic event was shorter in JAK 2 positive patients, which is noteworthy. Conclusions: The identification of JAK 2 mutation probably defines a sub entity in ET with aggressive behavior as evidenced by splenomegaly, higher total counts and transformation to PRV (n=6/8). The onset of JAK2 V617F mutation probably heralds progression to PRV.

Significance of haemostatic markers in ovarian carcinoma

Background: Most cancer patients with metastatic disease have abnormal coagulation parameters. Although many abnormal blood coagulation tests have been reported in malignancies, there is little agreement regarding which tests are most useful to predict disease progression and hence this study was undertaken. Methods: In this prospective study, baseline and special coagulation tests were performed on 23 patients with ovarian adenocarcinoma. The baseline tests were PT, APTT, TT and platelet count. The special tests included factor VIII, factor IX and fibrinogen assay and semiquantitative measurement of D-dimer and FDP levels The cases were grouped into early and advanced disease groups. The results of the coagulation tests were analysed using suitable statistical methods. The results were compared between limited and advanced disease by chi square and Mann Whitney U test Results: The percentage of cases with increased D-dimer and fibrin degradation products (FDP) values were higher in the advanced disease compared to early disease. Two cases in stage IV had DIC. The PT, APTT, TT and platelet count did not show any statistically significant differences between the early and advanced disease groups. Factor VIII, factor IX and fibrinogen levels were not significantly different between two groups. Conclusion: Elevated D dimer& FDP are associated with advanced stage ovarian adenocarcinoma.

Hb D: A Not So Rare Hemoglobinopathy

Dear Editor, Hb D is a b chain haemoglobin variant. It was first described by Itano in 1951 [1]. It differs in structure from Hb A at 121 position on b chain where glutamine replaces glutamic acid [2]. Hb D is known variously as Hb D Punjab, Hb D Los Angeles. It is the fourth most frequently occurring Hb variant [3]. Hb D Punjab occurs with greatest prevalence (2 %) in Sikhs of Punjab and in Gujarat (1 %). It is also found sporadically in blacks and Europeans, the latter usually seen in countries that have close association with India in the past [3]. HbD heterozygotes are clinically normal and homozygotes have a clinically mild phenotype. Hb D attains clinical significance in association with either b thalassemia or HbS. We describe 12 patients, 9 from South Indian population (three cases of Hb D trait and six cases of Hb SD) and 3 from West Bengal (one case homozygous HbDD, one case of HbD b thalassemia and one case of HbD trait). Blood samples collected in EDTA were subjected to complete blood counts, reticulocyte count and red cell indices on the Sysmex XT 1800i/XT 2000i/XT 4000i. Peripheral blood smears were prepared stained with Leishman’s stain and examined. Sickling test was done where indicated by using 1 % sodium metabisulphite. G6PD screening was done using dye reduction test. The HPLC was done on BioRAD Variant II. The clinical data was retrieved from the medical records department. HPLC was done on 1,460 cases over a period of 2 years from September 2009 to February 2012. Five hundred and eighty-nine cases of haemoglobinopathies were detected. b Thalassemia trait was most common with 373 cases (63 %) being detected. b Thalassemia major was seen in 36 cases (6.1 %) and b thalassemia intermedia in 13 cases (2.2 %). Sickle cell disease was the next common with 28 cases of Sickle cell trait (4.7 %), 25 cases of sickle cell anemia (4.2 %) and 18 cases of sickle b thalassemia (3 %). HbE was seen significantly in the migrant population from Bengal with 24 cases of HbEE disease (4 %), 27 cases of HbE trait (4.5 %) and 14 cases of HbE b thalassemia (2.3 %). Twelve cases (2.0 %) showing Hb D were detected of which six cases were double heterozygous HbSD, one case of homozygous HbDD, one case of HbD b thalassemia and four cases of HbD trait. Eleven cases (1.8 %) of hereditary persistence of foetal haemoglobin (HPFH), four cases (0.6 %) of HPFH trait and four cases (0.6 %) of a thalassemia were also seen. Hb D formed a significant percentage of the hemoglobinopathies (2 %). Most of them 9 of 12 cases were from South India and three cases from West Bengal. HbSD was seen in the South Indian population whereas homozygous HbDD and HbD b thalassemia seen in the migrant patients from West Bengal.

Hunt for the hidden trait

Objective: To assess the efficacy of a peripheral smear examination as a screening tool for β-thalassemia trait. Materials and Methods: 17 623 Leishman-stained peripheral smears were evaluated during the period from July 2006 to September 2007. The following parameters were studied: hemoglobin, red blood cell count, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration and red cell distribution width. All the cases that showed microcytosis, hypochromia, erythrocytosis and absence of anisopoikilocytosis were suspected of having the thalassemia trait (TT), and all these cases were further evaluated with Alkaline Hemoglobin Electrophoresis for confirmation. Results: Of the 17 623 smears examined, 60 cases were considered suspicious of having TT. Alkaline hemoglobin electrophoresis carried out on all these cases revealed an elevated HbA2 (Mean = 7.5%). Five cases evaluated were found to have other hemoglobinopathies (1 Sickle cell trait, 3 Hb-E, 1 thalassemia intermedia). Conclusion: Careful screening of peripheral smear is an invaluable screening tool for thalassemia trait (PPV - 95%). There must be awareness among the peripheral centers about the importance of peripheral smear screening and the affected persons should be counseled.

The MAHA clue - A case report

Microangiopathic hemolytic anemia (MAHA), is one of the causes of extra vascular hemolysis. It is seen in settings with pathologically altered small blood vessels. Disseminated carcinomas may rarely present as MAHA. A case of a 28 year old female with carcinoma stomach, who presented with MAHA as a first manifestation is reported. Acute onset of MAHA, may be the first manifestation of malignancy. In the absence of relatively common causes like disseminated intravascular coagulation,/Hemolytic uremic syndrome/thrombotic thrombocytopenic purpura, MAHA warrants extensive rapid investigations including bone marrow aspiration for possible metastatic deposits.