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Willebrand disease, acquired

Von Willebrand's disease (vWD) is the most common hereditary coagulation abnormality described in humans. It arises from a qualitative or quantitative deficiency of von Willebrand factor (vWF), a multimeric protein that is required for platelet adhesion. It is known to affect humans and, in veterinary medicine, dogs. more...

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Willebrand disease, acquired
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Symptoms

The various types of vWD present with varying degrees of bleeding tendency. Severe internal or joint bleeding is rare (only in type 3 vWD); bruising, nosebleeds, heavy menstrual periods (in women) and blood loss during childbirth (rare) may occur.

Diagnosis

When suspected, blood plasma of a patient needs to be investigated for quantitative and qualitative deficiencies of vWF. This is achieved by measuring the amount of vWF in a vWF antigen assay and the functionallity of vWF with a glycoprotein (GP)Ib binding assay, a collagen binding assay or, a ristocetin cofactor (RiCof) activity assay. Factor VIII levels are also performed as factor VIII is bound to vWF which protects the factor VIII from rapid break down within the blood. Deficiency of vWF can therefore lead to a reduction in Factor VIII levels. Normal levels do not exclude all forms of vWD: particularly type 2 which may only be revealed by investigating platelet interaction with subendothelium under flow (PAF), a highly specialistic coagulation study not routinely performed in most medical laboratories. A platelet aggregation assay will show an abnormal response to ristocetin with normal responses to the other agonists used. A platelet function assay (PFA) will give an abnormal collagen/adrenaline closure time but a normal collagen/ADP time. Type 2N can only be diagnosed by performing a "factor VIII binding" assay. Detection of vWD is complicated by vWF being an acute phase reactant with levels rising in infection, pregnancy and stress.

Other tests performed in any patient with bleeding problems are a full blood count (especially platelet counts), APTT (activated partial thromboplastin time), prothrombin time, thrombin time and fibrinogen level. Testing for factor IX may also be performed if hemophilia B is suspected. Other coagulation factor assays may be performed depending on the results of a coagulation screen.

Classification and types

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Platelet aggregation test
From Gale Encyclopedia of Medicine, 4/6/01 by Janis O. Flores

Definition

Platelets are disk-shaped blood cells that are also called thrombocytes. They play a major role in the blood-clotting process. The platelet aggregation test is a measure of platelet function.

Purpose

The platelet aggregation test aids in the evaluation of bleeding disorders by measuring the rate and degree to which platelets form a clump (aggregate) after the addition of a chemical that stimulates clumping (aggregation).

Precautions

There are many medications that can affect the results of the platelet aggregation test. The patient should discontinue as many as possible beforehand. Some of the drugs that can decrease platelet aggregation include aspirin, some antibiotics, beta blockers, dextran (Macrodex), alcohol, heparin (Lipo-Hepin), nonsteroidal anti-inflammatory drugs (NSAIDs), tricyclic antidepressants, and warfarin (Coumadin).

Description

There are many factors involved in blood clotting (coagulation). One of the first steps in the process involves small cells in the bloodstream called platelets, which are produced in the bone marrow. Platelets gather at the site of an injury and clump together to form a plug, or aggregate, that helps to limit the loss of blood and promote healing.

Inherited bleeding disorders (e.g., hemophilia or von Willebrand's disease) and acquired bleeding problems that occur because of another disorder or a medication can affect the number of platelets and their level of function. When these problems are present, the result is a drop in platelet aggregation and a lengthened bleeding time.

The platelet aggregation test uses a machine called an aggregometer to measure the cloudiness (turbidity) of blood plasma. Several different substances called agonists are used in the test. These agonists include adenosine diphosphate, epinephrine, thrombin, collagen, and ristocetin. The addition of an agonist to a plasma sample causes the platelets to clump together, making the fluid more transparent. The aggregometer then measures the increased light transmission through the specimen.

Preparation

The test requires a blood sample. The patient should either avoid food and drink altogether for eight hours before the test, or eat only nonfat foods. High levels of fatty substances in the blood can affect test results.

Because the use of aspirin and/or aspirin compounds can directly affect test results, the patient should avoid these medications for two weeks before the test. If the patient must take aspirin and the test cannot be postponed, the laboratory should be notified and asked to verify the presence of aspirin in the blood plasma. If the results are abnormal, aspirin use must be discontinued and the test repeated in two weeks.

Aftercare

Because the platelet aggregation test is ordered when some type of bleeding problem is suspected, the patient should be cautioned to watch the puncture site for signs of additional bleeding.

Risks

Risks for this test are minimal in normal individuals. Patients with bleeding disorders, however, may have prolonged bleeding from the puncture wound or the formation of a bruise (hematoma) under the skin where the blood was withdrawn.

Normal results

The normal time for platelet aggregation varies somewhat depending on the laboratory, the temperature, the shape of the vial in which the test is performed, and the patient's response to different agonists. For example, the difference between the response to ristocetin and other products should be noted because ristocetin triggers aggregation through a different mechanism than other agonists.

Abnormal results

Prolonged platelet aggregation time can be found in such congenital disorders as hemophilia and von Willebrand's disease, as well as in some connective tissue disorders. Prolonged aggregation times can also occur in leukemia or myeloma; after recent heart/lung bypass or kidney dialysis; and after taking certain drugs.

Key Terms

Aggregation
The blood cell clumping process that is measured in the platelet aggregation test.
Agonist
A chemical that is added to the blood sample in the platelet aggregation test to stimulate the clumping process.
Hemophilia
An inherited bleeding disorder caused by a deficiency of factor VIII, one of a series of blood proteins essential for blood clotting.
Platelets
Small, round, disk-shaped blood cells that are involved in clot formation. The platelet aggregation test measures the clumping ability of platelets.
Turbidity
The cloudiness or lack of transparency of a solution.
Von Willebrand's disease
An inherited lifelong bleeding disorder caused by a defective gene, similar to hemophilia. The gene defect results in a decreased blood concentration of a substance called von Willebrand's factor (vWF).

Further Reading

For Your Information

    Books

  • Handbook of Diagnostic Tests, edited by Matthew Cahill. Springhouse, PA: Springhouse Corporation, 1995.
  • Laboratory Test Handbook, edited by David S. Jacobs. Cleveland, OH: Lexi-Comp Inc., 1996.
  • Pagana, Kathleen Deska, and Timothy James Pagana. Mosby's Diagnostic and Laboratory Test Reference,. St. Louis: Mosby-Year Book, Inc., 1998.

Gale Encyclopedia of Medicine. Gale Research, 1999.

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