Diagnosis Of Von Williebrand Disease Biology Essay

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It all started with a man called Erik von Willebrand, a Finnish physician who discovered a new bleeding disorder in his patients. Using simple experiments he observed his patients with an abnormal platelet clotting factor and came to a conclusion that their blood was lacking the Von Willebrand factor (vwf). So with the help of Von Willebrand, scientists today can identify if a patient is lacking or has defective VWF. Now, different blood groups have different constituents and can have

a big factor, on if a patient has Von Willebrand Disease.

This is one of the most common hereditary disorders and it affects your blood's ability to clot. This prevention of clotting means bleeding will not stop and serious damage can happen to internal organs. This could lead to death if not treated immediately but is quite rare to get to this stage. The blood contains a protein called Von willebrand factor which determines whether it becomes a disease. The disease will show Von willebrand factor levels being low or deficient. Normally, when bleeding occurs this brings platelets along to the site and clots the wound, with the Vwf acting like glue to stick them together (Crowley L, 2009 p.231). With VWD, there is a problem with Vwf levels so clotting cannot take place. Here is a simple diagram showing the accumulation of platelets:


Left: Platelets attach to ultra large vWF multimers. Right: Platelet Thrombosis

Another important protein that's lacking in VWD is factor VIII, which helps in the clotting process.

There are three major types of VWD, firstly type 1 which shows low levels of von willebrand factor and factor VIII. This is the mildest of the conditions and the most common. Type 2 has VWF that's deficient and doesn't work the way they should. This group is divided into subtypes, 2A, 2B, 2M and 2N. These different subtypes are important because different gene mutations cause each type and have to be treated differently. The third type is where there's no von willebrand factor and low levels of factor VIII. This is the most serious form but it is rare.

Inheritance is where this disease comes form, with type 1 and 2 coming from a single parent and sometimes for type 3 comes from both parents. Some parents act as carriers where they will not be affected by the genes but can pass it onto their children. There are some people that attain this disorder later on in life from other medical conditions (Crowley L, 2009 p.231).

Now the signs and symptoms of this disorder is shown are shown by varying degrees of bleeding, usually from nosebleeds, bruising or even bleeding gums. Type 1 and 2 having the milder bleeding with type 3 having more serious bleeding for no reasons.

In women, heavy menstrual bleeding can show sings of this disorder but is quite rare. One of the main questions is how is it diagnosed. Well, first VWD should be diagnosed as early as possible to a better and more active life can be attained. Type 1 and 2 are harder to diagnose as the patient may not have major bleeding problems. So, a real diagnosis of this type can be assured after surgery or serious trauma. With type 3, this much easier to diagnose as the bleeding is random and can be treated at early age. A doctor would ask a series of question with regards to bleeding and previous signs of any disease.

A physical exam would be followed including a check of red blood cell count. A number of diagnostic tests are usually used to diagnose as no single test can. This could include Von willebrand factor antigen which measures amount the amount. A platelet function test which measures the working process and VWF ristocetin cofactor activity, which shows how well the VWF works.

Treatment is normally based on the type of VWD the patient has and how sever it is. Various medications can be used to increase production of von willebrand factor and to prevent the breakdown of blood clots. A specific treatment can include desmopressin (DDAVP) which increases production of VWF into the bloodstream and is normally taken via nasal spray. Replacement therapy can be used if DDAVP does not work or the patient has type 2 or 3. In most surgeries they have a medication called fibrin glue which is placed on the wound to stop bleeding. With women's heavy menstrual bleeding DDAVP can be used or a combination of birth control pills.

Humans have different blood groups which is given the name 'ABO blood group system' which includes several blood types. A patient's ABO type depends on the presence of absence on two genes, the A and B genes. The ABO system was discovered by Austrian scientist Karl Landsteiner who found the three blood groups A, B and O, with the fourth blood group discovered by Decastrello and Struli (Goldsby. RA et al, 2000 p122). They found they comprise of antigens, corresponding antibodies and their genes encoding the antigens. Patients that have the A antigen on their red blood cells, are said to have the A blood group with anti-B antibodies. Patients with the B antigen are said to have the B blood group with anti-A antibodies. Patients with the o blood group don't have antigen A or B but do contain anti-A and anti-B antibodies. AB blood group patients have both A and B antigens but no antibodies (Franchini M et al, 2007).

Most cases of VWD is hereditary but some can be acquired. Acquired VWD is when a patient has autoantibodies and this affects the VWF antibody complex and it's rapidly cleared from the circulation (Gill JC et al, 1987).


With the different genes in the ABO system, this gives us different blood types. So looking at the different antibodies and antigens present, a deduction of which blood group it belongs to can be assessed. This information can be used to determine if the patient has low or high von willebrand factor. The blood groups do have an effect on von willebrand factor and also show high correlation with increasing age (Gill JC, Endres-Brooks J, Bauer PJ, Marks WJ, Montgomery RR, 1987). O blood group individuals have lower vwf levels than non O blood group individuals which were proven by Bowen in 2002. This was proved by group O individuals being more susceptible to the hydrolytic effect of the cleaving protease ADAMTS13 when compared to non O individuals. Previous studies have shown that ABO blood group does influence the plasma levels of von Willebrand factor (VWF) (Gallinaro L et al, 2008).

Treatment of this disease depends on the severity. The medications used increase the release of Von Willebrand factor and factor VIII into the bloodstream. It replaces the Von Willebrand factor and prevents the breakdown of blood clots. Heavy menstrual bleeding is controlled in women with certain medications. An example is desmopressin which is taken by nasal spray or injection. This increases production of VWF and factor VIII and is mostly for type 1 patients. Von Willebrand replacement therapy is used if desmopressin does not work and the disease is more serious.

Antifibrinolytic medications are used to help prevent the breakdown of blood clots. To control the bleeding of a woman's menstrual cycle, a combination of oral contraceptives and DDAVP can be used.

Now, the techniques that can be used for this investigation is multiple regression analysis, where this will determine if age is significant in levels of Von Willebrand factor. This uses various statistical tools for example excel. Also reverse ABO typing which can be done on various blood groups to determine amount of Von Willebrand factor. A quantitative ELISA assay and ristocetin cofactor test can be performed.

My project is going to involve investigation in Von Williebrand Disease factor levels in different human blood groups by using a series of techniques. More specifically, I will be looking at the corresponding level of VWF and their mutations in relation to VWD. The specific antigens and antibodies in the different blood groups will have an effect on the VWF levels. The results can be compared with certified ranges to deduce which blood group is more prone to VWD.