• Tests of platelet function. At present no single test provides an adequate assessment of the complex functions of platelets. Aggregation tests that measure the response of platelets to certain agonists and qualitative and quantitative tests of von Willebrand factor (vWF) (which you will recall is required for platelet adherence to subvascular collagen) are both commonly used in clinical practice. An old test, the bleeding time, has some value but is time-consuming and difficult to standardize and is therefore performed only rarely. Newer instrument-based assays that provide quantitative measures of platelet function are being evaluated but are not yet available for routine use in the clinic.
In addition, more specialized tests are available that measure the levels of specific clotting factors and fibrin split products or assess the presence of circulating anti-coagulants.
Bleeding disorders may stem from abnormalities of vessels, platelets, or coagulation factors, alone or in combination. Bleeding resulting from vascular fragility is seen with vitamin C deficiency (scurvy) (Chapter 8), systemic amyloidosis (Chapter 5), chronic glucocorticoid use, rare inherited conditions affecting the connective tissues, and a large number of infectious and hypersensitivity vasculitides. Some of these conditions are discussed in other chapters; others are beyond the scope of this book. Bleeding that results purely from vascular fragility is characterized by the “spontaneous” appearance of petechiae and ecchymoses in the skin and mucous membranes (probably resulting from minor trauma). In most instances laboratory tests of coagulation are normal.
Bleeding also can be triggered by systemic conditions that inflame or damage endothelial cells. If severe http://ebooksmedicine.net enough, such insults convert the vascular lining to a pro-thrombotic surface that activates coagulation throughout the circulatory system, a condition known as disseminated intravascular coagulation (DIC) (discussed in the next section). Paradoxically, in DIC, platelets and coagulation factors often are used up faster than they can be replaced, resulting in deficiencies that may lead to severe bleeding (a condition referred to as consumptive coagulopathy).
Deficiencies of platelets (thrombocytopenia) also are an important cause of bleeding. These occur in a variety of clinical settings that are discussed later. Other bleeding disorders stem from qualitative defects in platelet function. Such defects may be acquired, as in uremia and certain myeloproliferative disorders and after aspirin ingestion; or inherited, as in von Willebrand disease and other rare congenital disorders. The clinical signs of inadequate platelet function include easy bruising, nosebleeds, excessive bleeding from minor trauma, and menorrhagia.
In bleeding disorders stemming from defects in one or more coagulation factors, the PT, PTT, or both are prolonged. Unlike platelet defects, petechiae and mucosal bleeding are usually absent. Instead, hemorrhages tend to occur in parts of the body that are subject to trauma, such as the joints of the lower extremities. Massive hemorrhage may occur after surgery, dental procedures, or severe trauma. This category includes the hemophilias, an important group of inherited coagulation disorders.
It is not uncommon for bleeding to occur as a consequence of a mixture of defects. This is the case in DIC, in which both thrombocytopenia and coagulation factor deficiencies contribute to bleeding, and in von Willebrand disease, a fairly common inherited disorder in which both platelet function and (to a lesser degree) coagulation factor function are abnormal.
With the foregoing overview as background, we now turn to specific bleeding disorders.