Journal Club

Hemophilia and Factor

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Instructions

Take Another Course

Post-Test

Objectives:

Upon completion of this course the participant will be able to:

• Define hemophilia and its causes
• List four symptoms and four causes of bleeding disorders
• Differentiate between prophylactic and on-demand therapy 
• List benefits and issues of prophylactic therapy, and
• Identify the effect of postponing prophylaxis on long-term clinical outcomes of the severe hemophilia patient

Hemophilia: Prophylaxis and the Question of Cost

 Recent advances in both the distribution and quality of factor available have led to an overall decrease in morbidity and mortality among hemophilic individuals. Furthermore, more advanced treatment regimens have led to much longer, more normal lives. There is an inevitable increase in healthcare costs associated with this improved quality of life, and so the question becomes one of, “of course it’s worth it no matter what the cost”, or “it’s worth it in terms of cost if the benefits are measurable and meet our goals”.

Five studies in this journal club look at prophylactic therapy and the clinical and quality of life indicators they affect. These studies point to distinct benefits with prophylaxis, using various entry points and with varying results, but all raise the cost question. Aside from the healthcare costs themselves, some of the authors look at time lost from work or school and other opportunity costs as a way of truly putting a price on living with hemophilia. And, as a way of getting the participant to think outside the box at the possible ramifications of this increased quality of life, we have included an additional observational study that discusses the severity of hemophilia and its long-term effects on intelligence test scores and academic achievement. 

The question is, then, does the benefit of prophylactic therapy outweigh the added cost? Is there enough clinical evidence to say that prophylactic therapy should be used on every hemophilic individual, or is it a question of providing prophylactic therapy only to those patients that warrant it. And while some of the authors parlay their views on what constitutes a good entry point for prophylaxis, in the end we find that it is still a largely subjective decision.

Let’s begin with some background information before we look at the studies.

History:

Hemophilia has been known for a long time. Transmission of the disease from mother to son was first described in the early 1800’s. And while hemophilia only affects males, females have been identified as carriers of the disease. It was not until 1952 that hemophilia A and B were recognized as two distinct diseases resulting from their respective lack of proteins, Factors VIII and IX. In the 1960’s clotting factors were identified and named. In the late 1960’s factor concentrates became available. Developed as freeze-dried powder concentrates, these could kept on had until needed. Unfortunately, many of these concentrates suffered from a lack of screening, allowing blood-borne diseases to spread through their use. Many persons with hemophilia were affected. In the 1990’s safety measures were put into place that improved the outlook for the use of these blood concentrates.

Background:
There are a wide range of bleeding disorders that lead to poor clotting and continuous bleeding. These disorders are known as coagulopathy, clotting disorders or abnormal bleeding.

A bleeding disorder usually manifests itself with longer than normal bleeding times. These disorders are caused either by congenital problems with the blood vessels themselves or abnormalities in the blood itself. These abnormalities may be in blood clotting factors or in platelets.

Blood clotting is the process that controls bleeding. During the bleeding process blood changes from a liquid to a fibrin solid. This process uses as many as 20 different plasma proteins. A complex chemical process is involved that uses these clotting factors to form a substance called fibrin.  Fibrin is responsible for stopping the bleeding. In hemophilia, where certain coagulation factors are deficient or missing, the process doesn't occur normally.

Immediately after injury, platelets within the blood come to rest around the wound. Numerous other blood products such as calcium, platelets, protein and other tissue factors react together and form a clot, which acts like a net over the wound. Over time, usually days, this net strengthens allowing wound healing.  Once healed, the net, or clot dissolves.

In Hemophilia these clotting factors are missing or work in a counterproductive manner. These abnormalities allow longer bleed times. People afflicted with bleeding disorders can have bleeding times differentials that range from mild to severe.