Bleeding disorders are disruptions in the body's ability to control blood clotting. Patients with these conditions bleed easily for longer periods of time than normal.
Description
Coagulation, or clotting, is a complex process involving at least 20 components of the blood, including various enzymes, messenger chemicals, and proteins. Under normal circumstances, the components necessary for coagulation circulate in the blood. When an injury occurs, they act together in a series of chain reactions to form a clot and prevent uncontrolled bleeding. Several disorders affect the blood's clotting components and diminish normal clotting capability. For people with these disorders, even a small injury could make them bleed to death.
Anatomy of a blood clot
In healthy individuals, clots begins when fibrin, an insoluble protein that forms the skeleton of the clot, forms at the wound site from fibrinogen, a soluble protein present in plasma. This chemical change is made possible by thrombin, an enzyme that itself is only created from the compound prothrombin when an injury occurs. Once fibrin strands are formed at the wound site, they trap platelets that flow past them. Platelets then initiate the contraction of damaged blood vessels so that less blood is lost. They also help plug damaged blood vessels and work with plasma to accelerate blood clotting.
Hemophilia A
Mild-to-moderate forms of hemophilia A may be controlled with desmopressin acetate, a synthetic form of a pituitary hormone that rapidly increases that amount of available factor VIII and von Willebrand factor. This drug is called DDAVP in the injectable form, and Stimate when formulated as a nasal spray. Severe bleeding episodes will require transfusions of human blood clotting factors. Many hemophiliacs, however, have become resistant to this form of treatment and have developed antibodies against it. For these patients, a synthetic protein called factor VIIa (tradename NovoSeven) can increase coagulation or prevent bleeding episodes altogether. Factor VIIa is made with recombinant DNA technology. Fetal tissue implants and gene therapies are also being studied as possible treatments for hemophilia.
Hemophilia B
The treatment for hemophilia B is similar to that for hemophilia A, with the infusion of synthetic and human blood products, such as factor IX concentrate or factor IX complex (prothrombin) concentrate, to promote coagulation.
Hemophilia C
Hemophilia C is most often treated with plasma, since concentrates of factor XI are not universally available in the United States, due to the disease's extreme rarity.
Unlike hemophilia, DIC, also known as consumption coagulopathy or defibrination syndrome, is neither hereditary nor common. It is almost always caused by another disease or condition, which in turn activates abnormal and uncontrolled clotting. This causes many small blood clots to form throughout the body, giving the disease its name. This overproduction of clots depletes the supply of clotting factors and platelets necessary to prevent hemorrhage when an injury (or surgery) occurs. Patients with DIC will bleed abnormally even though there is no history of coagulation disorder.
Thrombocytopenia (TCP)
Thrombocytopenia is a group of bleeding disorders characterized by severely diminished platelet counts, which cause internal bleeding. TCP can occur during pregnancy, as a reaction to certain medications, when the spleen and lymph produce antibodies against platelets, or for no known reason, a type called idiopathic TCP.
Other bleeding disorders
Von Willebrand's disease often requires no treatment because the bleeding is mild and controllable. DDAVP can help raise levels of the Von Willebrand factor and is the treatment of choice for many cases. However, if trauma or surgery is scheduled there are several methods that will reduce bleeding time and replace factor VIII, which will consequently replace the von Willebrand factor. This may include infusion of cryoprecipitate or plasma,. For severe bleeding, infusions of a viral inactivated factor VIII products such as Humane-P, Alphanate, and Koate DVI may be required.
Hypoprothrombinemia may be treated with concentrates of prothrombin. Acquired cases are often treated with vitamin. In bleeding episodes, the patient may receive plasma products.
Factor VII deficiency patients may be treated with normal plasma or concentrates containing factor VII or the biomedically engineered VIIa.
Hemophilia
Hemophilia A is usually inherited through a complex genetic system that passes a recessive gene on the female chromosome. If a woman carries the hemophila gene, each of her male children has a 50% chance of having hemophilia; each female child has a 50% chance of carrying the gene. About a third of all hemophilia patients develop the disease with no known genetic risk; these cases, called sporadic hemophilia, are assumed to be the result of spontaneous genetic mutation.
Hemophilia A is suspected with when patients exhibit numerous large, deep bruises along with painful and swollen joints caused by internal bleeding. Mild hemophilia may first be discovered when prolonged bleeding follows a surgical procedure. If this involves bleeding into the neck, head, or digestive tract, or of the bleeding is caused by an injury, emergency measures may be required.
Disseminated intravascular coagulation
Treatment for DIC depends on what other disease is causing it. If the patient is not yet actively bleeding, the underlying cause should be dealt with. This supportive treatment may eliminate the DIC and the need for emergency measures. In some instances, heparin, an anticoagulant, is used to dissolve the small clots throughout the body; given that DIC can result in hemorrhage, this therapy is controversial. If bleeding has begun, however, the patient may need infusions of blood, platelets, plasma, and other blood products. Heparin should not be used to treat DIC caused by heatstroke, snakebite, trauma, mismatched transfusions, and acute problems resulting from obstetrical complications, nor should it be administered to patients with head injuries or central nervous system bleeding.
Thrombocytopenia
Secondary acquired thrombocytopenia is best alleviated by treating the underlying cause or disorder. Sometimes, no treatment is necessary; the condition will resolve by itself. If treatment is required, it will depend on the underlying cause. Platelet transfusions can help alleviate TCP caused by chemotherapy, for example. In other cases, corticosteroids or immune globulin may be given to improve platelet production.
Diagnosis
There are hundreds of different tests to detect various bleeding disorders, each one geared to the hallmarks of the specific disease. In addition to blood tests, physicians will compile a medical history and perform a physical examination. In the case of acquired blood coagulation disorders, information such as prior or current diseases and medications will be important in determining the cause of the bleeding disorder.
Treatment
For mild bleeding disorders, treatment may involve drugs that help the body increase the amount of clotting factors available. In severe cases, however, bleeding may only stop if the missing clotting factor that is replaced through fresh frozen plasma or cryoprecipitate, the blood fraction containing factor VIII. Every care must be taken to ensure that these infusions are free of HIV and other contaminants. Unfortunately, for many patients, this was not always the case, and many hemophiliacs, like Ryan White, contracted AIDS. New bioengineered therapies that rely on recombinant DNA technology should prevent any possibility of transferring HIV/AIDS.
Prognosis
The prognosis for patients with mild forms of bleeding disorders is good; many lead normal lives and enjoy a normal life expectancy. Untreated bleeding episodes, however, cause severe muscle and joint pain that eventually becomes permanent damage. Any incident that causes blood to collect in the head, neck, or digestive system can be fatal without immediate medical attention.
The clots that form throughout the body with DIC can produce gangrene in the fingers, nose, or genitals, and can even cause strokes. The prognosis depends on early intervention and treatment of the underlying condition.
Health care team roles
Patients must communicate with their health care providers before undergoing procedures or tests that could cause bleeding. The best care is obtained when treatment is coordinated by a health care team with expertise in the field. The Centers for Disease Control and Prevention found that patients with severe or moderate hemophilia had 60% less mortality and morbidity when their treatment was coordinated by a comprehensive hemophilia treatment compared to those not seen by a comprehensive hemophilia treatment center.
Other health care providers, such as counselors, may help patients cope with their conditions or illnesses. Support groups can also be helpful in understanding the specific condition and in achieving goals for personal wellness.
Prevention
It is not always possible to prevent bleeding disorders. Some acquired conditions may be prevented by preventing underlying diseases such as cirrhosis, or discontinuing medications whose side effects cause bleeding. Hereditary disorders can be predicted with prenatal testing and genetic counseling. severe bleeding episodes may be prevented by refraining from activities that could cause injury, such as contact sports.
KEY TERMS
Blood clot—A clump of blood that forms as a result of coagulation when a blood vessel is injured. Without this process a person would bleed to death from a relatively small wound.
Coagulation—The blood's change from a liquid to a semisolid state through chemical reaction.
Clotting factor—Any of several components normally found in blood that are essential for clotting to occur.
Enzyme—A substance that causes a chemical reaction, usually a protein. Enzymes are secreted by cells.
Hemorrhage—Abnormal, uncontrolled bleeding from the blood vessels, usually internally.
Petechiae—Small pinpoint bruises caused by bleeding under the skin.
Platelets—Also called thrombocytes, these are small, colorless particles found in the only in mammalian blood that help form clots, keep various body chemicals in circulation, and devour foreign bodies, such as viruses.
Thrombosis—Formation of a clot that either blocks or partially blocks a blood vessel. The thrombus may lead to infarction, or tissue death.
BOOKS
Beutler, Ernest, M.D., et al. Williams Hematology. Sixth edition. New York: McGraw-Hill Professional Publishing, 2000.
Carr, Jacqueline H., and Bernadette F. Rodak. Clinical Hematology Atlas. London: W. B. Saunders Co., 1999.
Harmening, Denise, ed. Modern Blood Banking and Transfusion Practices. 4th ed. Philadelphia: F. A. Davis Co., 1999.
Hoffman, Ronald, ed., et al. Hematology: Basic Principles and Practice. 3rd ed. Edinburgh: Churchill Livingstone, 2000.
Shin, Linda M., and Karen Bellenir, eds. Blood and Circulatory Disorders Sourcebook: Basic Information About Blood and Its Components. Health Reference Series, vol 39. Detroit: Omnigraphics, Inc., 1998.
PERIODICALS
Girelli D., et al. "Polymorphisms in the Factor VII Gene and the Risk of Myocardial Infarction in Patients with Coronary Artery Disease." New England Journal of Medicine 343 (2000): 774–780.
Meijers J., et al. "High Levels of Coagulation Factor XI as a Risk Factor for Venous Thrombosis." New England Journal of Medicine 342 (2000): 696–701.
ORGANIZATIONS
National Heart, Lung and Blood Institute. Building 31, Room 4A21, Bethesda, MD 20892. (301) 496-4236. <http://www.nhlbi.nih.gov>.
National Hemophilia Foundation. 116 West 32nd St., 11th Floor, New York, NY 10001. 800-42-HANDI. <http://www.hemophilia.org>.
OTHER
Brochert, Adam. "Disseminated Intravascular Coagulation." Discovery Health: Diseases and Conditions. <http://health.discovery.com/diseasesandcond/encyclopedia/604.html>.
"What Is Hemophilia?" World Federation of Hemophilia. <http://www.wfh.org>.
