PNH revisited: Clinical profile, laboratory diagnosis and follow-up.

BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by intravascular hemolysis, marrow failure, nocturnal hemoglobinuria and thrombophila. This acquired disease caused by a deficiency of glycosylphosphatidylinositol (GPI) anchored proteins on the hematopoietic cells is uncommon in the Indian population. MATERIALS AND METHODS: Data of patients diagnosed with PNH in the past 1 year were collected. Clinical data (age, gender, various presenting symptoms), treatment information and follow-up data were collected from medical records. Results of relevant diagnostic tests were documented i.e., urine analysis, Ham's test, sucrose lysis test and sephacryl gel card test (GCT) for CD55 and CD59. RESULTS: A total of 5 patients were diagnosed with PNH in the past 1 year. Presenting symptoms were hemolytic anemia (n=4) and bone marrow failure (n=1). A GCT detected CD59 deficiency in all erythrocytes in 4 patients and CD55 deficiency in 2 patients. A weak positive PNH test for CD59 was seen in 1 patient and a weak positive PNH test for CD55 was seen in 3 patients. All patients were negative by sucrose lysis test. Ham's test was positive in two cases. Patients were treated with prednisolone and/or androgen and 1 patient with aplastic anemia was also given antithymocyte globulin. A total of 4 patients responded with a partial recovery of hematopoiesis and 1 patient showed no recovery. None of the patients received a bone marrow transplant. CONCLUSION: The study highlights the diagnostic methods and treatment protocols undertaken to evaluate the PNH clone in a developing country where advanced methods like flowcytometry immunophenotyping (FCMI) and bone marrow transplants are not routinely available.

How Robust are our Methods of Detecting Impaired Glomerular Filtration Rate in the Intensive Care Unit?

BACKGROUND: Serum creatinine is not a sensitive marker to assess early loss of renal function in acute kidney injury. Timed creatinine clearance and several formula used to predict glomreular filtration rate have not been validated. METHODS: In a prospective observational study in 50 adult patients admitted to the intensive care unit with apparent normal renal function, we assessed the glomerular filtration rate by the formula methods and timed creatinine clearance. RESULT: The mean serum creatinine was 0.77mg/dl, SD ± 0.15 (range 0.5-1.14 mg/dl). The mean measured creatinine clearance was 87.15 ml/min/1.73m(2), SD ± 20.5 (range 56.9-137 ml/min/1.73m(2)). In 25 (50%) patients, one hour urinary creatinine clearance was <80 ml/min/1.73m(2) and in two (4%) patients, the creatinine clearance was <60 ml/min/1.73m(2). Spearman correlation coefficient and regression analysis revealed a statistically significant correlation for the Cockcroft-Gault and predictive equations when compared with measured creatinine clearance. The differences between the predictive equations and creatinine clearance, as illustrated by the ±95% confidence interval in the Bland-Altman graphs was very significant [Cockcroft- Gault = -40.3 to 17.7 ml/min/ 1.73m(2), Modification of Diet in Renal Disease equation = -46.2 to 30.6 ml/min/1.73m(2) and the simplified Modification of Diet in Renal Disease equation = -72.8 to 24.8 ml/min/1.73m(2)]. CONCLUSION: Formula methods and creatinine clearance are more sensitive than serum creatinine in detecting early phase of acute kidney injury. However, there is no agreement between these methods of glomerular filtration rate estimation.

Splenic Syndrome due to Sickle Cell Trait amongst Indian Soldiers Serving in Kashmir.

BACKGROUND: Heterozygous transmission of gene for Haemoglobin S leads to sickle cell trait. Mostly the trait remains silent with no additional morbidity or mortality. When these persons migrate to higher altitudes, in times of high oxygen demand, some of them develop splenic infarction. This is a rare phenomenon and only 47 such cases had been reported till 2005. METHODS: This study was conducted at an Indian military hospital serving the troops deployed in Kashmir valley at altitudes ranging from 5500 ft to 13000 ft. When two consecutive splenectomies for splenic abscesses, turned out to be sickling induced infarction histopathologically, we reviewed splenectomy specimens received in last six years for evidence of sickling. RESULT: Out of 33 splenectomies performed during the period of study, 22 were due to trauma (gun shot injury 11; splinter injury one and blunt injury 10). Of the rest eleven, who presented without any history of trauma, seven had evidence of vascular occlusion with aggregates of sickled red blood cells. In none, Gram stain or Periodic Acid Schiff stain revealed any bacterial or fungal colonies. One patient of splenic syndrome was found to have unrecognised sickle cell trait and he was managed conservatively. CONCLUSION: Sickle cell trait should be excluded before considering splenectomy in ethnically vulnerable patients presenting with splenic syndrome. An uncomplicated splenic infarction can be managed conservatively.

Spectrum of Von Willebrand disease and inherited platelet function disorders amongst Indian bleeders.

Platelet function disorders (PFD) and Von Willebrand disease (VWD) are among the uncommon causes of bleeding in haematological practice. The inherited variety of PFD includes defects in platelet adhesion, aggregation, secretion and platelet procoagulant activities. VWD is classified into three major categories-type 1 and 3 (quantitative deficiency) and type 2 VWD (qualitative defect). In the present study, the profile and prevalence of inherited PFD and VWD in Indians are described. Two thousand eight hundred patients with history of muco-cutaneous bleeding and other bleeding disorders were investigated. The tests performed included platelet count, bleeding time, PT, APTT, F VIII assay, platelet factor 3 (PF3) availability, platelet aggregation studies, VWF:Ag, VWF:RCo and multimeric analysis. Out of 2,800 patients investigated, a total of 872 (31.1%) were characterized to have either inherited coagulation defects (64.2%) or inherited platelet function disorders (35.8%). Of these 872 patients, 312 (35.8%) cases were characterized to have inherited PFD and 94 (16.8%) patients as VWD. Among 312 inherited PFD patients, isolated PF3 availability defect (48.1%) was most common, followed by unclassified PFD (37.2%). Among 94 VWD patients, type 2 VWD was most common (44.7%), followed by type 3 VWD (34.5%) and type 1 VWD (21.3%), respectively. Bleeding manifestations included easy bruising (46%), undue prolonged bleeding from trivial injuries (50% in PFD and type 1 and type 2 VWD and 100% in type 3 VWD), menorrhagia (31%), gum bleeds (22%), epistaxis (55%), haematuria (6%), GI bleeds (11%) and rarely, haematomas and haemarthoses (4%). In conclusion, VWD and inherited platelet function disorders are not uncommon among Indian population presenting with bleeding disorders.

Cancer related thrombophilia: clinical importance and management strategies.

Acquired thrombophilic state associated with a significant risk of thrombosis is frequently encountered in malignancy. Venous and arterial thromboembolism is a common complication and patients with cancer, also present with a hypercoagulable state, even in the absence of thrombosis. Furthermore, clotting activation may play a role in tumor progression. The pathogenesis of thrombosis in cancer is multifactorial; however, a relevant role is attributed to the tumor cell capacity to interact with and activate the host hemostatic system. Among other factors, the prothrombotic action of antitumor therapies is also important. Thrombotic events can influence the morbidity and mortality of the underlying disease. Therefore, preventing these complications in cancer patients is a clinically relevant issue. Recently, new approaches to the prevention and cure of thrombosis in cancer have been investigated, and the hypothesis that the strategies to inhibit clotting mechanism may favorably affect malignant disease is gaining increasing interest. In this article the various aspects of the complex relationship between thrombosis and cancer, from pathophysiology to therapy, are reviewed.

Anti-D immunoglobulin in the treatment of idiopathic thrombocytopenic purpura.

Anti-D was evaluated in 8 RhD positive patients (6 males, 2 females) aged 2-21 years (mean 10 years) with Idiopathic Thrombocytopenic Purpura (ITP). Five patients with chronic ITP and 3 patients with acute ITP were administered Anti-D in the dosage of 50 micrograms/kg intramuscularly (IM) for 3 consecutive days. One patient of chronic ITP received two courses of Anti-D. Patients were followed up for 7 to 16 months (mean 9 months). All three cases of acute ITP had a complete response and are in remission between 3 to 12 months of follow up. Two of five cases of chronic ITP had a partial response. Rise in platelet count was observed within 72-124 hours, and duration of response varied between 10 to 15 days. None of these patients had any significant side effects of anti-D immunoglobulin therapy. Intramuscular administration of Anti-D is safe, effective and low cost alternative to IVIgG in the treatment of acute ITP.

Prognostic role of screening tests of haemostasis and underlying diseases in acute disseminated intra-vascular coagulation in adults.

The significance of precipitating causes of acute disseminated intra-vascular coagulation (DIC) and the severity of derangement of haemostasis based on laboratory investigations carried out initially were evaluated in 98 patients and was related to the fatal outcome in them. It was seen that septicaemia was the commonest precipitating cause. Survival was better in patients in whom DIC was precipitated by obstetric causes compared with those with septicaemia (P < 0.01). Death was also more frequently associated in patients with higher prothrombin time (PPT) ratio (> 1.5) and/or higher activated partial thromboplastin time (APTT) ratio (> 2.5) as compared to their lower values (P < 0.01 each). Death occurred in all the seventeen patients in whom septicaemia was present along with PPT ratio of > 1.5. It is concluded that deranged haemostasis and presence of septicaemia both independent of each other, contribute to the fatal outcome in acute DIC. Combination of both is associated with poorest prognosis.

Hypertension as a paraneoplastic phenomenon in childhood Hodgkin's disease.

A 14 year old girl with Hodgkin's disease presented with hypertension as an unusual paraneoplastic phenomenon. The elevated plasma renin activity recorded in this patient was possibly a result of Hodgkin's disease. Hypertension as well as plasma renin activity declined to normal values following her successful response to chemotherapy.

Hyperbilirubinemia following hepatitis A in a patient with G6pD deficiency.

A case of viral hepatitis A with G6PD deficiency is described. The condition should be suspected in the presence of indirect hyperbilirubinemia, and anemia in a patient with viral hepatitis; repeat G6PD testing 8 weeks later is recommended for diagnosis.