Hemophilia management guidelines CME .#1

INTRODUCTION

Hemophilia A and B are X-linked recessive disorders of coagulation characterized by deficiency of Factor VIII (FVIII) and Factor IX (FIX). Across all ethnic groups, the prevalence of hemophilia A is estimated to be 1 in 5000 males, and that of hemophilia B is 1 in 30,000.[ 1] It is estimated that hemophilia affects approximately 400,000 individuals in the world. Hemophilia A is more common than hemophilia B and represents 80% to 85% of the total hemophilia population. This article reviews the latest understanding of hemophilia and the significant progress that has been made in diagnosis and management during the past several decades.

CLASSIFICATION OF SEVERITY

The severity of disease is classified based on the residual plasma levels of circulating FVIII and FIX. The disease is classified as follows: severe if levels are <1%, moderate for levels of 1% to 5%, and mild for levels between 5% to 40% of normal.^[2] There are some limitations to this classification in that it does not recognize the clinical heterogeneity in bleeding observed in individuals with levels <1%.

It has been observed that 10% to 15% of patients with severe hemophilia as defined by factor levels may have a milder clinical profile.^[3] Additionally, this classification may not distinguish between the bleeding profiles of hemophilia A and B.^[4] Based on inpatient hospital admissions, factor consumption, and rates of joint arthroplasty, some reports suggest that hemophilia B may have a milder bleeding phenotype than hemophilia A,^[5-7] although a more recent study demonstrated that age at first bleed, age at first joint bleed, and age at first factor exposure were similar in patients with hemophilia A vs B.^[8] An additional issue that is unresolved is the classification of individuals with levels of 40% to 50%. Another important point that the current classification does not consider is the potential discrepancy between the 1- and 2-stage assays for FVIII (FVIII levels were lower with the 1-stage assay) in some patients with mild hemophilia A.^[9]

Despite these limitations, the current classification is widely accepted, and there is good correlation between age at diagnosis, age at first bleed/first joint bleed, and age at first treatment and the classification of disease severity based on circulating factor levels in most patients.^[ 10] In general, individuals with mild hemophilia bleed only in response to trauma, such as that experienced during surgery, tooth extractions, or major injuries, whereas patients with moderate hemophilia bleed excessively after relatively minor trauma, and those with severe hemophilia may bleed spontaneously or after trivial trauma.