Consensus Statement of the Indian Academy of Pediatrics in Diagnosis and Management of Hemophilia

Justification: Despite having standard principles of management of hemophilia, treatment differs in various countries depending onavailable resources. Guideline for management of hemophilia in Indian setting is essential.Process: Indian Academy of Pediatrics conducted a consultative meeting on Hemophilia on 18th September, 2016 in New Delhi, whichwas attended by experts in the field working across India. Scientific literature was reviewed, and guidelines were drafted. All expertcommittee members reviewed the final manuscript.Objective: To bring out consensus guidelines in diagnosis and management of Hemophilia in India.Recommendations: Specific factor assays confirm diagnosis and classify hemophilia according to residual factor activity (mild 5-40%,moderate 1-5%, severe <1%). Genetic testing helps in identifying carriers, and providing genetic counseling and prenatal diagnosis.Patients with hemophilia should be managed by multi-specialty team approach. Continuous primary prophylaxis (at least low-doseregimen of 10-20 IU/kg twice or thrice per week) is recommended in severe hemophilia with dose tailored as per response. Factorreplacement remains the mainstay of treating acute bleeds (dose and duration depends on body weight, site and severity of bleed).Factor concentrates (plasma derived or recombinant), if available, are preferred over blood components. Other supportive measures(rest, ice, compression, and elevation) should be instantly initiated. Long-term complications include musculoskeletal problems,development of inhibitors and transfusion-transmitted infections, which need monitoring. Adequate vaccination of children withhemophilia (with precautions) is emphasized

Heparin: Induced thrombocytopenia: Incidence and laboratory approach to diagnosis in Indians.

Background and objectives: One of the most common complications of heparin administration is heparin-induced thrombocytopenia (HIT) which can also lead to catastrophic thrombotic events. The problem of identifying the cause of thrombocytopenia, as due to heparin, in patients with multiple co-morbid conditions is very essential for management. Thus, the laboratory investigations for diagnosis of HIT play a pivotal role. The objective of the study was to arrive at the incidence of HIT in ethnic Indian population and provide a decision after analysis of tests used to diagnose HIT. Materials and Methods: 125 consecutive patients (Power of study being 80%) undergoing open heart surgery and receiving unfractionated heparin were taken as subjects. Blood samples were collected a day before the surgery and days 1, 3, 5 and 7 after surgery. The cases were categorized into probable and unlikely groups depending on the clinical presentation and degree fall of platelet count. Antiheparin PF4-associated antibodies were detected using rapid-ID gel microtyping system and ELISA tests. HIT was also tested using functional assays:- heparininduced platelet aggregation test (PAT) and the rapid luminographic assay of heparin-induced ATP release. Results: Of the 125 patients, 11 patients were clinically labeled as probable HIT and 29 patients were clinically labeled as unlikely HIT. There were seven confi rmed cases of HIT cases that were positive for one functional and one immunological assay. Only one case of HITT was encountered. Accordingly, the incidence of HIT was found to be 5.6 % and that of HITT to be 0.8%. ELISA tests were positive in 21 cases (17%) which demonstrated the presence of anti-HPF4 antibodies in non-HIT cases as well. It was found that the rapid gel test had sensitivity comparable to functional assay with better specifi city than ELISA. Interpretation and conclusions: Incidence of HIT in ethnic Indian population is 5.6%. Patients with a drop of >50% in platelet count should be perused as a likely candidate of HIT. These cases should be subjected to the ID-HPF4 antibody assay as this is a rapid test, can be done for individual cases, and has better specifi city and similar sensitivity than ELSIA. Cases with clinically probable HIT and a positive ID-HPF4 assay can be taken as confi rmed cases of HIT. However, cases clinically unlikely for HIT and a positive ID-HPF4 assay should be subjected to another test to establish the diagnosis of HIT.

Unusual case of pulmonary renal syndrome with autopsy findings.

Scleroderma renal crises (SRC) is a serious complication of systemic sclerosis whose prognosis remains serious despite management with angiotensin-converting enzyme inhibitors, antihypertensives and dialysis. Pulmonary renal syndrome (PRS), characterised by diffuse alveolar hemorrhage (DAH) and SRC, is rare and carries a grave prognosis. This case report discusses the clinicopathological features of a 43-year-old male presenting with severe hypertension and rapidly progressive renal failure who subsequently developed DAH and died. The clinical course, exhaustive investigative work-up and autopsy findings led to a diagnosis of diffuse systemic sclerosis with PRS subcategorized into PRS with thrombotic microangiopathy. The index case came without a prior diagnosis of systemic sclerosis, thereby posing a serious diagnostic challenge and management issues.

Role of homocysteine & MTHFR C677T gene polymorphism as risk factors for coronary artery disease in young Indians.

Background & objectives: Hyperhomocysteinaemia (HCA) either due to mutation of MTHFR gene or deficiency of vitamin B12 and folic acid, has been reported as a risk factor for coronary artery disease (CAD). The present study was aimed to determine plasma homocysteine (Hcy) levels and to evaluate MTHFR C677T gene polymorphism as risk factors for CAD, and to study the role of Hcy in conjunction with a few other risk factors of CAD in young Indians. The effect of vitamin B12 and folic acid supplements on the raised plasma Hcy levels in patients of CAD was also assessed. Methods: The present study included 199 consecutive angiography confirmed CAD patients, <45 yr of age, without any other known pro- coagulant state and 200 age- and sex-matched healthy controls. Fasting blood samples were collected in EDTA and plasma Hcy was estimated by ELISA test and the MTHFR C677T polymorphism detection was carried out by PCR-RFLP method. Results: Significant difference (P<0.001) was found between mean fasting levels of plasma Hcy in cases (22.14 ± 10.62 μmol/l) and controls (17.38 ± 8.46 μmol/l) with an Odds ratio as 1.93 (95% CI, 1.27-2.94). Levels of cholesterol, LDL, and triglycerides were significantly (P<0.001) higher in cases compared with controls. Interpretation & conclusions: Our study showed significant correlation between hyperhomocysteinaemia and coronary artery disease. Multivariate analysis by logistic regression of the various risk factors of CAD, found high levels of Hcy, cholesterol, LDL and low levels of HDL and smoking as independent predictors of CAD when all other factors were controlled. Significant post-treatment decrease found in HCA was easily modifiable by vitamin intervention irrespective to their CT or TT genotype of C677T MTHFR gene. Further studies to look at the plasma levels of folate and cobalamines and their association with Hcy are required to be done.